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Biomedical subjects

M Smith

Publications and source records attributed to M Smith.

At least 1,063 records · Page 59Linked to original sources

Sulfhydryl/disulfide forms of rat liver 3-hydroxy-3-methylglutaryl coenzyme A reductase.

Using radiation inactivation and immunoblotting techniques, evidence for functionally active forms of rat liver 3-hydroxy-3-methylglutaryl coenzyme A reductase with molecular weights of about 100,000 and 200,000 was obtained. In liver microsomes isolated from rats fed both mevinolin and colestipol, the Mr 100,000 form was the predominant species, whereas in microsomes from animals fed only colestipol, the Mr 200,000 species was the major form. This Mr 200,000 form could be converted to the Mr 100,000 form by addition of dithiothreitol or beta-mercaptoethanol. Although both forms appear to possess catalytic activity, the Mr 200,000 species displays sigmoidal kinetics with respect to the concentration of NADPH, whereas the Mr 100,000 form exhibits typical hyperbolic kinetics.

Animals↗

Aequorin detects increased cytoplasmic calcium in platelets stimulated with phorbol ester or diacylglycerol.

A biochemical pathway to platelet activation involving protein kinase C has been deemed "Ca2+-independent", because the intracellular fluorophore quin2 indicates no rise in cytoplasmic [Ca2+] in platelets stimulated by certain agonists. However, unlike quin2, the Ca2+-sensitive photoprotein aequorin demonstrates a rise in [Ca2+] when platelet aggregation is induced by phorbol ester or diacylglycerol. Aequorin and quin2 appear to report different aspects of Ca2+ homeostasis, and the absence of a quin2 signal may not be sufficient to establish that a metabolic pathway is "Ca2+-independent".

Aequorin↗

Activation of rat liver microsomal 3-hydroxy-3-methylglutaryl coenzyme A reductase by NADPH. Effects of dietary treatments.

The sigmoidal curves observed for rat liver microsomal 3-hydroxy-3-methylglutaryl-CoA (HMG-CoA) reductase with NADPH as the varied substrate were markedly affected by feeding the animals diets containing colestipol, mevinolin and colestipol or cholesterol. Feeding of mevinolin and colestipol decreased the S0.5 for NADPH from 270 to 40 microM, while cholesterol feeding increased the value to 1.3 mM. Immuno-blotting analysis revealed that the Mr 100,000 form of HMG-CoA reductase predominated in cases where the S0.5 value was lowest, and the Mr 200,000 species was the major form where the S0.5 values were highest. Activation of HMG-CoA reductase by NADPH was not due to conversion of the Mr 200,000 form to the 100,000 form.

Allosteric Regulation↗

Labor risk assessment in a rural community hospital.

Unanticipated perinatal catastrophe in a rural community hospital is responsible for the deaths of many potentially salvageable infants. An intrapartum risk scoring system was designed to help anticipate infants needing skilled resuscitation at the rural community hospital. Thirty-three percent of infants whose mothers scored as high risk (greater than or equal to 10) required resuscitation while only 6% of infants whose mothers scored less than 10 required resuscitation. Sequential Apgar scores of infants in need of resuscitation attended by a skilled resuscitator showed significant improvement compared with Apgar scores of infants not attended by a skilled resuscitator, suggesting at least a short-term benefit for early identification of the infant at risk.

Apgar Score↗

Measurement of ionized calcium in blood platelets with the photoprotein aequorin. Comparison with Quin 2.

The Ca2+-sensitive photoprotein aequorin (Mr = 20,000) was introduced into human blood platelets by incubation with 10 mM EGTA and 5 mM ATP. Platelet cytoplasmic and granule contents were retained during the loading procedure, and platelet morphology, aggregation, and secretion in response to agonists were normal after aequorin loading. Luminescence indicated an apparent resting cytoplasmic ionized calcium concentration [( Cai2+]) of 2-4 microM in media containing 1 mM Ca2+ and of 0.8-2 microM in 2-4 mM EGTA. The Ca2+ ionophore A23187 and the enzyme thrombin produced dose-related luminescent signals in both Ca2+-containing and EGTA-containing media. Peak [Cai2+] after A23187 or thrombin stimulation of aequorin-loaded platelets was 2-10 microM, while peak [Cai2+] determined using Quin 2 as the [Cai2+] indicator was at least 1 log unit lower. In platelets loaded with both aequorin and Quin 2, the aequorin signal was delayed but not reduced in amplitude. Aequorin loading of Quin 2-loaded cells had no effect on the Quin 2 signal. Ca2+ buffering by Quin 2 (intracellular concentration greater than 1 mM) is also supported by a reciprocal relationship between [Quin 2] and peak [Cai2+] stimulated by A23187 in the presence of EGTA. Parallel experiments with Quin 2 and aequorin may identify inhomogeneous [Cai2+] in platelets and give a more complete picture of platelet Ca2+ homeostasis than either indicator alone.

Aequorin↗

Antepartum fetal heart rate testing. XII. The effect of manual manipulation of the fetus on the nonstress test.

A prospective study of 790 patients was performed in order to examine the role of manual manipulation of the fetus in the nonstress test. The patients were assigned randomly to two groups based on the last two digits of their hospital number. The odd-numbered patients underwent manual manipulation of the fetus prior to the onset of the nonstress test; the even-numbered patients did not. There was no significant difference between the two groups with respect to the indications for testing and the total number of tests. There was no statistically significant difference between the two groups with respect to the ratio of reactive to nonreactive nonstress tests and the mean duration of testing. Simple manual manipulation of the fetus does not seem to change the outcome in antepartum fetal heart rate testing when the nonstress test is the primary one.

Diabetes Mellitus↗

Education for primary health care.

Postrevolutionary Nicaragua has developed a new health system in which primary health care is a central component. Great progress has been made in correcting the poor health conditions that existed prior to the revolution. As part of an interdisciplinary health team that emphasizes prevention and community service, physicians in the new system play a different role than they did previously. Training for health workers of all types has been expanded. However, scarce teaching and curricular resources have restrained progress in this area. The U.S. based Committee for Health Rights in Central America (CHRICA) has collaborated with the Nicaraguan Ministry of Health to organize two Colloquia on Health in Nicaragua in the past two years. These Colloquia brought together North American participants who provided current medical training and Nicaraguan participants who provided information about the new health system. The Colloquia, whose participants were eligible to receive CME credit from the UCSF School of Medicine, have led to continuing educational exchanges between health care personnel in the two countries.

Education, Medical↗

Efficient expression of the Escherichia coli leuB gene in yeast.

Efficient expression of the Escherichia coli leuB (beta-isopropylmalate dehydrogenase) gene occurred in yeast after in vitro DNase digestion and religation of plasmid bound leuB and the yeast HIS3 DNA which placed the 5' end of the yeast HIS3 gene immediately adjacent to the coding region of the E. coli leuB gene. Two structurally distinct classes of gene fusions were constructed, each involved portions of the yeast HIS3 gene which contributed DNA sequences responsible for leuB expression in yeast. The first class involved fusion of the HIS3 coding region to bacterial DNA resulting in the production of a fusion protein with beta-isopropylmalate dehydrogenase activity. The second class consisted of bacterial DNA, including the leuB coding region, fused to the HIS3 promotor region with the absence of any portion of the HIS3 coding region. In both constructions the HIS3 promotor region is required for transcription, however, translation of the class two fusion is initiated at a bacterial DNA coded AUG, and the 5' end of the mRNA coded by the leuB gene mapped predominantly at bacterial DNA sequences. The DNA sequence responsible for the 5' end of the HIS3 mRNAs remain in the class two gene fusions but this did not preclude the initiation of transcription at bacterial DNA sequences. The pattern of mRNA initiation at bacterial DNA suggests that DNA sequences at, or adjacent to, the site of transcription initiation are involved in the determination of the sites of initiation, and perhaps the frequency at which initiation occurs.

3-Isopropylmalate Dehydrogenase↗

Occult, high-risk endometrial cancer.

In a series of 173 consecutive patients with endometrial cancer treated by a fixed protocol 62 tumors (36%) appear "estrogen independent," i.e. there is no history of estrogen ingestion and no recognized risk factors such as obesity or diabetes mellitus. A high proportion of these tumors are of advanced stage and grade. Prognosis is poorer and mortality higher than for "estrogen-dependent" tumors. Twenty-two tumors were truly occult (no spontaneous vaginal bleeding). Factors which identify this high-risk group are described and the reasons for delay in diagnosis discussed. Spread by intraperitoneal dissemination is considered a major factor in the poorer prognosis. Cytology of peritoneal washings is a useful diagnostic and prognostic aid. An estrogen provocation test is suggested as a means of earlier recognition which could reduce mortality in this group.

Age Factors↗

Recreational softball injuries.

Every patient who presented to an urban teaching hospital's emergency department during one season complaining of an injury sustained while playing softball was interviewed to determine the parameters of play associated with the injury. Trends were noticed toward increased frequency of injury to experienced players late in the season. A fall was the most common mechanism of injury, and player location at the time of injury was equally divided between the basepath and defense. Very few players were injured at bat. No conclusion could be drawn about the protection afforded a player from the use of a mitt or cleats. The relative rate of injury was estimated to be 2.26 injuries per 1,000 players per day, making the risk of injury for softball participants about 50% of that for recreational skiers.

Adolescent↗

A student emergency medicine clerkship that uses new information technologies.

The effective teaching of clinical emergency medicine to medical students requires efficiency in the management of both student and faculty time. Presented is a course outline that makes use of the following elements to structure and augment clinical time in the emergency department (ED): Videotape to present a 19.7-hour series of faculty-produced lectures covering a "core" emergency medicine curriculum. A microcomputer to facilitate staggered scheduling of clinical time. A microcomputer test generation program that permits a secretary to formulate, administer, and grade a different final exam with each rotation. Computer-assisted recordkeeping for faculty evaluation of a student's clinical performance. Once established, this program can be administered with fewer than five faculty hours per month assisted by a part-time (25% full-time equivalent) clerical coordinator. The total cost for the instructional program is $86.37 per student using the new technologies, and $144.15 per student when presenting the same program using traditional teaching techniques. The use of new technologies in student teaching will therefore result in significant savings.

Clinical Clerkship↗

Intellectual and behavioural consequences of low level lead exposure: a review of recent studies.

Recent studies investigating the association between low levels of lead and children's IQ, behaviour and educational attainment are reviewed. The main emphasis is on the methodological issues and problems which face researchers carrying out these cross-sectional epidemiological studies, and in particular the problem of confounding social factors. It is concluded that body lead levels in children do to some extent act as a marker for socially disadvantageous factors, and that when these are controlled adequately, if there are any functional effects due to lead, then these are so small that they cannot be detected with any certainty, and they may not exist at all.

Behavior↗

A cost-effective emergency medicine clerkship.

Programs in emergency medicine for medical students are expected to become increasingly organized over the next several years with the development of emergency medicine teaching faculties by medical schools. In this article, the authors describe a clerkship design with three fundamental elements--clinical instruction, classroom instruction, and evaluation--that should be included in an emergency medicine clerkship. Through the use of optimal student scheduling and new information technologies, the yearly cost per student for the classroom teaching and student evaluation sections of the clerkship is $86.65.

Clinical Clerkship↗