The ypt proteins of Schizosaccharomyces pombe.
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Endocytosis↗
Biomedical subjects
S Bowden
Publications and source records attributed to S Bowden.
Alterations in intrahepatic expression of duck hepatitis B viral markers with ganciclovir chemotherapy.
Ducks congenitally infected with duck hepatitis B virus (DHBV) were treated with the guanosine analogue, ganciclovir, and the effect on serum and intrahepatic expression of DHBV DNA and viral proteins was examined. After 21 days of ganciclovir treatment, a substantial reduction in viraemia occurred; in contrast, the level of circulating DHBV surface antigen was unchanged. Ganciclovir therapy also substantially reduced the level of DHBV DNA replicative intermediates and the expression of viral core and surface antigen in hepatocytes. However, despite the antiviral treatment some liver cells, including the bile duct epithelial cells and putative oval cells, maintained their intense staining for the viral proteins. Furthermore, DHBV-infected cells in extrahepatic sites such as the pancreas, kidney and spleen were also unaffected by ganciclovir treatment. These results suggest that monotherapy with nucleoside analogues is unlikely to eliminate chronic hepadnaviral infection, and antiviral programs should be designed to target all cell populations infected by the virus.
Animals↗
Alcohol, thiamin deficiency, and neuropsychological disorders.
In this paper, two of the major themes in contemporary neuropsychological research are reviewed. These are the nature of cognitive impairment observed in alcohol related brain injury, and the cause or causes of alcohol related brain injury. Two experiments are briefly reported which address these issues. The first experiment concerns the nature of abilities which are involved in a test of memory (delayed matching to sample), which is fundamental to current experimental models of human amnesia. The second experiment involves preliminary data from a randomised, double-blind, multi-dose trial of intra-muscular thiamin for the treatment of alcohol related brain injury, in alcohol dependent subjects who do not show any overt signs of Wernicke-Korsakoff syndrome.
Adult↗
The use of ampligen alone and in combination with ganciclovir and coumermycin A1 for the treatment of ducks congenitally-infected with duck hepatitis B virus.
Ampligen, a known immunomodulator and interferon inducer, was used alone and in combination with other antiviral agents to treat ducks congenitally-infected with duck hepatitis B virus. These antiviral agents included the conventional nucleoside analogue ganciclovir and the prokaryotic DNA gyrase B inhibitor coumermycin A1. When used alone, ampligen decreased the amount of serum and liver viral DNA, but had no effect on circulating duck hepatitis B surface antigen (DHBsAg). In combination with ganciclovir, the antiviral effect appeared at least additive with a greater inhibition of viral DNA replication within the liver. The combination of ampligen with coumermycin A1 also resulted in inhibition of viral replication but to a lesser extent than ampligen alone. When all three agents were used together, viral DNA replication was again inhibited, but as with previous treatment regimes, serum DHBsAg levels remained unchanged. At the end of the treatment period for all regimes, analysis of viral DNA forms in the liver showed that the viral relaxed circular and supercoiled DNA forms had persisted. Within 1 week of cessation of therapy, viral replication had often returned to pre-treatment levels. Interferon-like activity was detected in the sera of the majority of the treated ducks during the ampligen therapy, but no clear relationship between the presence of interferon and antiviral effect could be established. These observations in the duck hepatitis B model may provide a rational basis for the use of combinations of antiviral and immunomodulatory regimes for the management of chronic hepatitis B infection in man.
Aminocoumarins↗
Function of the ypt2 gene in the exocytic pathway of Schizosaccharomyces pombe.
The ypt2 gene of the fission yeast Schizosaccharomyces pombe encodes a member of the ypt/rab family of small GTP-binding proteins, related in sequence to Sec4p of Saccharomyces cerevisiae but closer to mammalian rab8. We have introduced a mutation into the gene corresponding to a mutation identified in ypt1, in which a conserved valine residue was altered to asparagine. The mutated ypt2 gene was introduced into the S. pombe genome by gene replacement. The resulting strain was temperature-sensitive for growth. Normal growth was restored by introduction of a plasmid-borne wild-type ypt2 cDNA or by cDNA for rab8 but not by various other rab or ypt sequences. At restrictive temperature the mutant cells accumulated the secretory protein acid phosphatase in a form that appeared to be fully glycosylated and acquired a population of vesicles detectable by electron microscopy. Thus the ypt2 protein, and by inference rab8, appear to function in the last stage of the secretory pathway.
Acid Phosphatase↗
Schizosaccharomyces pombe ypt5: a homologue of the rab5 endosome fusion regulator.
The ypt/rab proteins are a family of small GTP-binding proteins thought to be required for different stages of membrane traffic. From the fission yeast Schizosaccharomyces pombe we have isolated and characterized ypt5, a gene encoding a homologue of rab5, a mammalian protein apparently involved in regulating fusion of early endosomes. Recombinant ypt5 protein bound GTP. The ypt5 gene was found to be essential for viability on minimal media, but ypt5-disrupted cells grew slowly on some rich media and accumulated a population of small vesicles not observed in wild-type cells. Canine rab5 cDNA could replace the ypt5 gene in S. pombe and restore normal growth and viability. Ypt5 protein expressed in mammalian cells colocalized with the transferrin receptor to early endosomes. Thus, molecular aspects of the early endocytic pathway may be conserved between mammalian cells and S. pombe and hence may be amenable to genetic analysis.
Amino Acid Sequence↗
Is there a need for improved pharmacy services to the operating theatre?
A study to assess the control and handling of drugs within an operating theatre complex (10 theatres) of an 850-bed hospital, has revealed the presence of unusable medication and thus highlighted the need for improved pharmacy services. The aims and objectives of the pharmacy department to enhance such services included improvement of drug control of stock medication and the introduction of clinical pharmacy services within the operating theatre. To undertake this, three systems were evaluated with reference to systems already in use in the U.S.A. Operating theatre visits by a clinical pharmacist, coupled with the expansion of the existing drug distribution service, were identified as the most cost-effective methods that would allow the objectives to be met. Consequently, this has now been implemented within the operating theatre complex.
Evaluation Studies as Topic↗
A homologue of the ras-related CDC42 gene from Schizosaccharomyces pombe.
A cDNA was isolated from the fission yeast, Schizosaccharomyces pombe, using mixed oligodeoxyribonucleotides encoding part of the GTP-binding site of the ras superfamily. The encoded protein is the homologue of the budding yeast CDC42 gene product and the human proteins, CDC42Hs and G25K.
Amino Acid Sequence↗
Neuropsychological functioning in adolescents with diabetes.
Investigated the relationship between disease variables, neuropsychological performance, and psychosocial status in adolescents with Insulin Dependent Diabetes Mellitus (IDDM). The study group consisted of 85 adolescents, aged 14 to 16.5 years who had been diabetic for longer than 12 months. Parameters of both recent and long-term metabolic control were determined, including diabetic incidents such as severe hypoglycemia or ketoacidosis. The mothers completed standardised measures of adolescent adjustment, and the adolescents provided self-reports of psychosocial status. Neuropsychological functioning was evaluated with standardised tests of verbal and nonverbal intelligence, memory and new learning, visuo-graphic skills, mental flexibility, and problem-solving ability. Using retrospective accounts of disease history, there was no relationship between neuropsychological functioning and variables such as age of onset, chronic poor control, or major metabolic crises. The findings emphasise the need for a long-term, prospective study of a cohort of diabetic children from the time of diagnosis to clarify causal relationships, if any, between illness variables, neuropsychological performance, and psychosocial factors.
Adolescent↗
Combination antiviral therapy controls severe post-liver transplant recurrence of hepatitis B virus infection.
The authors have successfully used combination ganciclovir and foscarnet chemotherapy to control viral replication following liver transplantation in a patient with severe recurrence of hepatitis B virus (HBV) infection. The disease was characterized by extremely high viraemias, deteriorating liver function, and high levels of intra-hepatic hepatitis B core antigen (HBcAg) and hepatitis B surface antigen (HBsAg). Treatment resulted in a greater than 30-fold reduction in serum HBV DNA and HBsAg levels. Liver function tests returned to normal and the histological progression of the disease was arrested. Hepatic cytoplasmic HBsAg decreased substantially but there was little change in HBcAg, implicating HBsAg rather than HBcAg in the liver injury. Combination antiviral chemotherapy using agents such as ganciclovir and foscarnet may offer a new approach to the management of post-transplant recurrence of HBV.
Adult↗
How to develop a staff development indicator.
In this article, the author describes a step-by-step approach to generating staff development indicators, as well as examples of the evolving indicator during the development process. Quality improvement indicators are necessary, not only for patient care activities, but also for service activities related to patient care. Staff development is one such service.
Humans↗