Changing the debate about health research for development. International Health Research Awards Recipients.
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Biomedical subjects
Publications and source records attributed to A Mishra.
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The gene for histone-like protein (hupB [Rv2986c]) of Mycobacterium tuberculosis has been identified as a singular target which allows differentiation of two closely related mycobacterial species, namely, M. tuberculosis and M. bovis of the MTB complex, by a PCR assay. The N and S primer-generated PCR amplicons differed in M. tuberculosis and M. bovis; these amplicons were determined to be 645 and 618 bp, respectively. This difference was localized to the C-terminal part of the gene by using primers M and S. The C-terminal PCR amplicons of M. tuberculosis and M. bovis were determined to be 318 and 291 bp, respectively. The differences in the C-terminal portion of the gene were confirmed by restriction fragment length polymorphism analysis and sequencing. Sequence analysis indicated that in M. bovis there was a deletion of 27 bp (9 amino acids) in frame after codon 128 in the C-terminal part of the hupB gene. In the present study 104 mycobacterial strains and 11 nonmycobacterial species were analyzed for hupB gene sequences. Of the 104 mycobacterial strains included, 62 belonged to the MTB complex and 42 were non-MTB complex strains and species. Neither the hupB gene-specific primers (N and S) nor the C-terminal primers (M and S) amplify DNA from any other mycobacteria, making the assay suitable for distinguishing members of the MTB complex from other mycobacterial species, as well as for differentiating between members of the MTB complex, namely, M. tuberculosis and M. bovis.
In the catfish H. fossilis, ovarian glucose and fructose levels showed significant annual variations that could be correlated with the gonado-somatic index. The concentration of the sugars, which was low in resting phase of gonad increased with the onset of oogenesis, reaching the peak in prespawning (June) phase. Glucose is the predominant monosaccharide in the late oogenesis, while fructose in early oogenesis and resting phase. Administration of a single injection of HCG (100 IU/fish) decreased glucose at 4 hr but increased fructose (6 hr) in the resting phase. In the preparatory phase (active oogenesis), fructose decreased significantly at 4 hr and glucose at 6 and 12 hr. In the prespawning phase, HCG administration induced a significant decrease in glucose level at 2 hr but increased it significantly at 16 and 18 hr. Fructose concentration, on the other hand, decreased > or = 4 hr. The involvement of different energy substrates (glucose, fructose, 2-deoxyglucose and pyruvate) on final oocyte maturation and viability of eggs were demonstrated in an in vitro study, employing incubation of mature oocytes in medium containing one or the other energy substrates. Glucose at 4 and 8 mM concentrations increased the viability of eggs without affecting germinal vesicle break down (GVBD) and at high concentrations (16 and 32 mM) marginally increased GVBD but decreased viability. Pyruvate at high concentrations (> or = 8 mM) produced a positive effect on both GVBD and viability. Fructose and 2-deoxyglucose did not elicit any effect on these parameters. The results suggest that glucose has an active role in catfish oogenesis and maintaining egg quality and HCG influences monosaccharide metabolism in a season-dependent manner.
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In mammals, extensive remodeling of uterine endometrial matrix occurs during reproductive cycle and blastocyst implantation. This is regulated by a variety of molecules such as hormones, growth factors, cytokines and proteases. In this article, we review the current state of knowledge available on various proteases and their inhibitors functionally involved in the embryo-endometrial tissues and present some data on endometrial proteases in hamsters and rats during estrous cycle and early pregnancy. We demonstrate the presence of at least four gelatinolytic activities in endometrial samples, belonging to gelatinase-A and -B categories and their dependence on calcium/zinc ions for enzyme activity and, their interrelationships between zymogen and active forms. We believe that the embryo-endometrial proteases are essential for hatching of blastocysts and for the dynamic remodeling of endometrial tissues, occurring during the critical peri-implantation period.
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The molecular regulation of mammalian peri-implantation development is complex and difficult to study in vivo. We successfully cultured hamster blastocysts through hatching and peri-attachment stages, using a chemically defined medium, HECM-2h. Using this system, we showed that a species-specific, embryonic cysteine-like protease is involved in blastocyst hatching and that the process is modulated by growth factors. In particular, heparin binding-epidermal growth factor (HB-EGF) or leukemia inhibitory factor (LIF) enhance blastocyst hatching, and the former also improves attachment and trophoblast outgrowth. We observed interesting changing patterns of expression of mRNA and/or immunoreactive protein for EGF, HB-EGF, LIF and transforming growth factor-beta (TGF-beta) in the embryo and/or endometrial tissue, during peri-implantation development. Together, it appears that hamster blastocyst hatching, attachment and trophoblast outgrowth are regulated by autocrine and/or paracrine growth factors, produced by the embryo-endometrial tissues.
BACKGROUND: Endoscopic ultrasound (EUS) is a relatively new method used in the investigation and staging of upper gastrointestinal tract (UGIT) disease. AIMS: To review practice and outcomes of EUS in an Australian university teaching hospital. METHODS: The first part of the study was a retrospective review of indications, safety, referral patterns and technical difficulties of all EUS procedures performed at Concord Hospital, New South Wales, Australia, over a 10-year period from 1990 to 2000. The second part of the study examined the impact of EUS on the management of 225 consecutive cases, as determined by a questionnaire completed by each of the referring doctors. RESULTS: A total of 537 EUS examinations was performed over the 10-year period. Indications for EUS included: (i) assessment of oesophageal lesions (241), (ii) assessment of gastric lesions (184) and (iii) assessment of pancreaticobiliary (112) disease. Cancer staging was performed in 46.7% of oesophageal and 31.4% of gastric cases. Sedation was achieved using intravenous midazolam (5.3+/-1.3 mg; mean +/- SD) and 52% of cases required additional intravenous pethidine (48.5+/-10.0 mg; mean +/- SD). Technical difficulties were encountered in 11% of cases and these were mainly related to nontraversable luminal stricturing. Of the 537 referrals, 48.2% were from within Central Sydney Area Health Services, and the remainder were from other Sydney hospitals, New South Wales regional centres and interstate. Of 225 questionnaires sent to referring doctors, 146 questionnaires were completed and returned for analysis. EUS aided staging of malignant disease, and confirmed or established a diagnosis in 86% of cases. The diagnostic accuracy of EUS was 76% when confirmed histologically. EUS avoided further diagnostic investigations in the majority of cases and in 25% of cases surgery was avoided. Fine-needle aspiration biopsy (FNAB) during EUS would have been useful in 30% of cases. Overall, clinical decision-making and management were changed in one-third of cases. CONCLUSIONS: Endoscopic ultrasound is an accurate, safe and useful imaging method in UGIT disease. The increasing demand for EUS and EUS-guided FNAB suggests an expanding future for EUS in Australia.
X-ray K-absorption near edge studies have been carried out on the binuclear copper (II) dithiocarbamate (dtc) complexes having the following general structure: [structure in text] where R = me (methyl); et (ethyl); npr (normal propyl); chx (cyclohexane) It has been found that the chemical shift values are higher in the chlorine adducts as compared to the values of chemical shift reported by us in an earlier work for the parent complexes, showing that the chlorine adducts are more ionic. The observed splitting of the principal absorption maximum (1s-4p) in the chlorine adducts has been explained in terms of the splitting of the metal 4p orbital degeneracy.
BACKGROUND: Cysticercosis cellulosae rarely involves the oral region in humans. METHODS: Six cases of oral cysticercosis were diagnosed, three each in lips and buccal mucosa. Diagnosis was made by characteristic gross and histopathologic appearances. RESULTS: Of 146 cases of cysticercosis, 6 (4.1%) were of the oral cavity. All 6 cases were initially seen with painless swellings. Clinical differential diagnosis ranged from retention cyst, lipoma, fibroma, neurofibroma, and angular stomatitis. Histopathologic examination revealed cysticercus larvae. CONCLUSIONS: The oral cavity is a rare site of involvement by cysticercosis, even in an endemic area. Histopathologic findings of the excised cyst are diagnostic of the lesion.
Total thyroidectomy is increasingly being accepted as a treatment of choice for differentiated thyroid cancer. However, because of presumed increased morbidity associated with this procedure, it is still not considered a viable option for management of benign thyroid disorders. To assess the safety and efficacy of total thyroidectomy for management of benign thyroid disorders, we analyzed our data from 127 total thyroidectomies performed for benign thyroid disorders. Demographic details, biochemical findings, indications for operation, specimen weight, and complications were noted. Among these patients, 52 had a toxic goiter and 75 had a nontoxic goiter. The mean duration of the goiters being present was 6.08 +/- 6.06 years (0.9--26.0 years), and the mean weight of the specimens was 136.88 +/- 120.68 g. The incidence of occult malignancy was 6.3% (n = 8), and those of permanent hypothyroidism and permanent recurrent laryngeal nerve palsy were 1.6% and 0.8%, respectively. Total thyroidectomy should be considered a treatment of choice for multinodular goiter and Graves' disease in a setting of palpable nodule(s) or ophthalmopathy (or both). It is particularly relevant in endemic regions where patients present with a long-standing, large nodular goiter with virtually no normal thyroid tissue. Reoperation for recurrent goiter in such a setting would be fraught with distressing complications.
Radioiodine therapy is currently the treatment of choice for metastasizing differentiated thyroid cancer (DTC); however, skeletal metastases are resistant to this form of therapy. The surgical removal of distant metastases from DTC offers the best chance for prolonged survival and improved quality of life. Furthermore, the surgical removal of a resectable skeletal metastasis can be a valuable complement to radioiodine therapy. This report describes two cases of sternal metastases from thyroid carcinoma that were managed successfully by surgery involving partial excision of the sternum followed by reconstruction of the chest wall with Marlex mesh. Both patients recovered uneventfully. Sternal resection with Marlex mesh reconstruction of the chest wall defect proved a simple and effective method for managing sternal metastasis. Thus, the surgical resection of distant bony metastases in patients with DTC is recommended as it can be curative, provide symptomatic palliation, or allow for more effective radioiodine treatment.
BACKGROUND: Perioperative stroke is a devastating complication after coronary artery bypass grafting (CABG). The reported incidence of neurologic complications after conventional CABG is 3% to 7%. With improved monitoring and surgical techniques, we have been able to achieve a drastic reduction in the stroke rate in our institution. This study evaluates the incidence of neurologic sequelae in patients who underwent off-pump CABG. METHODS: Over a 10-year period from January 1990 to September 2000, off-pump coronary artery bypass (OPCAB) operation was performed on 2,800 patients of the 18,037 patients undergoing CABG during that time frame at the Escorts Heart Institute and Research Centre. Initially, OPCAB was performed selectively in the high-risk group of patients (atheromatous aorta, renal impairment, chronic obstructive pulmonary disease, octogenarians, etc). Lately we performed multivessel OPCABs electively in about 60% to 65% of the patients undergoing CABG. Results. Mean age of the patients was 58.0 +/- 9.91 years (range 27 to 85 years) and mean number of grafts was 2.9 per patient. Neurologic complications (stroke/transient ischemic attack) occurred in 0.14% of patients. Overall hospital mortality in OPCAB patients was 2.14%, whereas mortality from neurologic complications was 0.07%. Predicted mortality (National Society of Thoracic Surgeons Cardiac Surgery Database Risk Model for CABG) for the entire patient group was 3.86% (p < 0.001). Conclusions. Although current techniques of monitoring and surgical procedures have significantly reduced the risk of stroke from CABG, our data strongly support OPCAB as a technique to further reduce stroke after CABG, especially in the high-risk group of patients.
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The Notch (N) signalling pathway is recruited for segregation of cell fates in a number of Drosophila tissue types. We show here that N dependent segmentation of Drosophila legs is regulated by a dynamic pattern of expression of its ligand, DELTA (DL). During third larval instar and early stages of pupation, high levels of DL expression is seen in stripes of cells in the leg imaginal discs which later form the proximal borders of leg joints. These domains also displayed heightened Dl enhancer activity. During subsequent stages of pupation, following segmentation of the leg primordium, DL expression becomes uniform throughout these segments barring the joints. We further show that regulatory Dl mutations or mis-expression of DL abolish leg segmentation. Domains of N signalling for segmentation of legs of flies are thus set up by a stringent spatial regulation of expression of its ligand at the segment border. Further, a comparable role of DL in antennal development reveals a common paradigm of DL-N signalling for segmentation of appendages in flies.
The synthesis and anti-inflammatory activity of 4,5-dihydroxy-3-methyl-1H-pyrazolo[3,4-c]pyridazine (4), 4,5-dichloro-3-methyl-1H-pyrazolo[3,4-c]pyridazine (5), 4,-benzoyloxy-3-methyl-1-benzoyl-1H-pyrazolo[3,4-c]pyridazin-5yl benzoate (6), 3-methyl-N4,N5-bis(4-methylphenyl)-1H-pyrazolo[3,4-c]pyridazine-4,5-diamine (7), 4[[5-(4-carboxyanilino)-3-methyl-1H-pyrazolo[3,4-c]pyridazin-4yl]amino]benzoic acid (8), N-[5-(benzoylamino)-3-methyl-1H-pyrazolo[3,4-c]pyridazin-4-yl]benzamide (9) and 3-methyl-N4,N5-bis[4-(1H-benzimidazol-2yl)phenyl]-1H-pyrazolo[3,4-c]pyridazine-4,5-diamine (10) are being reported.
The aim of the present study was to evaluate the efficacy of sildenafil citrate and its effects on quality of life (QoL) in men with erectile dysfunction (ED) using data from three multicenter, double-blind, placebo-controlled clinical trials. Efficacy was evaluated using a global efficacy question (improvement of erections) and questions from the International Index of Erectile Function (IIEF) addressing the ability to achieve and maintain erections. QoL directly related to ED was evaluated using questions 13 and 14 of the IIEF, several psychometric instruments, and a questionnaire addressing men's concerns about their erection problems. Seventy-nine [corrected] percent of patients receiving sildenafil reported improved erections compared with 23% of patients receiving placebo (p < 0.0001); also reported were improvements in the ability to achieve and maintain erections with sildenafil but not with placebo (p < 0.0001). Improvements were also seen for other aspects of sexual function (overall satisfaction with sex life, sexual relationships with partners, concerns about erectile problems, p < 0.0001) and general mental health (well-being, self-control, satisfaction with relationship, health relative to 1 year ago, mental health; p < or = 0.05) following treatment with sildenafil. Thus, treatment of ED with sildenafil can significantly improve key QoL parameters related to sexual dysfunction and general mental health.