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Biomedical subjects

T Brown

Publications and source records attributed to T Brown.

At least 379 records · Page 21Linked to original sources

Human parvovirus-associated arthritis: a clinical and laboratory description.

An outbreak of human parvovirus-associated erythema infectiosum in the Grampian region has enabled us to study the association between this small DNA virus and arthritis. This report deals with 42 patients with joint pains, in whom serological evidence of recent human parvovirus (HPV) infection was obtained. The clinical description of the disorder is based on 17 of the patients who were seen in the clinic and a further 13 patients for whom information was obtained by questionnaire. Detailed clinical features were not available for the remaining 12 patients. A rash was present in all 3 affected children but only 13 of the 27 adults. Viral prodromata were present in only 13 adults. 7 adults had neither rash nor viral prodromata. The arthritis was more common in adults than children and affected principally the female sex. In adults the arthritis was symmetrical, affecting the small joints of the hands, wrists, and knees most commonly. In all cases it was self-limiting, usually resolving within 4 weeks, although 1 adult had more persistent disease lasting almost 6 months. The 3 children reported in detail had less symmetrical and more persistent disease, which in 1 case has lasted over 7 months.

Adolescent↗

Chromosome damage and sister chromatid exchanges in lymphocyte cultures from patients with two primary cancers.

Sister chromatid exchanges (SCEs) and chromosome damage were scored in lymphocyte cultures from 11 patients with two or more primary cancers and were compared with normal controls. None of the patients had a constitutional chromosome anomaly, but six showed evidence of chromosome instability, which could not be accounted for by treatment, expressed either as elevated SCE frequency or increased nonspecific chromosome damage and chromosome loss. Chromosome damage included major rearrangements as well as deletions and gaps. The possibility of common mechanisms in chromosome instability leading to susceptibility to a heterogeneous group of primary cancers is discussed.

Aged↗

Teratogenicity of nitrofen (2,4-dichloro-4'-nitrodiphenyl ether) and its effects on thyroid function in the rat.

Nitrofen is a herbicide with potent teratogenic activity in rodent species. Previous studies have indicated that this agent has a stereochemical structure similar to thyroid hormone, and that exposure of adult mice results in depression of thryoxine (T4) levels. The present study was undertaken to determine if teratogenic exposure to nitrofen alters pituitary-thyroid function in nonpregnant, pregnant, and fetal rats, and if these potential alterations could be related to induction of birth defects. In adult thyroparathyroidectomized (TPTX) female rats, nitrofen exposure for 2 weeks resulted in a significant suppression of thyrotropin-stimulating hormone (TSH) levels. When a single dose of nitrofen was administered to euthyroid female rats, a trend toward reduction (p = 0.058) in the release of TSH after a thyrotropin-releasing hormone (TRH) challenge was observed 4 and 5 hr after exposure. Pregnant euthryoid rats given a single dose of nitrofen on Day 11 of gestation had significantly depressed TSH and T4 levels, and fetal T4 levels were markedly depressed at term. Administration of T4 on Day 2 through 22 of pregnancy plus nitrofen on Day 9 through 11 to TPTX dams resulted in a 70% reduction in the frequency of malformed fetuses, especially in regard to the frequency of heart anomalies, compared to nitrofen exposure alone. Competitive displacement studies in radioimmunoassays for T4 and T3 indicated that a nitrofen metabolite (4-hydroxy-2,5-dichloro-4'-aminodiphenyl ether) competed with [125I]T3 for antibody binding, while the parent compound and six isolated metabolites failed to compete with [125I]T4 for antibody binding. These results have been interpreted to indicate that nitrofen teratogenicity is mediated at least in part by alterations in maternal and/or fetal thyroid hormone status, and may be due to a premature and pharmacologic exposure to the embryo to a nitrofen-derived, T3-active metabolite.

Animals↗

Human parvovirus infection and aplastic crisis in hereditary spherocytosis.

This report records an episode of parvovirus-induced bone-marrow aplasia in a child with hereditary spherocytosis and arising during a local outbreak of erythema infectiosum (fifth disease or 'slapped-cheek syndrome'). Inapparent infection was found in two haematologically normal family contacts.

Anemia, Aplastic↗

Prostaglandin E2 and parathyroid hormone: comparisons of their actions on the rabbit proximal tubule.

Recent studies demonstrated that prostaglandin E2 (PGE2) participates in the regulation of glomerular and distal tubular function. A functional role for PGE2 on the proximal tubule has only recently been explored. Thus, we reported that PGE2 antagonizes the phosphaturic effect of PTH in the dog, which suggests that PGE2 may influence the transport functions of the mammalian proximal tubule. The present studies were designed to examine the direct effect of parathyroid hormone (PTH) and PGE2 on the fluxes of fluid (Jv) and phosphate (Jl-b PO4) in the rabbit proximal convoluted and straight tubules (PCT and PST). The activation of adenylate cyclase by the two agents was also examined. Finally, the combined effects of PTH and PGE2 on Jv and Jl-b PO4 were also studied in the PST. In the PCT, PTH (1 microgram/ml) inhibited Jv by 31% (P less than 0.05) but did not alter Jl-b PO4. PGE2 (10(-5) M) failed to act on either Jv or Jl-b PO4. In this segment, PTH stimulated adenylate cyclase but PGE2 did not. In the PST, PTH (1 microgram/ml) inhibited Jv and Jl-b PO4 by 34 and 20%, respectively (P less than 0.01). PGE2 (10(-5) M) also inhibited Jv and Jl-b PO4, by 33 and 12%, respectively (P less than 0.02). In contrast, PGF2 alpha, a related prostanoid, failed to influence these transport parameters. In the PST, PTH activated adenylate cyclase but PGE2 failed to do so. When both PTH (1 microgram/ml) and PGE2 (10(-7) M) were present simultaneously, Jv and Jl-b PO4 were comparable to that seen during control collections.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenylyl Cyclases↗

A method for quantitating antifibrillatory effects of drugs after coronary reperfusion in dogs: improved outcome with bretylium.

We developed a quantitative approach to assess the antifibrillatory effects of short-term interventions in a canine preparation of ventricular fibrillation caused by coronary reperfusion, and applied it to evaluate the antifibrillatory effects of bretylium tosylate. Twenty-five dogs were given 10 mg/kg infusions of bretylium over 10 min, subjected to a 20 min proximal left anterior descending coronary artery ligation followed by sudden release, and compared with 25 animals given saline placebo. Drug infusion was begun 90 min before reperfusion to avoid evaluation of outcome during the phase of drug-induced catecholamine release and to allow adequate time for bretylium uptake in the myocardium. The relationship between the likelihood of ventricular fibrillation during reperfusion and the amount of myocardium perfused by the occluded vessel (myocardium at risk) was analyzed with the logistic risk-regression model. This model was developed to control for the effects of amount of myocardium at risk on outcome. For both the bretylium and the placebo groups the incidence of ventricular fibrillation correlated significantly with amount of myocardium at risk. However, animals treated with bretylium had an improved outcome for a given amount of myocardium at risk. In other words, the curve relating outcome to myocardium at risk was shifted significantly to the right. The amount of myocardium at risk required for half the placebo-treated animals to fibrillate was 20.3 g and that required for half the bretylium-treated animals to fibrillate was 27.9 g, or 37% more than that for the placebo group. This logistic risk-regression analysis format permits quantification of treatment effects while accounting for variability in amount of myocardium at risk.

Animals↗

Chromosome aberrations in divers.

The incidence of chromosome gain and loss and chromosomal aberrations has been measured in 48-h lymphocyte cultures of divers and control subjects as part of an overall research program to identify possible long-term health hazards associated with commercial diving. When the two diving groups, air divers (n = 77) and helium-oxygen divers (n = 76), are compared with two control groups, oil rig workers (n = 75) and nonoil industry controls (n = 52), 3.9% (6 out of 153) had an unusually high number of structural aberrations in a small portion of the dividing lymphocytes. Similar damage was not found in controls. The remaining 147 divers had a similar low incidence of chromosomal aberrations to the two control groups. The factors responsible for this phenomenon are not known, but several aspects of diving can effectively be ruled out. These are: direct effects of pressure, breathing mixture, radiographic exposure, and viral infection. The causative agent must be acting locally on lymphocytes after their last maturation division. Further studies are continuing on this topic in an effort to identify the causative factor or factors.

Air↗

Use of inter-proton nuclear Overhauser effects to assign the nuclear magnetic resonance spectra of oligodeoxynucleotide and hybrid duplexes in aqueous solution.

Inter-proton nuclear Overhauser enhancements (NOEs) have been used to assign the aromatic, anomeric and 2' resonances in the 1H nuclear magnetic resonance spectrum of the duplex formed between d(T-C-A-C-A-T) and d(A-T-G-T-G-A). The same techniques have been applied to assignments in the hybrid duplex formed by d(T-C-A-C-A-T) with r(A-U-G-U-G-A). Comparison of intra-residue with inter-residue NOEs yields structural information which suggests that the conformations of both duplexes are similar. The NOEs are consistent with inter-proton distances measured from models of B-form DNA. Circular dichroic results confirm these deductions.

Chemical Phenomena↗

Molar size sequence in Australian Aboriginals.

Percentage frequencies for molar size sequence of first and second molars were calculated in a group of contemporary Australian Aboriginals using mesiodistal and buccolingual dimensions, as well as crown areas. Comparisons were made between sexes, arches, and dimensions within the Aboriginal group and also between Aboriginal data and those published for other populations. The frequencies of the M2 greater than M1 molar size sequence in the Aboriginals fell within the range of frequencies reported for other contemporary populations. Differences in the frequencies of the M2 greater than M1 sequence between the sexes and between arches, together with the relatively high frequency of asymmetry in molar size sequence within Aboriginals, supported the notion that local environmental conditions acting during odontogenesis, together with differential responses to other environmental influences, play an important role in determining observed patterns of molar tooth size.

Australia↗

Age changes in dental arch dimensions of Australian Aboriginals.

Breadths and depths of the dental arches were measured from standardized photographs of serial casts of Australian Aboriginals enrolled in a longitudinal growth study. The data were obtained from 1161 sets of casts representing 111 boys and 86 girls ranging in age from 6 to 19 years. Age changes in the arch dimensions conformed to previously described patterns in Caucasian children, namely, an increase in breadth and a decrease in depth. Corresponding dimensions and dimensional changes in the maxilla and mandible were strongly correlated, but breadth and depth changes were relatively independent. The disparity in size between arches increased with age, particularly in the breadth dimension of boys. Marked disparity in arch breadths characterizes an occlusal feature of this population that has been termed alternate intercuspation.

Adolescent↗

Progestins can mimic, inhibit and potentiate the actions of androgens.

There is an extensive background on the androgen responsiveness of the mouse kidney which can be demonstrated histologically by hypertrophy of the Bowman's capsule and the proximal convoluted tubule. Although androgens increase many renal proteins, beta-glucuronidase and ODC are distinguished by exquisite genetic regulation of the magnitude of the response induced by testosterone. Both the qualitative and quantitative expression of the genes for these enzymes are strain specific, and are dependent upon regulatory alleles. Ornithine decarboxylase is of particular interest since the response of this enzyme is rapid compared to that of beta-glucuronidase. Recent studies using a newly developed androgen receptor assay have demonstrated that the duration of retention of the androgen receptor complex in the nucleus correlates with the magnitude of the androgenic response. Progestins can mimic, inhibit, or potentiate the action of androgens. These responses have been termed the androgenic, antiandrogenic and synandrogenic actions of progestins, respectively. The androgenic and antiandrogenic action of this class of steroids are manifest on many tissues and on many endpoints within a given organ. These effects are believed to involve an early step(s) of androgen action which is common to all sensitive tissues. Results to date suggests that this early step involves the androgen receptor. By contrast, the synandrogenic action of progestins is limited in that it is not observed on all tissues, and not even on all endpoints within a single organ. In the mouse kidney, the synandrogenic actions of progestins have been most extensively studied on beta-glucuronidase. With this enzyme this unusual response to progestins can be demonstrated only in mice which carry the Gus-ra allele. This observation suggests that the potentiating action of progestins on beta-glucuronidase is manifest directly on the Gus gene complex. It is not certain at this time whether a similar mechanism is involved in the potentiation of androgen action on other organs such as the prostate. The androgenic action of progestins is believed to be similar to that of other androgens. Androgenic progestins such as MPA bind to the androgen receptors and translocate them to nuclei. This is followed by a dose dependent increase of proteins similar to what is observed after testosterone administration. In addition, the regulatory genes which modulate androgen action have the same effect on the androgenic effect of progestins. The fact that the potency of progestins such as MPA is less than that of testosterone is believed to relate in part to their lower affinity for the androgen receptors.(ABSTRACT TRUNCATED AT 400 WORDS)

Androgen Antagonists↗

Non-random chromosome loss in PHA-stimulated lymphocytes from normal individuals.

31773 lymphocyte metaphase cells from 280 karyotypically normal men aged 18-46 were examined for chromosome gain or loss. Chromosome loss was much more common than chromosome gain. Frequency of chromosome loss did not conform to a binomial distribution. There is a striking non-linear, inverse relationship between likelihood of loss and chromosome length. Chromosome gain shows a near binomial distribution between cells and no clear relationship to chromosome length. These facts indicate that the hypodiploid cells mostly arose as technical artefacts during slide preparation but that hyperdiploid cells were mainly due to non-disjunctional gain.

Adolescent↗

Validation of a short Orientation-Memory-Concentration Test of cognitive impairment.

A 6-item Orientation-Memory-Concentration Test has been validated as a measure of cognitive impairment. This test predicted the scores on a validated 26-item mental status questionnaire of two patient groups in a skilled nursing home, patients in a health-related facility, and in a senior citizens' center. There was a positive correlation between scores on the 6-item test and plaque counts obtained from the cerebral cortex of 38 subjects at autopsy. This test, which is easily administered by a nonphysician, has been shown to discriminate among mild, moderate, and severe cognitive deficits.

Aged↗