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Biomedical subjects

K Davidson

Publications and source records attributed to K Davidson.

At least 91 records · Page 5Linked to original sources
PubMed1991

Hydroxyurea accelerates loss of extrachromosomally amplified genes from tumor cells.

Gene amplification is one mechanism mediating the resistance of tumor cells to antineoplastic agents and the overexpression of a variety of oncogenes in diverse tumor types. There is mounting evidence that acentric extrachromosomal elements such as double minute chromosomes are common intermediates in the amplification process. These acentric structures partition unequally at mitosis and can be lost in the absence of selection. In the present study, we used human and hamster cell lines documented to contain extrachromosomally amplified drug resistance genes to investigate the feasibility of enhancing the loss rate of the extrachromosomally amplified genes to make the cells more sensitive to drug treatment. The results show that treatment of each of these lines with hydroxyurea accelerates the loss of the extrachromosomally amplified drug resistance genes. Loss of these extrachromosomal genes was associated with a corresponding increase in the drug sensitivity in the cases examined. The mechanism of accelerated loss does not appear to involve a differential effect on the replication of extrachromosomal DNA sequences. The results suggest that hydroxyurea treatment may provide a valuable tool for the general accelerated elimination of extrachromosomally amplified genes.

Aspartate Carbamoyltransferase↗
PubMed1991

Short report: plasma somatostatin concentrations in the irritable bowel syndrome.

The description of a patient with the irritable bowel syndrome whose symptoms were completely relieved by the administration of somatostatin raised the possibility that a deficiency of somatostatin may be involved in the pathogenesis of the disorder. We have examined this possibility by studying 11 healthy controls (35 +/- 12 years; mean +/- S.D. 8 female) and 10 irritable bowel syndrome patients (39 +/- 14 years; 7 female) complaining of frequency of defaecation of 4 or more times a day. Plasma somatostatin concentrations were determined by specific radioimmunoassay, fasting and at 15, 30, 45, 60, 90, 120 and 180 min after a standard breakfast. Irritable bowel syndrome patients and controls had similar fasting (27.4 +/- 5.1 vs. 35.2 +/- 4.3 pg/ml; mean +/- S.E.M. and integrated increment of post-prandial (5105 +/- 858 vs. 3885 +/- 793 pg.min/L) plasma concentrations of somatostatin, as assessed by student's t-test. These observations do not support the idea that a state of somatostatin deficiency exists in the irritable bowel syndrome.

Adult↗
PubMed1990

Endoglucanase E, produced at high level in Escherichia coli as a lacZ' fusion protein, is part of the Clostridium thermocellum cellulosome.

The Clostridium thermocellum celE gene was expressed at high level in Escherichia coli TG1 when placed under the transcriptional and translational control of lacZ' in pUC18; in the presence of a multicopy plasmid (pNM52) containing the lacIq gene, expression of full-length and truncated forms of celE was regulated by isopropyl-beta-D-thiogalactopyranoside. Catalytically active endoglucanase E (EGE) produced by E. coli was subject to proteolytic processing. The main protein species produced from full-length and truncated forms of celE was around 40 kDa in size and had an N-terminal amino acid sequence corresponding to that derived for mature EGE from the nucleotide sequence; in addition, larger species of about 75 kDa, presumably corresponding to full-size EGE, were produced by E. coli containing the full-length celE gene. Even after removal of the signal peptide sequence, EGE produced by E. coli was secreted into the periplasm. Up to 157 bp could be deleted from the 5' end of the celE gene without affecting the catalytic activity of EGE produced by E. coli. A polypeptide of Mr 86 kDa, immunoreactive with anti-EGE antiserum, was demonstrated in the high-molecular-weight, cellulose-binding multiprotein aggregate recoverable from C. thermocellum culture supernatant.

Amino Acid Sequence↗
PubMed1990

Cloning and sequencing of the celA gene encoding endoglucanase A of Butyrivibrio fibrisolvens strain A46.

Genomic DNA from Butyrivibrio fibrisolvens strain A46 was digested with EcoRI and ligated into lambda gt11. Two recombinant phages isolated from the gene bank hydrolysed carboxymethylcellulose and were shown to contain the same 2.3 kb EcoRI restriction fragment, which was cloned into pUC12 to generate pBA46. Escherichia coli JM83 harbouring pBA46 expressed an endoglucanase (EGA) which hydrolysed a range of other substrates including barley beta-glucan, Avicel, filter paper and p-nitrophenyl beta-D-cellobioside. Nucleotide sequencing of the B. fibrisolvens strain A46 DNA cloned in pBA46 revealed a single open reading frame (ORF) of 1296 bp, encoding a protein of 48,863 Da. Confirmation that the ORF coded for EGA was obtained by comparing the N-terminal sequence of the purified endoglucanase with that deduced from the nucleotide sequence. EGA contains a typical prokaryotic signal peptide at its N-terminus and shows some homology with the Bacillus family of cellulases. The enzyme does not contain distinct functional domains, which are prevalent in cellulases from Pseudomonas fluorescens subsp. cellulosa and Cellulomonas fimi.

Amino Acid Sequence↗
PubMed1990

The growth hormone releasing hormone (GHRH) response to a mixed meal is blunted in young adults with insulin-dependent diabetes mellitus whereas the somatostatin response is normal.

Following a standard mixed meal, plasma concentrations of growth hormone releasing hormone (GHRH), somatostatin (SMS) and growth hormone (GH) were measured every 30 min for 300 min in six young adults with type I insulin-dependent diabetes mellitus (IDDM) and five normal controls. Mean blood glucose concentrations were higher and mean free insulin levels lower in the diabetics compared with controls both in fasting specimens and at all times following the mixed meal. Basal concentrations (mean +/- SEM) of GHRH were similar in diabetic (12.7 +/- 1.8 pg/ml) and control subjects (11.8 +/- 1.1 pg/ml). Following ingestion of the mixed meal, a rise in GHRH was observed in the control subjects maximal between 30 and 240 min (P less than 0.025) but the response was blunted in the diabetics. Mean GHRH concentrations were greater in the controls than in the diabetic subjects at all stages during the test, the maximum difference being noted at 120 mins (P less than 0.04). Basal SMS concentrations and those observed after the mixed meal were similar in diabetic and control subjects. These results indicate that glucose and insulin may play a role in the regulation of GHRH release following a mixed meal but circulating levels of GHRH and SMS are unlikely to be relevant to the abnormal regulation of GH in IDDM.

Adolescent↗
PubMed1989

Octreotide.

Explore the source record for details and available documents.

Acromegaly↗
PubMed1989

Provocative testing in the diagnosis of dynamic carpal tunnel syndrome.

This study measures the effects of provocative testing on a series of patients with latent symptoms of carpal tunnel syndrome. Forty patients were studied for change in hand volume and loss of sensibility after stress. Thirty-four patients demonstrated significant measurable increase in hand volume after a 7-minute stress test. In 17 of 34 patients impaired sensibility associated with swelling developed and they were considered to have dynamic carpal tunnel syndrome. Surgical treatment was effective in correcting symptoms and sensory defects in these 17 individuals despite postoperative hand swelling that continued after the operation when the hand was subjected to stress.

Adult↗
PubMed1989

The pituitary-adrenal response to CRF-41 is unaltered by intravenous somatostatin in normal subjects.

We have previously reported that the hypothalamo-pituitary-adrenal response to insulin-induced hypoglycaemia is normal while the cortisol release to pituitary stimulation by corticotrophin releasing factor (CRF-41) is reduced in obesity. Impaired growth hormone (GH) secretion is also found in obesity which may result from altered central levels of somatostatin (SMS). We have investigated, by giving a simultaneous infusion of SMS to six volunteer normal weight men during a CRF test, whether it is possible for SMS to modify pituitary-adrenal function. Each subject received intravenous CRF-41 (0.5 micrograms/kg) on two occasions during an infusion of isotonic saline or SMS (4 micrograms/min) in a randomized double-blind study. Plasma GH, cortisol, ACTH and SMS were measured. Three subjects demonstrated GH peaks during saline infusion but no peaks were seen in any subject during SMS infusion. No significant difference was found between peak cortisol responses during saline or SMS infusion (SMS cortisol 443 +/- 61 nmol/l, saline cortisol 485 +/- 52 nmol/l); neither was there any difference in the ACTH responses. We conclude that SMS does not alter the pituitary response to CRF in normal weight men and is thus less likely to be responsible for the altered pituitary-adrenal function seen in obesity. Further studies of alternative mechanisms are required to explain the cause of this abnormality.

Adrenocorticotropic Hormone↗
PubMed1989

Psychotic illness following termination of pregnancy.

A case of a psychotic illness following an induced termination of pregnancy is described; this is discussed in relation to the literature on the subject, and possible aetiological factors in the case are reviewed.

Abortion, Induced↗
PubMed1988

Somatosensory evoked potentials quantify clinical improvement of cerebral vasospasm after intravenous administration of nimodipine.

The calcium antagonist nimodipine (Nimotop; Bayer AG Leverkusen) has been shown to prevent cerebral vasospasm after aneurysm surgery. Ten patients with clinical and angiographic evidence of vasospasm showed accompanying delays in central conduction time, quantified by somatosensory evoked potential measurements, but nimodipine infusion markedly improved neurological status and level of consciousness in all cases within 10-60 minutes. Conduction time was simultaneously reduced on the affected side. No focal deficits developed during therapy (mean 7.1 days) with nimodipine, which also appears to be effective in relieving existing vasospasm. Evoked potentials provided a noninvasive quantitative parameter that correlated well with vasospastically induced clinical signs.

Adult↗
PubMed1988

Structure of the transcription initiation and termination sequences of seven early genes in the vaccinia virus HindIII D fragment.

The vaccinia virus HindIII D fragment is 16,060 bp in length and encodes 13 complete genes [E.G. Niles et al. (1986). Virology 153, 96-112; S. L. Weinrich and D. E. Hruby (1986). Nucleic Acids Res. 14, 3003-3016]. Six of these genes are expressed only at early times after infection and one gene is expressed at both early and late times [G. -J. Lee-Chen and E. G. Niles (1988). Virology 163, 52-63]. Transcript mapping by S1 nuclease protection studies was carried out and compared to the results of primer extension analyses, in order to locate map positions of the 5' termini of each early mRNA. The lengths of the products of in vitro transcription, from DNA templates which possess the transcription start regions of each of the early genes, were determined and compared to the lengths of DNA products generated by S1 nuclease protection and primer extension, in order to demonstrate that the 5' termini identified by S1 mapping and primer extension are due to transcription initiation and not to mRNA processing. For each of the early genes in the HindIII D fragment, transcription starts within 25 nucleotides of the translation initiation codon. The precise location of the 3' termini of each early transcript was identified by S1 nuclease mapping. In all but one case, the 3' ends map within 75 nucleotides of the putative transcription termination signal TTTTTNT [G. Rohrmann, L. Yuen, and B. Moss (1986).

Base Sequence↗
PubMed1988

Preparation of social workers for a changing health care environment.

Rapid changes in health care have provided the impetus for social workers to reexamine their professional preparation for effective practice in health care settings today. Faculty teaching students and field instructors were asked to indicate on a questionnaire where specific subject matter is taught to social work students: in the classroom, in the field, or in both settings. Results of the study show a communication gap between school and field and a need for teaching models that enable educators to convey more of the profession's expanding knowledge base and to prepare students to deal with concurrent demands for expertise and expediency in practice. Programmatic changes to address these issues are suggested.

American Hospital Association↗
PubMed1986

Nucleotide sequence and genetic map of the 16-kb vaccinia virus HindIII D fragment.

We have determined the nucleotide sequence of the 16,059-bp HindIII D fragment from vaccinia virus strain WR. Translation in all 6 reading frames reveals a set of 22 open reading frames (ORFs), which are capable of encoding proteins ranging from 61 to 844 amino acids in length. With one exception, ORF 12, we have divided them into two primary sets according to their size. The minor group contains eight members ranging in length from 61 to 84 amino acids. The major group has thirteen members varying from 146 to 844 amino acids in length, and, in addition, due to its location on the DNA, one small ORF, 61 amino acids long. The neighboring major ORFs are closely packed along the DNA, being separated by 42 or fewer base pairs. In several instances the ends of adjoining ORFs overlap for up to 11 triplet codons. In three cases, 1 or 2 bases are shared between translation start and stop signals in adjacent ORFs. Regions of both strands of the DNA are transcribed. Two sets of temperature-sensitive mutations, totaling 17, which map to the HindIII D fragment, have been combined into eight complementation groups. The results of marker rescue analysis map one or more member of each group to a site in the HindIII D fragment within a defined open reading frame.

Amino Acid Sequence↗
PubMed1985

Notification of a cohort of workers at risk of bladder cancer.

Surviving members of occupational cohorts studied in retrospective analyses of mortality usually are not notified individually of positive study results. However, concern has arisen that such results may contain risk information pertinent to study subjects. To evaluate the effects and implications of individually notifying survivors of such cohorts, we conducted a pilot notification study. Members of a cohort of 1,385 chemical workers who had handled carcinogenic amines were notified by mail that they were likely to be at increased risk of bladder cancer. Also a bladder cancer screening and follow-up program was established. The study demonstrated that notification is a complex action and that much care needs to be taken when communicating information on risk. Notification requires development of (1) criteria as to what constitutes a notifiable risk and (2) programs to meet the medical and social needs of the various parties involved in notification.

Carcinogens↗
PubMed1984

Aromatase activity in uterine leiomyomata.

Of the 24 samples of leiomyoma tissues examined 14 were shown to have aromatase activity in vitro. In contrast only 1 of 12 samples of myometrium had any demonstrable activity. Measurements of tissue oestrogen levels showed no correlation with the amount of aromatase activity although oestradiol levels were consistently higher in the tumour tissues compared with the normal myometrium.

Androstenedione↗