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Biomedical subjects

M Ganguly

Publications and source records attributed to M Ganguly.

At least 19 recordsLinked to original sources
PubMed2006

PINK1 protein in normal human brain and Parkinson's disease.

Parkinson's disease is a common incurable neurodegenerative disease whose molecular aetiology remains unclear. The identification of Mendelian genes causing rare familial forms of Parkinson's disease has revealed novel proteins and pathways that are likely to be relevant in the pathogenesis of sporadic Parkinson's disease. Recently, mutations in a novel gene, PINK1, encoding a 581 amino acid protein with both mitochondrial targeting and serine/threonine kinase domains, were identified as a cause of autosomal recessive parkinsonism. This provided important evidence for the role of the mitochondrial dysfunction and kinase pathways in neurodegeneration. In this study, we report the first characterization of the PINK1 protein in normal human and sporadic Parkinson's brains, in addition to Parkinson's cases with heterozygous PINK1 mutations. The possible role of the PINK1 protein was also assessed in a number of neurodegenerative diseases characterized by proteinaceous inclusions. For these studies, rabbit polyclonal antibodies were raised against two peptide sequences within the N-terminal hydrophilic loops of PINK1 protein. Using immunohistochemistry and western blotting we were able to demonstrate that PINK1 is a ubiquitous protein expressed throughout the human brain and it is found in all cell types showing a punctate cytoplasmic staining pattern consistent with mitochondrial localization. Fractionation studies of human and rat brain confirm that PINK1 is localized to the mitochondrial membranes. In addition, we show that PINK1 is detected in a proportion of Lewy bodies in cases of sporadic Parkinson's disease and Parkinson's disease associated with heterozygous mutations in the PINK1 gene, which are clinically and pathologically indistinguishable from the sporadic cases. PINK1 was absent in cortical Lewy bodies, in neurofibrillary tangles in Alzheimer's disease, progressive supranuclear palsy and corticobasal degeneration, and in the glial and neuronal alpha-synuclein positive inclusions in multiple system atrophy. These studies provide for the first time in vivo morphological and biochemical evidence to support a mitochondrial localization of PINK1 and underpin the significance of mitochondrial dysfunction in the pathogenesis of nigral cell degeneration in Parkinson's disease.

Alzheimer Disease↗
PubMed2004

Frontotemporal lobar degeneration with ubiquitin-only-immunoreactive neuronal changes: broadening the clinical picture to include progressive supranuclear palsy.

The frontotemporal lobar degenerations (FTLDs) are a group of disorders in which the clinical picture is not necessarily predictive of the underlying neuropathology. The FTLD with ubiquitin-only-immunoreactive neuronal changes (FTLD-U) subtype is pathologically characterized by ubiquitin-positive, tau and alpha-synuclein-negative neuronal cytoplasmic inclusions in the frontotemporal cortex and hippocampal dentate fascia. When similar pathological changes are accompanied by histological features of motor neuron disease (MND), the term FTLD-MND is used. The latter pathological changes may be found in patients with or without clinical evidence of MND. We retrospectively reviewed the clinical details of three patients with a rapidly progressive, levodopa-unresponsive bradykinetic-rigid syndrome and frontal cognitive impairment. A diagnosis of progressive supranuclear palsy (PSP) had been considered in all three cases at initial presentation. Two of the cases fulfilled clinical diagnostic criteria for PSP, which was the final clinical diagnosis during life. Pathological analysis showed typical histological appearances of FTLD-MND in two cases and of FTLD-U in one case. Semi-quantitative analysis of pathological load seemed to correlate with the clinical phenotype. FTLD-U or FTLD-MND should be considered in the differential diagnosis of progressive frontal dementia with an akinetic rigid syndrome and supranuclear gaze palsy or Steele-Richardson-Olszewski disease.

Aged↗
PubMed1999

Posttranslational modifications of cardiac and skeletal muscle proteins by reactive oxygen species after burn injury in the rat.

OBJECTIVE: To determine the involvement of oxidative damage in muscle wasting after burn injury. SUMMARY BACKGROUND DATA: Burn injury damages tissue at the site of the burn and also affects peripheral tissue. There is evidence to suggest that reactive oxygen species may be generated in increased amounts after burn, and these may contribute to wound healing and to posttranslational modifications of tissue constituents distant from the wound site. METHODS: The oxidation of muscle proteins was assessed, using the dinitrophenylhydrazine assay for carbonyl content, in muscles of rats after a full-thickness skin scald burn covering 20% of the total body surface area, over a 6-week period. In this model, rats failed to incur normal body weight or muscle weight gain. RESULTS: Soleus, extensor digitorum longus, diaphragm, and heart ventricle proteins were oxidatively damaged after injury. The extent of tissue protein oxidation, however, differed depending on the time points studied. In general, higher levels of protein carbonyl group formation, an indicator of oxidative damage, were found to occur within 1 to 5 days after injury, and the oxidized protein content of the various tissues decreased during the later stages. Both sarcoplasmic and myofibrillar carbonyl-containing proteins accumulated in diaphragm 3 days after burn injury and were rapidly removed from the tissue during a 2-hour in vitro incubation. This coincided with increased proteolytic activity in diaphragm. CONCLUSIONS: These observations suggest that the loss of proteins modified by reactive oxygen species may contribute to the burn-induced protein wasting in respiratory and other muscles by a proteolytically driven mechanism.

Animals↗
PubMed1999

Potentiality of tricyclic compound thioridazine as an effective antibacterial and antiplasmid agent.

Thioridazine (Th), which is therapeutically used in psychiatric patients, was found to possess conspicuous antimicrobial activity when tested against 316 strains belonging to a number of Gram positive and Gram negative bacteria. Although Staphylococcus aureus, Vibrio chloerae and V. parahaemolyticus were found to be most sensitive, Th was highly bactericidal against S. aureus and bacteriostatic for vibrios and other Gram negative organisms. In the study of antiplasmid/curing effect of Th on twelve multiply antibiotic and Th resistant bacteria, it was observed that elimination of R plasmids was facilitated by choice of optimal concentration of Th. Significant elimination of single and combined antibiotic resistance occurred in E. coli and Shigella flexneri and not in S. aureus.

Anti-Bacterial Agents↗
PubMed1996

Sepsis increases oxidatively damaged proteins in skeletal muscle.

BACKGROUND: Muscle wasting and negative nitrogen balance are common findings in septic patients. It is not clear what signals this loss of body protein. Proteins modified by reactive oxygen species have been shown to be rapidly degraded. OBJECTIVE: To test the hypothesis that sepsis results in an increased amount of oxidatively damaged proteins in skeletal muscle. METHODS: Exposure of proteins to reactive oxygen species results in the incorporation of carbonyl groups into amino acids with metal binding sites. The formation of carbonyl group derivatives in sarcoplasmic and myofibrillar proteins was measured in the extensor digitorum longus and soleus muscles of septic rats 4 to 48 hours after cecal ligation and puncture and in control rats that underwent sham operation. RESULTS: Protein carbonyl content was increased 8 and 16 hours after cecal ligation and puncture in the extensor digitorum longus and soleus muscles, respectively. When muscles were incubated in vitro, the carbonyl content in protein decreased in muscles from septic rats but not in muscles from rats that had the sham operation. The loss of carbonyl groups in incubated septic muscles occurred also in energy-depleted muscles. CONCLUSIONS: Muscle proteins are oxidatively damaged during sepsis and an energy-independent proteolytic pathway participates in the degradation of these proteins. Damage to muscle proteins by reactive oxygen species may signal the selective removal of postsynthetically modified proteins, contributing to accelerated muscle protein degradation in sepsis.

Animals↗
PubMed1994

Studies on the existence of synergism between different antibiotics and a phenothiazine tranquilizer, promazine, possessing antimicrobial property.

Different antibiotics were tested for their capacity to exhibit synergism when used in combination with promazine (Pr), a tranquilizer endowed with powerful antimicrobial property. For this purpose the minimum inhibitory concentration (MIC) of different antibiotics and Pr was first determined by spot inoculation technique on nutrient agar plates to select the concentrations of the antibiotics and Pr to be used as well as the sensitive strains. It was observed that Pr in combination with tetracycline (Tc) demonstrated a marked enhancement of the inhibitory capacity of each drug, both against the Gram-positive and Gram-negative bacteria, following disc diffusion technique. The in vitro findings were further substantiated with the in vivo effects of Pr along with Tc using Salmonella typhimurium NCTC 74 as the challenge strain in mice. The synergism obtained was further corroborated in terms of the increase in the size of their inhibition zones compared with their unaltered individual zones to determine the level of significance. This result was also confirmed by the checkerboard test using doubling dilutions of both the agents.

Animals↗
PubMed1994

Role of computed tomography in preoperative evaluation of esophageal carcinoma.

The utility of computed tomography in pretherapy assessment of esophageal carcinoma is reviewed. Computed tomographic findings in 78 patients with histologically proved esophageal carcinoma were corelated with findings at surgery and histopathology. Computed tomography (CT) was found to be fairly accurate in assessing tumor extent, invasion of adjacent mediastinal structures and distant metastases but was of no help in detecting periesophageal lymph node involvement. The tracheobronchial tree invasion was detected with an overall accuracy of 96% whereas the same for invasion of aorta, percardium and gastroesophageal junction was 86%, 88% and 78% respectively. The sensitivity for the detection of periesophageal and perigastric lymphadenopathy was low (9% and 0% respectively) but was acceptably high in celiac lymphadenopathy (70%). CT is an excellent non invasive modality in pretherapy assessment of esophageal carcinoma and can guide the surgeon in determining the appropriate therapy.

Adolescent↗
PubMed1988

The effect of thyrotropin-releasing hormone stimulation on serum levels of gonadotropins in women during the follicular and luteal phases of the menstrual cycle.

Thyrotropin-releasing hormone (TRH) can stimulate the secretion of adenohypophyseal thyroid-stimulating hormone and prolactin (PRL). The effect of TRH on gonadotropin secretion has not been well defined. This study investigated the effect of TRH administration on the peripheral levels of luteinizing hormone (LH) and follicle-stimulating hormone (FSH) during the early follicular and midluteal phases of the menstrual cycle in five ovulatory, euthyroid, and normoprolactinemic women. Two hundred micrograms of TRH were administered intravenously on days 3 to 5 and on days 21 to 23 of the same cycle. LH and FSH were measured prior to and every 30 minutes for 2 hours following TRH injection. Ovulation was confirmed in all cycles by midluteal progesterone. All women had normal thyroid-stimulating hormone (TSH) and PRL responses to TRH stimulation in both cycle phases. Baseline and stimulated gonadotropin levels were analyzed by analysis of variance. Thirty minutes following TRH infusion, follicular and luteal levels of LH (mIU/ml, mean +/- standard error of the mean) significantly increased from 6.0 +/- 0.8 to 8.0 +/- 1.1 (P less than 0.005), and from 4.8 +/- 0.6 to 7.6 +/- 0.7 (P less than 0.005), respectively. Levels of FSH increased during both phases of the cycle, but the elevation was not statistically significant. These results suggest that TRH can stimulate gonadotrope secretion of LH, but not of FSH, in both the follicular and luteal phases of the cycle.

Adult↗
PubMed1984

Female hormones reduce neutrophil responsiveness in vitro.

Neutrophils were preincubated with 17 beta-estradiol and progesterone to determine the effects of these hormones on chemotactic peptide-stimulated superoxide anion (O2-) generation and degranulation. At pharmacologic levels 17 beta-estradiol was more active than progesterone with respect to inhibition of O2- generation as well as degranulation. An increase of preincubation time from 5 minutes to 25 minutes increased the percent inhibition. When 17 beta-estradiol and progesterone were combined at levels which approximate those measured during gestation, there was small but significant inhibition of O2- generation. Dexamethasone at equal molar concentration inhibited O2- generation only after 25 minutes of preincubation and at no time reached the level of inhibition attained by either of the sex hormones alone. Both estradiol and progesterone at pharmacologic levels significantly inhibited beta-glucuronidase and lysozyme release, whereas dexamethasone did not inhibit degranulation despite prolonged preincubation. Neutrophils isolated from women during various phases of the menstrual cycle and during the third trimester of pregnancy did not differ with respect to chemotactic peptide-stimulated O2- generation. These data suggest that inhibition of neutrophil responses requires the continuous presence of pharmacologic levels of estradiol and progesterone.

Dose-Response Relationship, Drug↗
PubMed1983

Radioimmunoassay of testosterone-estradiol-binding globulin in humans: a reassessment of normal values.

Antiserum against human testosterone-estradiol-binding globulin (hTeBG) was prepared in rabbits, and its specificity was demonstrated by crossed immunoelectrophoresis. A RIA for the measurement of hTeBG in serum was developed. With this assay, hTeBG was readily measured in 1-2 microliters serum. Interassay coefficients of variation for pools of serum from men, women, and women in late pregnancy were 7.7%, 5.5%, and 6.1%, respectively. Interassay coefficients of variation for the same pools were 10%, 12%, and 12%, respectively. The TeBG levels in a number of nonselected subjected determined by the present method show good correlations with those obtained by steady state polyacrylamide gel electrophoresis and dextran-coated charcoal assay. The concentrations of TeBG determined by the RIA in sera from men, women, and women in late pregnancy were 18 +/- 9 (n = 12), 54 +/- 13 (n = 8), and 374 +/- 55 (n = 6) pmol/ml (mean +/- SD), respectively.

Amniotic Fluid↗
PubMed1981

Pituitary response to LHRH stimulation in women on oral contraceptives: a followup dose response study.

Gonadotropic response to bolus intravenous injection of LHRH was measured in 36 women. Thirty of them were taking five different oral contraceptive preparations with six women in each category, and the remaining six served as controls. 150 micrograms LHRH was given during cycle days 20-25. Serum samples were obtained prior to the bolus injection and at 20 minute intervals for two hours. Five different oral contraceptive agents were selected to compare different progestins with same type and dose of estrogen, and different type or dose of estrogen with same type and dose of progestins. Significant suppression of LH response to LHRH stimulation ws observed in the agents containing 50 mcg of ethinyl estradiol or mestranol. No such suppression was noted in the product containing only 20 mcg of ethinyl estradiol. In comparing the different type of estrogenic or progestational components, no statistically significant differences in LH response were demonstrated. This finding suggests that it is not the individual component alone, but the combined action of estrogenic and progestational components which determines the potency of an oral contraceptive agent.

Contraceptives, Oral↗
PubMed1981

Diabetes, hypophysectomy, or thyroidectomy reduces nuclear L-triiodothyronine-binding capacity of rat lung.

L-T3 (T3) receptors of the lungs of rats were found to be under hormonal control. The apparent binding capacity of T3 receptors of lungs of diabetic, hypophysectomized, and thyroidectomized rats were 0.224 +/- 0.009, 0.195 +/- 0.007, and 0.102 +/- 0.008 pmol/mg DNA, as compared to 0.0321 +/- 0.014 pmol/mg DNA for normal animals. The binding affinities for T3 in normal, diabetic, hypophysectomized, and thyroidectomized rats were 256 +/- 3.24, 270 +/- 3.81, 249 +/- 4.03, and 260 +/- 8.2 pM, respectively. The magnitude of the maximum binding capacity in these cases was apparently not due to the loss of either T3 receptors or DNA during the incubation. Serum T3 and T4 concentrations in normal rats were 120.0 +/- 7.2 ng/dl and 5.9 +/- 0.5 micrograms/dl, respectively. Diabetes, hypophysectomy, and thyroidectomy lowered these values to 79 +/- 5.4, 60 +/- 5.8, and 30 +/- 1.6 ng/dl for T3 and 3.5 +/- 0.3, 2.7 +/- 0.4, and 1.9 +/- 0.2 micrograms/dl for T4, respectively.

Animals↗