Search PubMed⌕ Search

Biomedical subjects

J Clark

Publications and source records attributed to J Clark.

At least 289 records · Page 16Linked to original sources
PubMed1991

Human ADP-ribosylation factors. A functionally conserved family of GTP-binding proteins.

A new member, hARF4, of the ADP-ribosylation factor (ARF) family, a subset of the superfamily of regulatory GTP-binding proteins, has been cloned from a cDNA expression library. Two other human ARF cDNA sequences, designated human ARF1 and ARF3, have been reported previously and are 96% identical in amino acid sequence. A human ARF1 cDNA, significantly longer than previously described clones, was obtained, by cross-species hybridization using a bovine ARF1 cDNA probe. Bovine ARF1p and human ARF1p are 100% identical while each is only 80% identical to hARF4p. Thus, hARF4p is the most divergent of the mammalian ARF proteins identified. Northern blot analysis revealed the expression of at least three different ARF messages in human placenta and adrenal carcinoma cells. Both hARF1 and hARF4 encode GTP-binding proteins with predicted molecular masses of 20,000-21,000 Da. Biochemical analysis of the purified recombinant proteins revealed a high degree of conservation of nucleotide binding properties and in vitro ARF activities. ARF is an essential gene in the yeast, Saccharomyces cerevisiae, and is encoded by two genes. Expression of either hARF1p or hARF4p in yeast was found to rescue the lethal double mutant, arf1-arf2-, thus demonstrating the functional conservation of ARF functions between yeast and man. The combination of in vivo and in vitro assays for ARF function provides a specific and unambiguous means of determining bona fide ARF proteins from divergent species from among the rapidly increasing number of structurally related, small molecular weight GTP-binding proteins.

ADP-Ribosylation Factor 1↗
PubMed1991

Expression of members of the myf gene family in human rhabdomyosarcomas.

Northern analysis of tumour RNA has been used to examine the expression of members of the myf family of muscle determining genes (myf3, myf4, myf5 and myf6) in a series of 20 rhabdomyosarcomas. A 2.0 kb myf3 transcript was observed in 85% of tumours, a 1.8 kb myf4 transcript was detected in 70% of tumours and a 1.7 kb myf5 transcript was observed in 55% of tumours. Transcription of myf6 occurred in 28% of tumours, but there were several transcript sizes (1.2, 1.5, 2.0 and 3.5 kb) and in some individual tumours two or more transcripts were observed. Only two rhabdomyosarcomas, one classified as embryonal and one as pleomorphic, failed to exhibit transcription of members of the myf gene family. We were unable to detect transcription of myf genes in neuroblastomas, Wilms' tumours, hepatoblastomas, paediatric non-Hodgkin's lymphoma and leiomyosarcomas. When considered together these observations suggest that expression of myf genes could provide an extremely useful marker in the diagnosis of rhabdomyosarcoma.

Adolescent↗
PubMed1991

A clinical evaluation of an emergency procedures training program.

An emergency skills training program was undertaken in a long-term care setting to increase nursing knowledge about appropriate interventions. The program incorporated readiness activities and a walk-through laboratory approach to learning. Pre- and postcourse knowledge scores revealed improvements, as did a 3-month follow-up assessment of knowledge. Most of all, the response of staff to the program was overwhelmingly positive.

Education, Nursing, Continuing↗
PubMed1991

Prevention and management of oral mucositis induced by antineoplastic therapy.

Oral complications almost always occur as a consequence of treatment for head and neck cancer. In addition, approximately 40% of patients with nonhead and neck malignancies develop oral problems following exposure to chemotherapeutic agents and x-ray therapy. Patient-related risk factors for these problems include the type of malignancy, patient age, and the level of oral health before and during therapy. The authors discuss direct and indirect stomatotoxicity and present an overview of various methods of ameliorating and/or preventing oral mucositis.

Antineoplastic Agents↗
PubMed1991

Successful cryopreservation of human bone marrow does not require a controlled-rate freezer.

We studied CFU-GM recovery from bone marrow samples frozen either in a machine for controlled-rate freezing or in a -70 degrees C freezer. We found no statistically significant difference between the two methods. Cooling-curve investigations also demonstrated that it was possible to obtain satisfactory cooling rates simply by manipulation of the shape and volume of the marrow and its container. Five patients received a total of six successful autografts for which their marrow cells were frozen without controlled-rate freezing. Thus it is not necessary to use a sophisticated machine in order to obtain satisfactory cryopreservation of human marrow stem cells.

Bone Marrow↗
PubMed1990

Oral zidovudine, continuous-infusion fluorouracil, and oral leucovorin calcium: a phase I study.

A phase I clinical, pharmacologic, and biochemical evaluation of escalating oral zidovudine (AZT) given over 2 days with a fixed dose of continuous-infusion fluorouracil (800 mg/m2 per day X 3 days) and oral leucovorin calcium was performed. Eighteen patients were treated with doses of AZT ranging from 1.0 to 9.0 g/m2 per day. Nausea and vomiting were dose limiting, with a maximally tolerated dose of 7.5 g/m2 per day. Rash and mucositis occurred but were not dose limiting. A dose-related increase in peak plasma levels of AZT was observed, and the alpha half-life of AZT in plasma (75 min) was unaffected by these high doses. At doses above 4.0 g/m2 per day, trough levels significantly increased, perhaps reflecting prolonged absorption from the gut. No responses were observed; however, a significant increase in DNA single-strand breaks was observed in peripheral blood cells after a threshold dose of 4.0 g/m2 per day, confirming a biological effect of AZT in this regimen. Further trials with an intravenous formulation capable of maintaining plasma levels and circumventing dose-limiting toxicity are warranted.

Administration, Oral↗
PubMed1990

Prolactin stimulates milk protein promoter in CHO cells cotransfected with prolactin receptor cDNA.

A functional biological system was developed by cotransfecting mammalian cell lines with the cDNA of the prolactin receptor (PRL-R) and a fusion gene containing the promoter of the milk protein, ovine beta-lactoglobulin linked to the coding sequence of the chloramphenicol acetyltransferase (CAT) gene. Surprisingly, this system is effective even if a non-mammary cell line is used, since Chinese hamster ovary (CHO) cells transfected both transiently and stably with PRL-R cDNA respond to PRL, as observed by stimulation of the reporter gene. This newly developed system should help precisely define the functional domains of both the PRL-R molecule and of the regulatory elements of a PRL target gene.

Animals↗
PubMed1990

Combined time-lapse cinematography and immuno-electron microscopy.

A method was developed to record interactions between mobile non-adherent immunocytes by time-lapse cinematography and then to study the same cells by immuno-electron microscopy, using monoclonal antibodies against surface components. For this purpose a modified stage was designed to fit an inverted microscope. The attachment included a device to cool the culture chamber with N2 gas, a micro-injector for monoclonal antibody and immuno-gold treatment, and two pairs of washing needles to change the medium without disturbance. The technique was first employed to study the formation of aggregates around the antigen-presenting cells in cultures containing cells from hyper-immunized animals. Recently peripheral blood cells from normal subjects and patients with immune deficiency syndromes were stimulated with pokeweed mitogen, cluster formation was recorded, and the cells were processed for immuno-electron microscopy.

Animals↗
PubMed1990

Supportive care of the marrow transplant recipient: the Seattle Experience.

It is now almost 2 decades after the first successful human marrow transplants from HLA-identical siblings for the treatment of life-threatening hematologic diseases. Results have improved, especially for patients transplanted earlier in the course of disease. However, major problems remain in supporting patients through the transplant. More effective and less toxic conditioning regimens are needed. Acceleration of hematopoietic and immunologic reconstitution by use of various cytokines holds promise for decreasing infectious morbidity and mortality. Improved regimens to control acute and chronic GVHD and prevent opportunistic infections will play a major role in the advancement of supportive care of the marrow transplant recipient.

Anti-Infective Agents↗
PubMed1990

Excitotoxic lesions of the lateral hypothalamus made by N-methyl-d-aspartate in the rat: behavioural, histological and biochemical analyses.

The purpose of this study was to determine whether the excitotoxin N-methyl-d-aspartate (NMDA) could be used to make lesions within the lateral hypothalamus and what effect they had on regulatory behaviour. Larger doses of NMDA were effective in the lateral hypothalamus but tended to spread into adjacent structures; smaller doses made lesions which were contained within the lateral hypothalamus and zona incerta. Lesions which damaged the lateral hypothalamus and surrounding tissue had no effect on the concentration of dopamine (or its metabolites) in the dorsal or ventral striatum. The large lesions, including extrahypothalamic damage, were associated with long-term deficits in lab chow and water intake, but rats with lesions restricted to the lateral hypothalamus made good recoveries, eating and drinking normally from around the tenth day post-operation. Body weight gain was normal in these rats, though there was a long-term loss of body weight compared to controls. Unoperated rats with food intake yoked to lesioned rats showed identical long-term changes in body weight, suggesting that the changes in body weight of lesioned rats may be a reflection of changes in eating and drinking rather than a disruption of a body weight set-point mechanism. Motor deficits were not found; all rats were able to consume without difficulty saccharin solutions. All lateral hypothalamic lesioned rats failed to respond to dehydrating, dipsogenic or glucoprivic challenges. It is concluded that NMDA is an effective toxin in the rat lateral hypothalamus, sparing ascending dopamine fibres, and that the main effect of such lesions is an impairment in responding to physiological challenges.

3,4-Dihydroxyphenylacetic Acid↗
PubMed1990

Delayed radiation injury to the retrobulbar optic nerves and chiasm. Clinical syndrome and treatment with hyperbaric oxygen and corticosteroids.

Thirteen patients with delayed radiation injury to the optic nerves and chiasm were treated with hyperbaric oxygen (HBO) and corticosteroids. These patients experienced painless, abrupt loss of vision in one (6 patients) or both (7 patients) eyes between 4 and 35 months after receiving radiation doses of at least 4500 cGy to the region of the chiasm. Diagnostic evaluation including neuro-imaging and lumbar puncture showed no recurrent tumor and no other cause for visual loss. No patient's vision improved during treatment or follow-up lasting between 1 and 4 years. There were no serious complications of treatment.

Adrenal Cortex Hormones↗
PubMed1990

Minisatellite DNA profiles: rapid sample identification in linkage analysis.

Locus-specific minisatellite probes detect multiple alleles with heterozygosities of greater than 90% when hybridised to HinfI and AluI restriction digests of human DNA. We have hybridised 4 of these probes to a panel of DNAs digested with 6 of the restriction enzymes which commonly reveal di-allelic polymorphisms in the human genome. All 6 enzymes detected multiple resolvable alleles with at least 1 of the 4 minisatellite probes tested, thus providing a rapid and efficient means to check family relationships and paternity on filters already being used for linkage analysis.

Blotting, Southern↗
PubMed1990

Xenon-enhanced computed tomography compared with [14C]iodoantipyrine for normal and low cerebral blood flow states in baboons.

The correlation between the acute, invasive diffusible [14C]iodoantipyrine technique for cerebral blood flow and the noninvasive xenon-enhanced computed tomographic method has been assessed by simultaneous measurements in the baboon. Blood flows in small tissue volumes (about 0.125 cm3) were directly compared in normal and low flow states. These studies demonstrate a statistically significant association between the two methods (p less than 0.001). Similar correlations were obtained by both the Kendall (tau) and the Spearman (r) methods (r = 0.67 to 0.92, n greater than or equal to 19 for each study). The problems and limitations of such correlations are discussed.

Animals↗