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At least 199 records · Page 11Linked to original sources
PubMed2006

The folding pathway of spectrin R17 from experiment and simulation: using experimentally validated MD simulations to characterize States hinted at by experiment.

We present an experimental and computational analysis of the folding pathway of the 17th domain of chicken brain alpha-spectrin, R17. Wild-type R17 folds in a two-state manner and the chevron plot (plot of the logarithm of the observed rate constant against concentration of urea) shows essentially linear folding and unfolding arms. A number of mutant proteins, however, show a change in slope of the unfolding arm at high concentration of denaturant, hinting at complexity in the folding landscape. Through a combination of mutational studies and high temperature molecular dynamics simulations we show that the folding of R17 can be described by a model with two sequential transition states separated by an intermediate species. The rate limiting transition state for folding in water has been characterized both through experimental Phi-value analysis and by simulation. In contrast, a detailed analysis of the transition state predicted to dominate under highly denaturing conditions is only possible by simulation.

Amino Acid Sequence↗
PubMed1985

Anti-refluxing Roux-en-Y biliary drainage valve for hepatic portoenterostomy: animal experiments and clinical experience.

In five dogs, we have created an anti-refluxing Roux en-Y jejunal anastomosis by removing the antimesenteric half of the seromusculature from five cm of the biliary limb proximal to the anastomosis prior to coating the gastric and biliary limbs. In the presence of increasing intraluminal pressure in the gastric and vertical limbs of the Y, the wall of the biliary limb collapses and occludes the lumen, acting as a nonrefluxing one-way valve. All three limbs of the Y were then exteriorized as enterostomies. Saline was instilled into either the gastric or distal limb with the other clamped. There was never reflux from the biliary limb despite intraluminal pressures of 200 mm Hg. We have used the anti-refluxing valve in seven infants. Three are alive at 17, 7, and 2 months postoperatively, one of which had a brief episode of fever without leukocytosis or increasing jaundice. Three have died of unresolved obstruction and one has been lost to follow-up.

Animals↗
PubMed2002

Intracardiac phased-array imaging: methods and initial clinical experience with high resolution, under blood visualization: initial experience with intracardiac phased-array ultrasound.

OBJECTIVES: This study was designed to test the feasibility of high-resolution phased-array intracardiac imaging. BACKGROUND: Intracardiac echocardiographic imaging of the heart during interventional electrophysiologic (EP) procedures has been limited by inadequate ultrasound penetration and absence of Doppler hemodynamic and flow information produced by rotating mechanical ultrasound elements. METHODS: A 10F (3.2 mm) phased-array, variable 5.5 to 10 MHz frequency imaging catheter with a four-way deflectable tip was applied in 24 patients undergoing EP studies. Sixteen prespecified cardiac targets were imaged from a right heart venue. RESULTS: Fifteen patients had no underlying organic heart disease; nine had ischemic, cardiomyopathic, valvular or congenital heart disorders. Longitudinal and short-axis imaging readily disclosed each cardiac valve, support structures and chamber, as well as the pericardium, right and left atrial appendages, the junction of the right atrium and superior vena cava, crista terminalis, tricuspid valve isthmus, coronary sinus orifice, membranous fossa ovalis and pulmonary veins. The average target depth was 8.8+/-1.5 cm (range 0.5 to 15 cm), with adequate penetration at a 7.5 MHz imaging frequency. Color flow and Doppler utilities clearly characterized transaortic and pulmonic valve and pulmonary vein blood flow, including during low output states. CONCLUSIONS: These first human studies with this technology demonstrate the methods, feasibility and utility of intracardiac phased-array vector and Doppler imaging for long-axis, apex-to-base global cardiac imaging. High resolution of endocardial structures and catheters suggests additional utility for visualizing interventional procedures from the right heart.

Arrhythmias, Cardiac↗
PubMed2004

How do patients with rheumatic disease experience their relationship with their doctors? A qualitative study of experiences of stress and support in the doctor-patient relationship.

This study is evaluated what patients with rheumatic disease perceive as important in their medical encounters. We interviewed two groups of patients: one with a well-defined inflammatory condition (rheumatoid arthritis (RA) or ankylosing spondylitis) (n = 12) and one with non-inflammatory widespread chronic pain such as fibromyalgia (n = 14). Both groups focused on their relationship to their doctor. Two central themes emerged as of importance: 'to be seen' and 'to be believed'. However, these themes had different connotations for the two groups. For the patients with inflammatory conditions, 'to be seen' implied being seen as an individual and not as a mere diagnosis, and 'to be believed' as far as pain and suffering were concerned. For patients with non-inflammatory chronic pain 'to be seen' and 'to be believed' primarily implied being able to obtain a useful somatic diagnosis. Practical implications of these findings are discussed.

Adult↗
PubMed1999

Why have ten or so nontoxic, retrovirus integrase inhibitors not been made available for AIDS treatment? A ten-year experience [correction of experiment] must liberate them.

We detected in 1989, with the inhibitor test of proviral insertion into c-erb B erythroblastosis, two retrovirus integrase inhibitors: hydroxy-methyl-ellipticine and acriflavine. They have been used for ten years in AIDS patients with high efficacy and no toxicity. Since vitamin B12 and cobalt, which it contains, have been detected as HIV1-integrase inhibitors by an in-vitro test, we have also used vitamin B12 (combined with folic acid), whose clinical action has been remarkable. Ten or so other compounds have been detected by such in-vitro tests, among which there are many compounds (such as flavones) which are used in many conditions and are not toxic.

Acquired Immunodeficiency Syndrome↗
PubMed2000

Tapetoretinal degenerations: experiences, experiments and expectations.

Tapetoretinal degenerations are a common cause for vision problems, but have until recently not been amenable to rational treatment. With rapidly increasing insights into basic neurobiology and pathobiology this has now begun to change. From having been a relatively small group of largely unknown yet fairly prevalent disorders, they are rapidly forming a large set of well defined diseases, and it is easy to predict that our knowledge about them will continue to increase for many years to come. Vitamin A (15,000 IU daily) is currently the only rational treatment available. However, in experimental animals, therapy strategies are now actively being developed along several different lines. Apoptotic photoreceptor cell death can be delayed with different drugs, and at least one of them, diltiazem, is approved for human use in cardiovascular diseases. It remains to be seen if it has any clinically significant effect in human tapetoretinal degenerations. Other strategies aim at counteracting the production of harmful protein variants, acting either on DNA or mRNA levels. Transgenes can also be used to induce the production of important but missing metabolic components. Finally, cells or retina sheets can be transplanted, either to replace failing cells or as a source for missing trophic factors. Neither of these strategies has yet been transferred to humans, but trials are under way. With the high increase in the flow of new information on tapetoretinal disorders, much more precise diagnoses and much improved treatments are soon to be expected, augmenting considerably the possibilities for ophthalmologists to help patients with such diseases. It is not likely that there will be a single treatment for all the many varieties. Instead, we are most likely going to see pharmacological treatments for some of them, DNA transfers for some, and transplantations for others.

Amino Acid Sequence↗
PubMed1992

An audit of five years' experience of pregnancy in spinal cord damaged women. A regional unit's experience and a review of the literature.

In a retrospective review of pregnancy and delivery in 8 spinal cord damaged women managed at Hexham General Hospital Spinal and Maternity Units between 1986 and 1991, antenatal complications included urinary tract infection, anaemia, constipation, suspected deep venous thrombosis and pressure sores. Five of the 8 patients had adductor spasms. Autonomic hyperreflexia occurred in 2 patients in the antenatal period, and in one patient in the postpartum period. Four patients were delivered by caesarean section, and 4 of the 8 patients had breech presentation of the foetus at delivery. The perinatal outcome was good.

Female↗