Transcatheter Aortic Valve Implantation (TAVI): FDA approves expanded indication for two transcatheter heart valves for patients at intermediate risk for death or complications associated with open-heart surgery
Reporter: Aviva Lev-Ari, PhD, RN
UPDATED ON 8/23/2016
FDA approves expanded indication for two transcatheter heart valves for patients at intermediate risk for death or complications associated with open-heart surgery
about a third of patients referred for open-heart surgery for aortic-valve replacement fall into the intermediate-risk category, defined as having at least a 3% risk of death within 30 days of surgery.
For Immediate Release
August 18, 2016
Release
The U.S. Food and Drug Administration today approved an expanded indication for the Sapien XT and Sapien 3 transcatheter heart valves for patients with aortic valve stenosis who are at intermediate risk for death or complications associated with open-heart surgery. These devices were previously approved only in patients at high or greater risk for death or complications during surgery.
“This is the first time in the U.S. that a transcatheter aortic valve has been approved for use in intermediate risk patients,” said Bram Zuckerman, M.D., director of the division of cardiovascular devices at the FDA’s Center for Devices and Radiological Health. “This new approval significantly expands the number of patients indicated for this less invasive procedure for aortic valve replacement.”
Aortic valve stenosis increases with age as the aortic valve becomes narrow, causing the heart to work harder to pump enough blood through a smaller opening. It occurs in about three percent of Americans over age 75 and can cause fainting, chest pain, heart failure, irregular heart rhythms (arrhythmias), cardiac arrest or death. Patients with severe aortic valve stenosis generally need to have a heart valve replacement to improve blood flow through their aortic valve.
Traditionally, open-heart surgery has been the gold standard for aortic valve replacement in intermediate risk patients, but it involves a larger incision and longer recovery time than the minimally invasive procedure used to insert the transcatheter heart valve. About one-third of patients referred for open-heart surgery for aortic valve replacement fall into the “intermediate risk” category, which is defined as having a greater than three percent risk of dying within 30 days following surgery.
In a clinical study to evaluate safety and effectiveness, 1,011 aortic stenosis patients at intermediate risk for surgical complications were randomly selected to have a transcatheter aortic valve replacement procedure using the Sapien XT valve and 1,021 were randomly selected to have a traditional aortic valve replacement during open-heart surgery using a surgical tissue valve. In a second study, 1,078 intermediate risk patients were implanted with the Sapien 3 valve; and outcomes in these patients were compared to the same group of 1,021 surgical control patients in the first study. The two studies demonstrated a reasonable assurance of safety and effectiveness of the Sapien XT and Sapien 3 devices in intermediate risk patients.
Patients who receive either the Sapien XT or the Sapien 3 valve face a potential risk of serious complications from the device or implantation procedure, such as death, stroke, acute kidney injury, heart attack, bleeding, and the need for a permanent pacemaker.
The devices are contraindicated for patients who cannot tolerate blood thinning medication. They are also contraindicated for those who are currently being treated for a bacterial or other infection.
As part of the approval of these devices, the FDA is requiring the manufacturer to conduct a post-approval study to follow the patients treated with either device in the first and second clinical studies for 10 years to further monitor safety and effectiveness.
Sapien XT and Sapien 3 are manufactured by Edwards Lifesciences, LLC, based in Irvine, California.
The FDA, an agency within the U.S. Department of Health and Human Services, protects the public health by assuring the safety, effectiveness, and security of human and veterinary drugs, vaccines and other biological products for human use, and medical devices. The agency also is responsible for the safety and security of our nation’s food supply, cosmetics, dietary supplements, products that give off electronic radiation, and for regulating tobacco products.
Related Information
Transcatheter Aortic Valve Implantation (TAVI): Risky and Costly
On this Scientific Web Site, Frontiers in Cardiology and Cardiac Repair are reported as discovered and debated in the literature. Our address of the innovations involving the development of TAVI are reported as follows:
June 4, 2012 — Investigational Devices: Edwards Sapien Transcatheter Aortic Valve Transapical Deployment http://pharmaceuticalintelligence.com/2012/06/04/investigational-devices-edwards-sapien-transcatheter-heart-valve/
June 10, 2012 — Investigational Devices: Edwards Sapien Transcatheter Aortic Heart Valve Replacement Transfemoral Deployment http://pharmaceuticalintelligence.com/2012/06/10/investigational-devices-edwards-sapien-transcatheter-aortic-heart-valve-replacement-transfemoral-deployment/
June 19, 2012 — Executive Compensation and Comparator Group Definition in the Cardiac and Vascular Medical Devices Sector: A Bright Future for Edwards Lifesciences Corporation in the Transcatheter Heart Valve Replacement Market http://pharmaceuticalintelligence.com/2012/06/19/executive-compensation-and-comparator-group-definition-in-the-cardiac-and-vascular-medical-devices-sector-a-bright-future-for-edwards-lifesciences-corporation-in-the-transcatheter-heart-valve-replace/
Our reporting on Regulatory Affairs for Medical Devices was reported on 7/31/2012.
July 31, 2012 — Gaps, Tensions, and Conflicts in the FDA Approval Process: Implications for Clinical Practice http://pharmaceuticalintelligence.com/2012/07/31/gaps-tensions-and-conflicts-in-the-fda-approval-process-implications-for-clinical-practice/
On August 1, 2012, in BJM researchers at KCE, Belgian Health Care Knowledge Centre, Administratief Centrum Kruidtuin, Kruidtuinlaan 55, 1000 Brussels, Belgium; 2CEBAM, Belgian Centre for Evidence-Based Medicine and Branch of the Dutch Cochrane Centre, Leuven, Belgium — reported research results which are examining why the practice of TAVI has gone beyond the evidence.
Edwards Lifesciences shares closed down more than 2% yesterday after the British Medical Journal said many procedures using its Sapien heart valve “cannot be justified on medical or cost-effectiveness grounds.”
On August 1, 2012 — Shares of Edwards Lifesciences (NYSE:EW) slid 2.2% yesterday after an analysis published in the British Medical Journal claimed that “many” of the heart valve replacements using its flagship Sapien heart valve “cannot be justified” and leveled accusations of conflict of interest and unethical conduct against Edwards and Sapien inventor Dr. Martin Leon.
http://www.massdevice.com/news/edwards-lifesciences-slides-rebounds-negative-heart-valve-study
A trio of Belgian researchers said their “rigorous analysis of all the available data, in combination with a study of real world [transcatheter aortic valve implant] practice in Europe, led us to conclude that the arguments supporting the widespread use of TAVI do not stand up to scrutiny.”
“In addition, the Partner trial seems to have important problems, the most relevant being publication bias and lack of data transparency, unbalanced patient characteristics, and incompletely declared conflicts of interest,” wrote Hans Van Brabandt, Mattias Neyt and Frank Hulstaert, who were commissioned by the Belgian government to run the analysis.
Edwards shares closed on 8/1/2012 at $101.20, down 2.2%,
On 8/2/2012 it closed at 99.30 (0.75 below yesterday)
52wk Range: | 61.59 – 106.94 |
---|
The BMJ researchers wrote that Belgian health authorities should pay for only about 10% of the patients now considered for trancatheter aortic valve replacements in the lowland country – procedures using the Sapien heart valve and a competing device, Medtronic‘s (NYSE:MDT) CoreValve implant, should be limited to patients who aren’t good candidates for traditional open heart surgery. The CoreValve device is not yet approved for the U.S. market.
Edwards’ Partner trial for the Sapien valve was flawed due to potential bias on the part of Leon, according to the researchers. Leon founded a company to develop the implant that Edwards acquired in 2004, triggering a $6.9 million payout that was disclosed. But other milestone payments due to Leon were not disclosed, they wrote, creating “substantial financial interests that we do not believe were fully disclosed.””We believe Dr. Marty Leon has conducted himself throughout the Partner trial in accordance with the highest ethical standards. In his role as co-principal investigator of the trial, he has only been reimbursed for travel-related expenses,” an Edwards spokeswoman told MassDevice.com in an email today. “Dr. Leon also has – throughout the Partner trial – remained in compliance with the strict conflict-of-interest standards of both the FDA and Columbia University. As previously reported, the sale of PVT to Edwards took place in 2004 and the single milestone payment (that Dr. Leon donated to charity) was made in 2006, well before the beginning of the pivotal trial.”The Partner study was also biased by imbalance between the treatment and control groups in the TAVI cohort that favored Sapien, they wrote.Brabandt, Neyt and Hulstaert also claimed that repeated requests to Edwards and Leon for access to data from an FDA-ordered follow-on study of the Sapien device “went unanswered.”
“In our view, this behaviour is both ethically and scientifically unacceptable and should be legally regulated in
future [sic],” they wrote. “Study sponsors should be obliged to make the results of a negative trial public so that policy makers can reach rational and balanced decisions.”
Some of that data, from a 90-patient study of inoperable candidates, was presented at an FDA meeting in July 2011, according to the Belgian researchers. Those results demonstrated a higher risk of mortality after a year among the cohort treated with the Sapien valve (34.3% vs. 21.6%, they wrote).
The researchers also took a shot at the New England Journal of Medicine, which they approached after being rebuffed by Edwards and Leon. The NEJM editors passed the researchers’ “objections” on to the investigators, but the response convinced the editors that “while each of the points we raised deserved a thoughtful review, they did not, either individually or together, fundamentally place the findings of the Partner trial in serious doubt.”
“Based on current evidence, and considering efficient use of limited resources, it is difficult to see how healthcare payers can justify reimbursing TAVI for patients suitable for surgery, given that the risk of stroke is twice as high after TAVI,” the researches concluded. “In addition, TAVI is much more expensive, on average about €20,000 more per patient in our analysis of Belgian data. Based on observational data, the costs during the initial hospital admission, inclusive of an Edwards Sapien valve of €18,000, are on average €43,600 for TAVI versus €23,700 for surgical valve replacement.”
Transcatheter aortic valve implantation (TAVI): risky and costly
Many of the 40 000 transcatheter procedures so far carried out cannot be justified on medical or cost effectiveness grounds. Hans Van Brabandt, Mattias Neyt, and Frank Hulstaert examine why practice has gone beyond the evidence. The three researchers are:
Hans Van Brabandt researcher 1 2, Mattias Neyt researcher 1, Frank Hulstaert researcher 1
1KCE, Belgian Health Care Knowledge Centre, Administratief Centrum Kruidtuin, Kruidtuinlaan 55, 1000 Brussels, Belgium; 2CEBAM, Belgian Centre for Evidence-Based Medicine and Branch of the Dutch Cochrane Centre, Leuven, Belgium
Correspondence to: M Neyt mattias.neyt@kce.fgov.be
BMJ 2012;345:e4710 doi: 10.1136/bmj.e4710 (Published 31 July 2012) Page 1 of 5
Analysis
Around the world, tens of thousands of people have been treated for a life threatening heart condition using a minimally invasive technique that many see as the wave of the future. Transcatheter aortic valve implantation (TAVI) offers hope to patients too old or too ill for conventional aortic valve replacement operations, and since its introduction 10 years ago it has spread swiftly—by the end of 2011, an estimated 40 000 transcatheter implantations had been done.1 But serious unanswered questions remain over the clinical outcomes and the cost effectiveness of TAVI, as well as the regulatory process that enabled it to gain such a large market so rapidly, particularly in Europe.
Aortic stenosis, the progressive failure of the aortic valve to open fully, is the commonest type of valve disease in elderly people. It is usually treated by valve replacement surgery, but around a third of those who might benefit are turned down because the risks of surgery are too high or because problems such as a calcified aorta or scarring from previous surgery make them unsuitable for surgery.2 Untreated, most will die within five years.3 TAVI offers an alternative, in which a replacement valve is introduced through an artery via a small incision (usually the femoral artery) or, less often, surgically with an incision into the chest and then into the left ventricular apex—the transapical approach.
The numbers who could potentially benefit from TAVI are verylarge.4 Almost 3% of people over 75 have aortic valve disease,5which means that in England alone there are more than 100 000patients in whom aortic valve surgery might at a given moment be contemplated. But only around 1200 aortic valve replacements are carried out in this age group in England each year. This helps explain the enthusiasm with which TAVI has been taken up, and the large potential market. In April 2011, a New York securities analyst for the financial services company Wells Fargo estimated that TAVI could generate more than $2.4bn (£1.5bn; €2bn) in sales in the US and account for more than a third of aortic valve replacements by 2015.6 Cardiologists in the US also expect growing demand from patients who are suitable for conventional surgery but who prefer the quicker and less painful transcatheter option. Data reported at the European Society of Cardiology (EuroPCR) meeting in Paris in May7 suggested that transcatheter procedures have more than tripled in Europe since 2009, rising to 18 372 in 2011. Germany is far ahead of other European nations, being responsible for 43% of all TAVIs, followed by France (13%), Italy (10%), and the UK and Ireland (7%).1
Approval processes
Given the enthusiasm with which the procedure has been adopted, we might expect the evidence for its efficacy to be solid. But a health technology assessment we carried out, commissioned by the Belgian government, concluded that the Belgian health authorities should pay for TAVI in only a minority of patients (10%) of those currently considered for treatment—those who are deemed inoperable for technical reasons such as a series of previous operations or irradiation of the chest wall.8 The United Kingdom’s National Institute for Health and Clinical Excellence (NICE) guidance issued in March this year said that for patients considered unsuitable for surgery, the evidence for TAVI was adequate from a clinical point of view but it did not take costs into account.9 But NICE said that for patients for whom surgery is suitable, albeit risky, the evidence for using TAVI was inadequate, and it should be used in these circumstances only when special arrangements for clinical governance, consent, and data collection or research were in place.9
In the European Union, medical devices fall outside the scope of the European Medicines Agency and need only a simple quality certificate (CE mark) to gain access to the market, putting them on the same footing as domestic appliances such as toasters. Two different valves for transcatheter implantation gained their CE marks in 2007, long before any substantial clinical trial evidence was available: the Edwards Sapien valve and the Medtronics CoreValve. In the US the law demands evidence of efficacy in a randomised trial before the Food and Drug Administration can license any innovative device. Thus TAVI was in use in Europe four years before the FDA licensed the Sapien valve in November 2011, and—in contrast to Europe—only for the transfemoral approach and for patients considered unsuitable for standard valve surgery.10 The transapical route was not approved. In June 2012, a panel of expert advisers recommended that the FDA approved the Sapien valve for high risk operable patients, including a transapical delivery option.11 The advisory panel does not take economic considerations into account.
The European system for approving medical devices has already come in for criticism over breast and hip implants, with the new executive director of the EMA, Guido Rasi, acknowledging in January that there is an urgent need to regulate devices with the same care as medicines. “I think, at the end of the day, we will see everyone moving to increasing use of comparative trials,” Rasi said in an interview with Reuters.12 He expected that concerns about the now defunct French breast implant company Poly Implant Prosthese might help to speed the process. But while the evidence demanded by the FDA exceeded that required in Europe, we remain far from convinced that it is adequate. The Sapien valve was approved on the basis of a trial called PARTNER (Placement of Aortic Transcatheter Valve).
We reviewed the conduct and results of the trial through papers published in peer reviewed journals, proceedings from congresses, press releases, and direct contacts with the manufacturer, the FDA, the New England Journal of Medicine (NEJM) (where it was published), and the principal investigators.
Our rigorous analysis of all the available data, in combination with a study of real world TAVI practice in Europe, led us to conclude that the arguments supporting the widespread use of TAVI do not stand up to scrutiny. In addition, the PARTNER trial seems to have important problems, the most relevant being publication bias and lack of data transparency, unbalanced patient characteristics, and incompletely declared conflicts of interest.
What the evidence shows
PARTNER was a randomised controlled trial in 26 sites, most of them in the US. It allocated patients with severe aortic valve stenosis to two groups: those at very high risk from surgery (cohort A)13 and those deemed inoperable (cohort B).14 The 699 patients in cohort A were randomised either to TAVI or to surgical valve replacement, and the 358 in cohort B were randomised to TAVI or standard therapy, which was balloon aortic valvuloplasty in most cases, combined with medical supportive treatment.
The results showed that in the high risk operable patients, mortality at one year was similar for TAVI and surgical insertion (24.2% v 26.8%, P=0.44) (table⇓). PARTNER was designed as a non-inferiority trial, with a difference of 7.5 percentage points in survival set as the margin, so TAVI met this target. But strokes and transient ischaemic attacks were significantly commoner in the TAVI group at one year (8.3% v 4.3%, P=0.04) and major vascular complications significantly commoner at 30 days (11.0% v 3.2%, P=0.001). Major bleeding and new onset atrial fibrillation were significantly higher in the surgical group. At one year, symptoms were about the same in both groups.13
In the patients deemed inoperable, results were relatively better. Mortality at one year was significantly lower for TAVI (30.7% v 50.7%, P<0.001). Again, however, there was a higher incidence of stroke and major vascular events in the TAVI group (10.6% v 4.5%, P=0.04).14 Taken together, these results suggest that TAVI can be justified for inoperable patients on clinical grounds, though cost effectiveness calculations are more equivocal. But even this conclusion is thrown into doubt by a follow-up study authorised by the FDA, in which 41 inoperable patients were randomised to TAVI and 49 to standard therapy. This study remains unpublished, and our attempts to gain access to further details have been rebuffed by the FDA and the study sponsor. But the data presented at an FDA meeting on 20 July 2011 showed that the TAVI patients fared worse than those given standard therapy (one year mortality 34.3% v 21.6%).15
We have repeatedly sought access to further details of this follow-on trial, carried out under FDA auspices as a formally approved “continued access study,” the purpose of which is to enable sponsors of clinical investigations to continue to enroll patients while a market application is being sought. The FDA responded that any further data analysis of a premarket application is proprietary information and that it was up to the sponsor to release it, if so inclined. But our requests to the sponsor (Edwards) and the principal investigator went unanswered. In our view, this behaviour is both ethically and scientifically unacceptable and should be legally regulated in future. Study sponsors should be obliged to make the results of a negative trial public so that policy makers can reach rational and balanced decisions.
Given our failure to make progress with the FDA or the sponsor, we approached the NEJM which had published the PARTNER trial. We put our objections to the NEJM, which passed them on to the investigators. Their response convinced the NEJM editors that “while each of the points we raised deserved a thoughtful review, they did not, either individually or together, fundamentally place the findings of the PARTNER trial in serious doubt.” Asked what the responses of the investigators had been, NEJM responded that it had not requested permission from them to pass them on, since they were intended for its own confidential evaluation. We were recommended to request this information directly from the study sponsor, which we did, to no avail.
NEJM has, however, published two year follow-up results that essentially confirmed the one year data.16 17 However, it did so without demanding that the study sponsor publish or discuss the negative results of the follow-on trial. It is difficult to understand this decision. Our concerns about the PARTNER trial go further than this, however. Published data on the inoperable patients, who had the most convincing results, show that the treatment and control groups are unbalanced in a way that would favour TAVI. The control group contained more patients with comorbidities, more who had had a previous heart attack, and more who were classified as frail than the TAVI group. There were fewer patients with an extensively calcified aorta. All these differences could have arisen from a flawed randomisation or by chance; but since they favour TAVI, an analysis that adjusted for prognosis at baseline would have produced a more realistic estimate of the effect size.
Disclosure of interests
BMJ 2012;345:e4710 doi: 10.1136/bmj.e4710 (Published 31 July 2012) Page 1 of 5
Practice beyond the evidence
What concerns us most is that in Europe the use of TAVI in the transapical route far exceeds what is justified by the clinical evidence. The PARTNER trial does not provide clear evidence on this route. A subgroup analysis suggests that the transapical approach is not inferior to surgery but has double the risk of stroke. Although the FDA proposed it,19 the trial sponsor declined to include a transapical arm in inoperable patients. But despite this dearth of evidence, TAVI is widely used transapically in Europe.
The UK TAVI registry, for example, shows that 409 of 1620 TAVI patients (25%) were treated transapically, with a one year mortality of 25.5%.20 The FRANCE-2 registry shows that of 2430 patients treated in 2010 and 2011, 20% had transapical TAVI, with a six month mortality of 20.2%.21 We cannot know, of course, what the survival rate of these patients would have been if they had been treated medically or by standard surgery. A position statement by the British Cardiovascular Intervention Society and the Society of Cardiothoracic Surgeons does not distinguish between the transfemoral and transapical approaches despite the different evidence bases.22 It states that TAVI should currently be reserved for patients in whom “the risk/benefit ratio of open heart surgery versus TAVI favours TAVI.” It calls for randomised trials, but only when centres in the UK have got “beyond their learning curve.” Patients may be surprised to hear that trials are being delayed to allow cardiologists and surgeons time to learn the technique.
Concerns about transapical TAVI were heightened by the early termination of a Danish trial called STACCATO,23 which compared transapical TAVI against conventional surgery. Five of 34 TAVI patients and only one of 36 surgically treated patients had either died or had a major stroke or renal failure within 30 days, prompting the data safety monitoring board to call a halt. This discouraging result was reported at the 2011 transcatheter cardiovascular therapeutics conference in San Francisco and drew criticism from Michael Mack, of the University of Texas at Dallas, who said the study was poorly designed and poorly executed.24 Mack, an investigator in the PARTNER trial, said: “I think there is some misinformation here, based on an invalid trial design, that is likely to hurt the field.”
Leif Thuesen, of Aarhus University Hospital in Denmark, who presented the STACCATO results, was more concerned with patients than with the field. “There is no doubt that there are patients who can’t be operated on, and they should be treated with TAVI” he told heartwire. “But the patient who can be operated on—here, we should be very, very cautious. It’s the operable patients, the low-risk patients, they should not have the TAVI procedures, but that’s what is happening. We had one patient, for instance, who did not want the conventional operation, so he had the TAVI procedure in Canada. That’s how it is. Indications are slipping.”24 In contrast to the current situation in Europe, we recommend that marketing approval for a high risk device should be granted for specific indications only. Each of these indications should be supported by clinical evidence from high quality randomised trials. Patients may be at risk if the high risk device is routinely used outside those indications. Payers may have an interest in limiting reimbursement of such high risk devices only to those indications for which there is a high level of evidence of efficacy and cost effectiveness.25
Based on current evidence, and considering efficient use of limited resources, it is difficult to see how healthcare payers can justify reimbursing TAVI for patients suitable for surgery, given that the risk of stroke is twice as high after TAVI. In addition, TAVI is much more expensive, on average about €20,000 more per patient in our analysis of Belgian data. Based on observational data, the costs during the initial hospital admission, inclusive of an Edwards Sapien valve of €18 000, are on average €43 600 for TAVI versus €23 700 for surgical valve replacement. The average cost of transapical TAVI is higher than for the transfemoral approach (€49 800 v €40 900).26 The NICE guidance did not include a cost-benefit analysis, but these costs should be taken into account by local NHS commissioners in decisions about whether to fund the procedure. If policy makers are willing to pay for TAVI, they should give priority to anatomically inoperable patients.8 26 Europe’s lax licensing laws set up in an era where medical devices typically comprised hearing aids, walking frames, and spectacles are not appropriate for implantable devices. It should require high quality randomised trials to show clinical efficacy and safety before granting marketing approval to innovative, high risk medical devices. And a major improvement in transparency of information is also needed to allow clinicians to practise evidence based medicine, patients to make informed decisions, and health technology assessment agencies to make the right judgments.
REFERENCE
1 Nainggolan L. Germany tops TAVI table, but room for growth remains, 1 November, 2011. www.theheart.org/coverages.do.
2 Iung B, Cachier A, Baron G, Messika-Zeitoun D, Delahaye F, Tornos P, et al. Decision-making in elderly patients with severe aortic stenosis: why are so many denied surgery? Eur Heart J 2005;26:2714-20.
3 Varadarajan P, Kapoor N, Bansal RC, Pai RG. Survival in elderly patients with severe aortic stenosis is dramatically improved by aortic valve replacement: results from a cohort of 277 patients aged ≥80 years. Eur J Cardiothorac Surg 2006;30:722-7.
4 Ray S. Estimated population need for TAVI, data presented at a consensus meeting, 16 December 2008. www.ucl.ac.uk/nicor/audits/tavi/pdfs/estimated.
6 Cortez M. Edwards valve study may spur patient demand doctors aren’t ready to meet Bloomberg News 2011 Apr 4. www.bloomberg.com/news/2011-04-04/edwards-valvestudy- may-spur-patient-demand-doctors-aren-t-ready-to-meet.html.
7 TAVI numbers rise in Europe as reimbursement, expertise expands. Heartwire 2012 May 17. www.theheart.org/article/1401795.do.
9 NICE. Transcatheter aortic valve implantation for aortic stenosis. NICE interventional procedure guidance 421. NICE, 2012.
10 FDA. Edwards SAPIENTM transcatheter heart valve, model 9000TFX, sizes 23mm and 26mm and accessories. www.accessdata.fda.gov/cdrh_docs/pdf10/p100041a.pdf.
12 Hirschler B. EU medicines head urges tougher implant rules. 2012 www.reuters.com/ article/2012/01/06/us-breastimplants-ema-idUSTRE8050VL20120106.
13 Smith CR, Leon MB, Mack MJ, Miller DC, Moses JW, Svensson LG, et al. Transcatheter versus surgical aortic-valve replacement in high-risk patients. N Engl J Med 2011;364:2187-98.
15 FDA. SAPIEN THV briefing document—advisory committee meeting. FDA, 2011:301.
16 Makkar RR, Fontana GP, Jilaihawi H, Kapadia S, Pichard AD, Douglas PS, et al. Transcatheter aortic-valve replacement for inoperable severe aortic stenosis. N Engl J Med 2012;366:1696-704.
18 Medicine in conflict. Businessweek 2006 Oct 23. www.businessweek.com/magazine/ content/06_43/b4006081.htm.
19 FDA. FDA executive summary: Edwards SAPIEN THV. FDA, 2011.
20 Blackman D. Outcome of TAVI by valve type and access route: UK TAVI registry. 2011. www.pcronline.com/Lectures/2011/Outcome-of-TAVI-by-valve-type-and-access-route.- UK-TAVI-registry.
21 Gilard M. FRANCE II—French aortic national core valve and Edwards registry. EuroPCR conference, Paris, 17-20 May 2011.
22 British Cardiovascular Intervention Society, Society of Cardiothoracic Surgeons. Transcatheter aortic valve implantation (TAVI): a position statement. www.ucl.ac.uk/nicor/ audits/tavi/pdfs/bcisposition.
23 Nielsen HH, Klaaborg KE, Nissen H, Terp K, Mortensen PE, Kjeldsen BJ, et al. A prospective, randomised trial of transapical transcatheter aortic valve implantation vs. surgical aortic valve replacement in operable elderly patients with aortic stenosis: the STACCATO trial. EuroIntervention 2012. May 14. [Epub ahead of print].
24 O’Riordan M. STACCATO; transapical TAVI in surgery-eligible patients stopped due to adverse events. Heartwire 2011 Nov 10. www.theheart.org/article/1307437.do.
26 Neyt M, Van Brabandt H, Devriese S, Van De Sande S. A cost-utility analysis of transcatheter aortic valve implantation in Belgium: focusing on a well-defined and identifiable population. BMJ Open 2012;2:e001032.
Table
Table 1| One year mortality and stroke rate in the PARTNER trial13 14 15
Inoperable patients
High risk patients* Pivotal trial† Continued access study‡
TAVI AVR P value TAVI Control P value TAVI Control
No of patients 348 351 179 179 41 49
1 year all cause mortality (% (No of events))§ 24.2 (84) 26.8 (89) 0.44 30.7 (55) 50.7 (89) <0.001 34.3 (13) 21.6 (10)
1 year stroke rate (% (No of events))¶ 8.3 (27) 4.3 (13) 0.04 10.6 (19) 4.5 (8) 0.04 2.4 (1) 0 (0)
TAVI= transcatheter aortic valve implantation, AVR=surgical aortic valve replacement.
*Hazard ratio with TAVI in high risk patients: 0.93 (95% CI 0.71 to 1.22; P=0.62)
†Hazard ratio with TAVI in inoperable patients (pivotal trial): 0.55 (95% CI 0.40 to 0.74; P<0.001);
‡No P value or hazard ratio was published for the continued access study.
§ Kaplan-Meier estimates.
¶ Includes any stroke and transient ischaemic attack; stroke rate in continued access study includes “major stroke” only.
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PUT IT IN CONTEXT OF CANCER CELL MOVEMENT
The contraction of skeletal muscle is triggered by nerve impulses, which stimulate the release of Ca2+ from the sarcoplasmic reticuluma specialized network of internal membranes, similar to the endoplasmic reticulum, that stores high concentrations of Ca2+ ions. The release of Ca2+ from the sarcoplasmic reticulum increases the concentration of Ca2+ in the cytosol from approximately 10-7 to 10-5 M. The increased Ca2+ concentration signals muscle contraction via the action of two accessory proteins bound to the actin filaments: tropomyosin and troponin (Figure 11.25). Tropomyosin is a fibrous protein that binds lengthwise along the groove of actin filaments. In striated muscle, each tropomyosin molecule is bound to troponin, which is a complex of three polypeptides: troponin C (Ca2+-binding), troponin I (inhibitory), and troponin T (tropomyosin-binding). When the concentration of Ca2+ is low, the complex of the troponins with tropomyosin blocks the interaction of actin and myosin, so the muscle does not contract. At high concentrations, Ca2+ binding to troponin C shifts the position of the complex, relieving this inhibition and allowing contraction to proceed.
Figure 11.25
Association of tropomyosin and troponins with actin filaments. (A) Tropomyosin binds lengthwise along actin filaments and, in striated muscle, is associated with a complex of three troponins: troponin I (TnI), troponin C (TnC), and troponin T (TnT). In (more ) Contractile Assemblies of Actin and Myosin in Nonmuscle Cells
Contractile assemblies of actin and myosin, resembling small-scale versions of muscle fibers, are present also in nonmuscle cells. As in muscle, the actin filaments in these contractile assemblies are interdigitated with bipolar filaments of myosin II, consisting of 15 to 20 myosin II molecules, which produce contraction by sliding the actin filaments relative to one another (Figure 11.26). The actin filaments in contractile bundles in nonmuscle cells are also associated with tropomyosin, which facilitates their interaction with myosin II, probably by competing with filamin for binding sites on actin.
Figure 11.26
Contractile assemblies in nonmuscle cells. Bipolar filaments of myosin II produce contraction by sliding actin filaments in opposite directions. Two examples of contractile assemblies in nonmuscle cells, stress fibers and adhesion belts, were discussed earlier with respect to attachment of the actin cytoskeleton to regions of cell-substrate and cell-cell contacts (see Figures 11.13 and 11.14). The contraction of stress fibers produces tension across the cell, allowing the cell to pull on a substrate (e.g., the extracellular matrix) to which it is anchored. The contraction of adhesion belts alters the shape of epithelial cell sheets: a process that is particularly important during embryonic development, when sheets of epithelial cells fold into structures such as tubes.
The most dramatic example of actin-myosin contraction in nonmuscle cells, however, is provided by cytokinesisthe division of a cell into two following mitosis (Figure 11.27). Toward the end of mitosis in animal cells, a contractile ring consisting of actin filaments and myosin II assembles just underneath the plasma membrane. Its contraction pulls the plasma membrane progressively inward, constricting the center of the cell and pinching it in two. Interestingly, the thickness of the contractile ring remains constant as it contracts, implying that actin filaments disassemble as contraction proceeds. The ring then disperses completely following cell division.
Figure 11.27
Cytokinesis. Following completion of mitosis (nuclear division), a contractile ring consisting of actin filaments and myosin II divides the cell in two.
http://www.ncbi.nlm.nih.gov/books/NBK9961/
This is good. I don’t recall seeing it in the original comment. I am very aware of the actin myosin troponin connection in heart and in skeletal muscle, and I did know about the nonmuscle work. I won’t deal with it now, and I have been working with Aviral now online for 2 hours.
I have had a considerable background from way back in atomic orbital theory, physical chemistry, organic chemistry, and the equilibrium necessary for cations and anions. Despite the calcium role in contraction, I would not discount hypomagnesemia in having a disease role because of the intracellular-extracellular connection. The description you pasted reminds me also of a lecture given a few years ago by the Nobel Laureate that year on the mechanism of cell division.
PUT IT IN CONTEXT OF CANCER CELL MOVEMENT
The contraction of skeletal muscle is triggered by nerve impulses, which stimulate the release of Ca2+ from the sarcoplasmic reticuluma specialized network of internal membranes, similar to the endoplasmic reticulum, that stores high concentrations of Ca2+ ions. The release of Ca2+ from the sarcoplasmic reticulum increases the concentration of Ca2+ in the cytosol from approximately 10-7 to 10-5 M. The increased Ca2+ concentration signals muscle contraction via the action of two accessory proteins bound to the actin filaments: tropomyosin and troponin (Figure 11.25). Tropomyosin is a fibrous protein that binds lengthwise along the groove of actin filaments. In striated muscle, each tropomyosin molecule is bound to troponin, which is a complex of three polypeptides: troponin C (Ca2+-binding), troponin I (inhibitory), and troponin T (tropomyosin-binding). When the concentration of Ca2+ is low, the complex of the troponins with tropomyosin blocks the interaction of actin and myosin, so the muscle does not contract. At high concentrations, Ca2+ binding to troponin C shifts the position of the complex, relieving this inhibition and allowing contraction to proceed.
Figure 11.25
Association of tropomyosin and troponins with actin filaments. (A) Tropomyosin binds lengthwise along actin filaments and, in striated muscle, is associated with a complex of three troponins: troponin I (TnI), troponin C (TnC), and troponin T (TnT). In (more ) Contractile Assemblies of Actin and Myosin in Nonmuscle Cells
Contractile assemblies of actin and myosin, resembling small-scale versions of muscle fibers, are present also in nonmuscle cells. As in muscle, the actin filaments in these contractile assemblies are interdigitated with bipolar filaments of myosin II, consisting of 15 to 20 myosin II molecules, which produce contraction by sliding the actin filaments relative to one another (Figure 11.26). The actin filaments in contractile bundles in nonmuscle cells are also associated with tropomyosin, which facilitates their interaction with myosin II, probably by competing with filamin for binding sites on actin.
Figure 11.26
Contractile assemblies in nonmuscle cells. Bipolar filaments of myosin II produce contraction by sliding actin filaments in opposite directions. Two examples of contractile assemblies in nonmuscle cells, stress fibers and adhesion belts, were discussed earlier with respect to attachment of the actin cytoskeleton to regions of cell-substrate and cell-cell contacts (see Figures 11.13 and 11.14). The contraction of stress fibers produces tension across the cell, allowing the cell to pull on a substrate (e.g., the extracellular matrix) to which it is anchored. The contraction of adhesion belts alters the shape of epithelial cell sheets: a process that is particularly important during embryonic development, when sheets of epithelial cells fold into structures such as tubes.
The most dramatic example of actin-myosin contraction in nonmuscle cells, however, is provided by cytokinesisthe division of a cell into two following mitosis (Figure 11.27). Toward the end of mitosis in animal cells, a contractile ring consisting of actin filaments and myosin II assembles just underneath the plasma membrane. Its contraction pulls the plasma membrane progressively inward, constricting the center of the cell and pinching it in two. Interestingly, the thickness of the contractile ring remains constant as it contracts, implying that actin filaments disassemble as contraction proceeds. The ring then disperses completely following cell division.
Figure 11.27
Cytokinesis. Following completion of mitosis (nuclear division), a contractile ring consisting of actin filaments and myosin II divides the cell in two.
http://www.ncbi.nlm.nih.gov/books/NBK9961/
This is good. I don’t recall seeing it in the original comment. I am very aware of the actin myosin troponin connection in heart and in skeletal muscle, and I did know about the nonmuscle work. I won’t deal with it now, and I have been working with Aviral now online for 2 hours.
I have had a considerable background from way back in atomic orbital theory, physical chemistry, organic chemistry, and the equilibrium necessary for cations and anions. Despite the calcium role in contraction, I would not discount hypomagnesemia in having a disease role because of the intracellular-extracellular connection. The description you pasted reminds me also of a lecture given a few years ago by the Nobel Laureate that year on the mechanism of cell division.
PUT IT IN CONTEXT OF CANCER CELL MOVEMENT
The contraction of skeletal muscle is triggered by nerve impulses, which stimulate the release of Ca2+ from the sarcoplasmic reticuluma specialized network of internal membranes, similar to the endoplasmic reticulum, that stores high concentrations of Ca2+ ions. The release of Ca2+ from the sarcoplasmic reticulum increases the concentration of Ca2+ in the cytosol from approximately 10-7 to 10-5 M. The increased Ca2+ concentration signals muscle contraction via the action of two accessory proteins bound to the actin filaments: tropomyosin and troponin (Figure 11.25). Tropomyosin is a fibrous protein that binds lengthwise along the groove of actin filaments. In striated muscle, each tropomyosin molecule is bound to troponin, which is a complex of three polypeptides: troponin C (Ca2+-binding), troponin I (inhibitory), and troponin T (tropomyosin-binding). When the concentration of Ca2+ is low, the complex of the troponins with tropomyosin blocks the interaction of actin and myosin, so the muscle does not contract. At high concentrations, Ca2+ binding to troponin C shifts the position of the complex, relieving this inhibition and allowing contraction to proceed.
Figure 11.25
Association of tropomyosin and troponins with actin filaments. (A) Tropomyosin binds lengthwise along actin filaments and, in striated muscle, is associated with a complex of three troponins: troponin I (TnI), troponin C (TnC), and troponin T (TnT). In (more ) Contractile Assemblies of Actin and Myosin in Nonmuscle Cells
Contractile assemblies of actin and myosin, resembling small-scale versions of muscle fibers, are present also in nonmuscle cells. As in muscle, the actin filaments in these contractile assemblies are interdigitated with bipolar filaments of myosin II, consisting of 15 to 20 myosin II molecules, which produce contraction by sliding the actin filaments relative to one another (Figure 11.26). The actin filaments in contractile bundles in nonmuscle cells are also associated with tropomyosin, which facilitates their interaction with myosin II, probably by competing with filamin for binding sites on actin.
Figure 11.26
Contractile assemblies in nonmuscle cells. Bipolar filaments of myosin II produce contraction by sliding actin filaments in opposite directions. Two examples of contractile assemblies in nonmuscle cells, stress fibers and adhesion belts, were discussed earlier with respect to attachment of the actin cytoskeleton to regions of cell-substrate and cell-cell contacts (see Figures 11.13 and 11.14). The contraction of stress fibers produces tension across the cell, allowing the cell to pull on a substrate (e.g., the extracellular matrix) to which it is anchored. The contraction of adhesion belts alters the shape of epithelial cell sheets: a process that is particularly important during embryonic development, when sheets of epithelial cells fold into structures such as tubes.
The most dramatic example of actin-myosin contraction in nonmuscle cells, however, is provided by cytokinesisthe division of a cell into two following mitosis (Figure 11.27). Toward the end of mitosis in animal cells, a contractile ring consisting of actin filaments and myosin II assembles just underneath the plasma membrane. Its contraction pulls the plasma membrane progressively inward, constricting the center of the cell and pinching it in two. Interestingly, the thickness of the contractile ring remains constant as it contracts, implying that actin filaments disassemble as contraction proceeds. The ring then disperses completely following cell division.
Figure 11.27
Cytokinesis. Following completion of mitosis (nuclear division), a contractile ring consisting of actin filaments and myosin II divides the cell in two.
http://www.ncbi.nlm.nih.gov/books/NBK9961/
This is good. I don’t recall seeing it in the original comment. I am very aware of the actin myosin troponin connection in heart and in skeletal muscle, and I did know about the nonmuscle work. I won’t deal with it now, and I have been working with Aviral now online for 2 hours.
I have had a considerable background from way back in atomic orbital theory, physical chemistry, organic chemistry, and the equilibrium necessary for cations and anions. Despite the calcium role in contraction, I would not discount hypomagnesemia in having a disease role because of the intracellular-extracellular connection. The description you pasted reminds me also of a lecture given a few years ago by the Nobel Laureate that year on the mechanism of cell division.
PUT IT IN CONTEXT OF CANCER CELL MOVEMENT
The contraction of skeletal muscle is triggered by nerve impulses, which stimulate the release of Ca2+ from the sarcoplasmic reticuluma specialized network of internal membranes, similar to the endoplasmic reticulum, that stores high concentrations of Ca2+ ions. The release of Ca2+ from the sarcoplasmic reticulum increases the concentration of Ca2+ in the cytosol from approximately 10-7 to 10-5 M. The increased Ca2+ concentration signals muscle contraction via the action of two accessory proteins bound to the actin filaments: tropomyosin and troponin (Figure 11.25). Tropomyosin is a fibrous protein that binds lengthwise along the groove of actin filaments. In striated muscle, each tropomyosin molecule is bound to troponin, which is a complex of three polypeptides: troponin C (Ca2+-binding), troponin I (inhibitory), and troponin T (tropomyosin-binding). When the concentration of Ca2+ is low, the complex of the troponins with tropomyosin blocks the interaction of actin and myosin, so the muscle does not contract. At high concentrations, Ca2+ binding to troponin C shifts the position of the complex, relieving this inhibition and allowing contraction to proceed.
Figure 11.25
Association of tropomyosin and troponins with actin filaments. (A) Tropomyosin binds lengthwise along actin filaments and, in striated muscle, is associated with a complex of three troponins: troponin I (TnI), troponin C (TnC), and troponin T (TnT). In (more ) Contractile Assemblies of Actin and Myosin in Nonmuscle Cells
Contractile assemblies of actin and myosin, resembling small-scale versions of muscle fibers, are present also in nonmuscle cells. As in muscle, the actin filaments in these contractile assemblies are interdigitated with bipolar filaments of myosin II, consisting of 15 to 20 myosin II molecules, which produce contraction by sliding the actin filaments relative to one another (Figure 11.26). The actin filaments in contractile bundles in nonmuscle cells are also associated with tropomyosin, which facilitates their interaction with myosin II, probably by competing with filamin for binding sites on actin.
Figure 11.26
Contractile assemblies in nonmuscle cells. Bipolar filaments of myosin II produce contraction by sliding actin filaments in opposite directions. Two examples of contractile assemblies in nonmuscle cells, stress fibers and adhesion belts, were discussed earlier with respect to attachment of the actin cytoskeleton to regions of cell-substrate and cell-cell contacts (see Figures 11.13 and 11.14). The contraction of stress fibers produces tension across the cell, allowing the cell to pull on a substrate (e.g., the extracellular matrix) to which it is anchored. The contraction of adhesion belts alters the shape of epithelial cell sheets: a process that is particularly important during embryonic development, when sheets of epithelial cells fold into structures such as tubes.
The most dramatic example of actin-myosin contraction in nonmuscle cells, however, is provided by cytokinesisthe division of a cell into two following mitosis (Figure 11.27). Toward the end of mitosis in animal cells, a contractile ring consisting of actin filaments and myosin II assembles just underneath the plasma membrane. Its contraction pulls the plasma membrane progressively inward, constricting the center of the cell and pinching it in two. Interestingly, the thickness of the contractile ring remains constant as it contracts, implying that actin filaments disassemble as contraction proceeds. The ring then disperses completely following cell division.
Figure 11.27
Cytokinesis. Following completion of mitosis (nuclear division), a contractile ring consisting of actin filaments and myosin II divides the cell in two.
http://www.ncbi.nlm.nih.gov/books/NBK9961/
This is good. I don’t recall seeing it in the original comment. I am very aware of the actin myosin troponin connection in heart and in skeletal muscle, and I did know about the nonmuscle work. I won’t deal with it now, and I have been working with Aviral now online for 2 hours.
I have had a considerable background from way back in atomic orbital theory, physical chemistry, organic chemistry, and the equilibrium necessary for cations and anions. Despite the calcium role in contraction, I would not discount hypomagnesemia in having a disease role because of the intracellular-extracellular connection. The description you pasted reminds me also of a lecture given a few years ago by the Nobel Laureate that year on the mechanism of cell division.
PUT IT IN CONTEXT OF CANCER CELL MOVEMENT
The contraction of skeletal muscle is triggered by nerve impulses, which stimulate the release of Ca2+ from the sarcoplasmic reticuluma specialized network of internal membranes, similar to the endoplasmic reticulum, that stores high concentrations of Ca2+ ions. The release of Ca2+ from the sarcoplasmic reticulum increases the concentration of Ca2+ in the cytosol from approximately 10-7 to 10-5 M. The increased Ca2+ concentration signals muscle contraction via the action of two accessory proteins bound to the actin filaments: tropomyosin and troponin (Figure 11.25). Tropomyosin is a fibrous protein that binds lengthwise along the groove of actin filaments. In striated muscle, each tropomyosin molecule is bound to troponin, which is a complex of three polypeptides: troponin C (Ca2+-binding), troponin I (inhibitory), and troponin T (tropomyosin-binding). When the concentration of Ca2+ is low, the complex of the troponins with tropomyosin blocks the interaction of actin and myosin, so the muscle does not contract. At high concentrations, Ca2+ binding to troponin C shifts the position of the complex, relieving this inhibition and allowing contraction to proceed.
Figure 11.25
Association of tropomyosin and troponins with actin filaments. (A) Tropomyosin binds lengthwise along actin filaments and, in striated muscle, is associated with a complex of three troponins: troponin I (TnI), troponin C (TnC), and troponin T (TnT). In (more ) Contractile Assemblies of Actin and Myosin in Nonmuscle Cells
Contractile assemblies of actin and myosin, resembling small-scale versions of muscle fibers, are present also in nonmuscle cells. As in muscle, the actin filaments in these contractile assemblies are interdigitated with bipolar filaments of myosin II, consisting of 15 to 20 myosin II molecules, which produce contraction by sliding the actin filaments relative to one another (Figure 11.26). The actin filaments in contractile bundles in nonmuscle cells are also associated with tropomyosin, which facilitates their interaction with myosin II, probably by competing with filamin for binding sites on actin.
Figure 11.26
Contractile assemblies in nonmuscle cells. Bipolar filaments of myosin II produce contraction by sliding actin filaments in opposite directions. Two examples of contractile assemblies in nonmuscle cells, stress fibers and adhesion belts, were discussed earlier with respect to attachment of the actin cytoskeleton to regions of cell-substrate and cell-cell contacts (see Figures 11.13 and 11.14). The contraction of stress fibers produces tension across the cell, allowing the cell to pull on a substrate (e.g., the extracellular matrix) to which it is anchored. The contraction of adhesion belts alters the shape of epithelial cell sheets: a process that is particularly important during embryonic development, when sheets of epithelial cells fold into structures such as tubes.
The most dramatic example of actin-myosin contraction in nonmuscle cells, however, is provided by cytokinesisthe division of a cell into two following mitosis (Figure 11.27). Toward the end of mitosis in animal cells, a contractile ring consisting of actin filaments and myosin II assembles just underneath the plasma membrane. Its contraction pulls the plasma membrane progressively inward, constricting the center of the cell and pinching it in two. Interestingly, the thickness of the contractile ring remains constant as it contracts, implying that actin filaments disassemble as contraction proceeds. The ring then disperses completely following cell division.
Figure 11.27
Cytokinesis. Following completion of mitosis (nuclear division), a contractile ring consisting of actin filaments and myosin II divides the cell in two.
http://www.ncbi.nlm.nih.gov/books/NBK9961/
This is good. I don’t recall seeing it in the original comment. I am very aware of the actin myosin troponin connection in heart and in skeletal muscle, and I did know about the nonmuscle work. I won’t deal with it now, and I have been working with Aviral now online for 2 hours.
I have had a considerable background from way back in atomic orbital theory, physical chemistry, organic chemistry, and the equilibrium necessary for cations and anions. Despite the calcium role in contraction, I would not discount hypomagnesemia in having a disease role because of the intracellular-extracellular connection. The description you pasted reminds me also of a lecture given a few years ago by the Nobel Laureate that year on the mechanism of cell division.
PUT IT IN CONTEXT OF CANCER CELL MOVEMENT
The contraction of skeletal muscle is triggered by nerve impulses, which stimulate the release of Ca2+ from the sarcoplasmic reticuluma specialized network of internal membranes, similar to the endoplasmic reticulum, that stores high concentrations of Ca2+ ions. The release of Ca2+ from the sarcoplasmic reticulum increases the concentration of Ca2+ in the cytosol from approximately 10-7 to 10-5 M. The increased Ca2+ concentration signals muscle contraction via the action of two accessory proteins bound to the actin filaments: tropomyosin and troponin (Figure 11.25). Tropomyosin is a fibrous protein that binds lengthwise along the groove of actin filaments. In striated muscle, each tropomyosin molecule is bound to troponin, which is a complex of three polypeptides: troponin C (Ca2+-binding), troponin I (inhibitory), and troponin T (tropomyosin-binding). When the concentration of Ca2+ is low, the complex of the troponins with tropomyosin blocks the interaction of actin and myosin, so the muscle does not contract. At high concentrations, Ca2+ binding to troponin C shifts the position of the complex, relieving this inhibition and allowing contraction to proceed.
Figure 11.25
Association of tropomyosin and troponins with actin filaments. (A) Tropomyosin binds lengthwise along actin filaments and, in striated muscle, is associated with a complex of three troponins: troponin I (TnI), troponin C (TnC), and troponin T (TnT). In (more ) Contractile Assemblies of Actin and Myosin in Nonmuscle Cells
Contractile assemblies of actin and myosin, resembling small-scale versions of muscle fibers, are present also in nonmuscle cells. As in muscle, the actin filaments in these contractile assemblies are interdigitated with bipolar filaments of myosin II, consisting of 15 to 20 myosin II molecules, which produce contraction by sliding the actin filaments relative to one another (Figure 11.26). The actin filaments in contractile bundles in nonmuscle cells are also associated with tropomyosin, which facilitates their interaction with myosin II, probably by competing with filamin for binding sites on actin.
Figure 11.26
Contractile assemblies in nonmuscle cells. Bipolar filaments of myosin II produce contraction by sliding actin filaments in opposite directions. Two examples of contractile assemblies in nonmuscle cells, stress fibers and adhesion belts, were discussed earlier with respect to attachment of the actin cytoskeleton to regions of cell-substrate and cell-cell contacts (see Figures 11.13 and 11.14). The contraction of stress fibers produces tension across the cell, allowing the cell to pull on a substrate (e.g., the extracellular matrix) to which it is anchored. The contraction of adhesion belts alters the shape of epithelial cell sheets: a process that is particularly important during embryonic development, when sheets of epithelial cells fold into structures such as tubes.
The most dramatic example of actin-myosin contraction in nonmuscle cells, however, is provided by cytokinesisthe division of a cell into two following mitosis (Figure 11.27). Toward the end of mitosis in animal cells, a contractile ring consisting of actin filaments and myosin II assembles just underneath the plasma membrane. Its contraction pulls the plasma membrane progressively inward, constricting the center of the cell and pinching it in two. Interestingly, the thickness of the contractile ring remains constant as it contracts, implying that actin filaments disassemble as contraction proceeds. The ring then disperses completely following cell division.
Figure 11.27
Cytokinesis. Following completion of mitosis (nuclear division), a contractile ring consisting of actin filaments and myosin II divides the cell in two.
http://www.ncbi.nlm.nih.gov/books/NBK9961/
This is good. I don’t recall seeing it in the original comment. I am very aware of the actin myosin troponin connection in heart and in skeletal muscle, and I did know about the nonmuscle work. I won’t deal with it now, and I have been working with Aviral now online for 2 hours.
I have had a considerable background from way back in atomic orbital theory, physical chemistry, organic chemistry, and the equilibrium necessary for cations and anions. Despite the calcium role in contraction, I would not discount hypomagnesemia in having a disease role because of the intracellular-extracellular connection. The description you pasted reminds me also of a lecture given a few years ago by the Nobel Laureate that year on the mechanism of cell division.
I actually consider this amazing blog , âSAME SCIENTIFIC IMPACT: Scientific Publishing –
Open Journals vs. Subscription-based « Pharmaceutical Intelligenceâ, very compelling plus the blog post ended up being a good read.
Many thanks,Annette
I actually consider this amazing blog , âSAME SCIENTIFIC IMPACT: Scientific Publishing –
Open Journals vs. Subscription-based « Pharmaceutical Intelligenceâ, very compelling plus the blog post ended up being a good read.
Many thanks,Annette