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Biomedical subjects

M Egan

Publications and source records attributed to M Egan.

At least 55 records · Page 3Linked to original sources
PubMed1994

Immunoglobulin variable region usage in human intestinal B lymphocytes.

The B cell repertoire was studied in intestinal mononuclear cells from normal individuals and patients with inflammatory bowel disease (IBD) by examining Ig heavy chain variable gene (VH) usage. Using reverse transcription of intestinal mucosal RNA followed by polymerase chain reaction with primers specific for each VH family and a housekeeping gene, a semiquantitative assay of VH family content in RNA samples was developed. While all VH family members were expressed, differences in VH usage in lamina propria intestinal B cells were noted between Crohn's disease, ulcerative colitis, and normal individuals. mRNA transcripts for VH4 were present at seemingly higher levels than their genomic representation and transcripts for VH1 and VH4 appeared to have higher levels in active, compared to inactive, IBD. Thus, within the massive polyclonal intestinal B cell response, there is a skewed VH usage which may be relevant to the antigenic and/or autoimmune response noted in IBD.

B-Lymphocytes↗
PubMed1994

Anti-glutamate decarboxylase and other antibodies at the onset of childhood IDDM: a population-based study.

Sera obtained at diagnosis from 273 children (0-14 years) with insulin-dependent diabetes mellitus (IDDM) were studied to compare different autoantibody levels. The subjects comprise 75% of all incident cases in New South Wales, Australia, for a 2-year period (ascertainment > 99% complete). Antibodies against glutamate decarboxylase were measured by radioimmunoprecipitation, insulin autoantibodies (on 176 sera collected within 4 days of initiation of insulin therapy) by radioimmunoassay, thyroid peroxidase and antigliadin IgA antibodies by enzyme-linked immunoassay, and anti-endomysial IgA and islet cell antibodies by indirect immunofluorescence. Reference ranges for anti-glutamate decarboxylase and insulin autoantibodies were determined in a group of non-diabetic children. Of the sera 69% were positive for anti-glutamate decarboxylase, 65% for insulin autoantibodies, 71% for islet cell antibodies (> or = 20 Juvenile Diabetes Foundation units), 10% for anti-thyroid peroxidase, 2.6% for antigliadin and 3.0% for anti-endomysial antibodies. Islet cell antibodies and insulin autoantibodies were both negative in 13.7% of the sera, while only 5.8% were negative for all three of islet cell antibodies, insulin autoantibodies and anti-glutamate decarboxylase. There was a higher frequency of anti-glutamate decarboxylase among girls than boys (75% vs 63%, p = 0.03) and a negative correlation between the level of insulin autoantibodies and age at diagnosis (r = -0.41, p < 0.0001). A higher frequency of antithyroid peroxidase was found with increasing age (p = 0.05). Higher titres of islet cell antibodies were associated with a higher frequency of both anti-glutamate decarboxylase (p < 0.0001) and insulin autoantibodies (p = 0.003).(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1994

Coadministration of fluvoxamine increases serum concentrations of haloperidol.

Four patients with chronic schizophrenia were treated with a combination of fluvoxamine, haloperidol, and benztropine. The combination significantly impaired performance on tests of delayed recall memory and attentional function. Haloperidol concentrations in serum were monitored in three patients and were robustly elevated by fluvoxamine.

Adult↗
PubMed1993

Cytokine mRNA expression in intestine from normal and inflammatory bowel disease patients.

Cytokines are involved in the regulation of normal immune events and may be important in the development or perpetuation of immune events in inflammatory bowel disease. We have previously shown that normal human mononuclear cells from tonsil, spleen, and peripheral blood exhibit tissue and stimulus-specific patterns of cytokine mRNA expression. The aim of this study was to determine if disease-dependent differences of cytokine mRNA expression could be found in the intestine. Total RNA was isolated from intestinal mucosa and lamina propria mononuclear cells from inflammatory bowel disease patients and controls. cDNA probes specific for interleukins (IL)-1, -4, -5, and -6 and transforming growth factor-beta were used. IL-1 beta mRNA and TGF-beta mRNA steady state expressions were higher in inflammatory bowel disease specimens than in normal intestine. In addition, mononuclear cell specimens had stronger cytokine mRNA expression than mucosal specimens. The steady state mRNA expression of proinflammatory cytokines is higher in inflammatory bowel disease, consistent with the ongoing inflammation seen.

Blotting, Northern↗
PubMed1993

Spontaneous apoptosis in NS-1 myeloma cultures: effects of cell density, conditioned medium and acid pH.

Apoptosis is a form of cell death which plays an important role in many biological processes including the regulation of B and T lymphocyte functions. We report here the spontaneous development of extensive apoptosis in cultures of the NS-1 mouse myeloma cell line following overgrowth. The apoptosis was identified by both its ultrastructural features and its DNA fragmentation pattern. High cell density and conditioned medium, but not acid pH, were found to be major inducers of apoptosis in this experimental system.

Animals↗
PubMed1993

Resilience at the front lines: hospital social work with AIDS patients and burnout.

Hospital social work practice with AIDS patients has been described as difficult and linked to burnout. The need to help workers cope, reduce burnout and, thus, conserve needed social workers prompted this study of 128 hospital AIDS social workers. Potency, a resilience factor combining mastery, beliefs about self and the world, influenced social workers' perceptions of difficulties and burnout. Potency explained 5% of the variance in difficulty ratings and 10-15% of the variance in three burnout measures. Findings challenge the assumption that burnout is primarily an organizationally-induced phenomenon and affirm the influence of workers' self and world views on burnout. Hospital administrators, social work directors and educators are encouraged to foster workers' sense of mastery and self-esteem to prevent burnout.

Acquired Immunodeficiency Syndrome↗
PubMed1993

A measure of growth. A system's corporate ethics committee assesses its accomplishments and future direction.

In 1992 the Sisters of Mercy Health System (SMHS) Corporate Ethics Committee (CEC) developed a three-step evaluative process of the system's ethics programs. The evaluation consisted of a retrospective review of the minutes of CEC meetings since the committee's inception, an oral evaluation with current CEC members, and a written assessment of the committee's performance by current and former members. In the open discussion, 86 percent of participants indicated that the system needs the CEC because it facilitates in-depth examination of ethical issues and provides important research and consulting services to the system executive. Respondents completing the written evaluation indicated that the CEC's dominant strength is the diversity of its membership, which includes trustees, physicians, ethicists, nurses, administrators, managers, and chaplains. More than 57 percent of respondents reported the CEC has achieved all six of its goals, which included education, articulation, decision making, policy development, program development, and evaluation. A review of the CEC evaluation suggests that the committee has moved beyond the development stage and entered a period of active growth. CEC members have made great strides in educating themselves, and the committee must now consider whether to broaden its focus by developing its knowledge base and skills for bioethical education and policy recommendations. The CEC is currently testing an ethical decision-making model it recently developed.

Bioethical Issues↗
PubMed1992

Defective regulation of outwardly rectifying Cl- channels by protein kinase A corrected by insertion of CFTR.

Cystic fibrosis (CF) is a lethal genetic disease resulting in a reduced Cl- permeability, increased mucous sulphation, increased Na+ absorption and defective acidification of lysosomal vesicles. The CF gene encodes a protein (the cystic fibrosis transmembrane conductance regulator, CFTR) that can function as a low-conductance Cl- channel with a linear current-voltage relationship whose regulation is defective in CF patients. Larger conductance, outwardly rectifying Cl- channels are also defective in CF and fail to activate when exposed either to cyclic AMP-dependent protein kinase A or to protein kinase C. The role of the outwardly rectifying Cl- channel in CF has been questioned. We report here that expression of recombinant CF genes using adeno-associated virus vectors in CF bronchial epithelial cells corrects defective Cl- secretion, that it induces the appearance of small, linear conductance Cl- channels, and restores protein kinase A activation of outwardly rectifying Cl- channels. These results re-establish an involvement of outwardly rectifying Cl- channels in CF and suggest that CFTR regulates more than one conductance pathway in airway tissues.

Adenosine Triphosphate↗
PubMed1992

Malignant melanoma of the vulva: a clinicopathologic study of 18 cases.

In a study of 18 patients diagnosed with vulvar malignant melanoma between 1975 and 1991, the effect of clinical and pathologic variables on the survival was evaluated. The overall 5-year survival rate was 28.6%. In 14 cases the tumor was retrospectively microstaged with use of Breslow depth and Chung levels. International Federation of Gynecology and Obstetrics (FIGO) stage and Breslow depth did not correlate well with survival. Positivity of groin lymph nodes at initial surgery was associated with an insignificant worsening in survival. An inverse correlation, although statistically not significant, was demonstrated between advancing Chung levels and survival. It is concluded that since the data with respect to microstaging of vulvar malignant melanoma is, as yet, still limited, great caution should be used in electing less aggressive surgery than radical vulvectomy and bilateral groin lymphadenectomy for patients with early-microstage localized disease.

Aged↗
PubMed1992

Role of cholecystokinin in pancreatic adaptation to massive enterectomy.

Since pancreatic adaptation to massive proximal small bowel resection (PSBR) may be modulated through cholecystokinin (CCK) secretion, we tested the effect of the CCK antagonist CR-1409 on this response. Male Wistar rats (n = 72) weighing 220-225 g were randomised to receive either PSBR or transection/resuture followed by saline or CR-1409 (12 mg/kg daily subcutaneously). Rats were killed one, two, and three weeks post-operatively, at which time blood was obtained for CCK assay and the pancreas was assessed for proliferative activity by three parameters: nucleic acid and protein content, bromode-oxyuridine (BrdUrd) labelling index, and proliferating cell nuclear antigen (PCNA) expression. PSBR increased plasma CCK concentration by 83-102% at 1-3 weeks, irrespective of CR-1409 administration. Total pancreatic DNA content per 100 g body weight increased by 34% at two weeks (p less than 0.05) and by 82% at three weeks (p less than 0.05), while RNA content increased by 60% and 178% (p less than 0.001) and protein content by 20% and 57% (p less than 0.05). PSBR increased the BrdUrd labelling index and the percentage of PCNA immunoreactive cells. CR-1409 completely abolished this proliferative response and also prevented the rise in nucleic acid and protein contents. Apart from growth stimulation, PSBR also enhanced pancreatic exocrine function, as shown by ultrastructural evidence of an appreciable decrease in zymogen granules; CR-1409 also inhibited this functional effect of hypercholecystokininaemia. The results confirm the tropic role of CCK after PSBR, and CR-1409 prevents this pancreatic adaptation.

Animals↗
PubMed1992

Creatine kinase and enolase: intracellular enzymes serving as markers of central nervous system damage in neuropsychiatric disorders.

A frequently used method to assess cellular dysfunction and damage in humans is to document the presence of uniquely intracellular proteins in extracellular spaces. Thus, increased plasma levels of transaminases generally reflect hepatocellular damage (Lieber 1978), increases in the cardiac fractions of creatine kinase (CK, or CPK for creatine phosphokinase) or lactate dehydrogenase (LDH) are diagnostic for myocardial infarction (Armstrong et al. 1979; 1982), and increases of skeletal muscle fractions of CK may indicate myopathy (Goto 1974; Ford 1984). Similarly, a number of enzymes and proteins serve as tumor markers in a variety of malignant cancer (e.g., Concannon et al. 1974; Foti et al. 1977).

Biomarkers↗
PubMed1990

Auditory sensory gating in hippocampal neurons: a model system in the rat.

Diminished evoked response to repeated auditory stimuli, an example of sensory gating normally present in human subjects, is often absent in schizophrenics. To examine the mechanism of the normal response and to delineate possible sites of its abnormality in psychosis, it would be desirable to reproduce the phenomenon in laboratory animals. In this study, we show that the pattern of diminished response to the second of paired auditory stimuli is found in activity recorded from the CA3 region of the hippocampus of anesthetized rats. The evoked potential recorded from this area is predominantly an N40 wave, at identical latency to the prominent negative wave recorded from the skull surface of unanesthetized rats. Similar responses were not found in other areas, including the auditory neocortex and the medial geniculate nucleus. Amphetamine, which diminished sensory gating in both animals and humans, diminished the gating of the evoked potential recorded in the hippocampus. The effect of amphetamine was reversed by haloperidol. The rat hippocampus may therefore contain neurons that can be used to study the neurobiology of sensory gating.

Action Potentials↗
PubMed1990

Relationship between intraepithelial neoplasia of the cervix and the size and number of nucleolar organizer regions.

A silver colloid technique was applied to 18 colposcopic biopsies of the cervix. These comprised 7 cases of cervical intraepithelial neoplasia I (CIN I), 5 cases of CIN II, and 6 cases of CIN III. The nucleolar organizer regions subsequently visualized (AgNORs) were enumerated using an oil immersion lens. The maximum diameters of the AgNORs and aggregates thereof were measured, by hand, from carefully calibrated monochrome photographs. The mean numbers of AgNORs subsequently identified steadily increased, whereas the mean sizes of AgNORs decreased from CIN I to CIN III. In CIN I the mean AgNOR number was 2.3 (range 1.8-3.4) and the AgNOR mean maximum diameter (Dmax) was 1.28 microns (range 0.75-1.75). In CIN II the mean number was 3.5 (range 3.1-4.6) and the AgNOR Dmax was 0.98 micron (range 0.9-1.18). In CIN III the mean number was 4.7 (range 4.0-6.1) and the Dmax was 0.62 micron (range 0.51-0.9). CIN III could be distinguished from CIN I and CIN II on the basis of AgNOR sizes, and an inverse relationship between AgNOR numbers and sizes was established.

DNA, Neoplasm↗
PubMed1990

Apoptosis induced in macrophages and T blasts by the mycotoxin sporidesmin and protection by Zn2+ salts.

Incubation of 48 h concanavalin A stimulated spleen cells (T blasts) and murine peritoneal macrophages with the mycotoxin sporidesmin results in DNA fragmentation characteristic of apoptosis. Morphological changes, particularly condensed chromatin, observed following incubation of these cells with sporidesmin and the immunotoxin gliotoxin and related epipolythiodioxopiperazines (ETP) also show changes characteristic of apoptosis. The presence of Zn2+ salts in the culture medium at concentrations non toxic to the cells over the time period studied protects against DNA damage and morphological change. Interaction between Zn2+ and the reduced form of a simple ETP compound assessed by spectral changes demonstrated the formation of a weak complex between the two molecules. Complex formation between zinc and thiol however was insufficient to prevent oxidative damage to plasmid DNA in vitro by inhibiting auto-oxidation of the reduced ETP compound because of the looseness of the interaction. Cd2+, which appears to form a tighter complex with the dithiol does inhibit cleavage of plasmid DNA. These results establish that the toxicity of sporidesmin may be due in part to its ability to induce apoptosis or programmed cell death in sensitive cells. In addition the immunotoxin gliotoxin and related compounds have now been shown to induce the same characteristic morphological changes in cells of haemopoietic origin. The inhibition of apoptosis induced by ETP compounds by Zn2+ appears to be due to direct inhibition of apoptosis rather than Zn2+ acting as an antioxidant. These results demonstrate the inhibition of apoptosis induced by ETP compounds by Zn2+ and suggest an alternate explanation for the known prophylactic effect of Zn2+ on sporidesmin induced tissue damage.

Animals↗
PubMed1988

Increased central noradrenergic activity during benzodiazepine withdrawal: an electrophysiological study.

Spontaneous discharge rates of cerebellar Purkinje neurons were decreased in rats withdrawn from chronic treatment with alprazolam, diazepam, and lorazepam relative to discharge rates recorded from control rats. Prior treatment with 6-hydroxydopamine to deplete cerebellar levels of norepinephrine significantly reduced this effect of diazepam upon Purkinje cell firing rates. The data suggest that increased noradrenergic activity may be occurring during withdrawal from benzodiazepines.

Action Potentials↗