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Biomedical subjects

B Alexander

Publications and source records attributed to B Alexander.

At least 19 recordsLinked to original sources
PubMed1995

Transformation of astrocytes in transgenic mice expressing SV40 T antigen under the transcriptional control of the glial fibrillary acidic protein promoter.

There are many animal models of glioma, but few that represent the biology of low-grade tumors and allow the study of the genetic mechanisms of glial oncogenesis. We report the in vivo transformation of astrocytic cells in transgenic mice by the SV40 T antigen under the control of the 5'-flanking sequence of the murine glial fibrillary acidic protein (GFAP) gene. High levels of T antigen expression were detectable in a tissue distribution that mirrored the normal expression of GFAP. This was associated with a consistent phenotype in the founder mice. Diffuse proliferation occurred in cells of the periventricular subependymal zone with diffuse invasion into the brain parenchyma, leading to death by 19-30 days postnatally. Transformed cells exhibited secondary structuring, a typical histopathological feature of human astrocytomas. Early passage cultures of these cells expressed GFAP in vitro and were transformed on the basis of tumor formation after transplantation into nude mice. These results demonstrate the susceptibility of periventricular astrocytic cells in the immature brain to malignant transformation. Furthermore, this study demonstrates the potential of the transgenic approach for the in vivo determination of genetic events involved in astrocyte transformation and for the development of novel models of astrocytoma.

Animals↗
PubMed1995

The cost of comprehensive preventive medical services for adolescents.

OBJECTIVES: To address the need for clinical preventive services for 11- to 21-year-old males and females and provide cost estimates for those services under a fee-for-service system. Preventive services include screening, health promotion, and immunizations. DESIGN: The prevalence of adolescent morbidities was derived from national surveys. Estimated costs of these morbidities were obtained from published data and adjusted for 1992 dollars using the Consumer Price Index. The estimated costs of preventive services for adolescents under a fee-for-service system were derived from a 1993 survey of nine Blue Cross and Blue Shield plans and four insurance companies. MAIN OUTCOME MEASURES: The cost of adolescent morbidities includes only direct medical costs for a single year and excludes long-term and indirect costs. The cost of clinical preventive services is calculated at 100% participation levels. RESULTS: Each year, an estimated $33.5 billion is spent on medical treatment for select adolescent morbidities, approximately $859 per adolescent per year; this is a conservative estimate. The average cost of clinical preventive services per adolescent per year would be approximately $130 in a fee-for-service system, although these are not entirely "new" costs because payers already incur screening costs for some conditions. CONCLUSION: The cost-effectiveness of clinical interventions for various health risk behaviors among adolescents is unknown. It appears that preventive interventions would have to eliminate 15% of adolescent morbidities overall to break even in economic terms.

Accidents, Traffic↗
PubMed1995

Phlebotomine sandflies associated with a focus of cutaneous leishmaniasis in Valle del Cauca, Colombia.

A survey was made of the phlebotomine sandfly fauna of La Guaira, a village with coffee plantations near Cali, Colombia, from which cases of American cutaneous leishmaniasis had been reported due to Leishmania (Viannia) panamensis and Le. (V.) braziliensis. Among six species of sandfly collected on human bait, Lutzomyia youngi was most important in terms of biting nuisance. Lu.columbiana, Lu.lichyi and Lu.scorzai as well as Lu.youngi adults occurred throughout the year. Sandfly man-biting activity occurred throughout the night and was highest within 2 h of sunset. Despite its abundance in nocturnal samples, Lu.youngi was rarely taken in diurnal resting site collections. In contrast, Lu.lichyi was collected on tree-trunks during the day in large numbers and was the only species biting in daylight. The implications of these and other findings for leishmaniasis control measures in La Guaira are considered.

Animals↗
PubMed1995

Evaluation of deltamethrin-impregnated bednets and curtains against phlebotomine sandflies in Valle del Cauca, Colombia.

The effectiveness of bednets and curtains (nylon mesh 64 per cm2) impregnated with deltamethrin at 26 mg a.i./m2 in reducing the biting nuisance caused by three phlebotomine sandfly species: Lutzomyia columbiana, Lu.lichyi and the predominant Lu.youngi (Diptera: Psychodidae), was evaluated at La Guaira, a rural settlement in Valle de Cauca near Cali, Colombia. Pairs of volunteers collected sandflies under impregnated bednets, in rooms protected by impregnated curtains or in unprotected rooms in a randomized matched design. Collections were made in three houses per night on three consecutive nights, so that each house was sampled under each of the three treatments. This routine was repeated at 2-week intervals for 6 months. There was no significant difference between the overall numbers of sandflies collected in rooms with or without impregnated curtains. Only 0.14 sandflies/man-hour were caught on human bait under impregnated bednets, significantly fewer than the numbers collected on human bait outside the nets in the same room (1.91) or in unprotected rooms (3.29). In a second set of experiments carried out in La Guaira and the neighbouring community of Jiguales, the effect of deltamethrin impregnation was evaluated by comparing numbers of sandflies collected on human bait under treated and untreated nets. Significantly fewer were collected under the impregnated nets (0.25 v. 0.69/man-hour). Wild-caught female Lu.youngi exposed to treated netting for 2 min in the laboratory all died with 24 h. The impact of deltamethrin-impregnated bednets was considered to be useful against Lu.youngi and other potential vectors of leishmaniasis in such communities.

Animals↗
PubMed1995

A review of bartonellosis in Ecuador and Colombia.

A review of the literature regarding bartonellosis or Carrion's disease in Colombia and Ecuador is presented, together with observations made by the author in areas of both countries from which the disease has been recorded. There is evidence from pre-Columbian artifacts that verruga peruana, the cutaneous form of the disease, was present in Ecuador at least 1,000 years prior to the arrival of Europeans. These artifacts were discovered in the coastal province of Manabi, a low-lying area very different from the high Andean valleys of Peru with which bartonellosis is normally associated. Most of the cases recorded in recent years from this coastal area. The disease does not appear to have occurred in Colombia before the 1930s and only one case has been reported during the past 40 years. The possibility of many more subclinical cases being present in both Ecuador and Colombia is discussed, together with the possibility that the acquired immunodeficiency syndrome epidemic will reveal a higher prevalence among the inhabitants of endemic areas than previously suspected. Although the suspected vector of Bartonella bacilliformis, the sand fly Lutzomyia verrucarum, has not been recorded from Ecuador or Colombia, related species are present in endemic areas and may be involved in transmission.

Bartonella Infections↗
PubMed1993

Effect of changes in rate of vascular perfusion on release of substances into the effluent from the brain of the rabbit.

The cerebral vasculature of five anaesthetised rabbits was perfused with a perfluorocarbon emulsion via the internal carotid arteries, and the effluent from the jugular veins analysed for ATP, substance P (SP), endothelin (ET) and arginine vasopressin (AVP). Viability of the preparation was monitored periodically by the electrocorticogram, oxygen uptake, carbon dioxide release and perfusion pressure. The basal rate of infusion of 7.8 +/- 1.26 ml.min-1 resulted in an infusion pressure of 114.0 +/- 22.1 mmHg and when increased first to 10.5 +/- 1.53 ml.min-1 and then to 15.0 +/- 1.87 ml.min-1, rose to 163.0 +/- 33.1 mmHg and to 170.0 +/- 33.2 mmHg, respectively. Between each 3-min period of increased flow the rate was returned to the basal rate for 6 min. Of the four vasoactive substances, ET was released at the largest rate during the initial period of basal flow, 65.3 +/- 10.7 pmol.min-1. This increased further when the infusion rate rose to 10.5 ml.min-1, but was significant only when the infusion rate was increased to 15.0 ml.min-1. ATP was released at 41.5 +/- 11.5 pmol.min-1 during the initial period of basal flow. Its release significantly increased with flow and peaked at 15.0 ml.min-1. SP was released at a rate of 13.3 +/- 8.2 pmol.min-1 during the initial period of basal flow. Its rate of release was increased significantly the second time the flow was increased to 10.5 ml.min-1 and increased even further when the flow was increased to 15.0 ml.min-1.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenosine Triphosphate↗
PubMed1993

Electron-immunocytochemistry of peptides in endothelial cells of rabbit cerebral vessels following perfusion with a perfluorocarbon emulsion.

This study describes the localization of endothelin-1-, vasopressin- and substance P-like immunoreactivity in a subpopulation of endothelial cells of the basilar and posterior communicating arteries of the (i) normal rabbit brains and (ii) rabbit brains perfused with a perfluorocarbon emulsion (PFC). Following perfusion with the PFC at increased flow the endothelial cell ultrastructure appeared normal, although there was a decrease of immunoreactivity to these peptides. This suggests that these peptides may be involved in endothelial control of blood flow in cerebral vessels.

Animals↗
PubMed1992

Tumor-associated karyotypic lesions coselected with in vitro macrophage differentiation.

Several cytogenetic lesions in chromosomes 2, 5, 12, and 16 have been repeatedly coselected with in vitro macrophage differentiation in a clonal murine thymic tumor cell line. Parental-type subclones, which show an extremely immature hemopoietic phenotype, do not carry the aberrations. The frequency of the stable differentiated variants is elevated by 5-azacytidine and bromodeoxyuridine, consistent with chromosome breakage being responsible for the phenotype. The frequency is also raised by dexamethasone. Since variants are 300-3,000-fold more resistant to dexamethasone than parental clones, we interpret this to be largely due to selection. Three of the lesions, on chromosome 2, match those previously described as associated specifically with in vivo-generated murine myeloid tumors, induced by X irradiation and corticosteroid treatment. Several implications follow from these observations. (1) In vitro differentiation in clonal tumor cell lines can be used to select for tumor-associated lesions. This should allow genetic and molecular analysis of the chromosome 2 lesions and of others that may pinpoint genes critical to macrophage differentiation and transformation. (2) Myeloid and lymphoid tumors that occur in response to X irradiation may diverge from a common initiating tumor. (3) The hemopoietic lineage switch phenomenon, previously described by several authors, may be caused by similar or identical chromosome aberrations.

Abelson murine leukemia virus↗
PubMed1992

An isolated dual-perfused rabbit liver preparation for the study of hepatic blood flow regulation.

An original, isolated dual-perfused rabbit liver preparation was developed for investigations into mechanisms that control the hepatic vascular tone. The hepatic artery (HA) and portal vein (PV) were perfused at constant flows of 0.16 +/- 0.01 and 0.64 +/- 0.05 mL/g/min (n = 5), respectively. Responses of the hepatic arterial and portal venous vascular beds to noradrenaline (NA) were measured as changes in perfusion pressure. Noradrenaline injected directly into the hepatic artery and portal vein produced dose-dependent increases in pressure in the respective vascular beds, the maximum response in the hepatic arterial bed being two to three times greater than that in the portal venous bed. A restricted transmission of vasoconstrictor stimulus between the intrahepatic portal venous and hepatic arterial vasculature was demonstrated. The results demonstrate the suitability of the dual-perfused rabbit liver model for detailed studies of the control of hepatic vascular tone.

Animals↗
PubMed1992

An investigation of the composite resin/porcelain interface.

Failures at composite resin/porcelain interfaces under shear-like loading were examined. Porcelain surfaces were treated with hydrofluoric acid and/or one of two silane coupling agents, using two different composite resin cements. The results showed that after seven days storage, bond strengths of specimens which had undergone porcelain surface treatment were greater than the cohesive strength of the porcelain itself, resulting in brittle fracture of the porcelain. The diluted restorative composite resin performed as well as the commercial composite resin cement. Silane pretreatment of porcelain was important as the bond strength of etched/silane primed specimens was significantly higher than the etched only specimens. However, one primer appeared to be more efficient than the other in bond promotion. Some explanations for the differences in bond strengths are offered.

Acid Etching, Dental↗
PubMed1991

Central nervous system action of endothelin-3 to inhibit water drinking in the rat.

Endothelin-3, a vasoconstrictor peptide produced not only in endothelial cells but also within the brain interstitium in magnocellular neurons of the hypothalamo-neurohypophysial system, exerted significant, dose-related, inhibitory effects on water intake when administered into the third cerebroventricle of rats exposed to exogenous and endogenous stimuli for drinking. Passive immunoneutralization of endogenous endothelin-3 accentuated water drinking in response to angiotensin II administration suggesting a physiological role for the peptide in the central control of fluid and electrolyte homeostasis.

Angiotensin II↗
PubMed1991

Isolation and identification of Bacillus sphaericus strains pathogenic for mosquito larvae.

Three selective media for the isolation of Bacillus sphaericus have been compared. BATS medium and a formulation employing adenosine as the principal carbon source were the most effective for the recovery of spores of strain 1593. Anthranilic acid as the principal carbon source was less efficient. Eighty-four strains were isolated from mud samples using these media and were identified by computer. Identifications were confirmed for representative strains using DNA sequence homology. Most were B. sphaericus sensu stricto or members of an unnamed group. However, one strain (BSE 18) was identified as the DNA homology group IIB and this organism was found to be highly toxic toward larvae of Culex pipiens. Southern hybridization of BSE 18 DNA to a probe prepared from the cloned toxin gene from strain 1593 revealed that BSE 18 contained a typical gene for the 41.9-kDa toxin.

Animals↗
PubMed1991

Detoxification from benzodiazepines: schedules and strategies.

Management of benzodiazepine (BZD) tolerance is divided into low- and high-dose withdrawal. Low-dose withdrawal includes patients who have received manufacturer-recommended doses of BZD on a daily basis for longer than 1 month. Gradual tapering of the BZD over 4 weeks on an outpatient basis is suggested. High-dose withdrawal includes patients who have been ingesting doses of BZD greater than the equivalent of diazepam 40 mg/d for longer than 8 months. It is recommended that the patients be tolerance tested with diazepam and, if tolerant, tapered off medication as inpatients at a rate of 10% per day. Triazolobenzodiazepines may be exceptions to these recommendations. Alprazolam should be titrated at a rate of 0.5 mg three times a day regardless of whether the patient is being tapered for low- or high-dose withdrawal.

Anti-Anxiety Agents↗
PubMed1991

Nitric oxide is the mediator of ATP-induced dilatation of the rabbit hepatic arterial vascular bed.

1. Livers of 10 New Zealand White rabbits were perfused in vitro with Krebs-Bülbring buffer via the hepatic artery (HA) and portal vein (PV) at constant flows of 23 +/- 1 and 77 +/- 1 ml min-1 100 g-1 respectively. The tone of the preparation was raised with noradrenaline (concentration: 10 microM). 2. Dose-response curves for the vasodilatation produced by adenosine 5'-triphosphate (ATP), acetylcholine (ACh), adenosine, and sodium nitroprusside (SNP) were obtained following injection into the HA supply. Injections were then repeated in the presence of the L-arginine to nitric oxide pathway inhibitors N-monomethyl-L-arginine (L-NMMA, n = 6) and N-nitro-L-arginine methyl ester (L-NAME, n = 4) at concentrations of 30 microM and 100 microM for each inhibitor. 3. Both L-NMMA and L-NAME antagonized the responses to ATP and ACh; L-NAME was 2-3 times more potent than L-NMMA as an inhibitor of these endothelium-dependent vasodilatations. Neither L-NMMA nor L-NAME attenuated responses of the endothelium-independent vasodilators, adenosine and SNP. 4. These results indicate that nitric oxide is the mediator of ATP-induced vasodilatation in the HA vascular bed of the rabbit and that the receptor responsible for the release of nitric oxide, the P2y-purinoceptor, is located predominantly on the endothelium.

Acetylcholine↗
PubMed1991

Adenosine-induced dilatation of the rabbit hepatic arterial bed is mediated by A2-purinoceptors.

1. This study was carried out in order to identify the receptor responsible for adenosine-induced dilatation of the hepatic arterial vascular bed. 2. Livers of 10 New Zealand White rabbits were perfused in vitro with Krebs-Bülbring buffer via the hepatic artery and the portal vein at constant flows of 26 and 77 ml min-1 100 g-1 liver respectively. The tone of the preparation was raised by the presence of noradrenaline in the perfusate (concentration: 10(-5) M). 3. Dose-response curves for adenosine and its analogues 5'-N-ethyl-carboxamido-adenosine (NECA), the 2-substituted NECA analogue CGS 21680C, and R- and S-N6-phenyl-isopropyl-adenosine (R- and S-PIA) were obtained after their injection into the hepatic arterial supply. 4. The order of vasodilator potency of these agents was: NECA greater than CGS 21680C greater than adenosine greater than R-PIA greater than S-PIA. Their potency, expressed relative to that of adenosine, was in the approximate ratio 10:3:1:0.3:0.1, consistent with that resulting from activation of P1-purinoceptors of the A2 sub-type (which mediate vasodilatation due to adenosine). 5. The P1-purinoceptor antagonist 8-phenyltheophylline (10(-5) M) caused significant attenuation of the vasodilatation to adenosine and analogues. 6. It is concluded that adenosine-induced dilatation of the hepatic arterial vascular bed is mediated by P1-purinoceptors of the A2 sub-type.

Acetylcholine↗
PubMed1991

Characterization of P2X- and P2Y-purinoceptors in the rabbit hepatic arterial vasculature.

1. Responses to adenosine 5'-triphosphate (ATP) and its agonists were studied in the isolated liver of the rabbit dually perfused through the hepatic artery and the portal vein. 2. In the hepatic arterial vascular bed at basal tone, ATP and its agonists elicited vasoconstrictor responses with the rank order of potency alpha,beta-methylene ATP greater than 2-methylthio ATP greater than ATP, consistent with their action at the P2X-purinoceptor. 3. When tone was raised with noradrenaline (10(-5) M), vasodilator responses were produced with ATP and 2-methylthio ATP; alpha,beta-methylene ATP produced only further constriction. The rank order of vasodilator potency was 2-methylthio ATP greater than ATP much greater than alpha,beta-methylene ATP, consistent with their action at the P2Y-purinoceptor. 4. Methylene blue (10(-5) M) antagonized vasodilator responses to acetylcholine and ATP, but not those to adenosine or sodium nitroprusside. Addition of 8-phenyltheophylline (10(-5) M) antagonized responses to adenosine but not those to sodium nitroprusside. Responses to ATP remaining after antagonism with methylene blue were not further antagonized by 8-phenyltheophylline. 5. These results present evidence for discrete P2X- and P2Y-purinoceptors in the rabbit hepatic arterial bed which mediate vasoconstrictor and vasodilator responses respectively. 6. Vasodilatation produced by ATP was entirely due to direct action at the P2Y-purinoceptor, and not at a P1-purinoceptor following breakdown to adenosine. The antagonism of these responses by methylene blue is consistent with the view that vasodilatation by ATP takes place largely via endothelial P2Y-purinoceptors that lead to release of endothelium-derived relaxing factor. However, we cannot exclude the possibility that P2y-purinoceptors located on the vascular smooth muscle play a contributory role in ATP-induced vasodilatation.

Acetylcholine↗