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Biomedical subjects

J Armstrong

Publications and source records attributed to J Armstrong.

At least 19 recordsLinked to original sources
PubMed1992

Post-translational processing of Schizosaccharomyces pombe YPT proteins.

ras proteins are post-translationally processed at their carboxyl-terminal CAAX motif by a triplet of modifications: prenylation of C with farnesyl, proteolytic trimming of AAX, and carboxyl-methylation. These modifications co-operate with palmitoylation of nearby sites or a polybasic region to target plasma membrane localization. The related YPT/rab proteins in contrast are localized to compartments of the endo-membrane system and may be involved in directing membrane traffic. These proteins end in XCC or CXC motifs. We have analyzed the processing of members of this subfamily form the fission yeast Schizosaccharomyces pombe. We find using in vitro translation in reticulocyte lysates that YPT1, -3, and -5 are prenylated with geranylgeranyl and that they incorporate label from [3H]mevalonic acid when expressed in transfected COS cells in vivo. Furthermore, prenylation was necessary for membrane binding in vivo. The CXC protein YPT5, but neither of the two XCC proteins YPT1 and YPT3, was carboxyl-methylated in S. pombe and in COS cells in vivo. However, YPT5 was not carboxyl-methylated in vitro in lysates which were able to methylate ras protein. YPT3 was detectably palmitoylated when expressed in COS cells, though at a much lower level than ras.

Amino Acid Sequence↗
PubMed1992

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↗
PubMed1992

Protein prenylation in Schizosaccharomyces pombe.

S. pombe is shown to be a powerful system for studies concerning attachment of polyisoprenoid moieties to proteins, due to its ability to take up exogenous mevalonic acid efficiently. The fission yeast can take up about 5% of the exogenously added mevalonic acid and incorporate approximately 10% of this into protein. By contrast, the uptake obtained with the budding yeast S. cerevisiae is less than 0.5%. HPLC analysis of total S. pombe protein-bound isoprenoids revealed that approximately 55% of the counts co-migrated with the geranylgeraniol standard, while approximately 45% of the counts co-migrated with farnesol. We could not detect any effects of mevinolin or other HMG-CoA reductase inhibitors in S. pombe.

Chromatography, High Pressure Liquid↗
PubMed1992

Analysis of the BiP gene and identification of an ER retention signal in Schizosaccharomyces pombe.

We have cloned the gene for the resident luminal ER protein BiP from the fission yeast, Schizosaccharomyces pombe. The predicted protein product is equally divergent from the budding yeast and mammalian homologues. Disruption of the BiP gene in S. pombe is lethal and BiP mRNA levels are regulated by a variety of stresses including heat shock. Immunofluorescence of cells expressing an epitope-tagged BiP protein show it to be localized to the nuclear envelope, around the cell periphery and in a reticular structure through the cytoplasm. Unexpectedly, we find the BiP protein contains an N-linked glycosylation site which can be utilized. The C-terminal four amino acids of BiP are Ala-Asp-Glu-Leu, a new variant of the XDEL sequence found at the C-termini of luminal endoplasmic reticulum proteins. To determine whether this sequence acts as a sorting signal in S.pombe we expressed an acid phosphatase fusion protein extended at its C-terminus with the amino acids ADEL. Analysis of the sorting of this fusion protein indicates that the ADEL sequence is sufficient to cause the retention of proteins in the endoplasmic reticulum. The sequences DDEL, HDEL and KDEL can also direct ER-retention of acid phosphatase in S.pombe.

Acid Phosphatase↗
PubMed1992

Oral rabies vaccination of skunks and foxes with a recombinant human adenovirus vaccine.

A new recombinant rabies vaccine (human adenovirus 5 containing the rabies glycoprotein gene) was given to striped skunks (Mephitis mephitis) and red foxes (Vulpes vulpes). Groups of skunks received the vaccine in baits, by direct instillation into the mouth, or intramuscularly. Foxes were given vaccine by direct instillation into the oral cavity (DIOC). Selected groups of vaccinated skunks and foxes were challenged with street rabies virus. There were high rates of seroconversion (generally with high antibody titers) in both foxes and skunks, with survival of all challenged vaccinated animals (all challenge controls developed rabies). In skunks, vaccine given DIOC was effective over a broad range of doses (10(8.7), 10(7.6) and 10(6.4) median tissue culture infective doses). There was no evidence of pathogenic effects. The results indicate that this adenovirus recombinant has considerable potential as a wildlife oral rabies vaccine.

Adenoviruses, Human↗
PubMed1992

Optic neuropathy and central nervous system disease associated with primary Sjögren's syndrome.

Three cases of optic neuropathy associated with primary Sjögren's syndrome are reported. All three patients had clinical manifestations of primary Sjögren's syndrome, although two of the patients did not report sicca symptoms at initial examination. Two patients had focal neurologic signs in addition to optic neuropathy. The differentiation of this syndrome of optic neuropathy, focal neurologic signs, and Sjögren's syndrome from multiple sclerosis and antiphospholipid antibody syndrome is important for reasons of treatment and prognosis. This diagnostic differentiation was facilitated by positive tests for xerophthalmia and findings of positive minor salivary gland biopsy. High titers of antinuclear antibody, anti-SSA(Ro), and anti-SSB(La), and the absence of antiphospholipid antibodies provided additional help in the differential diagnosis. In 5 years of observation, none of the patients developed symptoms of multiple sclerosis or additional connective tissue disorders.

Adult↗
PubMed1992

The incidence of total hip replacement in orthognathic surgery patients receiving short-term steroid therapy.

It is well known that long-term corticosteroid therapy can lead to avascular necrosis of the femoral head. There is suspicion among orthopedic surgeons that short-term, high-dose steroid use poses similar risks. The records of 2,773 patients (1,497 who had total hip replacement and 1,276 who had orthognathic surgery) were retrospectively reviewed. No hip replacements had been done in the orthognathic surgery group and none of the patients in the total hip replacement group had undergone orthognathic surgery. The use of short-course, systemic corticosteroids to reduce postoperative swelling in orthognathic surgery did not seem to cause avascular necrosis of the femoral head.

Adrenal Cortex Hormones↗
PubMed1992

A reappraisal of the role of prophylactic cranial irradiation in limited small cell lung cancer.

The use of prophylactic cranial irradiation in limited stage small cell lung cancer remains controversial. Prospective trials have demonstrated that PCI can reduce central nervous system relapse rates, but the impact on survival remains questionable except for the possible evidence of a beneficial effect for long term survivors. With higher rates of thoracic control now obtainable with hyperfractionated radiation and concomitant chemotherapy, it becomes important to analyze the benefit of PCI in that setting. Before 1982, we included PCI in the management of all patients with limited stage small cell lung cancer; thereafter, we discontinued its use. This report compares the outcome of the two treatment approaches and addresses the role of PCI among patients who achieve durable local control. There were 36 limited stage small cell lung cancer patients treated with PCI from 1979-1982 and 26 patients treated without PCI from 1985-1989. Induction chemotherapy was followed in both groups by thoracic irradiation (45 Gy). The PCI patients received 30 Gy to the whole brain in 10 fractions. Both groups received maintenance chemotherapy. Of complete responders, brain failure was the first failure in 18% (4/22) of PCI (+) versus 45% (10/22) of PCI (-) (p = .04). Survival at 2 years was 42% for PCI (+) versus 13% for PCI (-) (p less than .05). When the analysis was limited to those patients permanently controlled in the thorax; there were 25% (4/16) brain failures PCI (+) versus 70% (7/10) PCI (-) (p = .03). For this same subset the 2-year survival was 56% PCI (+) versus 14% PCI (-) (p less than .05). There were no 5 year survivors without PCI compared to 38% (6/16) with PCI. These data suggest that PCI appears to be effective in enhancing survival of patients who achieve durable thoracic control. Prospective trials are necessary to evaluate the use of PCI combined with therapeutic regimens with a documented ability to achieve high rates of sustained control of thoracic disease.

Brain↗
PubMed1992

Bidirectional ion transport in thyroid: secretion of anions by monolayer cultures that absorb sodium.

Cultured porcine thyroid cell monolayers transport Na+ in an apical-to-basal direction, resulting in the development of a basal-positive transepithelial potential difference (TEP) and the formation of domes (fluid-filled elevations of the cell layer above the culture dish substrate). Stimulation by prostaglandin E2 (PGE2) increases the magnitude of the TEP, the short-circuit current (Isc) measured in Transwell Ussing chambers, and the height of domes in cultures grown on impermeable substrates. A phenamil-resistant, PGE2-stimulated component of the Isc in Transwells and of the TEP in monolayers in conventional culture dishes was inhibitable by bumetanide, a diuretic drug that blocks NaKCl2 symporters, mediating active transport of Cl-. The rate of decrease in height of domes in cultures after addition of phenamil, presumably indicative of transport of fluid in a basal-to-apical direction, was also reduced by bumetanide. Studies with Transwells in Cl(-)-free, HCO(3-)-free or Cl(-)- and HCO(3-)-free media indicated that thyroid cells transported HCO3- as well as Cl- in a basal-to-apical direction. It was concluded that the thyroid epithelium is both sodium absorbing and anion secreting.

Absorption↗
PubMed1991

A look-back investigation of patients of an HIV-infected physician. Public health implications.

BACKGROUND: Transmission of the human immunodeficiency virus (HIV) to five patients receiving care from an HIV-infected dentist in Florida has recently been reported. Current data indicate that the risk of HIV transmission from health care workers to patients is low. Despite this low risk, programs to notify patients of past exposure to an HIV-infected health care worker are being conducted with increasing frequency. METHODS: We recently conducted an investigation of all the patients cared for by an HIV-infected family physician during a period when he had severe dermatitis caused by Mycobacterium marinum on his hands and forearms. After reviewing the patients' records, we notified 336 patients who had undergone one or more procedures (digital examination of a body cavity or vaginal delivery) placing them at potentially increased risk of HIV infection. The patients were offered tests for HIV infection and counseling. RESULTS: Of the 336 patients, 325 (97 percent) had negative tests for HIV antibody, 3 (1 percent) refused testing, 1 (less than 1 percent) died of a cause unrelated to HIV infection before notification, and the HIV-antibody status of 7 (2 percent) remained unknown. The direct and indirect public health costs of this investigation were approximately $130,000. CONCLUSIONS: The results of this investigation raise important questions about the risk of HIV transmission from health care workers to patients and the usefulness of HIV look-back programs, particularly in the light of recently published recommendations from the Centers for Disease Control. We propose that before a look-back investigation is undertaken, there should be a clearly identifiable risk of transmission of the infection, substantially higher than the risk requiring limitation of an HIV-infected health care worker's practice prospectively.

AIDS Serodiagnosis↗
PubMed1991

The unseen sample in cohort studies: estimation of its size and effect. Multicenter AIDS Cohort Study.

Recruitment of disease-free subjects into cohort studies and measurement of their time from exposure/infection to disease selectively excludes individuals (the unseen sample) who had earlier exposure and who have shorter times to disease. The unseen and observed samples may differ in other characteristics in addition to incubation period and exposure/infection time. For data with known truncation times, we develop non-parametric maximum likelihood estimates of the size, exposure/infection dates and distribution of incubation time in the unseen sample. We provide procedures to estimate and compensate for the biasing effects due to exclusion of the unseen sample in descriptive and survival analysis. We give consistency properties of these estimates and assess variability using bootstrap methods. One can use imputation to derive the above estimates from data with unknown truncation times that have been estimated parametrically. Application is made to an AIDS cohort study of over 5000 homosexual men. Important estimates obtained from this application are the annual seroconversion rates from 1978 to 1983, not otherwise obtainable in this study population.

Acquired Immunodeficiency Syndrome↗
PubMed1991

Object-oriented design and programming in medical decision support.

The concept of object-oriented design and programming has recently received a great deal of attention from the software engineering community. This paper highlights the realisable benefits of using the object-oriented approach in the design and development of clinical decision support systems. These systems seek to build a computational model of some problem domain and therefore tend to be exploratory in nature. Conventional procedural design techniques do not support either the process of model building or rapid prototyping. The central concepts of the object-oriented paradigm are introduced, namely encapsulation, inheritance and polymorphism, and their use illustrated in a case study, taken from the domain of breast histopathology. In particular, the dual roles of inheritance in object-oriented programming are examined, i.e., inheritance as a conceptual modelling tool and inheritance as a code reuse mechanism. It is argued that the use of the former is not entirely intuitive and may be difficult to incorporate into the design process. However, inheritance as a means of optimising code reuse offers substantial technical benefits.

Adult↗
PubMed1991

Augmentation of cellular immune function during the early phase of zidovudine treatment of AIDS patients.

Twenty-five patients with AIDS in AIDS Clinical Trials Group Protocol 002 were treated with either low or high dosages of zidovudine. This resulted in moderate, transient increases by 10 and 20 weeks in lymphocyte blastogenesis and interferon-gamma (IFN-gamma) production in vitro in response to phytohemagglutinin with and without recombinant interleukin-2. Immune responses to cytomegalovirus and herpes simplex virus type 1 antigens were augmented less frequently during therapy. Natural killer (NK) cell lysis of uninfected and human immunodeficiency virus-infected cells was also transiently increased by 10 and 20 weeks. IFN-gamma production, the only immune parameter directly associated with increases in numbers of CD4+ T cells, peaked at 10 weeks of treatment. The limited efficacy of zidovudine treatment in AIDS patients is associated with moderate, temporary increases in nonspecific and herpesvirus-specific T lymphocyte responses and NK cell function.

Acquired Immunodeficiency Syndrome↗