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Biomedical subjects

J A Fletcher

Publications and source records attributed to J A Fletcher.

138 records · Page 8Linked to original sources
PubMed1987

Studies of the parathyroid hormone gene in normal subjects, and in subjects with primary hyperparathyroidism and familial benign hypercalcaemia.

Familial benign hypercalcaemia (FBH) closely resembles primary hyperparathyroidism (PHPT) both clinically and biochemically. Using a cDNA probe for the parathyroid hormone (PTH) gene we have studied restriction fragment length polymorphisms in normal British subjects and have shown them to be similar to those found in previous studies in a German population. The pattern of inheritance of these restriction fragment length polymorphisms in a family with FBH shows that the PTH gene is not involved in the pathogenesis of the condition. Limited studies in PHPT indicate that it is unlikely that a major structural defect or rearrangement is responsible for the sporadic form of the disease.

Alleles↗
PubMed1987

HLA and C4 polymorphism in diabetic microangiopathy.

We have reported an increased frequency of the rare B3 allotype of the fourth component of complement (C4B3) in insulin-dependent diabetics, especially in those with microangiopathy. This study has now been expanded--20 of 106 subjects with microangiopathy and 9 of 116 without possessed the C4B3 allotype (p less than 0.02). C4B3 is said to be in linkage disequilibrium with HLA-DR4. HLA typing was performed on 94 of these patients, 52 with and 42 without microangiopathy. There was no significant difference in the frequency of DR4 (62 vs 50%), DR3 (65 vs 52%), B8 (40 vs 40%) or B15 (32 vs 19%) respectively between these 2 groups. These results confirm an HLA-linked predisposition to microangiopathy, but do not determine whether the primary association is with C4B3, DR4 or another gene with which they are in linkage disequilibrium.

Complement C4↗
PubMed1986

Phenotypes of the heavy chains of immunoglobulins in patients with diabetic microangiopathy: evidence for an immunogenetic predisposition.

The B3 allotype of the fourth component of complement (C4B3) is associated with microangiopathy. As C4 is important in the humoral immune response phenotypic variation of other inherited components of the response such as the immunoglobulins could also be associated with microangiopathy. Phenotypes of the heavy chains of immunoglobulins (Gm) were compared in 48 insulin dependent diabetics with and 74 without microangiopathic complications. The Gm(zafnbg) phenotype was found significantly more often in insulin dependent diabetics with complications than in those without (16 (33%) out of 48 v 7 (9%) out of 74, respectively, p less than 0.01). Insulin dependent diabetics with both C4B3 and Gm(zafnbg) had an increased risk of complications compared with insulin dependent diabetics with neither or only one factor. Statistical analysis suggested that these two associations were additive, indicating that they increased risk by independent mechanisms. These findings suggest that susceptibility to diabetic microangiopathy is influenced by genes at or in linkage disequilibrium with both the major histocompatibility complex and the Gm loci.

Adult↗
PubMed1986

Spurious detection of terminal deoxynucleotidyl transferase in phytohemagglutinin-stimulated lymphocytes.

Expression of terminal transferase (TdT) is believed to be restricted to primitive lymphoid cells; recently, however, indirect immunofluorescent (IF) assays have been used to demonstrate the apparent presence of TdT in phytohemagglutinin (PHA)-stimulated peripheral blood lymphocytes and in various nonlymphoid malignancies. Using an IF assay, we found that a heteroantiserum to TdT reacted with cultured and PHA-stimulated human peripheral blood mononuclear cells, but we were unable to confirm the presence of TdT in these cells using immunoblotting and biochemical assays. We conclude that the IF results are spurious and most likely represent recognition by the heteroantiserum of inducible protein(s) other than TdT.

Clinical Enzyme Tests↗
PubMed1986

Low molecular weight proteinuria in insulin-dependent diabetes.

Although the protein leak of early diabetic nephropathy is said to be purely a glomerular lesion, there is still controversy as to the existence of a tubular component. We have, therefore, assessed the urine of insulin-dependent diabetics for tubular proteinuria as a feature of early diabetic nephropathy. The urine of 25 patients with increased albumin excretion rate was analyzed by sodium dodecyl polyacrylamide gel electrophoresis. One patient showed high molecular weight proteinuria, 2 showed low molecular weight proteinuria and 2 patients showed both low and high molecular weight proteinuria. The urine was also analyzed for 3 tubular proteins by single radial immunodiffusion. No patient showed elevated beta-2-microglobulin, but alpha-1-microglobulin (A1M) (corrected for creatinine excretion) was elevated in 3 out of 25 patients including 2 of the 4 patients with a low molecular weight pattern. One of the patients with raised A1M also had raised retinol-binding protein concentration. We conclude that, in early diabetic nephropathy, proteinuria can have a proximal tubular, as well as a glomerular, component.

Adult↗
PubMed1978

Factors affecting the permeability of skin. The relation between in vivo and in vitro observations.

At the same temperature and with adequate circulation of blood or receptor solution beneath it the permeability of the stratum corneum of the rabbit ear to T2O or to 32P-TPP was the same in vivo as in vitro. When skin permeability was measured in vitro, the subcutaneous adipose tissue present in the full-thickness skin of the rat delayed the penetration of CR, a lipophilic substance with a low water solubility, and decreased the permeability constant by nearly 3x. The retardant solvent PEG 300 did not penetrate the stratum corneum; it formed a hydrogen-bonded complex with the cholinesterase inhibitor VX, thereby reducing the thermodynamic activity and penetration rate of this compound through the stratum corneum. The accelerant solvent DMSO removed protein components from the stratum corneum; electron microscope studies showed that the cells of stratum corneum so treated became separated from one another, and their contents became stainable in bulk with Pb++, indicating the creation of new diffusion pathways. When the temperature, clearance of penetrant from the lower surface of the stratum corneum and penetrant formulation were the same in vivo as in vitro, and the surface of the stratum corneum was saturated with the penetrant or its solution, the results of permeability measurements made in vivo were similar to those made in vitro.

Adipose Tissue↗
PubMedDate not supplied

Gains of chromosome 8 are confined to mesenchymal components in pleuropulmonary blastoma.

Pleuropulmonary blastoma, an aggressive tumor that is emerging as a distinct entity of childhood, is characterized by mesenchymal elements (including undifferentiated blastema and often cartilaginous, rhabdomyoblastic, or fibroblastic differentiation) and epithelium-lined spaces. We investigated two patients with pleuropulmonary blastoma, a 3-year-old boy and an 11-year-old girl, both with large cystic masses replacing one lung. In both children, the post-chemotherapy resection specimens showed more maturation of rhabdomyoblasts and more nuclear pleomorphism in all mesenchymal cell lines, compared with biopsies sampled before treatment. Karyotypic analysis demonstrated gains in chromosome 8 in both cases and 17p deletion in one case. Fluorescent in situ hybridization analysis demonstrated that the chromosome 8 gains were present in all mesenchymal elements, including undifferentiated blastematous, rhabdomyoblastic, fibroblastic, and chondroblastic areas. Epithelial cells showed no chromosome 8 gains. The chromosome 8 aberrations were not appreciably different in pre- versus post-chemotherapy tissue. Our findings substantiate previous reports that polysomy of chromosome 8 is a consistent feature of pleuropulmonary blastoma. Further, they indicate that clonal proliferation in pleuropulmonary blastoma is restricted to the malignant mesenchymal elements, supporting the notion that the epithelial components of this tumor are non-neoplastic.

Antineoplastic Combined Chemotherapy Protocols↗
PubMedDate not supplied

Cystic neuroblastoma: emphasis on gene expression, morphology, and pathogenesis.

Cystic neuroblastoma (CN) is an unusual variant of neuroblastoma characterized by a grossly visible cyst(s) and almost always distinctive microcysts on light microscopy. Rarely, CN will appear solid grossly, but microcystification will be present. We examined the clinical, pathologic, and biologic features of 17 cases of CN. The majority of CN had been detected by prenatal ultrasound. The tumors were favorable stage, stroma-poor, but with low or intermediate mitotic-karyorhectic indices and had favorable biologic markers reflected by aneuploidy and by an absence of N-myc amplification and chromosome 1p deletions. However, the high trk expression typically identified in good risk tumors was absent. Although the complete natural history of CN is not fully defined, our experience suggests that some tumors progress in size, whereas others may spontaneously regress or mature. The clinical outcome is excellent, as is expected in localized and stage 4S neuroblastoma in infancy.

Adrenal Gland Neoplasms↗
PubMedDate not supplied

Cytogenetic analysis of effusions from malignant mesothelioma. A diagnostic adjunct to cytology.

Most patients with malignant mesothelioma (MM) present with an effusion, but distinguishing malignant from reactive mesothelial cells by conventional cytology may be difficult. We investigated the possibility of identifying clonal cytogenetic aberrations in pleural or peritoneal fluid from 10 patients with a clinical suspicion of MM. Direct metaphase harvests and short-term cultures were performed on fresh fluid. Clonal cytogenetic aberrations indicative of malignancy, with findings previously reported in association with mesothelioma, were found in all patients; these included del(1p), del(3p) and del(22q). Cytologic examination of the effusions showed malignant cells consistent with MM in 5 patients and atypical mesothelial cells suggestive of MM in 4. In one case the cytology of several samples of pleural fluid was within normal limits. Subsequent histology confirmed the diagnosis of MM in 9 of the 10 patients; medical complications precluded tissue biopsy in the 10th. We conclude that the cytogenetic analysis of effusions may be a useful and reliable adjunct to cytology in the diagnosis of MM.

Aged↗