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Biomedical subjects

J P Martin

Publications and source records attributed to J P Martin.

At least 19 recordsLinked to original sources
PubMed1992

Human inter-alpha-trypsin inhibitor: full-length cDNA sequence of the heavy chain H1.

Inter-alpha-trypsin inhibitor (ITI), called inter-alpha-inhibitor, is a 220 kDa serine proteinase inhibitor found in human serum. It is composed of at least three distinct polypeptide chains. These chains, named H1, H2 and L, are an independently synthesized and proteolytically processed precursor protein. Only the complete structure of H2 and L has been established so far. We used a PCR-based cloning approach and a cDNA screening library to isolate the full-length cDNA H1. The amino acid sequences of the two heavy chains deduced from the cDNA are highly similar (40% identity). Nevertheless, the structure of the signal peptide and propeptide in the N-terminal region is different in these two chains. A complex posttranslational cleavage at both ends of H1 and H2 may be proposed prior to assembly of the ITI chains.

Alpha-Globulins↗
PubMed1992

Modification of the amount of cholesterol in hepatic steatosis induced in susceptible and resistant mice infected with MHV3: a biochemical and ultrastructural study.

A mouse hepatitis virus-3 strain subcultured in our laboratory is a unique experimental model in which to study virus-induced liver steatosis. This strain produces massive lipid deposition not only in sensitive adult BALB/c mice but also (though less extensive) in virus-resistant adult A/J mice. Biochemical determinations have shown that this steatosis is characterized by an increased amount of neutral lipids (sterols and triglycerides) in infected livers of BALB/c mice and by a smaller increase in those of A/J mice. However, the relative percentage of cholesterol and triglycerides is similar in both strains. Liver phospholipid content was significantly decreased in both strains of mice. To discriminate between cytoplasmic and membrane cholesterol content in different types of liver cells, an ultrastructural study was performed with filipin, a specific cholesterol marker. This study shows on one hand an important increase in the cholesterol in the hepatocytes of BALB/c mice and a smaller increase in those of A/J mice, in agreement with biochemical data. However, marked cholesterol decrease and abnormal cholesterol distribution were observed in the endothelial liver cells of infected BALB/c mice. This decreased cholesterol content probably led to higher fluidity of these membranes, which could be related to the important drop in the number of endothelial cell fenestrae observed after mouse hepatitis virus-3 infection. Because in A/J infected mice neither a decrease in the amount and distribution of cholesterol nor decreased fenestration were observed in endothelial liver cells, these findings could be correlated with the resistance of these mice to the infection.

Animals↗
PubMed1992

Relation of serum elastin peptide concentration to age, FEV1, smoking habits, alcohol consumption, and protease inhibitor phenotype: an epidemiological study in working men.

BACKGROUND: In clinical investigations elastin peptide concentration has been proposed as one potential marker of lung elastin degradation. No epidemiological study has yet confirmed this hypothesis. METHODS: The relation of elastin peptide concentration to some factors closely related to pulmonary emphysema (age, smoking habits, FEV1 alpha protease inhibitor (PI) phenotype) and to alcohol consumption was examined in an epidemiological study of 310 working men. The elastin peptides used for obtaining antibodies and as reference in an ELISA assay were prepared from chemically hydrolysed elastin. RESULTS: The elastin peptide concentration significantly decreased with age from 2.92 (1.54) micrograms/ml among subjects younger than 30 years to 2.18 (1.14) micrograms/ml among subjects older than 50. Elastin peptide concentration did not differ with smoking habits and was clearly unrelated to FEV1. A lower elastin peptide concentration was observed in all groups of subjects with a protease inhibitor phenotype other than PI MM (PI FM, IM, MP, MS, MZ, and S phenotypes). CONCLUSIONS: The results cast doubts on the usefulness of the elastin peptide concentration as a marker of lung destruction in middle aged, predominantly healthy men. Blood elastin peptide concentration may reflect both elastin degradation and resynthesis. The results of this analysis suggest that several factors (age, alcohol consumption, non-PI MM phenotype) may be associated with decreased resynthesis of lung elastin. Further studies, conducted in various age groups and including estimates of the degree of lung destruction, are needed to unravel the mechanisms underlying lysis and resynthesis of lung elastin.

Adult↗
PubMed1992

[Keloid cicatrix of the face and neck. Apropos of 81 cases treated in Dakar].

The authors report their experience of the treatment of 81 cases of keloid scars in Africa. Many methods have been proposed and used but they do not consistently lead to good results. The fact that many operations have been indicates their back of efficacy. The natural tendency towards recurrence dictates the correct choice of operation. The best result is obtained by combining surgery with radiotherapy.

Adolescent↗
PubMed1992

Serum trypsin-like activity in chronic alcoholized men: possible relationship with lipids, apoA-1 and apoB lipoproteins.

Chronic alcoholization is known to increase plasma trypsin levels. One-hundred and forty-six male chronic alcohol users were tested for serum trypsin-like activity (STA), total cholesterol (TC), LDL-cholesterol (LDL-C), HDL-/cholesterol (HDL-C), triglycerides (TG), apoA-1 and apoB lipoproteins. STA was positively correlated to LDL-C, TG and apoB rates and the CT/HDL-C index and negatively correlated to HDL-C and apoA-1 rates and the apoA-1/apoB index. Eighty-four patients with high STA (group B) compared to 62 patients with normal STA (group A) showed significantly higher LDL-C, TG, apoB rates and TC/HDL-C index contrasting with significantly lower HDL-C and apoA-1 rates and the apoA-1/apoB index. The two groups were matched for age, overweight, cigarette smoking and glycemia. Hepatic dysfunction does not explain the differences in the lipoproteic parameters. Such results would suggest that there may be a tryptic alteration of apoproteins in vivo as already demonstrated in vitro and experimentally suspected in vivo in some other studies. Competition by the trypsin-activated alpha 2 macroglobulin for the chylomicron-remnant LDL receptor-related protein may be evoked.

Alcoholism↗
PubMed1991

[Inter-alpha-trypsin inhibitor and its derivatives in inflammatory syndromes].

Modifications of inter-alpha-trypsin inhibitor (ITI) in inflammatory syndromes were determined by studying its serum components: ITI 80 (the native form) and serum derivatives (SD), as well as urinary ITI derivatives (UID) excretion in 31 controls and 128 patients with inflammatory of various origins. The patients were divided into 4 groups: Group I bacterial infections (n = 29); Group II cancers (n = 50); Group III inflammatory diseases (n = 14); Group IV inflammatory syndromes due to other causes (n = 35). Other markers of inflammation were also studied. In bacterial infections and cancers ITI 80 concentrations were significantly decreased, with values of 0.55 +/- 0.15 g/l and 0.54 +/- 0.15 g/l respectively vs 0.65 +/- 0.11 g/l in controls. SD concentrations were significantly increased in all 4 groups: Gr I: 0.31 +/- 0.12 g/l; Gr II: 0.30 +/- 0.11 g/l; Gr III: 0.25 +/- 0.08 g/l; Gr IV: 0.24 +/- 0.10 g/l, as compared with 0.16 +/- 0.09 in controls. UID excretion was increased in all cases, particularly in bacterial infections and cancers (10.8 +/- 13.4 and 6.0 +/- 8.8 mg/mmol of creatinine vs 1.5 +/- 1.7 g/mmol). A significant correlation was observed between CRP levels and SD levels. In bacterial infections and cancers, a fall in ITI associated with a rise in SD and an increase in UID excretion is suggestive of degradation of the native form. In inflammatory diseases and inflammatory syndromes of other causes, the rise in SD without significant variations in ITI 80 suggests and increase in SD synthesis. The correlation between CRP and SD seems to indicate that SD are produced in the early stage of inflammatory syndromes.

Adult↗
PubMed1991

Altered pathogenicity in the liver induced by a mouse hepatitis virus type 3 thermosensitive mutant.

Intraperitoneal inoculation into sensitive BALB/c mice of D85, a thermosensitive (ts) mutant, provokes acute hepatitis followed by recovery of the mice. The ts mutant was able to replicate in the liver. However, the maximal viral titre was obtained 2 days later than was the case with the wild-type (wt) MHV 3 infection; the viral antigens remained localized within small foci and no invasion of the entire liver was observed. The hepatocytes infected with D85 showed strong steatosis similar to that induced by wt virus, but the other lesions induced by MHV 3 (closing of endothelial cell fenestrae and hepatocytolysis) were not seen. An important feature noticed with the D85 mutant concerned the establishment, in the surviving animals, of persistent infection: this phenomenon was demonstrated by the decrease of viral titre in the liver, viral RNA detection, and the fact that viral antigens gradually decreased until the 3rd month post-infection.

Animals↗
PubMed1991

Issues in the current treatment of hospice patients with HIV disease.

Hospice administrators and clinicians face many complex issues regarding the treatment of persons terminally ill with AIDS, at one end of the spectrum of HIV disease. Among these issues are: whether the hospice model applies to persons with AIDS; at what point does the person with AIDS receive palliative rather than curative therapy; and what alternatives exist for hospice care if the AIDS patient has no primary care provider or no home in which to receive care. This article delineates and discusses these issues.

Eligibility Determination↗
PubMed1991

Acquired immunity of A/J mice to mouse hepatitis virus 3 infection: dependence on interferon-gamma synthesis and macrophage sensitivity to interferon-gamma.

Coronavirus-free A/J mice (A/J-), in contrast to those naturally infected with coronavirus (A/J+), were shown to be susceptible to experimental infection with our strain of mouse hepatitis virus 3 (MHV3). A/J- mice experimentally hyperimmunized with inactivated MHV3 (A/Ji) became resistant to challenge with this virus. BALB/c mice free of (BALB/c-) or naturally infected with (BALB/c+) coronavirus, or hyperimmunized with inactivated MHV3 (BALB/ci), were always fully susceptible. All susceptible mice developed an acute hepatitis with a high virus titre in the tissues. Resistance mice developed a mild disease in which the low virus titres detected in the tissues were cleared. After infection, interferon (IFN)-gamma synthesis in A/J- mice was lower than that in A/J+ and A/J mice; IFN-gamma synthesis was very high in BALB/c+ and BALB/ci mice, but low in BALB/c- mice. Studies of the anti-MHV3 effect induced in macrophages in vitro showed that only IFN-gamma-activated A/J mouse macrophages were able to restrict partially the growth of MHV3, regardless of whether the animals had been immunized. The effect occurred only when the cells were activated with IFN-gamma before virus infection. The results indicate that the resistance of A/J mice to our strain of MHV3 is not natural but is acquired after immunization, and that the mechanism involved is dependent on T cell activity, IFN-gamma production and the sensitivity of macrophages to IFN-gamma.

Animals↗
PubMed1991

The prevalence of cognitive impairment in a community survey of multiple sclerosis.

A one in two alternate sample (N = 200) from a population-based register of 411 people with multiple sclerosis (MS) was studied. Out of this sample, 147 people with MS and 34 people with rheumatoid arthritis were interviewed at home and completed a battery of neuropsychological tests. Cognitive impairment was found in 46 per cent of those with MS, with memory impairment in 34 per cent and failure on tests of frontal lobe function in 33 per cent. Physical disability was associated with cognitive impairment. Memory impairment was more common in those who had had MS for 10 years or more. A significant minority of people with mild physical disability and some who had had MS for less than a decade nevertheless had cognitive impairment. Relationships between cognitive impairment, other disease variables and psychosocial factors were examined. Counselling and rehabilitation programmes for people with MS and their families should take account of cognitive deficits that may be present.

Adult↗
PubMed1991

The prevalence of multiple sclerosis in the Southampton and South West Hampshire Health Authority.

A first survey of the Southampton and South West Hampshire Health Authority showed an overall prevalence of multiple sclerosis of 99/100,000 in a population of 417,000 on 1 January 1987. This finding is similar to other recent first surveys in the South of the United Kingdom and only repeat surveys will show if case only repeat surveys will show if case ascertainment has been more complete in these than earlier first studies in Scotland.

Adolescent↗
PubMed1991

Alpha-1-antitrypsin (PI) polymorphism in France, with special regard to the PI*Z allele.

Alpha-1-antitrypsin (PI) phenotypes were studied in a sample of more than 5,000 individuals from cities throughout France. Special interest was paid to the PI*Z allele whose average frequency, based on the present work plus results from the literature, was 0.0130. This figure was used to estimate the number of PI Z homozygotes in France. In accordance with previous studies, the frequency of the PI*S allele was found to increase towards the southern parts of France.

Adult↗
PubMed1990

Structural analysis of the human inter-alpha-trypsin inhibitor light-chain gene.

The human inter-alpha-trypsin inhibitor (ITI) light-chain gene, which codes for the two proteins alpha 1-microglobulin (protein HC) and ITI-derived human inhibitor of 30 kDa (HI-30), was isolated from a human genomic library. This gene, present as a single copy in the human genome, is composed of 10 exons and 9 introns distributed over 20 kbp. A single transcriptional initiation site was identified in the 5'-flanking region which contained promoter elements, but no typical TATA box. However a sequence equivalent to the TATA box is present on both sense and anti-sense strands in the 5'-flanking region of the first exon coding for HI-30. The exon-intron organization suggests that the regions coding for protein HC and other members of the lipocalin superfamily evolved from a common ancestral gene that is probably different from that coding for HI-30. These data suggest that two distinct ancestral genes could have existed and fused during evolution. Several direct and one inverted repeats are also found within this gene, as well as potential glucocorticoid-receptor binding sites.

Alpha-Globulins↗