Search PubMed⌕ Search

Biomedical subjects

P Marsh

Publications and source records attributed to P Marsh.

At least 55 records · Page 3Linked to original sources

Atopy as a risk factor for cryptogenic fibrosing alveolitis.

In a case-control study of occupational and environmental causes of cryptogenic fibrosing alveolitis we recently observed a higher prevalence of self-reported symptoms of wheeze, rhinitis or conjunctivitis in cases than in controls. To determine objectively whether this was due to a higher prevalence of atopy amongst cases of CFA, we have measured skin sensitivity to common allergens (D. Pteronyssinus, grass pollen, and cat fur), eosinophil counts and total Immunoglobulin E (IgE) in venous blood in the 22 surviving CFA cases from that study who were willing to provide a blood sample, and in one matched control per case. At least one positive skin test was recorded in 13 cases and six controls, the matched odds of one or more positive test being significantly increased in cases by a ratio of 8.0 (95% confidence interval 1.01-64, P = 0.05). Geometric mean eosinophil counts and IgE levels were also increased amongst cases by factors of 1.6 (95% CI 0.96-2.6) and 1.9 (0.9-3.8) respectively, although these differences were not significant. Differences in skin sensitivity, eosinophil counts, and IgE levels all tended to be more obvious in the 13 case control pairs in which the case was not taking steroids or other immunosuppressive treatment. We conclude that cases of CFA showed increased skin sensitivity to common allergens, and had evidence of increased IgE and eosinophilia in peripheral blood. These findings suggest that atopy may be an important determinant of susceptibility to CFA.

Aged↗

Restricted expression of a zinc finger protein in male germ cells.

Zfp-37 is a zinc finger protein gene expressed in male germ cells. The cDNA detected two transcripts on Northern blots of testis RNA, with expression first detected at around day 19. To establish the pattern of expression of the protein we have raised antibodies to ZFP-37 and used them on thin sections of testis and on Western blots. On Western blots the antibody detected two proteins exclusively in testis extracts, confirming the previous mRNA expression data. A time-course study revealed that the larger of the two proteins appears at about day 22 but the smaller one is not detected until day 34. Analysis of the expression of these two proteins in purified germ cell preparations revealed that the smaller protein is only detectable in the elongating spermatids or residual bodies. Data from thin sections showed that most, but not all, of the protein recognized by the antibody is in the nucleus, a result further confirmed by Western blotting. These results are discussed in the light of the possible role of this protein in regulating spermatogenesis.

Animals↗

A clinicopathologic correlative study of noncontact transscleral Nd:YAG cyclophotocoagulation.

We studied the histopathologic changes of three eyes enucleated two weeks, eight weeks, and 17 months, respectively, after noncontact Nd:YAG cyclophotocoagulation. The histologic findings at two weeks were destruction of the nonpigmented and pigmented ciliary body epithelium, occlusion of the capillaries of the ciliary processes, and ciliary body stromal necrosis in the region of the processes. Hyperplasia of the pigmented and nonpigmented epithelium, fibrosis and near total atrophy of the ciliary processes, and partial atrophy of the ciliary muscles were present at eight weeks and 17 months. We concluded that application of treatment 1.0 to 1.5 mm posterior to the corneoscleral limbus selectively destroys the pars plicata, and that, histologically, the mechanism for reducing intraocular pressure appears to be destruction of ciliary processes with reduction of aqueous formation.

Aged↗

A comparison of health care offerings as perceived by employers.

This empirical study examines the health care coverage climate of 130 large and medium sized companies in New England. Human resource managers and/or benefits managers were asked to compare the plans that they currently offer their employees on a number of points. The primary focus was in the area of cost and cost containment. An attempt is made to identify the cost containment trends that are now a very high priority among employers.

Consumer Behavior↗

The B-cell binding site on human immunoglobulin E.

Immunoglobulin E comprises the main immunoglobulin class associated with allergy. Its multifarious activities are mediated by two types of Fc receptors found on different cell populations, Fc epsilon R1 on mast cells and basophils, and Fc epsilon R2 on inflammatory cells (monocytes, eosinophils and platelets) and B lymphocytes. Recombinant epsilon-chain fragments synthesized in Escherichia coli have provided the means of mapping the receptor-binding sites on human IgE, and blocking IgE-receptor interactions. We have previously shown that the Fc epsilon R1 binding site is contained within a sequence (Gln 301-Arg 376) spanning the C epsilon 2 and C epsilon 3 domains. Here we show that Fc epsilon R2 can recognize a motif in the C epsilon 3 domain that is formed on dimerization of one or both of the flanking (C epsilon 2 and C epsilon 4) domains. Glycosylation of IgE is not required for the activity of either receptor.

Antibodies, Monoclonal↗

The mast cell binding site on human immunoglobulin E.

Antibodies of the immunoglobulin E isotype sensitize mast cells and basophils for antigen-induced mediator release by binding through the Fc portion to a high-affinity receptor (Fc epsilon R1, Ka = 10(9)M-1) on the cell surface causing the clinical manifestations of type I hypersensitivity. As the amino acid sequence of the human epsilon chain is now known, attempts have been made to map the Fc epsilon R1 binding site on IgE to a fragment smaller than Fc epsilon using proteolytic cleavage products, none of which proved to be active. Cleavage between the C epsilon 2 and C epsilon 3 domains released two inactive fragments, suggesting that the junction between these segments could be important in receptor binding. This region is protected against protease digestion in the rat IgE complex with the receptor of rat basophilic leukaemia cells. Here we report the mapping of the mast cell receptor binding site on human IgE to a sequence of 76 amino acids at the C epsilon 2/C epsilon 3 junction. Recombinant peptides containing this sequence inhibit passive sensitization of skin mast cells in vivo and sensitize mast cells to degranulation by anti-IgE in vitro almost as efficiently as a myeloma IgE. Fragments containing the separate domains are inactive. Additional sequences are required for rapid assembly of fragments into disulphide-linked dimers, suggesting that a single chain can form the active site. In a three-dimensional model of the human Fc epsilon, the two identical segments are far apart. Each folds to generate a cleft between the C epsilon 2 and C epsilon 3 domains on the surface of the Fc epsilon. The docking of IgE on to mast cells could take place within this cleft.

Amino Acid Sequence↗

Detection of a unique human V kappa IV germline gene by a cloned cDNA probe.

We have cloned the cDNA encoding the KIV chain of a human antibody with specificity against the major carbohydrate antigen of Streptococcus A. The cDNA has been used as a genetic probe to estimate the number of germline VKIV genes in human DNA. The presence of unique hybridizing bands on digestion of human DNA with several restriction endonucleases and the equivalence of the DNA in a band to a single gene per haploid genome point to the conclusion that there is a unique human VKIV germline gene. The corollary of this conclusion is that the diversity of human VKIV chains must be exclusively due to somatic mutation. This is supported by examination of the sequences of human KIV chain genes and their KIV chain products. Fusion of the unique germline VKIV gene (1) with one of several JK segments, followed by somatic mutations in the V region of the rearranged KIV gene, can account for the known sequences. The restricted germline gene repertoire may account for the small proportion of human KIV chains in the human K chain sequence library (2).

Amino Acid Sequence↗

Male pseudohermaphroditism due to 17 alpha-hydroxylase deficiency: diagnosis by gas chromatography--mass spectrometry.

A case of male pseudohermaphroditism associated with 17 alpha-hydroxylase deficiency is reported in which the diagnosis was firmly established by gas chromatography-mass spectrometry. The patient was a 20-year-old genotypic male, phenotypic female who presented with primary amenorrhea, absence of body hair, and no breast development. She was hypertensive. Corticosterone and progesterone levels were very high and sex steroids were virtually absent. Gonadotropins were in the menopausal range. The results of radioimmunoassay were not diagnostic. Analysis of urine using gas chromatography-mass spectrometry revealed a striking absence of steroids with 17-oxygen function-nor were there any 18 or 19 carbon steroids. These results clearly establish a total deficiency of 17 alpha-hydroxylase activity.

Adrenal Hyperplasia, Congenital↗

Biological effects of long-term exposure of rats to 970-MHz radiofrequency radiation.

Rats (N = 16) exposed individually in circularly polarized waveguides to 970-MHz electromagnetic radiation (SAR = 2.5 mW/g, 22 h daily for 70 consecutive days) had significantly higher serum levels of triglycerides, albumin, and total protein compared with sham-irradiated controls. No difference was observed in the weights, hematologic profile, or in vitro lymphocyte responses to mitogens between these two groups. The higher serum levels of triglycerides in radiofrequency-radiation-exposed rats suggest a non-specific stress reaction.

Animals↗