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Biomedical subjects

P Ray

Publications and source records attributed to P Ray.

At least 37 records · Page 2Linked to original sources
PubMed1994

Enzymatic synthesis of folate and antifolate polyglutamates with Escherichia coli folylpolyglutamate synthetase.

Escherichia coli folylpolyglutamate synthetase was used to synthesize micromole quantities of polyglutamyl conjugates of folic acid, methotrexate, and other analogs of folic acid. The products of the enzymatic reactions were purified by semipreparative C18 HPLC. The position of each amide linkage (gamma or alpha carboxyl) in the polyglutamated products was determined by limited and exhaustive hydrolyses with hog kidney folylpolyglutamate hydrolase and with yeast carboxypeptidase Y. Under standard reaction conditions, the E. coli enzyme added up to five glutamyl residues to each monoglutamated substrate, primarily at the gamma carboxyl position. Thus, an enzyme which naturally adds only two glutamates to naturally occurring folates can be used synthetically to make higher polyglutamates of a wide range of synthetic substrates. The products of the reactions are valuable tools for the study of the metabolism of antifolate drugs as well as metabolic reactions involving folate cofactors.

Escherichia coli↗
PubMed1994

Inhibition of bioenergetics alters intracellular calcium, membrane composition, and fluidity in a neuronal cell line.

The effect of inhibited bioenergetics and ATP depletion on membrane composition and fluidity was examined in cultured neuroblastoma-glioma hybrid NG108-15 cells. Sodium cyanide (CN) and 2-deoxyglucose (2-DG) were used to block, oxidative phosphorylation and anaerobic glycolysis, respectively. Endoplasmic reticulum (ER) Ca(2+)-pump activity measured by 45Ca2+ uptake was > 92% inhibited in intact cells incubated with CN (1 mM) and 2-DG (20 mM) for 30 min. In addition, exposure of cells to CN and 2-DG caused a 134% increased release of isotopically labeled arachidonic acid (3H-AA) or arachidonate-derived metabolites from membranes. Removal of Ca2+ from the incubation medium ablated the CN/2-DG induced release of 3H-AA or its metabolites. Membrane fluidity of intact cells was measured by electron spin resonance spectroscopy using the spin label 12-doxyl stearic acid. The mean rotational correlation time (tau c) of the spin label increased 49% in CN/2-DG exposed cells compared to controls, indicating a decrease in membrane fluidity. These results show that depletion of cellular ATP results in inhibition of the ER Ca(2+)-pump, loss of AA from membranes, and decreased membrane fluidity. We propose that impaired bioenergetics can increase intracellular Ca2+ as a result of Ca(2+)-pump inhibition and thereby activate Ca(2+)-dependent phospholipases causing membrane effects. Since neurons derive energy predominantly from oxidative metabolism, ATP depletion during brain hypoxia may initiate a similar cytotoxic mechanism.

Adenosine Triphosphate↗
PubMed1994

Clinical evaluation of serum tissue polypeptide-specific antigen (TPS) in non-small cell lung cancer.

M3 is an epitope of the tissue polypeptide antigen detectable in the serum by immunoradiometric assay. This epitope is referred to as tissue polypeptide-specific antigen (TPS). We examined the pretreatment TPS level of 160 non-small cell lung cancer (NSCLC) patients and 71 patients who suffered from non-malignant pulmonary diseases. The upper limit of normal values was 140 U/l. Using this cutoff, the sensitivity and specificity were 36 and 90%, respectively. The TPS was significantly higher in NSCLC patients with an advanced stage, a mediastinal lymph node involvement or a poor performance status. This level was significantly higher in the group of patients for whom the disease proved to progress during chemotherapy. In univariate analysis, patients with a high TPS level proved to have a shorter survival than patients with a TPS < or = 140 U/l. In Cox's model analysis, performance status, stage of the disease and serum TPS were the only significant prognostic variables. The low sensitivity of TPS precludes its use for diagnosis. However, the pretreatment TPS level adds information to the management of NSCLC inasmuch as it predicts a low sensitivity to chemotherapy and a poor prognosis.

Adult↗
PubMed1994

Empirical prediction of physiological response to prolonged work in encapsulating protective clothing.

Work in moderate or hotter environments while wearing encapsulating protective clothing (PC) results in heat storage and substantial diminution of work productivity, as well as being a potential health risk. An ability to predict the responses of workers using PC would be very useful. Predictions were made of work times at 21 degrees C of 15 subjects performing prolonged hard work (450 W gross) while wearing PC, based upon prior measures of short-duration bench stepping in PC and heart rate responses. A simple model was derived that shows good potential for predicting work time in moderate temperatures in PC; Total Time = 7.2 (bench step duration) - 34 (bench comfort) + 4 (height); R2 = 0.83, C.V. = 13. Unexpectedly, models that incorporated recovery heart rate as a variable were not as effective. With further refinement, the prediction approach tested in this study would be immediately useful for managing military and civilian personnel working in PC. Additionally, it could be utilized at minimal cost during routine training.

Adult↗
PubMed1994

The cost of childhood chickenpox: parents' perspective.

The development of a varicella vaccine has raised questions about the cost effectiveness of vaccination, but little information on the costs of chickenpox exists. The purpose of this study was to evaluate medical costs and the value of work loss among families whose children had chickenpox. Interviews were conducted with 179 families who made advice nurse calls or urgent care clinic visits to three clinics in the Northern California Kaiser Permanente Medical Care Plan. Two-thirds of working mothers and one-third of working fathers missed work to care for children with chickenpox. The mean value of the work lost because of chickenpox was $293/family or $183/chickenpox case. The estimated costs of nonprescription medications were $20/family or $12.50/chickenpox case. Children were sick enough to need to stay home for only one-third as many days as chicken actually stayed home because of school exclusion policies. These empiric results differ from previous estimates of the medical and work loss costs of varicella and should be included in analyses of the cost effectiveness of proposed vaccination programs.

Absenteeism↗
PubMed1994

Serum antibody immunoglobulin G of mice convalescent from Plasmodium yoelii infection inhibits growth of Plasmodium falciparum in vitro: blood stage antigens of P. falciparum involved in interspecies cross-reactive inhibition of parasite growth.

We demonstrated that antibodies in the serum of BALB/c mice convalescent from Plasmodium yoelii infection inhibit the in vitro growth of Plasmodium falciparum. Blood stage P. falciparum antigens that cross-react with the convalescent-phase mouse serum antibodies were identified and partially characterized. Convalescent-phase mouse serum immunoglobulin G (IgG) reacted with P. falciparum lysates at up to a 1:15,000 dilution of the immune sera and bound to P. falciparum-parasitized erythrocytes at up to a 1:5,000 dilution of the sera. The cross-reactive moieties of antigens in parasite lysates were resistant to oxidation by periodate but sensitive to trypsinization. About 15 polypeptides (M(r)s of 15,000 to 110,000) of P. falciparum blood stages were recognized by the convalescent-phase mouse anti-P. yoelii sera; many of these antigens were metabolically 35S labeled and specifically immunoprecipitated. Also, virtually all of the cross-reactive antigens were recognized by human malaria-immune sera. The anti-P. yoelii serum antibodies bound, with high affinity, to at least five of the cross-reactive antigens (M(r)s of 107,000, 84,000, 53,000, 36,000, and 30,000). By phase separation in Triton X-114, eight interspecies cross-reactive antigens (M(r)s of 84,000, 76,000, 51,000, 31,000, 29,000, 28,000, 23,000, and 22,000) were found to be integral membrane proteins. Convalescent-phase mouse serum IgG strongly inhibited the differentiation of P. falciparum from schizonts to rings; 75 micrograms of IgG per ml caused 80% inhibition of release of merozoites and their invasion into erythrocytes. On the other hand, the anti-P. yoelii serum antibodies also inhibited intracellular development of P. falciparum from rings to schizonts; 25 micrograms of IgG per ml caused 50% inhibition. Inhibition of P. falciparum growth by anti-P. yoelii serum IgG suggests that some of the interspecies cross-reactive antigens contain important conserved epitopes and induce protective antibodies against P. falciparum.

Animals↗
PubMed1994

Risk factors for delayed immunization among children in an HMO.

OBJECTIVES: Improving the timely delivery of childhood immunizations has become a national imperative. This study aimed to identify nonfinancial predictors of delayed immunization among patients with good financial access to preventive care. METHODS: This prospective cohort study used telephone interviews and a computerized immunization tracking system to evaluate 13-month-old children (n = 530) in a regional group-model health maintenance organization. RESULTS: More than one third of parents interviewed did not know when the next immunization was due. Thirteen percent were late for the measles-mumps-rubella immunization, recommended at 15 months of age, by 90 days or more. Independent predictors of delayed immunization included having a larger number of children (odds ratio [OR] = 1.4, P < .01), not having a regular doctor (OR = 2.9, P < .05), not knowing when the shot was due (OR = 2.0, P < .01), and not worrying about the risks of shots (OR = 1.4, P < .05). CONCLUSIONS: Financial access alone does not guarantee timely childhood immunization. In managed care settings, which may cover increasing numbers of children under health care reform, interventions are needed to better inform parents of when immunizations are due.

California↗
PubMed1994

Plasmodium vivax: immune responses in a cross-section of the population in the Delhi area of India.

The immune status of the individuals living in the Delhi area of northern India where Plasmodium vivax is predominant is described. The majority of the individuals who were acutely infected with P. vivax had antibodies against crude blood-stage antigen and the recombinant antigen, PV9. In contrast, the peripheral blood mononuclear cells of the majority of these individuals did not show proliferation in the presence of either of these antigens. There was no correlation between antibody levels and T cell proliferation. Such an immune status of individuals living in endemic areas should be taken into account in the future in developing P. vivax malaria vaccines.

Adolescent↗
PubMed1993

Structural and functional characterization of the HPV16 E7 protein expressed in bacteria.

The E7 gene of the human papillomaviruses (HPV) encodes a 98-amino acid, multifunctional nuclear phosphoprotein with functional and structural similarities to adenovirus E1A and the papovavirus T antigens. E7 is a viral oncoprotein, which will cooperate with an activated ras oncogene to transform primary rodent cells, and can cooperate with the HPV E6 protein for the efficient immortalization of primary human keratinocytes. Due to the compelling epidemiological and experimental association between HPV infection and cervical cancer, we have undertaken a detailed study of the structure of the HPV16 E7 protein. The E7 protein was expressed in Escherichia coli as a native, unfused polypeptide, and soluble protein was purified by conventional chromatographic techniques. The purified protein was assessed for various biochemical and biophysical properties. Purified E7 binds the retinoblastoma protein avidly and specifically, and it can dissociate the E2F transcription factor when assayed in vitro. Circular dichroism spectroscopy indicated that E7 reversibly binds Zn2+ and Cd2+, resulting in a substantial increase in the alpha-helical content of the metal-bound E7 consistent with the stabilization of a hydrophobic core in the COOH terminus of the protein.

Amino Acid Sequence↗
PubMed1993

[CYFRA 21-1: a new marker of epidermoid cancer of the bronchi. Comparison with 3 other markers].

Cytokeratins are intermediate filaments of the cytoskeleton that are expressed by bronchial epithelium and its neoplastic counterpart, lung cancer. A new immunoradiometric assay referred to as CYFRA 21-1 makes it possible to titrate in the serum a cytokeratin 19 fragment. This study deals with the sensitivity, specificity and applicability of this serum marker in squamous cell carcinoma. Sera from non malignant pulmonary diseases were taken as controls. In comparison with carcinoembryonic antigen (CEA), squamous cell carcinoma antigen (SCC T-A4) and neuron specific enolase (NSE), CYFRA 21-1 was the most accurate marker. The area under the CYFRA 21-1 ROC curve was significantly greater than those of CEA, SCC T-A4 and NSE. Using a 3.6 ng/ml threshold, as determined by the ROC curve, CYFRA 21-1 was significantly correlated with tumor mass.

Antigens, Neoplasm↗
PubMed1993

Botulinum toxin inhibits arachidonic acid release associated with acetylcholine release from PC12 cells.

The molecular mechanisms of depolarization-induced calcium-dependent acetylcholine (ACh) release and its inhibition by botulinum neurotoxin type A (BoTx) are not clear. We studied these mechanisms in an in vitro cholinergic neuronal pheochromocytoma PC12 cell line model. Cultured monolayer PC12 cells were differentiated by treatment with 50 ng/ml nerve growth factor (NGF) for 4 days to enhance cellular ACh synthesis and release. Stimulation of these cells with high K+ (80 mM) in the perfusion medium caused a marked increase (three to four times) in [3H]ACh release in a Ca(2+)-dependent manner. K(+)-stimulated [3H]ACh release was totally inhibited by pretreatment of cells with BoTx (2 nM) for 2 h. High K+ also stimulated the release of arachidonic acid ([3H]AA) from the cell membrane, which was inhibited by BoTx (2 nM). Addition of phospholipase A2 (PLA2) inhibitors (quinacrine, 4-bromophenacyl bromide, manoalide) to the perfusion medium inhibited K(+)-stimulated [3H]ACh and [3H]AA release in a dose-dependent manner. Inclusion of exogenous AA, the PLA2 activator melittin, or PLA2 itself prevented the effect of BoTx. These results demonstrate that in NGF-differentiated PC12 cells, AA release is associated with ACh release, BoTx inhibits both processes, and increased AA can protect against BoTx.

Acetophenones↗
PubMed1993

In utero fetal muscle biopsy for the diagnosis of Duchenne muscular dystrophy in a female fetus "suddenly at risk".

DNA methods to diagnose Duchenne muscular dystrophy (DMD) are not always informative, and we have published previously the first instance of in utero muscle biopsy to assess dystrophin in a male fetus having the same "X" as an affected sib. We present here a female fetus with a de novo X,1 translocation with breakpoint at Xp21, detected on amniocentesis for advanced maternal age. The translocation breakpoint placed her at high risk for DMD. In utero muscle biopsy at 20 weeks of gestation produced a specimen positive for dystrophin immunofluorescence indicating a likely normal fetus. The pregnancy was continued, and at term the baby girl was found to have normal serum creatine kinase levels, and was therefore unaffected with DMD. Our experiences add de novo Xp21 translocation to the indications for in utero muscle biopsy for diagnosis of DMD.

Adult↗
PubMed1993

American Cancer Society--National Prostate Cancer Detection Project. Results from multiple examinations using transrectal ultrasound, digital rectal examination, and prostate specific antigen.

BACKGROUND: The American Cancer Society-National Prostate Cancer Detection Project is a prospective study of the feasibility of early prostate cancer detection by digital rectal examination (DRE), transrectal ultrasound (TRUS), and prostate specific antigen (PSA). Two thousand nine hundred ninety-nine men not previously suspected of having prostate cancer have been entered on study in ten participating clinical centers. METHODS: The study protocol requires these men to undergo testing with the three detection methods under investigation on an annual basis for up to 5 years. Data currently are available on 1972 men who have completed protocol requirements for two sequential series of examinations. RESULTS: At the first visit, it was recommended that 16.5% of subjects undergo biopsy based on the TRUS and/or DRE findings. Seventy-three (3.7%) men were found to have cancer after the first series of examinations. When the 1899 men who did not have cancer were reexamined, in 11.4%, a biopsy was recommended, and an additional 33 (1.7%) cancers were detected. Cancer detection rates were higher in older men, and the sensitivity of TRUS was higher than that of DRE at both examinations. The positive predictive values (PPV) of TRUS and DRE varied significantly depending on the PSA level; PPV decreased at the second examination. Positive findings during the second examination were associated with elevated PSA levels during the earlier visit and rising PSA levels between examinations. Analyses of the 106 cancers detected currently showed a preponderance of early-stage cancer and low Gleason scores. CONCLUSIONS: It may be possible to increase the early detection of prostate cancer by periodic examination by a combination of detection modalities.

Aged↗
PubMed1993

Renal cell carcinoma: the size variable.

Three hundred and thirty-seven renal cell carcinomas treated at University of Illinois Affiliated Hospitals were reviewed. There was an inverse correlation between tumor size and survival.

Carcinoma, Renal Cell↗
PubMed1993

Long-term effects of acute thrombolytic therapy on ventricular size and function.

To investigate the influence of thrombolytic therapy on the natural history of left ventricular size and regional function after myocardial infarction, 32 patients treated with acute thrombolytic therapy (treatment group) were studied by echocardiography on admission to the hospital and at 1 week, 3 months, and 1 year after myocardial infarction; they were compared with 40 patients who did not receive acute intervention (control group). The endocardial surface area index (cm2/m2) and the area of abnormal wall motion (cm2) were calculated from left ventricular dimensions and measurements of abnormal wall motion. Although no differences in the endocardial surface area index were noted over the year for the groups as a whole, a significant difference was noted in treated anterior infarctions with early functional infarct expansion compared with untreated infarct expansion (treatment group: 85.8 +/- 2.0 cm2/m2 [entry] to 77.4 +/- 2.7 cm2/m2 [1 week] to 69.9 +/- 4.2 cm2/m2 [3 months] to 67.2 +/- 6.4 cm2/m2 [1 year] versus control group: 84.0 +/- 6.4 cm2/m2 [entry] to 83.7 +/- 8.5 cm2/m2 [1 week] to 96.3 +/- 8.6 cm2/m2 [3 months] to 81.5 +/- 4.2 cm2/m2 [1 year]; p < 0.01). When early expansion was present, those receiving thrombolysis exhibited a consistent decrease in the initially enlarged endocardial surface area in contrast to control subjects, who demonstrated continued increases in endocardial surface area during the first 3 months. In all groups a decrease in the area of abnormal wall motion was observed during the year of follow-up. However, the magnitude and timing of the improvement was accelerated in the treatment group. Thus acute thrombolytic therapy alters the natural history of left ventricular size and function with a more rapid recovery of abnormal endocardial segments and reversal of functional infarct expansion.

Case-Control Studies↗
PubMed1993

Safety of combined oligosaccharide conjugate Haemophilus influenzae type b (HbOC) and whole cell diphtheria-tetanus toxoids-pertussis vaccine in infancy. The Kaiser Permanente Pediatric Vaccine Study Group.

The safety of the combined oligosaccharide conjugate Haemophilus influenzae (Hib) type b (HbOC) and whole cell diphtheria-tetanus toxoids-pertussis (DTP) vaccine (Tetramune, HbOC-DTP; Lederle) in infancy was evaluated in 6644 recipients of this vaccine and compared with 3914 recipients of separate injections of whole cell DTP and HbOC vaccines when given as a three dose regimen to infants at 2, 4 and 6 months of age in each group. Of the total number of infants in the study, a subset of 1435 were enrolled into the study and then randomly assigned to receive either the Hib-DPT combined vaccine or the separate components. This subset was used to assess local and systemic side effects which were evaluated utilizing telephone interviews 48 to 72 hours after vaccine. The remaining children in the study population were enrolled in a nonrandomized manner. For these children parents were offered the experimental Hib-DPT vaccine and refusers were given HbOC and DTP. Both of these groups of children as well as the randomized subset described above were used to assess rates of episodes of hospitalization, emergency room utilization and sudden infant death syndrome in HbOC-DTP recipients and children who received HbOC and DTP separately. Immunogenicity was evaluated in 123 children by collection of a single serum sample 30 days after the third dose of HbOC-DTP. The observed immunogenicity was comparable to that observed in other recent studies for HbOC and DTP component antigens. The profile of local and systemic side effects observed was virtually identical to that observed after DTP plus HbOC given separately.(ABSTRACT TRUNCATED AT 250 WORDS)

Bacterial Proteins↗
PubMed1993

Botulinum toxin A inhibits acetylcholine release from cultured neurons in vitro.

Clostridium botulinum type toxin A (BoTx) blocks stimulus-induced acetylcholine (ACh) release from presynaptic nerve terminals at peripheral neuromuscular junctions. However, the detailed mechanism of this effect remains elusive. One obstacle in solving this problem is the lack of a suitable in vitro homogenous cholinergic neuronal model system. We studied the clonal pheochromocytoma PC12 cell line to establish such a model. PC12 cells were differentiated in culture by treatment with 50 ng/ml nerve growth factor (NGF) for 4 days to enhance cellular ACh synthesis and release properties. Stimulation of these cells with high K+ (80 mM) in the perfusion medium markedly increased calcium-dependent [3H]ACh release compared to undifferentiated cells. Stimulated [3H]ACh release was totally inhibited by pretreatment of cells with 2 nM BoTx for 2 h. BoTx inhibition of [3H]ACh release was time- and concentration-dependent. A 50% inhibition was obtained after 2 h incubation with a low (0.02 nM) toxin concentration. The time required for 2 nM BoTx to cause a measurable inhibition (18%) of stimulated [3H]ACh release was 30 min. Botulinum toxin inhibition of stimulated ACh release was prevented by toxin antiserum and heat treatment, suggesting the specificity of the toxin effect. Our results show that by differentiation with NGF, PC12 cells can be shifted from an insensitive to a sensitive state with respect to BoTx inhibition of stimulated ACh release. This cell line, therefore, may serve as a valuable in vitro cholinergic model system to study the mechanism of action of BoTx.

Acetylcholine↗