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Biomedical subjects

J B Hamilton

Publications and source records attributed to J B Hamilton.

At least 19 recordsLinked to original sources

A microtiter plate assay for polyglutamine aggregate extension.

Polyglutamine (polyGln) aggregates are neuropathological markers of expanded CAG repeat disorders, and may also play a critical role in the development of these diseases. We have established a highly sensitive, fast, reproducible, and specific assay capable of monitoring aggregate-dependent deposition of polyglutamine peptides. This assay allows detailed studies on various aspects of aggregation kinetics, and also makes possible the detection and quantitation of low levels of "extension-competent" aggregates. In the simplest form of this assay, polyGln aggregates are made from chemically synthesized peptides and immobilized onto microplate wells. These wells are incubated for different times with low concentrations of a soluble biotinylated polyGln peptide. Europium-streptavidin complexation of the immobilized biotin, followed by time-resolved fluorescence detection of the deposited europium, allows us to calculate the rate (fmol/h) of incorporation of polyGln peptides into polyGln aggregates. This assay will make possible basic studies on the assembly mechanism of polyGln aggregates and on critical features of the reaction, such as polyGln length dependence. The assay also will be a valuable tool for screening and characterizing anti-aggregation inhibitors. It will also be useful for detection and quantitation of aggregation-competent polyGln aggregates in biological materials, which may prove to be of critical importance in understanding the disease mechanism.

Humans↗

Human immunodeficiency virus and the orthopaedic surgeon.

Human immunodeficiency virus is a devastating disease that ends in death. The fear that it engenders in healthworkers and patients may be out of proportion to the risks involved but an emotional response to the dangers is understandable. However, a careful study of the risks, the adoption of high standards of practice, and control of the clinical environment probably can eliminate most of the risk. There is a clear conflict of interest between the maintenance of confidentiality for the infected person and the right to information of those with whom they come into contact. Mandatory clinical testing for human immunodeficiency virus is likely to become the most contentious medicolegal issue of the next decade.

Ethics, Medical↗

Role of fine catheter peritoneal cytology and laparoscopy in the management of acute abdominal pain.

Laparoscopy and fine catheter peritoneal cytology (FCPC) have been advocated as aids in the assessment of acute abdominal pain. In all, 411 patients admitted to a district general hospital during a 10-month period were managed using a standard protocol incorporating these techniques. After initial assessment by a surgical registrar, 151 patients were excluded from further progress through the protocol (age less than 16 years, definite diagnosis made or contraindication to FCPC. The remaining 260 patients were placed in one of four management groups: (A) urgent operation (23 patients); (B) 'look and see' (40 patients); (C) 'wait and see' (59 patients); (D) urgent operation not indicated (138 patients). Eighty-eight of 99 patients (88 per cent) in groups B and C, where the need for operation was uncertain, underwent successful FCPC and 39 patients (39 per cent) underwent laparoscopy. In these patients the initial registrar management decision proved to be incorrect in 33 cases (33 per cent), but by following the protocol the number of management errors actually made was reduced to 13 (13 per cent, P less than 0.001). This would have been reduced to 8 per cent if the protocol had not been violated in five patients. This study demonstrates the effectiveness of a protocol using FCPC and laparoscopy to improve the management of patients with acute abdominal pain.

Abdomen, Acute↗

Strain differences in target organ weight changes among mice treated with androgens.

When raised together in a controlled environment, 26 inbred strains of mice differed considerably in weights of seminal vesicles (SV), submandibular glands (SG), and tests in healthy males 100 days of age. In representative strains (high, medium, and low weight SV) castrate mature males administered various regimens of identical doses of exogenous androgen gave SV and SG weights that increased with increasing androgen and maintained weights in similar rank order to those in untreated animals. The relative stability of these differences suggests the usefulness of these animals for models to study the biochemical and cellular mechanisms of target organ sensitivity to androgen and perhaps to suggest genetic influences or susceptibilities to hormonally induced or dependent pathology in animals and man.

Androgens↗

Effect of lithium on parathyroid hormone-induced calcium release from bone rudiments.

Lithium treatment of humans and animals has been associated with adverse effects on bone and mineral metabolism. In order to determine whether lithium was altering the skeletal response to parathyroid hormone, we incubated bone rudiments for 5 days in the presence or absence of the drugs. Lithium had no effect on either parathyroid hormone-induced cyclic AMP generation or 45Ca release from the bone rudiments. The data are consistent with the hypothesis that the skeletal effects of lithium are not mediated via inhibition of the parathyroid hormone-adenyl cyclase-cyclic AMP system.

Animals↗

Differences in survival among germfree mice following transfer to a conventional colony.

Sex and strain differences in survival were studied in 7-9 month old germfree mice following transfer to a conventional colony. One outbred and three inbred strains were observed. All outbred CD-1 mice survived transfer and in 4 months increased their weight by 50%. The majority of inbred mice survived 7 months after transfer. Sex differences in survival were evident throughout the experimental period and were most marked 7 months after transfer. An unexpected new finding was the viability of the male sex in germfree mice after transfer. Possible explanations are considered.

Animals↗

Testicular lipids in mice with testicular feminization.

Morphological, histochemical and biochemical studies of the testis of mice with testicular feminization (tfm/y) reveal a large accumulation of lipids in Leydig cells and in Sertoli cells. In Leydig cells of tfm/y mice, lipid droplets do not exhibit the special relationship with smooth endoplasmic reticulum that exists in normal adult Leydig cells. Compared to the surgically-cryptorchid control, the tfm/y testis contains more lipid in Leydig cells but less in Sertoli cells. There are also quantitative differences in testicular lipids in tmf/y and normal testes but no significant differences were noted between tfm/y and surgically-cryptorchid testes. The testes of both the genetically defective and surgically-cryptochid animals contain increased amounts of total lipids and phospholipids, and of free and esterified cholesterols. Exogenous testosterone has no effect on lipids or other characteristics of these cells. The present results suggest that the increased lipids in tfm/y mice result from a genetic disorder that asserts itself (1) in Leydig cells where it is associated with, and is probably a result of, impaired lipid metabolism and steroidogenesis, and (2) in Sertoli cells where it is perhaps attributable to arrested spermatogenesis and impaired steroidogenesis.

Androgen-Insensitivity Syndrome↗

Number of germ cells in known male and known female genotypes of vertebrate embryos (Oryzias latipes).

The number of primordial germ cells in embryos of known genotypic sex was the same in XY males and XX females until the gonad became recognizable as testis or ovary. It has been claimed that the heterogametic sex chromosome causes the gonad to differentiate as a testis in mammals and as an ovary in birds as a result of earlier and more mitoses. This claim was not supported in the present study where a sex difference in numbers of germ cells was first noted during differentiation of oocytes in the XX embryos.

Animals↗