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Biomedical subjects

J M Bell

Publications and source records attributed to J M Bell.

At least 19 recordsLinked to original sources

The influence of floral display size on selfing rates in Mimulus ringens.

Pollinators often visit several flowers in sequence on plants with large floral displays. This foraging pattern is expected to influence the rate of self-fertilization in self-compatible taxa. To quantify the effects of daily floral display on pollinator movements and selfing, we experimentally manipulated flower number in four replicate (cloned) arrays of Mimulus ringens (Scrophulariaceae), each consisting of genets with unique combinations of homozygous marker genotypes. Four display classes (two, four, eight and 16 flowers) were present in each array. Pollinator visitation rate per flower and seed set per fruit were unaffected by display. However, flower number strongly influenced the frequency of within-plant pollinator movements, which increased from 13.8% of probes on two-flower displays to 77.6% of probes on 16-flower displays. The proportion of within-plant movements was significantly correlated with selfing (r = 0.993). The increase from 22.9% selfing on two-flower displays to 37.3% selfing on 16-flower displays reflects changes in the extent of geitonogamous self-pollination. We estimate that approximately half of all selfing on 16-flower displays resulted from geitonogamy. Selfing also varied dramatically among fruits within display classes. Nested ANOVA indicates that differences among flowers on two-flower ramets accounted for 45.4% of the variation in selfing, differences among genets accounted for 16.1% of the variation, and statistical and sampling error accounted for 38.5% of the variation. Differences among flowers within ramets may reflect the order of sequential floral probes on a display.

Crosses, Genetic↗

Antimicrobial activities of garenoxacin (BMS 284756) against Asia-Pacific region clinical isolates from the SENTRY program, 1999 to 2001.

Between 1999 and 2001, 16,731 isolates from the Asia-Pacific Region were tested in the SENTRY Program for susceptibility to six fluoroquinolones including garenoxacin. Garenoxacin was four- to eightfold less active against Enterobacteriaceae than ciprofloxacin, although both drugs inhibited similar percentages at 1 microg/ml. Garenoxacin was more active against gram-positive species than all other fluoroquinolones except gemifloxacin. For Staphylococcus aureus, oxacillin resistance was high in many participating countries (Japan, 67%; Taiwan, 60%; Hong Kong, 55%; Singapore, 52%), with corresponding high levels of ciprofloxacin resistance (57 to 99%) in oxacillin-resistant S. aureus (ORSA). Of the ciprofloxacin-resistant ORSA isolates, the garenoxacin MIC was >4 microg/ml for only 9% of them. For Streptococcus pneumoniae, penicillin nonsusceptibility and macrolide resistance were high in many countries. No relationship was seen between penicillin and garenoxacin susceptibility, with all isolates being susceptible at <2 microg/ml. There was, however, a partial correlation between ciprofloxacin and garenoxacin MICs. For ciprofloxacin-resistant isolates for which garenoxacin MICs were 0.25 to 1 microg/liter, mutations in both the ParC and GyrA regions of the quinolone resistance-determining region could be demonstrated. No mutations conferring high-level resistance were detected. Garenoxacin shows useful activity against a wide range of organisms from the Asia-Pacific region. In particular, it has good activity against S. aureus and S. pneumoniae, although there is evidence that low-level resistance is present in those organisms with ciprofloxacin resistance.

Anti-Infective Agents↗

Prevalence of extended-spectrum beta-lactamase-producing Enterobacter cloacae in the Asia-Pacific region: results from the SENTRY Antimicrobial Surveillance Program, 1998 to 2001.

Enterobacter cloacae strains from hospitalized patients with a range of infections were collected by 17 laboratories in the Asia-Pacific region and South Africa. Isolates for which ceftriaxone MICs were above 1 microg/ml and/or ceftazidime MICs were above 2 microg/ml, as well as 46 strains for which ceftriaxone and/or ceftazidime MICs were at or below these values, were screened for levels of extended-spectrum beta-lactamase (ESBL) production through the use of broth microdilution for the detection of clavulanate enhancement of the activity of ceftriaxone, ceftazidime, and cefepime. Of the isolates examined, ceftriaxone and/or ceftazidime had elevated MICs for 44%, of which 36% were ESBL positive. ESBL-positive strains were commonly susceptible to piperacillin-tazobactam and more frequently resistant to several other antimicrobials studied. A cefepime MIC above 0.25 microg/ml had the highest sensitivity (100%) and specificity (74%) for predicting the presence of an ESBL.

Asia↗

Antimicrobial resistance trends in community-acquired respiratory tract pathogens in the Western Pacific Region and South Africa: report from the SENTRY antimicrobial surveillance program, (1998-1999) including an in vitro evaluation of BMS284756.

From 1998 to 1999, a large number of community-acquired respiratory tract isolates of Streptococcus pneumoniae (n=566), Haemophilus influenzae (n=513) and Moraxella catarrhalis (n=228) were collected from 15 centres in Australia, Hong Kong, Japan, China, the Philippines, Singapore, South Africa and Taiwan through the SENTRY Antimicrobial Surveillance Program. Isolates were tested against 26 antimicrobial agents using the NCCLS-recommended methods. Overall, 40% of S. pneumoniae isolates were resistant to penicillin with 18% of strains having high-level resistance (MIC > or =2 mg/l). Rates of erythromycin and clindamycin resistance were 41 and 23%, respectively. Penicillin-resistant strains showed high rates of resistance to other antimicrobial agents: 96% to trimethoprim-sulphamethoxazole (TMP-SMX), 84% to tetracycline and 81% to erythromycin. A significant proportion of penicillin-susceptible strains was also resistant to erythromycin (21%), tetracycline (29%) and TMP-SMZ (26%). Small numbers of strains were resistant to levofloxacin (0.7%), trovafloxacin (0.4%) and grepafloxacin (1.3%) where as all strains remained uniformly susceptible to quinupristin/dalfopristin and BMS284756 (MIC(90), 0.06 mg/l), a new desfluoroquinolone. beta-lactamases were, produced by 20% H. influenzae isolates and only rare strains showed intrinsic resistance to amoxycillin. Other beta-lactam agents showed good activity with rates of resistance less than 2% and all isolates showed susceptibility to cefixime, ceftibuten, cefepime and cefotaxime. Rates of resistance to tetracycline and chloramphenicol were also relatively low at 3%. The majority (98%) of M. catarrhalis isolates was found to be beta-lactamase-positive and resistant to penicillins, however, resistance to erythromycin and tetracycline was also low at 1.8%. Both H. influenzae and M. catarrhalis isolates were uniformly susceptible to the new desfluoroquinolone and tested fluoroquinolones.

Anti-Infective Agents↗

Lack of association of the (AAAT)6 allele of the GXAlu tetranucleotide repeat in intron 27b of the NF1 gene with autism.

A novel allele of the GXAlu tetranucleotide repeat in intron 27b of the neurofibromatosis 1 (NF1) gene has recently been reported to be present in 4.7% of autistic patients but not in controls. We have found the novel GXAlu allele absent in 204 patients from the South Carolina Autism Project and 200 controls. The autism population studied includes a significant number of patients with hypotonia, stereotyped behaviors, or postural, gait, and motor abnormalities similar to those seen in the patients previously reported to possess the novel GXAlu allele. This suggests that the novel (AAAT)6 GXAlu allele is not associated with autism.

Alleles↗

Chronic valproate treatment decreases the in vivo turnover of arachidonic acid in brain phospholipids: a possible common effect of mood stabilizers.

Both (Li(+)) and valproic acid (VPA) are effective in treating bipolar disorder, but the pathway by which either works, and whether it is common to both drugs, is not agreed upon. We recently reported, using an in vivo fatty acid model, that Li(+) reduces the turnover rate of the second messenger arachidonic acid (AA) by 80% in brain phospholipids of the awake rat, without changing turnover rates of docosahexaenoic or palmitic acid. Reduced AA turnover was accompanied by down-regulation of gene expression and protein levels of an AA-specific cytosolic phospholipase A(2) (cPLA(2)). To see if VPA had the same effect on AA turnover, we used our in vivo fatty acid model in rats chronically administered VPA (200 mg/kg, i.p. for 30 days). Like Li(+), VPA treatment significantly decreased AA turnover within brain phospholipids (by 28-33%), although it had no effect on cPLA(2) protein levels. Thus, both mood stabilizers, Li(+) and VPA have a common action in reducing AA turnover in brain phospholipids, albeit by different mechanisms.

Acyl Coenzyme A↗

Multicentre study of the in vitro activity of cefepime, a broad-spectrum cephalosporin, compared to other broad-spectrum agents.

The in vitro activity of cefepime was compared to that of a range of other broad-spectrum agents, using a gradient diffusion MIC method, against 995 recent clinical isolates of Enterobacteriaceae, Pseudomonas aeruginosa, other nonfermentative gram-negative bacilli, staphylococci (except oxacillin-resistant Staphylococcus aureus), streptococci, enterococci, and aerobic gram-positive bacilli. Cefepime had excellent activity against Enterobacteriaceae, including eight presumptive extended-spectrum beta-lactamase producers and 33 stably derepressed mutants of natural cephalosporinases. Activity against Pseudomonas aeruginosa was similar to ceftazidime and superior to cefpirome. Its activity against gram-positive cocci was also good, being more active against staphylococci and only slightly less active against streptococci than ceftriaxone. Cefepime maintained activity against bacteria resistant to aminoglycosides and ciprofloxacin. Enterococci, Bacillus species, Burkholderia cepacia and Stenotrophomonas maltophilia were predicably resistant. Cefepime has a spectrum of activity almost as broad as that of the carbapenems.

Cefepime↗

Methicillin-resistant Staphylococcal aureus evolution in Australia over 35 years.

Australia has a long association methicillin-resistant Staphylococcus aureus (MRSA). Its unique geographic and demographic features have led to the emergence and spread of three types of MRSA over 35 years. Classical multiresistant hospital-acquired MRSA were first noted in Australia in 1965. By the end of the 1970s, strains of this type of MRSA were well established in the complex tertiary care hospitals in the capital cities on the eastern seaboard of mainland Australia. Characterized by resistance to beta-lactams, erythromycin, tetracycline, gentamicin, and trimethoprim-sulfamethoxazole, these strains have persisted and diversified genetically and have acquired a variety of new resistances. They have proven pathogenicity and are a prominent cause of hospital infection in the endemic institutions. More recently they have become endemic in some central state tertiary care hospitals. Community-acquired strains of MRSA first appeared in the north of Western Australia in the mid-1980s. Strains have subsequently appeared in the south of the state and in the two adjacent central states, and are more frequently isolated from Aboriginal patients. Although harboring few or no additional resistances apart from resistance to beta-lactams initially, these strains are also accumulating additional resistances. A different variety of community-acquired MRSA has recently been noted in eastern Australia. It has a similar antibiogram to the western strains, but an entirely different epidemiology, resembling that currently being experienced in parts of New Zealand, and associated with patients of south Pacific island origin.

Australia↗

Genetic characterization of vanG, a novel vancomycin resistance locus of Enterococcus faecalis.

Enterococcus faecalis strain WCH9 displays a moderate level of resistance to vancomycin (MIC = 16 microgram/ml) and full susceptibility to teicoplanin but is negative by PCR analysis using primers specific for all known enterococcal vancomycin resistance genotypes (vanA, vanB, vanC, vanD, and vanE). We have isolated and sequenced a novel putative vancomycin resistance locus (designated vanG), which contains seven open reading frames, from this strain. These are organized differently from those of all the other enterococcal van loci, and, furthermore, the individual vanG gene products exhibit less than 50% amino acid sequence identity to other van gene products.

Amino Acid Sequence↗

Rapidly emerging antimicrobial resistances in Streptococcus pneumoniae in Australia. Pneumococcal Study Group.

OBJECTIVE: To examine the prevalence of resistance in Streptococcus pneumoniae to key antimicrobials in Australia during 1997. DESIGN: Prospective, Australia-wide, laboratory-based survey. SETTING: 11 microbiology laboratories from seven Australian States and Territories (five private laboratories and six public hospital laboratories) between March and November 1997. STRAINS: Up to 100 consecutive, clinically significant strains of S. pneumoniae isolated by each laboratory. MAIN OUTCOME MEASURES: Susceptibility to penicillin, amoxycillin-clavulanate, cefaclor, ceftriaxone, erythromycin, tetracycline, and sulfamethoxazole-trimethoprim (cotrimoxazole), measured by a gradient diffusion, minimum inhibitory concentration technique. RESULTS: Of 1020 strains, 16.8% had intermediate susceptibility to penicillin and 8.6% were resistant. Rates of resistance to other drugs were: amoxycillin-clavulanate, 3.1%; cefaclor, 21.4%; ceftriaxone, 3.1%; erythromycin, 15.6%; tetracycline, 15.7%; and cotrimoxazole, 33.4%. Non-invasive isolates harboured more resistances than invasive isolates, and resistance was more prevalent in isolates from children under two years. Multiple resistance was also common, with 21.2% of strains resistant to two or more classes of drug, and 9.3% of non-invasive and 1.7% of invasive isolates resistant to four classes. There were no obvious differences in resistance rates between private and public hospital laboratories. CONCLUSIONS: Rates of antimicrobial resistance are rising rapidly in S. pneumoniae in Australia. Recommendations for empiric treatment of invasive and respiratory infection need to take account of these changes.

Australia↗

Dynamics of docosahexaenoic acid metabolism in the central nervous system: lack of effect of chronic lithium treatment.

Using a method and model developed in our laboratory to quantitatively study brain phospholipid metabolism, in vivo rates of incorporation and turnover of docosahexaenoic acid in brain phospholipids were measured in awake rats. The results suggest that docosahexaenoate incorporation and turnover in brain phospholipids are more rapid than previously assumed and that this rapid turnover dilutes tracer specific activity in brain docoshexaenoyl-CoA pool due to release and recycling of unlabeled fatty acid from phospholipid metabolism. Fractional turnover rates for docosahexaenoate within phosphatidylinositol, choline glycerophospholipids, ethanolamine glycerophospholipids and phosphatidylserine were 17.7, 3.1, 1.2, and 0.2 %.h(-1), respectively. Chronic lithium treatment, at a brain level considered to be therapeutic in humans (0.6 micromol.g(-1)), had no effect on turnover of docosahexaenoic acid in individual brain phospholipids. Consistent with previous studies from our laboratory that chronic lithium decreased the turnover of arachidonic acid within brain phospholipids by up to 80% and attenuated brain phospholipase A2 activity, the lack of effect of lithium on docosahexaenoate recycling and turnover suggests that a target for lithium's action is an arachidonic acid-selective phospholipase A2.

Acyl Coenzyme A↗

Reduced palmitate turnover in brain phospholipids of pentobarbital-anesthetized rats.

Our laboratory has reported that pentobarbital-induced anesthesia reduced the incorporation of intravenously injected radiolabeled palmitic acid into brain phospholipids. To determine if this decrease reflected a pentobarbital-induced decrease in palmitate turnover in phospholipids, we applied our method and model to study net flux and turnover of palmitate in brain phospholipids (1). Awake, light and deep pentobarbital (25-70 mg/kg, iv) anesthetized rats were infused with [9,10-3H]palmitate over a 5 min period. Brain electrical activity was monitored by electroencephalography. An isoelectric electroencephalogram characterized deep pentobarbital anesthesia. Net incorporation rates (J(FA,i)) and turnover rates (Fi) of palmitate were calculated. J(FA,i) for palmitate incorporated into phospholipids was dramatically reduced by pentobarbital treatment in a dose-dependent manner, by 70% and 90% respectively for lightly and deeply anesthetized animals, compared with awake controls. Turnover rates for palmitate in total phospholipid and individual phospholipid classes were decreased by nearly 70% and 90% for lightly and deeply anesthetized animals, respectively. Thus, pentobarbital decreases, in a dose-dependent manner, the turnover of palmitate in brain phospholipids. This suggests that palmitate turnover is closely coupled to brain functional activity.

Adjuvants, Anesthesia↗

Fatty acid incorporation depicts brain activity in a rat model of Parkinson's disease.

Following pulse labeling with [3H]arachidonic acid ([3H]AA), its incorporation pattern in brain reflects regional changes in neurotransmitter signal transduction using phospholipase A2, that is, functional activity. In a rat model of Parkinson's disease, unilateral 6-hydroxydopamine lesion in the substantia nigra, [3H]AA acid incorporation from blood was increased in cerebral cortex, caudate putamen, globus pallidus, entopeduncular nucleus, subthalamic nucleus and substantia nigra pars reticulata ipsilateral to the lesion. This increased [3H]AA incorporation likely reflects disinhibition of basal ganglia and cortical circuits secondary to absent inhibitory nigrostriatal dopaminergic input.

Animals↗

Reconversion of bone marrow in Gaucher disease treated with enzyme therapy documented by MR.

BACKGROUND: Skeletal complications are responsible for significant morbidity in Gaucher patients. Plain radiographs have been unreliable in assessing bone marrow infiltration and activity. A way to assess bone marrow improvement is needed during enzyme therapy. OBJECTIVE: The purpose of this paper is to assess the usefulness of MR in following improvement of abnormal bone marrow in Gaucher patients on enzyme therapy. MATERIALS AND METHODS: Three patients aged 2, 7, and 24 years underwent serial MR scans of the lower extremities before and during treatment with Alglucerase (two patients) and Imiglucerase (one patient). T1-weighted, T2-weighted, STIR and FSE T2-weighted images were utilized. Two patients were imaged after 16 months of therapy, and one patient was imaged after 6 months of therapy. RESULTS: All patients had improvement in marrow signal consistent with partial reconversion to fatty marrow during treatment. The findings were more marked after prolonged therapy. T1-weighted images demonstrated findings most clearly. CONCLUSION: MR consistently showed improvement in marrow signal in Gaucher patients on enzyme therapy. As smaller doses of enzyme therapy are the trend, MR can be utilized to determine if therapy is effecting a change in the bone marrow.

Adult↗

A "reader's theater" intervention to managing grief: posttherapy reflections by a family and clinical team.

The sudden and accidental death of a child can be one of the most devastating events in the life of a family. This paper describes one couple's reflections of their grief and mourning following the death of their adolescent son as well as the clinical team's reflections of therapy. The uniqueness of this paper is that it offers a "reader's theater" intervention that enabled further change to occur. The clinical team used a belief model, emphasizing that altering constraining beliefs is at the heart of healing from such tragedies as sudden death (Wright, Watson, & Bell, 1996). This approach is operationalized through therapeutic conversations between family members, clinician, and clinical team. Interventions such as reflecting teams, therapeutic letters, and "homework tasks" were used to modify or challenge constraining beliefs of both the family members and the clinical team members. However, the intent to co-author a paper with this couple provided the serendipity intervention of a "reader's theater" that further served to identify, affirm, and solidify facilitating beliefs.

Adolescent↗

Emergence of vancomycin-resistant enterococci in Australia: phenotypic and genotypic characteristics of isolates.

Enterococci with resistance to glycopeptides have recently emerged in Australia. We developed multiplex PCR assays for vanA, vanB, vanC1, and vanC2 or vanC3 in order to examine the genetic basis for vancomycin resistance in Australian isolates of vancomycin-resistant Enterococcus faecium and E. faecalis (VRE). The predominant genotype from human clinical E. faecium isolates was vanB. The PCR van genotype was consistent with the resistance phenotype in all but six cases. One vanA E. faecalis isolate had a VanB phenotype, one vanB E. faecium isolate had a VanA phenotype, and four E. faecalis isolates were consistently negative for vanA, vanB, vanC1, and vanC2 or vanC3, even though they exhibited a VanB phenotype. These four isolates were subsequently examined for the presence of vanD by published methods and were found to be negative. No vancomycin-susceptible strains produced a PCR product. On the basis of our findings the epidemiology of VRE in Australia appears to be different from that in either the United States or Europe. Our multiplex PCR assays gave a rapid and accurate method for determining the genotype and confirming the identification of glycopeptide-resistant enterococci. Rapid and accurate methods are essential, because laboratory-based surveillance is critical in programs for the detection, control, and prevention of the transmission of glycopeptide-resistant enterococci.

Anti-Bacterial Agents↗

Evidence for decreased splanchnic glucose uptake after oral glucose administration in non-insulin-dependent diabetes mellitus.

The role of splanchnic glucose uptake (SGU) after oral glucose administration as a potential factor contributing to postprandial hyperglycemia in non-insulin-dependent diabetes mellitus (NIDDM) has not been established conclusively. Therefore, we investigated SGU in six patients with NIDDM and six weight-matched control subjects by means of the hepatic vein catheterization (HVC) technique. In a second part, we examined the applicability of the recently developed OG-CLAMP technique in NIDDM by comparing SGU and first-pass SGU during HVC with SGU during the OG-CLAMP experiment. The OG-CLAMP method combines a euglycemic, hyperinsulinemic clamp and an oral glucose tolerance test (75 g) during steady state glucose infusion (GINF). During HVC, SGU equals the splanchnic fractional extraction times the total (oral and arterial) glucose load presented to the liver. For OG-CLAMP, SGU was calculated as first-pass SGU by subtracting the integrated decrease in GINF over 180 min from 75 g. Cumulative splanchnic glucose output after oral glucose correlated significantly between both methods and was increased significantly in NIDDM patients (73.1+/-5.1 g for HVC, 76.5+/-5.5 for OG-CLAMP) compared with nondiabetic patients (46.7+/-4.4 g for HVC, 57.5+/-1.9 for OG-CLAMP). Thus, in NIDDM patients, SGU (7.4+/-2.1 vs. 37.8+/-5.9% in nondiabetic patients, P < 0.001) and first-pass SGU (4.7+/-1.7 vs. 26.5+/-5.1% in nondiabetic patients, P < 0.01) were decreased significantly during HVC, as was SGU during OG-CLAMP (3.9+/-1.7 vs. 23.4+/-2.5% in nondiabetic patients, P < 0.0001). SGU measured during OG-CLAMP correlated significantly with SGU (r = 0.87, P < 0.05 for NIDDM patients; r = 0.94, P < 0.01 for nondiabetic patients) and first-pass SGU (r = 0.87, P < 0.05 for NIDDM patients; r = 0.84, P < 0.05 for nondiabetic patients) during HVC. In conclusion, (a) SGU after oral glucose administration is decreased in NIDDM as measured by both methods, and (b) SGU during the OG-CLAMP is well-correlated to SGU and first-pass SGU during HVC in NIDDM. The decrease in SGU in NIDDM might contribute to postprandial hyperglycemia in diabetic subjects.

Administration, Oral↗

Brain incorporation of [1-11C]arachidonate in normocapnic and hypercapnic monkeys, measured with positron emission tomography.

Positron emission tomography (PET) was used to determine brain incorporation coefficients k* of [1-11C]arachidonate in isoflurane-anesthetized rhesus monkeys, as well as cerebral blood flow (CBF) using [15O]water. Intravenously injected [1-11C]arachidonate disappeared from plasma with a half-life of 1.1 min, whereas brain radioactivity reached a steady-state by 10 min. Mean values of k* were the same whether calculated by a single-time point method at 20 min after injection began, or by least-squares fitting of an equation for total brain radioactivity to data at all time points. k* equalled 1.1-1.2 x 10(-4) ml x s(-1) x g(-1) in gray matter and was unaffected by a 2.6-fold increase in CBF caused by hypercapnia. These results indicate that brain incorporation of [1-11C]arachidonate can be quantified in the primate using PET, and that incorporation is flow-independent.

Animals↗