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Biomedical subjects

A Joshi

Publications and source records attributed to A Joshi.

At least 91 records · Page 5Linked to original sources
PubMed2000

The effect of different light regimes on adult life span in Drosophila melanogaster is partly mediated through reproductive output.

The effects of different light regimes on the fitness of organisms have typically been studied using mean or median adult life span as the sole index of physiological well-being. It is, however, known that life span is inversely related to reproductive output in many species. Moreover, the effects of a given environmental treatment on life span can be due to effects on either age-independent mortality or the "rate of aging," or a combination of both. Drawing evolutionary inferences from the effects of light regime on mean or median adult life span alone is difficult and, at best, speculative. We examined the effects of constant light (LL), alternating light-dark cycles (LD 12:12 h), and constant darkness (DD) on the life span of reproducing and virgin flies in four populations of Drosophila melanogaster and also estimated lifetime fecundity in the three light regimes. The light regime effects on life span were further dissected by examining the age-independent mortality and the Gompertz rate of aging under the three light regimes. While mean adult life span of reproducing males and females and virgin females was significantly shorter in LL compared to LD 12:12 h and DD, life-time egg production was highest in LL. Life span of virgin males was not significantly affected by light regime. The rate of aging in reproducing females was higher in LL as compared to DD, whereas age-independent mortality was higher in DD. As reproductive output, especially early in life, is a far more significant contributor to fitness than is life span, our results suggest that the earlier reported deleterious effects of LL on fitness are partly an artifact of examining life span alone, without considering other components of adult fitness that trade off with life span. Our results suggest that detailed investigation of the effects of light regime on the physiological and behavioral processes that accompany reproduction is necessary to fully understand the effects of different light regimes on adult fitness in Drosophila.

Aging↗
PubMed2000

The traveling salesman problem: a hierarchical model.

Our review of prior literature on spatial information processing in perception, attention, and memory indicates that these cognitive functions involve similar mechanisms based on a hierarchical architecture. The present study extends the application of hierarchical models to the area of problem solving. First, we report results of an experiment in which human subjects were tested on a Euclidean traveling salesman problem (TSP) with 6 to 30 cities. The subject's solutions were either optimal or near-optimal in length and were produced in a time that was, on average, a linear function of the number of cities. Next, the performance of the subjects is compared with that of five representative artificial intelligence and operations research algorithms, that produce approximate solutions for Euclidean problems. None of these algorithms was found to be an adequate psychological model. Finally, we present a new algorithm for solving the TSP, which is based on a hierarchical pyramid architecture. The performance of this new algorithm is quite similar to the performance of the subjects.

Algorithms↗
PubMed2000

Poor diagnostic accuracy and applicability of Siriraj stroke score, Allen score and their combination in differentiating acute haemorrhagic and thrombotic stroke.

OBJECTIVE: To evaluate the relevance of bed side clinical diagnostic scoring systems--Siriraj stroke score (SSS), Allen score and their combined use for differentiating acute haemorrhagic and thrombotic stroke. MATERIAL AND METHODS: The study was conducted on 240 admitted patients of stroke over a period of two years. SSS was calculated immediately and Allen score, 24 hours after admission. CT scan was done immediately and 48 hours after admission if required. The sensitivity, specificity, positive predictive value, negative predictive value and diagnostic gain were calculated for both the scores. Comparability between the scores and CT scan finding was determined with the help of kappa statistic programme. Receiver operating characteristic curves (ROC) were plotted to assess the diagnostic accuracy of both scores over a range of cut-off points. RESULTS: One hundred and thirty four patients (55.83%) had infarction and 106 patients (44.17%) had haemorrhage. SSS was applicable in 66.25% patients (159 out of 240) while Allen score was applicable in only 61.25% patients (147 our of 240). The sensitivity, specificity, positive predictive value, negative predictive value and diagnostic gain for SSS were 73%, 85%, 85%, 71% and 30% for infarction and 85%, 73%, 71%, 85% and 27% for haemorrhage respectively, whereas the corresponding figures for Allen score were 91%, 60%, 77%, 82% and 18% for infarction and 60%, 91%, 82%, 77% and 41% for haemorrhage respectively. There was overall moderate comparability between SSS and Allen score for diagnosing supratentorial stroke (k = 0.396). The comparability of these scores in terms of certain results was worse (k = 0.143). However when the results that were within the diagnostic range with both the scores were considered, the agreement in diagnosing infarction and haemorrhage was almost perfect (k = 0.874). While considering CT scan finding as gold standard for differentiation of infarction and haemorrhage, the overall accuracy of SSS and Allen score was seventy eight percent. CONCLUSION: (a) Applicability of SSS only in 66.25% patients and wrong diagnosis in 22.01% patients does not reflect its usefulness because adequate management of stroke requires a gold standard diagnosis which is only possible by immediate CT scan. (b) Allen score is not useful because it can be assessed only after 24 hours of onset of stroke. This deprives the management to all thrombotic patients in speculated time window of modern management.

Acute Disease↗
PubMed1999

Imaging adenoviral-mediated herpes virus thymidine kinase gene transfer and expression in vivo.

The feasibility of noninvasive imaging of adenoviral-mediated herpes virus type one thymidine kinase (HSV1-tk) gene transfer and expression was assessed in a well-studied animal model of metastatic colon carcinoma of the liver. Tumors were produced in syngeneic BALB/c mice by intrahepatic injection of colon carcinoma cells (MCA-26). Seven days later, three different doses (3 x 10(8), 1 x 10(8), and 3 x 10(7) plaque-forming units (pfu) of the recombinant adenoviral vector ADV. Rous sarcoma virus (RSV)-tk bearing the HSV1-tk gene were administered by intratumoral injection in separate groups of mice. Two control groups of tumor-bearing mice received intratumoral injections of the control adenoviral vector dl-312 or buffer alone, respectively. T2-weighted magnetic resonance (MR) images of mice were obtained before administering the virus and provided an anatomical reference of hepatic tumor localization. Eighteen h after the virus injection, one group of animals was given i.v. injections of 300 microCi of no-carrier-added 5-[131I]-2'-fluoro-1-beta-D-arabinofuranosyluracil (FIAU) and imaged 24 h later with a gamma camera. In some animals, the tumors were sampled and processed for histology and quantitative autoradiography (QAR). The gamma camera images demonstrated highly specific localization of [131I]FIAU-derived radioactivity to the area of ADV.RSV-tk-injected tumors in the liver, which was confirmed by coregistering the gamma camera and T2-weighted MR images. There was no accumulation of [131I]FIAU-derived radioactivity in tumors that were injected with the control vector or injection solution alone. A more precise distribution of radioactivity in the area of transfected tumor was obtained by histological and QAR comparisons. A heterogeneous pattern of radioactivity distribution in transfected tumors was observed. A punctate pattern of radioactivity distribution was observed in peritumoral liver tissue in animals given injections of 3 x 10(8) and 1 x 10(8) pfu of ADV.RSV-tk but not in animals given injections of 3 x 10(7) pfu nor in control animals. A QAR-microscopic comparison showed that the punctate areas of radioactivity colocalized with cholangial ducts. The level of [131I]FIAU-derived radioactivity accumulation (HSV1-tk expression) in the transfected tumors was viral dose-dependent. The viral dose-dependency of radioactivity accumulation was more pronounced in peritumoral liver, which was confirmed by reverse transcription-PCR analysis. A separate group of tumor-bearing animals received different doses of ADV.RSV-tk vector followed by treatment with ganciclovir (GCV), 10 mg/kg i.p. b.i.d. for 6 days. The ADV.RSV-tk transfected tumors significantly regressed with GCV treatment; the control tumors continued to grow. During the GCV treatment, the levels of liver transaminases (ALT and AST) were significantly increased in animals that received injections of 3 x 10(8) and 1 x 10(8) pfu of ADV.RSV-tk but not in animals that received injections of 3 x 10(7) pfu and in control animals. The observed liver toxicity confirms the results of gamma camera and QAR imaging, which demonstrated an unwanted spread of ADV.RSV-tk vector and HSV1-tk expression in peritumoral and remote liver tissue at higher doses. These and our previous results indicate that noninvasive imaging of adenoviral-mediated HSV1-tk gene expression is feasible for monitoring cancer gene therapy in patients.

Adenoviridae↗
PubMed1999

Structure-function analysis of the protein-binding domains of Mac1p, a copper-dependent transcriptional activator of copper uptake in Saccharomyces cerevisiae.

The Mac1 protein in Saccharomyces cerevisiae is essential for the expression of yeast high affinity copper uptake. A positive transcription factor, Mac1p binds via its N-terminal domain to GCTC elements in the promoters of CTR1 and FRE1, encoding a copper permease and metal reductase, respectively. Mac1p-dependent transcriptional activation is negatively regulated by copper. We have mapped the domains in Mac1p responsible for its nuclear localization and for the protein-protein interactions that underlie its transcriptional activity. Immunofluorescence studies indicate that Mac1p contains two nuclear localization signals, one each in the N- and C-terminal halves of the protein. Yeast one-hybrid analysis demonstrates that the copper-dependent transcriptional activity in Mac1p resides primarily in a cysteine-rich element encompassing residues 264-279. Two-hybrid analysis indicates that a copper-independent Mac1p-Mac1p interaction linked to DNA binding is due primarily to a predicted helix in the C-terminal region of the protein encompassing residues 388-406. Point mutations within this putative helix abrogate the Mac1-Mac1 interaction in vivo and formation of a ternary (Mac1p)(2).DNA complex in vitro. When produced in normal abundance, Mac1pI396D and Mac1pF400D helix mutants do not support transcriptional activation in vivo consistent with an essential Mac1p dimerization in transcriptional activation. Lastly, the one- and two-hybrid data indicate that an intramolecular interaction between the DNA-binding and transactivation domains negatively modulates Mac1p activity.

Binding Sites↗
PubMed1999

Evidence for (Mac1p)2.DNA ternary complex formation in Mac1p-dependent transactivation at the CTR1 promoter.

The Mac1 protein in Saccharomyces cerevisiae is required for the expression CTR1 and FRE1, which, respectively, encode the copper permease and metal reductase that participate in copper uptake. Mac1p binds to a core GCTC sequence present as a repeated unit in the promoters of both genes. We show here that Mac1p DNA binding required an intact N-terminal protein domain that includes a likely zinc finger motif. This binding was enhanced by the presence of a TATTT sequence immediately 5' to the core GCTC, in contrast to a TTTTT one. This increased binding was demonstrated clearly in vitro in electrophoretic mobility shift assays that showed Mac1p.DNA complex formation to a single TATTTGCTC element but not to a TTTTTGCTC one. Furthermore, the fraction of Mac1p in a ternary (Mac1p)2.DNA complex in comparison to a binary Mac1p.DNA complex increased when the DNA included two TATTTGCTC elements. A similar increase in ternary complex formation was demonstrated upon homologous mutation of the FRE1 Mac1p-dependent promoter element. The in vivo importance of this ternary complex formation at the CTR1 promoter was indicated by the stronger trans-activity of this promoter mutated to contain two TATTT elements and the attenuated activity of a mutant promoter containing two TTTTT elements that in vitro supported only a weak ternary complex signal in the shift assay. The stronger binding to TATTT appeared due to a more favorable protein contact with adenine in comparison to thymine at this position. An in vivo two-hybrid analysis demonstrated a Mac1p-Mac1p protein-protein interaction. This Mac1p-Mac1p interaction may promote (Mac1p)2.DNA ternary complex formation at Mac1p-responsive upstream activating sequences.

Base Sequence↗
PubMed1999

Persistence of eclosion rhythm in Drosophila melanogaster after 600 generations in an aperiodic environment.

The ubiquity of circadian rhythms suggests that they have an intrinsic adaptive value (Ouyang et al. 1998; Ronneberg and Foster 1997). Some experiments have shown that organisms have enhanced longevity, development time or growth rates when maintained in environments whose periodicity closely matches their endogenous period (Aschoff et al. 1971; Highkin and Hanson 1954; Hillman 1956; Pittendrigh and Minis 1972; Went 1960). So far there has been no experimental evidence to show that circadian rhythms per se (i.e. periodicity itself, as opposed to phasing properties of a rhythm) confer a fitness advantage. We show that the circadian eclosion rhythm persists in a population of the fruitfly Drosophila melanogaster maintained in constant conditions of light, temperature, and humidity for over 600 generations. The results suggest that even in the absence of any environmental cycle there exists some intrinsic fitness value of circadian rhythms.

Adaptation, Physiological↗
PubMed1999

Flavonoids from Maclura tinctoria.

Seven flavonoids, including two new natural products, were isolated from an ethanol extract of the bark of Maclura tinctoria (L.) Gaud. The new compounds are steppogenin 4'-O-beta-D-glucoside and orobol 5,3'-di-O-methyl-8-C-glucoside. Orobol, steppogenin, aromadendrin, dihydromorin and orobol 7-O-beta-D-glucoside were also isolated.

Flavonoids↗
PubMed1999

Poisson distribution of male mating success in laboratory populations of Drosophila melanogaster.

Variation among males and females in reproductive success is a major determinant of effective population size. Most studies of male mating success in Drosophila, however, have been done under conditions very different from those in typical cultures. We determined the distribution of male mating success in five laboratory populations of D. melanogaster maintained on a 14 d, discrete generation cycle fairly representative of standard Drosophila cultures. Mating success was measured as the number of matings a male could achieve under conditions closely approximating a regular culture vial of these populations. Preliminary studies determined that most mating in these populations occurred within 14 h of the flies attaining sexual maturity. Consequently, individual virgin males were marked with white paint on their thorax, put into vials with varying numbers of unmarked virgin flies of both sexes, and monitored continuously for matings over a period of up to 14 h. At various times during the assay, virgin males and females were added to these vials in proportions simulating the pattern of eclosion in culture vials. The observed variation in the number of matings per male in the five populations was, by and large, consistent with a Poisson distribution, suggesting that male mating success in short-generation-time, discrete-generation laboratory cultures of D. melanogaster may fulfil a fundamental assumption of the Wright-Fisher model of genetic drift in finite populations.

Animals↗
PubMed1999

A general approach to the non-invasive imaging of transgenes using cis-linked herpes simplex virus thymidine kinase.

Non-invasive imaging of gene expression opens new prospects for the study of transgenic animals and the implementation of genetically based therapies in patients. We have sought to establish a general paradigm to enable whole body non-invasive imaging of any transgene. We show that the expression and imaging of HSV1-tk (a marker gene) can be used to monitor the expression of the LacZ gene (a second gene) under the transcriptional control of a single promoter within a bicistronic unit that includes a type II internal ribosomal entry site. In cells bearing a single copy of the vector, the expression of the two genes is proportional and constant, both in vitro and in vivo. We demonstrate that non-invasive imaging of HSV1-tk gene accurately reflects the topology and activity of the other cis-linked transgene.

Animals↗
PubMed1999

Primary tuberculosis of the glans penis.

A 60-year-old man presented with multiple superficial ulcers on the glans penis. Histopathology, a positive tuberculin test result, and therapeutic response to antituberculous therapy confirmed the diagnosis of penile tuberculosis. Examination was otherwise normal except for a solitary enlarged reactive lymph node on the right side. There was no evidence of coexistent tuberculous infection elsewhere.

Humans↗
PubMed1999

Port-wine-stain (nevus flammeus), congenital Becker's nevus, café-au-lait-macule and lentigines: phakomatosis pigmentovascularis type Ia--a new combination.

A 16-year-old male had brown macules in a geographic pattern with increased terminal hair on the back and dusky red partially blanchable non progressing macules on his left thigh since birth. Clinical diagnoses of Becker's nevus and port-wine-stain were made and confirmed histopathologically. In addition, he had multiple lentigines on the face and trunk and a single café-au-lait-macule on his chest.

Adolescent↗
PubMed1999

Intrapericardial streptokinase in purulent pericarditis.

Six consecutive children with proven purulent pericarditis were treated with pericardial irrigation with streptokinase. Mean (SD) 861 (678) ml (range 240-2000) of thick purulent fluid was drained, and five children had complete clearance of the pus within 3-8 days. One child developed intrapericardial haemorrhage with a submitral pseudoaneurysm and underwent patch closure of the neck of the aneurysm as well as anterior pericardiectomy. Follow up of 13 to 30 months revealed no pericardial constriction.

Child↗
PubMed1999

A phase I and pharmacokinetic study of losoxantrone and paclitaxel in patients with advanced solid tumors.

A Phase I and pharmacological study was performed to evaluate the feasibility, maximum tolerated dose (MTD), dose-limiting toxicities (DLTs), and pharmacokinetics of the anthrapyrazole losoxantrone in combination with paclitaxel in adult patients with advanced solid malignancies. Losoxantrone was administered as a 10-min infusion in combination with paclitaxel on either a 24- or 3-h schedule. The starting dose level was 40 mg/m2 losoxantrone and 135 mg/m2 paclitaxel (as a 24- or 3-h i.v. infusion) without granulocyte colony-stimulating factor (G-CSF). Administration of these agents at the starting dose level and dose escalation was feasible only with G-CSF support. The following dose levels (losoxantrone/paclitaxel, in mg/m2) of losoxantrone and paclitaxel as a 3-h infusion were also evaluated: 50/135, 50/175, 50/200, 50/225, and 60/225. The sequence-dependent toxicological and pharmacological effects of losoxantrone and paclitaxel on the 24- and 3-h schedules of paclitaxel were also assessed. The MTD was defined as the dose at which >50% of the patients experienced DLT during the first two courses of therapy. DLTs, mainly myelosuppression, occurring during the first course of therapy were noted in four of six and five of eight patients treated with 40 mg/m2 losoxantrone and 135 mg/m2 paclitaxel over 24 and 3 h, respectively, without G-CSF. DLTs during the first two courses of therapy were observed in one of six patients at the 50/175 (losoxantrone/paclitaxel) mg/m2 dose level, two of four patients at the 50/200 mg/m2 dose level, one of four patients at the 50/225 mg/m2 dose level, and two of five patients at the 60/225 mg/m2 dose level. The degree of thrombocytopenia was worse, albeit not statistically significant, when 24-h paclitaxel preceded losoxantrone, with a mean percentage decrement in platelet count during course 1 of 80.7%, compared to 43.8% with the reverse sequence (P = 0.19). Losoxantrone clearance was not significantly altered by the sequence or schedule of paclitaxel. Cardiac toxicity was observed; however, it was not related to total cumulative dose of losoxantrone. An unacceptably high rate of DLTs at the first dose level of 40 mg/m2 losoxantrone and 135 mg/m2 paclitaxel administered as either a 24- or 3-h i.v. infusion precluded dose escalation without G-CSF support. The addition of G-CSF to the regimen permitted further dose escalation without reaching the MTD. Losoxantrone at 50 mg/m2 followed by paclitaxel (3-h i.v. infusion) at 175 mg/m2 with G-CSF support is recommended for further clinical trials.

Adult↗