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S Saha

Publications and source records attributed to S Saha.

At least 37 records · Page 2Linked to original sources

Relationship between chaperone activity and oligomeric size of recombinant human alphaA- and alphaB-crystallin: a tryptic digestion study.

Alpha-crystallin, the major eye lens protein, exists as a large oligomer of two subunits, alphaA- and alphaB-crystallin. The individual subunits assemble into the oligomer in vitro. It is generally believed that oligomerization is pre-requisite for chaperone function, although there is no hard data available on this subject. We therefore undertook a study using limited tryptic digestion as a tool for examining the relationship between oligomeric size and chaperone activity of recombinant alphaA- and alphaB-crystallin. We showed that tryptic digested fragments of both alphaA- and alphaB-crystallin much smaller than the original subunits retain considerable chaperone activity. Our results indicate that chaperone activity depends more on the sequence of the reduced peptide than on its oligomeric size. The results also suggest that the presence of the alpha-crystallin domain and hydrophobic clefts on the protein surface, which correlate poorly with oligomeric size, are important for chaperone function.

Anilino Naphthalenesulfonates↗

A parvalbumin-containing, axosomatic synaptic network in the rat medial septum: relevance to rhythmogenesis.

The medial septal diagonal band complex (MS/DB), made up of cholinergic and GABAergic neurons, plays an important role in the generation of the hippocampal theta rhythm. A GABAergic neuron type in the MS/DB that has fast spiking properties was shown previously to contain parvalbumin immunoreactivity and to form axosomatic connections with unidentified somata. The aim in the current study was to determine the neurochemical identities of these target neurons. In slices and in perfused-fixed brain, staining for parvalbumin immunoreactivity first of all revealed the presence of two types of parvalbumin-positive somata in the MS/DB: medially located neurons with parvalbumin-positive basket-like terminals on them, and more laterally located neurons with fewer parvalbumin-positive contacts on them. In MS/DB slices, the terminals of fast spiking neurons filled with biocytin correspondingly made either numerous contacts that surrounded the parvalbumin-positive cell body in basket-like formation, or 1-5 contacts on a localized patch of the soma. These contacts were shown by electron microscopy to form synaptic junctions. No terminals of biocytin-filled fast spiking neurons were observed on cholinergic neurons, and dual staining in perfused-fixed brain did not reveal the presence of parvalbumin-containing terminals on cholinergic somata. Our results suggest therefore that there are two subtypes of parvalbumin-containing neuron in the MS/DB, and that these are interconnected via axosomatic synapses. The contrasting topographical organization of the two types of parvalbumin-containing neuron suggests that they may receive different types of afferent input, but this will require substantiation in future studies. We propose that generation of rhythmic activity in the MS/DB is controlled by contrasting contributions from two types of parvalbumin-positive neuron, and that the role of the cholinergic neuron is modulatory.

Action Potentials↗

Effects of education and other socioeconomic factors on middle age mortality in rural Bangladesh.

STUDY OBJECTIVE: To examine socioeconomic gradients in mortality in adult women and their husbands in Bangladesh, paying particular attention to the independent effects of the educational status of each spouse. DESIGN: Historical cohort study. SETTING: Matlab, a rural area 60 km south east of Dhaka, the capital of Bangladesh. PARTICIPANTS: 14803 married women aged 45 or over and their husbands who were resident in the Matlab Demographic Surveillance area between 30 June 1982 and 31 December 1998. MAIN RESULTS: Mortality was lower in women with formal or Koranic education compared with those with none (adjusted rate ratio for formal education = 0.68, 95% CI 0.53 to 0.86; adjusted rate ratio for Koranic schooling = 0.82, 95% CI 0.66 to 1.00). After adjusting for her own education, the husband's level of education or occupation did not have an independent effect on a woman's survival. Men who had attended formal education had lower mortality than those without any education (adjusted rate ratio = 0.84, 95% CI 0.75 to 0.93), but men whose wives had been educated had an additional survival advantage independent of their own education and occupation (adjusted rate ratio = 0.76, 95% CI 0.67 to 0.87). Mortality in both sexes was also significantly associated with marital status and the percentage of surviving children, and in men was associated with the man's occupation, religion, area of residence. CONCLUSIONS: The data suggest that socioeconomic status has a strong influence on mortality in adults in Bangladesh. They also illustrate how important the continued promotion of education, particularly for women, may be for the survival of both women and men in rural Bangladesh.

Bangladesh↗

Secretion of metastasis related gangliosides by mouse B16-melanoma in circulation in vivo and in culture media in vitro.

Mouse B16LuF1 melanoma cells of lower metastatic potential to lung were treated in vitro with same concentration (50 microM) of gangliosides prepared from plasma of mice bearing lung metastasis of B16LuF5, B16LuF9 or B16LuF10 melanoma cell lines of increasing metastatic potential to lung (LuF1 < LuF5 < LuF9 < LuF10) and injected to normal mice through tail vein. The number of metastatic tumor nodules formed in lung increased gradually in mice receiving B16LuF5, B16LuF9 and B16LuF10-ganglioside-treated B16LuF1 cells compared to mice receiving B16LuF1 cells without any ganglioside treatment. Similarly, mouse B16LuF1 melanoma cells treated in vitro with 50 microM concentration of gangliosides prepared from spent culture media of B16LuF5, B16LuF9 or B16LuF10 cells cultured in vitro were injected to normal mice through tail vein. The number of metastatic tumor nodules formed in lung increased gradually in mice receiving B16LuF5, B16LuF9 and B16LuF10-ganglioside-treated B16LuF1 cells compared to mice receiving B16LuF1 cells without any ganglioside treatment. The results indicated that metastasis-associated gangliosides present in plasma and culture media of B16-melanoma of increasing metastatic potential to lung enhanced metastatic potential of B16LuF1 cells. The increasing concentration of metastasis-associated gangliosides present in plasma and in culture media of B16-melanoma of increasing metastatic potential possibly determined increase in metastatic potential of B16LuF1-melanoma cells.

Animals↗

A 1 year prospective study of management and outcome of patients presenting with critical lower limb ischaemia.

OBJECTIVES: to determine management of patients with critical lower limb ischaemia (CLI) from first presentation to investigation and treatment. DESIGN: prospective study of critical ischaemia patients. METHODS: one-year prospective survey (May 2000-May 2001). Follow-up 3-15 months. RESULTS: some 873 arterial cases presented, 134 patients had CLI. Of the latter 49% were men, 30% diabetic, the median age was 81 years. Only 15 (24%) of 62 cases were referred to outpatients as urgent. Patients waited a median of 25 days (range 1-100) to be seen in outpatients, and had symptoms for a median of 8 weeks. Treatment was conservative for 70 patients, and 11 primary amputations, six secondary amputations, and 62 revascularisation procedures (34 operative, 28 percutaneous transluminal angioplasty) were performed. At follow-up (3-15 months, median 9 months), rates of major amputation and death were 12 and 27% respectively. Significantly more diabetics underwent major amputation (p < 0.02) than non diabetics. Patients presenting with ulceration or gangrene were at greater risk of death than those with rest pain alone (p < 0.01). CONCLUSION: patients with CLI often have symptoms for many weeks before being seen by a specialist, and 76% are referred as non-urgent cases. This compares with patients with suspected malignant disease in the U.K. who are required to be seen within 2 weeks.

Adult↗

Comparison of acute cardiovascular effects of cadmium and captopril in relation to oxidant and angiotensin converting enzyme activity in rats.

Cadmium (0.1, 0.32, 1.0 mg/kg i.v.) produced dose dependent hypertensive response in pentobarbitone anesthetized Sprague-Dawley (S-D) rats. The peak hypertensive effect was observed within 15 min of cadmium administration. This response gradually decreased over 1-h observation period. Heart rate did not change significantly. Serum malondialdehyde (MDA) levels increased with cadmium administration. The lower dose of cadmium (0.1 mg/kg i.v.) increased serum MDA to 0.14 +/- 0.02 nmol/mL as compared to 0.12 +/- 0.01 nmol/mL in the control group and was not statistically significant. However, mid (0.32 mg/kg i.v.) and high doses (1.0 mg/kg i.v.) raised serum MDA levels significantly (P < 0.01). Cadmium inhibited serum angiotensin converting enzyme (ACE) levels at all the three tested doses and was statistically significant (P < 0.01). Captopril (1.0, 3.2 mg/kg i.v.) produced a dose dependent mild hypotensive response. The peak effect was observed within 5 min. Cadmium produced inhibition of serum ACE levels, however, a dose response effect was not observed. Captopril (3.2 mg/kg i.v.) decreased serum ACE levels to 5.4 +/- 1.1 U/mL (control levels 10.7 +/- 1.4 U/mL). Serum MDA levels were decreased by captopril treatment. A correlation between serum ACE and MDA following higher dose of cadmium was found. These results indicate that acute administration of cadmium, an inorganic blocker of ACE and calcium channels cadmium produced hypertensive response while captopril produced mild hypotensive response in rats.

Angiotensin-Converting Enzyme Inhibitors↗

Common host genes are activated in mouse brain by Japanese encephalitis and rabies viruses.

This study identified nine genes whose expression is upregulated in the central nervous system (CNS) of mice during Japanese encephalitis virus (JEV) infection. These include: cathepsin S, oligoadenylate synthetase (OAS), GARG49/IRG2, lymphocyte antigen-6A (Ly-6A), macrophage activation gene-2 (Mpa2), early growth response gene1 (Egr1), pyrimidine 5'-nucleotidase (P5N), apolipoprotein D (ApoD) and STAT1. Activation of all nine genes during JEV infection was confirmed by Northern blot analysis. JEV replication was inhibited in the majority of mice immunized with Biken JEV vaccine, and these mice also exhibited reduced expression of JEV-inducible CNS genes. Thus, there is a good correlation between virus load and upregulation of host CNS genes. It was also demonstrated that all the CNS genes activated by JEV are also upregulated during rabies virus infection. In addition, GARG49, STAT1, cathepsin S and ApoD are known to be upregulated in the CNS by Sindbis virus, an alphavirus, and this supports the proposal that common host cell pathways are activated in the CNS by different neurotropic viruses.

2',5'-Oligoadenylate Synthetase↗

Oxidant, vitamin A and angiogenic markers in laryngeal cancer patients.

In this study the status of oxidant stress, vitamin A and angiotensin-converting enzyme (ACE) levels were evaluated in cases of laryngeal carcinoma patients from Northern India. In control subjects the levels of malondialdehyde (MDA), vitamin A and ACE were 0.23 +/- 0.07 nmole/ml, 2515 +/- 84 IU, and 1.4 +/- 0.8 U/ml respectively. Thirty laryngeal cancer patients were divided into three groups according to the TNM classification (American Joint Committee on Cancers). In laryngeal cancer patients according to tumour size, MDA and ACE levels increased to 0.32 +/- 0.04 nmole/ml and 4.7 +/- 0.5 U/ml respectively and the effect was statistically significant (p<0.01). The correlation coefficient between different subgroups was also highly significant (r=0.96, p<0.01). However, serum vitamin A levels decreased to 621 +/- 20 IU and the effect was statistically significant (p<0.01). In another two groups of laryngeal cancer patients, a similar pattern of various markers was obtained. Thirty patients with laryngeal carcinoma were divided into four different groups according to nodal involvement and it was observed that in laryngeal cancer patients with no nodal involvement, ACE levels were low 3.6 +/- 1.4 U/ml while patients with maximum nodal involvement had the highest levels of ACE 7.1 +/- 0.18 U/ml. The correlation coefficient between different groups is highly statistically significant (r=0.95, p<0.01). In patients with laryngeal cancer the serum MDA and vitamin A levels correlation coefficient between different groups was not significant. It is thus concluded that serum ACE might be a specific test marker for laryngeal cancer disease burden. The use of this marker enzyme for therapeutics is being planned.

Female↗

Correlation of gangliosides GM2 and GM3 with metastatic potential to lungs of mouse B16 melanoma.

Ten B16 mouse melanoma cell lines with increasing metastatic potential to lungs (B16LuF1 to B16LuF10) were generated by in-vitro & in-vivo selection technique starting with B16F1 melanoma cell line. The number of metastatic tumor nodules in lungs rose with increasing metastatic potential. Tumor cell gangliosides of B16LuF1 to B16LuF10 cell lines, analysed and compared with TLC, showed eight major ganglioside bands. Band1 to band6 corresponded with standard gangliosides GT1b, GD1b, GD1a, GM1, GM2 and GM3 respectively. Band7 and Band8 could not be identified. The concentration of total as well as individual ganglioside bands of B16LuF1 to B16LuF10 cells appeared to rise with increasing metastatic potential. Gangliosides from the plasma of these cell lines (B16LuF1 to B16LuF10) maintained in-vivo in C57BL/6 mice on TLC analysis gave eight major ganglioside bands, similar to those of cells. Plasma gangliosides appeared to rise with increasing metastatic potential. However, it was interesting to see that only band5 and band6 gangliosides in plasma increased almost linearly with increasing metastatic potential. The remaining six ganglioside bands in the plasma did not show such correlation. Band5 and Band6 gangliosides corresponded with standard gangliosides GM2 and GM3 respectively. Gangliosides of the spent culture media, secreted by these cell lines in-vitro in tissue culture also gave eight major ganglioside bands, similar to that of cells. Spent culture media gangliosides appeared to increase with increasing metastatic potential. However, concentration of only band5 and band6 gangliosides of spent culture media increased almost linearly with increasing metastatic potential, thus further confirming the role of band5(GM2) and Band6(GM3) gangliosides in regulating metastatic potential of B16-melanoma cells to lung.

Animals↗

Metastatic tumours of the ovary: a clinico-pathological study.

The ovary is a frequent site of metastasis. However the incidence of metastatic tumours to the ovary is not exactly known. The reported incidence in the literature varies from 2.95 to 27.8%. The gastrointestinal tract (GIT) and the breast have been reported to be the frequent primary sites of the metastatic deposits in the ovary. The aim of this study was to determine the incidence of metastatic ovarian tumours and analyse their detailed morphologic features. All the metastatic ovarian neoplasms diagnosed in the Department of Cytology and Gynaecologic Pathology, Post Graduate Institute of Medical Education and Research, Chandigarh from 1996 to 2000 were included in the study. Nineteen metastatic tumours out of a total of 363 ovarian neoplasms (5%) were identified. The patients frequently presented with abdominal distension and mass. The age ranged from 17 to 75 years. The primary site was unknown in ten cases. Uterus was the most common site (4 cases) followed by GIT (3 cases). Six Krukenberg's tumours were identified. In cases simulating the primary ovarian tumours, the following features were helpful to suggest the metastatic deposit in the ovary: bilaterality, no significant ovarian enlargement, vascular emboli, a Krukenberg's morphology, no omental deposits and the absence of transition from benign to malignant epithelium.

Adolescent↗

Enhancement of metastatic potential of mouse B16-melanoma cells to lung after treatment with gangliosides of B-16-melanoma cells of higher metastatic potential to lung.

Mouse B16LuF1 melanoma cells of lower metastatic potential to lung were treated in vitro with same concentration (50 microM) of gangliosides isolated from B16LuF5, B16LuF9 or B16LuF10 cells with higher metastatic potential to lung (LuF1< LuF5< LuF9< LuF10) and injected to groups of normal mice through tail vein. The number of metastatic tumor nodules formed in lung increased in mice receiving B16LuF5, B16LuF9 and B16LuF10-ganglioside-treated B16LuF1 cells compared to mice receiving B16LuF1 cells without any ganglioside treatment. Metastatic potential of B16LuF1 cells gradually increased after treatment with gangliosides of B 16-melanoma cells of increasing metastatic potential to lung. The six major gangliosides isolated from B16LuF10 cells corresponded with standard gangliosides GT1b, GD1b, GD1a, GM1, GM2 and GM3 respectively on TLC-analysis. When B16LuF1 cells were treated in vitro with each of these six individual gangliosides and injected to groups of normal mice through tail vein the number of tumor nodules formed in lung varied. The four groups of mice receiving B16LuF1 cells treated with each of four gangliosides corresponding to GT1b, GD1b, GD1a or GM1 produced lung metastasis comparable to that of untreated control group. Only remaining two gangliosides which corresponded with standard gangliosides GM2 and GM3 increased metastatic potential of B16LuF1 cells. Thus, these results indicated that gangliosides GM2 and GM3 of B16-melanoma cells are definitely associated with metastatic potential of these tumor cells.

Animals↗

Somatostatin immunoreactivity in axon terminals in rat nucleus tractus solitarii arising from central nucleus of amygdala: coexistence with GABA and postsynaptic expression of sst2A receptor.

Axon terminals synapsing on neurones in the nucleus tractus solitarii (NTS) that originate from the central nucleus of the amygdala (CeA) have been shown to contain gamma-aminobutyric acid (GABA) immunoreactivity. Here we investigated whether such terminals also contain somatostatin (SOM), a neuropeptide found in axons distributed throughout the NTS and in somata in the CeA, and known to modulate cardiovascular reflexes when microinjected into the NTS. With fluorescence microscopy, SOM immunoreactivity was seen in the varicosities of some axons throughout the NTS that were anterogradely labelled with biotin dextran amine injected into the CeA. Such varicosities were frequently observed in close proximity to dendrites of NTS neurones that were immunoreactive for the SOM receptor sst(2A) subtype, and in many cases also for catecholamine synthesising enzymes. In the caudal, cardioregulatory zone of NTS, SOM immunoreactivity was localised by electron microscopic pre-embedding gold labelling to boutons containing dense-cored and clear pleomorphic vesicles and forming symmetrical synapses, mostly onto dendrites. Additional post-embedding gold labelling for GABA suggested that a subpopulation (29%) of GABAergic terminals sampled in this area of NTS contained SOM. Almost all boutons anterogradely labelled from the amygdala were GABA-immunoreactive (-IR) and 21% of these were SOM-IR. A similar proportion of these boutons (22%) formed synapses onto dendrites containing immunoreactivity for the SOM receptor sst(2A) subtype. These observations provide evidence that some of the GABAergic projection neurones in the CeA that inhibit baroreceptor reflex responses in the NTS in response to fear or emotional stimuli could release SOM, which might modulate the activity of NTS neurones via an action on sst(2A) receptors.

Amygdala↗

Associations between water-treatment methods and diarrhoea in HIV-positive individuals.

This manuscript extends our previously published work (based on data from one clinic) on the association between three drinking water-treatment modalities (boiling, filtering, and bottling) and diarrhoeal disease in HIV-positive persons by incorporating data from two additional clinics collected in the following year. We conducted a cross-sectional survey of drinking water patterns, medication usage, and episodes of diarrhoea among HIV-positive persons attending clinics associated with the San Francisco Community Consortium. We present combined results from our previously published work in one clinic (n = 226) with data from these two additional clinics (n = 458). In this combined analysis we employed logistic regression and marginal structural modelling of the data. The relative risk of diarrhoea for 'always' vs. 'never' drinking boiled water was 0.68 (95% CI 0.45-1.04) and for 'always' vs. 'never' drinking bottled water was 1.22 (95 % CI 0.82-1.82). Drinking filtered water was unrelated to diarrhoea (1.03 (95% CI 0.78, 1.35) for 'always' vs. 'never' drinking filtered water]. Adjustment for confounding did not have any notable effect on the point estimates (0.61, 1.35 and 0.98 for boiled, bottled, and filtered water respectively, as defined above). The risk of diarrhoea was lower among those consuming boiled water but this finding was not statistically significant. Because of these findings, the importance of diarrhoea in immunocompromised individuals, and the limitations of cross-sectional data further prospective investigations of water consumption and diarrhoea among HIV-positive individuals are needed.

Adolescent↗

Early results of retrograde transpopliteal angioplasty of iliofemoral lesions.

PURPOSE: To assess whether the retrograde transpopliteal approach is a safe, practical and effective alternative to femoral puncture for percutaneous transluminal angioplasty (PTA). METHODS: Forty PTAs in 38 patients were evaluated. Intentional subintimal recanalization was performed in 13 limbs. Ultrasound evaluation of the popliteal fossa was carried out 30 min and 24 hr postprocedurally in the first 10 patients to exclude local complications. All patients had a follow-up of at least 6 weeks. RESULTS: The indication for PTA was critical ischemia in seven limbs and disabling claudication in the remainder. Stenoses (single or multiple) were present in 24 and occlusion in 15. The superficial femoral artery (SFA) was the commonest segment affected (36) followed by common femoral artery (CFA) in four and iliac artery in four. Technical success was achieved in 38 of 39 limbs where angioplasty was carried out. In one limb no lesion was found. Immediate complications were distal embolization in two and thrombosis in one. None of these required immediate surgery. There were no puncture site hematomas or popliteal arteriovenous fistulae. Symptomatic patency at 6 weeks was 85%. Further reconstructive surgery was required in three limbs and amputation in two. CONCLUSION: The transpopliteal approach has a high technical success rate and a low complication rate with a potential to develop into an outpatient procedure. It should be considered for flush SFA occlusions or iliac disease with tandem CFA/SFA disease where the contralateral femoral approach is often technically difficult.

Aged↗

A phosphatase associated with metastasis of colorectal cancer.

To gain insights into the molecular basis for metastasis, we compared the global gene expression profile of metastatic colorectal cancer with that of primary cancers, benign colorectal tumors, and normal colorectal epithelium. Among the genes identified, the PRL-3 protein tyrosine phosphatase gene was of particular interest. It was expressed at high levels in each of 18 cancer metastases studied but at lower levels in nonmetastatic tumors and normal colorectal epithelium. In 3 of 12 metastases examined, multiple copies of the PRL-3 gene were found within a small amplicon located at chromosome 8q24.3. These data suggest that the PRL-3 gene is important for colorectal cancer metastasis and provide a new therapeutic target for these intractable lesions.

Adenoma↗