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Biomedical subjects

J C Murray

Publications and source records attributed to J C Murray.

At least 253 records · Page 14Linked to original sources

Linkage analysis of Charcot-Marie-Tooth neuropathy (HMSN type I).

Fifteen HMSN families with 218 members and documented male-to-male transmission and slow motor nerve conduction velocities were informative for linkage to Duffy blood group (Fy), antithrombin III cDNA probe (AT3) and renin (REN). Our data support linkage to Fy in 8 families (lod score = 2.45 at theta = 0) consistent with HMSN type IB. Linkage to AT3 (lod score = 1.28 at theta = 0) and linkage of Fy to AT3 (lod score = 1.61 at theta = 0) is also supported in 3 of the 8 original families. Linkage to REN (lod score = 0.78 at theta = 0), linkage of Fy to REN (lod score = 0.89 at theta = 0), and linkage of AT3 to REN (lod score = 0.88 at theta = 0) is supported in only 2 of the 8 original families. Linkage to Fy was rejected in seven families, consistent with HMSN type IA (lod score = -4.34 at theta = 0.05). Linkage to AT3 was rejected in 12 families (lod score = -9.52 at theta = 0.05). Linkage to REN was rejected in 13 families (lod score = -11.07 at theta = 0.05). Our data provide support for the concept of genetic heterogeneity in CMT hypertrophic neuropathy (HMSN type I). The linkage of HMSN type IB to Fy seems to be tighter than to AT3 and REN, strongly suggesting the mapping of HMSN type IB locus on the proximal part of the long arm of chromosome 1, close to the centromere.

Antithrombin III↗

Effect of ultraviolet light on topical minoxidil-induced hair growth in advanced male pattern baldness.

Nine healthy men with type IVa or Va male pattern baldness completed a 4-month single-blinded controlled pilot study designed to assess the effect of ultraviolet light (UVL) on topical minoxidil-induced hair growth. Subjects applied 2% topical minoxidil solution twice daily to their balding scalps and to one target area on the upper arm. These men, all of whom had either skin type II or III, were randomized to also receive either incremental doses of UVB or PUVA (topical psoralen) twice weekly to one side of their scalp and to a 2.5 cm target area on the nonminoxidil-treated upper ipsilateral arm. Vellus, nonvellus, and total hair counts were done in two 1-inch in diameter circular target areas in symmetric regions of the scalp and on each upper arm at regular intervals. All nine subjects had an increase in target nonvellus hair and a net loss of vellus hair in scalp target area treated with topical minoxidil. Concomitant UVL did not have a significant synergistic nor adverse effect on topical minoxidil-induced hair growth.

Adult↗

The effects of melphalan and misonidazole on the vasculature of a murine sarcoma.

A method for estimating both structural and functional vascular volumes in murine sarcomas is described. Intact vessels were demonstrated by the presence of laminin, a basement membrane-associated antigen, using an immunofluorescent technique, and functional vessels in the same sample by prior injection with the DNA binding dye Hoechst 33342. No significant vascular effects were seen after melphalan but a very pronounced decrease in both functional and structural vascular volume was seen after MISO. Combined chemotherapy of a murine sarcoma with melphalan and MISO induced a rapid decrease in the functional vascular volume, and there was a resumption of blood flow prior to measurable regrowth. The fully regrown tumour retained the vascular characteristics of untreated tumours of similar size.

Animals↗

Combination chemotherapy followed by surgery or radiotherapy in patients with locally advanced cervical cancer.

Forty-seven patients with locally advanced cervical cancer at high risk of relapse received three cycles of chemotherapy with PVB (cisplatin, vinblastine and bleomycin) before definitive local treatment with either radical surgery or radiotherapy. Thirty-one of the 47 patients (66%) responded to initial chemotherapy, and 11 of them have relapsed compared with 13 of the 16 non-responders. Median time to recurrence was 31 weeks for PVB non-responders but has not yet been reached for PVB responders. After a median follow-up of 128 weeks, 14 of the 31 responders (45%) are alive and disease free compared with 3 of the 16 non-responders (19%). There was a positive correlation between response to chemotherapy and subsequent response to radiotherapy. PVB was in general well tolerated although one death is probably attributable to chemotherapy. A randomized study comparing radiotherapy alone with initial PVB chemotherapy followed by radiotherapy is in progress.

Antineoplastic Combined Chemotherapy Protocols↗

Von Recklinghausen neurofibromatosis: a linkage study of candidate and random marker genes.

Genotyping, using plasma proteins or DNA polymorphisms or both, was carried out on 30 families selected through probands with Von Recklinghausen disease. The data provide additional evidence for the exclusion of loci on chromosomes 3 and 5, and chromosome arms 1q, 2p, 4p, 4q, 6q, 7p, 9q, 11p, 11q, and 14q. There was no evidence for genetic heterogeneity at D1S1 (DNF15S2) on chromosome arm 3p, using the Morton test for heterogeneity.

Blood Proteins↗

Genetic linkage relationships of Charcot-Marie-Tooth disease (HMSN-Ib) to chromosome 1 markers.

Hereditary motor and sensory neuropathy-Ib (HMSN-Ib) is a common autosomal dominant disorder linked to the Duffy blood group locus on human chromosome 1. The gene for antithrombin III (AT3) is also located on the long arm of chromosome 1. Using a DNA restriction fragment length polymorphism for AT3, we have investigated the genetic linkage relationship of all three markers (HMSN-Ib, Duffy, and AT3) in two affected families. Neither HMSN-Ib nor Duffy was tightly linked to AT3. The loci for both HMSN-Ib and Duffy must be close to the centromere on chromosome 1, but precise localization and gene order require study of additional markers and more families.

Adolescent↗

Polymorphic human glucose transporter gene (GLUT) is on chromosome 1p31.3----p35.

The glucose transporter is a membrane glycoprotein that is involved in the uptake of glucose by most, if not all, animal cells. A cloned cDNA that encodes the human protein was used to map the gene to a specific chromosomal region and to identify a DNA polymorphism. The human gene (designated GLUT) was assigned to chromosome 1p31.3----p35 by hybridization of the probe to DNA from a panel of human-mouse somatic cell hybrids containing different human chromosomes and by in situ hybridization to isolated metaphase chromosomes. The most likely location of GLUT is in 1p33. A common two-allele restriction-fragment-length polymorphism was identified with Xba I.

Chromosome Banding↗

Linkage disequilibrium of plasminogen polymorphisms and assignment of the gene to human chromosome 6q26-6q27.

Linkage disequilibrium was observed between newly identified DNA polymorphisms and a previously described protein polymorphism for plasminogen. This finding implies that the two types of polymorphisms describe variation at the same locus. The plasminogen gene was mapped to chromosomal bands 6q26-q27 using somatic-cell hybrids and in situ hybridization. Linkage disequilibrium between protein and DNA polymorphisms has utility in substituting for protein typing in instances where only DNA samples are available, such as from deceased individuals or extinct species. The technique may be useful when cross-hybridizing sequences make the interpretation of Southern blot patterns difficult and may obviate the need for extensive DNA sequencing. In some cases, disequilibrium may provide information useful for determining the appropriate direction for chromosome walks from a marker locus to a target locus.

Alleles↗

Collagen metabolism in mouse lung after X irradiation.

Collagen and total protein synthesis rates have been determined in the lungs of CBA mice irradiated with single doses of X rays between 8 and 16 Gy. Mice were injected with [3H]proline accompanied by a large dose of unlabeled proline, and synthesis rates were measured at 2-month intervals from 8 to 31 weeks after irradiation. At 2 months after radiation treatment, collagen and total protein synthesis rates were significantly depressed but they had recovered by 4 months. By 6 months collagen synthesis rates had increased above control in a dose-dependent manner, so that in the 14-Gy dose group the fractional synthesis rate for collagen was 4.6 times higher than in control mice as measured by incorporation of [3H]proline. However, a significant net accumulation of collagen was seen only in the lungs of the highest dose group at 31 weeks, as indicated by total hydroxyproline measurements. There was a slight increase in the ratio of types I and III collagen. Late radiation damage in the CBA mouse lung is characterized by increased collagen metabolism, which may or may not lead to a net accumulation of collagen.

Animals↗

The action of pulsed magnetic fields on cyclic AMP levels in cultured fibroblasts.

Pulsed magnetic fields, similar to those used clinically to promote bone repair, have been applied to cultured fibroblasts obtained from chick embryo tendons and rabbit bone marrow. Cyclic adenosine monophosphate (cAMP) levels were found to be lower in field-treated cultures in response to hormones such as prostaglandin E2 and isoproterenol, and the fibroblasts appear less sensitive to environmental perturbation prior to hormone incubation. We propose that the adenylate cyclase complex is temporarily inactivated by prolonged exposure to pulsed magnetic fields, and that this effect might be analogous to desensitisation phenomena.

Animals↗

Cytomegalovirus transmission in a Midwest day care center: possible relationship to child care practices.

The epidemiology of cytomegalovirus (CMV) infection and transmission in a large Iowa day care center was studied. Over the 9 months of the study the overall CMV prevalence rates were 21% to 22%, with rates as high as 71% in toddlers. Titers of CMV in the urine or saliva of infected children were as high as 3 X 10(4) plaque-forming units of CMV per milliliter, similar to titers of CMV observed in some congenitally infected infants. Restriction enzyme analysis of CMV isolates from children in the center demonstrated two major clusters with similar patterns, one among 2- and 3-year-old children and another among infants. The clustering of similar CMV isolates among nonambulatory infants suggests that child care or hygienic practices may contribute to the spread of CMV infection in day care centers. Furthermore, the relatively high prevalence of CMV excretion in this center and the low seropositivity rates to CMV among adults in Iowa suggest that adults in the Midwest who have contact with children in day care centers may be at risk for primary CMV infection.

Child↗

Primary cutaneous lymphoma of the head and neck.

One hundred three patients with Stage I and II extranodal primary lymphomas of the head and neck were reviewed. Six patients (5%) presented with cutaneous lesions, five with single site and one with multiple sites of involvement. Histopathology was malignant lymphoma (ML) large cell (3), ML small cleaved cell (1), ML small lymphocytic (1), and ML mixed large and small cell (1). Five of six patients relapsed following initial treatment. Four patients were treated with primary radiation therapy, three of which had relapses outside the treatment area. One patient was treated with intralesional steroid injection and also recurred outside the treated area. One patient was treated with radiation and chemotherapy and recurred outside the treatment area. Three patients are alive without disease, two died of disseminated disease, and one died of unrelated causes. Isolated cutaneous presentation of head and neck lymphoma is uncommon. Radiation therapy appears to have been curative in one patient with localized disease. Four patients recurred outside the radiation portals despite careful staging, suggesting that systemic therapy may be necessary for disease control.

Aged↗

Atrophie blanche. A disorder associated with defective release of tissue plasminogen activator.

Atrophie blanche is a skin disorder characterized by recurrent ulceration and fibrosis. It is one of a group of cutaneous vasculitides associated with decreased blood fibrinolytic activity. We examined pre- and post-venous occlusion plasma from eight patients with atrophie blanche for release of vascular (tissue-type) plasminogen activator (t-PA). The average plasma level of releasable t-PA was only 0.03 IU/mL, compared with 0.70 IU/mL for 118 healthy controls. Therefore, the fibrinolytic disorder in atrophie blanche is associated with defective release of t-PA from blood vessel walls.

Atrophy↗

Modulation of collagen production in cultured fibroblasts by a low-frequency, pulsed magnetic field.

Primary cultures of chicken tendon fibroblasts have been exposed for various periods to a low-frequency, pulsed magnetic field, and the effects on protein and collagen synthesis have been examined by radioisotopic incorporation. Total protein synthesis was increased in confluent cells treated with a pulsed magnetic field for the last 24 h of culture as well as in cells treated for a total of 6 days. However, in 6 day-treated cultures, collagen accumulation was specifically enhanced as compared to total protein, whereas after short-term exposure, collagen production was increased only to the same extent as total protein. Levels of cyclic AMP were significantly decreased after 6-day pulsed magnetic field treatment, probably as a consequence of diminished adenylate cyclase activity. Exposure to pulsed magnetic field had no effect on cell proliferation or collagen phenotype. These results indicate that a pulsed magnetic field can specifically increase production of collagen, the major differentiated function of fibroblasts, possibly by altering cyclic-AMP metabolism.

Animals↗