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Biomedical subjects

D Sharp

Publications and source records attributed to D Sharp.

At least 19 recordsLinked to original sources
PubMed1992

Molecular cloning of cellular genes encoding retinoblastoma-associated proteins: identification of a gene with properties of the transcription factor E2F.

The retinoblastoma protein interacts with a number of cellular proteins to form complexes which are probably crucial for its normal physiological function. To identify these proteins, we isolated nine distinct clones by direct screening of cDNA expression libraries using purified RB protein as a probe. One of these clones, Ap12, is expressed predominantly at the G1-S boundary and in the S phase of the cell cycle. The nucleotide sequence of Ap12 has features characteristic of transcription factors. The C-terminal region binds to unphosphorylated RB in regions similar to those to which T antigen binds and contains a transactivation domain. A region containing a potential leucine zipper flanked by basic residues is able to bind an E2F recognition sequence specifically. Expression of Ap12 in mammalian cells significantly enhances E2F-dependent transcriptional activity. These results suggest that Ap12 encodes a protein with properties known to be characteristic of transcription factor E2F.

Amino Acid Sequence↗
PubMed1991

Sleep fragmentation and ventilatory responsiveness to hypercapnia.

It has been postulated that sleep disruption may change ventilatory chemoresponsiveness to hypercapnia and hypoxia and thereby contribute to the development of respiratory failure in some patients with obstructive sleep apnea syndrome (OSAS) or with other respiratory disorders. Some studies have demonstrated a reduction in ventilatory chemoresponsiveness in normal subjects after one night of total sleep deprivation. However, sleep fragmentation rather than total sleep deprivation is usual in patients. In this study, therefore, we measured hypercapnic ventilatory responsiveness (HCVR) and spirometry in 13 healthy male subjects (18 to 30 yr of age) after two consecutive nights of severe sleep fragmentation (arousal to an auditory stimulus after each minute of sleep) and compared the results with those obtained in the same subjects after normal sleep. Sleep fragmentation and normal sleep were separated by a week, and the order of intervention was randomized from patient to patient. No significant differences were observed in the slope or position of the HCVR curve after sleep fragmentation or in forced expiratory volumes. Although it is possible that a more prolonged period of sleep fragmentation than that used in this study may have an effect on HCVR, the results suggest that sleep fragmentation is an unlikely cause of progressive respiratory failure in patients with OSAS or with other respiratory disorders.

Adolescent↗
PubMed1991

Breast screening: a subject for debate.

The National Health Service Breast Screening Programme was instituted in 1988 following the recommendations of the Forrest report in 1986. From the beginning it has been controversial. Is breast cancer screening efficacious? Can the efficacy produced in trials be reproduced nationwide in the UK? Do the benefits of screening outweigh the adverse effects? Answers to all these questions are not yet available but in the light of current evidence, breast screening does appear to offer a realistic opportunity to reduce the mortality from a disease which constitutes a major public health problem in the UK. The role of the general practitioner and the primary care team is considered in the light of the experience gained in the first phase of the screening programme.

Breast Neoplasms↗
PubMed1988

Managing the difficult patient: practical suggestions from a study day.

A study day for general practitioners was arranged on the subject of managing the difficult patient. Participants were asked to supply written details of their most difficult patient and the problems they associated with him or her. The issues raised were addressed in a number of formal presentations and formed the basis for discussion in workshops. This paper focuses on the underlying similarities between the patients and discusses a practical approach to their management.

Adolescent↗
PubMed1986

Antenatal care.

Explore the source record for details and available documents.

Female↗
PubMed1983

Tuberous sclerosis in an infant of 28 weeks gestational age.

A case of tuberous sclerosis diagnosed at autopsy in a neonate at 28 weeks gestation is described. This is believed to be the earliest case yet reported. The CNS lesions consist of cortical tuberosities, heterotopic white matter nodules and subependymal nodules. These nodules consist predominantly of giant astrocytes but a small undifferentiated cell component is present as well. Multiple cardiac rhabdomyomas are also present. An explanation for neuronal hypocellularity within the cortical tuberosities is suggested.

Brain↗
PubMed1983

Paraneoplastic subacute necrotic myelopathy.

A 79 year old male acutely developed a Brown-Sequard syndrome two weeks following resection of renal cell carcinoma. The subsequent clinical course was marked by subacute progression of spinal cord signs. Pathologic studies showed extensive multifocal spinal cord necrosis that could not be attributed to vascular occlusion or to vasculitis. This case appears to be a rare example of paraneoplastic subacute necrotic myelopathy.

Aged↗
PubMed1983

Effects of erythromycin and gentamicin in experimental peritonitis.

Erythromycin and gentamicin were used to analyse the concept of bacterial synergy in an experimental model of acute appendicitis. Erythromycin given orally suppressed the aerobic flora other than the Enterobacteriaceae. When given by injection, a notable reduction in the counts of bacteroides and other anaerobic Gram-negative bacteria was also achieved. The addition of gentamicin, itself inactive against bacteroides, resulted in their total suppression. The implications of these findings are discussed.

Administration, Oral↗
PubMed1979

Dissociation of active from immobility components of sexual behavior in female rats by central 6-hydroxydopamine: implications for CA involvement in sexual behavior and sensorimotor responsiveness.

Ovariectomized female rats were given a hormone treatment (2 X 8 micrograms/kg estradiol benzoate) that normally supports only low levels of lordosis responding and no soliciting behavior in tests with sexually active males. When subjected to an intraventricular 6-hydroxydopamine (6-OHDA) procedure (with pargyline pretreatment) that produced 85% and 95% depletions of caudate dopamine and cortical norepinephrine respectively, these females exhibited a dramatic increase in the intensity and frequency of lordotic responding but no soliciting behavior over 3 weekly tests. The increase in lordosis was not due to a drug- or stress-induced release of adrenal progesterone, since dexamethasone suppressed the progesterone levels, as documented by radioimmunoassay, but not the higher receptivity of 6-OHDA treated females. In other ovariectomized females given a hormone regimen (2 X 50 micrograms/kg estradiol benzoate plus 500 micrograms progesterone) that supported maximal levels of lordosis and soliciting, the same 6-OHDA treatment prolonged the average duration of lordosis while actually decreasing the incidence and duration of soliciting. The hypothesis is put forward that the differential effects of interfering with catecholamine, and more likely dopamine function on the soliciting and lordosis components of female sexual behavior might best be understood as a dissociation between mutually antagonistic behavior patterns such that responsiveness involving active orientation and forward locomotion is suppressed, whereas responses requiring immobility are augmented.

Animals↗
PubMed1979

Intestinal bacterial metabolism of protein and bile acids: role in pathogenesis of hepatic disease after jejuno-ileal bypass surgery.

Jejunal bacterial colonization and intestinal metabolism of bile acids and protein by bacteria have been investigated in 12 patients with abnormal liver histology following jeujno-ileal bypass surgery for obesity. Aerobic and/or anaerobic colonic flora was present in jejunal aspirates from 8 of 12 bypass patients, but in none of the controls. Intestinal protein metabolism and bile acid deconjugation (measured by urinary indican excretion and 14C-glycocholic acid breath test) was significantly enhanced in bypass patients. Intestinal bacterial overgrowth, with abnormal intestinal metabolism by bacteria of ingested nutrients and bile acids, could contribute to hepatic disease after bypass surgery via the production of endogenous hepatotoxins.

Adult↗
PubMed1979

Radiation-induced mitotic and meiotic aneuploidy in the yeast Saccharomyces cerevisiae.

A number of genetic systems are described which in yeast may be used to monitor the induction of chromosome aneuploidy during both mitotic and meiotic cell division. Using these systems we have been able to demonstrate the induction of both monosomic and trisomic cells in mitotically dividing cells and disomic spores in meiotically dividing cells after both UV light and X-ray exposure. The frequency of UV-light-induced monosomic colonies were reduced by post-treatment with photoreactivity light and both UV-light- and X-ray-induced monosomic colonies were reduced by liquid holding post-treatment under non-nutrient conditions. Both responses indicate an involvement of DNA-repair mechanisms in the removal of lesions which may lead to monosomy in yeast. This was further confirmed by the response of an excision-defective yeast strain which showed considerably increased sensitivity to the induction of monosomic colonies by UV-light treatment at low doses. Yeast cultures irradiated at different stages of growth showed variation in their responses to both UV-light and X-rays, cells at the exponential phase of growth show maximum sensitivity to the induction of monosomic colonies at low doses whereas stationary phase cultures showed maximum induction of monosomic colonies at high does. The frequencies of X-ray-induced chromosome aneuploidy during meiosis leading to the production of disomic spores was shown to be dependent upon the stage of meiosis at which the yeast cells were exposed to radiation. Cells which had proceeded beyond the DNA synthetic stage of meiosis were shown to produce disomic spores at considerably lower radiation doses than those cells which had only recently been inoculated into sporulation medium. The results obtained suggest that the yeast sustem may be suitable for the study of sensitivities of the various stages of meiotic cell division to the induction of chromosome aneuploidy after radiation exposure.

Aneuploidy↗
PubMed1979

Detection of mitotic and meiotic aneuploidy in the yeast Saccharomyces cerevisiae.

A number of genetic systems are described which involve the use of the yeast Saccharomyces cerevisiae. The systems may be used to detect the production of aneuploid cells produced during both mitotic and meiotic cell division in the presence of genetically active chemicals. During mitotic cell division, monosomic colonies (2n - 1) may be detected by plating upon selective medium. Increases in such monosomic colonies are produced by exposure of cells to a number of chemical mutagens such as ethyl methane-sulfonate and mitomycin C. More importantly, monosomic colonies are also induced by nonmutagens such as sulfacetamide and saccharin, which suggests that such chemicals are capable of inducing aneuploidy (aneugenic) in the absence of mutagenic activity. Genetic analysis of aneuploid colonies produced on nonselective medium indicate that at least a proportion of the monosomic colonies were the result of mitotic nondisjunction. During meiotic cell division, disomic cells (n + 1) produced by chromosome nondisjunction may be detected by plating on selective media. The frequency of disomic cells has been shown to increase after exposure to p-fluorophenylalanine.

Aneuploidy↗