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Biomedical subjects

S O'Connell

Publications and source records attributed to S O'Connell.

At least 19 recordsLinked to original sources
PubMed1996

Tst-1/Oct-6/SCIP regulates a unique step in peripheral myelination and is required for normal respiration.

The terminal differentiation of myelinating glia involves complex interactions that culminate in the formation of myelin. The POU domain transcription factor Tst-1/Oct-6/SCIP is expressed transiently during myelination, and we report here that it has a critical role in this developmental process. Deletion of the Tst-1/Oct-6/SCIP gene produces a severe defect in peripheral myelination by arresting Schwann cell maturation before axonal wrapping. Unexpectedly, the activation of major myelin-specific genes appears to be unaffected by the Tst-1/Oct-6/SCIP mutation, demonstrating that multiple, independently regulated events are required for terminal differentiation of Schwann cells. In addition, aberrant differentiation and migration of specific neurons in Tst-1/Oct-6/SCIP mutant homozygotes is associated with a fatal breathing defect, providing a model for investigating the regulation of pulmonary homeostasis.

Animals↗
PubMed1996

A novel family of Cys-Cys, His-Cys zinc finger transcription factors expressed in developing nervous system and pituitary gland.

A screen designed to identify proteins that specifically bind to retinoic acid response elements resulted in the identification of a rat cDNA encoding a novel protein containing six Cys-Cys, His-Cys zinc fingers. This gene is expressed in a restricted fashion exhibiting distinct temporal and spatial patterns in the developing nervous system, primarily brain, spinal cord, sensory ganglia, retina, and nasal epithelia, as well as in the pituitary, and is referred to as neural zinc finger factor 1 (NZF-1). NZF-1 binds specifically to a cis-regulatory element of the beta-retinoic acid receptor (RAR beta) gene, as well as to other related DNA elements, including two in the upstream enhancer region of the mouse Pit-1 gene. In heterologous cells, NZF-1 activates transcription from promoters containing specific binding sequences and can synergize with other factors, such as Pit-1, to regulate gene expression. These results suggest that NZF-1 may exert regulatory roles in the developing and mature nervous system and in the pituitary gland. Identification of a second mouse gene highly homologous to NZF-1, encoded by a distinct genomic locus, reveals a dispersed gene family encoding proteins containing Cys-Cys, His-Cys motifs.

Amino Acid Sequence↗
PubMed1996

English language ability and mental health service utilisation: a census.

OBJECTIVE: To explore the relationship between English language proficiency and mental health service utilisation. METHODS: In September 1993, a sample census was conducted of all mental health services in the State of Victoria, including public and private hospital wards, outpatient consultations provided by psychiatrists and clinical psychologists, and primary mental health care provided by general practitioners. Response rates ranged from 37% for monolingual general practitioners (GPs) to 96% for inpatient units. Particular emphasis was placed on patients' English language proficiency and the role played by bilingual clinicians. RESULTS: Over 80% of inpatients received a diagnosis of either dementia or psychosis. This proportion was even greater in the case of patients with English language difficulties. The latter group of patients underutilised specialist outpatient services, and those using these services were less likely to receive psychotherapy than fluent English speakers. They utilised GPs for mental disorder at at least the same rate as other patients. There was a marked preference for bilingual GPs, with 80% of patients with poor English language skills consulting GPs who spoke their native language. CONCLUSION: There appears to be considerable underutilisation of specialist mental health services by patients who are not fluent in English. The liaison-consultation model of psychiatric care may be an effective way of addressing this problem, given the important role already played by billingual GPs in the psychiatric care of those whose native language is not English.

Adolescent↗
PubMed1995

The value of serological testing for Lyme disease in the UK.

Although the prevalence of Lyme disease (LD) in the UK is low, patients with clinical presentations compatible with the condition are common. Arthritis often complicates LD in North America, however it is a very rare complication of the condition in the UK. Many patients seen at St George's Hospital, London have visited endemic areas for LD within the UK, Europe and North America. To determine the value of serological testing for LD in the UK, we prospectively studied 120 patients seen at this hospital with clinical manifestations suggestive of LD (12 of whom were recruited to the LD clinic from outside the hospital catchment area), regardless of whether an alternative diagnosis seemed likely. A history of tick bite was obtained and serum antibodies to Borrelia burgdorferi detected initially by enzyme-linked immunosorbent assay (ELISA) and reactive samples immunoblotted to further assess antibody specificity. Tick bites were reported by 22 patients, 16 of whom were bitten in endemic areas for LD. A further 11 patients had exposure to tick habitats in endemic areas, but were unaware of a tick bite. Raised antibody levels were detected by ELISA in 14 individuals (seven of whom had a history of tick bite or tick exposure in an endemic area); however, only four of these had specific antibodies to B. burgdorferi confirmed on immunoblot. All of these four had a history of tick bite in an endemic area, all had arthritis and in three of the four, this was the only manifestation of the condition.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1995

Qualitative and quantitative analysis of T lymphocytes during normal human pregnancy.

PROBLEM: Human reproduction involves contact between cells which are allogeneic to one another, however the fetus not only survives but thrives. METHODS: Aspects of T-cell-mediated immunity during normal human pregnancy were studied. PBMNCs of pregnant and nonpregnant women were stimulated with PHA and cytomegalovirus antigens (CMV). The capacity of stimulated cells to proliferate, to produce IL-2 and IFN-gamma, to express IL-2 receptor (IL2R1) and the effect of rIL2 on the proliferation rate of lymphocytes were examined. FACS was utilized for T-cell subset comparisons. RESULTS: The proliferation rate, IL-2, and IFN-gamma synthesis were all significantly impaired at suboptimal concentration of PHA throughout pregnancy. Exogenous rIL-2 corrected this depression of cell-mediated immunity (CMI). At optimal concentration of PHA, proliferation rate and production of IFN-gamma and IL-2 were all decreased. Exogenous rIL-2 corrected these deficits only in the third trimester. Third trimester pregnant women demonstrated a significant depression of proliferation as well as IL-2 and IFN-gamma production after CMV stimulation, which was partially corrected by exogenous rIL-2. FACS analysis suggested that after stimulation by CMV and optimal concentration of PHA, T cells were activated and both CD4+ and CD8+ lymphoblasts expressed normal density of IL-2R1. With suboptimal PHA, the number of activated CD4+ and CD4+IL2R1+ cells were diminished and CD4+ and CD8+ T lymphoblasts expressed lower number of IL2R1. CONCLUSIONS: CD4 T helper (Th1) cell function is down regulated progressively during the three trimesters of pregnancy without changes in the quantity of T cell subsets.

Adult↗
PubMed1994

AIDS presenting as focal segmental membranous glomerulopathy.

The case of a young, heterosexual man who was investigated for proteinuria is reported. A renal biopsy specimen showed a focal and segmental membranous glomerulopathy. He was later found to be HIV positive and died from cerebral infarction associated with HIV vasculitis 16 months after his initial presentation. Unusual forms of immune complex mediated glomerulopathies should alert the pathologist to the possibility of HIV associated disease.

Acquired Immunodeficiency Syndrome↗
PubMed1994

In vivo effects of chromium.

The production of reactive oxygen species on addition of hexavalent chromium (potassium dichromate, K2Cr2O7) to lung cells in culture was studied using flow cytometer analysis. A Coulter Epics Profile II flow cytometer was used to detect the formation of reactive oxygen species after K2Cr2O7 was added to A549 cells grown to confluence. The cells were loaded with the dye, 2',7'-dichlorofluorescein diacetate, after which cellular esterases removed the acetate groups and the dye was trapped intracellularly. Reactive oxygen species oxidized the dye, with resultant fluorescence. Increased doses of Cr(VI) caused increasing fluorescence (10-fold higher than background at 200 microM). Addition of Cr(III) compounds, as the picolinate or chloride, caused no increased fluorescence. Electron paramagnetic resonance (EPR) spectroscopic studies indicated that three (as yet unidentified) spectral "signals" of the free radical type were formed on addition of 20, 50, 100, and 200 microM Cr(VI) to the A549 cells in suspension. Two other EPR "signals" with the characteristics of Cr(V) entities were seen at field values lower than the standard free radical value. Liver microsomes from male Sprague-Dawley rats treated intraperitoneally with K2Cr2O7 (130 mumole/kg every 48 hr for six treatments) had decreased activity of cytochromes P4503A1 and/or 3A2, and 2C11. Hepatic microsomes from treated female Sprague-Dawley rats, in contrast, had increased activities of these isozymes. Lung microsomes from male Sprague-Dawley rats had increased activity of P4502C11.

Animals↗
PubMed1994

Reversal of doxorubicin-impaired wound healing using Triad compound.

Triad is composed of Na pyruvate, vitamin E, and unsaturated fatty acids. We found that Triad, administered orally or topically, reverses wound healing that is impaired by doxorubicin (Doxo) in rats. Rats given Doxo (6 mg/kg IV) were wounded with linear dermal incisions, and the wound-breaking strength (WBS) was compared among groups of rats differently treated with TRIAD. Five groups of five rats each were studied. Triad was given orally using a 20 per cent TRIAD/rat chow mixture and topically as a 50 per cent TRIAD/petroleum base salve administered daily. All groups were wounded at postoperative day 0, at which time Doxo was given to groups II-IV. Group IV was fed oral TRIAD 7 days prior to wounding and until POD 21. All wounds were harvested at POD 21, and the mean WBS of each group was obtained using an Instron Tensiometer. Doxorubicin impaired normal wound healing by 40 per cent. Oral TRIAD restored WBS in Doxo-treated rats to 88 per cent of control values; topical TRIAD restored WBS to 80 per cent of control values. Moreover, treatment with topical TRIAD and oral TRIAD increased the WBS by 30 per cent and 50 per cent when compared with Doxo-only-treated animals. In conclusion, TRIAD has been shown to restore wound healing to nearly normal levels in doxorubicin-impaired wounds.

Administration, Oral↗
PubMed1994

Reversal of doxorubicin-impaired wound healing using triad compound.

Triad is composed of Na pyruvate, vitamin E, and unsaturated fatty acids. We found that Triad, administered orally or topically, reverses wound healing that is impaired by doxorubicin (Doxo) in rats. Rats given Doxo (6 mg/kg i.v.) were wounded with linear dermal incisions, and the wound-breaking strength (WBS) was compared among groups of rats differently treated with Triad. Five groups of five rats each were studied. Triad was given orally using a 20 per cent Triad/rat chow mixture and topically as a 50 per cent Triad/petroleum base salve administered daily. All groups were wounded at postoperative day 0, at which time Doxo was given to groups II-IV. Group IV was fed oral Triad 7 days prior to wounding and until POD 21. All wounds were harvested at POD 21, and the mean WBS of each group was obtained using an Instron Tensiometer. Doxorubicin impaired normal wound healing by 40 per cent. Oral Triad restored WBS in Doxo-treated rats to 88 per cent of control values; topical Triad restored WBS to 80 per cent of control values. Moreover, treatment with topical Triad and oral Triad increased the WBS by 30 per cent and 50 per cent when compared with Doxo-only-treated animals. In conclusion, Triad has been shown to restore wound healing to nearly normal levels in doxorubicin-impaired wounds.

Acrylic Resins↗
PubMed1993

Brn-3.0: a POU-domain protein expressed in the sensory, immune, and endocrine systems that functions on elements distinct from known octamer motifs.

Characterization of Brn-3.0 and identification of a highly related member (Brn-3.1) of the class IV POU-domain family suggest potential roles of Brn-3.0 in the development of retinal ganglion cells and sensory neurons, as well as potential roles in the pituitary gland and the immune system. Brn-3.0 is expressed in the pituitary gland and in a corticotroph cell line. A functional DNA response element has been identified in the proopiomelanocortin promoter. In contrast to previously described mammalian POU-domain proteins, Brn-3.0 binds relatively ineffectively to known octamer DNA motifs, but instead binds with high affinity to a distinct set of DNA elements, functioning as a transcriptional activator. Brn-3.0, Brn-3.1, and the Drosophila tI-POU share an N-terminal region of homology, referred to as the "POU-IV box," which is similar to a conserved functional domain in the c-myc gene family.

Age Factors↗
PubMed1993

Lyme disease: a review.

Lyme disease is an uncommon multisystem spirochaetal infection that has attracted public and media attention in the United Kingdom during the last few years. The spirochaete, Borrelia burgdorferi, is transmitted through the bite of an infected tick. Ticks are found throughout the UK in rural habitats and areas of urban parkland which attract many visitors. The illness can present with skin, nervous system, joint or other manifestations although infection may be asymptomatic. The risk of infection is small and can be reduced further by employing simple precautions to avoid tick bites.

Humans↗
PubMed1993

Chronic active toxoplasmosis in an immunocompetent patient.

We report the case of an apparently immunocompetent woman whose symptoms and signs have persisted for 8 years following a serologically and histologically confirmed diagnosis of toxoplasmosis. During this period she had two successful pregnancies despite persistently increased anti-toxoplasma IgM antibodies. Neither child is infected.

Adult↗
PubMed1993

Identification of a seven transmembrane helix receptor for corticotropin-releasing factor and sauvagine in mammalian brain.

We have identified and characterized cDNAs encoding a novel receptor that is a member of a distinct class of seven transmembrane helix, Gs-coupled receptors. This receptor mediates ligand-dependent stimulation of intracellular cAMP levels in response to physiologic concentrations of corticotropin-releasing factor (CRF) and to the related frog skin peptide, sauvagine. The pattern of CRF receptor mRNA expression in the brain, pituitary gland, and other organs corresponds precisely to that predicted for the classic CRF receptor, suggesting that this receptor serves to mediate the known biological effects of CRF on behavior, stress, and homeostasis. Alternative splicing events generate a second, relatively abundant gene product expressed in a distinct ontogenic pattern. These findings serve to identify the receptor for an important neuropeptide.

Alternative Splicing↗