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Biomedical subjects

M J Smith

Publications and source records attributed to M J Smith.

At least 163 records · Page 9Linked to original sources
PubMed1995

Retardation of mentation in depressives: Posner's covert orientation of visual attention test.

A double-key version of Posner's covert orientation of visual attention test, which involves shifting of preparation for response from one side to another, was administered to 32 depressives and 32 controls to evidence retardation of mentation in depressives and compare it to symptom-rating scales. Results showed depressives' overall response times to be consistently slower than controls. The time of maximal response preparation occurred later in depressives than in controls, showing clear evidence of pure retardation of mentation (not mixed with motor processes). This slowing of mentation was strongly correlated with observable psychomotor retardation but not with depressive severity.

Adult↗
PubMed1995

Tropine dehydrogenase: purification, some properties and an evaluation of its role in the bacterial metabolism of tropine.

Tropine dehydrogenase was induced by growth of Pseudomonas AT3 on atropine, tropine or tropinone. It was NADP(+)-dependent and gave no activity with NAD+. The enzyme was very unstable but a rapid purification procedure using affinity chromatography that gave highly purified enzyme was developed. The enzyme gave a single band on isoelectric focusing with an isoelectric point at approximately pH 4. The native enzyme had an M(r) of 58,000 by gel filtration and 28,000 by SDS/PAGE and therefore consists of two subunits of equal size. The enzyme displayed a narrow range of specificity and was active with tropine and nortropine but not with pseudotropine, pseudonortropine, or a number of related compounds. The apparent Kms were 6.06 microM for tropine and 73.4 microM for nortropine with the specificity constant (Vmax/Km) for tropine 7.8 times that for pseudotropine. The apparent Km for NADP+ was 48 microM. The deuterium of [3-2H]tropine and [3-2H]pseudotropine was retained when these compounds were converted into 6-hydroxycyclohepta-1,4-dione, an intermediate in tropine catabolism, showing that the tropine dehydrogenase, although induced by growth on tropine, is not involved in the catabolic pathway for this compound. 6-Hydroxycyclohepta-1,4-dione was also implicated as an intermediate in the pathways for pseudotropine and tropinone catabolism.

Alcohol Oxidoreductases↗
PubMed1995

Nerve extracts and substance P activate the phosphatidylinositol signaling pathway and mitogenesis in newt forelimb regenerates.

We investigated the inositol phospholipid transmembrane signaling pathway as a possible mediator of neurotrophic (mitogenic) signals in the newt limb regeneration blastema. Blastema mesoderm tissues were prelabeled with myo-[3H]inositol, treated with 10 mM LiCl and then exposed to substance P or to extracts of spinal ganglia, brain, or spinal cord. Stimulation with substance P resulted in a rapid dose-dependent reduction of [3H]phosphatidylinositol 4,5-bisphosphate and [3H]phosphatidylinositol 4-phosphate, correlated with a rapid accumulation of inositol 1,4,5-triphosphate. This effect was inhibited when the blastema tissue was treated with neomycin, a known inhibitor of inositol phospholipid turnover. In addition, substance P stimulated the incorporation of [3H]thymidine into DNA of blastema mesoderm cells, and this effect was also suppressed by neomycin, at a dose corresponding to that required to inhibit inositol phosphate accumulation. Extracts of neural tissues, especially spinal ganglia, induced the formation of inositol phosphates and extract activity was attenuated following treatment with heat or trypsin. These findings suggest a role for mitogen-activated inositol phospholipid signaling, initiating events that ultimately lead to cell proliferation.

Animals↗
PubMed1995

The molecular phylogeny of five eastern north Pacific octopus species.

The DNA sequence of a 612-nucleotide fragment of the mitochondrial cytochrome oxidase subunit III gene from five Octopus species has been determined. The COIII gene in these species shows an extreme bias against G in the DNA sense strand with a moderately low C composition. The bias against G and C severely restricts the codon usage in Octopus COIII genes. The aligned DNA sequences were subjected to distance, maximum-likelihood, and parsimony analyses to ascertain the phylogenetic relationship of the species. The results of all of the analyses were concordant. The analyses indicate that O. bimaculoides and O. bimaculatus are the least diverged of the species and fall into a separate clade from O. dolfleini and O. californicus, which are also closely related. O. rubescens is about equally removed from the other species, but parsimony, distance, maximum-likelihood, and logdet analyses suggest that it is more closely aligned with the O. bimaculoides/O. bimaculatus lineage.

Amino Acid Sequence↗
PubMed1995

A critique of instruments and methods to detect, diagnose, and rate delirium.

This document reviews existing instruments for evaluation of delirium. Instruments have been grouped into four categories: tests that screen for cognitive impairment, delirium diagnostic instruments, delirium-specific numerical rating scales, and laboratory and paraclinical exams. Analysis of instruments was based on comparison of their psychometric properties as well as subjective judgment. Guidelines are suggested for choosing the appropriate instrument according to the type of clinical evaluation or delirium research envisaged. Important factors in choosing an instrument, besides the appropriateness of its psychometric characteristics, include administration time constraints, level of rater expertise, and patient capabilities. By familiarizing investigators with the variety of evaluation instruments available, this work should permit more appropriate instrument selection in future studies on delirium.

Cognition Disorders↗
PubMed1995

Low-dose aspirin does not attenuate platelet aggregation or atherosclerosis in miniature swine but decreases production of aortic wall prostacyclin.

The objectives of this study were to determine if, and at what dose, aspirin could attenuate atherosclerosis in hypercholesterolemic Yucatan miniature swine, and to determine the influence of aspirin on aortic wall prostacyclin production and platelet aggregation. 30 Yucatan miniature swine (age 3 months) were fed either regular diet (RD), atherogenic diet (AD), or AD plus one of four aspirin dosages (2,4,8, or 16 mg/kg/d) for 6 months. The extent of atherosclerotic lesions in the abdominal aorta and coronary arteries was evaluated by sudanophilic staining and histological grading using Stary's classification, respectively. Aortic wall production of prostacyclin (PGI2) and platelet aggregation were assessed. Lesions were similar among the AD groups (45.3 +/- 4.3%) and significantly higher than RD (1.4 +/- 0.4%). PGI2 production was significantly lower (p < 0.05) in all aspirin-treated groups. Platelet aggregation was not affected by treatment. It is concluded that the range of aspirin dosages (2-16 mg/kg/d) does not attenuate the development of atherosclerosis.

6-Ketoprostaglandin F1 alpha↗
PubMed1995

Psychometric characteristics of ideational retardation in depressives.

In two studies we tested the assumption that slowing of ideation (the ideational counterpart of psychomotor retardation) reflects a dimension distinct from severity of depression. Specifically, we hypothesized that an objective measure of ideational retardation would be correlated with a psychomotor retardation rating scale but not with a depression severity rating scale. There was in-patients in Study 1 and 30 out-patients in Study 2; all satisfied DSM-III criteria for major depressive episode. Measurements of ideational retardation, and notably latency of response, were derived from patient responses to the Rorschach plates (Study 1) and to simplified non-figurative line drawings (Study 2). As expected, results showed that latencies of response were not significantly correlated with depression severity scores on the Montgomery and Asberg Depression Rating scale (r = .19 in Study 1, r = -.08 in Study 2), but were significantly correlated with the scores on the Salpétrière Retardation Rating Scale (subscale for observable items, SRRSo)(r = .71, p < .0005 in Study 1; r = .55, p < .005, in Study 2).

Adult↗
PubMed1995

Reduced parasympathetic control of heart rate in obese dogs.

We investigated why resting heart rate is elevated in dogs fed a high saturated fat diet for 12.7 +/- 1.8 wk. Obese dogs exhibited elevated body weight (59%), blood pressure (14%), and heart rate (25%). Differences in resting heart rate (control, 58 +/- 5 beats/min; obese, 83 +/- 7 beats/min) were abolished after hexamethonium, indicating an autonomic mechanism. Hexamethonium also reduced blood pressure in obese (20 +/- 4 mmHg) but not control (9 +/- 6 mmHg) animals. Propranolol did not affect heart rate in either group, excluding a beta-adrenergic mechanism. Subsequent administration of atropine increased heart rate more in control than in obese dogs (110 +/- 9 vs. 57 +/- 11 beats/min). The sensitivity of the cardiac limb of the baroreflex (Oxford method) was reduced by 46% in the obese group, confirming impairment of the parasympathetic control of heart rate. The standard deviation of blood pressure measurements was normal when expressed as a percentage of the mean arterial blood pressure (control, 11.2 +/- 0.4%; obese, 11.2 +/- 0.5%). Our results indicate that the development of obesity in dogs fed a high saturated fat diet is accompanied by an attenuated resting and reflex parasympathetic control of heart rate.

Animals↗
PubMed1995

Blockade of C5a and C5b-9 generation inhibits leukocyte and platelet activation during extracorporeal circulation.

Complement activation contributes to the systemic inflammatory response induced by cardiopulmonary bypass. At the cellular level, cardiopulmonary bypass activates leukocytes and platelets; however the contribution of early (3a) versus late (C5a, soluble C5b-9) complement components to this activation is unclear. We used a model of simulated extracorporeal circulation that activates complement (C3a, C5a, and C5b-9 formation), platelets (increased percentages of P-selectin-positive platelets and leukocyte-platelet conjugates), and neutrophils (upregulated CD11b expression). to specifically target complement activation in this model, we added a blocking mAb directed at the human C5 complement component and assessed its effect on complement and cellular activation. Compared with a control mAB, the anti-human C5 mAb profoundly inhibited C5a and soluble C5b-9 generation and serum complement hemolytic activity but had no effect on C3a generation. Additionally, the anti-human C5 mAb significantly inhibited neutrophil CD11b upregulation and abolished the increase in P-selectin-positive platelets and leukocyte-platelet conjugate formation compared to experiments performed with the control mAb. This suggests that the terminal components C5a and C5b-9, but not C3a, directly contribute to platelet and neutrophil activation during extracorporeal circulation. Furthermore, these data identify the C5 component as a site for therapeutic intervention in cardiopulmonary bypass.

Antibodies, Monoclonal↗
PubMed1995

Altered insulin secretory responses to glucose in subjects with a mutation in the MODY1 gene on chromosome 20.

This study was undertaken to test the hypothesis that the diabetes susceptibility gene on chromosome 20q12 responsible for maturity-onset diabetes of the young (MODY) in a large kindred, the RW family, results in characteristic alterations in the dose-response relationships between plasma glucose concentration and insulin secretion rate (ISR) that differentiate this form of MODY from MODY in subjects with glucokinase mutations. Ten marker-positive subjects and six matched nondiabetic marker-negative subjects from the RW family received graded intravenous glucose infusions on two occasions separated by a 42-h continuous intravenous glucose infusion designed to prime the beta-cell to secrete more insulin in response to glucose. ISR was derived by deconvolution of peripheral C-peptide levels. Basal glucose and insulin levels were similar in marker-negative and marker-positive groups (5.3 +/- 0.2 vs. 5.0 +/- 0.2 mmol/l, P > 0.2, and 86.1 +/- 3.9 vs. 63.7 +/- 12.1 pmol/l, P > 0.1, respectively). However, the marker-positive subjects had defective insulin secretory responses to an increase in plasma glucose concentrations. Thus, as the glucose concentration was raised above 7 mmol/l, the slope of the curve relating glucose and ISR was significantly blunted in the marker-positive subjects (13 +/- 4 vs. 68 +/- 8 pmol.min-1.mmol-1 x 1, P < 0.0001).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1994

Sex determination. Turning on sex.

The orphan nuclear receptor, steroidogenic factor 1, is central to the differentiation of male and female mammalian gonads. It controls the fate of the initially bipotential gonad as well as later male-specific functions.

Animals↗
PubMed1994

Expression of the co-stimulatory molecule B7 on melanoma cells.

The induction of T-cell responses against tumor cells is believed to depend on both recognition of antigen and receipt of co-stimulatory signals from interaction of ligands such as B7 with its receptors CD28 or CTLA-4 on T cells. In the present study the expression of B7 on cultured human melanoma cells was studied at the mRNA level by reverse PCR analysis and surface expression by flow cytometric analysis with monoclonal antibodies (MAbs). PCR analysis revealed mRNA for B7 in 3 of 6 (50%) cultured primary melanoma and 8 of 19 (42%) cultures of metastatic melanoma. Analysis of B7 expression by flow cytometry using the BB1 MAb revealed low levels of expression in 3 of 10 melanoma that had mRNA for B7. In 2 of the latter (but not 4 other PCR+ lines) expression could be increased by culture in GM-CSF, IL-2, IFN-gamma and IFN-alpha 2. Our results indicate that although mRNA for B7 is present in 40-50% of melanoma cell lines, expression at the protein level is at low or undetectable levels in the majority of the cell lines. Expression of B7 protein was also not detected in studies on tissue sections from 11 primary and 9 metastatic melanomas.

B7-1 Antigen↗
PubMed1994

Assembly of Alzheimer-like filaments from full-length tau protein.

The principal fibrous component of neurofibrillary pathology in Alzheimer's disease, the paired helical filament, is formed from hyperphosphorylated microtubule-associated protein tau. Here we show that recombinant tau protein either in a non-phosphorylated state or following phosphorylation with brain extract can be assembled in vitro into filaments resembling those seen in Alzheimer's disease.

Alzheimer Disease↗
PubMed1994

Male-induced oestrus and ovulation in female brush-tailed bettongs (Bettongia penicillata) suckling a young in the pouch.

Female brush-tailed bettongs isolated from males usually do not come into oestrus or ovulate. Individuals isolated during pregnancy and at parturition do not ovulate post partum and are in the unusual condition for a macropodoid of suckling a pouch young but lacking a quiescent corpus luteum or a diapause embryo. Females in this condition were tested for their ability to come into oestrus and to ovulate after re-introduction to the male. When returned to the male on Day 1 of lactation, females generally mated before Day 2 and ovulated; at all later stages of lactation, six or seven days after being returned to the male > or = 50% of females came into oestrus, mated and ovulated. The vaginal smears of most females in isolation were typical of post oestrus on Day 2; after being returned to the male on Day 11, these females came into oestrus in seven days, mated and ovulated. The results show that suckling a young in the pouch does not suppress ovulation in this species provided that an adult male is present. Moreover, the results indicate that the mechanism of male-induced ovulation 24 h post partum differs from that of the remainder of the pouch suckling period.

Animals↗