Biomedical subjects

M T Smith

Publications and source records attributed to M T Smith.

332 records · Page 19Linked to original sources

PubMedDate not supplied

ABO and Rh(D) blood group frequencies in the Ards Peninsula, northeastern Ireland: evidence for the continuing existence of a major politico-religious boundary.

Data are presented on the ABO and Rh(D) frequencies of 1685 individuals living in the Ards Peninsula, northeastern Ireland. Previous investigations based on surname analysis and linguistic studies showed a basic north-south population divide that could be traced back at least to the early seventeenth century. The current survey indicates the continuation of this divide, which is coincident with known patterns of religious persuasion.

ABO Blood-Group System↗

PubMedDate not supplied

Genetic structure of the Azores: marriage and inbreeding in Flores.

Flores is one of the smallest and most westerly islands of the Atlantic archipelago of the Azores. This preliminary account of the population's demography and genetic structure uses dispensations to contract consanguineous marriages taken from the Roman Catholic marriage registers in order to estimate mean inbreeding rates in the population over the period 1860-1980. Comparisons are made with inbreeding rates on the Portuguese mainland and elsewhere in Western Europe, and reasons suggested to explain the rather high rates of inbreeding encountered on Flores.

Azores↗

PubMedDate not supplied

Estimating inbreeding from the Faculty Office Registers, 1534-1540.

Estimates of inbreeding are rather scarce for British populations. A number of studies, especially of Scottish island populations, have focused on pedigree analysis, whilst others have used survey methods or inference from isonymy. By comparison with continental Europe, however, little is known of the historical development of inbreeding. This is undoubtedly due to the lack of evidence from dispensations to marry blood relatives, which are routinely available in the records of marriage of the Roman Catholic church. The paper uses as its data source the Faculty Office Registers, 1534-1540, which were the product of a new system of issuing dispensations following the Dispensations Act of 1533, and which are among the earliest administrative records of the Church of England, founded as a result of Henry VIII's breach with Rome. Dispensations are recorded in the Faculty Office until 1540, when all prohibitions on marriage beyond the proscribed relationships laid down in Leviticus were lifted. The data suggest surprisingly low levels of consanguineous marriage, including a lack of first-cousin marriages. These findings are discussed in terms of the reliability of the archive, and of the social and religious views attending marriage between blood relatives in the medieval and early modern periods.

Consanguinity↗

PubMedDate not supplied

Rationale for selecting exfoliated bladder cell micronuclei as potential biomarkers for arsenic genotoxicity.

Biomarkers of effect have important potential in epidemiology, since they may enable ascertainment of exposure-effect associations in relatively inexpensive cross-sectional studies, with confirmation by short follow-up after cessation of exposure. Arsenic is known to cause human skin and lung cancer, and may also cause various internal cancers including bladder, kidney, and liver cancer. The strongest epidemiological association between arsenic ingestion and an internal cancer is that with bladder cancer. Epidemiological studies of a Taiwanese population exposed to high levels of arsenic from drinking water reported relative risks for bladder cancer well above any other known environmental carcinogen. Populations at increased risk for bladder cancer from other exposures, such as smoking and schistosomiasis infection, have elevated frequencies of micronuclei in exfoliated bladder cells. We have therefore proposed that the bladder cell micronucleus assay could be an appropriate biological marker of genotoxic effect of arsenic exposure. In this paper, we present the rationale for choosing the bladder cell micronucleus assay as a potential biomarker of effect for arsenic. We also briefly describe the studies we are conducting using this biomarker in currently exposed populations.

Arsenic↗

PubMedDate not supplied

Novel biomarkers of genetic damage in humans: use of fluorescence in situ hybridization to detect aneuploidy and micronuclei in exfoliated cells.

Here we describe new techniques that employ fluorescence in situ hybridization (FISH) with centromeric and chromosome-specific DNA probes to detect aneuploidy and micronucleus formation in exfoliated human epithelial cells. Micronuclei arise from chromosome breakage or lagging, which results in chromosome fragments and whole chromosomes being left outside of the main nucleus at telophase. By using a centromeric DNA probe to detect the presence of whole chromosomes in micronuclei and propidium iodide as a general DNA stain in exfoliated nasal, buccal, and bladder cells, we have developed a new fluorescent method that can detect micronuclei and determine the mechanism of formation. The new fluorescent technique gave results that were very similar to those obtained with the standard Feulgen-fast green method. The spontaneous levels of micronuclei in healthy volunteers were buccal, 0.13%, nasal, 0.21%, and urothelial, 0.07%, in approximately 1500 cells per data point. These values are lower than that found in cultured lymphocytes, 0.4-0.8%. Approximately 50% of the exfoliated cell micronuclei contained whole chromosomes (centromeric DNA). FISH was also used to detect aneuploidy in exfoliated buccal and bladder cells. A DNA probe specific for chromosome 9 was used. Average frequencies for 0, 1, 2, 3, and 4 hybridization regions were 4.8, 9.3, 84.8, 0.8, and 0.3% for urothelial cells and 8.2, 9.9, 80.1, 1.4, and 0.4% for buccal cells. The estimated frequency of aneuploidy in exfoliated cells is similar to that found in human lymphocytes analyzed by FISH with the same probe for chromosome 9. These techniques are potentially useful for epidemiological studies of exposed populations and are currently being applied in our laboratory for studies of arsenic- and formaldehyde-exposed populations.

Adult↗

PubMedDate not supplied

Geotrichum capitatum septicaemia in neutropenic patients: case report and review of the literature.

We report a case of systemic infection with Geotrichum capitatum in a patient with acute myeloid leukaemia. Three days before death, the patient developed acute renal failure, probably caused by occlusion of glomerula with hyphae of G. capitatum. Up until now, prophylaxis and treatment of infections caused by Geotrichum capitatum have not been established. However, the prophylactic administration of high-dose itraconazole and the therapeutic use of liposomal amphotericin B are subjects of discussion.

Acute Disease↗

PubMedDate not supplied

Quantitative analysis of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine metabolism in isolated rat hepatocytes.

The biotransformation of the tertiary amine 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) was studied in isolated rat hepatocytes, in order to assess the relative contributions of the metabolic reactions previously described in studies with subcellular preparations. The oxidative pathway which produces the toxic metabolite 1-methyl-4-phenylpyridinium ion (MPP+) via the generation of the 2,3-dihydropyridinium derivative, MPDP+, accounted for approximately 90% of MPTP metabolism by hepatocytes. Mitochondrial monoamine oxidase type B (MAO B) was specifically responsible for the initial step of this conversion. In the endoplasmic reticulum, cytochrome P-450 catalyzed the demethylation of MPTP to form PTP, while the flavin-containing monooxygenase (FMO) was responsible for the generation of MPTP N-oxide. No other metabolite was detected in our hepatocyte incubations under any of the experimental conditions used. After pretreatment with the specific MAO B inhibitor, deprenyl, the rates of production of the two microsomal metabolites were enhanced, but the overall rate of MPTP conversion decreased by more than 60%. On the other hand, no significant difference in the rate of MPTP metabolism was found after the inhibition of cytochrome P-450 by SKF 525-A or with the use of methimazole, a competitive substrate for FMO. The SKF 525-A and methimazole treatments selectively inhibited the formation of PTP and MPTP N-oxide, respectively, but had no significant effect on the rate and extent of MPTP toxicity. MPP+ was the only metabolite which accumulated within the cell compartment under all the experimental conditions.(ABSTRACT TRUNCATED AT 250 WORDS)

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine↗

PubMedDate not supplied

Increased micronuclei in exfoliated bladder cells of individuals who chronically ingest arsenic-contaminated water in Nevada.

It is well established that inorganic arsenic is causally associated with lung cancer via inhalation and skin cancer via ingestion. Epidemiological evidence based on studies in Taiwan suggests that ingestion of inorganic arsenic may also cause other more fatal internal cancers, with the highest relative risks reported for bladder cancer. Here, we have used a biological marker of response, the micronucleus assay in exfoliated bladder cells, to evaluate the possible genotoxic effects of chronic arsenic ingestion on the bladder. The overall objective of this study was to compare the frequency of micronucleated cells in exfoliated bladder and buccal cells between a group of 18 individuals in Nevada who chronically ingested high levels of inorganic arsenic from their well water (average level, 1,312 micrograms/liter) and an individually matched control group with low exposure to arsenic (average level, 16 micrograms/liter). A 1.8-fold increase (90% confidence interval, 1.06-2.99) was observed in the weighted mean frequency of micronucleated bladder cells in the exposed group (2.79 per 1000 cells) compared with the unexposed group (1.57 per 1000 cells). In addition, the frequency of micronucleated bladder cells was positively associated with the urinary concentration of inorganic arsenic plus its methylated metabolites (Spearman correlation = 0.33; P = 0.03). In contrast, there was no increase in micronucleated buccal cells associated with arsenic ingestion (frequency ratio = 1.0; 90% confidence interval, 0.65-1.53). The results of this study provide evidence that chronic ingestion of high levels of inorganic arsenic in drinking water is associated with an increased frequency of micronucleated bladder cells. These findings are consistent with a genotoxic effect of arsenic on bladder cells, but a larger study is needed to confirm them.

Adolescent↗