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Biomedical subjects

S Pai

Publications and source records attributed to S Pai.

At least 55 records · Page 3Linked to original sources
PubMed1996

Abnormality in translational regulation of catalase expression in disorders of peroxisomal biogenesis.

Peroxisomal disorders are a newly described group of inherited neurological diseases. In disorders of peroxisomal biogenesis, e.g., Zellweger syndrome, owing to the lack of peroxisomes, catalase, a peroxisomal enzyme, is found to be present in the cytoplasm instead. We observed higher catalase activity (7.59 +/- 0.41 mU/ mg of protein) in cultured skin fibroblasts from Zellweger patients than in control fibroblasts (4.45 +/- 0.29 mU/mg of protein). Moreover, we also found that the majority of the catalase in Zellweger cells was present in the inactive form. The specific activities following reactivation in Zellweger and control cells were 12.1 and 4.9 mU/mg of protein, respectively. To understand the molecular basis of higher levels of catalase in Zellweger than control cells, we examined the rate of synthesis and turnover of catalase and levels of catalase mRNA and protein levels in Zellweger cells as compared with control cells. The initial rates of synthesis of catalase in Zellweger (1.68 +/- 0.15 mU/mg of protein) and control (1.51 +/- 0.14 mU/mg of protein) cells were similar. The rates of turnover of catalase in Zellweger (t1/2 = 47 +/- 8 h) and control (t1/2 = 49 +/- 7 h) were also similar. Consistent with the enzyme activity, the levels of catalase protein were higher in Zellweger cells as compared with control cells. On the other hand, there was no difference in the level of catalase mRNA between control and Zellweger cells. Although the rate of synthesis in Zellweger and control cells was initially similar, it was down-regulated to a lower level at approximately 72 h of culture in control fibroblasts as compared with Zellweger cells, which continued to synthesize catalase at the same rate up to 5 days in culture. The presence of similar levels of mRNA in control and Zellweger cells and continued synthesis of catalase in Zellweger cells at a higher level as compared with control cells suggest a loss of regulation at the translational level.

Adrenoleukodystrophy↗
PubMed1996

Effects of synthetic form of tracheal antimicrobial peptide on respiratory pathogens.

We have synthesized a C-terminal portion of tracheal antimicrobial peptide (TAP) with 38 amino acids and tested it for efficacy on various clinical isolates of Pseudomonas aeruginosa strains from patients with cystic fibrosis and also on Aspergillus fumigatus. Our results indicate that the synthetic TAP has both potent bactericidal and fungicidal activities and that a combination of TAP and amphotericin B showed strong additive effects of growth inhibition on A fumigatus. These results suggest that TAP is potentially an effective therapy for Aspergillus and multi-drug-resistant Pseudomonas, pathogens that are often a serious threat to patients with cystic fibrosis.

Anti-Bacterial Agents↗
PubMed1996

A synthetic form of tracheal antimicrobial peptide has both bactericidal and antifungal activities.

We have chemically synthesized tracheal antimicrobial peptide (TAP) with 38 amino acids and examined efficacy of the peptide on various organisms. The synthetic peptide showed potent bactericidal effect on both gram positive and negative bacteria. The action of bactericidal effect was relatively quick and 99.9% of E. coli cells were killed within 90 minutes at a concentration of 2.5 micrograms/ml of TAP. The peptide also showed antifungal activity against both mycelia (Aspergillus fumigatus) and yeast (Candida albicans) forms of fungi. Our domain analysis with a series of synthetic peptides of various lengths indicates that 17 amino acid residues of the C-terminal end is the minimum functional domain of the bactericidal activity.

Amino Acid Sequence↗
PubMed1995

Pharmacokinetic-pharmacodynamic (PK-PD) modeling for a new antihypertensive agent (neutral metalloendopeptidase inhibitor SCH 42354) in patients with mild to moderate hypertension.

SCH 42354, a neutral metalloendopeptidase (NEP) inhibitor, is the pharmacologically active form of the prodrug SCH 42495. It exerts antihypertensive effects by potentiating atrial natriuretic peptide (ANP) activity through inhibition of its hydrolysis by NEP. The objective of this study was to characterize the pharmacokinetics (PK) and pharmacodynamics (PD) of SCH 42354 in hypertensive males. SCH 42495 12.5 to 400 mg was administered orally to hypertensive men twice daily in a double-blind, placebo controlled multiple-dose parallel group design. Plasma SCH 42354 concentration and diastolic blood pressure (DBP) data were used to develop a PK-PD model using two approaches. In the first (non-integrated) approach, the ¿link¿ model was used to predict effect-site concentrations, and was applied to data obtained at the 300 and 400 mg BID doses only; data at the other (lower) doses were not amenable to modeling because of high variability. Effect-site concentration and DBP data were then fit to a sigmoid Emax PD model. For the 300 mg BID dose, PD parameters were: maximum effect (Emax), 8.1 mmHg; no-drug effect (Eo), 3.6 mmHg; concentration corresponding to 50% of maximum response (EC50), 0.87 microgram x ml(-1); and gamma, 3.9. In the second (time-integrated) approach, plasma SCH 42354 concentration and effect data obtained over the entire dose range were integrated with respect to time. Average plasma concentration and DBP data were then fit to a simple Emax PD model. PD parameters obtained over the dose range were: Emax, 10.3 mmHg; Eo, 2.0 mmHg; and EC50 0.7 microgram x ml(-1). These were similar to the estimates obtained from the first approach, demonstrating that the integrated (average) data allow PK-PD modeling over the (entire) dose range. The analysis showed that, at steady-state, a 400 mg BID dose of SCH 42495 produced an approximate 10 mmHg decrease in DBP in hypertensive males; the average plasma SCH 42354 concentration attained at this dose was approximately 1.8 microgram x ml(-1).

Adult↗
PubMed1995

Vasopressin gene related products are markers of human breast cancer.

Immunohistochemical analysis for products of vasopressin and oxytocin gene expression was performed on acetone-fixed tissues from 19 breast cancers representing a variety of tumor sub-types. Studies employed the avidin-biotin complex (ABC) immunohistochemical procedure and utilized rabbit polyclonal antibodies to arginine vasopressin (VP), provasopressin (ProVP), vasopressin-associated human glycopeptide (VAG), oxytocin (OT), oxytocin-associated human neurophysin (OT-HNP), and a mouse monoclonal antibody to vasopressin-associated human neurophysin (VP-HNP). Western Blot analysis was performed on protein extracts of fresh-frozen tissues from 12 additional breast tumors. While VP gene related proteins were not detected in normal breast tissue, immunohistochemistry revealed the presence of VP, ProVP, and VAG in all neoplastic cells for all of the tumor tissues examined. Vasopressin-associated human neurophysin was evident in only one of 19 acetone-fixed tumor preparations. However, Western blot analysis for all 12 fresh-frozen tumor samples showed the presence of two proteins, 42,000 and 20,000 daltons, that were immunoreactive with antibodies to VP, VP-HNP, and VAG. Oxytocin and OT-HNP, by immunohistochemistry, were found to be common to cells of normal breast tissues. For tumors, positive staining for OT was observed in 8 of 18 tumors, while OT-HNP was not detected in any of the tumors examined. These findings indicate that VP gene expression is a selective feature of all breast cancers, and that products of this expression might therefore be useful as markers for early detection of this disease and as possible targets for immunotherapy.

Antibodies, Monoclonal↗
PubMed1995

A new isocenter shift method for ideal geometric matching of two adjacent fields.

The most commonly used technique for matching two adjoining parallel opposed fields has been geometric matching with a skin gap calculation. Many modifications have been suggested in order to minimize the shortcomings of this technique. Most of these, however, are more complex and time consuming in clinical practice, with little dosimetric improvement. We propose a simple new method for adjacent field abutment that eliminates hot and cold spots due to different beam divergences. This method is based upon the use of a single match plane for both the cephalad and caudad parallel opposed beams. The divergence angle of these opposed beams is forced to be equal at the junction through the use of the same field length and the same target axis distance (TAD). For the isocentric treatment case, the procedure is summarized as follows. After setting up the cephalad AP/PA fields to midplane in the conventional manner, the patient support couch is shifted longitudinally in the cephalad direction by a precise distance equal to the cephalad field length. The superior collimator of the caudad field is kept the same as for the cephalad field to ensure equal divergence angles. The actual irradiated volume of the caudad field is adjusted as needed by a large block or an asymmetric jaw. An analogous procedure is described for the nonisocentric case. This new isocenter shift method culminates in several distinct advantages over the other geometric methods.(ABSTRACT TRUNCATED AT 250 WORDS)

Film Dosimetry↗
PubMed1994

Ovarian myxoma in a premenarchal girl.

A case of ovarian myxoma in a 12-year-old premenarchal girl is reported. This paper details the clinical presentation, gross and microscopic pathology, Immunocytochemical profile, and behavior of this rare tumor. The differential diagnosis and possible histogenesis is briefly discussed.

Child↗
PubMed1994

Bathing suit delivery of 8-methoxypsoralen for psoriasis: a double-blind, placebo-controlled study.

Twenty-four patients, 15 men and 9 women, aged 18-70 years with stable plaque-type psoriasis involving more than 20% of the body surface were subjected to a randomized, double-blind, age- and sex-matched, placebo-controlled study. Containers containing 25 mL of either 1% 8-MOP or a color-matched placebo were randomly numbered and stored. To 2 L of water was added 0.8 mL of 1% 8-MOP to obtain a concentration of 3.75 mg/L3, into which a bathing suit was soaked for 5 min. The suits were then gently squeezed to remove excess water and the patients were advised to put on the suit covered by a raincoat for 15 min. Immediately after removal of the raincoat and the suit, patients were irradiated with an initial dose of 4 J/cm2 UVA with increments of 0.5 J/cm2 on alternate days in a whole-body phototherapy unit obtained from the National Biological Corporation, Ohio. Erythema, scaling, and thickness (EST) of the index lesions were assessed on a 3-point scale (Table 1) and photographs were taken before and after completion of the study.

Adolescent↗
PubMed1994

Adult acute lymphoblastic leukemia: results of an aggressive regimen in India.

A total of 42 adults with acute lymphoblastic leukemia were treated with an aggressive induction/consolidation chemotherapy (MCP-841) between June 1986 and December 1991. 32 patients (76.19%) achieved complete remission at the end of induction. There were 9 induction deaths, 6 of them due to infection. All patients received cranial irradiation in the dose of 20 Gy and intrathecal methotrexate for CNS prophylaxis. Twelve patients relapsed, 10 in the bone marrow, one case had isolated CNS relapse and the other relapsed in the bone marrow and CNS. The actuarial overall survival of all patients at the end of 5 years was 41.94%. Patient characteristics including age, sex, FAB morphology, phenotype, WBC count, platelet count and LDH did not influence survival significantly.

Adult↗
PubMed1993

Head and neck synovial sarcomas.

Eleven cases of synovial sarcoma of the head and neck are analyzed. Patients presented with a mass either in the parapharynx, pharyngeal wall, or nape of the neck. The tumors ranged in size from 3 to 8 cm. Microscopically, the classic biphasic pattern was seen in 10 tumors. Immunohistochemistry and electron microscopy were useful in the diagnosis of the single monophasic variant of synovial sarcoma. Radical surgery was the mainstay of treatment with post-operative radiotherapy for residual disease. Five patients were dead of disease while 6 were alive for periods varying from 9 months to 15 years. The purpose of this presentation is to accrue data on this sarcoma at a rare site, and to highlight the histopathological differential diagnosis, which includes both carcinomas and sarcomas. Treatment decisions would be affected by the histology report.

Adolescent↗
PubMed1993

Prinomide tromethamine pharmacokinetics: mutually dependent saturable and competitive protein binding between prinomide and its own metabolite.

Prinomide tromethamine, a nonsteroidal antiinflammatory drug, was orally administered at doses of 250, 500, and 1000 mg every 12 hr for 28 days to healthy male volunteers. The pharmacokinetic behavior of prinomide and its primary plasma metabolite displayed nonlinear characteristics, while those of free prinomide and its metabolite were dose proportional. The nonlinear pharmacokinetic behavior of total prinomide and p-hydroxy metabolite was found to be caused by both saturable and mutually dependent competitive Langmuir-type plasma protein binding between prinomide and its p-hydroxy metabolite. The extent of the protein interaction displayed at steady state was due to the extensive accumulation of the p-hydroxy metabolite. While ligand-protein interactions are known for xenobiotic competitors, the characteristic behavior of prinomide is the first known example to be reported for a competitive protein interaction between a xenobiotic and its own in vivo generated metabolite. The findings of this study may have implications regarding the disposition of other extensively bound nonsteroidal antiinflammatory drugs with long-lived metabolites.

Adult↗
PubMed1993

Emotional distress in disaster victims. A follow-up study.

One hundred thirteen adult victims of a major Latin American disaster were screened for emotional distress 1 and 5 years after the catastrophe. We used the Self-Reporting Questionnaire to identify emotionally distressed victims. Results indicate that the prevalence of emotional distress decreased from 65% in 1986 to 31% in 1990. However, a comparison of the symptomatology on these two assessments indicates a similarity in the frequency and profiles of symptoms among the distressed. Also, the most frequent symptoms and the strongest predictors of emotional distress were essentially the same. These findings provide empirical support to the clinically observed course of emotional symptomatology of disaster victims and to the focused training of health workers on selected emotional problems that are consistently present over time.

Adult↗
PubMed1993

L-asparaginase related hyperglycemia.

L-asparaginase is a valuable chemotherapeutic agent used in the induction of remission and improvement of long term survival in patients with acute lymphoblastic leukemia. Hyperglycemia is a well known side effect of L-asparaginase. Fourteen patients developed hyperglycemia during induction therapy of acute lymphoblastic leukemia with L-asparaginase, prednisolone, vincristine and daunorubicin. Hyperglycemia was observed after a mean of five doses of L-asparaginase (range 2-10). Seven of fourteen patients had neutropenic related infective episodes. Hyperglycemia resolved in all patients within 12 days (range 4-25) and two patients died of neutropenic septicemia. During reinduction therapy with the same drugs, only one out of ten patients developed hyperglycemia E-coli-L-asparaginase was replaced by Erwinia asparaginase in two patients one of who had recrudescence on further therapy. Close monitoring during L-asparaginase therapy for hyperglycemia will enable prompt recognition and early correction and prevent delay in therapy of acute lymphoblastic leukemia.

Adolescent↗
PubMed1992

Assessment of geometric treatment accuracy using time-lapse display of electronic portal images.

During the past two years, several electronic portal imaging systems have been introduced to the market by therapy accelerator manufacturers and other vendors. While these systems differ substantially in their detection technology, they are all capable of displaying portal images on a video screen in near real-time, and of creating multiple static (or "movie") images during each treatment. Major questions confront the users of such systems as to the best utilization of this wealth of information, and to its value in comparison to traditional weekly portal film methods. Using an "in-house" video based system, a new technique was established to aid in the assessment of on-line images so that immediate "go/no-go" decisions can be made by the therapy technologist. A video "movie-loop" is displayed which consists of the static image of the initial (approved) set-up, and the current treatment image. Multiple images of successive treatments can also be viewed in this "time-lapse" display mode to provide a quick visual means for review of an entire course of therapy. The on-line imaging system hardware is composed of a combination copper-plate/fluorescent-screen detector, a front surface mirror angled at 45 degrees to remove the camera from the direct radiation beam, and a high sensitivity SIT video camera. This assembly is attached to a rigid base and mounted directly to the isocentric gantry. The geometry is fixed to within +/- 1 mm and assures the precise day-to-day reproducibility which is necessary for the success of the time-lapse display technique. Experience with this technique shows it to enhance the user's ability to notice small changes in patient's position with respect to the radiation field. Radiation treatment sites reviewed using this procedure were Hodgkin's (mantle), Lung, Brain and extremities. Shifts in patient position on the order of several millimeters were readily detectable, as will be demonstrated in this paper. Somewhat surprisingly, grosser movements (greater than 1 cm) were also noted despite overall technical excellence as assessed by weekly portal filming. The eye senses day-to-day movement with greater ease when the fields are seen in time-lapse display than when compared as discrete portal images. Ultimately, persistent movement appreciated on the time-lapse display can suggest the need for a change in patient set-up or immobilization technique.

Humans↗
PubMed1992

Psychiatric disorders among emotionally distressed disaster victims attending primary mental health clinics in Ecuador.

Previous studies in developing countries have demonstrated post-disaster stress disorders in a substantial share of the people living through a natural calamity, but questions have remained as to the severity of these mental health problems. This article reports information derived from a 1987 study of Ecuadorian earthquake victims that shows many of the victims had diagnosable psychiatric disorders and provides insight into the nature of those disorders.

Adult↗
PubMed1992

[Psychiatric disorders among victims of disasters in Ecuador].

Previous studies in developing countries have demonstrated post-disaster stress disorders in a substantial share of the people living through a natural calamity, but questions have remained as to the severity of these mental health problems. This article reports information derived from a 1987 study of Ecuadorian earthquake victims that shows many of the victims had diagnosable psychiatric disorders and provides insight into the nature of those disorders.

Adolescent↗
PubMed1991

Psychiatric disorders among poor victims following a major disaster: Armero, Colombia.

We evaluated 102 adult victims of low socioeconomic status living in tent camps 8 months following the Armero disaster in Colombia to ascertain the level of psychiatric morbidity. Ninety-one percent of the subjects identified by the screening instrument as being emotionally distressed met DSM-III criteria for a psychiatric disorder. The most frequent diagnoses were posttraumatic stress disorder and major depression. These findings indicate that a simple screening instrument can be reliably used for the detection of significant emotional problems among disaster victims. They also show that these victims are not merely distressed; rather, they present clear and treatable psychiatric disorders that center on anxiety and depression. Interventions for their adequate management need to be designed, implemented, and evaluated. In a developing country, however, the high prevalence of mental disorders among disaster victims far exceeds the specialized mental health resources. The general health sector, particularly the primary level of care, must participate actively in the delivery of mental health services to meet this need, particularly for a socioeconomically disadvantaged population. The narrow range of psychiatric disorders detected among the disaster victims makes it possible to circumscribe the training of the primary care worker in disaster mental health to these priority conditions.

Adult↗