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Biomedical subjects

J M Bell

Publications and source records attributed to J M Bell.

At least 37 records · Page 2Linked to original sources
PubMed1997

Sequelae of parenteral domoic acid administration in rats: comparison of effects on different metabolic markers in brain.

Parenterally administered domoic acid, a structural analog of the excitatory amino acids glutamic acid and kainic acid, has specific effects on brain histology in rats, as measured using different anatomic markers. Domoic acid-induced convulsions affects limbic structures such as hippocampus and entorhinal cortex, and different anatomic markers can detect these neurotoxic effects to varying degrees. Here we report effects of domoic acid administration on quantitative indicators of brain metabolism and gliosis. Domoic acid, 2.25 mg/kg i.p., caused stereotyped behavior and convulsions in approximately 60% of rats which received it. Six to eight days after domoic acid or vehicle administration, the animals were processed to measure regional brain incorporation of the long-chain fatty acids [1-(14)C]arachidonic acid ([14C]AA) and [9,10-(3)H]palmitic acid ([3H]PA), or regional cerebral glucose utilization (rCMRglc) using 2-[1-(14)C]deoxy-D-glucose, by quantitative autoradiography. Others rats were processed to measure brain glial fibrillary acidic protein (GFAP) by enzyme-linked immunosorbent assay. Domoic acid increased GFAP in the anterior portion of cerebral cortex, the caudate putamen and thalamus compared with vehicle. However, in rats that convulsed after domoic acid GFAP was significantly increased throughout the cerebral cortex, as well as in the hippocampus, septum, caudate putamen, and thalamus. Domoic acid, in the absence of convulsions, decreased relative [14C]AA incorporation in the claustrum and pyramidal cell layer of the hippocampus compared with vehicle-injected controls. In the presence of convulsions, relative [14C]AA incorporation was decreased in hippocampus regions CA1 and CA2. Uptake of [3H]PA into brain was unaffected. Relative rCMRglc decreased in entorhinal cortex following domoic acid administration with or without convulsions. These results suggest that acute domoic acid exposure affects discrete brain circuits by inducing convulsions, and that domoic acid-induced convulsions cause chronic effects on brain function that are reflected in altered fatty acid metabolism and gliosis.

Animals↗
PubMed1997

Antimicrobial resistance testing of Helicobacter pylori: a comparison of Etest and disk diffusion methods.

Routine antimicrobial resistance testing of Helicobacter pylori is more commonly performed since the correlation between metronidazole resistance and failure to eradicate using this drug, has been made. While resistance testing of H. pylori by Etest is simple to perform, it is expensive compared to disk diffusion methods. In this study the Etest was compared with a modified Kirby-Bauer disk diffusion (NCCLS) method for routine resistance screening of H. pylori. Fifty one pre-treatment isolates were tested against amoxycillin, metronidazole, tetracycline and erythromycin by both Etest and disk diffusion using NCCLS guideline strength disks. Clarithromycin was tested by Etest only. Nitroimidazole and macrolide resistance were detected using the modified Kirby-Bauer disk diffusion method which correlated with Etest minimum inhibitory concentration (MIC). Resistance rates were 49% for metronidazole and 8% for clarithromycin. Cross resistance occurs with macrolides against H. pylori and allows testing of erythromycin to predict resistance to clarithromycin. The very low MICs obtained with H. pylori against amoxycillin and tetracycline require the use of Etest or lower strength disk methods to be used.

Amoxicillin↗
PubMed1997

Incorporation of [U-14C]palmitate into rat brain: effect of an inhibitor of beta-oxidation.

We examined the effect of a clinically therapeutic dose of methyl 2-tetradecylglycidate (McN-3716, methyl palmoxirate, MEP) (2.5 mg/kg), an inhibitor of beta-oxidation of fatty acids, on incorporation of radiolabeled palmitic acid ([U-14C]PAM) from plasma into brain lipids of awake rats. Four hour pretreatment with 2.5 mg/kg MEP significantly increased the incorporation of [U-14C]PAM into brain lipids and substantially decreased aqueous radiolabeled metabolites in brain that can constitute unwanted background signal when analyzed by quantitative autoradiography. MEP treatment increased the lipid to aqueous background radioactivity from 0.8 to 3.0. Net rate of incorporation, k*, was significantly increased (60%) by MEP and was attributed to incorporation of [U-14C]PAM into phospholipid and triglyceride brain compartments. MEP treatment did not affect the size of the fatty acyl-CoA pool or the distribution of the various molecular acyl-CoA species. These results indicate that MEP, at a dose of 2.5 mg/kg (per os), can be used to increase incorporation of [1-(11C)]PAM for studying brain lipid metabolism in humans by positron emission tomography (PET).

Acyl Coenzyme A↗
PubMed1996

Lithium decreases turnover of arachidonate in several brain phospholipids.

In vivo rates of incorporation and turnover of palmitate and arachidonate in brain phospholipids were measured in awake rats treated chronically with lithium, following intravenous infusion of radiolabeled palmitate and arachidonate, respectively. Chronic lithium, at a brain level considered to be therapeutic in humans, decreased turnover of arachidonate within brain phosphatidylinositol, phosphatidylcholine and phosphatidylethanolamine by up to 80% (P < 0.001). In contrast, lithium had a minimal effect on turnover of palmitate, causing only a 26% reduction in turnover in phosphatidylcholine (P < 0.01). These results suggest that a major therapeutic effect of lithium is to reduce turnover specifically of arachidonate, possibly by inhibiting phospholipase A2 involved in signal transduction. The effect may be secondary to the known action of lithium on the phosphoinositide cycle, by inhibiting the activity of inositol monophosphatase.

Animals↗
PubMed1996

Drug-resistant Streptococcus pneumoniae: the beginning of the end for many antibiotics? Australian Group on Antimicrobial Resistance (AGAR)

OBJECTIVE: To determine the levels of antibiotic resistance in Streptococcus pneumoniae in Australia. DESIGN: Prospective, Australia-wide, laboratory-based survey. SETTING: 27 hospital and private laboratories around Australia, from January 1994 to August 1995. SUBJECTS: First 100 patients with clinically significant isolates of S. pneumoniae at each laboratory. OUTCOME MEASURES: Resistance to penicillin (determined from penicillin minimum inhibitory concentration [MIC] measured by the Etest), erythromycin, trimethoprim-sulfamethoxazole, tetracycline, chloramphenicol, cefotaxime and ceftriaxone. RESULTS: A total of 2396 isolates were tested (including 537 invasive isolates and 740 from children). Penicillin resistance was seen in 161 isolates (6.7%), including 17 with high level resistance. Penicillin resistance rates were significantly lower in invasive than in non-invasive strains (3.7% versus 7.6%; odds ratio [OR], 0.47; 95% confidence interval [CI], 0.28-0.77; P = 0.001). There was no significant difference in penicillin resistance rates between children (< 15 years) and adults (7.3% versus 6.5%; OR, 1.14; 95% CI, 0.80-1.63; P = 0.47). Resistance rates were higher for most other antibiotics than for penicillin (chloramphenicol, 6%; erythromycin, 11%; tetracycline, 15%; and trimethoprim-sulfamethoxazole, 42%). No high level resistance was seen to third generation cephalosporins, but 17 of 109 penicillin-resistant isolates tested (16%) displayed intermediate resistance to cefotaxime. Rates of antibiotic resistance varied between States, with the lowest rates in Tasmania. CONCLUSIONS: Antibiotic resistance levels in S. pneumoniae are increasing in Australia and high level penicillin resistance is being encountered for the first time (including in invasive strains). This will lead to an increasing number of therapeutic dilemmas and possible therapeutic failures, especially important in meningitis.

Adolescent↗
PubMed1996

Telomeric associations in the progression of chromosome aberrations in pediatric solid tumors.

Telomeric association (tas) is a cytogenetic phenomenon in which chromosome ends fuse to form dicentric, multicentric, and ring chromosomes. We observed clonal tas in six pediatric solid tumors of various types and histological grades studied using short-term in situ culture and G-banding techniques. These tumors included a neurilemoma, an undifferentiated (embryonal) sarcoma of the liver (UESL), two anaplastic astrocytomas (AA), one case of glioblastoma multiforme (GBM), and a neuroblastoma (NB) of the kidney. Cytogenetic data from all six tumors demonstrated multiple numerical and structural aberrations including tas. The tas appeared to be a secondary aberration in these tumors, however, it was possible to follow the progression of the telomeric chromosome aberrations in several cases. In all but one case (UESL) the loss of chromosome segments occurred. Tas of 11p was observed in three of the six tumors, two of which showed the subsequent loss of 11p (AA and AB). In addition, tas of 4p was seen in three tumors, two of which showed clonal tas of 4p with 22q. Tas of 10p, 21p, and 22q were all observed in at least two different tumors. The clonal telomeric fusions of 4p with 22q, recurring tas of 11p, and the subsequent loss of the short arm of 11 demonstrated here, suggests that some chromosome regions are subject to nonrandom instability and sometimes loss.

Adolescent↗
PubMed1996

Preferential in vivo incorporation of [3H]arachidonic acid from blood in rat brain synaptosomal fractions before and after cholinergic stimulation.

Awake adult male rats were infused intravenously with [3H]arachidonic acid for 5 min, with or without prior administration of an M1 cholinergic agonist, arecoline (15 mg/kg i.p.). Methylatropine was also administered (4 mg/kg s.c.) to control and arecoline-treated animals. At 15 min postinfusion, the animals were killed, brains were removed and frozen, and subcellular fractions were obtained from homogenates of whole brain. Total radioactivity and radioactivity in various lipid classes were determined for each fraction following normalization for exposure by use of a unidirectional incorporation coefficient, k*brain. In control animals, incorporation was greatest in synaptosomal and microsomal fractions, accounting for 50 and 30% of total label incorporated into membrane lipids, respectively. Arecoline increased incorporation in these two fractions by up to 400% but did not increase incorporation into the myelin, mitochondrial, or cytosolic fractions. Of the incorporated radioactivity, 50-80% was in phospholipid in microsomal and synaptosomal fractions, indicating that phospholipid is the major lipid affected by cholinergic stimulation. These results demonstrate that plasma [3H]arachidonic acid is preferentially incorporated into phospholipids of synaptosomal and microsomal fractions of rat brain. Cholinergic stimulation increases incorporation into these fractions, likely by activation of phospholipase A2 and/or C in association with acyltransferase activity, Thus, intravenously infused radiolabeled arachidonic acid can be used to examine synapse-mediated changes in brain phospholipid metabolism in vivo.

Animals↗
PubMed1996

Oxygen concentration influences proton pump inhibitor activity against Helicobacter pylori in vitro.

Omeprazole and lansoprazole are proton pump inhibitors that have shown activity against Helicobacter pylori and other Helicobacter species when tested by agar dilution. Lansoprazole was more active against H. pylori than was omeprazole, and the activity was independent of urease production. Disk susceptibility tests and agar dilution MIC determinations were performed to investigate the effects of incubation under different sets of atmospheric conditions on H. pylori inhibition. Oxygen concentration was found to influence proton pump inhibitor activity in vitro, with higher concentrations leading to greater susceptibility. The method of testing is important in determining the anti-Helicobacter activity of proton pump inhibitors.

2-Pyridinylmethylsulfinylbenzimidazoles↗
PubMed1996

Postexercise heart rates and pulse palpation as a means of determining exercising intensity in an aerobic dance class.

OBJECTIVE: To establish the accuracy of the traditional method of measuring the intensity of exercise in aerobic dance classes, that is, intermittent pulse palpation performed during a brief cessation of activity. METHODS: A short wave telemetry system was used to record heart rates during a class in a group of 12 healthy women aged 26 (SD 6) years. Subjects palpated their pulses for 10 s following high and low intensity exercise [78(8)% and 69(9)% of mean predicted maximum heart rate respectively]. Recorded exercising heart rates, averaged over 60 s preceding pulse palpation [ExHR(rec)], were compared with the recorded postexercise heart rates averaged over the 10 s palpation period [PostExHR(rec)] and with the palpated counts (PalpHR). Differences were assessed using Student's t test and Wilcoxon signed rank test. RESULTS: Differences between ExHR(rec) and PostExHR(rec) following high and low intensity exercise [3(6) beats.min-1 and 5(7) beats.min-1 respectively] were not significant. However, the wide variation between subjects means that a postexercise heart rate is unreliable as a measure of individual exercise intensity. PalpHR was significantly lower than ExHR(rec) (P < 0.01). Every individually palpated count underestimated the exercising heart rate (range 9 to 95 beats.min-1). CONCLUSIONS: While postexercise heart rate adequately represents the exercise heart rate for a group, the individual variation is too wide for this to be a useful measurement.

Adult↗
PubMed1996

Ca(2+)-dependent mitogen-activated protein kinase activation in spontaneously hypertensive rat vascular smooth muscle defines a hypertensive signal transduction phenotype.

The mechanisms responsible for altered vascular smooth muscle cell (VSMC) function in hypertension remain unknown. In the spontaneously hypertensive rat (SHR) model of genetic hypertension, there are multiple abnormalities in VSMC function, including increased growth, Na(+)-H+ exchange, and increased signal transduction by protein kinase C. The family of kinases termed mitogen-activated protein (MAP) kinases has recently been shown to be essential mediators of growth factor signal transduction. In the present study, alterations in MAP kinase function in the hypertensive phenotype were investigated using early-passage SHR and Wistar-Kyoto (WKY) VSMCs stimulated with angiotensin II (Ang II, 100 nmol/L) or platelet-derived growth factor-BB (PDGF-BB, 10 ng/mL). MAP kinase activity was measured by in-gel kinase assays and Western blot analysis. Two differences between SHR and WKY rats were observed for Ang II-mediated MAP kinase activation: (1) Inactivation after Ang II stimulation was more rapid in SHR than WKY VSMCs. (2) Activity in SHR VSMCs showed a greater dependence on Ca2+ mobilization, since chelation of intracellular Ca2+ with BAPTA inhibited maximal activity by 95% in SHR VSMCs but by only 50% in WKY VSMCs. In contrast to the results with Ang II, no differences in PDGF-stimulated MAP kinase activity were observed. These findings establish activation of MAP kinase by Ang II as a feature that distinguishes SHR VSMCs from WKY VSMCs and suggest that differences in regulation of MAP kinase signaling may alter cellular events that are increased in the SHR genetic model of hypertension.

Angiotensin II↗
PubMed1995

Nonrandom chromosome breakpoints at Xq26 and 2q33 characterize cemento-ossifying fibromas of the orbit.

BACKGROUND: Cytogenetic reports of histologically benign fibroosseous lesions are rare, with only nine previously reported cases. None of these previous studies revealed consistent numerical or structural chromosome aberrations, and to the authors' knowledge, no karyotypic abnormalities in cemento-ossifying fibromas of the orbit have been reported. METHODS: Short term in situ culture and Giesma-band chromosome methods were used to analyze three cementifying fibromas of the orbit: one from a 13-year-old African American male, one from a 14-year-old Hispanic male, and one from a 17-year-old white male. RESULTS: Cytogenetic findings in these three cases revealed the presence of identical chromosomal breakpoints occurring in all three tumors at bands Xq26 and 2q33. Two of the tumors showed an identical t(X;2)(q26;q33) reciprocal translocation as the sole abnormality. The third tumor revealed an interstitial insertion of bands 2q24.2q33 into Xq26 as the sole abnormality. CONCLUSIONS: The authors described new nonrandom breakpoints in fibroosseous lesions of the orbit, which can result from at least two different types of structural chromosomal aberrations. The identification of recurring breakpoints at Xq26 and 2q33 provides a new cytogenetic tumor marker for the identification of this tumor subtype. The sublocalization of breakpoints in this tumor should provide important information for the precise localization and characterization of genes involved in the histiogenesis of these lesions.

Adolescent↗
PubMed1995

Gastric teratoma with intramural extension.

Gastric teratoma is an extremely rare neoplasm which accounts for less than two percent of all teratomas. Unlike other teratomas, gastric teratomas are all benign and predominantly occur in males. As gastric teratomas generally present as a palpable abdominal mass, more aggressive solid masses of childhood must be excluded. In this case, CT imaging delineates both cystic and fatty components characteristic of teratoma and displays the rare gastric origin of the lesion.

Humans↗
PubMed1995

Low-carbohydrate diet alters intracellular glucose metabolism but not overall glucose disposal in exercise-trained subjects.

Dietary composition has been strongly implicated as an important determinant of in vivo insulin sensitivity. However, the metabolic alterations associated with extreme changes in diet have not been well described. We compared glucose metabolism after a standard diet ([STD] 35% fat, 51% carbohydrate, and 14% protein) with the effects of a 3-week adaptation to a low-carbohydrate, high-fat diet ([LCD] 75% fat, 8% carbohydrate, and 17% protein). Ten healthy men were studied using the euglycemic clamp technique, indirect calorimetry, and percutaneous vastus lateralis muscle biopsies for analysis of glycogen synthase (GS) and pyruvate dehydrogenase (PDH) activities in the basal and insulin-stimulated states. Insulin-stimulated glucose disposal was unchanged (STD 46.1 +/- 4.3 v LCD 46.0 +/- 4.3 mumol/kg.min, P = NS), but marked alterations in the routes of glucose disposal were noted. Insulin-stimulated glucose oxidation (Gox) was markedly reduced following LCD (STD 18.6 +/- 1.9 v LCD 8.23 +/- 1.9 mumol/kg.min, P = .0001), and nonoxidative glucose metabolism (Gnox) was enhanced by LCD (STD 24.9 +/- 0.9 v LCD 38.9 +/- 4.3 mumol/kg.min, P = .03). Following LCD, both the total and active forms of PDH (PDHt and PDHa) were significantly depressed. After LCD, GS activates (FV0.1, %I, and A0.5) were unaffected in the basal state, but were greater than for STD (P = .004) after insulin stimulation. The apparent increase in the sensitivity of GS to activation by insulin following LCD correlated strongly with maximal O2 consumption ([VO2max] r = .97, P = .001), suggesting that physical conditioning interacted with the metabolic impact of LCD. In summary, LCD did not induce changes in net glucose disposal.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1995

Validation of a modified Kirby-Bauer disk diffusion method for metronidazole susceptibility testing of Helicobacter pylori.

Triple antimicrobial therapy that includes metronidazole has been recommended as a first-line therapy for Helicobacter pylori because it has the highest eradication rates. However, resistance in H. pylori to metronidazole has been reported worldwide and its presence may reduce the efficacy of triple therapy. Various methods for testing H. pylori against metronidazole have been used including agar dilution, disk diffusion and the Etest but there has been little standardization of methods. One hundred isolates of H. pylori from different patients were tested for susceptibility to metronidazole by agar dilution, Etest and disk diffusion (5 micrograms disk). The agar dilution results confirmed the MIC susceptibility breakpoint to be < or = 8 micrograms/ml. Using this breakpoint there was close agreement (98%) between Etest and agar dilution results. For susceptible strains, MICs by E-test were generally one twofold dilution lower. Using the error-rate bounded method, agreement between disk diffusion zone diameter and MIC was 98% for agar dilution with breakpoints of > or = 12 mm and < or = 8 micrograms/ml and 100% for Etest with breakpoints of > or = 12 mm and < or = 8 micrograms/ml. The Etest discriminated better than agar dilution between susceptible and resistant strains and was simple to perform. The disk diffusion test is a reliable and cheaper alternative to the Etest with susceptibility being a zone diameter > or = 12 mm with a 5 micrograms disk. The prevalence of metronidazole resistance in this study was 40% by Etest.

Diffusion↗
PubMed1995

A noninvasive method to measure splanchnic glucose uptake after oral glucose administration.

We have developed a noninvasive method to estimate splanchnic glucose uptake (SGU) in humans (oral glucose clamp technique [OG-CLAMP]), which combines a hyperinsulinemic clamp with an oral glucose load (oral glucose tolerance test). We validated this method in 12 nondiabetic subjects using hepatic vein catheterization (HVC) during an oral glucose tolerance test. During HVC, splanchnic blood flow increased from 1,395 +/- 64 to 1,935 +/- 109 ml/min, returning to basal after 180 min and accounted for 45 +/- 7% of SGU in lean and 19 +/- 5% in obese subjects (P < 0.05). SGU estimated during the OG-CLAMP was 22 +/- 2% of the glucose load, and this was significantly correlated (r = 0.90, P < 0.0001) with SGU (35 +/- 4%) and with first pass SGU (24 +/- 3%; r = 0.83, P < 0.001) measured during HVC. SGU was higher in obese than in lean subjects during OG-CLAMP (27 +/- 1% vs 18 +/- 3%, P < 0.01) and HVC (44 +/- 4% vs 26 +/- 5%, P < 0.05). In conclusion, SGU during the OG-CLAMP is well correlated to SGU measured during HVC. An increase in splanchnic blood flow is a major contributor to SGU in lean subjects. SGU is increased in obese subjects as measured by both methods.

Adult↗
PubMed1995

Incorporation of [1-carbon-11]palmitate in monkey brain using PET.

UNLABELLED: We determined regional incorporation coefficients (k*) of plasma [1-11C]palmitate into stable brain lipids of anesthetized monkeys with PET. METHODS: Carbon-11-palmitate was injected intravenously in untreated animals and in animals pretreated with methyl palmoxirate (MEP), an inhibitor of beta-oxidation of palmitate in the brain and periphery. Plasma radioactivity was followed, and brain radioactivity was determined at various times using PET. A least-squares method was used to fit the data to an operational equation to obtain regional values of k* and of cerebral blood volume (Vb) in individual experiments. RESULTS: MEP significantly decreased the integral of plasma [11C]CO2 following 11C-palmitate infusion. Mean values of k* in monkeys not given MEP were 4.9, 4.2, 4.9, 4.0 and 2.9 x 10(-5) ml/sec.g for the temporal, frontal, parietal and occipital cortices and white matter, respectively. With the exception of k* in white matter, which was increased by MEP, k* in the other brain regions was not significantly changed by MEP. The Vb ranged from 0.035 ml/g to 0.048 ml/g in gray matter regions and equaled 0.022 ml/g in white matter. CONCLUSION: PET can be used to determine regional incorporation coefficients of 11C-palmitate into the primate brain in vivo. Combined with MEP, 11C-palmitate could be used with PET to examine regional brain phospholipid metabolism in humans in normal and pathological conditions.

Animals↗
PubMed1994

Effect of inhibition of beta-oxidation on incorporation of [U-14C]palmitate and [1-14C]arachidonate into brain lipids.

The purpose of the present study was to determine the effect of inhibiting the mitochondrial beta-oxidation of free fatty acids on the incorporation of radiolabeled free fatty acids into brain lipids. To this end, methyl 2-tetradecylglycidate (MEP), an irreversible inhibitor of carnitine palmitoyltransferase I, was given orally to male rats 2, 4, and 6 h prior to an intravenous infusion of the saturated fatty acid [U-14C]palmitic acid (PA) or the polyunsaturated fatty acid [1-14C]arachidonate (AA). With [U-14C]PA, MEP (10-25 mg/kg) increased brain organic radioactivity 2-fold and decreased brain aqueous radioactivity 3- to 5-fold relative to control values at all pretreatment times. The effect was due to prolongation of the plasma integral of [U-14C]PA due to peripheral inhibition of beta-oxidation, and to direct inhibition of beta-oxidation of the tracer within the brain. MEP had no effect on brain organic radioactivity after infusion of [1-14C]AA. Increasing the interval between MEP administration and [U-14C]PA infusion from 2 to 6 h resulted in a dramatic redistribution of [U-14C]PA within brain lipids. The percentage of radioactivity in phospholipids decreased from 65 to 33%, whereas that in the free fatty acid fraction increased from 10 to 47% and that in triglycerides was elevated 2-3 fold over control levels. These results indicate that MEP may facilitate the use of radiolabeled PA as an in vivo probe of brain lipid metabolism using quantitative autoradiography or positron emission tomography.

Animals↗