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S Saha

Publications and source records attributed to S Saha.

At least 73 records · Page 4Linked to original sources
PubMed2001

Intranasal inoculation with the olfactory bulb line variant of mouse hepatitis virus causes extensive destruction of the olfactory bulb and accelerated turnover of neurons in the olfactory epithelium of mice.

Viral upper respiratory infections are the most common cause of clinical olfactory dysfunction, but the pathogenesis of dysosmia after viral infection is poorly understood. Biopsies of the olfactory mucosa in patients that complain of dysosmia after viral infection fall into two categories: one in which no olfactory epithelium is seen and another in which the epithelium is disordered and populated mainly by immature neurons. We have used intranasal inoculation with an olfactory bulb line variant of MHV to study the consequences of viral infection on peripheral olfactory structures. MHV OBLV has little direct effect on the olfactory epithelium, but causes extensive spongiotic degeneration and destruction of mitral cells and interneurons in the olfactory bulb such that the axonal projection from the bulb via the lateral olfactory tract is markedly reduced. Moreover, surviving mitral cells apparently remain disconnected from the sensory neuron input to the glomerular layer, judging from retrograde labeling studies using Dil. The damage to the bulb indirectly causes a persistent, long-term increase in the turnover of sensory neurons in the epithelium, i.e. the relative proportion of immature to mature sensory neurons and the rate of basal cell proliferation both increase. The changes that develop after inoculation with MHV OBLV closely resemble the disordering of the olfactory epithelium in some patient biopsies. Thus, damage to the olfactory nerve or bulb may contribute to a form of post-viral olfactory dysfunction and MHV OBLV is a useful model for studying the pathogenesis of this form of dysosmia.

Administration, Intranasal↗
PubMed2001

Functional consequences following infection of the olfactory system by intranasal infusion of the olfactory bulb line variant (OBLV) of mouse hepatitis strain JHM.

The present study assessed the functional consequences of viral infection with a neurotropic coronavirus, designated MHV OBLV, that specifically targets central olfactory structures. Using standard operant techniques and a 'go, no-go' successive discrimination paradigm, six BALB/c mice were trained to discriminate between the presentation of an air or odor stimulus (three mice for each of the odorants propanol and propyl acetate). Two additional BALB/c mice were trained to discriminate between the presentation of air and the presentation of either vanillin or propionic acid. Following criterion performance, each mouse received an additional 2000 trials of overtraining. At completion of overtraining one mouse from the propanol and propyl acetate groups were allocated as untreated. The remaining six mice were inoculated with 300 microl of the OBLV stock per nostril for a total of 1.5 x 10(6) p.f.u. in 600 microl. Following a 1 month rest, untreated and inoculated animals were again tested on their respective air versus odor discrimination task. Untreated animals immediately performed at criterion levels. In contrast, inoculated animals varied in their capacity to discriminate between air and odorant. Five of the six inoculated mice showed massive disruption of the olfactory bulb, including death of mitral cells; the other was more modestly affected. In addition, the density of innervation of the olfactory mucosa by substance P-containing trigeminal fibers is also affected by inoculation. Those mice that remained anosmic to the training odorants had the most severe reduction in mitral cell number and substance P fiber density among the inoculated animals.

Administration, Intranasal↗
PubMed2001

Ratio of invaded to removed lymph nodes as a prognostic factor in adenocarcinoma of the distal esophagus and esophagogastric junction.

This study examined the influence of nodal harvest and the proportion of positive nodes on survival in 59 patients with adenocarcinoma of the distal esophagus and esophagogastric junction undergoing esophagectomy with curative intent. A total of 754 lymph nodes were harvested (median 13, range 0-28). Two hundred and twenty-eight positive nodes were found on histology (median 4, range 1-23) in 43 (79%) patients with a higher incidence from T3/T4 than T1/T2 lesions (P < 0.003). Overall 1- and 3-year survival rates were 73% and 47% respectively. Node positivity increased with increased total nodal harvest, but was not influenced by the site of tumors or surgical approaches. There was no survival benefit for patients with <20% over >20% nodal positivity (P=0.31). Only negative lateral resection margin emerged as a significant factor in both univariate (P < 0.01) and multivariate analysis (P < 0.05). We conclude that the degree of nodal positivity in adenocarcinoma is less important than resection margin status as a prognostic factor.

Adenocarcinoma↗
PubMed2001

RNA expression analysis using an antisense Bacillus subtilis genome array.

We have developed an antisense oligonucleotide microarray for the study of gene expression and regulation in Bacillus subtilis by using Affymetrix technology. Quality control tests of the B. subtilis GeneChip were performed to ascertain the quality of the array. These tests included optimization of the labeling and hybridization conditions, determination of the linear dynamic range of gene expression levels, and assessment of differential gene expression patterns of known vitamin biosynthetic genes. In minimal medium, we detected transcripts for approximately 70% of the known open reading frames (ORFs). In addition, we were able to monitor the transcript level of known biosynthetic genes regulated by riboflavin, biotin, or thiamine. Moreover, novel transcripts were also detected within intergenic regions and on the opposite coding strand of known ORFs. Several of these novel transcripts were subsequently correlated to new coding regions.

Amino Acid Sequence↗
PubMed2001

Fragile X syndrome in Calcutta, India.

Fragile-X-linked mental retardation usually results from amplification of the CGG repeat in the 5' untranslated region of the FMR1 gene. To assess the extent of variation of the CGG repeat in the population from the eastern region of India we studied 98 mentally retarded individuals living in and around Calcutta and identified 21 distinct alleles ranging in size from 8 to 44 CGG repeats. A repeat size of 28 was the most frequent; this value is different from the most frequent repeat size found in other studies, indicating a racial or ethnic variation. Patients with the clinical features of the syndrome have been found to carry expanded CGG repeats. Thus, it can be inferred that the expansion of CGG repeats may be a frequent cause of the syndrome in our population.

Adolescent↗
PubMed2001

Suppression of Ehrlich subcutaneous solid tumor growth by immunization with ganglioside GT1b of its origin, its IgM antibody or anti-idiotype antibody.

Mice vaccinated with purified Ehrlich tumor-plasma GT1b admixed with Freund's adjuvant suppressed subcutaneous growth of the same tumor cells inoculated in vivo by 37.9%. The suppression was dose-dependent and was a result of humoral immune response against GT1b. Further, when mice were injected with varying doses of rabbit polyclonal anti-GT1b IgM antibody and challenged with Ehrlich tumor cells subcutaneously, a significant reduction in tumor growth (47.3%) was observed. Again, the suppression was dose-dependent. To strengthen furthier the observed therapeutic potential of this immunogenic GT1b, mice were immunized with anti-idiotype antibodies to GT1b raised in female Sprague Dawley rats by immunization with rabbit anti-GT1b IgM, which is expected to carry the structural image of GT1b. Immunization of mice with this anti-idiotype antibody was observed to suppress Ehrlich subcutaneous solid tumor growth by 60%. The results indicated therapeutic potential of immunogenic tumor-associated ganglioside in solid tumor model.

Animals↗
PubMed2001

Aberrant drainage and missed micrometastases: the value of lymphatic mapping and focused analysis of sentinel lymph nodes in gastrointestinal neoplasms.

Lymph node analysis is essential for staging gastrointestinal (GI) neoplasms. Our group has conducted several studies of intraoperative lymphatic mapping and sentinel lymphadenectomy (LM/SL) for the staging of GI neoplasms. LM is performed following injection of 0.5-1 ml of isosulfan blue dye, and blue-stained sentinel lymph nodes (SLNs) are analyzed by hematoxylin and eosin (H&E) staining, multiple sectioning, and cytokeratin immunohistochemistry. In feasibility trials, LM identified at least one SLN in 121 of 126 patients. Of the 58 cases with nodal metastasis, 50 (89%) had at least one positive SLN and 24 (42%) had nodal metastasis only in the SLN. In 25 cases, tumor deposits were identified by multiple sectioning (n = 8) or immunohistochemistry (n = 17) only. In 10 cases (8%), LM identified aberrant lymphatic drainage that altered the extent of the lymphadenectomy. Our cumulative experience indicates that focused analysis of the SLNs draining GI neoplasms can increase the detection of micrometastases and may improve selection of patients for adjuvant treatment.

Adenocarcinoma↗
PubMed2001

Ultrastaging of colorectal cancer by sentinel lymph node mapping technique--a multicenter trial.

Sentinel lymph node (SLN) mapping accurately diagnoses the status of nodal basin with >95% accuracy in melanoma and breast cancer. A multicenter trial for SLN mapping was performed on 203 patients with colorectal cancer to determine accuracy, upstaging, skip metastasis, and aberrant drainage. Lymphazurin 1% was injected subserosally around the tumor and 1-4 blue staining nodes were marked as SLNs for detailed histological analysis. SLN mapping was successful in 98% of patients with an average of 1.7 SLNs per patient. SLNs were negative in 63% of the patients and positive in 37% of the patients. Skip metastasis was seen in 8 of the patients. Occult micrometastasis was found in 14% of patients. In 5% of the patients, unusual lymphatic drainage lead to an alteration of the extent of lymphadenectomy. This multicenter trial proved that SLN mapping in patients with colorectal cancer is simple, cost effective, and upstages at least 14% of patients from AJCC stage I/II to stage III. These patients may then benefit from adjuvant chemotherapy.

Adult↗
PubMed2001

Diagnosis and management of febrile children using the WHO/UNICEF guidelines for IMCI in Dhaka, Bangladesh.

OBJECTIVE: To determine whether the fever module in the WHO/UNICEF guidelines for the integrated management of childhood illness (IMCI) identifies children with bacterial infections in an area of low malaria prevalence. METHODS: Physicians assessed a systematic sample of 669 sick children aged 2-59 months who presented to the outpatient department of Dhaka Shishu Hospital, Bangladesh. FINDINGS: Had IMCI guidelines been used to evaluate the children, 78% of those with bacterial infections would have received antibiotics: the majority of children with meningitis (100%), pneumonia (95%), otitis media (95%) and urinary tract infection (83%); and 50% or less of children with bacteraemia (50%), dysentery (48%), and skin infections (30%). The current fever module identified only one additional case of meningitis. Children with bacteraemia were more likely to be febrile, feel hot, and have a history of fever than those with dysentery and skin infections. Fever combined with parental perception of fast breathing provided a more sensitive fever module for the detection of bacteraemia than the current IMCI module. CONCLUSIONS: In an area of low malaria prevalence, the IMCI guidelines provide antibiotics to the majority of children with bacterial infections, but improvements in the fever module are possible.

Bacterial Infections↗
PubMed2001

Fragile X syndrome a case report of a family.

Fragile X syndrome is the most common of the inherited disorders causing mental retardation. This disorder results from an abnormal expansion in (CGG)n in repeat found in the coding sequence of the FMRI gene, located at Xq 27.3. Previously it was detected by Karyotyping. With the advent of Molecular Biology PCR, has become the best method in the diagnosis of this disorder. This is a case report of a family with this disorder detected by PCR.

Adolescent↗
PubMed2000

In vitro culture of bovine preantral follicles.

Bovine preantral follicles (40-100 microm diameter at collection) were collected from ovaries of slaughtered cows and cultured in vitro with one of the four treatments: follicle stimulating hormone (FSH; 100 ng/ml) alone; FSH plus epidermal growth factor (EGF; 100 ng/ml); FSH plus insulin-transferrin-selenium (ITS; +1%) or FSH plus hypoxanthine (4 mM) in tissue culture medium (TCM 199) supplemented with 10% fetal calf serum (FCS), 0.1 mg/ml sodium pyruvate, 100 IU/ml of penicillin and 100 microg/ml streptomycin. The control culture medium was TCM 199 with supplements without any treatments. Follicles of each size were cultured separately in groups of one to three in 24-well multidishes each containing 500 microl of the appropriate culture medium. Culture commenced at follicle recovery (day 1) and continued for 10 days (harvested on day 11). In each case, half the medium was removed and replaced by fresh medium every third day. Follicle diameters were recorded on days 1, 5 and 11 of the experiment. At the end of the 10-day culture period, half of the follicles were stained with trypan blue to assess their potential viability and half were stained with bisbenzimide plus propidium iodine to estimate various morphological features of the follicles. Follicles of all initial sizes, on all culture treatments, increased in diameter during in vitro cultures with the greatest increases, both in absolute and proportional size, occurring between days 1 and 5 of culture. All of the culture medium supplements caused greater increases in follicle diameters than control medium at both days 5 and 11 of culture for all initial sizes of follicles (p<0.01). The most effective culture supplements for follicles of 40-, 60- and 80-microm initial diameter were FSH alone and FSH+EGF. The size of these follicles at both days 5 and 11 of culture on both the treatments was significantly larger (p<0.01) than follicles cultured in the presence of the other two supplementary treatments. The growth of follicles of 100-microm initial diameter did not differ between culture medium supplements. None of the culture media caused follicle size to increase to the initial diameters of the next larger size category during the 10 days of culture although follicles of 100-microm diameter achieved a diameter of 120 microm, after 4 days of culture. The overall follicular viability and morphology were better with treatments than the controls in all cases; however, there was no significant difference (p>0.05) among them. From this experiment, FSH and FSH plus EGF may be recommended for in vitro culture of smaller (40, 60 and 80 microm) follicles.

Animals↗
PubMed2000

Selective deuterium exchange during superheated heavy water chromatography-nuclear magnetic resonance spectroscopy-mass spectrometry of sulfonamides.

Superheated deuterium oxide has been investigated as an eluent for reversed-phase HPLC on a polystyrene-divinylbenzene column with UV, 1H NMR and MS detection using a series of sulfonamides as model compounds. In the course of these studies, a selective, specific and efficient deuteration of the methyl groups on a pyrimidine ring was observed during chromatography of certain of the sulfonamides. The potential of this methodology for producing deuterium-labelled compounds from substances bearing suitable substituents is considered. The utility of HPLC-NMR-MS as a means for studying on-column reactions is discussed.

Chromatography, Liquid↗
PubMed2000

Expression and function of the protein tyrosine phosphatase SHP-1 in oligodendrocytes.

Previous studies in this laboratory have shown that the SH-2 domain-containing protein tyrosine phosphatase SHP-1 is expressed in CNS glia and functions to modulate cytokine activities in these cells. The present study demonstrates that SHP-1 is expressed within multiple regions of the CNS in vivo, especially in white matter. Interestingly, we show that mice genetically lacking in SHP-1 (motheaten mice) in the CNS displayed dysmyelination. We therefore examined the expression of SHP-1 in the myelin-forming oligodendrocytes. Oligodendrocytes present in either mixed glial cultures or pure cultures expressed high levels of SHP-1 in the cytoplasm of cell bodies and processes. Oligodendrocytes isolated from motheaten mice did not express SHP-1. To test possible functions for SHP-1 in oligodendrocytes in controlling cytokine signaling, we compared the responsiveness of oligodendrocytes isolated from either motheaten or normal littermate mice with IL-6. IL-6 induced higher levels of STAT3 phosphorylation and STAT3-responsive c-fos gene expression in pure oligodendrocyte cultures of motheaten compared with normal littermate mice. These studies demonstrate that oligodendrocytes express SHP-1 and that SHP-1 functions to control IL-6 signaling. SHP-1 may therefore be a critical regulator of oligodendrocyte differentiation in response to IL-6 family cytokines. Further, these findings may relate to dysmyelination in mice lacking SHP-1.

Animals↗
PubMed2000

Three different proteins recognize a multifunctional determinant that controls replication initiation, fork arrest and transcription in Tetrahymena.

Type I elements regulate the initiation of DNA replication, elongation of replication forks and transcription of the Tetrahymena thermophila rDNA minichromosome. Previous studies identified a 24 kDa protein, ssA-TIBF, which binds the A-rich strand of type I elements. Here we describe two additional type I element binding activities (native mol. wt approximately 65 and approximately 250 kDa) that interact with DNA via previously unidentified 32 and 110 kDa polypeptides. The 65 kDa activity was purified to homogeneity and consists of a homodimer of a 32 kDa polypeptide. In contrast to the other type I element binding factors, the 65 kDa activity partitions preferentially to the nuclear fraction during isolation. Levels of the 65 kDa activity increase dramatically in starved cells, raising the possibility that it might negatively regulate replication or transcription. By comparison, the other two binding activities were elevated slightly during macronuclear development, when the rDNA was undergoing DNA replication. Previous studies indicate that the initiation of rDNA replication is regulated by long range interactions between dispersed type I elements. Competitive DNA binding or cooperative protein-protein interactions between the factors described here may play a regulatory role in replication or expression of the rDNA minichromosome.

Animals↗
PubMed2000

Allele-specific protein-DNA interactions between the single-stranded DNA-binding protein, ssA-TIBF, and DNA replication determinants in Tetrahymena.

Type I elements are multifunctional, cis-acting determinants that regulate the initiation of DNA replication, replication fork movement and transcription of the Tetrahymena thermophila rDNA minichromosome. Previous studies identified a protein, ssA-TIBF, that binds specifically to the A-rich strand of type I elements. Here, we examine interactions of ssA-TIBF with the wild-type C3 allele, and a natural variant, B rDNA, which manifests a defect in replication initiation and fork pausing. Purified ssA-TIBF is a homotetramer that binds one substrate molecule and contacts DNA via a single 24 kDa subunit. Both the A-rich and T-rich strands of type I elements are bound by ssA-TIBF, suggesting that this protein might stabilize replication origins in their unwound state. Nucleotides downstream of type I elements contribute to DNA binding, with the extent of DNA-protein contact being greater for wild-type C3 rDNA compared to B rDNA. Allele-specific protein-DNA contacts also occur within the conserved type I element itself. Despite these differences, the binding affinities of ssA-TIBF for C3 and B rDNA substrates are indistinguishable. Consequently, the mode of DNA binding must account for any role ssA-TIBF might play in the regulation of rDNA replication.

Alleles↗
PubMed2000

Variation in axillary node dissection influences the degree of nodal involvement in breast cancer patients.

BACKGROUND AND OBJECTIVES: The number of positive axillary lymph nodes predicts prognosis and is often important in determining adjuvant chemotherapy in breast cancer patients. This study was undertaken to determine if differences in the extent of axillary node dissection would alter the number of reported positive nodes. METHODS: The study population consisted of 302 patients with invasive breast cancer who underwent complete (level I/II/III) axillary lymph node dissection. Assuming that all patients had undergone a level I/II dissection, it was determined how frequently a patient's nodal category (0, 1-3, 4-9, >10 positive nodes) would have been altered if a level I or level I/II/III dissection were performed. RESULTS: Assuming that all 302 patients had undergone a level I/II dissection, performing only level I dissection would have resulted in a change in nodal category in 15.9% of all patients and 36.1% of patients with positive nodes. The corresponding changes for a level I/II/III dissection would have been 4.3% and 9.5%, respectively. CONCLUSIONS: Variations in the level of axillary node dissection for breast cancer can result in significant changes in the number of positive axillary nodes. This can potentially bias adjuvant chemotherapy recommendations if treatment decisions are based on this prognostic factor.

Axilla↗