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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
PubMed1998

Characterization of lymphocytic subsets and cytokine production in gastric biopsy samples from Helicobacter pylori patients.

BACKGROUND: This study characterized the phenotypic subsets of isolated gastric lymphocytes and the cellular immune response in cultured gastric biopsy specimens. METHODS: Endoscopy specimens from 40 Helicobacter pylori-positive and 40 H. pylori-negative patients were studied. a) Isolated gastric lymphocytes were analysed for CD4+, CD8+ T-lymphocyte subsets, activated T cells, and natural killer cells on a fluorescence-activated cell sorter, using monoclonal antibodies. b) The supernatant of cultured gastric biopsy specimens were assayed for interleukin (IL)-2, IL-4, and IL-6 levels. RESULTS: In H. pylori-positive patients there was (a) a decrease in CD4+/CD8+ T cells, no change in activated T cells, and an increase in natural killer cells, and (b) no change in IL-2 levels and a significant increase in IL-4 and IL-6 levels. CONCLUSIONS: There is an increase in CD8+ lymphocytes and natural killer cells, and the observed increase in IL-4 and IL-6 might be important in H. pylori-associated gastritis.

Adult↗
PubMed1998

Varicella serology among school age children with a negative or uncertain history of chickenpox.

BACKGROUND: Clinicians who offer varicella vaccination to school age children face the dilemma of whether to serotest or vaccinate presumptively. Varicella seroprevalence among 7- to 12-year-old children with negative or uncertain histories has not previously been studied. Our main objective was to describe varicella seroprevalence among children ages 7 to 12 years with a negative or uncertain history of chickenpox. METHODS: This was a cross-sectional study of children whose clinicians had ordered varicella serotesting. Guidelines from the medical group's regional pediatric infectious disease specialists recommended obtaining varicella serology on all children 7 to 12 years old with a negative or uncertain history. Parents were interviewed by telephone about the child's history of chickenpox before test results were completed. RESULTS: Varicella seroprevalence ranged from 9% among 7-year-olds whose parents said they had definitely not had chickenpox to 68% among 11-year-olds whose parents were not sure whether they had had chickenpox. Among children whose parents were uncertain about their chickenpox history, almost one-half (48%) were seropositive. Twenty-five percent of children whose parents said they definitely had not and 32% of children whose parents said they had probably not had chickenpox were seropositive. Of parents whose children had experienced serotesting, 73% said they would prefer to have the blood test first rather than presumptive vaccination. For a large health maintenance organization, it was projected to be most cost-effective (in terms of cost per chickenpox case prevented) to recommend testing for children 9 to 12 years old with uncertain histories of chickenpox. CONCLUSIONS: We conclude that among children 7 to 12 years old with negative or uncertain histories of chickenpox, varicella seroprevalence ranges from 9 to 68% depending on age and clinical history. Parents are generally receptive to serotesting, although individual preferences vary. In the population we studied it would be most cost-effective to recommend testing before deciding about vaccination for children 9 to 12 years old with uncertain histories of chickenpox.

Chickenpox↗
PubMed1998

Inhibitory effect of amiloride on the urokinase plasminogen activators in prostatic cancer.

The diuretic drug amiloride (AMLD), which competitively inhibits the catalytic activity of urokinase plasminogen activators (UPA), was used to study its effects on the proteolytic enzymes implicated in the invasiveness and metastases in a prostatic tumor model carrying two different sublines of adenocarcinoma of the prostate. Our data showed that UPA activity was significantly higher, both in the cytosol and pellet of R3327-AT3, a fast-growing highly metastatic and androgen-insensitive tumor, as compared to the G3327-G subline, a slow-growing nonmetastatic tumor of the prostate. The UPA activity in AT3 tumor dropped when the rats were treated with AMLD for 3 weeks. The UPA activity in the sera and tumor effusions from rats with AT3 tumor was significantly higher as compared to those with G subline tumor. The number of pulmonary metastatic foci was the same in untreated rats as compared to those treated with AMLD. The lymph node inspection after 3 weeks revealed no secondary tumor in the AMLD-treated group. The role of UPA in the metastases of prostate cancer is discussed.

Adenocarcinoma↗
PubMed1998

AIDS-related primary pulmonary lymphoma.

We describe 12 cases of AIDS-related primary pulmonary lymphoma occurring between 1986 and 1996 in a large French cohort of HIV-infected patients. Diagnostic criteria were: (1) histologically proven lymphomatous pulmonary involvement; (2) absence of mediastinal and/or hilar adenopathy on chest radiography; (3) absence of extrathoracic lymphoma extension. All patients were severely immunodeficient at the time of diagnosis. All but one patient presented with B and/or nonspecific respiratory symptoms. Chest radiography showed one or more marginated nodule(s) or large mass. CT scan showed a cavitary lesion in five patients. No lymph node enlargement or specific pleural effusion was detected. Transthoracic needle biopsies were performed in 10 patients and avoided open-lung biopsy for the diagnosis of lymphoma in five patients. All but one of the primary pulmonary lymphoma were high-grade B-cell non-Hodgkin's lymphomas. Using antilatent membrane protein-1 antibodies and an Epstein-Barr-Virus-encoded RNA transcript-specific probe, latent EBV infection of tumor cells was demonstrated in every case. All but one of the patients received chemotherapy. The median survival time was 4 mo, and no patient was still alive at the cut-off date for this analysis. Progessive pulmonary lymphoma was the main cause of death, but infections were also frequent.

AIDS-Related Opportunistic Infections↗
PubMed1998

Protease in normal human epidermal keratinocytes.

An in vitro normal human epidermal keratinocytes (NHEK) model was used to study and to characterize the protease stimulated by the mustards 2-chloroethyl ethyl sulphide (CEES), 2-chloro-N-(2-chloroethyl)-N-methylethanamine hydrochloride (nitrogen mustard, HN2), and Bis-2-chloroethyl sulfide (sulfur mustard, HD). The results obtained by using a chromozym (TRY) peptide substrate protease assay showed the optimum mustard concentration and time for protease stimulation to be about 200 microM CEES, 100 microM HN2 or HD, and 16 hours. The mustard-stimulated protease was membrane-bound, and was inhibited by adding a Ca2+ chelator EGTA (2 mM), BAPTA AM (50 microM) or a serine protease inhibitor diisopropyl fluoro-phosphate DFP (1 mM), or a protein synthesis inhibitor cycloheximide (10 microM) in the extracellular medium. These results suggest that one of the mechanisms of mustard toxicity is via the stimulation of a trypsin/chymotrypsin like serine protease, which is dependent on Ca2+ and new protein synthesis. Sodium dodecyl sulfate polyacrylamide gel electrophoresis revealed a mustard-stimulated approximately equal to 70-80 KDa protein band that was associated with protease activity which was inhibitable by EGTA, BAPTA, DFP or cycloheximide. This mustard-stimulated protein (protease) may serve as a diagnostic tool for mustard exposure as well as an assay for screening prospective antivesicant protease inhibitor drugs.

Cells, Cultured↗
PubMed1998

Race and serum prostate-specific antigen levels: current status and future directions.

Prostate cancer (PC) is a serious public health problem in the United States, especially in African-American men (AAs). AAs have higher incidence and mortality rates and present with higher stage and grade of PC than other racial/ethnic groups. Given the importance of serum prostate-specific antigen level (PSA) as a screening tool for PC and its prognostic value among patients with PC, exploring the relationship between PSA and race has gained enormous interest lately. The number of studies addressing such relationships has increased tremendously over the past few years. Most of these studies indicate a higher PSA in AAs than whites in men with or without PC even after adjustment for patients' age and prostate volume (in men without PC) and for PC grade and stage (in men with PC). The etiology of higher PSA levels in AAs is not completely understood and might be secondary to biological, environmental/socioeconomic reasons, or both. Studying serum PSA dynamics among AAs may help in elucidating the epidemiological features of PC in AAs.

Biomarkers, Tumor↗
PubMed1997

Regulated overexpression of interleukin 11 in the lung. Use to dissociate development-dependent and -independent phenotypes.

Standard overexpression transgenic approaches are limited in their ability to model waxing and waning diseases and frequently superimpose development-dependent and -independent phenotypic manifestations. We used the clara cell 10-kD protein (CC10) promoter and the reverse tetracycline transactivator (rtTA) to create a lung-specific, externally regulatable, overexpression transgenic system and used this system to express human interleukin 11 (IL-11) in respiratory structures. Gene induction could be achieved in utero, in neonates and in adult animals. Moreover, gene expression could be turned off by removal of the inducing stimulus. When gene activation was initiated in utero and continued into adulthood, subepithelial airway fibrosis, peribronchiolar mononuclear nodules, and alveolar enlargement (emphysema) were noted. Induction in the mature lung caused airway remodeling and peribronchiolar nodules, but alveolar enlargement was not appreciated. In contrast, induction in utero and during the first 14 d of life caused alveolar enlargement without airway remodeling or peribronchiolar nodules. Thus, IL-11 overexpression causes abnormalities that are dependent (large alveoli) and independent (airway remodeling, peribronchiolar nodules) of lung growth and development, and the CC10-rtTA system can be used to differentiate among these effector functions. The CC10-rtTA transgenic system can be used to model waxing and waning, childhood and growth and development-related biologic processes with enhanced fidelity.

Aging↗
PubMed1997

Transcription factor GATA-3 is differentially expressed in murine Th1 and Th2 cells and controls Th2-specific expression of the interleukin-5 gene.

Interleukin-5 (IL-5), which is produced by CD4(+) T helper 2 (Th2) cells, but not by Th1 cells, plays a key role in the development of eosinophilia in asthma. Despite increasing evidence that the outcome of many diseases is determined by the ratio of the two subsets of CD4(+) T helper cells, Th1 and Th2, the molecular basis for Th1- and Th2-specific gene expression remains to be elucidated. We previously established a critical role for the transcription factor GATA-3 in IL-5 promoter activation in EL-4 cells, which express both Th1- and Th2-type cytokines. Our studies reported here demonstrate that GATA-3 is critical for expression of the IL-5 gene in bona fide Th2 cells. Whereas mutations in the GATA-3 site abolished antigen- or cAMP-stimulated IL-5 promoter activation in Th2 cells, ectopic expression of GATA-3 in Th1 cells or in a non-lymphoid, non-IL-5-producing cell line activated the IL-5 promoter. During the differentiation of naive CD4(+) T cells isolated from T cell receptor transgenic mice, GATA-3 gene expression was up-regulated in developing Th2 cells, but was down-regulated in Th1 cells, and antigen- or cAMP-activated Th2 cells (but not Th1 cells) expressed the GATA-3 protein. Thus, GATA-3 may play an important role in the balance between Th1 and Th2 subsets in immune responses. Inhibition of GATA-3 activity has therapeutic potential in the treatment of asthma and other hypereosinophilic diseases.

Animals↗
PubMed1997

Risk of chronic arthropathy among women after rubella vaccination. Vaccine Safety Datalink Team.

CONTEXT: A review by the Institute of Medicine found a possible relationship between rubella vaccination and chronic arthritis among women. OBJECTIVE: To evaluate the risk of persistent joint and neurologic symptoms in rubella seronegative women subsequently vaccinated with RA 27/3 rubella vaccine. DESIGN: Retrospective cohort study based on computerized laboratory data and medical record review. Records were reviewed for symptoms occurring within 2 years before and after the date of serological testing and to identify vaccinees. Possible cases were evaluated by a rheumatologist blinded to serological findings and vaccination status. SETTING: Large health maintenance organization in northern California. PATIENTS: Women aged 15 to 59 years serotested for rubella during 1990 with continuous health plan membership for 2 years before and after the date of their serological test. Seronegative women immunized within 1 year of serotesting (n=971) were defined as exposed. Primary comparison groups included all unvaccinated, seronegative women (n=924) and randomly selected seropositive, unvaccinated women (n=2421) matched to exposed subjects on serological test date and age (+/-3 years). MAIN OUTCOME MEASURES: Prevalence and incidence of chronic joint and neurologic symptoms during 1-year follow-up period stratified by age and serological findings, immunization, and postpartum status. RESULTS: No significantly increased risk was associated with receipt of rubella vaccine for any outcome except for prevalence of carpal tunnel syndrome in vaccinated women at least 30 years old compared with seropositive, unvaccinated women (2.9% vs 1.4%; P=.03). A total of 34 women had onset of conditions within the 1-year follow-up period; 9 of these were in the group of seronegative, immunized women, of whom 6 had onset of symptoms within 6 weeks of vaccination. Among these 6 women, symptoms included transient arthritis or arthralgias (<6 weeks duration) in 4 women, arthralgia of indeterminate chronicity in 1 woman, and carpal tunnel syndrome in 1 woman. Postpartum women across all groups were less likely to be seen for nontraumatic arthropathies than nonpostpartum women (4.5% vs 7.2%, P=.08 in vaccinated women; 4.8% vs 8.1%, P=.09 in seronegative controls; and 4.8% vs 10.0%, P=.01 in seropositive controls). CONCLUSIONS: In this large retrospective cohort analysis there was no evidence of any increased risk of new onset chronic arthropathies or neurologic conditions in women receiving the RA 27/3 rubella vaccine. These data support the continued vaccination of rubella-susceptible women to reduce the risk of congenital rubella syndrome.

Adolescent↗
PubMed1997

Selective up-regulation of cytokine-induced RANTES gene expression in lung epithelial cells by overexpression of IkappaBR.

We previously reported the cloning of a cDNA for IkappaBR (for IkappaB-related) from human lung alveolar epithelial cells. IkappaBR is related to the IkappaB proteins that function as regulators of the NF-kappaB family of transcription factors. Here, we investigated the consequence of IkappaBR overexpression on the expression of NF-kappaB-regulated chemokine genes in lung alveolar epithelial cells. Chemokines play an important role in many inflammatory diseases such as asthma and AIDS. Overexpression of IkappaBR in the lung cells resulted in a rapid 50-100-fold greater production of the RANTES (regulated upon activation, normal T expressed and presumably secreted) protein upon cytokine-induction compared with control cells. IkappaBR overexpression, however, did not enhance interleukin-8 or MIP-1alpha gene expression, despite the fact that the expression of all three chemokine genes are regulated by NF-kappaB. The up-regulation of RANTES gene expression resulting from overexpression of IkappaBR correlated with increased amounts of a unique RANTES-kappaB binding activity and decreased binding of p50 homodimers. Previous studies have shown that p50 homodimers function as repressors of certain kappaB sites. Our studies suggest that IkappaBR can aid activation of select NF-kappaB-regulated genes by sequestering p50 homodimers.

Base Sequence↗
PubMed1997

Acetylcholine exocytosis in PC12 cells deficient in SNAP-25.

Stimulus-induced acetylcholine (ACh) exocytosis from presynaptic nerve terminals involves two important steps: fusion of ACh loaded vesicles at presynaptic release sites, followed by release into the synaptic cleft. We studied the role of the putative vesicle fusion protein SNAP-25 in this process. The nerve growth factor-differentiated PC12 cell line was used as an experimental model. A bee venom tetradecapeptide (INLKALAALAKKIL-NH2) phospholipase A2 (PLA2) activator, mastoparan, was used to induce ACh release. Treatment of PC12 cells with appropriate antisense oligonucleotides blocked SNAP-25 expression, as judged by Western blot protein analysis with a specific monoclonal antibody. Despite apparent elimination of SNAP-25, treatment of differentiated PC12 cells with mastoparan and high (80 mM) K+ induced ACh exocytosis. The results indicate that in PC12 cells, ACh exocytosis due to mastoparan plus K+ can occur in the absence of SNAP-25.

Acetylcholine↗
PubMed1997

Repression of interleukin-6 gene expression by 17 beta-estradiol: inhibition of the DNA-binding activity of the transcription factors NF-IL6 and NF-kappa B by the estrogen receptor.

The cytokine interleukin-6 (IL-6), a key mediator of immune and acute phase responses of the liver, has also been implicated in uterine functions. Estrogens are potent repressors of IL-6 production by uterine stromal cells. In the endometrial adenocarcinoma cell line Ishikawa, phorbol ester-induced activation of the IL-6 promoter was inhibited to basal levels by 17 beta-estradiol (E2) in a wild-type receptor-dependent fashion. Although tamoxifen has been shown to have estrogenic effects on the endometrium, it did not inhibit induction of the IL-6 promoter. We previously showed that inhibition of IL-6 gene expression by E2 does not involve high-affinity binding of the estrogen receptor (ER) to IL-6 DNA. We now report that the ER can directly interact with the transcription factors NF-IL6 and NF-kappa B and can inhibit their ability to bind DNA which might be the molecular basis for repression of IL-6 gene expression by estrogens.

Adenocarcinoma↗
PubMed1997

Fine-needle aspiration biopsy in fungal infections.

To evaluate the role of fine-needle aspiration biopsy (FNAB) in diagnosis of fungal infections, a retrospective analysis of 26 cases of fungal infection is described. The spectrum of various fungi encountered on cytologic microscopy of aspirated material and fungal culture was as follows: Aspergillus sp (16 cases), Cryptococcus neoformans (six cases), Mucorales (one case), Candida sp (one case), Phialophora parasiticus (one case), Sporothrix schenkii and Cladosporium sp (the last two isolated from a single case). In majority (71%) of cases, fungal infection was not clinically suspected but was picked up on cytologic material in all the cases. An accurate diagnosis based on morphology could be made in 21 cases (80%). Predisposing factor was found in three patients, two of them had diabetes mellitus and one was on immunosuppression. HIV serology was negative in seven cases tested. Commonest tissue reaction (75%) was foreign body giant cells with foamy macrophages and variable amount of necrosis. Although FNAB is helpful in the rapid diagnosis of fungal infections, culture is essential for more accurate identification.

Adolescent↗
PubMed1997

Computer-generated recall letters for underimmunized children: how cost-effective?

OBJECTIVE: To evaluate the effectiveness and cost effectiveness of computer-generated recall letters to parents of children overdue for immunizations. METHODS: This randomized controlled trial included children of two facilities in a regional health maintenance organization. Parents of 20-month-olds who had not yet received a measles-mumps-rubella (MMR) immunization were identified via a computerized immunization tracking system. One half were mailed personalized letters that included the recommended immunization schedule and a request to call for an appointment; the other half served as a control group. Receipt of the MMR between 20 and 24 months of age was evaluated with the computerized tracking system. A telephone survey was conducted with parents whose children had not received the MMR by 24 months. Decision analysis was used to project the theoretical outcomes and costs of a recall letter policy for other populations. RESULTS: Among 20-month-old children 10% had not received the MMR; 289 families were included in the analysis. Of families who were mailed letters, 54% (82 of 153) received the MMR by 24 months of age, compared with 35% (47 of 136) of those in the control group (P = 0.001). The telephone survey was completed with 110 parents of children who still did not appear on the health plan computer as having received the MMR by 24 months. Fifteen percent said the child had received an immunization at an outside provider, and of the rest 62% said they had not been aware that an immunization was due. In the cost effectiveness analysis it was projected that recall letters would increase the immunization rate for the regional population of approximately 30000 children from 86% to 90% at a total cost of $5031 annually. The cost per additional child appropriately immunized was $4.04. In sensitivity analyses this cost effectiveness ratio varied depending on the baseline population coverage rate as well as the estimated effectiveness of recall letters. CONCLUSIONS: Computer-generated letters to recall children overdue for immunizations resulted in a higher proportion of children appropriately immunized in this setting. However, the strategy was not as cost-effective as intuition might suggest. Further studies in health maintenance organization (HMO) settings should compare the cost effectiveness of letters with other low cost strategies including automated telephone reminders.

California↗
PubMed1997

Safety and immunogenicity of Chiron/Biocine recombinant acellular pertussis-diphtheria-tetanus vaccine in infants and toddlers.

OBJECTIVE: To evaluate the safety and immunogenicity of the recombinant acellular pertussis-diphtheria-tetanus (aPDT) vaccine (C-aPDT, Chiron/Biocine). STUDY DESIGN: This is a randomized blinded trial evaluating the safety and immunogenicity of the recombinant aPDT vaccine (C-aPDT, Chiron/Biocine) in 2000 infant recipients compared with 498 controls who received whole cell diphtheria-pertussis-tetanus (wDPT; Connaught) vaccine at 2, 4 and 6 months of age. In addition the safety and immunogenicity of the same C-aPDT vaccine were evaluated as a booster dose in a subset of the same population when given at 15 to 18 months of age and compared with licensed Lederle aPDT vaccine. RESULTS: The C-aPDT vaccine was associated with very few local or systemic reactions when compared with wDPT. In toddlers the local and systemic side effects observed were similar after either acellular vaccine. When the immunogenicity of the C-aPDT vaccine was compared with the wDPT (Connaught) in infancy, the vaccines were equivalent for anti-diphtheria response, the wDPT developed higher anti-tetanus response and the C-aPDT vaccine was significantly more immunogenic for all other antigens tested. In toddlers the C-aPDT acellular vaccine exhibited equal or improved immunogenicity for antigens tested as compared with Lederle aPDT except for a higher anti-filamentous hemagglutinin response with the Lederle aPDT vaccine. CONCLUSION: The Chiron/Biocine aPDT vaccine offers an improved safety profile as well as improved immunogenicity when compared with a licensed wDPT product.

Antibodies, Bacterial↗
PubMed1997

Risk of hospitalization because of aseptic meningitis after measles-mumps-rubella vaccination in one- to two-year-old children: an analysis of the Vaccine Safety Datalink (VSD) Project.

OBJECTIVE: To assess the level of increased risk, if any, of hospitalizations for aseptic meningitis after Jeryl-Lynn mumps strain measles-mumps-rubella (MMR) vaccine in the Vaccine Safety Datalink population. STUDY DESIGN: A possible increased risk of aseptic meningitis 8 to 14 days after receipt of MMR was observed in a preliminary screening analysis of automated data from the Vaccine Safety Datalink (VSD) project Year 2 analysis. To further evaluate this association a retrospective 10-year matched case-control study was undertaken in the four health maintenance organizations (HMOs) in the VSD project. Cases ascertained from a broad scan of the automated data were validated against a standard case definition. Two controls matched on age, sex, HMO and HMO membership were assigned per case. RESULTS: The VSD project involves the cooperative collection of automated vaccination and medical outcome data from four large HMOs that currently have 500,000 children younger than 7 years of age under surveillance. Review of automated screening results from the first 2 years of data revealed a possible increased risk of aseptic meningitis 0 to 14 days after MMR with a relative risk of 3.61 (95% confidence interval, 1.0 to 13.1) although the total number of cases was small. Although the automated data had suggested a possible association of aseptic meningitis with MMR containing the Jeryl-Lynn strain of mumps, review of validated hospitalized cases during the observation period did not reveal evidence of an increased risk of aseptic meningitis after MMR containing the Jeryl-Lynn strain of mumps (odds ratio < 1.0 for all analyses). CONCLUSION: Although it is recognized that hospitalized cases represent a minority of the total cases of aseptic meningitis, it is reassuring that in this evaluation no increased risk of aseptic meningitis after MMR vaccine was found.

Case-Control Studies↗