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Biomedical subjects

M Lewis

Publications and source records attributed to M Lewis.

At least 289 records · Page 16Linked to original sources

Association of wake time and the onset of myocardial infarction. Triggers and mechanisms of myocardial infarction (TRIMM) pilot study. TRIMM Study Group.

A morning increase in onset of acute myocardial infarction (MI) has been documented, but its association with wake time and possible triggering events is unclear. The community-based, ongoing Triggers and Mechanisms of Myocardial Infarction (TRIMM) study was designed to investigate the factors associated with the transition from chronic coronary artery disease to acute MI. During the pilot phase in 1989, 224 consecutive hospitalized MI patients (176 men and 48 women, aged 60.3 +/- 9.2 years) of the prospectively defined Monitoring of Trends and Determinates of Cardiovascular Disease (MONICA) Augsburg MI register were interviewed 16.8 +/- 6.5 days after the event. The frequency of onset of MI was significantly higher (p less than 0.01) during the morning from 6 to 9 AM compared with other times of day. After adjustment for individual wake times, the peak of onset of MI was markedly sharper; the relative risk of MI during the 3-hour peak interval (the 3 hours after awakening) compared with other times of day increased from 1.8 (95% confidence interval, 1.3-2.4) to 2.4 (95% confidence interval, 1.8-3.1). Sixty-seven percent of the patients reported possible acute triggers of MI and/or unusual life events; among those, 52% reported stress or emotional upset. The TRIMM pilot study demonstrated the feasibility of a community-based study of possible triggering events of MI. The circadian variation of MI appears to result primarily from increased onset after awakening. This narrowing of the time frame of increased risk of MI should facilitate study of pathogenic mechanisms and aid in the design of more effective preventive regimens.

Adrenergic beta-Antagonists↗

Visitation to a neonatal intensive care unit.

Preterm newborns may experience extended periods of hospitalization which disrupt the normal early contact between the newborn and its family. Variations in the frequency of visits to 164 preterm neonates in a neonatal intensive care unit were examined in relation to infant and family status variables and compliance with follow-up appointments at 3 months postterm. The mean number of visitors decreased from day 2 to day 12 of hospitalization and then remained stable through day 21. There was a corresponding increase in the number of days with no visitors through day 12, and then stabilization. Neonates who had intraventricular hemorrhages, whose parents did not live together, and who were not firstborn had the most days with no visitors. While the mother was hospitalized herself, her condition was the only variable related to percentage of no-visitor days. The sicker the mother, the more likely the newborn had no visitors. The greater the number of days with no visitors, the poorer the likelihood that the infant was brought to a 3-month follow-up clinic appointment.

Child Health Services↗

A region of proto-dbl essential for its transforming activity shows sequence similarity to a yeast cell cycle gene, CDC24, and the human breakpoint cluster gene, bcr.

Proto-dbl is a human proto-oncogene, whose oncogenic activation was initially detected by DNA transfection. We report significant sequence similarity between the predicted proto-dbl product and the products of CDC24, a Saccharomyces cerevisiae cell division cycle gene required for correct budding and establishment of cell polarity, and bcr, a gene implicated in the pathogenesis of chronic myelogenous leukemia (CML). Of 925 residues of the predicted proto-dbl protein, a stretch of 238 residues showed 29% and 22% identity over a region of similar length of the CDC24 and bcr proteins, respectively. When evolutionarily conservative substitutions were taken into account, the similarities were 68.8% and 71.6% for proto-dbl/CDC24 and proto-dbl/bcr gene products, respectively. Moreover, all three sequences were predicted to be markedly hydrophilic over this region. Very small deletions within the conserved region completely abolished transforming activity of dbl, while extensive deletion outside of this region had no effect. Even substitutions over a small stretch of close similarity with the other proteins substantially impaired transforming activity. Cells transformed by the dbl oncogene, like cdc24 mutants arrested at the nonpermissive temperature, form multinucleate cells. Thus, our findings indicate that the conserved region is an essential domain that may reflect important functional similarities among these otherwise highly divergent molecules.

Amino Acid Sequence↗

Characterization of putative cytoskeletal proteins from a trypanosomatid and their comparative binding to microtubules and soluble tubulin.

The corset of microtubules which encloses the cell body of Crithidia fasiculata displays cross-links joining tubules to each other and to plasma membrane. Two proteins, designated COP-33 and COP-61 on the basis of their subunit Mr values, have been considered putative components of this apparatus because of their abundance in isolated cytoskeleton and their ability to cross-link brain microtubules in vitro. The oligomeric structures of the native proteins have now been characterized, and they have been shown to be basic, rather symmetrical, and to require detergent for solubilization. Using monospecific antibodies, enzyme-linked immunoassays of subcellular fractions have shown that each is 5-fold enriched in the microtubule plasma membrane fraction and absent from flagellar and some internal membranes. The binding of each to soluble tubulin and to microtubules has been systematically studied and compared with that of two noncytoskeletal protein ligands (glycolytic enzymes). The observed positive cooperatively was unexpected for binding of these large ligands to microtubules. In each case the maximum number of mol of ligand bound per mol of tubulin (0.5-1.0) was identical whether the latter was dissociated or assembled and so were the dissociation constants (1.3-6.0 x 10(-7) M) for three of the ligand proteins.

Alkaloids↗

Epidural anaesthesia and long term backache after childbirth.

OBJECTIVE: To examine the relation between epidural anaesthesia and long term backache after childbirth. DESIGN: Data from postal questionnaire on morbidity after childbirth sent to women who had delivered in one maternity hospital between 1978 and 1985 were linked to maternity case notes for each woman. SETTING: Maternity hospital in Birmingham. SUBJECTS: 11,701 Women who had delivered their most recent baby at the maternity hospital during the defined period and who returned their completed questionnaires. MAIN OUTCOME MEASURES AND RESULTS: Of the 1634 women who reported backache, 1132 (69%) had had it for over a year. A significant association was found between backache and epidural anaesthesia (relative risk = 1.8); 903 of 4766 women (18.9%) who had had epidural anaesthesia reported this symptom, compared with 731 of the 6935 women (10.5%) who had not had epidural anaesthesia. This association was consistent in both "normal" and "abnormal" deliveries, the only exception being after an elective caesarean section when no excess backache occurred after epidural anaesthesia. CONCLUSIONS: The relation between backache and epidural anaesthesia is probably causal. It seems to result from a combination of effective analgesia and stressed posture during labour. Further investigations on the mechanisms causing backache after epidural anaesthesia are required.

Anesthesia, Epidural↗

Molecular cloning and expression of a receptor for human tumor necrosis factor.

A human tumor necrosis factor (TNF) binding protein from serum of cancer patients was purified to homogeneity and partially sequenced. Synthetic DNA probes based on amino acid sequence information were used to isolate cDNA clones encoding a receptor for TNF. The TNF receptor (TNF-R) is a 415 amino acid polypeptide with a single membrane-spanning region. The extracellular cysteine-rich domain of the TNF-R is homologous to the nerve growth factor receptor and the B cell activation protein Bp50. Human embryonic kidney cells transfected with a TNF-R expression vector specifically bind both 125I-labeled and biotinylated TNF-alpha. Unlabeled TNF-alpha and TNF-beta were equally effective at displacing the binding of labeled TNF-alpha to TNF-R expressing cells. Northern analysis indicates a single species of mRNA for the TNF-R in a variety of cell types. Therefore, the soluble TNF binding protein found in human serum is probably proteolytically derived from the TNF-R.

Amino Acid Sequence↗

Characterization of the basement membrane glycoprotein entactin synthesized in a baculovirus expression system.

A cDNA clone encoding the entire open reading frame of mouse entactin was constructed. This cDNA was inserted into Autographa californica multiple nuclear polyhedrosis virus and expressed in Spodoptera frugiperda, Sf9, insect cells. The recombinant entactin was produced in large quantities under the control of the polyhedrin promoter. Amino terminus sequence analysis indicated that the signal peptide in the preprotein was correctly cleaved. Polyclonal antibodies prepared against either the naturally occurring or recombinant entactin cross-reacted with both molecules in the native and denatured states. The recombinant molecule promoted cell attachment and exhibited a calcium- and temperature-dependent self-aggregation. These properties reflect those of the naturally occurring mouse molecule. Although entactin is an extracellular matrix component that is normally exocytosed, the vast majority of the molecules were localized inside the cell by immunoelectron microscopy where the molecules formed insoluble aggregates.

Animals↗

Linkage between the Colton blood group locus and ASSP11 on chromosome 7.

In an attempt to assign the Colton blood group locus (CO) we have successfully revisited chromosome 7. CO is linked to the argininosuccinate synthetase pseudogene 11 locus (ASSP11) with z = 5.79 at theta = 0.07 for combined paternal and maternal meioses. We propose a 7p position for CO.

Argininosuccinate Synthase↗

Primary structure and biological activity of a novel human neurotrophic factor.

During development, each tissue receives and maintains a number of specific neuronal projections that are adequate to sustain its function. The mechanism by which this intricate process occurs is not well understood, but it has been proposed that diffusible neurotrophic factors derived from the target tissue may be involved. Here we describe the identification of a novel human protein that is important for the growth, differentiation, and survival of primary sympathetic and placode-derived sensory neurons. This polypeptide, designated neuronotrophin-3, has a broad tissue distribution and is structurally related to both nerve growth factor and brain-derived neurotrophic factor. Its unique range of trophic and differentiation-inducing activities suggests that it is likely to play a wide role in defining the fate and function of nerve cells during development.

Amino Acid Sequence↗

lac repressor: crystallization of intact tetramer and its complexes with inducer and operator DNA.

The intact lac repressor tetramer, which regulates expression of the lac operon in Escherichia coli, has been crystallized in the native form, with an inducer, and in a ternary complex with operator DNA and an anti-inducer. The crystals without DNA diffract to better than 3.5 A. They belong to the monoclinic space group C2 and have cell dimensions a = 164.7 A, b = 75.6 A, and c = 161.2 A, with alpha = gamma = 90 degrees and beta = 125.5 degrees. Cocrystals have been obtained with a number of different lac operator-related DNA fragments. The complex with a blunt-ended 16-base-pair strand yielded tetragonal bipyramids that diffract to 6.5 A. These protein-DNA cocrystals crack upon exposure to the gratuitous inducer isopropyl beta-D-thiogalactoside, suggesting a conformational change in the repressor-operator complex.

Base Sequence↗

Early language ability as a function of ventricular dilatation associated with intraventricular hemorrhage.

This study examined the impact of right and left lateral ventricle dilatation on early language function associated with intraventricular hemorrhage (IVH). Because language is controlled primarily by the left cerebral hemisphere, it was hypothesized that language ability would be related to extent of left side dilatation more than to right. The relations of the number of other common complications of prematurity and socioeconomic status to language also were explored, and their independent contributions to the variance in the outcome were determined. The receptive and expressive language abilities of 45 low birth weight preterms, 18 of whom suffered IVH, were evaluated at a mean age of 16 months. Correlational analyses indicated that left, but not right, ventricle dilatation was inversely related to the expressive language measure. Partial correlations, holding the effects of medical complications and socioeconomic status constant, indicated that the impact of left ventricle dilatation was independent of these variables. Number of medical complications also had an independent relation to expressive language outcome that was equivalent to that of the left ventricle dilatation. Implications of these findings are discussed.

Cerebral Hemorrhage↗

Return of ovarian function following spontaneous abortion.

Assays of first morning urine samples for oestrone-3-glucuronide, LH and pregnanediol-3-glucuronide, were used to study endocrine function and return to ovulation in 18 subjects following spontaneous miscarriage. On the basis of the endocrine data, ovulation occurred in all 18 women in the cycle prior to first menses at a mean of 29 days post-partum (range 13-103 days) with one subject conceiving in that cycle. Compared with the second cycle, the first cycle after spontaneous abortion had similar levels of follicular phase peak ovulatory oestrone excretion but lower levels during the late luteal phase (P less than 0.02), lower levels of peak LH (50.5 IU/g creatinine (C) cf. 68.8 IU/g C; P less than 0.04) and lower late secretory peak pregnanediol (4.6 mg/g C cf. 6.1 mg/g C; P less than 0.02). The mean luteal phase length of 12.9 days in the first cycle was shorter than the mean of 14.4 days in the second cycle (P less than 0.02). These data show that, although there is some disturbance of endocrine function in the first cycle after spontaneous abortion, the majority of women have a rapid return to ovulation, making the early use of contraception necessary for those wishing to avoid conception.

Abortion, Spontaneous↗

Adverse learning strategy: the Adelaide Diagnostic Learning Inventory and its subscale replicability in a medical student population.

The Adelaide Diagnostic Learning Inventory (ADLIMS) is a measure of learning styles and learning pathologies that was designed to investigate the impact of traditional approaches to learning versus problem-based learning and to identify students whose approach to learning tasks predicted poor academic performance. In this study, some important psychometric properties of the ADLIMS were examined, including its factor structure. In this study, factor replicability across samples was argued to provide a more robust and psychologically meaningful factor solution than that which can be obtained using traditional mathematical criteria. The results of the factor analysis did not confirm the presence of the four factor solution earlier reported for the ADLIMS, but did identify three clear factors that had very high replicability. An inspection of the items comprising these three factors showed that factor 1 tapped subjective distress related to poor study habits, lack of motivation to study, and distraction from social activities. Factor 2 tapped distress arising from high achievement expectations that were hampered by superficial or disorganized study habits that did not enable the student to grasp the relationships between concepts and ideas. Factor 3 tapped positive feelings and a sense of satisfaction associated with a problem-based approach to the learning of new study material. Although the internal reliability of the ADLIMS subscales met the requirements of a measure to be used in general research such as in the investigation of correlates among groups of medical students, they did not meet the higher requirements of a measure to be used to identify or predict individuals with pathological learning styles.

Humans↗

Oral manifestations of previously undiagnosed non-insulin dependent diabetes mellitus.

The oral manifestations are described of 43 patients with previously undiagnosed non-insulin dependent diabetes mellitus (NIDD) who presented to an Oral Medicine Unit in a 24-month period. The diagnosis of diabetes mellitus was confirmed by measurement of fasting blood glucose and where necessary by a glucose tolerance test. Sixteen patients had burning mouth syndrome, ten patients had unusually prolonged fungal and/or bacterial infections, nine patients had a nonspecific condition such as altered taste, six patients had an oral mucosal lesion such as erosive lichen planus, one patient had sialosis and one patient complained of sialorrhoea. The frequency of undiagnosed NIDD was twice that expected among the general population. Treatment directed at improving glycemic control also produced resolution of the patients' oral symptoms in most cases.

Aged↗

Dissection of H-2Db-restricted cytotoxic T-lymphocyte epitopes on simian virus 40 T antigen by the use of synthetic peptides and H-2Dbm mutants.

Five distinct cytotoxic T-lymphocyte (CTL) recognition sites were identified in the simian virus 40 (SV40) T antigen by using H-2b cells that express the truncated T antigen or antigens carrying internal deletions of various sizes. Four of the CTL recognition determinants, designated sites I, II, III, and V, are H-2Db restricted, while site IV is H-2Kb restricted. The boundaries of CTL recognition sites I, II, and III, clustered in the amino-terminal half of the T antigen, were further defined by use of overlapping synthetic peptides containing amino acid sequences previously determined to be required for recognition by T-antigen site-specific CTL clones by using SV40 deletion mutants. CTL clone Y-1, which recognizes epitope I and whose reactivity is affected by deletion of residues 193 to 211 of the T antigen, responded positively to B6/PY cells preincubated with a synthetic peptide corresponding to T-antigen amino acids 205 to 219. CTL clones Y-2 and Y-3 lysed B6/PY cells preincubated with large-T peptide LT220-233. To distinguish further between epitopes II and III, Y-2 and Y-3 CTL clones were reacted with SV40-transformed cells bearing mutations in the major histocompatibility complex class I antigen. Y-2 CTL clones lysed SV40-transformed H-2Dbm13 cells (bm13SV) which carry several amino acid substitutions in the putative antigen-binding site in the alpha 2 domain of the H-2Db antigen but not bm14SV cells, which contain a single amino acid substitution in the alpha 1 domain. Y-3 CTL clones lysed both mutant transformants. Y-1 and Y-5 CTL clones failed to lyse bm13SV and bm14SV cells; however, these cells could present synthetic peptide LT205-219 to CTL clone Y-1 and peptide SV26(489-503) to CTL clone Y-5, suggesting that the endogenously processed T antigen yields fragments of sizes or sequences different from those of synthetic peptides LT205-219 and SV26(489-503).

Amino Acid Sequence↗