Biomedical subjects

C J Thomas

Publications and source records attributed to C J Thomas.

At least 55 records · Page 3Linked to original sources

PubMed1998

Integrating clinical and laboratory data in genetic studies of complex phenotypes: a network-based data management system.

The identification of genes underlying a complex phenotype can be a massive undertaking, and may require a much larger sample size than thought previously. The integration of such large volumes of clinical and laboratory data has become a major challenge. In this paper we describe a network-based data management system designed to address this challenge. Our system offers several advantages. Since the system uses commercial software, it obviates the acquisition, installation, and debugging of privately-available software, and is fully compatible with Windows and other commercial software. The system uses relational database architecture, which offers exceptional flexibility, facilitates complex data queries, and expedites extensive data quality control. The system is particularly designed to integrate clinical and laboratory data efficiently, producing summary reports, pedigrees, and exported files containing both phenotype and genotype data in a virtually unlimited range of formats. We describe a comprehensive system that manages clinical, DNA, cell line, and genotype data, but since the system is modular, researchers can set up only those elements which they need immediately, expanding later as needed.

Clinical Laboratory Information Systems↗

PubMed1998

Surveillance of cryptococcosis in Alabama, 1992-1994.

PURPOSE: Although cryptococcosis is a significant opportunistic infection among patients with human immunodeficiency virus (HIV), there is conflicting information on rates of cryptococcosis among HIV-positive and HIV-negative patients. Precise state-wide epidemiologic data for cryptococcosis are not available in Alabama. METHODS: We conducted an active laboratory and hospital medical record-based surveillance for cryptococcosis in Alabama from October 1, 1992 to September 30, 1994. A case of cryptococcosis was defined as a patient's initial episode of cryptococcal disease and based on either a positive culture for C. neoformans from any normally sterile site, a positive latex agglutination serologic test for cryptococcal antigen in CSF or serum, or histopathologic findings consistent with C. neoformans. RESULTS: Over the two year period, 153 cases were identified. The diagnosis was based on positive culture (37%), positive antigen (24%), positive autopsy culture (2%), and histopathologic findings (4%). Further, 33% of the total cases were diagnosed from combined positive culture, antigen, or histopathology. Of the total 153 cases, 55% were in HIV-positive patients and 44% were in HIV-negative individuals and one case (1%) had an unknown HIV status. The overall annual incidence rate of cryptococcosis was 1.89 cases per 100,000 population. The incidence was 1638.7 per 100,000 in the HIV-positive population and 0.84 per 100,000 in the HIV-negative population. CONCLUSION: The first Alabama statewide active surveillance system for cryptococcosis confirms previous observations that rates of cryptococcosis are consistently higher in HIV-infected individuals than in their HIV-negative counterparts. In Alabama, cryptococcosis occurs more commonly in urban residents and in men. Cryptococcosis in HIV-positive persons is more likely to occur in the 20 to 44 year age group, whereas cryptococcosis in HIV-negative persons is more likely to occur in those greater than 45 years old.

AIDS-Related Opportunistic Infections↗

PubMed1998

Effectiveness of two methods of denture sterilization.

Species of Candida and in particular Candida albicans may be involved in the aetiology of denture stomatitis. Studies have shown that Candida and other oral micro-organisms including Streptococcus gordonii are associated with denture plaque; hence denture hygiene is an important factor in the prevention and treatment of the disease. The aim of this investigation was to test in vitro the efficacy of two methods of denture sterilization: (1) microwave irradiation and (2) sodium hypochlorite soak. Twenty upper acrylic dentures were prepared for microbiological assay; 10 were inoculated with C. albicans H1 and 10 with S. gordonii LGR2. Within each group, five dentures were tested in a domestic microwave oven for optimal exposure time and temperature to ensure sterilization; the five control dentures were not microwaved. Microbiological analyses showed that the inoculated dentures became sterile after six min of irradiation at medium setting (2450 MHz, 350 W). Damage to the microorganisms after microwave irradiation was clearly visible by scanning electron microscopy (SEM). Following the same protocol as above, experimental dentures were soaked for 8 h in either 0.02%, or 0.0125% sodium hypochlorite solution and control dentures soaked in distilled water. Microbiological analyses showed that the experimental dentures inoculated with C. albicans H1 became sterile. By contrast, those inoculated with S. gordonii LGR2 did not become sterile, and the SEM procedures confirmed these findings. The results of this study indicate that microwaving may be a more effective method of denture sterilization than denture soaking in sodium hypochlorite. However, compared with microwaving, hypochlorite reduces the levels of residual non-viable micro-organisms attached to the denture surface.

Acrylic Resins↗

PubMed1998

Candida-associated denture stomatitis. Aetiology and management: a review. Part 1. Factors influencing distribution of Candida species in the oral cavity.

Candida species are yeasts and within the oral cavity, Candida albicans is the most frequently isolated. There is clear evidence that C. albicans adheres to oral surfaces including acrylic dentures and mucosa. The mechanisms of attachment differ, with candidal adhesion to inert surfaces under the control of hydrophobic and electrostatic forces and adhesion to mucosa dependent on a number of complex ligand-recognition systems. Other factors within the oral environment such as saliva, pH, bacteria and hyphal formation have been shown to influence adhesion of candida species to surfaces in the mouth.

Acrylic Resins↗

PubMed1998

Candida-associated denture stomatitis. Aetiology and management: a review. Part 2. Oral diseases caused by Candida species.

Certain systemic conditions and/or defects in the immune system may predispose the host to oral candidal infection and the commonest form of oral candidosis is candida-associated denture stomatitis. Until recently there has been controversy concerning the aetiology of the disease. Although some earlier investigators linked denture stomatitis with trauma or bacterial infection, others had isolated Candida albicans from the mouths of patients with the condition. Current studies indicate that denture stomatitis lesions are associated with the detection of candida species while other factors such as denture hygiene, trauma, systemic diseases and deficiencies of the immune system may be involved.

Bacterial Infections↗

PubMed1998

Candida-associated denture stomatitis. Aetiology and management: a review. Part 3. Treatment of oral candidosis.

Treatment of oral candidosis with topical antifungal agents such as nystatin and amphotericin B is effective initially. However, medication can produce side effects in some patients and when therapy is stopped the condition can recur. Alternative treatment involving the use of antiseptics and disinfecting agents has been shown to play an important role in the control of dental plaque. The use of sodium hypochlorite as an overnight denture soak has been shown to eliminate denture plaque and recent investigations have demonstrated that microwave irradiation of dentures at a specified setting and exposure time is bactericidal and candidacidal.

Anti-Infective Agents, Local↗

PubMed1998

Localization of a baculovirus-induced chitinase in the insect cell endoplasmic reticulum.

Confocal immunofluorescence microscopy was used to demonstrate that the Autographa californica nucleopolyhedrovirus (AcMNPV) chitinase was localized within the endoplasmic reticulum (ER) of virus-infected insect cells. This was consistent with removal of the signal peptide from the chitinase and an ER localization motif (KDEL) at the carboxyl end of the protein. Chitinase release from cells, a prerequisite for liquefaction of virus-infected insect larvae, appears to be aided by synthesis of the p10 protein. Deletion of p10 from the AcMNPV genome delayed the appearance of chitinase activity in the medium of virus-infected cells by 24 h and also delayed liquefaction of virus-infected Trichoplusia ni larvae by the same period.

Amino Acid Sequence↗

PubMed1998

Chronic hypoxia decreases nitric oxide production and endothelial nitric oxide synthase in newborn pig lungs.

To examine the effect of chronic hypoxia on nitric oxide (NO) production and the amount of the endothelial isoform of nitric oxide synthase (eNOS) in lungs of newborn piglets, studies were performed using 1- to 3-day-old piglets raised in room air (control) or 10% O2 (chronic hypoxia) for 10-12 days. Exhaled NO output and plasma nitrites and nitrates (collectively termed NOx-) were measured in anesthetized animals. NOx- concentrations were measured in the perfusate of isolated lungs. eNOS amounts were assessed in whole lung homogenates. In the intact piglets, exhaled NO outputs and plasma NOx- were lower in the chronically hypoxic (exhaled NO output = 0.2 +/- 0.1 nmol/min; plasma NOx- = 10.3 +/- 3.7 nmol/ml) than in control animals (exhaled NO output = 0.8 +/- 0.2 nmol/min; plasma NOx- = 22.3 +/- 4.3 nmol/ml). In perfused lungs, the perfusate accumulation of NOx- was lower in chronic hypoxia (1.0 +/- 0.3 nmol/min) than in control (2.6 +/- 0.6 nmol/min) piglets. The amount of whole lung homogenate eNOS from the chronic hypoxia piglets was 40 +/- 8% less than that from the control piglets. The reduced NO production observed in anesthetized animals or perfused lungs of chronically hypoxic newborn piglets is consistent with the finding of reduced lung eNOS protein amounts. Decreased NO production might contribute to the development of chronic hypoxia-induced pulmonary hypertension in newborns.

Animals↗

PubMed1998

ANP and bradycardic reflexes in hypertensive rats: influence of cardiac hypertrophy.

In previous studies we demonstrated that in normotensive rats, but not in spontaneously hypertensive rats (SHR), atrial natriuretic peptide (ANP) enhances bradycardic reflexes through an action on cardiac vagal afferent pathways. The present study aimed to determine whether cardiac hypertrophy, hypertension, or a nonreversible genetic factor accounted for the insensitivity of SHR to ANP action on cardiac reflex pathways. SHR were treated with the angiotensin-converting enzyme (ACE) inhibitor perindopril (3 mg/kg per day) for 6 weeks from 4 to 9 weeks of age (SHR-S, n=10) or for 9 weeks from 4 to 12 weeks of age (SHR-L, n=10) or were untreated (SHR, n=10) to produce differential effects on blood pressure and left ventricle/body weight ratio (LV/BW). Untreated normotensive Wistar-Kyoto rats (WKY, n=10) were also studied. At 13 weeks of age, all rats were instrumented with aortic and jugular catheters, and at 14 weeks we measured heart rate reflexes to rapid intravenous infusions of methoxamine (100 microg/kg, cardiac baroreflex) and serotonin (5 to 60 microg/kg, von Bezold-Jarisch cardiac chemosensitive reflex), with either alpha-rat ANP (150 ng/kg per minute IV) or saline vehicle (270 microL/h IV) infusion. Perindopril treatment for 6-week (SHR-S) and 9-week (SHR-L) durations maintained blood pressure at normotensive levels in both groups. SHR-S exhibited a small degree of cardiac hypertrophy (LV/BW was 8% higher than in WKY but 11% less than in untreated SHR), but LV/BW was normalized in SHR-L (to within 1% of WKY LV/BW). In WKY, ANP significantly (P<0.05) enhanced bradycardic responses to both the cardiac baroreflex (by 42+/-10%) and von Bezold-Jarisch chemosensitive reflex (by 17+/-5%) activation but had no effect in SHR. The cardiac reflex action of ANP was restored in SHR-L (ANP enhanced reflex bradycardia by 28+/-12% and 36+/-8%, baroreflex and von Bezold-Jarisch reflex, respectively; P<0.05), but SHR-S, which developed some cardiac hypertrophy, remained unresponsive to ANP. Our results suggest that the inability of ANP to sensitize cardiac vagal (nonarterial) afferents in SHR was not due to an inherited irreversible component, or the hypertension per se, but was associated with the presence of cardiac hypertrophy. A functional consequence of hypertension-induced cardiac hypertrophy may be the inhibition of the cardioprotective action of ANP through cardiac vagal reflexes.

Angiotensin-Converting Enzyme Inhibitors↗

PubMed1997

Liquefaction of Autographa californica nucleopolyhedrovirus-infected insects is dependent on the integrity of virus-encoded chitinase and cathepsin genes.

We examined the role of the Autographa californica nucleopolyhedrovirus (AcMNPV)-encoded chitinase in virus pathogenesis in Trichoplusia ni larvae. In conjunction with the AcMNPV-encoded cathepsin, it promotes liquefaction of the host in the latter stages of infection. Insects infected with virus mutants lacking either the chitinase A gene (chiA) or cathepsin gene (cath) remained intact several days after death. However, if both viruses were used to infect insects, liquefaction of the host was restored. Chitinase was readily detected in AcMNPV-infected insects using a chitinase-specific antibody, but it was absent from insects infected with a chiA deletion mutant (AcchiA-). The chitinase was also detected in polyhedra purified from AcMNPV-infected insects but not in those from AcchiA-. However, polyhedra derived from a virus lacking an intact chiA were no less effective in initiating an infection in second instar T. ni larvae than those of the unmodified AcMNPV. It was also demonstrated that the virus chitinase retained high levels of activity between pH 3.0 and 10.0. In contrast, chitinases isolated from Serratia marcescens, although active under acidic conditions, rapidly lost activity above pH 7.0 illustrating that despite 57% sequence identity, the two proteins have distinct enzymic activities.

Animals↗

PubMed1997

The Listeria monocytogenes gene ctpA encodes a putative P-type ATPase involved in copper transport.

A Tn917 transposon derivative was used to construct a lacZ transcriptional fusion mutant in Listeria monocytogenes DRDC8 that displayed increased beta-galactosidase activity in response to cation stress. A 4.3 kb fragment of L. monocytogenes chromosomal DNA flanking the lacZ fusion was cloned and sequenced. A 1962 bp open reading frame was identified, and designated ctpA. Analysis of the deduced 653 amino acid sequence revealed significant similarity to the family of ATP-dependent enzymes involved in copper transport in prokaryotes and eukaryotes. CtpA is distinctive by virtue of an N-terminal truncation in the domain responsible for cation binding. Growth of ctpA insertion mutants was restricted by the copper-chelating agent 8-hydroxyquinoline. DNA/RNA hybridisation studies revealed that levels of ctpA mRNA were increased following growth in media containing low and high copper concentrations. These results suggest the isolation of a region of DNA that encodes a novel copper-transporting system in L. monocytogenes.

Adenosine Triphosphatases↗

PubMed1997

Mutants in the CtpA copper transporting P-type ATPase reduce virulence of Listeria monocytogenes.

The CtpA protein from pathogenic Listeria monocytogenes, is a P-type adenosine triphosphatase involved in copper homeostasis. To establish a role in pathogenicity for CtpA, a mutant strain was constructed by insertion of an antibiotic resistance cartridge into the ctpA gene. This mutant was then compared to the wild-type in tissue culture invasion assays and mouse infection studies. Mutants in CtpA, were unaltered for intracellular growth in J774 and HeLa cell lines. However, recovery of mutants from tissue of infected mice was dramatically reduced compared with the wild-type, and a significant impairment in terms of in vivo persistence in mixed-infection competition experiments was observed. These results demonstrate the significance of CtpA in establishing an in vivo infection by L. monocytogenes, and highlight some inadequacies of in vitro tissue culture monolayer assays for determining invasion and intracellular growth of a pathogen.

ATP-Binding Cassette Transporters↗

PubMed1997

Pilot-scale extraction of PHB from recombinant E. coli by homogenization and centrifugation.

A new method of poly-beta-hydroxybutyrate (PHB) extraction from recombinant E. coli is proposed, using homogenization and centrifugation coupled with sodium hypochlorite treatment. The size of PHB granules and cell debris in homogenates was characterised as a function of the number of homogenization passes. Simulation was used to develop the PHB and cell debris fractionation system, enabling numerical examination of the effects of repeated homogenization and centrifuge-feedrate variation. The simulation provided a good prediction of experimental performance. Sodium hypochlorite treatment was necessary to optimise PHB fractionation. A PHB recovery of 80% at a purity of 96.5% was obtained with the final optimised process. Protein and DNA contained in the resultant product were negligible. The developed process holds promise for significantly reducing the recovery cost associated with PHB manufacture.

Biotechnology↗

PubMed1997

Titanium for removable dentures. II. Two-year clinical observations.

Titanium (Ti) is a relatively new metal in prosthodontics. As a possible material for removable partial dentures (RPDs), it was used in its pure form to make 10 RPDs which were compared with 10 identical cobalt-chromium (Co-Cr) alloy RPDs in a clinical trial. The dentures were used alternately for four weeks, the subjects were asked to answer a questionnaire and then the Co-Cr dentures were withdrawn. The Ti dentures were then followed up for 2 years and another standardized questionnaire administered. A survival rate of rests and retainers of 91% was recorded and the dentures were found to be more comfortable (55%) and preferred (64%) than the Co-Cr dentures. Factors to increase the success rates are discussed.

Chromium Alloys↗

PubMed1997

Treatment of blastomycosis with higher doses of fluconazole. The National Institute of Allergy and Infectious Diseases Mycoses Study Group.

Recent clinical data suggest that fluconazole at daily doses of 200 to 400 mg for at least 6 months is moderately effective therapy for non-life-threatening blastomycosis. To examine the usefulness of higher doses of fluconazole therapy for this disorder, we conducted a multicenter, randomized, open-label study to determine the efficacy and safety of two different daily doses of fluconazole (400 and 800 mg) in the treatment of non-life-threatening blastomycosis. Of 39 patients evaluable for efficacy analysis, 34 (87%) were successfully treated, including 89% and 85% of patients who received 400 and 800 mg, respectively. Five (83%) of six patients for whom prior antifungal therapy had failed were successfully treated. The mean duration of therapy was 8.9 months for successfully treated patients. Nineteen patients (48%) reported adverse events, although most were minor. We conclude that fluconazole at daily doses of 400 to 800 mg for at least 6 months is effective therapy for non-life-threatening blastomycosis.

Adolescent↗

PubMed1997

ANP enhances bradycardic reflexes in normotensive but not spontaneously hypertensive rats.

Baroreflex control of heart rate in spontaneously hypertensive rats (SHR) is defective, largely because of a poor vagal contribution to the reflex. We have demonstrated previously that atrial natriuretic peptide (ANP) enhances reflex bradycardia in normotensive rats through an action on nonarterial vagal afferent pathways. In the present study, we investigated whether ANP could reverse the baroreflex abnormality in SHR. Heart rate reflexes were activated by three different methods in conscious, instrumented SHR and Wistar-Kyoto rats (WKY) in the presence of intravenous infusions of vehicle (saline) or rat ANP (150 ng/kg per minute). Heart rate responses were measured by (1) the steady-state changes in blood pressure after alternating slow infusions (over approximately 15 to 30 seconds) of a pressor (methoxamine) and depressor (nitroprusside) drug (stimulating predominantly arterial baroreceptors), (2) the ramp method of rapid infusion of methoxamine (over < 10 seconds; stimulating arterial and cardiopulmonary baroreceptors), and (3) the von Bezold-Jarisch method of activating chemically sensitive cardiac receptors through serotonin injections. ANP enhanced the heart rate range of the arterial baroreflex (steady-state method) by 13 +/- 3% in WKY but had no significant effect on the sensitivity or any other parameter of the steady-state baroreflex. When a very rapid rise in blood pressure was elicited by the ramp method in WKY, ANP significantly enhanced baroreflex bradycardia (sensitivity increased by 29 +/- 9%, P < .05). ANP also enhanced the bradycardia of the von Bezold-Jarisch reflex (by 33 +/- 16%, P < .05) in WKY. By contrast, ANP did not influence baroreceptor or chemoreceptor heart rate reflex responses in SHR. We conclude that in normotensive rats, ANP facilitates cardiopulmonary bradycardic reflexes. The lack of effect of ANP in SHR may be related to an underlying structural or genetic alteration in their cardiac sensors, perhaps associated with cardiac hypertrophy, that prevents the ANP-induced activation of cardiac sensory afferents, resulting in cardioinhibition.

Animals↗

PubMed1996

Biostereometric quantification of clinical denture tooth wear.

In this study the wear of mandibular acrylic resin teeth opposed by porcelain maxillary teeth arranged in a lingualized occlusal scheme over a period of 3 years was measured. Six edentulous subjects received complete dentures as above and with three baseline markers of amalgam. At yearly intervals casts were made of the mandibular occlusal surfaces, including markers, and plotted by stereophotogrammetry. Volumetric loss of material was quantifiable. Ranges of 0.62-3.33 mm3/mm2 on the left side and 0.71-1.64 mm3/mm2 on the right were recorded. Friedman two-way ANOVA test indicated significant wear on teeth 35, 36, 45 and 46 but not on 34 and 44. A one-sided chewer displayed greater wear on the contralateral side, a finding difficult to explain.

Acrylic Resins↗

PubMed1996

Treatment of lymphocutaneous and visceral sporotrichosis with fluconazole.

Thirty patients with documented sporotrichosis were treated with 200-800 mg of fluconazole daily. Fourteen patients had lymphocutaneous infection; only five (36%) of these patients had any underlying illnesses. Sixteen patients had osteoarticular or visceral sporotrichosis; 12 (75%) of these patients had underlying diseases, mostly alcoholism, diabetes mellitus, and chronic obstructive pulmonary disease. Eleven of the 30 patients had relapsed after prior antifungal therapy. Most patients were treated with 400 mg of fluconazole; however, four received 200 mg of fluconazole daily for the entire course, and four received 800 mg of fluconazole daily for a portion of their therapy or for the entire course of therapy. Fluconazole therapy cured 10 (71%) of 14 patients with lymphocutaneous sporotrichosis. However, only five (31%) of 16 patients with osteoarticular or visceral sporotrichosis responded to therapy; the conditions of two of these five patients improved only, and there was no documented cure of their infections. With the exception of alopecia in five patients, toxic effects were minimal. Fluconazole is only modestly effective for treatment of sporotrichosis and should be considered second-line therapy for the occasional patient who is unable to take itraconazole.

Adult↗