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Biomedical subjects

J C Murray

Publications and source records attributed to J C Murray.

At least 271 records · Page 15Linked to original sources

Pulsed electromagnetic fields promote collagen production in bone marrow fibroblasts via athermal mechanisms.

Primary and passaged cultures of fibroblasts (RBMFs) raised from the bone marrow stroma of young rabbits were treated with pulsed electromagnetic fields (PEMFs) from the start of each culture until 1 week after they became confluent. the PEMF treatment had no effect on cell proliferation, estimated by phase contrast microscopy, by 3H-thymidine incorporation into DNA, or by total DNA assay. Collagen production, estimated by conversion of 3H-proline to 3H-hydroxyproline in nondialyzable material was markedly elevated in postconfluent cultures, but not in cultures that had only just reached confluence. About 65 of 3H-hydroxyproline was in low molecular weight form, and a correlation between collagen breakdown and cyclic AMP (cAMP) levels in RBMFs was demonstrated by adding dibutyryl cAMP or prostaglandin E3 (PGE2) to the culture medium concurrently with 3H-proline. The PEMF apparatus caused an insufficient temperature rise (less than 0.1 degree C) to account for these results. We propose that the rise in collagen production is consistent with the hypothesis that PEMFs act by reducing cAMP levels in RBMFs, and that thermal effects are insignificant.

Animals↗

Bullous pemphigoid. Occurrence in a patient with mycosis fungoides receiving PUVA and topical nitrogen mustard therapy.

A 57-year-old woman with mycosis fungoides developed blisters within cutaneous plaques while receiving PUVA therapy and topical nitrogen mustard. Direct and indirect immunofluorescence studies showed the findings of bullous pemphigoid. Her bullous disease was controlled after cessation of these therapies and institution of prednisone and methotrexate. During the 5 months following completion of a course of electron-beam therapy, she has been free of the cutaneous manifestations of both diseases. Previous instances of PUVA-related pemphigoid have occurred in psoriatics. The role of ultraviolet light in the induction of pemphigoid is discussed, particularly with regard to its possible interaction with the altered skin of psoriasis or mycosis fungoides. Some of the rare cases of bullous mycosis fungoides might actually have represented ultraviolet-unmasked bullous pemphigoid.

Administration, Topical↗

Dandy-Walker malformation: etiologic heterogeneity and empiric recurrence risks.

The Dandy-Walker malformation (DWM) includes hydrocephalus, incomplete cerebellar vermis and a posterior fossa cyst. Genetic influences and recurrence risks for DWM have not been well characterized. We report a retrospective study of 21 autopsy-proven cases of DWM and review the literature regarding an additional 92 subjects. DWM represents marked genetic and etiologic heterogeneity. Recurrence risk for siblings may be high when DWM is associated with a single gene disorder such as the autosomal recessive Warburg and Meckel-Gruber syndromes. DWM may also result from chromosomal anomalies or environmental factors. When the evidence suggests that DWM has not occurred as part of a Mendelian or chromosomal disorder then the recurrence risk is relatively low (on the order of 1 to 5%). There appears to be an increased frequency of the association of DWM with congenital heart disease, cleft lip/palate and neural tube defects. Based on our study we provide guidelines for the genetic counseling of families having a child with DWM.

Abnormalities, Drug-Induced↗

Defective actin organization in cultured skin fibroblasts from individuals with inherited colon adenocarcinoma is not restored by addition of fibronectin.

Cultured skin fibroblasts from patients with hereditary adenomatosis of the colon and rectum (ACR) have a disorganized cytoskeleton. Since fibronectin has been found to restore normal cytoskeletal and cellular morphology to transformed cells, we investigated the fibronectin pattern in ACR cells. We found that although both fibronectin synthesis and binding to the cell surface were apparently normal, addition of fibronectin did not restore a normal distribution of actin cables to ACR cells. The data suggest that coupling of cell surface-bound fibronectin to the cytoskeleton might be constitutively defective in ACR cells.

Actins↗

Linkage disequilibrium and evolutionary relationships of DNA variants (restriction enzyme fragment length polymorphisms) at the serum albumin locus.

Four additional DNA variants (restriction enzyme fragment length polymorphisms) making a total of eight polymorphic sites at the human albumin locus have been identified. These eight sites were found after screening 689 of 20,000 nucleotides by using cDNA probes for albumin with 27 different restriction enzymes. One in 85 nucleotides was therefore potentially polymorphic. The average nucleotide diversity between any two randomly chosen chromosomes was calculated to be 1/500. We observed marked linkage disequilibrium between the eight variants. Only 7 haplotypes among 256 possible combinations were observed in 160 chromosomes from Caucasoids, Blacks, and Asians. Two haplotypes were found in all three human races, indicating that their origin predated human racial divergence. The three rarest haplotypes appear to represent recombinational events between the more common haplotypes. All crossovers occurred in the same general region. Studies of several nonhuman primates indicated that the origin of one haplotype predated the human-African ape divergence. Although it is not possible to rule out maintenance of this tight linkage by selection or fixation, it is suggested that the limited number of haplotypes at the chromosomal site of the albumin gene near the centromere of chromosome 4 may be the result of decreased recombination.

Animals↗

Epidermal growth factor stimulates type-V collagen synthesis in cultured murine palatal shelves.

The effects of epidermal growth factor (EGF) on the synthesis of collagen and fibronectin in murine palatal shelves in serum-free organ culture have been examined. Palatal shelves grown in the presence of EGF were substantially larger and showed dramatic increases in immunofluorescent localization of fibronectin, possibly reflecting increased synthesis compared to controls cultured without EGF. EGF also prevented the normal dissolution of the medial palatal epithelium. Net protein synthesis in experimental palatal shelves increased by 18%, whereas net collagen synthesis was approximately 10% of protein synthesis in both conditions. There was, however, an apparent shift in collagen isotypes. Under the influence of EGF, there was a significant increase in synthesis of the alpha 1 (V) and alpha 2 (V) chains of type-V collagen.

Animals↗

Investigation of the attachment of bovine corneal endothelial cells to collagens and other components of the subendothelium. Role of fibronectin.

Bovine corneal endothelial cells adhered equally well to a variety of collagens (types I, III, IV and V) consistent with a role for fibronectin in this process. They did not exhibit a preferential binding to collagen type IV--as might be anticipated if laminin were to play a significant role in their adhesion. Inhibition studies with anti-fibronectin antibodies demonstrated the importance of endogenous fibronectin in the mediation of attachment. Consistent with this, binding did not appear to require the presence of exogenous protein, since cells bound to collagens equally well in the presence or absence of added fibronectin and binding was not stimulated by pretreatment of collagens with this protein.

Animals↗

Rh isoimmunization related to amniocentesis.

We report on the incidence of Rh isoimmunization after genetic amniocentesis at our institution. In 115 Rh negative women who underwent amniocentesis and subsequently delivered Rh positive infants, there were 4 (3.4%) sensitizations before birth. This was significantly greater than the 1.5% rate of gestational sensitization found in pooled populations of women who did not undergo amniocentesis. We also noted a significant increase in the number of sensitizations that occurred before 28 weeks. The results were consistent with those of previous studies of this issue, and are discussed in relation to current policies for managing Rh negative women who have second trimester amniocentesis.

Adult↗

Molecular genetics of human serum albumin: restriction enzyme fragment length polymorphisms and analbuminemia.

By using cDNA probes for the human albumin gene, four restriction enzyme fragment length polymorphisms (RFLPs) were discovered that were transmitted by codominant autosomal inheritance. Among Caucasians, the gene frequencies were 0.04/0.96 for Msp I/5', 0.43/0.57 for Hae III/3', 0.44/0.56 for Hae III/5', and 0.04/0.42/0.54 for Pst I/5'. These common variants provide a marker for chromosome 4 (q11-q13). A calculation of the extent of DNA variation at the albumin locus revealed that 1/95 nucleotide sites was affected by a RFLP, a figure similar to that found in the globin system. Restriction enzyme fragment study of the DNA of a human analbuminemic individual revealed no gross structural rearrangements of the albumin locus. The exact nature of abnormality will require more study.

Alleles↗

Restriction endonuclease mapping of globin genomic regions of HEL (human erythroleukemia) line.

The restriction endonuclease map of the alpha and beta globin genomic region of the new human erythroleukemia line, HEL, was compared with that of normal human DNA. The HEL line, which produces mainly fetal (G gamma and A gamma) but no adult (delta and beta) globin chains, was shown to have the same pattern of DNA fragments as that of normal human DNA. This suggests that the selective expression of the gamma globin genes observed in HEL cells is not due to a major deletion or rearrangement in the epsilon-G gamma-A gamma-delta-beta gene complex. Thus, the HEL line provides a model for studying the control of globin developmental switching in cells with structurally intact globin gene regions.

Cell Line↗

Pyoderma gangrenosum with IgA gammopathy.

A 46-year-old man with pyoderma gangrenosum and IgA gammopathy is described. This patient had no other identifiable associated systemic disease. His condition was unresponsive to oral corticosteroids, sulfones, and sulfapyridine therapy. His course was complicated by chronic sinusitis and necrotizing pneumonia. He was treated with clofazimine.

Arthritis↗

Serum triglyceride elevation following high-dose vitamin A treatment for pityriasis rubra pilaris.

We describe two patients with pityriasis rubra pilaris in whom hypertriglyceridemia developed following the oral administration of high-dose vitamin A (retinol). The effects of transient hypertriglyceridemia are unknown, as both patients tolerated high-dose vitamin A therapy with minor, if any, other side effects. Both patients had minimal clinical improvement with this therapy. Patients being treated with 1,000,000 IU of vitamin A each day for ten to 14 days should have frequent determinations of serum lipid levels and liver function during the period of drug administration.

Humans↗

Localization of the human fibronectin (FN) gene on chromosome 8 by a specific enzyme immunoassay.

The fibronectin produced by clonal murine-human hybrid cell lines containing various complements of human chromosomes was measured. Human and murine fibronectins were assayed by specific immunoassay, and the production of human fibronectin was correlated with karyology and isozyme markers for specific human chromosomes. The data show a 100% concordance between the expression of human fibronectin and glutathione reductase, a marker for human chromosome 8, indicating that chromosome 8 codes for the fibronectin polypeptide.

Animals↗

Keloids: a review.

Keloids are predominantly fibrous tumors which appear as firm, variably pruritic or tender growths near a site of injury. Usually appearing between the ages of 10 and 30, most keloids are located on the upper back, shoulders, earlobes, and anterior portion of the chest. The etiology remains unknown, but the accumulated fibrous tissue is associated with increased cellularity and increased metabolic activity of keloid fibroblasts. Isolated keloid fibroblasts demonstrate normal growth characteristics along with increased collagen and proteoglycan synthesis. Numerous keloid treatments have been attempted, but variable success has followed either single use or combinations of intralesional corticosteroid injection, surgery, pressure devices, radiation, cryosurgery, and systemic chemotherapy.

Adolescent↗

The epidermal cell which selectively adheres to a collagen substrate is the basal cell.

In order to determine whether a specific subpopulation of epidermal cells selectively attaches to collagen substrates in vitro, epidermal cell suspensions, obtained by trypsinization of guinea pig skin, were incubated on type I or type IV collagen-coated glass cover slips. It was noted, morphologically and by electronic volume measurements, that small round cells, as opposed to the larger angulated flat cells, adhered to the collagen substrates. To further characterize the attached cells, the percentage of basal cells was determined in the attached cell population and in the initial epidermal cell suspension. Basal cells were identified by indirect immunofluorescence in 2 ways: (1) by the presence of pemphigoid antigen and (2) by the absence of upper cytoplasmic antigen, which is present in all keratinocytes except the basal cells. Whereas in the initial guinea pig epidermal cell suspensions about 50% of the cells were basal cells using either of these 2 criteria, 86-97% of the cells which adhered to the collagen substrates were basal cells. Human basal cells, as defined by pemphigoid antigen, also selectively adhered to the collagen substrates.

Animals↗

Adhesion characteristics of murine metastatic and nonmetastatic tumor cells in vitro.

We have studied the attachment of mouse fibroblasts, transformed nonmetastatic fibroblasts, and metastatic fibrosarcoma cells to various substrates. The metastatic cells attach preferentially to type IV (basement membrane) collagen in the absence of serum, compared to type I collagen and plastic. In the presence of fibronectin, these cells attach well to both type I and type IV collagens. The normal and transformed fibroblasts attach to all these substrates, although the transformed fibroblasts attach more slowly. The ability to attach to type I collagen and plastic is correlated with the levels of fibronectin and collagen produced by these cells. The data indicate that the transformed and metastatic cells differ from normal cells in their attachment properties and ability to synthesize matrix proteins. The metastatic cells possess a unique system for binding to type IV collagen that could be important in enabling these cells to penetrate tissues bounded by basement membranes.

Animals↗