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Biomedical subjects

S Gorman

Publications and source records attributed to S Gorman.

15 recordsLinked to original sources

Transmission of two Australian strains of murine cytomegalovirus (MCMV) in enclosure populations of house mice (Mus domesticus).

To control plagues of free-living mice (Mus domesticus) in Australia, a recombinant murine cytomegalovirus (MCMV) expressing fertility proteins is being developed as an immunocontraceptive agent. Real-time quantitative PCR was used to monitor the transmission of two genetically variable field strains of MCMV through mouse populations after 25% of founding mice were infected with the N1 strain, followed by the G4 strain 6 weeks later. Pathogen-free wild-derived mice were released into outdoor enclosures located in northwestern Victoria (Australia). Of those mice not originally inoculated with virus, N1 DNA was detected in more than 80% of founder mice and a third of their offspring and similarly, G4 DNA was detected in 13% of founder mice and in 3% of their offspring. Thus, prior immunity to N1 did not prevent transmission of G4. This result is promising for successful transmission of an immunocontraceptive vaccine through Australian mouse populations where MCMV infection is endemic.

Animals↗

Mutation of a nuclear receptor gene, NR2E3, causes enhanced S cone syndrome, a disorder of retinal cell fate.

Hereditary human retinal degenerative diseases usually affect the mature photoreceptor topography by reducing the number of cells through apoptosis, resulting in loss of visual function. Only one inherited retinal disease, the enhanced S-cone syndrome (ESCS), manifests a gain in function of photoreceptors. ESCS is an autosomal recessive retinopathy in which patients have an increased sensitivity to blue light; perception of blue light is mediated by what is normally the least populous cone photoreceptor subtype, the S (short wavelength, blue) cones. People with ESCS also suffer visual loss, with night blindness occurring from early in life, varying degrees of L (long, red)- and M (middle, green)-cone vision, and retinal degeneration. The altered ratio of S- to L/M-cone photoreceptor sensitivity in ESCS may be due to abnormal cone cell fate determination during retinal development. In 94% of a cohort of ESCS probands we found mutations in NR2E3 (also known as PNR), which encodes a retinal nuclear receptor recently discovered to be a ligand-dependent transcription factor. Expression of NR2E3 was limited to the outer nuclear layer of the human retina. Our results suggest that NR2E3 has a role in determining photoreceptor phenotype during human retinogenesis.

Amino Acid Sequence↗

Cloning and characterization of T-cell lymphoma invasion and metastasis 2 (TIAM2), a novel guanine nucleotide exchange factor related to TIAM1.

TIAM1 is a guanine nucleotide exchange factor that was identified in a screen for genes that increase the invasiveness of T lymphoma cell lines (Habets et al., 1994, Cell 77(4): 537-549). We have identified a gene, T-cell lymphoma invasion and metastasis 2 (HGMW-approved symbol TIAM2), with significant identity to the carboxyl-terminal region of the TIAM1 and mapped it to 6q25. TIAM2 is expressed as an approximately 3.3-kb transcript in cerebrum and as an approximately 4.4-kb transcript in the cerebellum and testis. The approximately 4. 4-kb message encodes a longer form of the approximately 3.3-kb mRNA predicted protein, and both contain homology to the Dbl-homologous region (70%) and Pleckstrin-homologous (54%) regions of TIAM1. We have purified TIAM2 and shown it to have GDP-GTP exchange activity. In situ hybridizations demonstrate TIAM2 expression in the E13.5 telencephalon of mouse embryos and in the cerebral cortex, hippocampus, and ependyma of adult mouse brains.

Amino Acid Sequence↗

The affliction of Job: poisoned!

The story of Job has been an inspiration for centuries to those familiar with the story. It has also been a source of curiosity as to what affliction he suffered. A critical reappraisal of the clinical manifestations of his illness support the contention that he was a victim of poisoning. There is historical evidence to support that the poison was available in his time and already in use for poisoning. Finally, there is even documentation in the story of Job as to the identity of his poisoner.

Arsenic↗

Open-label, single-dose pharmacokinetic study of modafinil tablets: influence of age and gender in normal subjects.

An open-label, single-center, single-dose, parallel-group study was performed in healthy young males and females as well as healthy elderly males to examine the influence of age and gender on the pharmacokinetics of modafinil following administration of a single 200 mg oral dose. Twelve subjects were enrolled in each of the following three groups: young males, young females, and elderly males. Each fasted (overnight) subject received 2 x 100 mg modafinil tablets. Blood and urine samples were collected at various times up to 72 hours postdose for the determination of plasma and urine levels of modafinil as well as the acid and sulfone metabolites. The plasma concentrations of the individual isomers, d- and l-modafinil, were also determined. Pharmacokinetic parameters were determined by noncompartmental methods. Modafinil was well tolerated at a single oral dose of 200 mg. The most commonly reported adverse events were headache, fever, pharyngitis, and asthenia. There were no clinically meaningful differences with respect to the incidence rate of treatment-emergent adverse events among the young female, young male, and old male groups. Modafinil was rapidly absorbed after oral dosing and slowly cleared (t1/2 approximately 11-14 hr) from the body. Modafinil acid was the major urinary metabolite, which accounted for 35% to 60% of the dose. Results from this study indicated that there were age and gender effects on modafinil clearance processes. In this regard, the clearance rate of modafinil in males decreased with age while young females cleared modafinil at a faster rate than young males. Stereospecific pharmacokinetics of modafinil were also demonstrated. The d-modafinil was eliminated three times faster than the l-modafinil.

Adult↗

A recombinant adenovirus that directs secretion of biologically active kappa-bungarotoxin from mammalian cells.

A novel Cre-lox system was used to construct an adenovirus encoding kappa-bungarotoxin (kappa-Bgt), modified to be secreted by attachment of a bovine prolactin signal sequence at the N-terminus of the toxin. Western blot of medium from HEK-293 cells infected with the virus demonstrated that recombinant kappa-Bgt (R-kappa-Bgt) was secreted. The biological activity of the secreted R-kappa-Bgt was investigated in Xenopus oocytes that expressed neuronal nicotinic acetylcholine receptor (nAChR) subtypes alpha3beta2 and alpha2beta2. The recombinant toxin inhibited the response of alpha3beta2 type AChRs to ACh, but did not inhibit the response of alpha2beta2 type AChRs. These data demonstrated that the recombinant adenovirus directs the secretion of biologically active kappa-Bgt from a mammalian cell line. Because adenovirus can be used to infect post-mitotic cells, recombinant adenoviruses encoding biologically active peptides may be of use as delivery vehicles for in vivo experiments where repeated application of the purified peptide is unfeasible.

Adenoviridae↗

Influence of selective decontamination of the digestive tract on microbial biofilm formation on endotracheal tubes from artificially ventilated patients.

The effect of selective decontamination of the digestive tract on the nature and incidence of microbial biofilm formation on endotracheal tubes was assessed. Thirty endotracheal tubes were obtained post-extubation from patients in the intensive care unit who had been ventilated for a 1 to 15 day period and who did or did not receive the antibiotic regimen. Extensive biofilm formation was identified by scanning electron microscopy on 97% of tubes examined. Endotracheal tube biofilm in tubes obtained from patients who received selective decontamination of the digestive tract showed a high prevalence of colonization with yeast (4 of 15 tubes) and gram-positive bacteria (streptococci, staphylococci and diphtheroids) (14 of 15 tubes). Staphylococcus aureus was isolated only from this group. Pseudomonas spp. were isolated from 2 of 15 tubes in both patient groups. Enteric gram-negative organisms (coliforms, Klebsiella and Proteus spp.) were isolated only from tubes of patients who did not receive the antibiotic regimen (4 of 15 tubes). Yeasts, however, were not isolated from these tubes. Group D streptococcal isolates were resistant to tobramycin as were half of the Staphylococcus aureus isolates. For gram-negative bacteria, the MIC of tobramycin was in the range 1-64 micrograms/ml and the MIC of polymyxin in the range 0.5-16 micrograms/ml. Although a reduction was observed in the incidence of gram-negative microorganisms, this antibiotic regimen does not inhibit biofilm formation on the endotracheal tube by other pathogens associated with pneumonia in ventilated patients. This persistent nidus may be a factor in the pathogenesis of nosocomial pneumonia.

Adolescent↗

Case report: tuberculous colitis mimicking Crohn's disease.

Although intestinal tuberculosis is rare in this country, increasing numbers of patients are now being seen, particularly in the immigrant population. We present the history of a lady who had acute diarrhoea and in whom the radiological and endoscopic findings looked very similar to those seen in Crohn's disease. The radiological presentation included widespread aphthous ulceration, a feature that has rarely been reported in tuberculous colitis.

Colitis↗

Psychological morale and job satisfaction among homecare workers who care for persons with AIDS.

This paper reports the findings of a study of 103 home care workers who have cared for PWAs. It investigated degree of "exposure" to AIDS cases, perception of risk of occupational contagion, client/worker relationships, attitudes toward homosexuality and drug abuse and other work related factors for their relationship with psychological morale and job satisfaction. Multivariate analyses found sociodemographic characteristics and physical health to be the strongest predictors of morale. The quality of client/worker relationships and risk perception were the strongest predictors of job satisfaction. These findings, and that of the relative lack of importance of exposure to AIDS cases and attitudes toward the risk groups in accounting for job satisfaction, are discussed in terms of qualitative data collected from respondents during informal small group discussions.

Acquired Immunodeficiency Syndrome↗

Value of lymph node biopsy in the treatment of patients with the human immunodeficiency virus.

The indications and value of lymph node biopsy in patients infected with the human immunodeficiency virus (HIV) are not clearly defined. We reviewed 29 consecutive lymph node biopsies performed on 24 patients with the HIV over a 4-year period. Indications for biopsy included: (1) new or worsening medical symptoms with no detectable etiology in patients with lymphadenopathy, (2) disproportionately larger or enlarging lymph node in patients with generalized adenopathy, and (3) exclusion of concomitant disease in patients with previously defined infectious or neoplastic processes. The biopsy samples exhibited a diversity of histologic appearances including atypical and reactive hyperplasia, malignancy, and infection. Nineteen biopsies (64%) resulted in the institution or alteration of treatment. The absolute number of T-helper cells prior to biopsy was significantly lower in patients with a diagnosis of malignancy or infection (p < 0.05), as well as in those who eventually died (p < 0.05). Four (14%) minor complications resulted from lymph node biopsy. Based on our results, we conclude that lymph node biopsy is indicated in the above three subsets of HIV-infected patients. Biopsy can be performed with minimal morbidity and significantly alters therapy in the majority of patients.

AIDS-Related Complex↗

Plasma catecholamine concentration during sedation in ventilated patients requiring intensive therapy.

The effects of isoflurane and midazolam sedation on the catecholamine responses of ventilated patients were studied over a 24-h period. Sixty ventilated patients admitted to our intensive therapy unit were allocated randomly to receive either isoflurane or midazolam sedation. Arterial blood samples for plasma catecholamine concentrations were taken at baseline, 6 h after starting sedation and at the end of the study period. Patients sedated with isoflurane showed a progressive reduction in both adrenaline and noradrenaline concentrations during the period of sedation which reached statistical significance for adrenaline at 6 h (p less than 0.02) and at the end of the study (p less than 0.001). Patients sedated with midazolam showed no significant changes of adrenaline or noradrenaline concentrations. Overall, a more satisfactory degree of sedation was achieved with isoflurane.

Administration, Inhalation↗

Superoxide dismutase in Didymium iridis: characterization and changes in activity during senescence and sporulation.

The myxomycete Didymium iridis displays a single cytoplasmic superoxide dismutase in the diploid plasmodial stage. The enzyme was purified and appears to be a manganese-containing protein of approximately 32000 molecular weight. Superoxide dismutase specific activity was constant throughout the cell cycle and showed no significant change over the majority of plasmodial life span. Elevated superoxide dismutase activity, relative to that of other cytoplasmic enzymes, occurred during necrosis of senescent plasmodia, staling, and starvation-induced sporulation.

Cell Cycle↗

Power and effective nursing practice.

Underlying the Nursing Knowledge Program were the beliefs that professionals can be prepared to function more effectively in organizations and that organizations can be designed to promote better use of professional skills. The training program, therefore, included both educational and structural solutions for the problems of powerlessness experienced by nurses in the hospital setting. Educationally, the program was designed to empower the participating nurses by teaching them the analytic and interpersonal skills they needed to develop and implement plans for change. Structurally, it established new lines of communication between staff nurses and nurse administrators, linked the nurses to needed resources, and gave the nurses more control over working conditions. Due to the quasi-experimental nature of the research design used in the project, the findings cannot be generalized to all nurses in all hospitals. There is no question, however, that each of the four strategies can be a valuable administrative approach for increasing nursing power. Confirming the strategies and moving groups of nurses through a series of activities specifically designed to use the strategies can bring significant change in the perceptions of nurses about themselves and their profession. For the administrator, the strategies are a way to develop a more effective and satisfied nursing staff, to encourage new leadership, and to create a stronger constituency among staff members. They also create a new source of energy and ideas for resolving the very real problems of professional practice.

Humans↗