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Biomedical subjects

G Gibson

Publications and source records attributed to G Gibson.

At least 91 records · Page 5Linked to original sources

Mosquito responses to carbon dioxide in a west African Sudan savanna village.

Mosquito responses to carbon dioxide were investigated in Noungou village, 30 km northeast of Ouagadougou in the Sudan savanna belt of Burkina Faso, West Africa. Species of primary interest were the main malaria vectors Anopheles gambiae s.s. and An.arabiensis, sibling species belonging to the An.gambiae complex. Data for An.funestus, An.pharoensis, Culex quinquefasciatus and Mansonia uniformis were also analysed. Carbon dioxide was used at concentrations of 0.04-0.6% (cf. 0.03% ambient concentration) for attracting mosquitoes to odour-baited entry traps (OBETs). The "attractiveness' of whole human odour was also compared with CO2 emitted at a rate equivalent to that released by the human bait. In a direct choice test with two OBETs placed side-by-side, the number of An.gambiae s.l. entering the trap with human odour was double the number trapped with CO2 alone (at the human equivalent rate), but there was no significant difference between OBETs for the other species of mosquitoes. When OBETs were positioned 20 m apart, again CO2 alone attracted half as many An.gambiae s.l. and only 40% An.funestus, 65% Ma.uniformis but twice as many An.pharoensis compared to the number trapped with human odour. The dose-response for all mosquito species was essentially similar: a linear increase in catch with increasing dose on a log-log scale. The slopes of the dose-response curves were not significantly different between species, although there were significant differences in the relative numbers caught. If the dose-response data are considered in relation to a standard human bait collection (HBC), however, the behaviour of each species was quite different. At one extreme, even the highest dose of CO2 did not catch more An.gambiae s.l. than one HBC. At the other extreme, the three highest doses of CO2 caught significantly more Ma.uniformis than did one HBC. An.pharoensis and Cx quinquefasciatus showed a threshold response to CO2, responding only at doses above that normally released by one man. An.funestus did not respond to CO2 alone at any dose in sufficient numbers to assess the dose response. Within the An.gambiae complex, An.arabiensis "chose' the CO2-baited trap with a higher probability than An.gambiae s.s. Also An.arabiensis, the less anthropophilic of the two species, was more abundant in CO2-baited OBETs than in human bait collections.

Animals↗

Genetics, ecology and behaviour of anophelines.

The efficiency with which mosquitoes transmit malaria is related to how closely associated they are with the human host. For example, the relative vectorial capacity of two species may be determined by differences in their degree of preference for human blood or in their degree of preference for blood-feeding indoors versus outdoors. Species complexes, such as Anopheles gambiae sensu lato, allow us to investigate how species differences in genetics, ecology and behaviour can lead to significant differences in vectorial capacity. The potential exists for identification of behaviour-regulating genes for exploitation by novel control measures. Close correlations have been demonstrated between certain behaviours and karyotypes in the An. gambiae s.l. complex, but the physiological basis for these correlations has yet to be determined. Recent evidence from behavioural studies suggests that differences in host preference may reflect differences in the relative responsiveness to CO2 and other, more specific, host odours.

Animals↗

Molecular cloning and expression of a cDNA for human kidney cysteine conjugate beta-lyase.

Kidney cysteine conjugate beta-lyase (glutamine transaminase K, kyneurenine aminotransferase, EC 2.6.1.64) metabolises the cysteine conjugates of certain halogenated alkenes and alkanes to form reactive metabolites which can produce nephrotoxicity and neurotoxicity in experimental animals and man. Using a combination of hybridisation screening and PCR techniques we have isolated a full-length cDNA for human kidney cysteine conjugate beta-lyase. Comparison of the deduced amino acid sequence with that of the rat enzyme indicated an 82% overall similarity, with 90% similarity around the pyridoxal phosphate binding site, many of the changes being conservative in nature. Expression of the cDNA in Cos-1 cells resulted in the production of a cytosolic enzyme which showed both cysteine conjugate beta-lyase and glutamine transminase K activity. Preliminary mapping of the gene for human cysteine conjugate beta-lyase by PCR analysis of genomic DNA from human-rodent hybrid cells indicated that it is located on human chromosome 9.

Amino Acid Sequence↗

Parathyroid hormone decreases in vivo insulin effect on glucose utilization.

Hyperparathyroidism is associated with impaired glucose tolerance, and parathyroidectomy may improve carbohydrate homeostasis. It has been suggested that parathyroid hormone (PTH) suppresses insulin secretion but it is unclear whether it also interferes with the peripheral action of insulin. To evaluate in vivo effects of PTH on insulin-mediated glucose utilization, 15 male Sprague Dawley rats were continuously infused with rat PTH (1-34) using an Alzet miniosmotic pump at a rate of 0.03 nm/hour. Controls were infused with the vehicle alone. Following 5 days of PTH infusion, plasma calcium (Ca) levels were higher in the PTH-infused rats (12.3 +/- 0.2 versus 9.9 +/- 0.1 mg/dl, P < 0.01). On the 5th day, glucose (700 mg/kg) and insulin (0.175 U/kg) were given as a bolus infusion through the left femoral vein, blood samples were obtained from the right femoral vein, and plasma glucose and insulin were measured at basal (0 minutes) and at 2, 5, 10, and 20 minutes postinfusion. Basal, nonfasting glucose levels were higher (166 +/- 4 versus 155 +/- 4 mg/dL, P < 0.04) in the PTH-infused rats but their insulin levels were similar to those of controls (6.5 +/- 0.6 versus 5.6 +/- 0.5 ng/ml). Postinfusions and maximal (2 minutes) glucose and insulin levels were similar in both groups. However, although insulin levels were similar in both groups at all measured time points, glucose levels at 20 minutes were higher in the PTH-treated rats (205 +/- 13 versus 173 +/- 9; P < 0.03).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

3,4-diaminopyridine as a treatment for amyotrophic lateral sclerosis.

The slow potassium channel blocker 3,4-diaminopyridine (DAP) enhances acetylcholine release from the nerve terminal and improves conduction in unmyelinated nerve. In this open label pilot study, we examined the effect of DAP combined with inpatient rehabilitation in seven patients with motor weakness due to amyotrophic lateral sclerosis (ALS). A single daily 20 mg oral dose of DAP was gradually increased to the maximum tolerated dose, and serum DAP concentrations were measured. Videotaped motor examination (for subsequent "blinded" review and assignment of a quantitative motor score), Functional Independence Measure (FIM) assessment, nerve conduction studies and neuropsychological evaluations were performed on admission, 1 h after maximum DAP dose, and post-treatment. DAP was tolerated in all patients, though dose was limited by gastrointestinal side effects in five patients. The mean peak serum level was 128 (+/- 50) ng/ml, occurring 1.0 (+/- 0.50) h after dose. A modest but statistically significant (p = 0.045) peak in motor score occurred on DAP. A significant (p = 0.045) improvement from baseline in FIM performance was apparent with DAP. Nerve conduction studies showed small increases in evoked response amplitudes and conduction velocities on DAP, but they did not reach statistical significance. No cognitive or affective changes were apparent. This unblinded pilot study shows that DAP is tolerated in ALS patients, and may be associated with functional and electrophysiologic improvement.

4-Aminopyridine↗

Effects of long-term lithium infusion on normal parathyroid tissue.

BACKGROUND: Approximately 10% of patients taking lithium for manic-depressive disorders become hypercalcemic. It remains unclear whether lithium initiates disease or promotes underlying hyperparathyroidism. We have previously demonstrated that at therapeutic concentrations lithium stimulates in vitro incorporation of both tritiated thymidine and bromodeoxyuridine into abnormal human parathyroid tissue, reflecting growth-promoting properties. Whether lithium has similar growth-promoting properties in normal parathyroid tissue remains unresolved. METHODS: We infused lithium (0 mmol/L, 3 mmol/L, or 10 mmol/L) through implantable subcutaneous pumps into normal rats for 3 months and measured levels of serum lithium, serum calcium, and serum parathyroid hormone (PTH) (with a radioimmunoassay specific for rat PTH 1-34.) On completion of the infusion, bromodeoxyuridine (30 mg/kg) was administered intraperitoneally. The parathyroid glands were removed and measured in two dimensions to calculate gland volume [V = (pi/6) x (d1) x (d2)2.] Parathyroid incorporation of bromodeoxyuridine was assessed by using immunocytochemistry. RESULTS: Serum lithium level was significantly (p < 0.05) different between groups and constant within groups. Levels of serum calcium and PTH were inversely related to each other; however, no significant differences were noted between groups with respect to level of serum calcium or serum PTH at any measurement. Similarly, no significant differences were noted between groups with respect to gland size or number of bromodeoxyuridine-positive cells. CONCLUSIONS: Long-term lithium infusion in rats for a period representing approximately 15% of their life span failed to evoke changes in parathyroid gland size or function. These data are consistent with (1) lithium as a promoter of hyperparathyroidism and (2) resection of abnormal parathyroid tissue and resumption of lithium for patients requiring long-term therapy.

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The department of Veterans Affairs oral health services and eligibility.

The Department of Veterans Affairs (VA) operates one of the largest health care systems in the nation; more than 2.5 million veterans receive care annually. Among the special foci of care within VA is the Dental Service. The Department of Veterans Affairs Dental Service is the largest dental care system in the nation and the largest hospital-based dental care system in the world, receiving more than 1.2 million visits annually. The authors describe the VA dental care system and the larger health care system in which it is embedded. How the system is organized, who is eligible for services, who uses care, and what types of services are used are detailed. Compared with medical care, eligibility for VA dental care is more complex and differs for inpatients and outpatients. Outpatients account for 65% of patient visits and 76% of treatment provided in VA dental clinics. The two largest groups of users are inpatients with compelling medical needs (17%) and outpatients who are totally disabled (24%). A wide variety of services is provided, ranging from diagnostic and preventive care to insertion of crowns, bridges, and removable prostheses. Changes in the nation's health care system mandate introspection by all health agencies. The goal of the VA Dental Service is to become veterans' first choice for dental care. Information needed by VA to best respond to the needs of veterans include the following: (1) reasons for why eligible veterans do not use VA dental care; (2) veterans' oral health needs; (3) definition of optimum care and whether it varies as a person moves from functional independence to dependence; (4) whether VA is providing the most cost-efficient care possible and is best utilizing allied health professions; and (5) whether this care is best provided in a hospital setting. Modifications of data gathering systems are required as a first step to providing the needed information.

Aged↗

Research issues related to the oral health status of aging veterans.

This article reviews the research on the oral health status of aging veterans and offers recommendations for a research agenda that will improve their oral health and quality of life. Uniform definitions, or a "composite" measure, of overall oral health status would facilitate oral health status measurement. Because such a measure is not available, traditional oral epidemiologic indexes or treatment-needs data have been used to identify oral health status in aging veterans. Few studies of national scope have been conducted on veterans. A cost-effective alternative may be cooperative studies within the Department of Veterans Affairs (VA) and other organizations. The Department of Veterans Affairs Dental Longitudinal Study (DLS), begun in 1968, provides the richest data on an aging veteran population. More frequently, VA investigators have examined local or regional veteran populations. These studies have examined oral health status and risk factors associated with oral diseases. Unlike the DLS, most studies have been cross-sectional, and a few studies have examined the effect of systemic disease on oral health and vice versa. Key research agenda items and recommendations include: Development and validation of functional measures of oral health status; Implementation of multicenter, cooperative, descriptive, and analytic epidemiologic studies; Implementation of focused cross-sectional and longitudinal studies on oral health status, treatment needs, and patient outcomes; Enumeration of data sets in the VA system that can be shared with non-VA investigators; Implementation of targeted studies of aging populations who have specific comorbidities prevalent in VA; and Use of VA continuum of care to study the relation between oral and systemic diseases.

Aged↗

Comparative induction of cytochrome P4504A in rat hepatocyte culture by the peroxisome proliferators, bifonazole and clofibrate.

1. The influence of imidazole and triazole antifungal drugs on cytochrome P450 levels in male Wistar primary rat hepatocyte culture for 70 h has been investigated and compared with clofibrate. 2. Bifonazole, clotrimazole, geniconazole clofibrate induced total P450 in hepatocytes, whereas itraconazole, miconazole and UK-47,265 did not. 3. When the CYP4A subfamily was examined, only bifonazole and clofibrate induced CYP4A as assessed by both Western blot analysis and the 11- and 12-hydroxylation of lauric acid. 4. By analysis of concentration-response curves in hepatocyte culture, bifonazole was 160 and 40 times more potent than clofibrate for induction of the 11- and 12-hydroxylation of lauric acid respectively. 5. Taken collectively, our data have identified bifonazole as a relatively potent, non-carboxylate inducer of CYP4A and the mechanism of induction and specificity of this azole is discussed.

Animals↗

Induction of cytochrome P4504A by the peroxisome proliferator perfluoro-n-octanoic acid.

The influence of a single dose of the peroxisome proliferator, perfluoro-n-octanoic acid (PFOA) on hepatic and renal mixed-function oxidase activities has been examined in rats. Peroxisome proliferation was confirmed by increases in peroxisomal palmitoyl-CoA oxidation and carnitine acetyl transferase activity, particularly in liver. The liver was also more susceptible than the kidney to PFOA-dependent induction of the 12-hydroxylation of lauric acid, suggesting induction of the CYP4A sub-family. This was further confirmed by Western blot analyses, wherein an anti-CYP4A1 antibody revealed a substantial PFOA-dependent induction of CYP4A1 in a pattern similar to that observed for the classical peroxisome proliferator, clofibrate. In addition, using a cDNA probe to CYP4A1 in Northern blot analysis, PFOA treatment resulted in a marked increase in the steady state level of CYP4A1 mRNA, again more extensively in liver than in kidney. Taken collectively, our data provide compelling evidence that PFOA, like other peroxisome proliferators, is also an inducer of the CYP4A subfamily.

Animals↗

Induction of the CYP4A subfamily by perfluorodecanoic acid: the rat and the guinea pig as susceptible and non-susceptible species.

Male Wistar rats and male Duncan Hartley guinea pigs were treated with one i.p. dose of perfluorodecanoic acid (PFDA) resulting in pronounced hepatomegaly in the rat but not the guinea pig. PFDA treatment also resulted in a 4-fold induction of lauric acid 12-hydroxylase activity in the rat but not the guinea pig, indicating induction of the CYP4A subfamily of isoenzymes. Consistent with this latter conclusion, Western blot analysis of rat liver microsomes using an antibody to CYP4A1 and Northern blot analysis of RNA extracts using a CYP4A1 cDNA probe, revealed PFDA-dependent induction of the CYP4A subfamily in the rat but not the guinea pig. Taken collectively, our data has demonstrated that PFDA, like other peroxisome proliferators, is also a CYP4A inducer and conforms to the well-documented species specificity in induction for this class of compound.

Animals↗

Behavioral response of host-seeking mosquitoes (Diptera: Culicidae) to insecticide-impregnated bed netting: a new approach to insecticide bioassays.

The response of Anopheles gambiae Giles s.s and Culex quinquefasciatus Say to insecticide-treated netting in a wind tunnel permeated with guinea pig odors was recorded on videotape. With no insecticide present, mosquitoes spent 99% of the time on the netting, either at rest or occasionally walking across it. On nylon netting, permethrin at 50, 400, and 1,000 mg m-2 irritated the mosquitoes, causing them to spend significantly more time away from the netting and relatively more time walking than at rest when they were on the netting. These effects increased with dose, but the total contact time was always enough to cause 100% mortality. At the two highest doses, knockdown occurred before the end of the 10-min observation period. A wash-resistant formulation of permethrin (ICI patent) reduced irritancy without affecting mortality or knockdown. A mixture of pirimiphos-methyl and permethrin also was less irritating than permethrin alone. Pirimiphos-methyl at 400 mg m-2 was the least irritating of all treatments tested. Lambda-cyhalothrin at 2.5, 6, and 25 mg m-2 was less irritating than permethrin, even though the doses of lambda-cyhalothrin used were far more toxic than the permethrin doses as measured by LT50. Cotton netting significantly reduced the toxicity and irritancy of the permethrin treatments. Cx. quinquefasciatus was less irritated by permethrin but more irritated by lambda-cyhalothrin, than was An. gambiae. Our study indicated that mosquitoes are so strongly attracted to a host protected by netting, they will tolerate relatively high doses of irritating insecticides long enough to pick up lethal doses.

Animals↗