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Biomedical subjects

G Pearson

Publications and source records attributed to G Pearson.

At least 73 records · Page 4Linked to original sources

The differentiated form of nasopharyngeal carcinoma contains Epstein-Barr virus DNA.

Immunologic studies of Epstein-Barr virus (EBV) have implicated EBV in undifferentiated and partially differentiated, non-keratinizing nasopharyngeal carcinoma (NPC). Patients with the well-differentiated, keratinizing form of NPC have EBV serologic patterns similar to those of control populations. In addition, viral DNA has not been detected in the differentiated tumors using viral cRNA probes to DNA immobilized on filters. In this study we have tested for EBV DNA using recombinant DNA probes to Southern blots of DNA from 33 NPC specimens. The 24 undifferentiated and 4 partially differentiated specimens generally contained a relatively high number of EBV genome equivalents, while the 5 well-differentiated NPC all contained detectable EBV, but at low copy number. The viral DNA from one of the well-differentiated specimens was cloned into a cosmid vector. Five recombinant clones representing the fused viral termini were obtained, indicating the presence of episomal, intracellular DNA in the tumor. These findings indicate that all histologic subsets of NPC contain EBV DNA.

Antibodies, Viral↗

Detection of Epstein-Barr virus-associated antigens and DNA in salivary gland biopsies from patients with Sjogren's syndrome.

Sjogren's syndrome (SS) is an autoimmune disorder characterized by lymphocytic infiltration of salivary and lacrimal glands. To determine whether Epstein-Barr virus (EBV) might play a role in the pathogenesis of this disorder, we used monoclonal antibodies and DNA probes to detect evidence of viral gene products and genomes in these patients' tissue biopsies and saliva. Cytoplasmic staining of epithelial cells (i.e., ductal and/or acinar cells) with monoclonal antibody against the EBV-encoded early antigen (EA-D) was noted in 8/14 salivary gland biopsies from SS patients. This antibody did not react with normal salivary glands or salivary gland tumors, nor with other tissues from SS patients. The reactive antigen in SS biopsies had a m.w. of 52,000 on the basis of immunoblotting experiments, similar to the EA-D antigen found in lymphoblastoid cells lytically infected with EBV. EBV DNA was detected in parotid biopsies from two SS patients in amounts ranging from 0.1 to 3 pg per 20 micrograms of cellular DNA. Southern blotting was used to demonstrate the reactivity with Bam V, Eco D, and Bam M probes. Parotid saliva samples from 8/20 SS patients contained EBV DNA detectable by slot blot hybridization. EBV DNA was not detected in saliva of age-matched controls, rheumatoid arthritis patients lacking sicca symptoms, or patients with benign parotid tumors. The presence of EBV in salivary gland and saliva samples was associated with clinically more severe SS, as manifested by extraglandular symptoms such as vasculitis, occurrence of "pseudolymphoma", and marked abnormalities in immunoglobulin levels. These results demonstrate an elevated content of EBV in salivary glands of SS patients, and suggest that this virus may play a role in pathogenesis.

Antibodies, Monoclonal↗

Rheumatoid arthritis synovial membrane contains a 62,000-molecular-weight protein that shares an antigenic epitope with the Epstein-Barr virus-encoded associated nuclear antigen.

A monoclonal antibody, selected for reactivity with the Epstein-Barr virus (EBV)-encoded antigen EBNA-1, exhibited strong reactivity with the synovial lining cells in joint biopsies from 10 of 12 patients with rheumatoid arthritis (RA) and adherent cells eluted from these tissues. No staining of RA synovial membrane frozen tissue sections or eluted synovial-lining cells was obtained with monoclonal antibodies directed against other EBV-encoded antigens (anti-p160, anti-gp200/350) or with monoclonal antibodies directed against antigens encoded by cytomegalovirus, herpes simplex viruses, or human T cell leukemia virus type I. Among 12 osteoarthritis and normal synovial biopsies only rare reactive cells were noted. Characterization of the antigen(s) in RA synovium by the Western immunoblotting technique revealed a 62,000-molecular-weight (mol-wt) protein, in contrast to the 70,000-85,000-mol-wt EBNA-1 antigen found in EBV-transformed cells. The structural basis for the cross-reactivity of the RA synovial membrane 62,000-mol-wt protein and the EBNA-1 antigen appears to reside in the glycine-alanine rich region of these molecules. A rabbit antibody directed against a synthetic peptide (IR3-VI-2) derived from the glycine-alanine-rich region of EBNA-1 reacted with the 70,000-85,000-mol-wt EBNA-1 antigen in EBV-infected cells and with the 62,000-mol-wt molecule in RA synovial membrane extracts. Since strong antibody responses to EBNA-1 are known to exist in RA patients, these results suggest that immune responses to a cross-reactive antigen may play a role in the pathogenesis of RA.

Animals↗

The public's perception of psychiatrists: a telephone survey.

A random telephone survey in the Christchurch toll free area showed: The public generally lacks knowledge about psychiatrists particularly the 60+ age group in their knowledge of whether or not psychiatrists are medical doctors, where they work and what treatments they use; he public's most common association with where psychiatrists work in Christchurch is Sunnyside Hospital, the local public psychiatric hospital and with talking/psychotherapy as a form of treatment they use; and (3) although psychiatrists are perceived negatively compared with family doctors, dentists and lawyers and although people seem reluctant to say a psychiatrist could help them if they had personal problems, nearly half the sample thought there were not enough psychiatrists in New Zealand.

Humans↗

Radiotherapy alone for patients with operable carcinoma of the lung.

Between 1966 and 1980, 72 patients with operable carcinoma of the lung were treated primarily with radiotherapy because coexisting, nontumor related medical problem, or patient refusal prevented thoracotomy. We compared results obtained in this group with results obtained by thoracotomy in 123 consecutive patients over the age of 70, who were assessed in a similar fashion, but who underwent thoracotomy. All patients in both groups had proven, nonsmall cell carcinoma of the lung without clinical, laboratory, or radiologic evidence of tumor spread. All patients in both groups had a negative staging mediastinoscopy, and bronchoscopic findings consistent with operability. Many of the patients treated with radiotherapy had less than a curative dose as their general medical condition prevented a course of radical radiotherapy. It is apparent, however, that the results of radiotherapy for patients with operable carcinoma of the lung may be disappointing and that for patients who are marginal in terms of operative risk, the benefits of surgical resection may warrant the risks involved.

Actuarial Analysis↗

Persisting illness and fatigue in adults with evidence of Epstein-Barr virus infection.

Clinical, serologic, virologic, and immunologic evaluations for 31 adults with chronic illness and fatigue suggested that 23 had persisting Epstein-Barr virus infection. Among these 23 patients, cellular immune mechanisms were generally normal, but 4 had mild immunoglobulin deficiencies. However, 20 patients had abnormal serologic profiles specific for Epstein-Barr virus shown by significantly elevated titers of antibodies to the viral capsid antigen or early antigen, or by a deficiency of late-appearing antibodies. In 11 of 15 patients tested, circulating immune complexes were found. Circulating interferon was not found in 18 patients tested, but the activity of 2-5 oligoadenylate synthetase, an interferon-induced enzyme, was increased in 5 patients studied. Of 19 patients, 18 had persisting suppressor T-cell activity typically found in patients recovering from acute infectious mononucleosis. We believe that the Epstein-Barr virus may be associated with chronic illness in adults.

Adolescent↗

Chronic mononucleosis syndrome.

We present data on 14 patients with chronic symptoms of disabling fatigue in association with serologic evidence of active Epstein-Barr virus (EBV) infection. Two thirds were women, and the average age at onset was 29.6 years. Forty-three percent were known to have had previous infectious mononucleosis, but the usual criteria for that diagnosis were not helpful with the present syndrome. Eighty-six percent had serologic evidence of cytomegalovirus (CMV) infection. Profound immunodeficiency was not present, but 71% had partial hypogammaglobulinemia, and minor abnormalities of T cell subsets were noted in six of seven patients studied. Fifty-seven percent achieved temporary serologic and symptomatic remission after an average duration of 33 months. Only one patient has a sustained remission. Comparison is made with other reported chronic, recurrent, and persistent EBV syndromes, and tentative diagnostic criteria for chronic mononucleosis syndrome are presented. Recently available EBV serologic techniques allow for identification of patients who have reactivated EBV infection, and this reactivation may be related to symptoms.

Adolescent↗

Immunological characterization of Hodgkin's and non-Hodgkin's lymphoma patients with high antibody titers against Epstein-Barr virus-associated antigens.

We have studied nine Hodgkin's lymphoma (HD) and ten non-Hodgkin's lymphoma (NHL) patients with extraordinarily high anti-viral capsid antigen (VCA) titers (greater than 5120). Controls were 13 HD and 23 NHL patients with anti-VCA titers between 40 and 2560. High anti-VCA titers were present in NHL patients at the time of diagnosis or within 16 months, whereas the rise of anti-VCA titers in HD patients appeared to be a late event during the clinical course of the disease (mean time from diagnosis, 68 months). In particular, we have asked whether the exceptionally high anti-Epstein-Barr virus (EBV) titers in some HD and NHL patients can be correlated to some of the EBV-specific and -nonspecific parameters of cell-mediated immunity. The battery of non-EBV-specific immunological tests included the assessment of natural killer cell activity and the analysis of T-lymphocyte subclasses according to surface markers, together with spontaneous and mitogen-induced DNA synthesis and their helper or suppressor activity on PWM-generated immunoglobulin synthesis. Outgrowth inhibition (Ol) and leukocyte migration inhibition were used to assess EBV-specific cell-mediated immunity. The majority of the high-titer HD and NHL patients showed a drastically reduced OKT4:OKT8 ratio in their peripheral lymphocyte population. Low-titer HD and NHL patients showed no such reduction. There was no strict correlation between the number of OKT8-positive cells and suppressor activity in the functional PWM-induced immunoglobulin production test. Part of the high-titer HD patients showed defective cellular responses in the outgrowth inhibition test, directed against the proliferation of EBV-transformed (EBV-determined nuclear antigen-positive) cells. Some of them showed also a deficient leukocyte migration inhibition response to EBV-determined nuclear antigen but, interestingly, not to early antigen-VCA. In the NHL group, only one of the high-titer patients showed a similar defect. None of the low-titer HD and NHL patients showed such defects.

Adult↗

Effect of circulating fibronectin on stimulation of leukocyte oxygen consumption and serum opsonizing function in burned patients.

In a study of 27 thermally burned patients (mean TBSA, 58%; range, 32-96%) serum fibronectin levels were decreased with parallel decreased oxygen consumption of stimulated peripheral blood phagocytes and decreased EGTA-blocked burn serum opsonizing activity which correlated with serum fibronectin changes postburn. Normal and burn sera fibronectin content also correlated with the opsonizing times for zymosan and Staphylococcus aureus but not for Enterobacteriaceae. Although in vivo 14 cases showed circulating fibronectin 140 micrograms/ml or lower and a marked decrease in Staphylococcus aureus opsonization, only two patients from this group revealed positive Staphylococcus aureus blood cultures and serum fibronectin levels were higher in patients with Staphylococcus aureus sepsis than in patients with Enterobacteriaceae sepsis. Supplementary experiments on leukocyte oxidative response after zymosan stimulation in normal, fibronectin-depleted, and fibronectin-reconstituted serum demonstrated that the lag period of oxygen burst is a fibronectin-dependent reaction.

Adolescent↗

The induction of parturition in sows using prostaglandin F2alpha.

Intramuscular injections (10 mg) of prostaglandin F2alpha were administered to 19 pregnant sows in one herd on either the 112th or 113th day of gestation and a similar number of untreated sows served as controls. Induced sows for up to 6h after injection generally showed more walking, drinking defaceating and postural changes. Over the last 20 h prepartum they spent more time lying and urinated more frequently. Mean interval from injection to onset of parturition in treated sows was 24.5 h and 16 of them commenced farrowing during the working day, compared with 6 in the control group. Induction of parturition did not influence litter size at birth, piglet body-weights at birth or 14 days of age, the incidence of the mastitis, metrititis agalactae syndrome, re-breeding interval of the sow or size of the subsequent litter at birth. Farrowing time was significantly longer (6.48 h v 4.08 h) for treated sows and litter pre-weaning mortality was higher but not significantly so. Most piglet deaths in each group resulted from overlaying or starvation but mortality from anaemia and septicaemia occurred only in the treated group. It is considered that the technique could have practical application on well-managed intensive pig units.

Journal Article↗

Immune deficiency in the X-linked lymphoproliferative syndrome. I. Epstein-Barr virus-specific defects.

Eleven males with XLP were evaluated for EBV-specific antibodies during periods of 2 to 7 yr. Variable responses to EBV-specific antigens were found. All 11 patients had subnormal anti-EBNA titers, which probably reflected a T cell deficiency. The patients showed four different patterns in their anti-VCA response: 1) two boys who had experienced malignant lymphoma mounted no antibodies at all; 2) two patients showed intermittent anti-VCA titers; 3) four males had persistently elevated anti-VCA titers; and 4) three patients showed normal anti-VCA titers. ADCC against EBV-infected cells was abnormally low in six patients and was elevated in two patients given gamma-globulin. ADCC titers did not correlate with anti-VCA titers. However, most patients with XLP failed to effect regression of autologous EBV-infected lymphoblastoid cell lines, indicating a deficiency in long-lived T cell-mediated immunity to EBV.

Antigens, Viral↗

Gastric pull-up vs deltopectoral flap for reconstruction of the cervical esophagus.

Reconstruction of the cervical esophagus and pharynx after a total laryngopharyngectomy for patients with advanced hypopharyngeal cancer still remains a problem for surgeons. The results of two procedures, the tubed deltopectoral flap reconstruction and the gastric pull-up operation with pharyngogastric anastomosis, which are used in fulfilling postoperative deglutition requirements, were compared. There were nine patients in the gastric pull-up group and eight patients in the deltopectoral flap group. The groups were reasonably comparable with regard to age, sex, preoperative radiotherapy, and stage of tumor. Three of the patients in the gastric pull-up group were operated on for palliation alone. Average operation-to-swallow time was 12 days for the gastric pull-up groups and 90 days for the deltopectoral flap group. Reconstruction of the gullet with the stomach pull-up operations seems to be superior to the tubed deltopectoral flap. This is especially true if the operation is palliative because the patient is unlikely to survive more than one year after surgery.

Adult↗

The effect of the convulsant agent, catechol, on neurotransmitter uptake and release in rat brain slices.

1 The effect of catechol on uptake and K+-stimulated release of gamma-aminobutyric acid (GABA), D-aspartate, noradrenaline and acetylcholine has been studied in slices of cerebral cortex and thalamus. 2 Low concentrations of catechol did not influence the uptake of any of the neurotransmitters in either brain area. 3 Noradrenaline release was unaffected by catechol. 4 Acetylcholine release from both cortical and thalamic slices was inhibited by high concentrations of catechol. This phenomenon is unlikely to be related to catechol-induced convulsions. 5 Catechol (100 microM) inhibited GABA release from cortical slices by 28%. However, at a concentration of 10 microM catechol enhanced the release of D-aspartate from thalamic slices by over 100%. 6 Potentiated release of excitatory amino acid transmitters may contribute to the enhanced excitability of thalamic cells which occurs during sensory myoclonus induced by low doses of catechol.

Acetylcholine↗

Cellular immune defects to Epstein-Barr virus-determined antigens in young males.

Three males with the X-linked lymphoproliferative syndrome (XLP) with hypo- or agammaglobulinemia following Epstein-Barr virus (EBV) infection and two males with the chronic mononucleosis syndrome were investigated for immune responses to EBV-determined antigens. Males with XLP showed profound cellular immune defects. Markedly diminished responses of natural killer cell and interferon-activated killer cell activities and impaired leukocyte migration inhibition responses to phytohemagglutinin were determined in patients with XLP. The two patients with chronic mononucleosis showed less severe defects. All patients showed partial or complete impairment of their EBV-specific immune responses as measured by leukocyte migration inhibition. EBV-specific antibodies were markedly diminished against EBV-associated nuclear antigen, early antigen, and viral capsid antigen in males with XLP. In contrast, patients with chronic mononucleosis had elevated antibodies to most EBV-specific antigens. Individuals with life-threatening EBV-induced lymphoproliferative disorders may exhibit multiple defective immune mechanisms against the virus.

Adolescent↗

Cell-mediated immune reactions in three patients with malignant lymphoproliferative diseases in remission and abnormally high Epstein-Barr virus antibody titers.

Two patients with Hodgkin's disease in remission and one chronic lymphatic leukemia patient with extraordinarily high anti-Epstein-Barr virus (EBV) (viral capsid antigen) antibody titers (greater than 10,000) were selected to study a spectrum of cell-mediated immune responses, including natural killer, interferon-boosted killer, antibody-dependent lymphocytotoxicity, and T-cell-mediated reactions. The purpose was to compare these reactions in patients with immunosuppression and a high EBV load who can hold their EBV-carrying cells under control with the corresponding reactions in patients with EBV-carrying lymphoproliferative disease. In contrast to the latter group, the three patients of the present study showed a less profound and less general suppression of the immune responses. Multiple effector mechanisms probably safeguard against the proliferation of EBV-transformed B-cells. Clinically manifest EBV-carrying lymphoproliferative disease occurs only in very severe immunodeficiencies effecting multiple effectors.

Adolescent↗