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Biomedical subjects

S Naik

Publications and source records attributed to S Naik.

At least 55 records · Page 3Linked to original sources

Pigmented nails and Strongyloides stercoralis infestation causing clinical worsening in a patient treated for immunoproliferative small intestinal disease: two unusual observations.

Immunoproliferative small intestinal disease (IPSID) is commonly reported from developing countries with poor socioeconomic conditions, hygiene, and high frequency of gastrointestinal infections and infestations. The disease requires anti-malignant chemotherapy in lymphomatous stage. Reported here is a 20-year old man with IPSID lymphoma who responded to anti-malignant chemotherapy initially, but later deteriorated due to Strongyloides stercoralis infestation, which was treated successfully with mebendazole. Importance of an early recognition and adequate treatment for gastrointestinal infections and infestations before anti-malignant chemotherapy for this disease is highlighted considering the occurrence of this disease in the developing world. The patient developed alternate brown black and white lines in the finger nails after combination chemotherapy, which has not been reported earlier in this disease; the nail changes disappeared 6 months after the withdrawal of doxorubicin suggesting this drug as the cause for such nail changes during anti-malignant combination chemotherapy.

Adult↗

RNase L dimerization in a mammalian two-hybrid system in response to 2',5'-oligoadenylates.

RNase L, a key enzyme in the anti-viral activity of interferons, requires activation by 2',5'-linked oligoadenylates (2-5A) to cleave viral and cellular single-stranded RNA. Here we demonstrate that 2-5A causes formation of stable dimers of RNase L in intact human cells as measured with a mammalian two-hybrid system. Hybrid proteins consisting of the GAL4 DNA binding domain fused to RNase L and the VP16 transactivation domain fused to RNase L were able to associate and drive transcription of a reporter gene, but only after cells were transfected with 2-5A. Several functional forms of 2-5A, such as p3A2'p5'A2'p5'A, were capable of activating transcription in human HeLa cells. In contrast, p3A2'p5'A, which can neither activate nor dimerize RNase L, did not induce gene expression. Evidence for the involvement of the C-terminal region of RNase L in dimerization was obtained by expressing truncated forms of RNase L. These findings describe a convenient, high-throughput screening method for RNase L activators which could lead to the discovery of novel anti-viral and anti-cancer agents.

Adenine Nucleotides↗

Manoeuvres to elevate mean airway pressure, effects on blood gases and lung function in children with and without pulmonary pathology.

UNLABELLED: During mechanical ventilation, mean airway pressure (MAP) can be increased by a variety of manoeuvres, for example increasing inspiratory time or elevating the positive end expiratory pressure (PEEP). It seemed likely that the effect on blood gases and lung function of a particular manoeuvre to increase MAP would be influenced by the presence of respiratory pathology and thus the manoeuvre best at improving respiratory status in children with an abnormal chest radiograph appearance would differ from that most efficacious in children without such a problem. The aim of this study was to test that hypothesis. Twenty-two children, median age 15 months (range 2.5 weeks-10 years) were examined. Group 1 (n = 10) had no chest radiograph abnormalities and group 2 (n = 12) lobar collapse and/or consolidation. The patients were studied at baseline settings and at an elevated MAP resulting from (in random order) an increase in inspiratory time (T1), pressure PEEP or peak inspiratory pressure (PIP). In group 1, elevating PIP improved oxygenation and carbon dioxide elimination (P < 0.01) and prolonging T1 improved oxygenation (P < 0.05). In group 2, only raising PEEP significantly improved oxygenation (P < 0.01), but this was associated with carbon dioxide retention (P < 0.01). CONCLUSION: The presence of lung pathology does influence which manoeuvre should be used to elevate MAP to improve blood gases in the paediatric population.

Airway Resistance↗

Vaccination of langur monkeys (Presbytis entellus) against Leishmania donovani with autoclaved L. major plus BCG.

The protective potential of killed Leishmania major (ALM) along with BCG was evaluated against L. donovani in Indian langur monkeys in single and triple dose schedules. A delayed protection was observed in monkeys after a single dose schedule of ALM (3 mg)+BCG (3 mg) given intradermally 2 months before intravenous challenge with L. donovani. Triple dose schedule each of 1 mg ALM + 1 mg BCG was more effective. The status remained unchanged until the end of the experiment (approximately 8 months). The study indicates that a combination of ALM + BCG may be a good candidate vaccine for exploiting against human Kala-azar.

Adjuvants, Immunologic↗

Perinatal lung function measurements and prediction of respiratory problems in infancy.

The aim of this study was to determine which lung function test employed in the perinatal period gave the results most significantly associated with respiratory problems in infancy. The ratio of the proportion of time to reach peak tidal expiratory flow to total expiratory time (tPTEF:tE), thoracic gas volume (TGV) and airway resistance (R(aw)) (from which specific conductance (SG(aw)) was calculated) measurements were examined from 85 infants born at or near term. The infants were followed until at least one year of age and described as symptomatic if they wheezed for at least 24 hours. Twenty-three infants were symptomatic in the first year. The symptomatic group, compared to the asymptomatic, had a higher median FRC (p < 0.01) and R(aw) (p < 0.001); their median SG(aw) was lower (p < 0.001). It was possible to obtain tPTEF:tE results from only 61 infants; the median tPTEF:tE did not differ significantly between symptomatic and asymptomatic infants. Logistic regression analysis demonstrated a high R(aw) and FRC, but not a low tPTEF:tE, independently related to positive symptom status. A high R(aw) (>26 cm H2O (1 s(-1))(-1)) was the most sensitive (83%) predictor of subsequent respiratory problems, but all the tests examined had low positive predictive values.

Child↗

Proteinase activity & virulence of Entamoeba histolytica on passage through hamster liver.

This study was undertaken to determine the enzymatic differences in the process of increasing the degree of virulence in E. histolytica successively passaged in hamster liver. Substrate gel electrophoresis was used to compare proteinase banding patterns under reducing conditions from whole cell lysates of one axenic E. histolytica (strain HM1:IMSS) and five xenic isolates of the same strain of E. histolytica passaged five times through hamster liver. Trophozoites successively passaged in hamster liver showed in supernatants, major bands in the 56-97 kDa region whereas only the axenic strain produced additional band at 34 KDa. Inoculation of amoebic trophozoites into hamster led to progressive increase in proteinase activity of supernatants as well as increased virulence of amoebae; proteinase activity of amoebae showed an excellent correlation with their virulence. All the infected animals died when activity of proteinase was 0.152 mg of protein.

Animals↗

Lack of in vitro lymphoproliferative response to hepatitis B surface antigen in healthy vaccine recipients.

A majority of HBsAg vaccine recipients show good anti-HBs antibody responses but poor antigen specific lymphoproliferative responses. We investigated the basis for this poor in vitro antigen specific proliferative responsiveness in vaccinees who had received the standard three dose schedule (0, 1 and 6 months) of plasma derived HBsAg vaccine. Peripheral blood mononuclear cells (PBMC) from 26 of 29 (89.7%) vaccinees failed to show lymphoproliferative responses to HBsAg in spite of having a very good anti-HBs antibody response (geometric mean titre 3154 IU/1). The mitogen (phytohaemagglutinin, PHA) and antigen (purified protein derivative, PPD) driven lymphoproliferative responses in these individuals were normal. Addition of exogenous recombinant interleukin-2 (rIL-2) along with HBsAg had no effect in the response to HBsAg in six of nine vaccinees, who were tested six months after the third vaccine dose or in four unvaccinated controls. However, in three vaccinees who did not have lymphoproliferative response to HBsAg alone, addition of exogenous rIL-2 resulted in a synergistic response. These data suggest that HBsAg reactive cells are few in the peripheral circulation of a majority of individuals following the standard three dose schedule of vaccination and addition of exogenous rIL-2 induces a response only in a subgroup of individuals. The inability of HBsAg to induce a T cell proliferative response may have implications for the maintenance of protective immunity and immunological memory following vaccination.

Adult↗

Effect of bacterial association on virulence of Entamoeba histolytica to baby hamster kidney cell monolayers.

Axenic E. histolytica trophozoite strain NIH:200 and HMI:IMSS when co-associated with aerobic bacteria Escherichia coli strain K12 and serotype 056 showed marked increase in virulence as observed by destruction of baby hamster kidney (BHK) monolayers. However, when incubated with anaerobic bacterial strains Clostridium perfringens and Bacteroides fragilis virulence remained unaltered. Further, adherence of E. histolytica to BHK monolayer was found to be mediated by N-acetyl-D-galactosamine.

Acetylgalactosamine↗

Interferon action and apoptosis are defective in mice devoid of 2',5'-oligoadenylate-dependent RNase L.

2',5'-Oligoadenylate-dependent RNase L functions in the interferon-inducible, RNA decay pathway known as the 2-5A system. To determine the physiological roles of the 2-5A system, mice were generated with a targeted disruption of the RNase L gene. The antiviral effect of interferon alpha was impaired in RNase L-/- mice providing the first evidence that the 2-5A system functions as an antiviral pathway in animals. In addition, remarkably enlarged thymuses in the RNase L-/- mice resulted from a suppression of apoptosis. There was a 2-fold decrease in apoptosis in vivo in the thymuses and spleens of RNase L-/- mice. Furthermore, apoptosis was substantially suppressed in RNase L-/- thymocytes and fibroblasts treated with different apoptotic agents. These results suggest that both interferon action and apoptosis can be controlled at the level of RNA stability by RNase L. Another implication is that the 2-5A system is likely to contribute to the antiviral activity of interferon by inducing apoptosis of infected cells.

Adenine Nucleotides↗

Transcriptional activation of the intercellular adhesion molecule 1 (CD54) gene by human T lymphotropic virus types I and II Tax is mediated through a palindromic response element.

In vitro infection of T cells with human T lymphotropic virus types I and II (HTLV-I and HTLV-II) resulted in constitutive expression of ICAM-1. Higher levels of ICAM-1 mRNA were expressed in HTLV-transformed cell lines (MT-2, MoT, C8166) when compared with uninfected T cell lines (A301). We demonstrate that this activation is conferred through a site on the ICAM-1 promoter that is activated in trans by the Tax protein of HTLV-I and HTLV-II. Enhanced promoter activity was detected when the ICAM-1 construct (-1162/+1) was transfected into HTLV-I-infected (MT-2), HTLV-II-infected (MoT, AI 1050), or an HTLV-I Tax-only-expressing (C8166) cell line as compared to the uninfected T cell line (A3.01). Cotransfection of the uninfected T cell line A3.01 with the ICAM construct along with Tax-I and Tax-II expression plasmid also resulted in increased promoter activity. Furthermore, experiments with deletion constructs of the ICAM-1 promoter region indicated that a region between -88 and -53 bp relative to the transcription start site is sufficient for Tax-inducible CAT expression. This segment includes an 11-bp palindromic segment (TTTCCGGGAAA) that has homology with the IFN-gamma and IL-6 response element. An 11-bp segment containing this regulatory region proved to be sufficient to confer Tax-I and Tax-II inducibility on a heterologous promoter (TK-CAT). Taken together these findings indicate that constitutive expression of ICAM-1 by HTLV-infected cells is influenced by the viral trans-activator protein Tax. This increased expression of ICAM-1 in response to the Tax protein may play an important role in the lymphoproliferation associated with HTLV infection.

Cell Line↗

First trimester invasive procedures: effects on symptom status and lung volume in very young children.

First trimester procedures have been associated with perinatal lung function abnormalities that may suggest subsequent respiratory problems. Our aim was, therefore, to assess the impact of first trimester invasive procedures [early amniocentesis (EA) and chorion villus sampling (CVS)] on respiratory morbidity in very young children. A questionnaire was issued to parents of 439 EA and 453 CVS (subjects), and 435 controls (their mothers had undergone no invasive procedures) when their children were one year old. Data were also obtained from diary cards issued to a subset of 278 of the EA, 262 of the CVS, and 264 of the control infants followed prospectively. Functional residual capacity (FRC) was measured at a median age of 5 months (range: 0.25-24) in 159 children whose mothers had undergone EA, 168 following CVS and in 165 controls. Analysis of the one-year questionnaire demonstrated an excess of symptomatic infants in the EA group (31%) compared to the CVS (22%; P < 0.01) and control groups (17%; P < 0.01). Findings from the prospective follow-up study confirmed those results and also demonstrated an increase in chest-related hospital admissions in the EA group (3%) compared to the controls (0.4%; P < 0.05). Logistic regression analysis revealed that positive symptom status related significantly to EA and CVS interventions (P < 0.0001), bottle feeding (P < 0.001), parental smoking (P < 0.01), a family history of atopy (P < 0.01), and immaturity (P < 0.01). In the control group, FRC correlated best with weight (r = 0.92). The mean FRC of the EA and CVS groups was higher than that of the controls (P < 0.01). A higher proportion of children had an FRC two standard deviations above the controls' mean in the EA group (n = 14) compared to the CVS group (n = 3; P < 0.01). The symptomatic infants tended to have higher FRCs than the asymptomatic children. We conclude that first trimester procedures are associated with increased respiratory morbidity in very young children.

Amniocentesis↗

The effect of blood transfusion on oxygenation in premature ventilated neonates.

UNLABELLED: The effect of blood transfusion to maintain a preset packed cell volume (PCV) level in preterm ventilated infants has been investigated. Fifty infants, median gestational age 26 (range 23-33) weeks and postnatal age 4 (1-29) days, transfused a median of 15 ml/kg of blood in response to a PCV < or = 40% were retrospectively identified and their medical records reviewed to determine the change in PCV and haemoglobin resulting from the transfusions. In addition, their mean airway pressure (MAP) was noted and, as an index of oxygenation, their oxygenation index (OI), alveolar/arterial oxygen gradient (AaDO2) and arterial/alveolar (a/A) ratio calculated 12 h, 6 h and immediately prior to the transfusion and immediately post, 12, 18 and 24 h after the transfusion. The transfusion improved the PCV and haemoglobin (P < 0.0001). No significant changes in MAP or level of oxygenation were experienced in the 12 h prior to the transfusion. Post transfusion, despite no significant change in MAP, the AaDO2 OI and a/A ratios compared to immediately prior to the transfusion were significantly better at 12, 18 and 24 h. CONCLUSION: It is useful to transfuse ventilated preterm infants to maintain their PCV above a preset level.

Blood Gas Analysis↗

Risk factors for hyperinflation in young schoolchildren born prematurely.

UNLABELLED: Lung function abnormalities, including hyperinflation, are common in young children born prematurely. The aim of this study was, in such patients, to determine factors associated with hyperinflation, that is an elevated lung volume. Lung volume was estimated by measuring functional residual capacity (FRC) before and after bronchodilator therapy in 41 5-year-old children who had been born prematurely at a median of 30 weeks gestational age. Hyperinflation was defined as an FRC greater than 120% of that predicted for height and a positive bronchodilator response as a greater than or equal to 10% change in FRC. Twelve (29%) of the children were symptomatic at 5 years, their median FRC (132%) was significantly higher than that of the asymptomatic children (109%), P < 0.01). Twelve (29%) children were hyperinflated; a greater proportion of the hyperinflated compared to the non-hyperinflated patients were symptomatic at 5 years (7 or 58% versus 5 or 17%) (P < 0.05) and responded to bronchodilator therapy (9 or 75% versus 4 or 14%) (P < 0.01). Regression analysis demonstrated that hyperinflation related significantly only to current symptom status, but not perinatal variables. CONCLUSION: Hyperinflation in young children born prematurely reflects current symptom status and not adverse neonatal events.

Bronchodilator Agents↗

Invasive antenatal procedures and requirement for neonatal intensive care unit admission.

Neonatal respiratory difficulties are increased following second trimester amniocentesis. In preterm, prolonged rupture of the membranes, respiratory outcome is particularly poor when rupture occurs in the first trimester. It therefore seems likely that first trimester/ early amniocentesis (EA) would be associated with severe respiratory problems necessitating a high neonatal intensive care unit (NICU) admission rate. To test that hypothesis, the requirement for admission to the NICU of 278 infants whose mothers had undergone EA, 262 whose mothers had undergone chorion villus sampling (CVS group) and 264 controls whose mothers had undergone no invasive procedures were reviewed as were their diagnoses if they needed admission. There was no significant difference in the mode of delivery, gestational age or gender distribution of the three groups and the median maternal age of the EA and CVS groups was similar. Nineteen EA, eight CVS and five control infants required admission to the NICU (EA versus controls, P < 0.01; EA versus CVS plus controls, P < 0.005). Nine EA, one CVS and four control infants had suffered respiratory problems (EA versus CVS P < 0.05). Logistic regression analysis demonstrated that immaturity and EA were significantly associated with a requirement for NICU admission. We conclude infants whose mothers have undergone EA may be at increased risk for NICU admission, this is partly due to respiratory problems but the association is uncommon.

Amniocentesis↗

In vitro effect of gold sodium thiomalate and methotrexate on tumor necrosis factor production in normal healthy individuals and patients with rheumatoid arthritis.

We studied the in vitro action of gold sodium thiomalate (GSTM) and Methotrexate (MTX) on spontaneous and lipopolysaccharide (LPS) stimulated TNF alpha production by peripheral blood mononuclear cells (PBMC) of patients with rheumatoid arthritis (RA) and normal healthy individuals. GSTM and MTX (10 microg) each were added to the cultures of PBMC either in medium alone (spontaneous) or in the presence of 10 microg of LPS. GSTM and MTX augmented spontaneous TNF alpha production in normal individuals and patients with RA but did not influence LPS stimulated TNF alpha production. However, TNF alpha production by the PBMC of normal individuals was inhibited if the PBMC were stimulated with LPS, for 6 or 12 h, washed to remove LPS and subsequently incubated with GSTM. These data indicate that GSTM can inhibit TNF alpha production when the PBMC are preactivated by LPS.

Animals↗