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Biomedical subjects

P Clark

Publications and source records attributed to P Clark.

302 records · Page 17Linked to original sources

Lung function in an Australian population: contributions of polygenic factors and the Pi locus to individual differences in lung function in a sample of twins.

A study of lung function in 203 twin pairs aged 18-34 years living in Sydney detected significant genetic variation in females and males. There was no evidence of family environmental effects in either sex and most of the repeatable variation in females was heritable. However, there was evidence for systematic environmental differences between males affecting lung function so that the heritability was lower in males (about 0.6) than females (about 0.8). An effect of smoking on lung function was detected but accounted for less than 3% of the variance. Lung function in females was greater in the M subtype heterozygotes at the Pi locus than in the M subtype homozygotes or in other Pi phenotypes with low alpha 1-antitrypsin activity. The Pi polymorphism accounted for approximately 9% of the total variance in female lung function. No effect of the Pi locus was found in males.

Adolescent↗

Effects of the protease inhibitor (Pi) polymorphism on alpha-1-antitrypsin concentration and elastase inhibitory capacity in human serum.

The concentration of alpha-1-antitrypsin (AAT) and its elastase inhibitory capacity (EIC) have been investigated in vitro in sera from 1688 healthy Canberra blood donors typed for electrophoretic variants of the protease inhibitor (Pi) locus. Nine Pi alleles were recorded in the sample, of which M1 was found at a frequency of nearly 70% and the other eight were each at frequencies below 15%. As a class, heterozygotes among the three Pi M subtype alleles, M1, M2 and M3, have higher means and lower variances for AAT and EiC than do the three M subtype homozygotes. Among the three homozygotes M1M1 has highest AAT and EIC and among the heterozygotes dominance in M1M2 and M1M3 is towards or beyond the high M1M1 values. Of the six other Pi alleles recorded, two (F and G) have similar values to the M subtypes but the other four (I, N, S and Z) have lower values. The patterns of means and variances in AAT and EIC for the different M subtype genotypes do not support the precise threshold function postulated by Martin and Oakeshott (1983) to relate activity to Darwinian fitness. Nevertheless, several aspects of the results are consistent with a general positive relationship between activity and fitness.

Adolescent↗

Distinct patterns of microvascular endothelial cell morphology are determined by extracellular matrix composition.

Endothelial interactions with the extracellular matrix (ECM) play important roles in angiogenesis but whether specific ECM signals can determine specific cellular morphologies is unclear. The authors compared in vitro ECM-induced morphological responses of the phenotypically distinct human placental microvascular endothelial cells (HPMECs) with large vessel endothelial cells (HUVECs). HPMECs showed distinct patterns of reorganization in response to collagen-I or collagen-IV (monolayer disruption, sprouting, migration) and Matrigel or laminin-A (intussusception, cord formation, tubulogenesis), and an intermediate response to fibrin; whereas HUVECs responded similarly to collagen-1 and Matrigel (elongation, lattice formation, vacuolation) and showed little response to fibrin. Although the extent of collagen and Matrigel responses of HPMECs were increased by serum, acidic or basic fibroblast growth factor (aFGF, bFGF), or vascular endothelial growth factor (VEGF), and varied with matrix protein concentration, the basic patterns were matrix specific, and were independent of fibronectin. The collagen responses correlated with disruption of adherens and tight junctions and the formation of filopodial protrusions. Matrigel responses were associated with up-regulated junctional localization of VE-cadherin, and tubulogenesis developed mainly through paracellular remodeling rather than intracellular vacuolation. Overall, these findings suggest that distinct ECM interactions stimulate specific morphological responses. These signals may regulate morphological behaviour in the angiogenesis cycle, switching endothelial cells between migratory and vasculogenic phenotypes.

Antigens, CD↗

In vitro effects of clarithromycin on human polymorphonuclear leukocyte functions.

BACKGROUND: It has been shown that antibacterial agents affect polymorphonuclear leukocytes (PMNs), which are active in the body's first line of defense, in different ways. However, few studies have investigated the effects of tablet dosage forms as opposed to pure powder forms. There is a need to demonstrate the clinical relevance of previous results with commercially available products. METHODS: We examined the effects of clarithromycin solutions, prepared separately from either pure powder or commercially available tablets (250 mg), on human PMNs. The in vitro effects of each solution, adjusted to therapeutic concentration (1 mg/l), on PMN adherence, chemotaxis, phagocytosis, candidacidal capacity and superoxide production were studied. RESULTS: Solutions prepared from pure clarithromycin powder did not affect the adherence, phagocytosis or superoxide production of PMNs, but did inhibit (p<0.05) chemotaxis and candidacidal capacity. By contrast, a decrease (p<0.05) in all functions except phagocytosis was observed with solutions prepared from the tablet dosage form of clarithromycin. CONCLUSION: The results of this study suggest that the tablet dosage form of clarithromycin may have a more pronounced inhibitory effect on human PMN functions than solutions prepared from the pure powder form.

Anti-Bacterial Agents↗

A comparison of two studies of the pressure distribution under the feet of normal subjects using different equipment.

There is growing interest in the use of foot pressure measurement both clinically and in the study of normal subjects. A number of systems are now commercially available, but comparison of the results is complicated by the different techniques employed. This paper compares the results of two studies. The first examined a large group of normal subjects using the dynamic pedobarograph. The second was identical to the first except that the EMED F system was used. The second study was carried out in order to verify existing results and to assess the clinical significance of the expected differences. Comparison of the results from the two studies showed that the median peak pressures demonstrated similar patterns with the highest pressure in the forefoot under the second/third metatarsal heads and the toes taking gradually reduced pressure from the first to the fifth toe. The EMED F showed higher peak pressures than the dynamic pedobarograph under the heel, the medial four metatarsal heads, and the great toe and showed lower peak pressures and shorter contact times under the lateral four toes. The pattern of loading across the metatarsal heads was further analyzed using an objective method of splitting the subjects into groups. Four groups were isolated from both sets of results, and this has confirmed that only a proportion of normal subjects demonstrate highest loading under the first metatarsal head whereas the remainder show highest loading centrally within the forefoot.

Adult↗

Structure elucidation of a purple peptide found during the purification of a recombinant protein from Escherichia coli.

A purple substance (4) partially co-purified with a recombinant human B-type natriuretic peptide (hBNP), following an E. coli fermentation. The structure of the compound was elucidated by NMR, electrospray and FAB mass spectrometry. The chromophore is a 1,4-naphthoquinone condensed with the N-terminal cysteine of a heptapeptide by its NH2- and SH-groups to form a dihydro-thiazine ring. The peptide sequence was determined as Cys-Lys-Val-Leu-Arg-Arg-His by mass spectrometric techniques. CID and data base matching identified it as the C-terminus of the 32-amino-acid recombinant peptide hBNP. This modification of an N-terminal Cys may be a more general phenomenon with implications for the production of heterologous proteins by microorganisms.

Amino Acid Sequence↗

Primary adenocarcinoma of the gland of the nictitating membrane in a cat.

An 11-year-old, neutered, male domestic shorthair was presented with a five-month history of recurrent, unilateral, seromucoid discharge from the right eye. A verrucous mass extended from the posterior aspect of the nictitating membrane. Adenocarcinoma of the gland of the nictitating membrane (GNM) was diagnosed upon biopsy. The cat subsequently developed metastases to the lungs, pleura, mediastinum, liver, and kidneys and died six months after clinical signs first were observed. Little is known about the biological behavior of adenocarcinoma of the GNM in cats. This is the first report that describes the natural progression of this disease.

Adenocarcinoma↗

A special request.

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Employment↗

[Anticardiolipin antibodies. Clinical significance and limits of the method].

Recently we have available immunologic techniques with high sensitivity (nanogram 10(-9) g) useful for recognizing antibodies, including the antiphospholipid antibodies. As a consequence, a clinical syndrome termed precisely antiphospholipid or anticardiolipin syndrome was described in 1983. This clinical entity has manifestations pertaining to several medical fields such as cardiology, angiology, neurology, obstetrics and rheumatology. It is necessary to set limits for the information provided by such tests in each laboratory. In our hands the positive predictive value is very low for establishing a diagnosis of autoimmune disease. It is better as a negative predictive value to exclude that possibility. However, as is the case in almost all data generated through biological assays, a result of anticardiolipin antibody detection by ELISA is meaningful only in a clinical context. This fact is emphasized, making the point of the necessity of prospective controlled studies.

Adult↗

Cluster deaths in long-term care institutions: an investigation of excess deaths in two Ontario institutions.

OBJECTIVE: To review clusters of deaths in two Ontario long-term care institutions and to establish whether common etiologic factors could be identified. METHOD: Retrospective review of the health care records of all residents who died to assess the events leading to death and the actions of the institutions and local coroners in response to the deaths. RESULTS: A respiratory infectious outbreak appeared to lead to many of the deaths in both institutions. Several deficiencies were identified with respect to charting practices, coroners' case investigations and institutional responses to the infectious outbreaks. No formal mechanisms were in place to assist in the early detection of cluster deaths in these institutions. CONCLUSIONS: Infectious outbreaks may be an important cause of cluster deaths in long-term care institutions. Standards should be developed for patient charting, coroners' investigations and for the prevention, identification and management of infectious outbreaks in such settings.

Aged↗

Male order problems.

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Erectile Dysfunction↗