Biomedical subjects
C Cox
Publications and source records attributed to C Cox.
Immunization of common marmosets with Epstein-Barr virus (EBV) envelope glycoprotein gp340: effect on viral shedding following EBV challenge.
Epstein-Barr virus (EBV), the cause of infectious mononucleosis, is involved in the pathogenesis of several human cancers, the highest frequency of association being found in undifferentiated nasopharyngeal carcinoma and endemic Burkitt's lymphoma. The development of animal models in which potential vaccines can be tested is important. EBV infection of the common marmoset, using the M81 strain originally derived from a patient with nasopharyngeal carcinoma, induces a carrier state in this animal. Persistent infection is characterized by the production of antibodies to viral antigens, and the secretion of EBV DNA into buccal fluids. Following immunization with envelope glycoprotein gp340 derived from a bovine papilloma virus expression vector, prior to EBV infection, viral DNA was detected significantly less frequently in the buccal fluids of immunized, than of nonimmunized, infected animals, indicating that although the carrier state had not been abolished, it had been altered. A reduction in virus load was also observed when offspring of seronegative, and on occasion seropositive, parents were immunized neonatally, before EBV challenge.
Biological monitoring of workers exposed to carbon disulfide.
Urinary 2-thiothiazolidine-4-carboxylic acid (TTCA) concentrations and corresponding personal breathing zone carbon disulfide (CS2) air concentrations were measured for worker populations at a Tennessee rubber product facility and a Virginia viscose rayon plant. At the rubber product facility, all of the 19 workers had urinary TTCA levels less than the limit of detection (LOD) of about 0.03 mg/L, equivalent to less than 0.5 ppm of CS2 in air. At the viscose rayon plant, five of six workers, although wearing half-mask cartridge respirators, showed increased urinary TTCA during the workshift. The cutters and spinners had the largest increases in urinary TTCA concentrations; they also had the highest breathing zone exposures to CS2. The TTCA concentrations for three cutters and spinners did not return to normal preshift levels of < 0.3 mg/g creatinine before the start of the next shift. The arithmetic mean respirator workplace protection factor (WPF) was 7.0 +/- 2.2. Increase in urinary TTCA concentration during the workshift and postshift urinary TTCA concentration reflected CS2 air concentration equally well. In conjunction with air monitoring results, urinary TTCA concentrations allow determination of the WPF afforded workers wearing respirators and identify workers not adhering to safety rules and good work practices. Workers at risk of adverse health effects from overexposure to CS2 for any reason may thus be identified.
Antipsychotic drug regulation of AMPA receptor affinity states and GluR1, GluR2 splice variant expression.
We recently reported that chronic administration of antipsychotic drugs dramatically elevated [3H]AMPA binding, with minimal elevation of [3H]CNQX binding in rat brain. The aim of the current study was to examine the mechanism of this effect. Chronic haloperidol minimally increased the total number of binding sites (total Bmax) compared to saline-injected animals. Specifically, haloperidol dramatically increased the proportion of high-affinity-site AMPA receptors (approximately 30% increase) without inducing a significant change in the low-affinity constant. In situ hybridization for flip and flop isoforms of GluR1 and GluR2 (AMPA receptors) was not altered in a pattern or degree that compared to the changes seen in AMPA receptor binding. These findings suggest that the long-term action of antipsychotic drugs may be to regulate AMPA receptor responsiveness to agonist stimulation via posttranscriptional means, and is unlikely to be related to GluR1 or GluR2 splice variant expression. This effect may have relevance to both the therapeutic effects and side effects of antipsychotic drugs in humans.
Correlates of photoreceptor rescue by transplantation of human fetal RPE in the RCS rat.
This study uses a water maze paradigm as a tool to assess posttransplantation changes in behavior associated with a visual stimulus. A set of dystrophic RCS rats received bilateral injections of freshly isolated human fetal RPE cells into the subretinal space of the superior equatorial hemisphere. Five age-matched control dystrophic RCS rats received subretinal injections of vehicle. All animals were immunosuppressed. At 2 months posttransplantation, each rat was tested in the water escape apparatus. The rat used a single light source, randomly located on the edge of the tank, to locate a submerged platform, placed directly in front of the light. Each rat was timed and videotaped during 10 consecutive trials. The swimming paths and times for all rats were recorded and statistically analyzed. Subsequent to the water escape trials, the eyes were embedded for histologic analysis which included quantitative assessment of photoreceptor cells in predefined retinal regions. The water escape data indicated the differences between the sham and experimental groups changed significantly over time (P = 0.0017). Over time, the transplanted animals learned to use light as a clue (P < 0.0001), whereas the sham animals did not (P = 0.73). Transplanted eyes had a significantly greater mean number of photoreceptors in the superior, grafted region than seen in the inferior region of the same eyes and compared with either region of sham-injected eyes (P = 0.0023). Statistical analyses demonstrated a functional advantage for visually guided behavior in RCS rats transplanted with human fetal RPE cells and a statistically significant PRC rescue effect at 2 months after transplantation.
Acute respiratory exposure of human volunteers to octamethylcyclotetrasiloxane (D4): absence of immunological effects.
Humans are exposed to silicones in a number of commercial and consumer products. Some of these silicones, including octamethylcyclotetrasiloxane (D4), are volatile. Therefore, there is a potential for respiratory exposure. A pharmacokinetic analysis of respiratory exposure to D4 is presented in the accompanying paper (M. J. Utell et al., 1998, Toxicol. Sci. 44, 206-213). Possible immune effects of respiratory exposure to D4 are investigated in this paper. Normal volunteers were exposed to 10 ppm D4 or air for 1 h via a mouthpiece using a double-blind, crossover study design. Assays were chosen to screen for immunotoxicity or a systemic inflammatory response. Assessment of immunotoxicity included enumeration of peripheral lymphocyte subsets and functional assays using peripheral blood mononuclear cells. Because in humans there is no direct test for adjuvant effect of respiratory exposure, we analyzed proinflammatory cytokines and acute-phase reactants in peripheral blood, markers for a systemic inflammatory response, as surrogate markers for adjuvancy. These tests were repeated when the volunteers were reexposed to D4 approximately 3 months after this initial exposure. Blood was obtained prior to exposure, immediately postexposure, and 6 and 24 h postexposure. In these short-term, controlled human exposures, no immunotoxic or proinflammatory effects of respiratory exposure to D4 were found.
DNA cytometry and chromosome 9 aberrations by fluorescence in situ hybridization of irrigation specimens from bladder cancer patients.
OBJECTIVES: To determine the sensitivity and specificity of combining fluorescence in situ hybridization (FISH) measurement of chromosome 9 and DNA cytometry of bladder irrigation specimens in the detection of bladder cancer. METHODS: Bladder irrigation specimens were obtained from 37 normal control patients and 317 bladder cancer patients during cystoscopic examinations. Bladder cancer patients were sampled in the absence of observable tumor (256 specimens) and concurrently with tumor (204 specimens). Chromosome 9 copy number was determined on a cellular basis by FISH, and cellular DNA content was determined by Feulgen DNA staining and image cytometry. RESULTS: Sensitivity of chromosome 9 FISH was 42% for all tumors and was not correlated to transitional cell carcinoma tumor grade, while the sensitivity of DNA cytometry was 55% and improved with increasing grade from 38% for grade 1 to 90% for grade 3 tumors. The results of FISH and DNA cytometry were combined, resulting in specificity of 92% and sensitivity of 69% for grade 1, 76% for grade 2, and 97% for grade 3 tumors. CONCLUSIONS: The lack of increase with grade in the percentage of positive specimens by FISH supports the hypothesis that chromosome 9 aberrations are critical events in bladder tumorigenesis for many patients. These data demonstrate the presence of cells in irrigation specimens with specific genomic lesions of chromosome 9 and DNA content. Combining FISH on chromosome 9 and DNA cytometry provides an increase in sensitivity to transitional cell carcinoma over either test alone.
Sonochemicals increase the mutation frequency of V79 cells in vitro.
Phosphate buffered saline (PBS) was insonated or sham-insonated (1 MHz, 35 W/cm2, continuous wave, 30 min) in rotating (200 rpm) sterile polystyrene culture tubes. After treatment, the PBS was used immediately to suspend washed Chinese hamster V79 cells in vitro. Cells were incubated in the PBS at 37 degrees C for 15 min and then transferred to complete growth medium. Some insonation regimens also involved the inclusion of Albunex (ALX; an ultrasound microbubble contrast agent) to enhance ultrasound-induced inertial cavitation. Following exposure to the pretreated PBS and 6 d of subculture in complete medium, the cells were assayed for plating efficiencies and mutation frequencies (resistance to 6-thioguanine). X-rays (3 Gy) served as a positive control. Cells exposed to insonated PBS with or without ALX or x-rays had statistically significantly elevated mean mutation frequencies (4.37+/-0.97, 4.54+/-1.00, and 24.28+/-3.83 mutant colonies/10(6) viable cells, respectively) relative to corresponding control regimens (ultrasound sham, 2.44+/-0.56; x-ray sham, 2.96+/-0.88 mutant colonies/10(6) viable cells. The data supported the hypothesis that sonochemicals resulting from inertial cavitation have mutagenic potential.
Troponin I release and myocardial protection with diltiazem in coronary artery bypass surgery.
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Experiences of administering and receiving therapeutic touch in intensive care.
This article describes the experiences of a practitioner who administered therapeutic touch (TT) to two patients in an intensive care unit and the experiences of the two patients who received TT. The experiences are presented as two case studies. Each of the patients presented in the case studies received either five or ten treatments of TT lasting five minutes each. Following each administration of TT the practitioner described what she sensed verbally and in writing. However, owing to the medical conditions of the patients, only brief interviews were conducted in which the patients were asked to describe their experiences of receiving TT. The experiences, which have been reflected in the case studies, indicate TT assists patients to relax, brings comfort and a sense of peace. Much like meditation, TT helps patients become more in touch with themselves. They come to understand more about themselves and reality. TT is recommended as a practice which could contribute to the psychological well-being of patients in intensive care as it promotes relaxation, comfort and a sense of peace.
Quantitative and qualitative differences in the verbal learning performance of elderly depressives and healthy controls.
We compared the verbal learning and memory performance of 57 inpatients with unipolar major depression and 30 nondepressed control participants using the California Verbal Learning Test. The effect of age within this elderly sample was also examined, controlling for sex, educational attainment, and estimated level of intelligence. Except for verbal retention, the depressive had deficits in most aspects of performance, including cued and uncued recall and delayed recognition memory. As well, there were interactions between depression effects and age effects on some measures such that depressives' performance declined more rapidly with age than did the performance of controls. The results are discussed in the context of recent contradictory reports about the integrity of learning and memory functions in late-life depression. We conclude that there is consistent evidence, from this and other studies, that elderly depressed inpatients have significant deficits in a range of explicit verbal learning functions.
Effects of dietary coconut oil, butter and safflower oil on plasma lipids, lipoproteins and lathosterol levels.
OBJECTIVE: The aim of this present study was to determine plasma levels of lathosterol, lipids, lipoproteins and apolipoproteins during diets rich in butter, coconut fat and safflower oil. DESIGN: The study consisted of sequential six week periods of diets rich in butter, coconut fat then safflower oil and measurements were made at baseline and at week 4 in each diet period. SUBJECTS: Forty-one healthy Pacific island polynesians living in New Zealand participated in the trial. INTERVENTIONS: Subjects were supplied with some foods rich in the test fats and were given detailed dietary advice which was reinforced regularly. RESULTS: Plasma lathosterol concentration (P < 0.001), the ratio plasma lathosterol/cholesterol (P=0.04), low density lipoprotein (LDL) cholesterol (P<0.001) and apoB (P<0.001) levels were significantly different among the diets and were significantly lower during coconut and safflower oil diets compared with butter diets. Plasma total cholesterol, HDL cholesterol and apoA-levels were also significantly (P< or =0.001) different among the diets and were not significantly different between buffer and coconut diets. CONCLUSIONS: These data suggest that cholesterol synthesis is lower during diets rich in coconut fat and safflower oil compared with diets rich in butter and might be associated with lower production rates of apoB-containing lipoproteins.
Enhancement by polylysine of transient, but not stable, expression of genes carried into cells by polyoma VP1 pseudocapsids.
Gene transfer to provide long-term expression of a therapeutic product, without introducing unwelcome genetic information, is a goal being sought for therapy of both hereditary and acquired diseases. Polyoma virus pseudocapsids, generated from a VP1-expressing recombinant baculovirus, lack viral DNA and have been successfully used to introduce small exogenous genes stably into cells in vitro by a process designated 'pseudofection'; although pseudocapsids protect only about 3 kbp of exogenous DNA, low efficiency transfer of a larger fragment (6.2 kbp) has been observed. Here, expression of a 7.2 kbp plasmid (pCMV beta) encoding the beta-galactosidase gene was assessed to monitor not only efficiency, but the ability of pseudocapsids to transfer larger-sized DNA on their own, or in the presence of the polycation, poly-L-lysine, added to protect nonencapsidated DNA. When complexed to pseudocapsids only, the efficiency of expression of the transferred beta-galactosidase gene (in human or rodent cells), although low, appeared to stabilise with time. In the presence of polylysine, unencapsidated DNA was shown to be protected against DNase activity, but electron microscopy (EM) revealed the formation of large mixed aggregates. The addition of pseudocapsids to these aggregates, and measurement of mobilities of the complexes in CsCl equilibrum centrifugation, indicated that they contained negligible amounts of VP1. For subsequent pseudofection experiments, DNA was complexed first with pseudocapsids, then polylysine was added. The latter did not appear to displace pseudocapsids from DNA, and was found to increase the efficiency of short-term expression both in in vitro and in vivo experiments. Gene expression, analysed histochemically or by the polymerase chain reaction, revealed transcriptional activity of the input gene, with expression first diminishing, then stabilising over time. The presence of pseudocapsids, in complexes with DNA with or without polylysine, allowed for stable and persistent gene expression.
Hospice care for persons with AIDS: findings from a national study.
Hospices are in a position to play major roles in the care of terminally ill patients with AIDS. These findings from a national survey of hospices in the United States show that the majority of hospices have cared for at least one PWA. Major factors determining hospice involvement include geographic location and resources. In comparison to other patients in hospice, PWAs are younger, more likely to be male, Black or Hispanic, and covered by Medicaid. The results indicate that hospices are reaching women with AIDS and IVDUs but that minorities continue to be underrepresented in comparison to their distribution among the total AIDS cases in the United States.
Preliminary evidence of psychological distress among reservists in the Persian Gulf War.
This study was conducted as a preliminary investigation into the presence and nature of psychological distress among military reserve personnel as a result of their participation in the Persian Gulf War. Eleven months after cessation of hostilities in the Gulf War, a self-report survey was mailed to the home of each of the 1090 members who had been assigned to the study Air National Guard unit during this period. After unit activation in December 1990, 517 of these individuals were deployed to the Persian Gulf as participants in Operation Desert Storm. The remainder of the unit participated in their military service during this period without being deployed to the Persian Gulf. The survey consisted of a demographic section, the Mississippi Scale for Combat Related Posttraumatic Stress Disorder (M-PTSD), the revised Symptom Checklist 90 (SCL-90-R), and an anecdotal response section; 46% of those surveyed responded. The major finding of the study was that 6.8% of the respondents who served in the combat theater had elevated M-PTSD scores. This was a statistically significant finding compared with the 1.7% of those surveyed who had elevated M-PTSD scores having served at home (chi2 = 6.25, df = 1, p = .01). These elevated M-PTSD scores were found despite low levels of traditional combat stressors and strong levels of perceived public support. SCL-90-R scores were also higher in deployed versus nondeployed respondents. Although the clinical presence of PTSD was not established by this study, the preliminary finding of elevated M-PTSD scores in the deployed group is suggestive of the possibility of clinical PTSD. This finding supports the need for further PTSD research among reservists who are exposed to nontraditional combat stressors. Elevated SCL-90-R scores in the deployed group also suggest that other forms of psychological distress may have developed in a significant number of combat veterans of the Persian Gulf War.
Efficacy and tolerability of carbamazepine for agitation and aggression in dementia.
OBJECTIVE: The efficacy, safety, and tolerability of carbamazepine in the treatment of agitation and aggression associated with dementia were assessed. METHOD: In a 6-week, randomized, multisite, parallel-group study of 51 nursing home patients with agitation and dementia, individualized doses of carbamazepine were compared with placebo. Except for a physician monitor and a pharmacist, all participants were blind to treatment. The primary outcome measures were the Brief Psychiatric Rating Scale (BPRS) and Clinical Global Impression (CGI) global improvement rating. Secondary measures included measures of behavior, aggression, cognition, functional status, staff time, safety, and tolerability. Intent-to-treat analysis was performed. RESULTS: The modal carbamazepine dose at 6 weeks was 300 mg/day, and a mean serum level of 5.3 micrograms/ml was achieved. The study was terminated after a planned interim analysis showed that carbamazepine provided more benefit than did placebo. Over 6 weeks the mean total BPRS score decreased 7.7 points for the carbamazepine group and 0.9 for the placebo group, and the weekly scores showed a gradual divergence between the two groups. CGI ratings showed global improvement in 77% of the patients taking carbamazepine and 21% of those taking placebo. Secondary analyses confirmed that the positive changes were due to decreased agitation and aggression. The drug was generally well tolerated, and no change in cognition or functional status occurred. The perception of staff time needed to manage agitation showed a decrease for carbamazepine but not placebo. CONCLUSIONS: This controlled study showed significant short-term efficacy of carbamazepine for agitation with generally good safety and tolerability.
Medical illness burden, trait neuroticism, and depression in older primary care patients.
OBJECTIVE: The authors tested the hypotheses that medical illness burden is independently associated with depression and that this association is moderated by neuroticism. METHOD: Multiple regression techniques were used to determine the independent associations of medical burden and neuroticism with depression in a group of 196 subjects, 60 years of age and older, recruited from primary care settings. RESULTS: Medical burden and neuroticism were independently associated with major depression, depressive symptoms, and psychiatric dysfunction. CONCLUSIONS: These findings support models in which medical disorders may contribute directly to depression. At the same time, the role of neuroticism in later-life depression warrants further study.
Lewy body disease: can we diagnose it?
The authors assessed the accuracy of published clinical criteria and their own modifications of those criteria in diagnosing Lewy body disease (LBD). Clinical diagnoses were made by two clinicians, blinded to neuropathologic diagnoses, using the Rochester Alzheimer's Disease Center database and traditional medical records. Neuropathologic diagnoses were made according to published guidelines. Results from 21 Alzheimer's disease and 18 LBD patients indicated that no set of clinical criteria was accurate in diagnosing LBD. The only significant predictor of LBD in this population was depression, which was more common in LBD than in Alzheimer's disease. The authors conclude that clinical identification of LBD is an important but unresolved neurological problem.