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Biomedical subjects

D A Lewis

Publications and source records attributed to D A Lewis.

At least 109 records · Page 6Linked to original sources
PubMed1999

Identification of the znuA-encoded periplasmic zinc transport protein of Haemophilus ducreyi.

The znuA gene of Haemophilus ducreyi encodes a 32-kDa (mature) protein that has homology to both the ZnuA protein of Escherichia coli and the Pzp1 protein of H. influenzae; both of these latter proteins are members of a growing family of prokaryotic zinc transporters. Inactivation of the H. ducreyi 35000 znuA gene by insertional mutagenesis resulted in a mutant that grew more slowly than the wild-type parent strain in vitro unless ZnCl(2) was provided at a final concentration of 100 microM. Other cations tested did not restore growth of this H. ducreyi mutant to wild-type levels. The H. ducreyi ZnuA protein was localized to the periplasm, where it is believed to function as the binding component of a zinc transport system. Complementation of the znuA mutation with the wild-type H. ducreyi znuA gene provided in trans restored the ability of this H. ducreyi mutant to grow normally in the absence of exogenously added ZnCl2. The wild-type H. ducreyi znuA gene was also able to complement a H. influenzae pzp1 mutation. The H. ducreyi znuA isogenic mutant exhibited significantly decreased virulence (P = 0.0001) when tested in the temperature-dependent rabbit model for experimental chancroid. This decreased virulence was not observed when the znuA mutant was complemented with the wild-type H. ducreyi znuA gene provided in trans.

Amino Acid Sequence↗
PubMed1999

Hypoglycemia and torpor in Siberian hamsters.

We tested whether reduced blood glucose concentrations are necessary and sufficient for initiation of torpor in Siberian hamsters. During spontaneous torpor bouts, body temperature (Tb) decreases from the euthermic value of 37 to <31 degrees C. Among hamsters that displayed torpor during maintenance in a short-day length (10 h light/day) at an air temperature of 15 degrees C, blood glucose concentrations decreased significantly by 28% as Tb fell from 37 to <31 degrees C and increased during rewarming so that by the time Tb first was >36 degrees C, glucose concentrations had returned to the value preceding torpor. Hamsters did not display torpor when maintained in a long-day length (16 h light/day) and injected with a range of insulin doses (1-50 U/kg body mass), some of which resulted in sustained, pronounced hypoglycemia. We conclude that changes in blood glucose concentrations may be a consequence rather than a cause of the torpid state and question whether induction of torpor by 2-deoxy-D-glucose is due to its general glucoprivic actions.

Animals↗
PubMed1999

Aerobically generated CO(2) stored during early exercise.

Previous studies have shown that a metabolic alkalosis develops in the muscle during early exercise. This has been linked to phosphocreatine hydrolysis. Over a similar time frame, the femoral vein blood pH and plasma K(+) and HCO(-)(3) concentrations increase without an increase in PCO(2). Thus CO(2) from aerobic metabolism is converted to HCO(-)(3) rather than being eliminated by the lungs. The purpose of this study was to quantify the increase in early CO(2) stores and the component due to the exercise-induced metabolic alkalosis (E-I Alk). To avoid masking the increase in CO(2) stores by CO(2) released as HCO(-)(3) buffers lactic acid, the transient increase in CO(2) stores was measured only for work rates (WRs) below the lactic acidosis threshold (LAT). The increase in CO(2) stores was evident at the airway starting at approximately 15 s; the increase reached a peak at approximately 60 s and was complete by approximately 3 min of exercise. The increase in CO(2) stores was greater, but the kinetics were unaffected at the higher WR. Three components of the change in aerobically generated CO(2) stores were considered relevant: the carbamate component of the Haldane effect, the increase in CO(2) stores due to increase in tissue PCO(2), and the E-I Alk. The Haldane effect was calculated to be approximately 5%. Physically dissolved CO(2) in the tissues was approximately 30% of the store increase. The remaining E-I Alk CO(2) stores averaged 61 and 68% for 60 and 80% LAT WRs, respectively. The kinetics of O(2) uptake correlated with the time course of the increase in CO(2) stores; the size of the O(2) deficit correlated with the size of the E-I Alk component of the CO(2) stores. We conclude that a major component of the aerobically generated increase in CO(2) stores is the new HCO(-)(3) generated as phosphocreatine is converted to creatine.

Adult↗
PubMed1999

Lamina-specific alterations in the dopamine innervation of the prefrontal cortex in schizophrenic subjects.

OBJECTIVE: Abnormalities in dopamine neurotransmission in the prefrontal cortex have been implicated in the pathophysiology of schizophrenia. However, the integrity of the dopamine projections to the prefrontal cortex in this disorder has not been directly examined. METHOD: The authors employed immunocytochemical methods and antibodies against tyrosine hydroxylase, the rate-limiting enzyme in dopamine biosynthesis, and the dopamine membrane transporter to examine dopamine axons in the dorsomedial prefrontal cortex (area 9) from 16 pairs of schizophrenic and matched control subjects. RESULTS: Compared to the control subjects, the total length of tyrosine hydroxylase-immunoreactive axons was unchanged in the superficial and middle layers of the schizophrenic subjects but was reduced by an average of 33.6% in layer 6. The total length of tyrosine hydroxylase-positive axons in layer 6 was decreased in 13 of the schizophrenic subjects compared to their control subjects. Axons immunoreactive for the dopamine membrane transporter showed a similar pattern of change. In contrast, axons labeled for the serotonin transporter did not differ between schizophrenic and control subjects in any layer examined. In addition, the density of tyrosine hydroxylase-containing axons did not differ between monkeys chronically treated with haloperidol and matched control animals. CONCLUSIONS: These findings reveal that schizophrenia is associated with an altered dopamine innervation of prefrontal cortex area 9 that is lamina- and neurotransmitter-specific and that does not appear to be a consequence of pharmacological treatment. Together, these data provide direct evidence for a disturbance in dopamine neurotransmission in the prefrontal cortex of schizophrenic subjects.

Adult↗
PubMed1999

Alterations in chandelier neuron axon terminals in the prefrontal cortex of schizophrenic subjects.

OBJECTIVE: Abnormalities in prefrontal cortical gamma-aminobutyric acid (GABA) neurotransmission may contribute to cognitive dysfunction in schizophrenia. The density of chandelier neuron axon terminals (cartridges) immunoreactive for the GABA membrane transporter (GAT-1) has been reported to be reduced in the dorsolateral prefrontal cortex of schizophrenic subjects. Because cartridges regulate the output of pyramidal cells, this study analyzed the laminar distribution of GAT-1-immunoreactive cartridges to determine whether certain subpopulations of pyramidal cells are preferentially affected. METHOD: Measurements were made of the density of GAT-1 -immunoreactive cartridges in layers 2-3a, 3b-4, and 6 of dorsolateral prefrontal cortex area 46 in 30 subjects with schizophrenia, each of whom was matched to one normal and one psychiatric comparison subject. GAT-1-immunoreactive cartridge density was also examined in monkeys chronically treated with haloperidol. RESULTS: Relative to both comparison groups, the schizophrenic subjects had significantly lower GAT-1-immunoreactive cartridge density in layers 2-3a and 3b-4. The decrease was most common and most marked in layers 3b-4, where 80% of the schizophrenic subjects exhibited an average 50.1% decrease in cartridge density in comparison with the matched normal subjects. In contrast, GAT-1-immunoreactive cartridge density was unchanged in the haloperidol-treated monkeys. CONCLUSIONS: These findings demonstrate that the density of GAT-1-immunoreactive cartridges is reduced in the majority of schizophrenic subjects and that this alteration may most prominently affect the function of pyramidal cells located in the middle cortical layers. This abnormality may reflect a number of underlying deficits, including a primary defect in dorsolateral prefrontal cortex circuitry or a secondary response to altered thalamic input to this region.

Animals↗
PubMed1999

Clinical characteristics and service use of persons with mental illness living in an intermediate care facility.

OBJECTIVE: The study examined the characteristics of residents living in a 450-bed intermediate care facility for persons with severe mental illness in Illinois and sought to determine the factors predicting their utilization of mental health services. METHODS: Data on 100 randomly selected residents with a chart diagnosis of schizophrenia were collected using chart review and interviews. Data for 78 residents whose diagnosis of schizophrenia or schizoaffective disorder was confirmed using the Structured Clinical Interview for DSM-IV were included in the analyses. RESULTS: Fifty-three percent of the residents used facility-based specialty mental health services beyond medication management, such as group therapy or a day program. Persons with the least severe psychiatric illnesses and with higher levels of motivation for overall care used the most mental health services. Thirty-five percent of the residents had been discharged to an inpatient psychiatric unit during the previous year. Residents most likely to be discharged to those settings were young men with a history of homelessness who refused facility-based health services. CONCLUSIONS: Despite recent policy-driven efforts to improve care in this intermediate care facility for persons with mental illness, the facility continues to have problems addressing the mental health needs of the residents.

Adult↗
PubMed1999

A one-year survey of gonococcal infection seen in the genitourinary medicine department of a London district general hospital.

The results of a one-year clinical, epidemiological and microbiological survey of gonococcal infection presenting to the Patrick Clements Clinic (PCC), a London district general hospital (DGH) genitourinary medicine (GUM) clinic, are presented. Clinical and epidemiological patient data were collected by a combination of questionnaire and retrospective case-note review. Microscopy performance within the PCC, outcome of treatment, return for tests of cure and efficacy of contact tracing were assessed. Isolates were tested for susceptibility to penicillin, tetracycline and ciprofloxacin. The study showed the PCC continues to diagnose and treat over 200 cases of gonorrhoea per year. High level resistance to penicillin, tetracycline and ciprofloxacin was documented among the year's isolates and antibiotic resistance was linked to acquisition of gonorrhoea overseas. Despite interviewing 183 patients concerning health advice and contact tracing issues, only 55% of new episodes re-attended for a first test of cure. In addition, only 29% of reported sexual contacts attended GUM clinics for investigation and treatment.

Adolescent↗
PubMed1999

Sleep in patients with respiratory disease.

Recent studies have emphasized the high prevalence and significant consequences of sleep abnormalities in patients who have underlying respiratory disease. Such abnormalities include the nocturnal increase in airway resistance in patients who have asthma, the impaired sleep quality and nocturnal desaturation (particularly during REM sleep) in patients who have chronic obstructive pulmonary disease, and the sleep-related hypoventilation and hypoxemia in patients who have various restrictive respiratory disorders. This article discusses the salient features, underlying pathophysiologic mechanisms, and treatment of these abnormalities of sleep in patients who have respiratory disease.

Asthma↗
PubMed1998

Alterations in mRNA for inducible and endothelial nitric oxide synthase and plasma nitric oxide with rejection and/or infection of allotransplanted lungs.

BACKGROUND: Experiments were designed to determine expression of type II (iNOS) and type III (ecNOS) nitric oxide synthase in lung parenchyma and systemic endothelial cells with rejection and/or infection of single lung allografts. METHODS: After single lung allotransplantation, dogs were maintained on standard triple immunosuppressive therapy for 5 days and then placed into one of three groups. Group I (n=4) was maintained on immunosuppressants, group II (n=7) immunosuppression was withdrawn to allow acute rejection of the allograft, and group III (n=6) infection was induced by bronchoscopic inoculation of Escherichia coli. RESULTS: At postoperative days 7-9, no histological evidence of rejection or infection was observed in transplanted lungs of group I. In lungs of group II, rejection ranged from mild to severe; in lungs of group III, infection was severe. Some animals had both rejection and infection (n=8) and were studied separately. Plasma levels of nitric oxide increased comparably with rejection and/or infection compared to preoperative values. Expression of mRNA for ecNOS decreased significantly in lung parenchyma but not in aortic endothelial cells from dogs of groups II and III. However, expression of mRNA for iNOS increased with both rejection and/or infection in both lung parenchyma and aortic endothelial cells. CONCLUSIONS: iNOS is induced locally within the graft and systemically in aortic endothelial cells with rejection and/or infection of lung allografts. Plasma levels of nitric oxide are elevated with both rejection and infection and may not be useful in the differential diagnosis of these processes after lung transplantation.

Animals↗
PubMed1998

A subclass of prefrontal gamma-aminobutyric acid axon terminals are selectively altered in schizophrenia.

In the primate cerebral cortex, morphologically and functionally diverse classes of local circuit neurons containing the inhibitory neurotransmitter gamma-aminobutyric acid (GABA) differentially regulate the activity of pyramidal cells, the principal type of excitatory output neurons. In schizophrenia, GABA neurotransmission in the prefrontal cortex (PFC) appears to be disturbed but whether specific populations of GABA neurons are affected is not known. The chandelier class of GABA neurons are of particular interest because their axon terminals, which form distinctive arrays termed "cartridges," provide inhibitory input exclusively to the axon initial segment of pyramidal cells. Thus, chandelier cells are positioned to powerfully regulate the excitatory output of pyramidal neurons and, consequently, to substantially affect the patterns of neuronal activity within the PFC. In this study, an antibody directed against the GABA membrane transporter GAT-1 was used to label GABA axon terminals in postmortem human brains. The relative density of GAT-1-immunoreactive axon cartridges furnished by chandelier neurons was decreased by 40% in the PFC of schizophrenic subjects compared with matched groups of normal control and nonschizophrenic psychiatric subjects. In contrast, markers of the axon terminals of other populations of GABA neurons were not altered in the schizophrenic subjects. Furthermore, the density of GAT-1-immunoreactive axon cartridges was not altered in psychiatric subjects who had been treated with antipsychotic medications. The changes in GAT-1-immunoreactive axon cartridges of chandelier neurons in schizophrenia are likely to reflect altered information processing within the PFC and in its output connections to other brain regions and could contribute to the cognitive impairments seen in this disorder.

Autopsy↗
PubMed1998

Structural integrity of implanted WMT infinity hip and Osteonics Omnifit hip in fresh cadaveric femurs.

Five matched pairs of fresh human femurs were used to quantitatively assess the structural integrity of the implanted Wright Medical Technology modular Infinity hip and the Osteonics single-piece Omnifit hip. The results showed that neither bone implant system was able to recreate the femoral anteversion of the intact femur (p < 0.05). Although the micromotion at the bone-implant interface was well within the limits of achieving bone ingrowth, the axial micromotion was greater for the Infinity hip than for the Omnifit hip (p < 0.05), but the rotational micromotion did not show a significant difference between the two bone implant systems (p > 0.5). The anterior proximal femur deformation patterns were similar for both the two bone implant systems and intact femurs. However, the medial proximal femur deformation patterns showed that the Infinity hip-implanted femur was more similar to the intact femur than the Osteonics Omnifit hip-implanted femur.

Cadaver↗
PubMed1998

Synaptic targets of pyramidal neurons providing intrinsic horizontal connections in monkey prefrontal cortex.

xũ I sLxxJ In monkey prefrontal cortex, the intrinsic axon collaterals of supragranular pyramidal neurons extend horizontally for considerable distances through the gray matter and give rise to stripe-like clusters of axon terminals (Levitt et al. [1993] J. Comp. Neurol. 338:360-376). Because understanding the functional role of these connections requires knowledge of their synaptic targets, we made injections of biotinylated dextran amine (BDA) into layer 3 of macaque prefrontal area 9 and examined the labeled intrinsic axon collaterals by electron microscopy. Labeled axon terminals formed exclusively asymmetric synapses, and 95.6% of the postsynaptic structures were dendritic spines, presumably belonging to other pyramidal neurons. The remaining postsynaptic structures were dendritic shafts, many of which had the morphological characteristics of local circuit neurons. The prefrontal injections also labeled associational projections that traveled through the white matter to terminate in other areas of prefrontal cortex. All of the synapses formed by these associational axons were asymmetric, and 91.9% were onto dendritic spines. The similarities in synaptic targets of the prefrontal intrinsic and associational axon terminals suggested that these projections might arise from the same neurons, an interpretation confirmed in dual label, retrograde tracing studies. To determine the specificity of the synaptic targets of these prefrontal connections, two additional comparisons were made. In the posterior parietal cortex (area 7a), 94.2% of the synapses furnished by BDA-labeled intrinsic collaterals of supragranular pyramidal neurons were also with dendritic spines. In contrast, only 75.6% of unlabeled asymmetric synapses in the prefrontal cortex were onto dendritic spines. These comparisons suggest that the axons of supragranular pyramidal neurons in primate association cortices are preferentially directed to specific targets. Finally, after injections of BDA, a small number of retrogradely labeled pyramidal neurons were observed within the anterogradely labeled clusters of intrinsic axon terminals. At the ultrastructural level, synapses between anterogradely labeled axon terminals and retrogradely labeled dendritic spines were identified. These findings suggest that reciprocal, monosynaptic connections may exist between pyramidal neurons located in different stripe-like clusters, providing a potential anatomical substrate for reverberating excitatory circuits within the primate association cortices.

Animals↗
PubMed1998

Plasma nitric oxide before and after smoking cessation with nicotine nasal spray.

Nicotine may affect cardiovascular function through release of neurotransmitters from autonomic nerves or release of vasoactive substances from the vascular endothelium. Nitric oxide is a neurotransmitter and endothelium-derived factor that reduces tone of vascular smooth muscle. Experiments were designed to determine whether or not use of nicotine nasal spray for smoking cessation affects plasma levels of nitric oxide. Forty smokers self-administered nicotine by nasal spray (one 0.5 mg spray to each nostril). Blood samples were taken before the use of the nasal spray and at treatment day 7 for the measurement of cotinine by high pressure liquid chromatography and nitric oxide (NOx) by chemiluminescence. Age-comparable controls were never-smokers nonnicotine users recruited from laboratory personnel. Mean plasma concentrations of NOx from smokers before treatment were significantly greater compared with nonsmokers (23 +/- 10, n = 40 and 15 +/- 6, n = 13 nmoles/mL [mean +/- SD], respectively, P < 0.01). Plasma NOx in smokers was not significantly correlated with the average daily number of cigarettes smoked (r2 = 0.02, P > 0.05) but was positively and linearly correlated with plasma cotinine (r2 = 0.13, P < 0.02). In 32 self-reported abstinent smokers (confirmed by expired carbon monoxide < 9 ppm) using nicotine nasal spray, cotinine decreased by 64% from pretreatment levels of 284 +/- 103 to posttreatment levels of 90 +/- 58 ng/mL. Plasma NOx was unchanged and went from 23.0 +/- 10.1 at pretreatment to 21 +/- 12 nmoles/mL with nicotine treatment. These results suggest that nicotine-use, independent of cigarette smoking, affects plasma NOx.

Administration, Intranasal↗
PubMed1998

A comparison between single-dose fosfomycin trometamol (Monuril) and a 5-day course of trimethoprim in the treatment of uncomplicated lower urinary tract infection in women.

This study is a comparison of the microbiological and clinical efficacy of single-dose fosfomycin trometamol therapy and a 5 day course of trimethoprim in the treatment of uncomplicated urinary tract infection in female patients. Urine dip-slide samples were obtained from 547 female patients aged 18-65 by 22 General Practitioners (GPs) participating in the study from 21 centres in the UK. All patients were diagnosed as having a urinary tract infection by their GP on the basis of history and clinical examination. Patients were randomised to receive either single dose fosfomycin trometamol or a 5 day course of trimethoprim in a 2:1 ratio. Patients who had significant bacteriuria (> or = 10(5) c.f.u/ml) at the first visit (300) were included in the microbiological analysis. The two commonest urinary pathogens isolated were Escherichia coli and Staphylococcus saprophyticus. Trimethoprim resistance was more frequent amongst E. coli isolates whereas fosfomycin trometamol resistance was more common amongst S. saprophyticus isolates. Microbiological cure was demonstrated in 83.3% of the trimethoprim treated group and 83% of the fosfomycin trometamol treated group. Persistence of the infecting bacteria was seen in 17% of each treatment arm.

Adult↗
PubMed1998

Survey of Canadian human blood plasma for ochratoxin A.

Blood plasma samples collected from 144 healthy volunteers in 16 locations across Canada in 1994 were analysed for ochratoxin A (OTA). The method of analysis included cleanup by C18 solid phase extraction and immunoaffinity columns followed by liquid chromatography (LC) with fluorescence detection, which gave 86.5% (s.d. = 9.7) recovery (n = 31) of OTA (added at 2 ng/ml) with a detection limit of 0.15 ng/ml. The arithmetic mean concentration found in the plasma samples, corrected for volume of anticoagulant added, was 0.88 ng/ml with a standard deviation of 0.35 ng/ml and a range of 0.29-2.37 ng/ml. Confirmation of identity of OTA was by methyl ester formation for 65 samples and by LC-tandem mass spectrometry for 17 samples (some of which were included in pooled samples). Statistical analysis, by ANOVA of the log OTA plasma concentrations, showed a highly significant effect due to location in Canada (p = < 0.0001) but no effect due to age, sex or blood group of donors. The highest mean concentration was found in Winnipeg, significantly different (p = 0.05) by the Student-Newman-Keuls multiple range test from the lowest levels found in Toronto, Vancouver and Saint John.

Adult↗