Biomedical subjects
C Stewart
Publications and source records attributed to C Stewart.
IL-12-deficient mice are defective in IFN gamma production and type 1 cytokine responses.
IL-12 is a cytokine that can exert regulatory effects on T and NK cells and promote Th1 responses. To delineate further the physiologic role of IL-12 in immunity, mice deficient for this cytokine were generated. IL-12-deficient mice were impaired but not completely lacking in the ability to produce IFN gamma following endotoxin administration and to mount a Th1 response in vivo, as measured by antigen-induced IFN gamma secretion by immune lymph node cells in vitro. In contrast, secretion of IL-4 was enhanced, while proliferation and secretion of IL-2 and IL-10 were normal following antigen stimulation. DTH responses were significantly reduced in IL-12-deficient mice, but no defect in allogeneic CTL responses was observed. These results indicate that IL-12 plays an essential role in regulating IFN gamma production and in facilitating normal DTH responses. However, other phenomena associated with Th1 responses and cell-mediated immunity, i.e., IL-2 secretion and CTL generation, were not compromised in the absence of IL-12.
Oral diseases, mycology and periodontal microbiology of HIV-1-infected women.
HIV-1 infection is increasing more rapidly among heterosexual women. Relatively limited information is available on HIV-related oral pathoses in these individuals. To gain insight into the type and occurrence of oral lesions in this population, 25 HIV-1 infected women including asymptomatic, symptomatic and AIDS patients were examined clinically and sampled for detection of oral yeast and characterization of their subgingival microbial flora. Sixty percent of the subjects were African-American, with 80% infected via heterosexual contact. Oral candidiasis was the most common nonperiodontal oral lesion, observed in 44% of the patients. Oral yeast was cultured from all women with candidiasis and 76% of the total subjects. Oral hairy leukoplakia was clinically diagnosed in 16% of the subjects. Clinically mild to moderate gingivitis and periodontitis were observed in 84% and 52% of the patients, respectively. Candidiasis and the presence of cultivable yeast were observed in patients with low, intermediate, and high CD4+ T lymphocyte numbers. Plaque samples were collected from each subject and enumerated by predominant cultivable methods, selective media and microscopy. No differences were detected in the microflora associated with seropositive women with existing periodontitis relative to those without periodontitis or to seronegative women with periodontitis. Candidiasis was the most notable oral clinical manifestation in the HIV-1-infected women and may be a useful clinical indicator of early immune dysfunction mediated by HIV-1.
Patient sedation for routine genital examination.
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Oral complications associated with the use of immunosuppressive agents in a renal transplant patient.
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Creation and characterization of E-selectin- and VCAM-1-deficient mice.
A variety of adhesion molecules have been identified which mediate the interaction of leukocytes with endothelial cells. In order to define the role of individual molecules in inflammation we have produced lines of mice which are deficient in the synthesis of specific adhesion molecules. Null mutations were introduced into the genes encoding E-selectin or vascular cell adhesion molecule-1 (VCAM-1) in embryonic stem cells and these cells were used to produce lines of mice carrying the mutation. E-selectin-deficient mice were viable and exhibited no developmental defects. The roles of E- and P-selectin in the influx of neutrophils were examined using these mice. The data suggest that the two selectins are functionally redundant in mediating neutrophil emigration in a model of chemically induced peritonitis. VCAM-1-deficient mice are not viable. Analysis of VCAM-1 gene expression in wild-type embryos and phenotypic analysis of VCAM-1 -/- embryos suggests that VCAM-1 is required for development of the extraembryonic circulatory system and the embryonic heart.
Speech dysfunction in early Parkinson's disease.
The purpose of this study is to determine if subjects in the early stages of untreated Parkinson's disease (PD) or PD treated with deprenyl alone suffer from motor speech abnormalities. Speech defects are common in advanced PD, including disturbances of respiration, phonation, and articulation. We studied 12 subjects with early PD (Hoehn and Yahr stage < or = 2, mean duration disease 3.2 years) who were not taking symptomatic therapy and tested them under two conditions: on and off deprenyl. None of the subjects was depressed or demented (Mini Mental Status mean 29.9/30; Hamilton Depression Rating mean 2.7/52). All functioned independently (Schwab and England Activities of Daily Living mean 93.1/100). Acoustic and speech productions were assessed using the DSP Sona-Graph 5500 and an evaluation of dysarthria. All 12 had at least two characteristics of dysarthria on examination, although 8 were not aware of it. Vocal tremor was identified on narrow band spectrogram for four subjects. Deprenyl did not have a consistent effect on speech. Ten subjects had no detectable change in speech on deprenyl, one was worse, and one was improved.
Synovial fluid from rheumatoid arthritis patients contains sufficient levels of IL-1 beta and IL-6 to promote production of serum amyloid A by Hep3B cells.
The presence of positive acute phase proteins within the circulation of rheumatoid arthritis patients suggests that elevated cytokine production associated with this chronic inflammatory disorder initiates the hepatic acute phase response. Cytokines produced at inflammatory lesions are believed to travel via the circulation to the liver where they induce acute phase protein production by hepatocytes. To test whether serum from rheumatoid arthritis patients contained sufficient levels of cytokines to promote an acute phase response in vitro, a bioassay was developed that employed the human hepatoma cell line Hep3B. These cells produced the acute phase protein serum amyloid A (SAA) in response to a combination of recombinant IL-1 beta and IL-6 or to monocyte conditioned medium. Serum (or plasma) from normal individuals or from rheumatoid arthritis patients did not induce SAA production by Hep3B cells. Moreover, these serum samples did not prevent SAA production induced by monocyte conditioned medium, indicating that they did not contain inhibitors of cytokine activity. Despite the inactivity of serum samples, synovial fluid samples obtained from rheumatoid arthritis patients were active in the hepatocyte bioassay and promoted SAA synthesis. One synovial fluid sample was analysed in detail to identify cytokines responsible for the SAA-inducing activity. Neutralizing antisera against IL-6 and IL-1 beta blocked this activity by > 90% whereas anti-IL1 alpha and anti-TNF-alpha sera were without effect. Absolute cytokine levels within the synovial fluid sample were determined by ELISA; IL-6, IL-beta and TNF-alpha, but not IL-1 alpha, were confirmed to be present. Moreover, the synovial fluid sample contained a large amount of the IL-1 receptor antagonist. These data indicate, therefore, that synovial fluid recovered from an inflamed joint contains all the necessary cytokines in balance with inhibitors to promote SAA production by Hep3B cells. The steady state levels of these factors within the plasma compartment, however, were insufficient to induce the acute phase response by cultured Hep3B cells, suggesting that this system does not mimic the relationship between the circulation and the liver that likely exists in rheumatoid arthritis patients.
Correlation between meta(tetrahydroxyphenyl)chlorin (m-THPC) biodistribution and photodynamic effects in mice.
Analysis of sensitizer kinetics is essential for the performance of light irradiation when tumour concentration and tumour-to-normal tissue ratios are optimal. In this study nude mice were grafted with human adenocarcinoma 15 days before meta(tetrahydroxyphenyl)chlorin (m-THPC) intra-peritoneal (IP) injection. Fluorescence was recorded through an optic fibre spectrofluorometer at 650 (the most intense) and 714 nm, with intensity being proportional to injected dose. In tumour, skin and muscle the maximum fluorescence was obtained with 1.6 mg kg-1 72 h after injection (44 counts per second). Tumour-to-skin and tumour-to-muscle ratios obtained by high performance liquid chromatography (HPLC) analysis and spectrofluorometric measurements decreased between 12 and 72 h (from 15 to 1.5), indicating that tumour selectivity decreases with time. This contrast between selectivity and fluorescence levels was also observed with photodynamic therapy (PDT) results, for which no differences were observed when 10 J cm-2 were delivered at 100 or 200 mW. PDT results were better 24 h after drug administration than at 72 h. Tumour growth decrease (-40%) was found when 1.6 mg kg-1 were injected 24 h before irradiation. For other groups a slower increase (12% vs. 23%) was noted in the first few days after PDT. The paradoxal correlation between fluorometric or HPLC measurements and PDT effects suggests that m-THPC localizes differently with time in tumour components.
Voice failure after tracheoesophageal puncture: management with botulinum toxin.
Primary or secondary tracheoesophageal puncture with a speaking prosthesis has provided rehabilitation of speech in most patients after total laryngectomy. Persistent constrictor spasm is thought to be responsible for a small percentage of these patients' inability to speak with the prosthesis. Management of these patients has included bougienage and pharyngeal myotomy and/or pharyngeal neurectomy. Botulinum toxin injections of the cricopharyngeus muscle complex in six patients have been successfully used diagnostically and therapeutically for tracheoesophageal puncture failures. The assessment, technique, and results are discussed.
Exclusion mapping of chromosomal regions which cross hybridise to FSHD1A associated markers in FSHD1B.
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Platelet size in stroke patients.
BACKGROUND AND PURPOSE: Large platelets are more reactive, produce more prothrombotic factors, and aggregate more easily. Platelet size can be readily estimated using automated analyzers, although accurate estimation depends on precise methodology. The disparate results from previous studies of mean platelet volume in cerebral ischemia may be explained by varying methodology. We have studied these variables using a precise methodology in an unselected group of stroke patients and compared them with data from age- and sex-matched control subjects. METHODS: We studied 58 stroke patients consecutively admitted to a geriatric medical unit. Platelet variables were measured in the acute (< 48 hours after stroke) and chronic (> 6 months) phases of cerebral ischemia and compared with control variables. Control patients, admitted to the same unit, were of similar age and sex and without evidence of acute vascular events. RESULTS: Mean platelet volume was higher in acute stroke (11.3 compared with 10.1 fL in control subjects; P < .001, Student's t test). In addition, platelet count was reduced in stroke patients (255 x 10(9)/L) compared with control subjects (299 x 10(9)/L; P < .01). Repeated measurements of mean platelet volume and platelet count in available survivors showed no significant change from the acute phase. Platelet changes did not relate to outcome measured at 6 months. CONCLUSIONS: With the use of more precise methodology, these findings show that an increase in mean platelet volume and a reduction in platelet count are features of both the acute and nonacute phases of cerebral ischemia. It is possible that these changes precede the vascular event, and further studies are warranted.
Dyspnea in dystonia. A functional evaluation.
BACKGROUND: Dystonia consists of action-triggered sustained focal muscle contractions, worsened by effort, and resulting in voice changes, abnormal posturing, and dyspnea. The cause of dyspnea, previously unexplained, is the basis of this report. METHODS: Since the maximal efforts required to perform pulmonary function testing (PFT) could worsen the muscular contractions in dystonic patients, we used several tests to identify possible causes of dyspnea. These included spirometry with flow volume loops (FVL), tidal volume breathing, maximum voluntary ventilation (MVV), and inspiratory and expiratory muscle pressures (PImax, PEmax), sitting and supine. We used cycle ergometry with arterial blood gas (ABG) values to detect cardiac/pulmonary limitations and respiratory inductive plethysmography (RIP) to assess chest wall/abdominal movements for synchrony. Dynamic videofluoroscopy (VF) assessed and recorded the action-triggered muscle activity of the upper airways and the diaphragm during quiet breathing, speech, swallowing, and maximal respiratory maneuvers similar to the efforts required during PFT. RESULTS: Twenty-six dystonic patients, 12 women and 14 men, ages 14 to 70 years (mean age, 52.3 years) were evaluated. Their neurologic classification included 22 primary (idiopathic) and 4 secondary (2 postneuroleptic use, 2 posstraumatic). Four patients originally classified as having focal dystonia had dyspnea and were found to have diaphragmatic and/or upper airway dysfunction too. The PFTs showed abnormal FVL and/or tidal volume breathing patterns, with intermittent interruptions of air flow during inspiration or expiration in 20 of 24 patients. The VF was abnormal in 24 of 26 patients: 19 patients had combined upper airway (UA) and diaphragmatic dysfunction (DD); 1 patient had UA dysfunction alone, and 4 patients had DD alone. Except for poor effort and/or dystonic movements, cycle ergometry was normal in 18 of 21 patients. The ABG values and/or pulse oximetry were normal in 19 of 22 patients. CONCLUSION: Dyspnea in dystonia appears to be due to excessive and/or dysynchronized contractions of the upper airways and/or diaphragm, with usually normal gas exchange. These spasmodic and irregular muscular contractions during speech and daily activities are associated with the sensation of excessive effort to overcome the spasms. Excessive spasms can be triggered during PFT and are best detected on FVL patterns coupled with dynamic VF.
Serum screening for Down's syndrome. Keeping the concept of risk simple.
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LTP-like synaptic efficacy changes following electroconvulsive stimulation.
Synaptic plasticity is thought to represent a mechanism for memory formation. Memory disturbances commonly follow electroconvulsive therapy (ECT) for depression. Accordingly, we examined the development and duration of the effects of electroconvulsive stimulation (ECS) on hippocampal synaptic plasticity in rats. Daily recording of field potentials during 10 spaced ECS revealed an increase in the dentate gyrus evoked response, reaching a maximum after the fifth seizure. In a second experiment, an identical ECS series substantially reduced the degree to which electrically induced synaptic changes (long-term potentiation--LTP) could be elicited under anaesthesia for up to 40 days. These findings suggest that ECS induces LTP-like long-lasting synaptic changes which may underlie the neuropsychological sequelae of ECT treatment in humans.
Mapping and sequencing of two yeast genes belonging to the ATP-binding cassette superfamily.
ATP-binding cassette (ABC) transporters share significant sequence identity within their ATP-binding domains. Degenerate oligonucleotides based on highly conserved portions of the ATP-binding domain genes were used to clone portions of two members of the ABC gene superfamily from Saccharomyces cerevisiae DNA. These genes were designated MDL1 and MDL2 (for multidrug resistance-like). Each MDL gene is predicted to encode a single set of transmembrane domains and a single ATP-binding domain, thus the MDL gene products are 'half-molecule' ABC proteins. The two genes were mapped to precise regions on chromosomes XII and XVI and show a considerable similarity to the mammalian P-glycoprotein/multidrug resistance (MDR) and peptide transporter (TAP) genes. Preliminary analysis of null mutants constructed by gene replacement has indicated that the MDL genes are not essential for viability of yeast. The sequences have been deposited in the GenBank data library under Accession Numbers L16958 (Locus YSCBCSA) and L16959 (Locus YSCBCSB).
A computerised cancer registry data and validation system in India--its implications for developing countries.
The cancer registration system in India, and an appropriate computer program to validate the cancer patient data it generates, are described, with the resource inputs, and outputs of research, training, awareness creation and cancer control, in the context of local health care systems. Computer packages already available mostly address the type of data obtainable from western health care systems. The same factors that limit health care systems in India, and probably most other developing countries--inadequate health care facilities, skeletal medical records systems, meagre and unavailable vital statistics, few trained staff, funding and computer facilities--also limit the data sent to the National Cancer Registry Programme. The computer program we developed checks for the reliability and validity of various cancer diagnostic, spread, therapeutic and outcome variables. The program is in HIBASIC for a CPM operating system with a minimum of 64 kB memory, adaptable to MS-DOS systems, population-based cancer registry data, and perhaps to other types of chronic disease registries, with relevant modifications. Since reliable cancer registry data are needed for effective cancer control measures, this program may help in such efforts in developing countries.
The use of peat in the historical monitoring of trace metals in the atmosphere.
The concentrations of lead, zinc, copper, manganese, cadmium and calcium have been measured in three peat bogs. The distribution of Pb, Zn, Mn and Ca are dependent on the position and fluctuations of the water table. They all become depleted in the waterlogged, anaerobic zone. Copper and cadmium are uniformly distributed and appear to be immobilised, probably by the formation of metal/organic complexes, and independent of the acid and redox conditions existing in the bogs. The use of the concentration profiles of the metal ions as a means of historical monitoring of trace metal contamination is complex for Pb, Zn, Mn and Ca but may be more straightforward for Cu and Cd.