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Biomedical subjects

J Clark

Publications and source records attributed to J Clark.

At least 325 records · Page 18Linked to original sources

Molecular cloning, sequence analysis and mRNA expression of human ADP-ribosylation factor.

The ADP-ribosylation factor (ARF) is the small (21 kb) GTP-binding protein required for the efficient cholera toxin-catalyzed ADP-ribosylation of purified Gs, the stimulating regulatory component of adenylate cyclase. Human ARF cDNA clones were obtained from a human cDNA library by cross-species hybridization with bovine ARF1, and the nucleotide and deduced amino acid sequences were determined. Comparison of the sequences of human and bovine ARF1 showed 90% identity at the nucleotide level and 100% identity at the amino acid level, demonstrating the highly conserved nature of the ARF protein. Using human ARF cDNA as the probe, we have detected ARF messenger RNA (approximately 2.2-2.3 kb) in a wide variety of human tissues and tumor cell lines.

ADP-Ribosylation Factor 1↗

Determination of nine inorganic elements in human autopsy tissue.

A survey of nine elements of accepted clinical relevance has been performed on tissue sets comprising of kidney, liver, heart and muscle taken at autopsy from healthy individuals killed as the result of an accident. The concentrations are reported using tissue wet weight, dry weight and nitrogen content as frames of reference. This has allowed direct comparisons to be made with other studies without resort to the use of conversions, using average factors, between one frame of reference and another. Such conversions are shown to be unreliable and may generate spurious differences. The results obtained are largely consistent with those reported from studies in other parts of the world.

Adolescent↗

Fluorescent lights, ultraviolet lamps, and risk of cutaneous melanoma.

Exposure to solar radiation is increasingly being associated with a risk of cutaneous melanoma, and some risk has also been attributed to exposure to fluorescent lights. The risk of cutaneous melanoma associated with exposure to some sources of artificial ultraviolet radiation was examined in a case-control study in a Scottish population with fairly low exposure to natural ultraviolet radiation. The risk was not significantly or consistently raised for exposure to fluorescent lights at home or at work. The use of ultraviolet lamps and sunbeds, however, was associated with a significantly increased risk (relative risk = 2.9; 95% confidence interval 1.3 to 6.4), and the risk was significantly related to duration of use. The risk was particularly raised among people who have first used [corrected] ultraviolet beds or lamps more than [corrected] five years before presentation (relative risk = 9.1; 95% confidence intervals 2.0-40.6), in whom it was significantly related to cumulative hours of exposure. The risks associated with exposure to ultraviolet lamps and sunbeds remained significant after adjustment for other risk factors for melanoma.

Adolescent↗

Geographic distribution of HTLV-I and identification of a new high-risk population.

Epidemiologic studies indicate that human T-cell lymphotropic virus type I (HTLV-I), the causative agent of most cases of adult T-cell leukemia/lymphoma (ATLL) in Southeast Japan and the Caribbean islands and the probable cause of a progressive neurological disorder often referred to as tropical spastic paraparesis, occurs with unusual geographic clustering. The current large-scale serosurvey was undertaken to improve our understanding of HTLV-I prevalence in different parts of the world. We analyzed 43,445 serum samples collected from various geographic locales worldwide; 76% of these sera came from clinically healthy donors. Samples were initially screened by an enzyme-linked immunosorbent assay (ELISA) and 4,353 were further evaluated by means of competition assays. In this study, which did not include sera from endemic areas of Japan, a high prevalence of infection was observed in several countries in the Caribbean basin. A significant age-sex difference was observed between populations in the Caribbean and non-endemic regions of Japan. The reason for the male excess in non-endemic areas of Japan will require further study, while the female excess in the Caribbean basin is compatible with the previously described pattern for other HTLV-I-endemic areas. A newly recognized area of possible endemicity was southern Florida, where evidence of infection with HTLV-I or a related virus was found in a group of native Americans whose sera were collected in 1968. In certain parts of the world, particularly sub-Saharan Africa, important problems in determining specificity of reactivity occurred, probably because of cross-reacting antibodies. No pattern was detected that could explain the cross-reactivity solely on the basis of geographic areas, specific patterns of non-viral parasitic infection, or methods of handling the specimens. It is possible that these cross-reactivities are antibodies to proteins from HTLV-I-related retroviruses yet to be discovered.

Adult↗

Molecular cloning and DNA sequence analysis of the human guanine nucleotide-binding protein Go alpha.

The nucleotide sequence of human Go alpha was determined from a partial human brain cDNA clone and the sequence of the first two 5' coding exons of a human genomic Go alpha clone. Comparison of this sequence with bovine and rat Go alpha shows greater than 90% homology at the nucleotide and deduced amino acid level. There is 100% identity at the amino acid level for the cholera and pertussis toxin-catalyzed ADP ribosylation sites, the putative guanine nucleotide binding, and the GTP hydrolysis sites.

Amino Acid Sequence↗

Elevated creatine phosphokinase MB in a patient with neuroendocrine carcinoma of the colon--evidence for a tumor marker. Report of a case.

Elevated creatine phosphokinase (CPK) MB isoenzyme has become accepted as a highly specific criterion for the diagnosis of myocardial infarction (MI). A patient with metastatic neuroendocrine carcinoma of the colon who had marked and persistent elevation of CPK-MB isoenzyme, in the absence of clinical and cardiographic evidence for MI, is described. The CPK-MB level was 25 percent (normal, less than 3 percent) on admission, 39 percent postoperatively, and 57 percent on discharge. A prompt decline in serum CPK-MB activity (11 percent, less than 3 percent) paralleled chemotherapy-induced tumor regression. Resurgence of the isoenzyme heralded recurrent disease. These findings suggest that CPK-MB may be a valuable adjunct marker in the diagnosis and monitoring of neuroendocrine carcinomas.

Biomarkers, Tumor↗

Site-specific melanocytic naevus counts as predictors of whole body naevi.

Counts of melanocytic naevi of 2 mm or greater diameter on all body sites were conducted in 197 Caucasian adults in Scotland. Mean naevus numbers were greater in young than in older adults, and in females than in males. Naevus counts on the upper limbs, lower limbs, and trunk were strongly and significantly correlated with each other and with whole body counts. Thus, where whole body counts are impractical, counting naevi at any of these individual sites should provide a satisfactory method for studying naevus distribution in large populations.

Arm↗

Chemotherapy and hormonal therapy in combination.

The advantage of adding hormones to chemotherapy for the treatment of patients with breast carcinoma is uncertain, and benefits and disadvantages have been reported. An analysis of published randomized clinical trials reveals that the growth function (differentiation-inducing function v mitogenic function) of the hormone used may determine the ultimate benefit of combined modality treatments.

Antineoplastic Combined Chemotherapy Protocols↗

Serum soluble IL-2 receptor as a tumor marker in patients with hairy cell leukemia.

Activated T cells synthesize and express a cell membrane-bound receptor for interleukin-2 (IL-2) and have recently been shown to secrete a soluble form of the same receptor. Hairy cell leukemia is a chronic disorder caused by expansion of a clonal population of an unusual mononuclear cell of B cell origin. These cells have previously been shown to express an IL-2 receptor on the cell membrane. The sera of 26 patients with hairy cell leukemia were examined for the presence of a soluble IL-2 receptor before and during therapy with either recombinant interferon alpha-2a or 2'-deoxycoformycin. Before therapy, all patients had markedly elevated levels of this soluble IL-2 receptor ranging from five to 60 times the highest level observed in normal control sera. In individual patients changes in the level during therapy correlated well with clinical assessments of tumor response; levels fell to near the normal range in patients responding to therapy. Patients not responding to interferon alpha had no significant change in the soluble IL-2 receptor level. These results suggest that hairy cells secrete a soluble IL-2 receptor and that serial measurements of the level of this receptor in the serum can be used as a noninvasive means to assess disease response to therapy.

Biomarkers, Tumor↗

A comparison of biscuits used in emergency relief feeding programmes in Ethiopia and eastern Sudan--1985/86.

Twenty-nine samples of food-aid biscuits were collected during a survey of feeding programmes in Ethiopia and Sudan. A further seven brands were included in the study but were not found in Ethiopia or Sudan. All but two brands were produced in Europe. Only 20 brands were recommended for use as emergency rations or as nutritious supplements; eight brands were similar to traditional baked biscuits and four were infant rusks. The compared biscuit characteristics included ingredients, energy density, unit size, protein content, fortification with vitamins and minerals and costs. A wide range in all characteristics was found. Biscuits high in protein tended to have a low energy density. Energy density and unit size influenced the volume eaten and ease of transport, storage and also distribution to recipients. The cost of energy (per 500 kcal) ranged between 14.0 p for baked biscuits and 47.5 p for the unbaked compressed products.

Bread↗

HTLV-I--associated B-cell CLL: indirect role for retrovirus in leukemogenesis.

Serum containing antibodies to the human T-lymphotropic virus type I (HTLV-I) has been observed at a higher than expected frequency in patients with B-cell chronic lymphocytic leukemia (CLL) in an area endemic for HTLV-I. An attempt was made to determine whether the cells from patients with this leukemia were HTLV-I antigen-committed B cells that had undergone malignant transformation. Cells from two HTLV-I seropositive Jamaican patients with CLL were fused with a human B-lymphoblastoid cell line. The hybridoma cells that resulted from the fusion of CLL cells from patient I.C. produced an immunoglobulin (IgM) that reacted with the p24 gag protein from HTLV-I, HTLV-II, and HTLV-III (now referred to as HIV), but showed preferential reactivity with HTLV-I. The specific immunoglobulin gene rearrangement (IgM, kappa) in the CLL cell was demonstrated in the hybridoma cell line, indicating that the captured immunoglobulin was from the CLL cells. The IgM secreted by the fusion of CLL cells from patient L.L. reacted only with HTLV-I-infected cells and with the HTLV-I large envelope protein (gp61) on Western blots. The CLL cells from these patients appear to be a malignant transformation of an antigen-committed B cell responding to HTLV-I infection, suggesting an indirect role for this retrovirus in leukemogenesis.

Antibodies, Viral↗