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Biomedical subjects

G Fraser

Publications and source records attributed to G Fraser.

15 recordsLinked to original sources

Malignant glioma-derived soluble factors regulate proliferation of normal adult human astrocytes.

Malignant gliomas are characteristically surrounded by marked gliosis. To assess whether glioma-derived products contribute to the proliferation of astrocytes, a feature of the gliosis response, we evaluated the influence of culture supernatants from malignant human glioma lines and tumor cyst fluids collected from two patients with glioblastoma multiforme on the proliferation of non-transformed adult human astrocytes. Both the culture supernatants and cyst fluids significantly increased DNA synthesis in astrocytes as assessed by a double immunofluorescence glial fibrillary acidic protein-bromodeoxyuridine technique. The net proliferative effect mediated by glioma cell line supernatants was tumor growth phase-dependent, being preferentially expressed during the logarithmic phase of glioma cell growth. Specific growth factor molecules and cytokines known to be secreted by gliomas (epidermal growth factor, fibroblast growth factor, platelet-derived growth factor, transforming growth factor-beta, interleukin-6, and tumor necrosis factor-alpha) could not reproduce the mitogenic effects of the glioma-derived soluble factors. Cytokines which can induce DNA synthesis by adult human astrocytes in vitro, gamma-interferon and interleukin-1, were not detected in the culture supernatant of glioma lines used in this study. In conjunction with the documented effects of glioma products on endothelial and lymphoid cells, the current study suggests that soluble glioma products can contribute to the production of surrounding gliosis observed in vivo.

Astrocytes

Screening for colorectal neoplasia: a multicenter study in Israel.

We report the design and results of the first Israeli multicenter screening program for colorectal neoplasia. The screening protocol comprised a risk questionnaire, fecal occult blood testing, flexible sigmoidoscopy and colonoscopy. A total of 5,601 individuals were screened in five medical centers, 55% being asymptomatic with low or average risk. Colorectal tumors were found in 12.3% of screenees, the majority being adenomas. The risk for large bowel neoplasia was greatest in persons with a personal history of colorectal neoplasia (neoplasia rate 473.2/10(3)) and was increased in those with inflammatory bowel disease, a family history of colorectal tumor, or past history of cured breast cancer. European-born Jews had a 50% greater risk than non-European-born Jews. Persons at high risk were more likely to return for repeat screening than those at low or average risk. However, approximately 15% of persons at high risk actually thought that they were of average risk. Fecal occult blood testing was markedly less reliable than flexible sigmoidoscopy and had a false-negative rate of 84.4%. The results demonstrate that existing medical facilities in Israel can be used to screen at least those individuals with increased risk for colorectal neoplasia.

Adenoma

Fluoridation.

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Fluoridation

Waiting lists.

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General Surgery

Auditory evoked potentials in panic disorder.

Neuroimaging studies of behavioral-induced anxiety in non-patients and of lactate-induced anxiety in panic disorder patients have indicated that normal and pathological anxiety may share a common pathway involving the temporal poles. As panic-related anxiety may reflect faulty temporopolar evaluative processing of input, the objective of this study was to examine sensory reactivity in panic disorder patients via scalp recordings of the late auditory evoked 'vertex' potential (LAEP) which appears to have a predominantly temporal lobe origin. Twelve patients diagnosed according to DSM-III criteria as panic disorder and ten normal controls served as subjects in this study. EEG was recorded from 16 scalp sites using a monopolar fronto-occipital derivation and LAEPs were separately averaged in response to four acoustic intensities. Analysis focused on group and electrode-site differences in the negative (N1) and positive (P2) component amplitudes of the LAEPs. Panic disorder patients were found to exhibit significantly larger N1 amplitudes across all stimulus intensities and across all recording sites. No significant group differences were observed with P2. Although the results provide indirect support for a temporal focus, other modulating influences must be considered in data interpretation.

Adult

A cAMP-activated chloride channel in the plasma membrane of cultured human gastric cells (HGT-1).

Hydrochloric acid (HCl) secretion by gastric parietal cells involves an apical Cl- conductance, the properties of which have not been defined. In the present study, forskolin and histamine [agonists that increase intracellular cyclic adenosine monophosphate (cAMP)], and dibutyryl cAMP, activated channels in previously quiescent cell-attached membrane patches on cultured human gastric cells (HGT-1). In the cell-attached configuration (Cl- 149 mmol/l in bath and pipette), channels exhibited outward rectification, voltage dependence, inward current (-0.7 pA) at zero holding potential and a reversal potential of +24 mV, consistent with the presence of a Cl- conductive pathway. In excised inside-out patches, channels (i) exhibited degrees of outward rectification and voltage dependence that were comparable to those seen in cell-attached patches, (ii) demonstrated a -21 mV shift of their reversal potential when bath Cl- was decreased from 149 mmol/l to 53 mmol/l (calculated Cl-:cation permeability ratio 17:1), and (iii) were highly sensitive to the Cl- channel blocker diphenylamine-2-carboxylic acid (DPC, 10(-3) mol/l). This cAMP-activated Cl- channel bears many similarities to other Cl- channels within intestinal epithelia, and may represent the apical Cl- channel operating in HCl-secreting gastric parietal cells.

Adenocarcinoma

Ventilation during sleep onset in young adult females.

Ventilation is known to decrease from wakefulness to non-rapid-eye-movement sleep. In males, the change is associated with the commencement of theta activity in the electroencephalogram (EEG). The magnitude of the decrease is greater than that required by the reduction in metabolic rate at sleep onset and it has been suggested that the nonmetabolic component reflects the loss of a wakefulness drive to respiration. The effect of sleep onset on ventilation in female subjects was of interest because previous studies on changes in respiratory activity during sleep in this population have produced inconsistent results, a phenomenon that may relate to the menstrual cycle and the role of progesterone in respiratory activity. The present experiment sought to investigate ventilation during sleep onset in young adult females as a function of the menstrual cycle, and to compare the results with data collected from male subjects in an earlier experiment. Sleep onset was studied in five subjects in a series of single subject designs. The data were consistent with those of the male subjects and showed decreases in ventilation associated with the onset of theta activity in the EEG. Furthermore, no menstrual phase differences were apparent. The results indicate that in females, as in males, sleep is associated with loss of a wakefulness drive to ventilation.

Adolescent

Proliferative haemorrhagic enteropathy.

This study indicates that viable Campylobacter sputorum subsp mucosalis are not present or are present in small numbers in the mucosa of pigs dying of proliferative haemorrhagic enteropathy. The changes present in the mucosa are similar to those seen in pigs recovering from adenomatosis and the evidence obtained indicates that the intracellular organisms observed in this condition are indeed mucosalis. The presence of large amounts of IgA in the altered tissue of both proliferative haemorrhagic enteropathy and porcine intestinal adenomatosis indicates that the failure to recover bacteria may be immunologically mediated but is not simply related to the presence or absence of antibody in the respective conditions.

Animals

An electron microscopic study of MDBK cells persistently infected with Newcastle disease virus.

Ultrastructural examination of a line of MDBK cells persistently infected with Newcastle disease virus (MDBKpi cells) revealed the presence of cytoplasmic aggregates of both smooth and granular nucleocapsids. Only granular nucleocapsids aligned under modified areas of plasma membrane and were incorporated into virus particles. On the grounds of morphogenesis, there was no apparent explanation for the persistent, not-cytocidal nature of the infection. Both nuclear and cytoplasmic aggregates of smooth nucleocapsids were present in MDBKpi cells which had been held without subculture for between 40 and 130 days (aged MDBKpi cells). Modified areas of plasma membrane with associated alignment of nucleocapsids were not present in aged MDBKpi cells, and neither budding nor released virus particles were observed, indicating a block in virus maturation. It is suggested that the granular material coating granular nucleocapsids allows them to interact with modified areas of plasma membrane, thereby inducing virus budding. A deficiency of this material, as apparently occurs in aged MDBKpi cells, would therefore cause a block in virus maturation. The nature of this granular material is discussed, and we suggest that it consists of M protein.

Animals

Experience with bretylium tosylate by a hospital cardiac arrest team.

The effect of bretylium tosylate (BT) was determined in 27 consecutive cases of resistant ventricular fibrillation (VF) encountered by a hospital cardiac arrest team. The VF was sustained and completely resistant to multiple injections of lidocaine, sequential DC shocks at 400 watt-sec and one or a combination of intravenous propranolol, diphenylhydantoin or procainamide. Following 30 min of sustained cardiac massage, BT (5 mg/kg i.v.) was administered. In 20 patients, VF was terminated within 9-12 min after DC shock. Eight of these patients failed to recover while 12 (44%) of all patients resuscitated survived to be discharged from hospital. Eleven out of 20 (55%) of all patients who had a cardiac arrest outside the CCU were survivors; only one out of seven in the CCU were successfully resuscitated. While receiving maintanance BT post-resuscitation (5 mg/kg i.m. q 8-12 hrs x 48 hrs), half the patients developed hypotension and three required vasopressors and/or fluid replacement. The data indicate that BT is a useful agent in patients with sustained VF refractory to repeated lidocaine injections, some other antiarrhythmic agents, and multiple DC shocks.

Bretylium Compounds

Accidental persistent infection of cell lines by Newcastle disease virus, showing three unusual features--defective neuraminidase, temperature sensitivity and intranuclear inclusions.

A persistent, defective infection by an unknown strain of Newcastle disease virus (NDV) appeared accidentally in established lines of pig, ox and sheep kidney cells. Virus particles released from the persistently infected cells were not infectious and were deficient in neuraminidase activity. Synthesis of some of the virus-specified proteins in the persistently infected cells was temperature-sensitive. Co-cultivation of mixed populations of carrier cells and healthy chick embryo cells induced cell fusion with the formation of multinucleate heterokaryons and intra-nuclear inclusions. The development of inclusions in the chicken nuclei was not accompanied by 'rescue' of infectious NDV.

Animals

Sudden hemolysis indicating prosthetic valve dysfunction.

Ten months after aortic valve replacement (Björk-Shiley prosthesis) a 57-year-old man had thrombotic encapsulation of his prosthetic valve. The only clinical manifestation of this serious complication was gross hemoglobinuria. The management of the patient is described. The slightest change in the condition of a patient after prosthetic valve replacement should be viewed as a possible sign of thrombosis.

Anticoagulants