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Biomedical subjects

A Marshall

Publications and source records attributed to A Marshall.

At least 91 records · Page 5Linked to original sources

Inactivation of wild-type and rad mutant Caenorhabditis elegans by 8-methoxypsoralen and near ultraviolet radiation.

Survival of wild-type and four radiation-sensitive (rad) mutants of the nematode Caenorhabditis elegans was determined after near-UV irradiation in the presence of 8-methoxypsoralen (8-MOP). Three sets of inactivation profiles were generated for each strain by irradiating synchronous populations of either early embryos, late embryos or first-stage larvae (L1s). Late embryos were consistently the most sensitive. Curiously, none of the four rad mutants were even moderately hypersensitive. Split-dose experiments indicated that DNA-DNA crosslinks were primarily responsible for lethality. Crosslink induction and repair were determined using two different assays. In both cases, little if any repair was observed in wild-type. This lack of repair thus explains why the rad mutants were not hypersensitive to 8-MOP photoinactivation. Since early embryos undergo extensive cell cycling, their resistance to 8-MOP photoinactivation suggests that replication is highly refractory to both monoadducts and crosslinks, as has been demonstrated previously for UV radiation-induced photoproducts (Hartman et al., 1991, Mutat. Res., 255, pp. 163-173).

Animals↗

Postexercise reflex control of forearm vascular resistance during calcium antagonism with slow-release oral isradipine.

In untreated hypertensive patients, blood pressure is decreased during the hours that follow a single bout of exercise, but the mechanisms involved are as yet unknown. As antihypertensive chemotherapy may interfere with cardiovascular regulation, we investigated the effects of calcium antagonism with isradipine (slow-release oral formulation, SRO) on postexercise blood pressure and on the reflex control of forearm vascular resistance in patients with mild-to-moderate hypertension. The results show that isradipine SRO exerted an additional blood pressure-lowering effect after exercise that was associated with a further decrease in forearm vascular resistance. The reflex changes in forearm vascular resistance were potentiated after exercise, but were not further affected by isradipine SRO. Therefore, isradipine SRO does not interfere with the cardiovascular mechanisms that act to decrease blood pressure after exercise in patients who have hypertension.

Administration, Oral↗

The DNF15S2 locus at 3p21 is transcribed in normal lung and small cell lung cancer.

Small cell lung cancer (SCLC) has been associated with a deletion of the short arm of chromosome 3. One SCLC cell line, H748, has an interstitial deletion of chromosome 3p and shows allele loss for the DNF15S2 locus detected by the probe lambda H3. Conservation of DNF15S2 sequences in mouse indicated that this human genomic fragment may contain coding sequences. Screening of a normal lung cDNA library with chromosome 3-specific fragments of the lambda H3 probe resulted in the isolation of 18 positive clones. The cDNA clones detect an additional DNA polymorphism that is in linkage disequilibrium with the HindIII polymorphism of the DNF15S2 locus. Sequence analysis indicated that the DNF15S2 locus could potentially code for a previously unreported protein of 67 kDa which has 26 cysteine residues. DNF15S2 is part of the coding region of a 3.3-kb mRNA expressed in lung. Northern analysis indicated that this mRNA was not detectable in one of five SCLC lines. This SCLC line, H128, also lacks the enzyme aminoacylase 1.

Amino Acid Sequence↗

Rat clusterin isolated from primary Sertoli cell-enriched culture medium is sulfated glycoprotein-2 (SGP-2).

Clusterin, a glycoprotein originally isolated from ram rete testis fluid, is a dimer composed of monomers with non-identical NH2-terminal amino acid sequences. In view of its possible role in cell-cell interactions in the seminiferous epithelium, we sought to identify such a protein in the rat. Using the bioassay developed for the ovine protein, rat clusterin was purified to apparent homogeneity by HPLC from primary Sertoli cell-enriched culture media. This protein is also a heterodimer consisting of monomers of Mr 43,000 (alpha) and Mr 35,000 (beta). NH2-Terminal amino acid sequence analysis indicated that the alpha subunit has a sequence of NH2-SLMPLSHYGPLSFHNMFQPFFDMIHQAQQA and the beta subunit, NH2-EQEFSDNELQELSTQGSRYVNKEIQNAVQG. These two subunits show marked similarity with the corresponding subunits of ram clusterin isolated from rete testis fluid. Using an antibody against the alpha subunit of rat clusterin, a cDNA clone was isolated from a rat testicular lambda gt11 cDNA library. Analyses of the amino acid sequence derived from the isolated rat clusterin cDNA and of the NH2-terminal amino acid sequences indicate that rat clusterin is identical to a Sertoli cell glycoprotein previously designated sulfated glycoprotein-2.

Amino Acid Sequence↗

Genes for human vitamin K-dependent plasma proteins C and S are located on chromosomes 2 and 3, respectively.

cDNAs encoding human proteins C and S have been used to screen a panel of mouse-human somatic cell hybrids to determine the chromosomal location of their respective genes. The gene for human protein C is located on chromosome 2, whereas that for protein S is located on chromosome 3. Analysis of human genomic DNA restriction endonuclease fragmentation patterns suggests that the human protein S gene is greater than 40 kb in size and contains a minimum of 11 introns.

Animals↗

Adult polyglucosan body disease (APBD).

Three patients aged 63, 63 and 74 years had various combinations of progressive lower and upper motor neuron dysfunction, sensory loss, urinary incontinence and dementia. Postmortem examinations in two cases showed moderate cerebral and spinal atrophy, ill-defined areas of incomplete myelin loss in white matter and small necrotic foci in the white matter of gyri, around the basal ganglia and near the dentate nuclei. The main microscopic abnormality was a massive accumulation of PAS-positive polyglucosan bodies (PB) of various sizes and shapes in the cerebral hemispheres, brainstem, cerebellum, spinal cord, nerve roots and nerves. These PB were found in the processes of nerve cells and astrocytes, but not in their perikarya. Similar PB were present in peripheral nerves and in the lungs, heart, liver and kidneys. In the third case, a nerve biopsy revealed several, unusually large, PB in the axons of myelinated fibers. These clinicopathologic features are consistent with adult polyglucosan body disease (APBD) and are distinctive from other conditions in which PB may accumulate. Twelve similar cases have been reported previously. The diagnosis can be made by nerve biopsy. The pathogenesis of APBD is not known, but it may be a polysaccharide storage disease.

Aged↗

Restriction fragment length polymorphism studies show consistent loss of chromosome 3p alleles in small cell lung cancer patients' tumors.

Previous karyotypic analysis of human small cell lung cancer cell lines has demonstrated a consistent deletion of a portion of the short arm of chromosome 3(p14-23). DNA prepared from tumors and normal tissues obtained from 24 small cell lung cancer and two extrapulmonary small cell cancer patients was hybridized to four probes that detect restriction fragment length polymorphisms within chromosome region 3p14-21. Of the 25 patients who were heterozygous for at least one marker in this region in the DNA from normal tissue, 23 (92%) showed an unequivocal loss of heterozygosity in the DNA from their tumor tissue. From these studies we conclude that loss of alleles from the short arm of chromosome 3 is a consistent finding in unselected small cell lung cancer patients' tumor DNA.

Adult↗

Assignment of the lactotransferrin gene to human chromosome 3 and to mouse chromosome 9.

Lactotransferrin (LTF), a member of the transferrin family of genes, is the major iron-binding protein in milk and body secretions. The amino acid sequence of LTF consists of two homologous domains homologous to proteins in the transferrin family. Recent isolation of cDNA encoding mouse LTF has expedited the mapping of both mouse and human LTF genes. Southern blot analysis of DNA from mouse-Chinese hamster and human-mouse somatic cell hybrids maps the LTF gene to mouse chromosome 9 and to human chromosome 3, respectively. Furthermore, analysis of cell hybrids containing defined segments of human chromosome 3 demonstrates that the gene is located in the 3q21-qter region. These results suggest that LTF and associated genes of the transferrin family have existed together on the same chromosomal region for 300-500 million years.

Animals↗

Chromosomal assignments of genes for tissue plasminogen activator and urokinase in mouse.

The genes encoding the two plasminogen activators, tissue plasminogen activator and urokinase, were mapped to mouse chromosomes using probes derived from the respective mouse cDNAs. DNA from mouse-Chinese hamster and mouse-rat somatic cell hybrids was digested with BamHI and EcoRI, respectively, and analyzed by Southern blot hybridization for the segregation of the two genes. Tissue plasminogen activator and urokinase cosegregated with mouse chromosomes 8 and 14, respectively. The plasminogen activator genes thus fall into two syntenic groups that are conserved in human and mouse.

Animals↗

Hemopexin is localized to human chromosome 11.

Hemopexin, a plasma protein that migrates during electrophoresis with the beta-globulins, transports free heme to sites of its catabolism in the liver. A hemopexin cDNA clone has been utilized for mapping the hemopexin (HPX) gene to human chromosome 11 in the region pter----p11 by somatic cell hybrid analysis.

Animals↗

Localization of human SAA gene(s) to chromosome 11 and detection of DNA polymorphisms.

A human serum amyloid A (SAA) cDNA was used as a probe in chromosome mapping studies to detect human SAA gene sequences in DNA isolated from human/mouse somatic cell hybrids. Southern analysis of DNA from 20 hybrid cell lines, including some with translocations of human chromosomes, placed the SAA gene(s) in the p11----pter region of chromosome 11. Screening of human DNA from unrelated individuals by Southern analysis using the SAA cDNA probe revealed restriction fragment polymorphisms for HindIII and PstI. An analysis of the segregation of these polymorphisms with other markers on the short arm of chromosome 11 should more precisely map the SAA gene(s).

Amyloid↗

Outbreak of Salmonella eimsbuettel in newborn infants spread by rectal thermometers.

Over a six-week period there were 25 episodes of Salmonella eimsbuettel infection in newborn infants, mothers, and staff in a modern maternity hospital with 3600 annual deliveries. The probable source was a mother and her child, and the organism was spread by rectal thermometers in the labour suite and one of the wings (wards). When the thermometers were withdrawn from use and correctly disinfected the outbreak in babies ceased. Environmental cross-infection of staff was halted by closure, cleaning, and disinfection of the clinical area mainly affected. Some babies had diarrhoea but quickly recovered, and none came to harm. The infected staff had no symptoms and returned to duty after three negative cultures. Measurement of temperature is still an important observation in the care of newborn infants, but for everyday care it is recommended that rectal thermometry be discontinued and replaced by axillary measurement.

Cross Infection↗

Nicotine chewing gum in general practice: effect of follow up appointments.

Two hundred smokers who were judged by their general practitioner to be motivated to stop smoking were allocated to one of two groups. All were offered an initial appointment at which they were advised to stop smoking and offered nicotine gum. One group then received no further appointments. The other was offered four further appointments over three months. Both groups were followed up at six and 12 months. At one year follow up 15.5% overall had stopped smoking, 14% in the low and 17% in the high contact group. This is better than most results so far reported for nicotine chewing gum in general practice, suggesting that general practitioners can use it to good effect. We compare this result with others achieved in general practice.

Chewing Gum↗