Biomedical subjects

S Gupta

Publications and source records attributed to S Gupta.

At least 163 records · Page 9Linked to original sources

PubMed2003

Investigations of 99mTc morpholino pretargeting in mice.

This laboratory is exploring the use of morpholinos (MORFs), synthetic DNA analogues, for nuclear medicine applications, including pretargeting. The anti-CEA antibody MN14 was conjugated with an 18 mer MORF and with diethylenetriaminepentaacetic acid (DTPA) for 111In labelling. In a dual label pretargeting study, tumour-bearing nude mice received different doses of (MN14-DTPA-111In+MN14-MORF) followed, at various times after i.v. injection, by 0.15 microg complementary MORF (cMORF) radiolabelled with 99mTc via MAG(3). Animals were killed 3 h thereafter and tissues were counted for both radionuclides. The 99mTc-cMORF was also administered to tumour bearing mice that, 2 days previously, had received different doses of unlabelled MN14-MORF IgG or, as control, unlabelled Sandoglobulin IgG-MORF (Sandoz-MORF). Tumour uptake was higher at all time points for the labelled antibody itself versus labelled cMORF (8-10 vs 1.3-2.3%ID/g, respectively) in part due to the rapid clearance of cMORF through the kidneys. However, target to non-target ratios were superior for pretargeting at all time points and in all tissue except blood and kidneys. By pretargeting alone, these ratios were highest in all tissues for 15 microg compared to higher MN14-MORF dosages and in all cases were superior to that of the Sandoz-MORF control. The superior target to non-target ratios for pretargeting can be partially explained through calculations based on both radiolabels: after 24 h, only 0-6% of MORF on MN14 was bound by 99mTc-cMORF in liver and spleen suggesting that the antibody is sequestered in these organs and 'invisible' to labelled MORF. Fortunately, this was not the case in tumours in which 50-60% was bound. It is concluded that pretargeting using MORFs provided encouraging results in one mouse model/anti-tumour antibody system. The advantages of pretargeting in this model were evident in the superior target to non-target ratios obtained over conventional imaging.

Animals↗

PubMed2003

Apophysomyces elegans: an emerging zygomycete in India.

Apophysomyces elegans was considered a rare but medically important zygomycete. We analyzed the clinical records of eight patients from a single center in whom zygomycosis due to A. elegans was diagnosed over a span of 25 months. We also attempted a DNA-based method for rapid identification of the fungi and looked for interstrain polymorphism using microsattelite primers. Three patients had cutaneous and subcutaneous infections, three had isolated renal involvement, one had rhino-orbital tissue infection, and the final patient had a disseminated infection involving the spleen and kidney. Underlying illnesses were found in two patients, one with diabetes mellitus and the other with chronic alcoholism. A history of traumatic implantation was available for three patients. All except two of the patients responded to surgical and/or medical therapy; the diagnosis for the two exceptions was made at the terminal stage of infection. Restriction enzyme (MboI, MspI, HinfI) digestion of the PCR-amplified internal transcribed spacer region helped with the rapid and specific identification of A. elegans. The strains could be divided into two groups according to their patterns, with clustering into one pattern obtained by using microsatellite [(GTG)(5) and (GAC)(5)] PCR fingerprinting. The study highlights the epidemiology, clinical spectrum, and diagnosis of emerging A. elegans infections.

Adult↗

PubMed2003

HSP60, Bax, and cardiac apoptosis.

HSP60 has long been known as an important chaperonin and as having key folding functions within the mitochondria. However, it has now become evident that significant amounts of HSP60 are found in extra-mitochondrial locations. This extra-mitochondrial HSP60 in the heart has key anti-apoptotic functions. Extra-mitochondrial HSP60 complexes with both bax and bak, but not with bcl-2. Reduction in HSP60 is sufficient to precipitate apoptosis. In the setting of hypoxia and reoxygenation HSP60 decreases with reoxygenation, but the apoptotic cascade has already been triggered by end-hypoxia. Redistribution of cytosolic HSP60 to the plasma membrane during hypoxia appears to contribute to the initiation of the apoptotic cascade with hypoxia and reoxygenation.

Animals↗

PubMed2003

Effects of cortisol and oestradiol on hepatic 11beta-hydroxysteroid dehydrogenase type 1 and glucocorticoid receptor proteins in late-gestation sheep fetus.

In the late-gestation sheep, increased fetal plasma cortisol concentration and placental oestradiol (E(2)) output contribute to fetal organ maturation, in addition to the onset of parturition. Both cortisol and E(2) are believed to regulate the enzyme 11beta-hydroxysteroid dehydrogenase type 1 (11beta-HSD1), which interconverts bioactive 11-hydroxy glucocorticoids and their inactive 11-keto metabolites. 11beta-HSD1, abundantly expressed in fetal liver, operates primarily as a reductase enzyme to produce bioactive cortisol and thus regulates local hepatic glucocorticoid concentrations. Cortisol acts through the glucocorticoid receptor (GR) present in the liver. In this study, we examined the effects of cortisol and E(2) on hepatic 11beta-HSD1 and GR in the liver of chronically catheterized sheep fetuses treated with saline (n=5), cortisol (1.35 mg/h; n=5), saline+4-hydroxyandrostendione, a P450 aromatase inhibitor (4-OHA; 1.44 mg/h; n=5), or cortisol+4-OHA (n=5). Cortisol infusion resulted in increased plasma concentrations of fetal cortisol and E(2); concurrent administration of 4-OHA attenuated the increase in plasma E(2) concentrations. Using immunohistochemistry, we showed that fetal hepatocytes expressed both 11beta-HSD1 and GR proteins. Cortisol treatment increased GR in both cytosol and nuclei of hepatocytes; concurrent administration of 4-OHA was associated with distinct nuclear GR staining. Western blot revealed that cortisol, in the absence of increased E(2) concentrations, significantly increased concentrations of 11beta-HSD1 (34 kDa) and GR (95 kDa) proteins. 11beta-HSD1 enzyme activity was measured in the liver microsomal fraction in the presence of [(3)H]cortisone (10(-)(6) M) or [(3)H]cortisol (10(-)(6) M) and NADPH (reductase activity) or NADP(+) (dehydrogenase activity) respectively. 11beta-HSD1 reductase activity was significantly greater in the presence of cortisol. In summary, we found that, in sheep during late gestation, cortisol increased both 11beta-HSD1 and GR in the fetal liver, and these effects were accentuated in the absence of increased E(2).

11-beta-Hydroxysteroid Dehydrogenases↗

PubMed2003

Pulmonary manifestations in brucellosis: a report on seven cases from Bikaner (north-west India).

OBJECTIVES: Pulmonary manifestations of Brucellosis are rare. We came across seven patients with predominant symptomatology of pulmonary involvement amongst 98 patients of active brucellosis seen in last four years. MATERIAL AND METHODS: The study is related to patients of brucellosis whose principal presenting features were related to respiratory symptom (cough, expectoration, pain in chest and breathlessness) along with fever and other constitutional symptoms. It included seven patients amongst 98 patients of active brucellosis seen during June 1996 to Feb. 2000 at PBM Hospital Bikaner. Diagnosis was confirmed by demonstration of the raised brucella agglutination titre of 1:320 or more in the serum. All patients were treated with rifampicin 900 mg daily and doxycyclin 100 mg twice daily for six week. The treatment was extended for another four weeks in two patients because of persistence of skiagram abnormalities. RESULT: Three patients had abnormality in skiagram chest in the form of pleural effusion, multiple paranchymal opacities and pneumonia. The skiagram chest was normal in remaining four patients. The response of treatment started with 10-15 days and all the patients became symptom-free at the end of six weeks except one patient. Skiagram chest at this time was normal in patients of pleural effusion but there was persistence of haziness and few opacities in other two patients. Follow up skiagram chest at the end of six months and twelve months was normal in all patients except calcified opacity in one patient. There was no evidence of relapse in any patient at the end of one year follow up. Liver function tests remained within normal range and no drug toxicity was observed. CONCLUSION: Pulmonary manifestations of brucellosis are rare. Treatment with rifampicin and doxycylin showed marked clinical and radiological improvement. All patients were completely disease-free at the end of one year follow up.

Adolescent↗

PubMed2003

Testicular torsion: a twist to the tale.

Testicular torsion is a surgical emergency that requires prompt exploration if testicular viability is to be maintained. Although rare, it is essential to be aware that it may occur despite previous fixation (orchidopexy). Testicular torsion occurring after previous orchidopexy is rare, but recognition of this possibility is essential to prevent testicular infarction and subsequent orchidectomy. During scrotal exploration a wide variety of methods for orchidopexy exist. We present a case of testicular torsion despite previous fixation and discuss the merits of various techniques available for orchidopexy.

Acute Disease↗

PubMed2003

Comparison of two methods for predicting difficult intubation in obstetric patients.

Preoperative airway assessment for prediction of difficult laryngoscopy and intubation was done using the modified Mallampati test and Wilson risk sum score in three hundred and seventy two obstetric patients undergoing elective as well as emergency Cesarean section under general anesthesia. 25 (6.7%) patients had laryngoscopy grade III or IV of whom 24 (6.4%) patients were difficult at tracheal intubation. Mallampati class III or IV predicted 15 of the 23 patients while Wilson risk sum score > or = 2 predicted 9 of the 14 patients in whom tracheal intubation was difficult. As a screening test for prediction of difficult intubation Wilson risk sum score was less sensitive (36%) but had almost same specificity (98.5%) and positive predictive value (64%) in comparison to modified Mallampati test (62.5%, 97.7% and 65% respectively). When used as a predictor of difficult laryngoscopy sensitivity, specificity and positive predictive value for modified Mallampati test were 60%, 97.6% and 65% respectively and for Wilson risk sum they were 36%, 98.5% and 64% respectively, but when both tests were combined as predictors (with either of tests positive) sensitivity improved to 100% while specificity was marginally decreased to 96.2% and positive predictive value (64.8%) remained almost the same. There was no significant association between age and laryngoscopy grade III or IV but there was significant (P < 0.01) relationship with weight and external laryngeal manipulation. The advantage of the above tests lies in, incorporating them into the preoperative protocol, rather than using them as sole predictors of difficult laryngoscopy and intubation.

Adolescent↗

PubMed2003

A randomized controlled comparison of minialpartomy and lapartomy in ectopic pregnancy cases.

BACKGROUND: As ectopic pregnancy is associated with significant maternal mortality and morbidity it may be worthwhile to find alternative surgical method to traditional laparotomy. AIMS: To compare the efficacy, safety and cost effectiveness of minilaparotomy surgery for ectopic pregnancy cases with standard laparotomy method. SETTING AND DESIGN: A total of 60 patients of ectopic pregnancy were randomized for minilaparotomy and laparotomy (30 cases each) for three years from January. 1998 to March 2001 in a medical college hospital. MATERIAL AND METHODS: Patients history, clinical examination, intraoperative, preoperative and postoperative data were recorded and compared in minilaparotomy and laparotomy groups. STATISTICAL ANALYSIS USED: Chi-square and Fischer chi-square test is used using P value of less than 0.05 as level of significance. RESULTS: Mean operative time was significantly less in minilaparotomy (38 minutes) than in laparotomy group (54 minutes). Postoperative complications were fever in 4(13.33%) and 6(20%) cases, paralytic ileus in 3(10%) and 8(26.66%) cases, urinary tract infection in 2(6.66%) and 3(10%) cases and wound infection in 1(3.33%) and 5(16.66%) cases respectively in the two groups and were significantly less in the minilaparotomy cases. Mean day of mobility, starting normal diet and discharge from the hospital were 10 hours and 24 hours, 1.5 days and 3.1 days and 3.4 days and 6.9 days respectively in the two groups and were significantly less in the minilaparotomy group than the laparotomy group. CONCLUSIONS: Surgery by minilaparotomy technique in ectopic pregnancy cases appears to be a safe and feasible method and is superior to conventional laparotomy as there are minimum perioperative and postoperative complications and patients can be discharged early from the hospital without the need of expensive equipment.

Adult↗

PubMed2002

Cytosolic heat shock protein 60, hypoxia, and apoptosis.

BACKGROUND: Heat shock protein (HSP)60 is an abundant protein found primarily in the mitochondria, though 15% to 20% is found in the cytosol. Previously we observed that HSP60 complexes with bax in the cytosol. Reduction in HSP60 precipitates translocation of bax to the mitochondria and apoptosis. We hypothesized that HSP60 would decrease with hypoxia/reoxygenation and that this would precipitate bax translocation to the mitochondria and release of cytochrome c. METHODS AND RESULTS: Adult rat cardiac myocytes were studied at end-hypoxia and at 10 and 24 hours of reoxygenation. HSP60 levels were unchanged at end-hypoxia and decreased 33% and 40% at 10 and 24 hours of reoxygenation, whereas HSP72 increased 80% and 110%. Bax and bcl-2 decreased during reoxygenation. However, cytochrome c release occurred at end-hypoxia, before reoxygenation. Cell fractionation was done to analyze this further. In normal myocytes, bax and HSP60 were present in the cytosol, and bax coimmunoprecipitated with cytosolic HSP60. At end-hypoxia, mitochondrial HSP60 was unchanged, but cytosolic HSP60 had disappeared and was now in the plasma membrane fraction. Concurrently, bax was no longer in the cytosol but now in the mitochondria. Thus, although total HSP60 remained the same, it no longer complexed with bax, and bax was free to translocate to the mitochondria and precipitate apoptosis. Reduction in ATP had a similar effect. CONCLUSIONS: These studies show that hypoxia results in disassociation of the HSP60-bax complex with translocation of cytosolic HSP60 to the plasma membrane and bax to the mitochondria. This is sufficient to trigger apoptosis.

Adenosine Triphosphate↗

PubMed2002

Decay of an ultracold fermionic lithium gas near a Feshbach resonance.

We studied the magnetic field dependence of the inelastic decay of an ultracold, optically trapped fermionic 6Li gas of different spin compositions. The spin mixture of the two lowest hyperfine states showed two decay resonances at 550 and 680 G, consistent with the predicted Feshbach resonances for elastic s-wave collisions. The observed lifetimes of several hundred ms are much longer than the expected time for Cooper pair formation and the phase transition to superfluidity in the vicinity of the Feshbach resonance.

Journal Article↗

PubMed2002

Contrast interferometry using Bose-Einstein condensates to measure h/m and alpha.

The kinetic energy of an atom recoiling due to absorption of a photon was measured as a frequency, using an interferometric technique called "contrast interferometry." Optical standing wave pulses were used to create a symmetric three-path interferometer with a Bose-Einstein condensate. Its recoil phase, measurable with a single shot, varies quadratically with additional recoils and is insensitive to errors from vibrations and ac Stark shifts. We have measured the photon recoil frequency of sodium to 7 ppm precision, using a simple realization of this scheme. Plausible extensions should yield sufficient precision to attain a ppb-level determination of h/m and the fine structure constant alpha.

Journal Article↗

PubMed2002

The neurogenetics of mucolipidosis type IV.

BACKGROUND: Mucolipidosis type IV (MLIV) is an autosomal recessive disease caused by mutations in the MCOLN1 gene that codes for mucolipin, a member of the transient receptor potential (TRP) gene family. OBJECTIVE: To comprehensively characterize the clinical and genetic abnormalities of MLIV. METHODS: Twenty-eight patients with MLIV, aged 2 to 25 years, were studied. Ten returned for follow-up every 1 to 2 years for up to 5 years. Standard clinical, neuroimaging, neurophysiologic, and genetic techniques were used. RESULTS: All patients had varying degrees of corneal clouding, with progressive optic atrophy and retinal dystrophy. Twenty-three patients had severe motor and mental impairment. Motor function deteriorated in three patients and remained stable in the rest. All had a constitutive achlorhydria with elevated plasma gastrin level, and 12 had iron deficiency or anemia. Head MRI showed consistent characteristic findings of a thin corpus callosum and remained unchanged during the follow-up period. Prominent abnormalities of speech, hand usage, and swallowing were also noted. Mutations in the MCOLN1 gene were present in all patients. Correlation of the genotype with the neurologic handicap and corpus callosum dysplasia was found. CONCLUSIONS: MLIV is both a developmental and a degenerative disorder. The presentation as a cerebral palsy-like encephalopathy may delay diagnosis.

Adolescent↗

PubMed2002

Mangiferin protects the streptozotocin-induced oxidative damage to cardiac and renal tissues in rats.

The role of oxidative stress in streptozotocin (STZ)-induced toxicity and its prevention by a xanthone glucoside, mangiferin was investigated. To induce diabetes mellitus, adult male Wistar rats were injected STZ intravenously at 55 mg/kg body weight. The effect of mangiferin (10 and 20 mg/kg, i.p., 28 days) was investigated in STZ-induced diabetic male rats. Insulin-treated rats (6 U/kg, i.p., 28 days) served as positive control. Diabetic rats given normal saline served as negative control. Normal rats that neither received STZ nor drugs served as normal control. On day 28, the diabetic rats showed significant increase in serum creatine phosphokinase (CPK) and total glycosylated haemoglobin. Kidney revealed tubular degeneration and decreased levels of superoxide dismutase (SOD) and catalase (CAT) with an elevation of malonaldehyde (MDA). Cardiac SOD, CAT and lipid peroxidation were significantly increased. Histopathological findings revealed cardiac hypertrophy with haemorrhages. Analysis of erythrocyte revealed significantly elevated levels of MDA with insignificant decrease in CAT and SOD. Repeated intraperitoneal injections of mangiferin (10 and 20 mg/kg) and insulin (6 U/kg) controlled STZ-induced lipid peroxidation and significantly protected the animals against cardiac as well as renal damage. From the study, it may be concluded that oxidative stress appears to play a major role in STZ-induced cardiac and renal toxicity as is evident from significant inhibition of antioxidant defence mechanism in renal tissue or a compensatory increase in antioxidant defence mechanism in cardiac tissue. Intraperitoneal administration of mangiferin exhibited significant decrease in glycosylated haemoglobin and CPK levels along with the amelioration of oxidative stress that was comparable to insulin treatment.

Animals↗

PubMed2002

Cytosolic heat shock protein 60, apoptosis, and myocardial injury.

BACKGROUND: Heat shock proteins (HSPs) are well known for their ability to "protect" the structure and function of native macromolecules, particularly as they traffic across membranes. Considering the role of key mitochondrial proteins in apoptosis and the known antiapoptotic effects of HSP27 and HSP72, we postulated that HSP60, primarily a mitochondrial protein, also exerts an antiapoptotic effect. Methods and Results- To test this hypothesis, we used an antisense phosphorothioate oligonucleotide to effect a 50% reduction in the levels of HSP60 in cardiac myocytes, a cell type that has abundant mitochondria. The induced decrease in HSP60 precipitated apoptosis, as manifested by the release of cytochrome c, activation of caspase 3, and induction of DNA fragmentation. Antisense treatment was associated with an increase in bax and a decrease in bcl-2 secondary to increased synthesis of bax and degradation of bcl-2. A control oligonucleotide had no effect on these measurements. We further demonstrated that cytosolic HSP60 forms a macromolecular complex with bax and bak in vitro suggesting that complex formation with HSP60 may block the ability of bax and bak to effect apoptosis in vivo. Lastly, we show that as cytosolic (nonmitochondrial) HSP60 decreases, a small unbound fraction of bax appears and that the amount of bax associated with the mitochondria and cell membranes increases. CONCLUSIONS: These results support a key antiapoptotic role for cytosolic HSP60. To our knowledge, this is the first report suggesting that interactions of HSP60 with bax and/or bak regulate apoptosis.

Animals↗

PubMed2002

Two-species mixture of quantum degenerate Bose and Fermi gases.

We have produced a macroscopic quantum system in which a 6Li Fermi sea coexists with a large and stable 23Na Bose-Einstein condensate. This was accomplished using interspecies sympathetic cooling of fermionic 6Li in a thermal bath of bosonic 23Na. The system features rapid thermalization and long lifetimes.

Journal Article↗

PubMed2002

A three-step strategy for targeting drug carriers to human ovarian carcinoma cells in vitro.

To improve tumor-to-tissue ratios of anticancer agents in radioimmunotherapy, a three-step targeting approach was used to deliver biotinylated liposomes to human ovarian cancer cells (NIH:OVCAR-3, SK-OV-3) in vitro. Targeting was based upon the use of two antibodies specific for the CA-125 antigen that is highly expressed on NIH:OVCAR-3 cells but not expressed on SK-OV-3 cells. Briefly, the approach consists of prelabeling target cells with biotinylated anti-CA-125 antibody and FITC-labeled streptavidin (SAv) prior to administration of biotinylated liposomes containing a marker dye for visualization by confocal laser scanning microscopy (CLSM). In addition, the two anti-CA-125 antibodies (B27.1 and B43.13) were labeled with FITC and incubated with ovarian cancer cells at 37 degrees C from 30 min to 24 h to study binding and uptake kinetics. Shedding kinetics of bound antibody from tumor cells was performed using radiolabeled B27.1. Results demonstrated that both B27.1 and B43.13 specifically bound to the cell surface of OVCAR-3 cells but not to SK-OV-3 cells. Biotinylation, FITC-labeling and radiolabeling of the antibodies did not compromise immunoreactivity. Less than 6% of the bound B27.1 was shed from tumor cells by 4 h following incubation, and the antibody-antigen complex resided predominantly on the cell surface by 4 h at 37 degrees C with slow internalization by 12-24 h. Biotinylated, conventional liposomes were specifically and effectively delivered to OVCAR-3 cells prelabeled with biotinylated B27.1 and SAv. The slow internalization and shedding properties of these antibodies are useful for multistep pretargeting methods. Thus, a modified targeting strategy, utilizing a bispecific antibody and liposomes, may be feasible for radioimmunoliposomal therapy of ovarian cancer.

Antibodies, Monoclonal↗

PubMed2002

Antimutagenic effects of black tea (World Blend) and its two active polyphenols theaflavins and thearubigins in Salmonella assays.

Almost two thirds of the world population consume tea everyday. Tea is processed differently in different parts of the world to give green (20%), black (78%) or oolong tea (2%). The antimutagenic and anticarcinogenic activities of green tea were extensively investigated compared with those of black tea. Considering the potent antimutagenic effects of green tea we recognized the need to evaluate the antimutagenic effects of black tea (World Blend Tea, Southern Tea Co., Marietta, GA) in Salmonella strains TA97a, TA98, TA100 and TA102 in preincubation tests, both with and without S9 activation. Attempts have also been made to compare the results of the tea extracts with their two active polyphenols theaflavins and thearubigins. Antimutagenicity assays were carried out in bacterial plates treated with different concentrations (1%, 2.5%, 5%, 10% and 20%) of tea extracts against known bacterial mutagens sodium azide, 4-nitro-o-phenylenediamine, cumine hydroperoxide, 2-aminofluorene and danthron. A significant decrease in the number of revertant colonies was observed in the plates treated with 1% to 20% of tea extract plus positive mutagen when compared with positive mutagen only. Both the active polyphenols theaflavins and thearubigins extracted from the black tea (World blend) also showed significant antimutagenic effects against known positive compounds in these strains. In the experiments with S9 activation, the antimutagenic effects were significantly higher. These results indicate that black tea and its two polyphenols have significant antimutagenic effects in Ames Salmonella assays.

Animals↗

PubMed2002

Plasmodium falciparum: in vitro interactions of artemisinin with amodiaquine, pyronaridine, and chloroquine.

In the scenario of drug-resistant Plasmodium falciparum malaria combination therapy represents an effective approach. Artemisinin and its derivatives are of special interest because they represent the most effective group of compounds against multidrug-resistant malaria with a rapid onset of action and a short half-life. Interactions of artemisinin with amodiaquine, pyronaridine, and chloroquine were therefore investigated against three strains of P. falciparum using a 48-h in vitro culture assay. Two of the strains were chloroquine sensitive and one was partially chloroquine resistant. Observed effective concentrations (O) of the combined compounds at different concentration ratios were calculated for different degrees of inhibition (EC50, EC90, EC99) and compared to expected calculated effective concentrations (E) using a probit method. Synergism with mean O/E EC90 values of 0.25 and 0.8 were found with the combination of artemisinin and the two Mannich bases, amodiaquine and pyronaridine, respectively, whereas chloroquine showed addition with a mean value of 1.2. Although both amodiaquine and chloroquine are 4-aminoquinolines, their interaction with artemisinin appears to be different. The combination of artemisinin with amodiaquine represents an important option for the treatment of falciparum malaria.

Amodiaquine↗