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Biomedical subjects

S M Clarke

Publications and source records attributed to S M Clarke.

35 records · Page 2Linked to original sources

The effect of minor gastric surgery on gastric emptying in the rat.

A new minimally invasive technique has recently been described which enables gastric emptying to be assessed on repeated occasions without the need for animal sacrifice. This technique has been applied to study the effect of a laparotomy or gastrotomy on gastric emptying in the rat. Groups of 10 animals underwent either a laparotomy or a gastrotomy, or were unoperated controls. Solid and liquid gastric emptying studies were performed preoperatively, and for two postoperative months. Emptying was unchanged in unoperated controls. Laparotomy animals showed delayed emptying of both solids and liquids, returning to normal by two months. Gastrotomy animals showed a similar delay in solid emptying, but liquid emptying was within the normal range postoperatively. It is concluded that minor abdominal surgery causes marked alteration in gastric emptying. The comparable emptying delay for patients is unknown, but this should be considered when patients are recovering from operation, and when interpreting postoperative gastric emptying studies.

Animals↗

Exercise myocardial perfusion scintigraphy with technetium-99m methoxy isobutylisonitrile: a comparative study with thallium-201.

The evaluation of technetium-99m methoxy isobutylisonitrile for the diagnosis of coronary artery disease requires comparative validation against thallium-201, the established perfusion imaging agent. We have compared myocardial and lung uptake of both radiotracers following maximal exercise in 52 patients: 40 with angiographically proven coronary disease. Qualitative and quantitative image analysis showed the diagnostic sensitivity of technetium-99m methoxy isobutylisonitrile to compare favourably with that of thallium-201 as reflected by the mean number of ischaemic segments identified: 5.6 +/- 2.5 vs 4.8 +/- 2.1 by qualitative analysis, and 5.7 +/- 3.2 vs 5.0 +/- 2.6 segments by quantitative analysis. More reversibly ischaemic segments per patient were identified with technetium-99m methoxy isobutylisonitrile than with thallium-201: 3.6 +/- 2.3 vs 1.8 +/- 1.9. There was a higher exercise myocardial to background count ratio with technetium-99m methoxy isobutylisonitrile: 3.16:1 vs 2.58:1, and the mean exercise lung uptake normalised to left ventricular uptake ('lung index'), was lower for technetium-99m methoxy isobutylisonitrile than for thallium-201 (36 +/- 8% vs 40 +/- 10%). Five of the six patients with abnormal elevation of the thallium-201 exercise lung index also had elevation of the technetium-99m methoxy isobutylisonitrile exercise lung index, and all had extensive coronary artery disease. These results indicate that technetium-99m methoxy isobutylisonitrile is at least as effective as thallium-201 for detecting exercise induced myocardial ischaemia. However, technetium-99m methoxy isobutylisonitrile provides a better image quality and may be a more sensitive marker of defect reversibility. For both radiotracers lung uptake is increased with extensive coronary artery disease and measurement of this variable provides prognostic information.

Coronary Disease↗

Acute effects of ultraviolet-B irradiation on the corneal surface of the pigmented rabbit studied by quantitative scanning electron microscopy.

The eyes of female pigmented rabbits were exposed to a single dose of UV-B (300 +/- 9 nm, 0.05 J/cm2 total dose) between 13.30 and 15.00 h. The average irradiance was 225 +/- 36 microW/cm2 delivered over 191 to 264 s. At various time periods thereafter (24, 48, 72 and 96 h post-irradiation), the animals were euthanized by pentobarbital overdose and the eyes fixed with 2% glutaraldehyde in 80 mM cacodylate buffer (pH 7.4, total osmolarity of 330-340 mOsm/L). Corneal quadrants were examined by high resolution scanning electron microscopy at 100 X and 500 X at-stage magnification at central, mid-peripheral and peripheral sites. The micrographs from the central cornea were subjected to a quantitative analysis using a computer based digitization system. A peak effect was observed at 48 h at which cellular exfoliation was noted at the corneal apex. In the region immediately adjacent to the exfoliating cells, the number of light and dark electron reflex cells decreased to 48 h while the numbers of medium-reflex cells decreased after 48 h. The relative surface area of all cells was also decreased at 48 h compared to unirradiated controls. Significant recovery was observed by 96 h. Mid-peripheral and peripheral sites were largely unaffected by this just supra-threshold irradiation.

Animals↗

A human cell beryllium acute toxicity assay.

A rapid, inexpensive beryllium acute toxicity assay using human erythrocyte ATP levels has been developed. The assay uses a photometric measurement of the luciferin-luciferase reaction in erythrocytes incubated in HEPES buffer with the tested toxicant. Incubation in HEPES significantly increases the sensitivity of erythrocytes to beryllium when compared to incubation in either plasma or physiological saline. After a one-hour incubation period in HEPES buffer and beryllium there is a loss of 50% of the erythrocyte ATP at 3 micrograms/ml of beryllium, and an 80% loss of ATP at 5 micrograms/ml of beryllium. The source of human erythrocytes does not appear to influence the test. Erythrocytes from 10 individuals, one with chronic beryllium disease and another with an acute sensitivity to beryllium, all gave similar biphasic dose-response curves to beryllium.

Adenosine Triphosphate↗

Primary explant culture: an in vitro model of the human prostate.

Human prostate tissue gave rise to essentially pure cultures of basal cells in vitro. Careful analysis by phase-contrast microscopy and photography suggested that these cells attempt to differentiate into secretory acinar cells. This was confirmed by immunocytochemical analysis for prekeratin which is present only in basal cells in situ and for prostatic acid phosphatase, prostate-specific antigen, and prostate fluid antigen, which are present only in secretory acinar cells in situ.

Acid Phosphatase↗

Monoclonal antibodies against a soluble cytoplasmic antigen in human prostatic epithelial cells.

Antibodies against a soluble cytoplasmic protein contained in prostate epithelial cells were developed using the hybridoma technique. This was done to provide markers for these cells that can be used to identify acinar cells in culture and to follow their development and/or differentiation over long periods of time. The antibodies do not recognize prostatic acid phosphatase nor the prostate antigen. They do recognize prostate acinar cells in formalin fixed tissue sections. The basal cells underlying the prostate epithelial acinar cells do not appear to contain the antigen. The antigen detected is believed to be a product of differentiated prostatic acinar cells.

Animals↗

Primary cultures of human prostatic epithelial cell from transurethral resection specimens.

The objective of this work was to design a simple and reproducible method of culturing human prostatic epithelial cells from attainable tissue. This type of system is essential for in vitro studies of prostatic cancer and benign prostatic hyperplasia (BPH). The most readily available source of prostatic tissue is the transurethral prostatic resection (TURP). This tissue can be obtained at surgery and processed immediately in the laboratory using standard cell culture techniques. By detailed sectioning and careful histologic examination of the tissue which represented the mirror image of each explant that was cultured, we found that tissue containing viable glandular structure yielded epithelial outgrowths. Pieces of tissue that did not yield epithelial outgrowth were composed only of fibromuscular stroma or contained acini which were damaged (usually cauterized). We concluded that this type of system can be used routinely to study prostatic disease on an individual basis.

Cells, Cultured↗

Characterization of prostate cells.

It is obvious from this brief review that the weakest link in the successful application of in vitro models to answer questions related to prostatic cancer is the lack of adequate markers to permit characterization of the cells with regard to organ and tissue origin and their neoplastic status. In our opinion there is little to be gained in defining markers for other purposes until we can manage these basic areas of recognition.

Cell Differentiation↗

Studies on the iodinated surface membrane proteins and concanavalin A agglutination of transformed Syrian hamster cells.

Chemically transformed Syrian hamster cells exhibit marked agglutination in the presence of the plant lectin, concanavalin A. In this report, we describe conditions which can alter this concanavalin A agglutinability, and compare the surface proteins from transformed cells which express different degrees of agglutinability. Lactoperoxidase-catalyzed iodination of tertiary Syrian hamster cells reveals the major iodinatable protein to be approximately 220 000 daltons. The transformed Syrian hamster cells do not contain this protein in an iodinatable form. Analyses of the transformed cells grown under conditions which decrease the concanavalin A agglutinability do not demonstrate any iodination of the 220 000 mol. wt. protein. These results depict the effects of growth and dibutyryl cyclic AMP on the iodinatable cell surface proteins of transformed cells and indicate that the absence of the I-220 000 mol. wt. protein is probably not a major determinant of concanavalin A agglutination.

Animals↗

The effects of specific antibody-complement-mediated cytotoxicity on transformed and untransformed Syrian hamster cells.

Antibodies were produced against 220,000-molecular-weight proteins of Syrian hamster embryo cells. The antiserum containing these antibodies is capable of immunologically staining the surfaces and a fibrillar network around untransformed Syrian hamster embryo cells. The staining is removed by adsorption of the antiserum with Syrian hamster embryo cells and by mild trypsin treatment. Several lines of neoplastically transformed Syrian hamster embryo cells isolated and cloned after treatment with chemical carcinogens show little or no immune staining. Adsorption of the antiserum with certain transformed cells does not significantly reduce the immune staining of untransformed Syrian hamster embryo cells. The immune antiserum, in the presence of complement, is selectively cytotoxic to the untransformed Syrian hamster embryo cells. However, the transformed lines show resistance to this treatment. Analysis of the lactoperoxidase-catalyzed, iodinated cell surface proteins by sodium dodecyl sulfate-polyacrylamide gel electrophoresis reveals that the transformed lines have either no detectable labeling or a marked reduction in the labeling of 220,000-molecular-weight proteins that are major iodinatable cell surface proteins on untransformed Syrian hamster embryo cells.

Antibodies↗

Has there been a turning point in the numbers of AIDS and HIV antibody positive cases in Ireland?

BACKGROUND: Major developments in the prevention and treatment of human immunodeficiency virus (HIV) infection and acquired immunodeficiency syndrome (AIDS) have taken place in recent years. Changes in the size of the HIV and AIDS epidemic need to be monitored to assess these developments and plan future services. AIMS: To describe temporal trends in the incidence of HIV and AIDS in Ireland, describing separately the major risk groups, and to explore possible associations between these trends with developments in care. METHODS: The annual numbers of HIV and AIDS in Ireland were analysed to determine whether there has been a turning point in incidence. RESULTS: For AIDS, there has been an overall decrease in numbers since 1993, with both homosexual and intravenous drug users (IDU) risk groups exhibiting a decrease. For HIV antibody positive individuals, overall numbers have remained constant. However, there has been an upward trend in the heterosexual risk group and a downward trend in the IDU risk group. Thus both AIDS and HIV numbers exhibit turning points. CONCLUSIONS: Declines in HIV and AIDS incidence in the homosexual and IDU risk groups are indirectly attributable to health safety and treatment programmes. The increase in HIV antibody positive cases among heterosexuals may reflect a relapse in safe sex behaviour.

Acquired Immunodeficiency Syndrome↗

Application of beryllium antibodies in risk assessment and health surveillance: two case studies.

This paper demonstrates that current standards used by the Occupational Safety and Health Administration (OSHA) to establish an area free from potential beryllium contamination may be inadequate. Using the Beryllium Antibody Assay, it was shown that workers exposed to former beryllium work areas, thought to be sanitized and to meet OSHA standards, experienced statistically significant rises in blood beryllium antibody titers. This finding raises the question of whether the equipment currently required to protect workers in beryllium-laden environments is sufficient. The project mission of decommissioning/decontaminating the former nuclear weapons plant at Rocky Flats Environmental Technology Site (RFETS), instituted in 1992, has necessitated development of new technology directed toward safe and responsible cleanup. Challenges have been posed not only by the need to dispose of radioactive and chemical waste, but also by the problem of cleaning up hazardous metals such as the element beryllium. Beryllium was used extensively in research and the manufacture of nuclear weapons components at Rocky Flats for over 40 years. Since inhalation of this element can induce chronic beryllium disease (Eisenbud and Lisson, 1983), an antibody assay was developed to screen workers for internal exposure to beryllium. Exposure is indicated by a titer of antibodies greater than two standard deviations above a normal population control (defined as the mean titer of pooled samples from 51 individuals with no known exposure to beryllium) and a p-value of < 0.05. This paper describes two new applications for the assay: risk assessment and health surveillance. Case study 1 involves a team of three workers who cleaned a beryllium plenum and whose beryllium antibody titers provided a quantitative assessment of their exposure. Case study 2 describes the use of the antibody assay to determine the probable manner in which one worker was exposed to beryllium while performing his duties as an architectural engineer.

Air Pollutants, Occupational↗