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Biomedical subjects

J Scott

Publications and source records attributed to J Scott.

At least 523 records · Page 29Linked to original sources

The human apolipoprotein AII gene: structural organization and sites of expression.

The complete nucleotide sequence of the human apolipoprotein All gene together with 911 bases of 5' flanking sequence and 687 bases of 3' flanking sequence have been determined. The mRNA coding region is interrupted by three introns of 169, 293 and 395bp. The Intro-exon structure of the apo All gene is similar to that of the apo AI, apo CIII and apo E genes: three introns separate 4 coding sequences specifying the 5' untranslated region, pre-peptide, a short N-terminal domain and a C-terminal domain composed of a variable number of lipid-binding amphipathic helices. Intron II carries a 33bp dG-dT repetitive element adjacent to the 3' splice junction which has the potential to adopt the Z-DNA conformation. The 5' and 3' terminuses of the mRNA have been identified by primer extension and S1 nuclease mapping. A number of short direct repeats are found in the 5' flanking region and an inverted repeat occurs between the CAAT and TATA boxes. Downstream of the the gene is an Alu family repeat containing a polymorphic MspI site, the deletion of which is associated with increased circulating levels of apoAII. ApoAII gene expression was demonstrated in adult human liver and HepG2 cells but not in human small intestine. Of ten Rhesus monkey tissues examined apo All mRNA was detected only in liver.

Amino Acid Sequence↗

Serum and thyroid hormones T3 and T4 regulate nerve growth factor mRNA levels in mouse L cells.

Mouse L cells synthesize and secrete a neurotrophic factor related to the beta subunit of the submaxillary gland nerve growth factor (NGF) of male mice. Use of a cDNA probe which encodes the beta-NGF mRNA demonstrated that L cells produce a transcript identical in size to that of the submaxillary gland. Moreover, target sites of restriction enzymes EcoRI, PstI and BamHI were not significantly rearranged in the beta-NGF gene locus of these cells. The abundance of the beta-NGF transcript was found to depend on culture conditions. Removal of serum depressed the cellular content of polyadenylated RNA by a factor of 1.7, and decreased specifically the pool of beta-NGF transcript by an additional factor of 4. The presence of 10(-7) M testosterone in the serum-free medium did not modify the level of beta-NGF mRNA, while addition of 10(-7) M T3 (or T4) increased this level by a factor of 1.5. These data provide the first evidence that the beta-NGF mRNA of L cells is subjected to regulation, but in a way apparently different from that described for the submaxillary gland.

Animals↗

High-density lipoprotein composition is altered by a common DNA polymorphism adjacent to apoprotein AII gene in man.

25 of a group of 87 White men had Msp 1 restriction site polymorphism within an Alu sequence 3' to the human apo AII gene. Homozygosity for the polymorphism in 8 men was associated with a significant increase in serum apo AII levels (35.4 +/- 1.70 mg/dl, mean +/- SEM) and altered HDL composition, compared with heterozygotes (31.7 +/- 1.29; n = 17) and normal subjects (29.4 +/- 0.64; n = 62). This is the first account of a common variant of an HDL apoprotein gene that affects HDL composition. In view of its association with a high apo AII concentration homozygosity may protect against atherosclerosis.

Apolipoprotein A-I↗

Levels of nerve growth factor and its mRNA in the central nervous system of the rat correlate with cholinergic innervation.

The levels of nerve growth factor (NGF) and its mRNA in the rat central nervous system were determined by two-site enzyme immunoassay and quantitative Northern blots, respectively. Relatively high NGF levels (0.4-1.4 ng NGF/g wet weight) were found both in the regions innervated by the magnocellular cholinergic neurons of the basal forebrain (hippocampus, olfactory bulb, neocortex) and in the regions containing the cell bodies of these neurons (septum, nucleus of the diagonal band of Broca, nucleus basalis of Meynert). Comparatively low, but significant NGF levels (0.07-0.21 ng NGF/g wet weight) were found in various other brain regions. mRNANGF was found in the hippocampus and cortex but not in the septum. This suggests that magnocellular cholinergic neurons of the basal forebrain are supplied with NGF via retrograde axonal transport from their fields of innervation. These results, taken together with those of previous studies showing that these neurons are responsive to NGF, support the concept that NGF acts as trophic factor for magnocellular cholinergic neurons.

Animals↗

Localization of genes encoding apolipoproteins CI, CII, and E to the p13----cen region of human chromosome 19.

The genes encoding apolipoproteins CI, CII, and E have been previously localized to chromosome 19. By use of rodent-human hybrid cell lines containing translocations of chromosome 19 we have now mapped these three genes to the region 19p13-19q13 and most probably 19p13-19cen. The clustering of APOC1, APOC2, and APOE must reflect their common evolutionary background and suggests that they may be coordinately regulated. Polymorphisms detected for any one gene will be useful for inheritance studies of all three.

Animals↗

Human alpha 2-macroglobulin gene is located on chromosome 12.

A cDNA clone encoding amino acids 809-1451 of the protease inhibitor alpha 2-macroglobulin has been isolated from an adult human liver cDNA library. This cDNA was used to examine DNA samples prepared from a panel of human-mouse somatic cell hybrids with different numbers and combinations of human chromosomes for the presence of the human alpha 2-macroglobulin gene. The cosegregation of this gene and chromosome 12 in the cell hybrid panel indicated that the alpha 2-macroglobulin structural gene (designated A2M) is on human chromosome 12.

Amino Acid Sequence↗

The effect of amphotericin B on 67Ga biodistribution.

The effect of Amphotericin B (AMB) on radiogallium biodistribution in mice was studied at various time intervals. Two doses of AMB (1 mg/kg and 10 mg/kg) were administered intraperitoneally into mice bearing EMT-6 mammary sarcomas. The tumor and tissue uptakes of 67Ga were calculated when the radioactivity was administered either as 67Ga-citrate or 67Ga-transferrin (Ga-Tf). The role of transferrin was also investigated by using doubly-labeled 67Ga-125I-Tf. Our results indicate that both the doses of AMB and the chemical form of the radiogallium administered affect the pattern of distribution in some distinct fashion. It was also found that although the administration of AMB results in an increase in tumor-associated transferrin, this does not necessarily result in a concomitant increase in radiogallium uptake. In general, the effects of AMB on various tissues uptake of 67Ga appear to be related to both acute and subacute toxicity.

Amphotericin B↗

A technique for the long term measurement of intra-compartmental pressure in the lower leg.

The early diagnosis of an acute compartmental pressure syndrome is often difficult, but can be facilitated by long term, up to several days, measurement of intra-compartmental pressures. A measuring system has been developed, together with its associated surgical and operational procedures, which may be applied in a variety of situations, including an immobile patient or a patient mobilized following surgery. If the technique is adopted as soon as the patient enters hospital, or immediately postoperatively, an acute compartmental syndrome may be recognized early and measures taken to alleviate its consequences.

Biomedical Engineering↗

Dry socket incidence compared after a 12 year interval.

A survey was conducted over a 3 month period in 1983 to examine the influence of clinical factors on the incidence of dry socket (DS) after extractions of permanent teeth under local analgesia. The findings were compared with those of a similar 3 month survey in the same hospital in 1971. Age, sex and extraction site each significantly influenced the incidence of DS. The major difference from the 1971 survey was an increase in the DS incidence from 3.0% to 4.0% of extractions. This occurred mainly following multiple extractions and may indicate that patients, particularly in this group, are nowadays less tolerant of any post-extraction discomfort and hence more readily return for attention. This is particularly relevant in the present study since the broad definition of DS used in both surveys embraced even the mildest presentations of disturbed socket healing.

Adolescent↗

Malignant mixed salivary tumor presenting as a mandibular metastasis.

A rare case of a central mandibular metastatic mixed salivary gland tumor is reported which presented following a 45-year history of recurrent benign mixed salivary gland tumor of the parotid gland on the same side. The mandibular tumor included a predominantly benign mixed salivary gland component as well as frankly invasive adenocarcinoma. The clinicopathologic features of the mandibular and residual parotid tumors suggested that the metastatic event may have occurred prior to the development of frank carcinoma in the parotid tumor.

Adenocarcinoma↗

Effect of hypoxia on pig heart short-chain acylcarnitines.

The right ventricles of pig heart were perfused with hypoxic blood and the left ventricles were perfused with normally ventilated arterial blood. Free carnitine and short-chain acylcarnitines in hypoxic ventricles were lower than in perfused controls, and much lower than in non-perfused heart. Acetylcarnitine levels decreased and the branched-chain acylcarnitines and propionylcarnitine were elevated in the hypoxic perfused ventricles. These data indicate that both hypoxia and anaesthesia caused loss of carnitine and short-chain acylcarnitines from the heart and hypoxia also changed the distribution of short-chain acylcarnitines in the heart.

Animals↗

Chromosomal locations of the human and mouse genes for precursors of epidermal growth factor and the beta subunit of nerve growth factor.

DNA probes for pre-pro-epidermal growth factor (EGF) and the precursor of the beta subunit of nerve growth factor (NGF) were used to chromosomally map human and mouse EGF and NGF genes in panels of human-mouse and mouse-Chinese hamster somatic cell hybrids. The EGF and NGF genes were mapped to human chromosomes 4 and 1, respectively, by using human-mouse cell hybrids. A combination of regional mapping using a chromosome 1 translocation and comparative gene mapping suggests that the human NGF gene is in the p21-p22.1 region of chromosome 1. In mouse-Chinese hamster cell hybrids, both genes were assigned to mouse chromosome 3. A knowledge of the chromosomal assignment of these genes should help in our understanding of their regulation and role in development and disease.

Animals↗

A histological analysis of the early effects of alcohol and tobacco usage on human lingual epithelium.

Macroscopically normal tongues were examined from 161 necropsies. Two types of lingual epithelium were investigated by morphometry and the results were statistically analysed in relation to known levels of alcohol and tobacco usage in each case. Alcohol and tobacco were each associated with a reduction in epithelial thickness brought about by a reduction in the maturation layer due mainly to cell shrinkage. By contrast, the progenitor layer increased in size, due to hypertrophy rather than hyperplasia. Changes occurred in each type of epithelium and were more severe with alcohol. There was no significant interaction between alcohol and tobacco. The structural changes appeared to be non-specific reactions to local toxic effects of alcohol and tobacco. They could, if accompanied by equivalent functional decrements, indicate an increased vulnerability to carcinogens, whether or not these derive from alcoholic drinks or tobacco smoke.

Adolescent↗

Morphometric analysis of atrophic changes in human lingual epithelium in iron deficiency anaemia.

A stereological analysis of epithelial structure at the lateral surface of the tongue showed that iron deficiency anaemia was associated with reduced epithelial thickness despite the absence of overt mucosal abnormalities. The epithelial atrophy was entirely due to a reduction in the size and number of cells in the maturation compartment. By contrast, the progenitor cell compartment was increased in thickness due to an increase in the number of cells. This hyperplastic reaction may be a trophic response to the overall loss of epithelium in this condition.

Adolescent↗

The structure and biosynthesis of epidermal growth factor precursor.

The structure of mouse submaxillary gland epidermal growth factor (EGF) precursor has been deduced from complementary DNAs. The mRNA is approximately 4800 bases and predicts prepro EGF to be a protein of 1217 amino acid residues (133 X 10 Mr). EGF (53 amino acid residues) is flanked by polypeptides of 188 and 976 residues at its carboxy and amino termini, respectively. The amino terminus of the precursor contains seven cysteine-rich peptides that resemble EGF. Towards the carboxy terminus is a 20-residue hydrophobic membrane spanning domain. The mild portion of the EGF precursor shares a 33% homology with the low density lipoprotein receptor, which extends over 400 amino acid residues. These features suggest that EGF precursor could function as a membrane-bound receptor. RNA dot-blot analysis and in situ hybridization show EGF mRNA to be abundant in the submaxillary gland, kidney and incisor tooth buds. Lower EGF mRNA levels were found in the lactating breast, pancreas, small intestine, ovary, spleen, lung, pituitary and liver. In the kidney EGF mRNA was most abundant in the distal convoluted tubules. Analysis of EGF precursor biosynthesis in organ culture of the submaxillary gland and kidney showed differential processing of the precursor in the two tissues. In the submaxillary gland immunoreactive low molecular weight EGF was produced, but in the kidney the high molecular weight precursor was not processed. In the distal convoluted tubule of the kidney EGF precursor may act as a receptor that is involved in ion transport.

Amino Acids↗