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Biomedical subjects

E Hall

Publications and source records attributed to E Hall.

At least 55 records · Page 3Linked to original sources
PubMed1996

In vitro effect of lead on Ca(2+)-ATPase in synaptic plasma membranes and microsomes of rat cerebral cortex and cerebellum.

Earlier investigations from this laboratory suggest that lead interferes with the calcium homeostasis of rat brain through modulation of an inositol polyphosphate second-messenger system. The present investigation was initiated to study the comparative effects of lead chloride and lead acetate on synaptosomal and microsomal Ca(2+)-ATPase of rat cerebral cortex and cerebellum in vitro. The synaptic plasma membranes and microsomes were prepared by using sucrose gradient (1.2-0.8 M). The assay of Ca(2+)-ATPase was done by hydrolysis of ATP and the liberated inorganic phosphate was estimated. Both lead chloride and lead acetate at micromolar concentrations significantly inhibited the Ca(2+)-ATPase of synaptic plasma membranes and microsomes of cerebral cortex and cerebellum in a concentration-dependent manner. The IC50 values of Ca(2+)-ATPase for both lead salts in synaptosomes were significantly lower (P < 0.05) than that of microsomes, indicating more sensitivity. Significantly (P < 0.05) lower IC50 values for both synaptosomal and microsomal Ca(2+)-ATPase were obtained for lead acetate than for lead chloride. The results suggest that lead acetate is more potent than lead chloride in inhibiting the Ca(2+)-ATPase. The microsomal Ca2+ uptake was also studied in cerebellum and cerebral cortex in the presence of different concentrations of both the lead salts. However, these lead salts in vitro did not reveal a significant (P < 0.05) change in the microsomal Ca2+ uptake of cerebellum and cerebral cortex. But earlier investigations indicated that in vitro lead (0.25-2 microM) inhibits inositol 1,4,5-triphosphate-mediated Ca2+ uptake and release in microsomes of rat cerebellum.

Adenosine Triphosphate↗
PubMed1996

A modular questionnaire for the assessment of longterm quality of life in leukaemia patients: the MRC/EORTC QLQ-LEU.

We describe the psychometric analysis of a supplementary quality of life measure (MRC/EORTC QLQ-LEU) for evaluating long term sequelae of leukaemia treatments. The questionnaire under development was administered to 388 patients entered into the EORTC-GIMEMA AML 8A and the MRC AML10 clinical trials who were in complete remission for at least one year after completion of treatment on these trials. Results indicated a measure which is useful in evaluating the long-term effects of treatment in relation to chronic graft-vs-host disease and infection susceptibility. The performance of this measure in terms of its sensitivity and specificity between treatment arms was established by comparisons between the three treatment modalities in the above-mentioned trials and is the subject of further investigation. The new Leukaemia Module can be recommended for use alongside generic QOL instruments as a measure of long-term quality of life in leukaemia trials.

Acute Disease↗
PubMed1996

Transgenic white clover. Studies with the auxin-responsive promoter, GH3, in root gravitropism and lateral root development.

We report improved method for white clover (Trifolium repens) transformation using Agrobacterium tumefaciens. High efficiencies of transgenic plant production were achieved using cotyledons of imbibed mature seed. Transgenic plants were recovered routinely from over 50% of treated cotyledons. The bar gene and phosphinothricin selection was shown to be a more effective selection system than nptII (kanamycin selection) or aadA (spectinomycin selection). White clover was transformed with the soybean auxin responsive promoter, GH3, fused to the GUS gene (beta-glucuronidase) to study the involvement of auxin in root development. Analysis of 12 independent transgenic plants showed that the location and pattern of GUS expression was consistent but the levels of expression varied. The level of GH3:GUS expression in untreated plants was enhanced specifically by auxin-treatment but the pattern of expression was not altered. Expression of the GH3:GUS fusion was not enhanced by other phytohormones. A consistent GUS expression pattern was evident in untreated plants presumably in response to endogenous auxin or to differences in auxin sensitivity in various clover tissues. In untreated plants, the pattern of GH3:GUS expression was consistent with physiological responses which are regarded as being auxin-mediated. For the first time it is shown that localised spots of GH3:GUS activity occurred in root cortical tissue opposite the sites where lateral roots subsequently were initiated. Newly formed lateral roots grew towards and through these islands of GH3:GUS expression, implying the importance of auxin in controlling lateral root development. Similarly, it is demonstrated for the first time that gravistimulated roots developed a rapid (within 1 h) induction of GH3:GUS activity in tissues on the non-elongating side of the responding root and this induction occurred concurrently with root curvature. These transgenic plants could be useful tools in determining the physiological and biochemical changes that occur during auxin-mediated responses.

Agrobacterium tumefaciens↗
PubMed1996

In vitro and in vivo effects of lead, methyl mercury and mercury on inositol 1,4,5-trisphosphate and 1,3,4,5-tetrakisphosphate receptor bindings in rat brain.

In vitro and in vivo effects of mercury (Hg), methyl mercury (MM) and lead (Pb) on [3H]inositol 1,4,5-trisphosphate (IP3) and [3H]inositol 1,3,4,5-tetrakisphosphate (IP4) receptor binding in the Sprague-Dawley rat brain cerebellar membranes were studied. In vitro studies indicate that binding of [3H]IP3 and [3H]IP4 to cerebellar membranes was inhibited by Hg while they were stimulated by MM or Pb in a concentration-dependent manner. MM was more potent (EC50 3.4 microM) than Pb (EC50 18.2 microM) in stimulating the [3H]IP3 receptor binding activity whereas Pb (IC50 30 microM) was more potent than MM (IC50 133 microM) in stimulating the [3H]IP4 receptor binding. When the rats were treated (i.p) with Hg (5 mg/kg body wt.) or MM (5 mg/kg body wt.) or Pb (25 mg/kg body wt.) for 3 or 24 h, no significant alterations in [3H]IP3 receptor binding were observed in cerebellum and cerebral cortex. But the above treatment of Pb or MM for 3 or 24 h to rats resulted in an increase of [3H]IP4 receptor binding in the membranes of cerebral cortex. However, the rats treated with Hg (1 mg/kg body wt./day) or Pb (25 mg/kg body wt./day) for 7 days did not show any alteration in binding of [3H]IP3 to its receptors in cerebellar membranes but an increase in this receptor binding was noticed with the treatment of MM (2.5 mg/kg body wt./day) for 7 days. The cerebellum and cerebral cortex of rats with the above treatment of MM or Pb for 7 days exhibited an increase in [3H]IP4 receptor binding. These in vitro and in vivo data suggest that alterations in inositol polyphosphate receptor binding by metals could result in alterations in intracellular calcium levels which may influence neuronal activity.

Analysis of Variance↗
PubMed1996

Pigmented basal cell carcinoma in Hispanics.

BACKGROUND: Pigmented basal cell carcinoma (PBCC) may occasionally be misdiagnosed as melanoma. In the Hispanic population, PBCC is common. OBJECTIVE: We attempted to determine the prevalence of PBCC in a Hispanic population. METHODS: A randomized, blinded, retrospective study was designed to assess histologic slides for the presence of microscopic pigment. Basal cell carcinoma (BCCs) from 30 patients with a Hispanic surname were compared histologically with BCCs from 30 patients with a northern European surname. In the prospective phase of the study, 15 Hispanic and 44 non-Hispanic patients with clinically suspected BCC or PBCC completed a questionnaire about their ethnic background and skin type to determine whether PBCC is more common in Hispanics. RESULTS: Pigment was identified twice as frequently in BCCs from patients with a Hispanic surname than in BCCs from patients with a northern European surname. In the prospective clinical study, 66% of clinically diagnosed PBCCs were found in Hispanic patients, whereas only 11% of nonpigmented BCCs came from Hispanic patients (p < 0.01). CONCLUSION: In patients with a BCC, PBCCs are more common in Hispanics than non-Hispanics. This may reflect an increased incidence of PBCCs in the Hispanic population.

Basal Cell Carcinoma↗
PubMed1995

Modulation of protein kinase C by heavy metals.

Protein kinase C (PKC) regulates a variety of intracellular and extracellular signals across the neuronal membrane. PKC requires calcium and phospholipid, particularly phosphatidylserine (PS) for its activation. The data indicates that mercury (Hg), lead (Pb) and methyl mercury (CH3Hg) in vitro inhibited the PKC activity at micromolar concentrations in a concentration-dependent manner with IC50 values of 1.5, 2.12 and 0.22 microM, respectively. The IC50 values indicate that CH3Hg was more potent in inhibiting the enzyme activity than Hg or Pb. The basal PKC activity was also inhibited by Pb or Hg. However, the PS-stimulated PKC activity was more sensitive to Pb or Hg than the basal enzyme. The phorbol ester binding to PKC was also found to be inhibited by micromolar concentrations of these metals in vitro. Hg and CH3Hg were more potent inhibitors of phorbol ester binding than Pb. Dithiothreitol (DTT), a dithiol, but not glutathione (GSH) a monothiol, protected the activities of both PS-stimulated and basal PKC from metal-inhibition in a concentration-dependent manner. The present study suggests that the dithiols but not monothiols effectively protect metal-inhibited activity of PKC in rat brain.

Animals↗
PubMed1995

Gangliosides and spinal cord ischemia secondary to aortic cross-clamping in the rat model.

Gangliosides, complex glycolipids of the nervous system cell membranes, have been found effective both in reducing the degree of ischemic injury and in stimulating neuronal regeneration during the recovery period. In order to investigate their neuroprotective effect during spinal cord ischemia, 60 male Sprague-Dawley rats underwent occlusion of the thoracic aorta and both subclavian arteries for 13 min. In the postoperative period, function of hindlimbs was appraised, daily for 30 days, by a deficit score (0-15). The animals were then killed and spinal cord injury was assessed by a histologic score (0-3) based on the degree of gray and white matter gliosis, number of motor neurons, and white matter myelination. The rats received intraperitoneal injection of placebo (n = 29) or GM-1 30 mg/kg (n = 31) daily, from 2 days prior to surgery to 15 days after. The scores of each group for each day were analyzed by repeated measures analysis of variance. The rate of recovery was better for GM-1 (P < 0.001) from the 15th to the 30th day. A trend was seen toward lower scores in the GM-1 group (P = 0.056). Mean histologic scores (placebo = 1.14 +/- 0.23 SE, GM-1 = 1.58 +/- 0.22 SE) did not differ (Wilcoxon, P = 0.17). The present data support the hypothesis that functional improvement after spinal cord ischemia due to aortic occlusion is enhanced by the administration of gangliosides. Optical microscopy could document only irreversible injury and might not be sensitive enough to detect subtle changes during recovery of neural elements.

Animals↗
PubMed1995

Relationship between the discriminative stimulus effects and plasma concentrations of intramuscular cocaine in rhesus monkeys.

The relationship between the discriminative stimulus effects and plasma pharmacokinetics of cocaine was evaluated in six rhesus monkeys trained to discriminate cocaine (0.4 mg/kg, IM) from saline under a FR30 schedule of food presentation. The same monkeys were tested in two procedures. In a cumulative dosing procedure, five cumulative doses of cocaine (0.013-1.3 mg/kg) were administered and discriminative stimulus effects were evaluated 10 min after the administration of each dose. Cocaine plasma concentrations were measured in separate sessions using the same doses and interdose intervals. In a single dosing procedure, the time-courses of the discriminative stimulus effects and plasma concentrations of cocaine were assessed after the administration of cocaine (0.4 mg/kg). A close correspondence between cocaine's discriminative stimulus effects and plasma concentrations was obtained in both procedures. Cocaine was virtually undetectable in plasma at doses that produced saline-appropriate responding (0.013 and 0.04 mg/kg), whereas increasing plasma concentrations were measured at doses that produced primarily cocaine-appropriate responding (0.13 mg/kg or higher). The time-course of the discriminative stimulus effects of cocaine was characterized by a rapid onset (within 1-3 min post-cocaine) and offset (within 20-60 min post-cocaine). Peak plasma levels were obtained at 10 min post-cocaine. No differences in plasma concentrations were found 10 min after the administration of a cumulative versus a single dose of cocaine 0.4 mg/kg (mean, 75.8 and 74.0 ng/ml, respectively). Cocaine plasma concentrations lasted longer than its discriminative stimulus effects. The results of the present study confirm that the cumulative dosing procedure used yields plasma concentrations of cocaine that are similar to the concentrations obtained after single cocaine dosing.

Animals↗
PubMed1995

Mycobacterium marinum disease in Anne Arundel County: 1995 update.

A retrospective survey of 41 cases of culture-positive Mycobacterium marinum disease in Anne Arundel County, Maryland, showed that most infection was related to recreational exposure to the Chesapeake Bay and its tributaries. Three quarters of cases consisted of skin or joint/tendon infection of the upper extremity, particularly the hand. An empiric drug regimen for a granulomatous soft tissue infection in this context should include rifampin and ethambutol or cotrimoxazole (trimethoprim/sulfamethoxazole). A reactive tuberculin skin test in Anne Arundel County is more likely to represent M. marinum infection than tuberculous infection.

Adolescent↗
PubMed1994

Mortality in relation to consumption of alcohol: 13 years' observations on male British doctors.

OBJECTIVE: To assess the risk of death associated with various patterns of alcohol consumption. DESIGN: Prospective study of mortality in relation to alcohol drinking habits in 1978, with causes of death sought over the next 13 years (to 1991). SUBJECTS: 12,321 British male doctors born between 1900 and 1930 (mean 1916) who replied to a postal questionnaire in 1978. Those written to in 1978 were the survivors of a long running prospective study of the effects of smoking that had begun in 1951 and was still continuing. RESULTS: Men were divided on the basis of their response to the 1978 questionnaire into two groups according to whether or not they had ever had any type of vascular disease, diabetes, or "life threatening disease" and into seven groups according to the amount of alcohol they drank. By 1991 almost a third had died. All statistical analyses of mortality were standardised for age, calendar year, and smoking habit. There was a U shaped relation between all cause mortality and the average amount of alcohol reportedly drunk; those who reported drinking 8-14 units of alcohol a week (corresponding to an average of one to two units a day) had the lowest risks. The causes of death were grouped into three main categories: "alcohol augmented" causes (6% of all deaths: cirrhosis, liver cancer, upper aerodigestive (mouth, oesophagus, larynx, and pharynx) cancer, alcoholism, poisoning, or injury), ischaemic heart disease (33% of all deaths), and other causes. The few deaths from alcohol augmented causes showed, at least among regular drinkers, a progressive trend, with the risk increasing with dose. In contrast, the many deaths from ischaemic heart disease showed no significant trend among regular drinkers, but there were significantly lower rates in regular drinkers than in non-drinkers. The aggregate of all other causes showed a U shaped dose-response relation similar to that for all cause mortality. Similar differences persisted irrespective of a history of previous disease, age (under 75 or 75 and older), and period of follow up (first five and last eight years). Some, but apparently not much, of the excess mortality in non-drinkers could be attributed to the inclusion among them of a small proportion of former drinkers. CONCLUSION: The consumption of alcohol appeared to reduce the risk of ischaemic heart disease, largely irrespective of amount. Among regular drinkers mortality from all causes combined increased progressively with amount drunk above 21 units a week. Among British men in middle or older age the consumption of an average of one or two units of alcohol a day is associated with significantly lower all cause mortality than is the consumption of no alcohol, or the consumption of substantial amounts. Above about three units (two American units) of alcohol a day, progressively greater levels of consumption are associated with progressively higher all cause mortality.

Adult↗
PubMed1994

Ambulatory case mix funding systems in Canada.

The implementation of inpatient case mix funding in Alberta and Ontario does not allow for adequate incentives to shift resources to an outpatient basis, where appropriate, or to provide outpatient care efficiently. This paper explores the prospects and problems of further extending case mix tools into this area. The availability of tools to characterize output for day surgery, special clinics and emergency care is surveyed. We conclude that case mix funding is desirable and feasible for ambulatory surgery; however, it is questionable for emergency care and special clinics. However, developments in this area in the United States will continue, and this will likely maintain an interest in Canada.

Alberta↗
PubMed1994

Palliation of malignant intestinal obstruction using octreotide.

Vomiting due to malignant intestinal obstruction is an unpleasant terminal event in many cancer patients, which responds poorly to conventional therapies. Somatostatin and its long-acting analogues reduce intestinal secretion. For this reason, octreotide was used in a phase I/II study of patients with intractable vomiting secondary to intestinal obstruction due to malignant disease. Vomiting was controlled or the volume of nasogastric aspirate was markedly reduced in 18 of 24 (75%) patients receiving a subcutaneous infusion of octreotide (median initial dose 300, range 100-600 micrograms/day) for a median of 9.4 (range 1-38) days. A further 2 patients had partial relief of their symptoms. Octreotide is an effective treatment of nausea and vomiting due to malignant bowel obstruction.

Adult↗
PubMed1994

Immunological and virological changes associated with decline in CD4/CD8 ratios in lymphoid organs of SIV-infected macaques.

The decline in CD4/CD8 ratios in lymph nodes (LNs) of SIV macaques and HIV-infected individuals occurs later than that in blood. In a previous study, long-term SIV-infected macaques were delineated into two groups: (1) those whose LNs had normal CD4/CD8 ratios and (2) those whose LNs had low CD4/CD8 ratios. In the present investigation, LNs, spleens, and blood from these groups have been further analyzed to ascertain the cellular and virological events, particularly those involving CD8+ cells, that occur concomitantly with LN CD4% decline. An increase in the percent of CD69-, IL-2R(p75)-, CD45RA1o CD8+ cells was the most constant event observed in lymphoid tissue from mid- to late-stage SIV-infected monkeys. Such cells were sometimes observed in LNs prior to any other immunological or morphological changes. However, decline in LN CD4/CD8 ratios and the associated degeneration of follicular dendritic cells (FDCs) in the germinal centers (GCs) of these nodes were observed only when both CD8+ cell infiltration of GCs and accumulation of viral antigens within the FDC network could be demonstrated. These dramatic changes were also associated with significantly reduced responsiveness to mitogens throughout the lymphoid compartment. In terms of viral burden, immunological and structural collapse of LNs was not always associated with increased viral DNA levels. Despite the CD4+ cell decline in blood during HIV and SIV infections, the immunological and architectural collapse of the lymphoid compartment, which comprises the bulk of the lymphocytes in the body, appears to be a critical event leading to the onset of AIDS. The present findings suggest that increased CD8+ cell activity as well as decrease in CD4+ cell function both contribute to this process.

Acquired Immunodeficiency Syndrome↗