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Biomedical subjects

P Ray

Publications and source records attributed to P Ray.

At least 55 records · Page 3Linked to original sources
PubMed2001

Activated Akt protects the lung from oxidant-induced injury and delays death of mice.

Oxidant-induced injury to the lung causes extensive damage to lung epithelial cells. Impaired protection and repair of the lung epithelium can result in death. The serine-threonine kinase Akt has been implicated in inhibiting cell death induced by different stimuli including growth factor withdrawal, cell cycle discordance, DNA damage, and loss of cell adhesion in different cell types. However, the in vivo relevance of this prosurvival pathway has not been explored. Here we show that a constitutively active form of Akt introduced intratracheally into the lungs of mice by adenovirus gene transfer techniques protects mice from hyperoxic pulmonary damage and delays death of mice. This is the first demonstration of the in vivo protective function of Akt in the context of oxidant-induced lung injury.

Animals↗
PubMed2001

Preimplantation genetic diagnosis (PGD), a collaborative activity of clinical genetic departments and IVF centres.

Preimplantation genetic diagnosis (PGD) requires the combined efforts of geneticists and workers in the field of reproductive medicine. This was studied on the basis of a questionnaire, sent to 35 members of the PGD Consortium of the European Society of Human Reproduction and Embryology (ESHRE). A reply was obtained from 20 centres. They represent the majority of activities in the field of PGD in the world. It is obvious that many of the activities (in vitro fertilisation, embryo culture and biopsy) take place in IVF units while others (counselling and diagnosis) are the responsibility of genetic diagnostic centres. The distances between both units vary considerably. In all but one centre sex determination is offered. Aneuploidy screening is offered in 13 out of 20 centres. PGD of translocations and other structural chromosome abnormalities is offered in all but one centre. The number of monogenic diseases offered varies considerably. In comparison to prenatal diagnosis PGD is more expensive. The majority of these costs are due to the IVF or ICSI procedure. The charges for PGD vary between about 600 euro and 4000 euro. In 16 out of 20 centres the parents to be must sign an informed consent form.

Aneuploidy↗
PubMed2001

A critical role for NF-kappa B in GATA3 expression and TH2 differentiation in allergic airway inflammation.

The transcription factor GATA-3 is expressed in T helper 2 (TH2) but not TH1 cells and plays a critical role in TH2 differentiation and allergic airway inflammation in vivo. Mice that lack the p50 subunit of nuclear factor kappa B (NF-kappa B) are unable to mount airway eosinophilic inflammation. We show here that this is not due to defects in TH2 cell recruitment but due to the inability of the p50-/- mice to produce interleukin 4 (IL-4), IL-5 and IL-13: cytokines that play distinct roles in asthma pathogenesis. CD4+ T cells from p50-/- mice failed to induce Gata3 expression under TH2-differentiating conditions but showed unimpaired T-bet expression and interferon gamma (IFN-gamma) production under TH1-differentiating conditions. Inhibition of NF-kappa B activity prevented GATA-3 expression and TH2 cytokine production in developing, but not committed, TH2 cells. Our studies provide a molecular basis for the need for both T cell receptor and cytokine signaling for GATA-3 expression and, in turn, TH2 differentiation.

Animals↗
PubMed2001

Concerted inhibition of the transcriptional activation functions of the enhancer-binding protein NIFA by the anti-activator NIFL.

The Azotobacter vinelandii NIFL regulatory flavoprotein responds to the redox, energy and nitrogen status of the cell to inhibit transcriptional activation by the sigmaN-dependent enhancer binding protein, NIFA, via the formation of a NIFL-NIFA protein complex. The NIFA protein contains three domains: an N-terminal domain of unknown function; a central catalytic domain required to couple nucleotide hydrolysis to activation of the sigmaN-RNA polymerase holoenzyme; and a C-terminal DNA-binding domain. We report that truncated NIFA proteins that either lack the amino-terminal domain or contain only the isolated central domain remain responsive to inhibition by NIFL but, in contrast to native NIFA, continue to hydrolyse nucleotides when NIFL is present. We also report that NIFL is competent to inhibit the DNA-binding function of NIFA. Taken together, these results suggest that NIFL inhibits NIFA via a concerted mechanism in which DNA binding, catalytic activity and, potentially, interaction with the polymerase are controlled by NIFL in order to prevent transcriptional activation under detrimental environmental conditions.

Azotobacter vinelandii↗
PubMed2001

Monitoring gene therapy with reporter gene imaging.

Rapid advances in imaging technologies and gene transfer strategies offer a great opportunity to optimize clinical trials of human gene therapy. Reporter genes are emerging as very powerful tools to monitor the delivery, magnitude, and time variation of therapeutic gene transfer in vivo. Several reporter genes, such as the herpes simplex virus type 1 thymidine kinase, the dopamine type 2 receptor, and the somatostatin receptor type 2, are currently being successfully used with gamma camera, single photon emission computed tomography, and positron emission tomography imaging. These reporter genes can be coupled with a therapeutic gene of interest to indirectly monitor the expression of the therapeutic gene. Finally, applications of the reporter gene technology to other areas, such as cell trafficking studies and transgenic animal models, are now possible.

Animals↗
PubMed2001

Incidence and hospitalization rates of varicella and herpes zoster before varicella vaccine introduction: a baseline assessment of the shifting epidemiology of varicella disease.

BACKGROUND: A 15-year postmarketing evaluation of the impact of varicella vaccine on the age distribution of varicella disease is being conducted at Kaiser Permanente Medical Care Program, Northern California (KPMCP). We report on a baseline assessment of the age-specific incidence and hospitalization rates of varicella and herpes zoster that was conducted before vaccine introduction. METHODS: To assess the annual incidence of varicella, a telephone survey was conducted in a random sample of approximately 8,000 youths 5 to 19 years of age. The annual incidence of hospitalizations for varicella and herpes zoster in 1994 was assessed with the use of the computerized database at KPMCP. RESULTS: Varicella annual incidence was 10.3% in 5- to 9-year-olds, 1.9% in 10- to 14-year-olds and 1.2% in the 15- to 19-year age groups, respectively. Hospitalization rates among the entire KPMCP membership were 2.6 and 2.1 per 100,000 person years for varicella and zoster, respectively. Varicella incidence in the 15- to 19-year age group was higher among African-Americans than among Caucasians. CONCLUSIONS: Varicella rates were similar in the 5- to 9- and 10- to 14-year age groups to rates from other published studies conducted in 1972 to 1978, 1980 to 1988 and 1990 to 1992; however, the rate in 15- to 19-year-olds was 2 to 4 times higher than published rates in the same age category.

Adolescent↗
PubMed2001

Outbreak of Pichia anomala infection in the pediatric service of a tertiary-care center in Northern India.

An outbreak of nosocomial fungemia due to the unusual yeast, Pichia anomala occurred in the pediatric wards of our hospital over a period of 23 months (April 1996 to February 1998). A total of 379 neonates and children (4.2% admissions) were infected. The probable index case was admitted to the pediatric emergency ward, with subsequent transmission to the premature nursery, pediatric intensive care units, and other children wards. Carriage on the hands of health care personnel was likely to be responsible for dissemination of the fungus. The outbreak could only be controlled after a health education campaign to improve hand-washing practices was instituted and after nystatin-fluconazole prophylaxis to all premature neonates and high-risk infants was introduced. In a case-control study, we identified a lower gestational age, a very low birth weight (<1,500 g), and a longer duration of hospital stay as significant risk factors associated with P. anomala fungemia in premature neonates. We conducted a culture prevalence survey of 50 consecutive premature neonates and found that 28% were colonized with P. anomala at a skin or mucosal site on the date of delivery and that 20% of these neonates subsequently developed P. anomala fungemia. We performed multilocus enzyme electrophoresis on 40 P. anomala outbreak isolates (including patient and health care workers' hand isolates), and the results suggested that these isolates were identical. Our study highlights the importance of P. anomala as an emerging nosocomial fungal pathogen.

Antifungal Agents↗
PubMed2001

Group A streptococcal sore throat in a periurban population of northern India: a one-year prospective study.

OBJECTIVE: To estimate the incidence and risk factors of group A streptococcus (GAS) sore throat among school-aged children living in a periurban slum area of Chandigarh, North India. METHODS: A total of 536 children aged 5-15 years from 261 families identified by a systematic random selection method were enrolled in the study. Episodes of sore throat were recorded through fortnightly home visits over a one-year period. The local vernacular (Hindi) terms gala kharab (bad throat) and khansi jukam (cough and cold) were used to identify symptoms of sore throat, and throat swab specimens were collected from children who had these symptoms on the day of the home visit. Bacterial culture was carried out and the isolation of GAS was confirmed using group-A-specific antiserum. FINDINGS: The incidences of sore throat and GAS sore throat were, respectively, 7.05 and 0.95 episodes per child-year. The incidence was higher in the following situations: among 11-year-olds, during the winter (November to January) and rainy (August) months (a bimodal peak), among children living in houses where there was no separate room for the kitchen, and in homes that included a tobacco smoker. CONCLUSION: The results show that the incidence of GAS sore throat was related to age, season, and indoor air pollution.

Adolescent↗
PubMed2001

Mycobacterium fortuitum wound infection following laparoscopy.

During a six week period in 1999, seven patients who underwent laparoscopic tubectomies at small town health centres near Chandigarh developed chronic discharging sinuses at the site of incision. Mycobacterium fortuitum was isolated from wound discharge of the five patients by standard methods and two patients were smear positive. Environmental samples e.g., tap water, and a variety of fluids did not yield any mycobacteria and swabs from different parts of the laparoscope were sterile. All patients responded to ciprofloxacin and amikacin therapy. Our observation demonstrates that M. fortuitum is a clinically important nosocomial pathogen in setting of surgical wound infection in our country.

Amikacin↗
PubMed2001

Health related quality of life differences between black and white men with prostate cancer: data from the cancer of the prostate strategic urologic research endeavor.

PURPOSE: Understanding the potential consequences of racial differences in prostate cancer outcomes, from survival rates to quality of life considerations, is important for the clinician and patient. We examined demographic, clinical and health related quality of life data comparing black with white patients just after treatment of prostate cancer and 1 year later. MATERIALS AND METHODS: We analyzed data on 1,178 patients who were newly diagnosed with prostate cancer in the Cancer of the Prostate Strategic Urologic Research Endeavor, a national observational database of men recruited from 35 community and academic urology practices throughout the United States. Patient demographics, clinical characteristics and validated health related quality of life questionnaires were reviewed. A total of 958 white and 161 black patients with prostate cancer who completed at least 2 surveys were compared. RESULTS: The black patients were younger, and had lower income and education levels than white patients. Controlling for age, education and income differences, black patients generally had worse clinical characteristics at presentation and lower baseline health related quality of life data scores in most generic and disease specific categories at treatment. The most notable exception was sexual function, which was the only score that was higher in black patients at treatment. With time, health related quality of life improved in both groups but black patients had slower rates of improvement for general health, bodily pain, physical function, role function, disease worry and bowel function. They continued to have higher sexual function. CONCLUSIONS: Significant differences exist in clinical presentation, sociodemographic characteristics, and health related quality of life between black and white men with prostate cancer. These health related quality of life differences remain after treatment. Physicians should not assume that outcomes in black men would be similar to other patients.

Black or African American↗
PubMed2001

Bacterial adherence to polymethylmethacrylate posterior chamber intra ocular lenses.

PURPOSE: Bacterial adherence to intraocular lenses (IOLs) has been incriminated in the pathogenesis of postoperative endophthalmitis. Staphylococcus epidermidis is the most common organism isolated. We studied the in-vitro adhesion of Staphylococcus epidermidis to Polymethylmethacrylate (PMMA) IOLs and the effect of duration of exposure to adherence. METHODS: Two groups of 10 IOLs each were incubated in Staphylococcus epidermidis suspension for 2 minutes and 20 minutes respectively. Adhesion of bacterial cells was determined by counting the number of viable bacteria attached to IOLs. RESULTS: The mean bacterial adherence with 2 minutes incubation was 12,889 +/- 7,150 bacteria/ IOL and with 20 minutes incubation was 84,226 +/- 35,024 bacteria/IOL (P< 0.01). CONCLUSION: Our results show that Staphylococcus epidermidis adheres to PMMA IOLs in vitro and the degree of adherence is less for shorter duration of exposure. We conclude that viable bacteria irreversibly adherent to IOLs may play a role in the pathogenesis of postoperative endophthalmitis. Shorter duration of operative manipulation and exposure to contaminating sources may decrease the chances of postoperative endophthalmitis.

Bacterial Adhesion↗
PubMed2000

Self-assessed health-related quality of life in men who have completed radiotherapy for prostate cancer: instrument validation and its relation to patient-assessed bother of symptoms.

The purpose of this study was to develop a psychometrically reliable and valid questionnaire to assess the disease-specific dimensions of health-related quality of life (HRQOL) in the urinary function (UF), bowel function (BF), and sexual function (SF) domains of prostate cancer (PCa) patients treated with radiation therapy. Patients were given a six-page questionnaire using Likert-type questions assessing three HRQOL dimensions during their follow-up visits after completing radiotherapy. Scales created from an earlier study were utilized and tested for reliability and validity. In addition, we assessed the relationship between these dimensions and the degree to which a decreased HRQOL increases the degree to which patients feel bothered about their symptoms. There are two scales within each dimension: BF, Urgency and Daily Living; UF, Urgency and Weakness of Stream; SF, Interest/Satisfaction and Impotence. Internal-consistency reliability coefficients (Cronbach's alpha) for the proposed scales range from 0.48 to 0.92, and all item-scale correlations and divergence correlations validate the use of the scales, ranging from 0.49 to 0.89. The validity of these scales is also confirmed by the rising median scores with rising reported levels of patient-perceived "bother." The different dimensions have differing quantitative influences on patients. We have developed a prostate-specific HRQOL instrument that is an adequate and suitable tool for measuring HRQOL along three distinct dimensions for patients who have completed radiotherapy for PCa. Psychometric standards for reliability and validity were met for the proposed scales. Moreover, positive correlations were found between these dimensions and how bothered patients were by their symptoms, suggesting important relationships that should be followed in PCa patients after radiotherapy. Certain scales have strong influences on patient-perceived "bothersomeness" of symptoms, such as loss of control of BF, urgency of BF, urgency of urination, and level of interest/satisfaction in sex. Compared to our earlier study on patients being treated with radiotherapy for PCa, this study produced very similar results. With some modification, the same questionnaire could be used for both groups of patients. Int. J. Cancer (Radiat. Oncol. Invest.) 90, 163-172 (2000).

Adult↗
PubMed2000

Immunological tolerance as an adjunct to allogeneic tissue grafting.

Since its clinical inception, our group has worked in clinical and experimental transplantation. The exciting early results of composite tissue allografts (CTA) attracted our attention during the 1980s, when some of the first experimental CTA literature appeared. The recent extraordinary results of clinical CTA grafts, primarily the Louisville and Lyon results, have been highlighted at this meeting. Interestingly, this success followed not long after the first International meeting in Louisville in 1997. This is clearly an exciting new application of transplant techniques to one of the newest and most unique types of transplants. Previous studies used immunosuppression for skin allografting. Early results seem quite exciting and we expect to see a rapid growth of interest and activity in this area. We believe that the entire field would benefit from the novel, highly effective and minimally toxic immune tolerance induction using CD3-immunotoxin (CD3-IT) and deoxyspergualin (DSG).

Animals↗
PubMed2000

Novel endogenous inhibitor of sulfur mustard-stimulated protease in cultured human epidermal keratinocytes: possible application in vesicant intervention.

Protease stimulation at the dermal-epidermal junction may be responsible for the skin blistering (vesication) action of sulfur mustard (HD). We have purified a protease to homogeneity from cultured normal human epidermal keratinocytes (NHEK) exposed to 300 microM HD. In this report, we describe the results of our studies on purification and characterization of an endogenous inhibitor of HD-stimulated protease in NHEK. Purification to homogeneity was accomplished by chromatographic separation of the dialyzed Triton X-100-solubilized inhibitor using ion-exchange DEAE-cellulose. Analysis of the purified inhibitor by sodium dodecyl sulfate polyacrylamide gel electrophoresis revealed one polypeptide with an apparent molecular mass of 116 kDa. Activity of the inhibitor was screened by incubating different column elute fractions with protease purified from the same cells. Preliminary results showed that the purified inhibitor effectively inhibited the protease isolated from NHEK, whereas other naturally occurring inhibitors, e.g. soybean trypsin-chymotrypsin inhibitors, elafin and aprotinin, were ineffective. Although complete characterization and regulation of this inhibitor remain to be resolved, this purification may be a major step towards developing a specific protective measure against HD-induced toxicity.

Blister↗
PubMed2000

An innovative approach of risk planning for space programs.

According to the current rule-based risk management approach at the National Aeronautics and Space Administration (NASA), the effort is directed to contain all identified risks of a program. The identification of hazards and mitigation effort proceeds along with the development of the system hardware, till all the tradable resources for a program is exhausted. In this process, no conscious effort is made to evaluate risks and associated cost, and the final design is likely to have undesirable residual risks. This approach also results in allocating a significant amount of resources to gain only marginal mitigation of hazard and leave some undesirable hazards in the system due to the budget limitation. The approach in the proposed knowledge-based risk planning system makes a conscious attempt to trade risk with other resources, e.g., schedule, cost, reliability, performance, and others in a judicious and cost-effective way. A knowledge of the feasible option sets requiring high incremental cost for a marginal gain in hazard reduction helps the management to make decision for residual risk that falls within an acceptable range for an option set.

Algorithms↗
PubMed2000

Comparison of seven and fourteen days of lansoprazole, clarithromycin, and amoxicillin therapy for eradication of Helicobacter pylori: a report from India.

BACKGROUND: In developed countries, a 1-week regimen of combined proton pump inhibitors and two antibiotics is considered adequate for Helicobacter pylori eradication. However, there is a paucity of reports from developing countries on treatment duration of less than 14 days. We compared efficacy of 7 and 14 days of lansoprazole (L), clarithromycin (C), and amoxicillin (A) combinations for eradication of H. pylori. PATIENTS AND METHODS: Forty-six consecutive patients who presented with upper gastrointestinal symptoms and tested positive for H. pylori infection were included in the study. In every patient, after performance of upper gastrointestinal endoscopy, antral biopsies were obtained. H. pylori infection was diagnosed by positive rapid urease test and identification of organisms on antral histology. Patients were randomly selected to receive lansoprazole, 30 mg once daily, plus clarithromycin, 250 mg twice daily, plus amoxicillin, 500 mg three times daily for 2 weeks (group 1; n = 24; age, 36 +/- 12 years; 18 men) or 1 week (group 2; n = 22; age, 45 +/- 15 years; 12 men). One month after completion of treatment, repeat upper gastrointestinal endoscopy was performed. H. pylori eradication was defined as absence of organism on histopathological examination of both antrum and body of stomach and negative rapid urease test. RESULTS: Eradication rate was higher in group 1 (23 of 24; 96%) as compared to group 2 (12 of 22; 54%; p <.05). One patient in group 1 had diarrhea, and one patient in group two had skin rash and itching. CONCLUSIONS: Fourteen-day therapy with lansoprazole, clarithromycin, and amoxicillin is highly effective in eradication of H. pylori. Reducing duration of therapy to 7 days significantly lowers eradication rates.

2-Pyridinylmethylsulfinylbenzimidazoles↗
PubMed2000

A methodology for the development of software agent based interoperable telemedicine systems: a tele-electrocardiography perspective.

Telemedicine involves the integration of information, human-machine, and healthcare technologies. Because different modalities of patient care require applications running on heterogeneous computing environment, software interoperability is a major issue in telemedicine. Software agent technology provides a range of promising techniques to solve this problem. This article discusses the development of a methodology for the design of interoperable telemedicine systems (illustrated with a tele-electrocardiography application). Software interoperability between different applications can be modeled at different levels of abstraction such as physical interoperability, data-type interoperability, specification-level interoperability, and semantic interoperability. Software agents address the issue of software interoperability at semantic level. A popular object-oriented software development methodology - unified modeling language (UML) - has been used for this development. This research has demonstrated the feasibility of the development of agent-based interoperable telemedicine systems. More research is needed before widespread deployment of such systems can take place.

Computer Systems↗