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Biomedical subjects

J Mitchell

Publications and source records attributed to J Mitchell.

At least 289 records · Page 16Linked to original sources
PubMed1988

Non-availability of the IUD and contraceptive choice.

The Copper 7 and Lippes Loop IUD are no longer distributed in the United States, and the cost of the Progestasert precludes usage in many family planning clinics. The impact of the loss of this widely used contraceptive method was assessed in a pilot study at the UCLA Family Planning Clinic. The clients who would have selected an IUD at the time of their clinic visit between March and December of 1986 instead chose oral contraceptive pills (55%) or barrier methods (45%) but their level of dissatisfaction with the methods they received was significantly greater than that of all other contraceptors, and this led to their subsequent selection of another method which, in the majority (66%), was of lower efficacy than the IUD. There were two unplanned conceptions amongst twenty women who would have chosen an IUD, both due to non-compliance with oral contraceptive pills; and at the time of survey in March 1987, no clients had opted for sterilization. Women who no longer have their choice of the IUD represent a high risk for contraceptive dissatisfaction and failure, but have not made precipitous decisions to undergo permanent sterilization.

Adolescent↗
PubMed1988

Validity testing of the TDx Cocaine Metabolite Assay with human specimens obtained after intravenous cocaine administration.

Clinical specimens obtained from human subjects after intravenous cocaine administration were analyzed by the TDx Cocaine Metabolite Assay (TDx) and by GC/MS for benzoylecgonine. The TDx results were significantly correlated with results by GC/MS assay with no evidence of bias in the TDx assay. All cocaine metabolite positive specimens (greater than or equal to 300 ng/ml) were confirmed by GC/MS. Detection times to the last positive specimen by TDx assay and GC/MS assay of four subjects after a 20-mg intravenous dose of cocaine ranged from 29.3 to 39.1 h and 27.9 and 36.6 h, respectively. Overall, the TDx assay was found to be highly specific and accurate for the detection and measurement of benzoylecgonine in urine.

Cocaine↗
PubMed1988

Effects of calcium deprivation on n-6 fatty acid metabolism in growing rats.

Two separate experiments examining the effects of calcium deficiency on plasma and liver fatty acids in rats were conducted. In Experiment I, weanling male Sprague-Dawley rats were fed a calcium-deficient diet with or without the supplementation of 5 or 20 g/kg calcium for 22 days. There were no significant differences in plasma and liver fatty acid distribution between the two calcium-supplemented groups. However, calcium deficiency significantly elevated the levels of 18:3n-6 in plasma and liver cholesteryl esters and liver phospholipids, while it reduced the levels of 20:3n-6 in plasma cholesteryl esters. In Experiment II, weanling rats were fed a calcium-deficient diet supplemented with 5 g/kg calcium for 22 days. After overnight fast, animals were given by intragastric feeding a dose of 4 g/kg body wt gamma-linolenic acid concentrate (containing 92% 18:3n-6 ethyl ester), and were killed 22 hr later. The levels of 18:3n-6 were significantly higher, whereas the levels of 20:3n-6 were either not changed or lower than those in calcium-supplemented group. In both experiments, the ratios of (20:3n-6 + 20:4n-6)/18:3n-6 in plasma and liver lipids were significantly reduced in calcium-deficient rats. These results suggest that calcium may play an important and specific role in the process of elongation of 18:3n-6 to 20:3n-6.

Aging↗
PubMed1988

Structural brain changes in patients with anorexia nervosa.

Twenty-five patients with anorexia nervosa were compared with 17 normal healthy control subjects in terms of their cerebral computed tomographic (CT) scan appearances. The patients displayed significantly greater ventricular and sulcal enlargement when compared to control subjects. There were no relationships between the CT scan appearance and clinical indices of illness severity or weight loss in the patient group. In 14 patients who had repeat scans after attaining normal body weight, no significant change was observed in the ventricular appearance, but there was a significant lessening in the degree of sulcal widening.

Adult↗
PubMed1988

Basic radiobiology.

Experimental studies of the biological effects of radiation were started soon after the discoveries of x-rays in 1895, but there is still much that is not known. This article includes some research objectives that are essentially pragmatic in nature, intended to support and improve the current practice of radiotherapy, but the central thrust is the understanding of the mechanisms involved in the biological effects of radiation at the cellular and molecular levels. The article was written by a consortium of scientists and suffers inevitably from the drawback that writing styles are inconsistent, and coverage is not uniform. However, it benefits from the enormous advantage that it reflects the accumulated wisdom and judgment of more than a dozen scientists who, in their own areas of expertise, are recognized as being at the cutting edge of radiation research. The niceties of style and syntax are sacrificed in favor of the quality of the science and the maturity of judgment. The study of DNA damage as a mechanism for cell injury in early- and late-responding tissues, as well as a comparison of DNA damage that leads to lethality, as opposed to transformation and mutagenesis, are key items. The study of cell lethality with cells in culture led to the identification of repair, both sublethal and potentially lethal, as well as the dose-rate effect, and has had a considerable impact on radiotherapy. Future studies should focus on understanding the factors that determine radiosensitivity/radioresistance. A variety of approaches are available, including the study of genetically deficient cell lines from cancer-prone individuals. A parallel approach is the application of the techniques of molecular biology to clone the repair genes in mammalian cells, and to understand genetic defects that alter gene regulation, or to regulate biochemical factors in the cell. Substantial progress has been made in developing in vitro assays for mutagenesis, particularly using hybrids of rodent and human cells. Better methods are needed to study the effects of mutation on gene expression, and sensitive systems are needed that can detect low doses of radiation. Assays of oncogenic transformation, the in vitro counterpart of carcinogenesis, have been used to investigate the oncogenic potential of various types of radiation and chemotherapy agents. Key topics in future will include the investigation of supra-additivity between different agents, the identification and characterization of oncogenes that may be activated by radiation, the development of quantitative assays based on human cells, and further studies involving cell-to-cell communication.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1988

Parathyroid hormone desensitization in renal membranes of vitamin D-deficient rats is associated with a postreceptor defect.

We examined the characteristics of PTH resistance in vitamin D-deficient rats employing renal membranes in vitro. Homologous desensitization was characterized by diminished PTH-stimulated adenylate cyclase activity and was associated with a reduction in PTH-binding capacity, but not affinity. Heterologous desensitization was also seen, as manifested by decreased calcitonin (CT)-stimulated adenylate cyclase activity with normal CT receptor binding. The reduced capacity of the nonhormonal effectors NaF and guanylylimidodiphosphate to stimulate adenylate cyclase indicated a postreceptor defect at the level of the guanyl nucleotide-binding protein (G protein), whereas a normal forskolin response was consistent with a fully functional catalytic component. The G protein deficiency was confirmed by demonstrating that the addition of extracts of vitamin D-sufficient membranes to preparations of vitamin D-deficient membranes restored the normal responses to NaF and guanylylimidodiphosphate. In addition, cholera toxin- and pertussis toxin-catalyzed labeling of vitamin D-deficient renal membranes with [32P]NAD revealed a decrease in both the stimulatory and inhibitory binding proteins. Experiments with testicular membranes in vitro indicated that the adenylate cyclase abnormality was absent in tissue lacking PTH receptors. The results suggest that a major contribution to PTH resistance in vitamin D-deficient animals is a postreceptor defect at the level of the G proteins and that this defect is manifest only in tissue expressing the PTH receptor.

Adenosine Diphosphate Ribose↗
PubMed1988

In vivo distribution of parathyroid hormone receptors in bone: evidence that a predominant osseous target cell is not the mature osteoblast.

Previous studies in vitro and in vivo have demonstrated the presence of receptor sites for PTH on cells of the osteoblast phenotype. Nevertheless, it is unclear whether the diverse functions of this hormone in bone can all be attributed to its interaction with a single cell type. In this study, we have used a radioautographic method to examine the competitive binding of 125I-labeled rat PTH-(1-34) to the long bones of rats in vivo. Our studies confirm the presence of competitive binding to mature osteoblasts and the absence of significant competitive binding to multinucleated osteoclasts. However, by light and electron microscopic radioautographic analysis, the majority of specific competitive PTH binding was present over a cell in the intertrabecular space of the metaphyseal region, which was distinct from the mature osteoblast. This large mononuclear cell with multiple cytoplasmic extensions appeared to interface with both the bone matrix and the microvascular osseous circulation and may provide an additional target to mediate hormonal effects on the skeleton.

Animals↗
PubMed1988

Influence of the amino-terminus on in vitro and in vivo biological activity of synthetic parathyroid hormone-like peptides of malignancy.

We compared the bioactivities of a synthetic truncated NH2-terminal fragment of the human (h) PTH-like peptide (PLP) associated with malignancies [hPLP-(3-34)], an intact NH2-terminal fragment [hPLP-(1-34)], and an NH2-terminal fragment of PTH [hPTH-(1-34)]. Although hPLP-(1-34) was less potent than hPTH-(1-34) in stimulating adenylate cyclase in rat renal membranes, hPLP-(1-34) and hPTH-(1-34) were equipotent in stimulating adenylate cyclase in OK renal cells as well as in UMR 108 osteosarcoma cells in vitro. In osteosarcoma cells, each of these peptides could desensitize adenylate cyclase responses to itself and to the other peptide, but could not reduce stimulation by prostaglandin E2. Renal membranes of vitamin D-deficient rats with secondary hyperparathyroidism had a reduced PLP-stimulated as well as PTH-stimulated adenylate cyclase response. The truncated analog hPLP-(3-34) was only a weak partial agonist and an antagonist in vitro, produced equivalent inhibition of hPLP-(1-34) and hPTH-(1-34) in renal and osseous cells, and could not desensitize agonist responses. In thyroparathyroidectomized rats in vivo, hPLP-(1-34) and hPTH-(1-34) increased cAMP excretion, enhanced phosphaturia, maintained plasma calcium, and reduced calciuria. Equimolar concentrations of hPLP-(3-34) produced no increases above control levels; however, high concentrations of this peptide mimicked PTH actions on renal and plasma ion handling while modestly augmenting cAMP excretion. These results demonstrate the importance of the first two residues of PLP for bioactivity, indicate that PLP and PTH interact at common receptor sites in vivo as well as in vitro, suggest that PLP may not be less potent than PTH in renal target cells, and indicate that the net result of interaction of these peptides with their common receptor in target tissues may reflect both activation and desensitization of receptor-mediated events.

Adenylyl Cyclases↗
PubMed1988

Rotavirus and Cryptosporidium shedding in dairy calf feces and its relationship to colostrum immune transfer.

Twenty Holstein calves received 2 L of colostrum twice within 12 h after birth; the first feeding occurred within 2 h of parturition. The increase in adsorption efficiency was related to the gamma globulin provided in the first colostrum feeding. Absorption efficiency ranged from 2.4 to 46.1%. The number of sheddings of rotavirus and Cryptosporidium by the calves during their first 4 wk of life was associated with serum gamma globulin concentration 24 h after birth and absorption efficiency. Absorption efficiency and body weight combined accounted for 60.4% of the variation in the number of sheddings; heavier calves shed more than lighter calves. During the first 4 wk, calves that shed more frequently gained less weight; weight gain was also associated with serum gamma globulin levels 24 h after birth. Colostrum composition varied between quarters of the same cow. Total protein and gamma globulin content of colostrum from the rear quarters was higher than from the front quarters. The association between number of sheddings and absorption efficiency suggest that calves should not be fed colostrum containing less than 9 g/100 ml of total protein.

Animals↗
PubMed1988

The Abbott IMx automated benchtop immunochemistry analyzer system.

We describe a new clinical laboratory instrument, the IMx, used to automate immunoassay testing in the clinical laboratory. The IMx incorporates a novel technology called Microparticle capture Enzyme ImmunoAssay (MEIA) for assays of high-molecular-mass analytes, and fluorescence polarization immunoassay (FPIA) for hapten assays. A front-surface fluorometer is used to quantify the enzymatic generation of fluorescent product at a rate proportional to the concentration of the analyte in an MEIA, and a fluorescence polarization optical system is used to quantify results in an FPIA. The microprocessor-based instrument uses a robotic arm with two degrees of freedom and a rotating carousel to process the samples for assay. One assay can be done on each of 24 patients' specimens in 30 to 40 min with "walk-away" automation. Calibration curves are stable for at least two weeks. Instrument control involves software-labeled "command keys," a numeric keypad, and an interactive display. Results are output to a thermal printer or computer interface.

Autoanalysis↗
PubMed1988

The co-localisation of substance P and VIP in cholinergic-type terminals of the rat parotid gland.

Parotid glands from the rat were examined for substance P (SP) and vasoactive intestinal polypeptide (VIP)-like immunoreactivity with the peroxidase-antiperoxidase (PAP) and immunogold methods. The majority of nerve terminals associated with the acinar secretory cells contained numerous small agranular vesicles measuring 40-60 nm in diameter and a few larger vesicles which had an electron-dense core and measured 90-120 nm in diameter. Electron-dense peroxidase reaction product indicative of SP and/or VIP-like immunoreactivity was found within the larger dense-cored vesicles and attached to the outer membrane of the small agranular vesicles. Some nerve terminals associated with the acinar cells contained no reaction product irrespective of whether sections were incubated for SP or VIP. With the immunogold method gold particles indicative of SP and/or VIP-like immunoreactivity were found associated with the larger dense-cored vesicles with very little gold labelling over the small agranular vesicles. When ultrathin sections were incubated for both SP and VIP-like immunoreactivity all of the labelled terminals examined contained gold particles indicative of the presence of both peptides. In several terminals individual dense-cored vesicles contained gold particles of different sizes which indicates co-existence of SP and VIP within the same vesicle. Several nerve terminals associated with the acinar cells contained no gold labelling of their synaptic vesicles. Occasionally nerve terminals were found around blood vessels that were positive for SP-like immunoreactivity and VIP-like immunoreactivity but none was found, using the immunogold method, that contained both peptides. Very few nerve terminals were found associated with ducts and none contained reaction product or gold particles indicative of SP or VIP-like immunoreactivity. The ultrastructural features of the nerve terminals containing SP and/or VIP-like immunoreactivity could not be distinguished from those that have been described as representing cholinergic terminals. The fact that the postganglionic parasympathetic secretomotor neurons contain, in addition to acetylcholine, two neuropeptides and the possible functional implications thereof are discussed.

Animals↗
PubMed1988

The pathology of intrauterine thyrotoxicosis: two case reports.

The autopsy findings are described in two infants of hyperthyroid mothers in whom the clinical symptomatology, laboratory data, and autopsy findings strongly suggested intrauterine thyrotoxicosis secondary to transplacental thyroid-stimulating immunoglobulin. Documented intrauterine thyrotoxicosis is extremely rare, and we believe these to be the first detailed pathologic descriptions of the entity. Autopsy findings included slim habitus, massive thyromegaly, hypertrophic cardiomegaly, congestive visceromegaly, pulmonary hypertension, adenopathy, and prominent amniotic fluid aspiration. Both cases illustrate the positive contribution that a carefully performed autopsy, even in the severely macerated stillborn, can make toward better understanding of intrauterine disease.

Adult↗
PubMed1988

Proliferative changes in the pulmonary arterial wall during short-term hyperoxic injury to the lung.

Injury to the lung during in vivo exposure to hyperoxia results in vascular restructuring and pulmonary hypertension. This study reports the pattern of cellular proliferation that occurs in proximal intrapulmonary arteries over time during vessel wall injury and adaptation to increased partial pressures of oxygen. Although the remodeling of the capillary bed has been emphasized particularly during oxygen injury to the lung, this report identifies significant proliferative changes within the vessel wall of proximal arterial segments isolated from rats exposed to 85% oxygen. An increased incorporation of 3H-thymidine by endothelial cells is the earliest and most dramatic vessel wall response. The labeling index of these cells is increased more than tenfold by the end of 7 days in hyperoxia. Proliferation of medial smooth muscle cells and adventitial fibroblasts is also significantly increased. The increased cell number within these compartments is noted especially for its contribution to the overall vessel wall hypertrophy observed in chronic hyperoxic pulmonary hypertension. This general proliferative response is accompanied by specific shifts in the relative percentages of different actin protein isoforms as identified by two-dimensional gel electrophoresis. Changes in the distribution of actin isoforms are discussed as potential markers of a phenotypic modulation among vascular smooth muscle cells that occurs during the progression of pulmonary vessel wall remodeling.

Animals↗
PubMed1987

Benefits of effective hospital services for elderly people.

An age related hospital service for elderly people was set up in Waltham Forest Health Authority to provide acute medical care when needed. Despite a reduction in the allocation of funds over the years 1982-4 the health authority increased the number of district general hospital beds available for elderly patients and improved home nursing services. The outcomes of the changes made were assessed against the aims of the service by using data from the Hospital Activity Analysis, SH3 returns, government population estimates, and yearly figures collected in our department. It is concluded that introducing an age related service in our health authority has benefited people aged over 65.

Aged↗