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At least 865 records · Page 48Linked to original sources
PubMed2004

Domain swapping is a consequence of minimal frustration.

The same energy landscape principles associated with the folding of proteins into their monomeric conformations should also describe how these proteins oligomerize into domain-swapped conformations. We tested this hypothesis by using a simplified model for the epidermal growth factor receptor pathway substrate 8 src homology 3 domain protein, both of whose monomeric and domain-swapped structures have been solved. The model, which we call the symmetrized Gō-type model, incorporates only information regarding the monomeric conformation in an energy function for the dimer to predict the domain-swapped conformation. A striking preference for the correct domain-swapped structure was observed, indicating that overall monomer topology is a main determinant of the structure of domain-swapped dimers. Furthermore, we explore the free energy surface for domain swapping by using our model to characterize the mechanism of oligomerization.

Binding Sites↗
PubMed1989

Otitis media. Update on a common, frustrating problem.

Otitis media is extremely common in infants and young children and has important ramifications for the children, their families, and society in general. The essential elements of management are early diagnosis, adequate therapy with appropriate antibacterial agents, and conscientious follow-up to promptly detect and treat potential and actual complications. The primary care physician who treats young children is the critical health-care provider in the diagnosis of otitis media, initial treatment, and timely referral when appropriate.

Child↗
PubMed1991

Alzheimer's disease. Recognizing and treating a frustrating condition.

Alzheimer's disease is a costly illness affecting large numbers of older Americans, and its prevalence is increasing. The major symptom of the condition is progressive forgetfulness. The course is variable, depending on which areas of the brain are affected earliest and most severely. In diagnosing Alzheimer's disease, it is important to rule out other types of dementia that may be treatable, as well as systemic and affective disorders and other brain diseases. The Mini-Mental State Examination and the category fluency test are often diagnostically useful. There is no evidence that any of the therapeutic agents studied so far are of much value, but pharmacologic agents can be useful in treating the depression, psychoses, and anxiety that may accompany cognitive decline. Patients cared for at home need a structured, orderly environment that has been modified for their safety.

Alzheimer Disease↗
PubMed2004

A neglected but frustrating ergonomic issue: the thoracoscopic trocar.

One of the problems encountered during thoracoscopic operations is the frequent soiling of the endoscope by blood dripping along the trocar sheath. This study was conducted in order to evaluate the reality of this problem. The study consisted of three parts: a questionnaire was sent to surgeons performing thoracic procedures, data were collected during thoracoscopic operations, and a literature study was done in the patents index. The questionnaire was sent to 210 surgeons. Sixty-eight of them replied. During 44 operations the following data were recorded: Type and duration of the operation, number of times the lens and the trocar had to be cleaned. On the Internet and in a patents index [ 1 ] a search was conducted with the key words "thoracoscopy", "trocar" and "bleeding". All solutions for the problem mentioned above were listed. Ninety-seven percent of surgeons answered and recognised the problem: 68% of the respondents considered it is a troublesome one. Data were collected during 44 operations. In 41% of the operations the problem did not occur, which means it was not necessary to clean either the lens or the cannula. In 34% it happened one to two times and in 25% of the procedures it occurred even more often. If it occurred, the scope had to be cleaned on average once in about 10 minutes and the trocar had to be cleaned once in about 15 minutes. The longer the operation lasted the more often the lens and/or the trocar had to be cleaned. Out of the 11 procedures that lasted less than 15 minutes, the trocar was never cleaned, and the lens had to be wiped only 0.18 times per procedure. Out of the 18 procedures that lasted more than 20 minutes, the lens was cleaned 2.8 times per procedure and the trocar 1.6 times per procedure. Soiling of the endoscope during thoracoscopic procedures is a real concern that calls for new technical solutions in order to make video-assisted thoracic surgery safer for the patient and more pleasant to the surgeon.

Journal Article↗
PubMed2002

Male infertility: tales of progress and frustration.

This article describes andrology research, inspired by Professor Michael Hull, to develop sperm function tests and to understand the basic causes of male infertility. No generally acceptable sperm function test has yet been devised. Computer-assisted semen analysis (CASA) proved of limited value in predicting the outcome of in vitro fertilization (IVF) although it was more useful in donor insemination. High intracellular Ca2+ activity, [Ca2+]i, is involved in decreasing motility in cryopreserved sperm. Capacitative calcium entry after depletion of intracellular stores may generate the sustained increase in [Ca2+]i that initiates the acrosome reaction. Our data support the presence of Ca2+ stores as thapsigargin increased [Ca2+]i in sperm in Ca2+ -free medium. Recent observations indicate that cAMP enhances capacitative calcium entry, acting upstream of emptying of the store. Excess reactive oxygen species (ROS) is an important cause of sperm pathology but at low concentrations ROS regulate capacitation. Our evidence shows that ROS are produced by leucocytes present in sperm suspensions. We have been unable to demonstrate that human sperm produce ROS. The relationship between ROS production and lipid peroxidation indicates that sperm from some men are resistant to lipid peroxidation, possibly because of better antioxidant defences. We conclude that the future of andrology lies in the identification of the basic causes of infertility and not in more detailed descriptions of the properties of semen.

Diagnostic Techniques, Endocrine↗