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S Saha

Publications and source records attributed to S Saha.

At least 55 records · Page 3Linked to original sources
PubMed2001

Secreted and cell surface genes expressed in benign and malignant colorectal tumors.

Serial analysis of gene expression was used to identify transcripts encoding secreted or cell surface proteins that were expressed in benign and malignant tumors of the colorectum. A total of 290,394 tags were analyzed from normal, adenomatous, and cancerous colonic epithelium. Of the 21,343 different transcripts observed, 957 were found to be differentially expressed between normal tissue and adenoma or between normal tissue and cancer. Forty-nine transcripts were elevated > or =20-fold in adenomas, 40 transcripts were elevated > or =20-fold in cancers, and 9 transcripts were elevated > or =20-fold in both. Products of six of these nine transcripts (TGFBI, LYS, RDP, MIC-1, REGA, and DEHL) were predicted to be secreted or to reside on the cell surface, and these were analyzed in more detail. The abnormal expression levels predicted by serial analysis of gene expression were confirmed by quantitative PCR analyses of each of these six genes. Moreover, the cell types responsible for the elevated expression were identified by in situ hybridization and by PCR analyses of epithelial cells immunoaffinity purified from primary tumors. This study extends knowledge of the differences in gene expression that underlie various stages of neoplasia and suggests specific diagnostic approaches that may be useful for the early detection of colorectal neoplasia.

Adenomatous Polyposis Coli↗
PubMed2001

Cloning and biochemical analysis of the tetrahymena origin binding protein TIF1: competitive DNA binding in vitro and in vivo to critical rDNA replication determinants.

Cis-acting type I elements regulate the initiation of DNA replication, replication fork movement, and transcription of the Tetrahymena thermophila rDNA minichromosome and are required for cell cycle-controlled replication and developmentally programmed gene amplification. Previous studies identified three in vitro single-stranded type I element binding activities that were proposed to play distinct roles in replication control. Here we describe the cloning of one of these genes, TIF1, and we provide evidence for its association with type I elements in vivo. Furthermore, we show that TIF1 interacts (in vitro and in vivo) with pause site elements (PSE), which co-localize with replication initiation and fork arrest sites, and are shown to be essential. The in vivo accessibility of PSE and type I elements to potassium permanganate suggests that origin regions are frequently unwound in native chromatin. TIF1 contains sequence similarity to the Solanum tuberosum single strand-specific transcription factor, p24, and a related Arabidopsis protein. Antisense inhibition studies suggest that TIF1 competes with other proteins for PSE and type I element binding. TIF1 displays a marked strand bias in vivo, discriminating between origin- and promoter-proximal type I elements. We propose that this bias selectively modulates the binding of a different subset of proteins to the respective regulatory elements.

Amino Acid Sequence↗
PubMed2001

The mechanism of action of bacimethrin, a naturally occurring thiamin antimetabolite.

The mechanism of bacimethrin (2) toxicity has been determined. This compound is converted to 2'-methoxy-thiamin pyrophosphate (10) by the thiamin biosynthetic enzymes. Of the seven thiamin pyrophosphate utilizing enzymes in Escherichia coli, 2'-methoxy-thiamin pyrophosphate inhibits alpha-ketoglutarate dehydrogenase, transketolase, and deoxy-D-xylulose-5-phosphate synthase. Bacimethrin does not cause repression of the genes coding for the thiamin biosynthetic enzymes.

Antimetabolites↗
PubMed2001

The first epidermal growth factor-like domain of the low-density lipoprotein receptor contains a noncanonical calcium binding site.

Removal of cholesterol-containing particles from the circulation is mediated by the low-density lipoprotein (LDL) receptor. Upon ligand binding, the receptor-ligand complex is endocytosed, and the ligand is released. The important biological role of the LDL receptor (LDLR) has been highlighted by the identification of more than 400 LDLR mutations that are associated with familial hypercholesterolemia. The extracellular region of the LDLR is modular in nature and principally comprises multiple copies of ligand binding, epidermal growth factor-like (EGF), and YWTD-type domains. This report describes characterization of the calcium binding properties of the tandem pair of EGF domains. While only the C-terminal EGF module contains the consensus sequence associated with calcium binding, a noncanonical calcium binding site in the N-terminal domain has been revealed using solution NMR spectroscopy. The calcium dissociation constants for the N- and C-terminal sites have been measured under physiologically relevant pH and ionic strength conditions using a combination of solution NMR, intrinsic protein fluorescence, and chromophoric chelator methods to be approximately 50 microM and approximately 10-20 microM, respectively. Identification of the novel calcium binding motif in LDLR sequences from other species suggests that it may confer specificity within the LDLR gene family. Comparison of the K(d) for the C-terminal site with the calcium concentration in late vesicles indicates that the binding properties of this module may be tuned to titrate upon endocytosis of the LDL receptor-ligand complex, and thus calcium binding may play a role in the ligand dissociation process.

Amino Acid Sequence↗
PubMed2001

Molecular staging of early colon cancer on the basis of sentinel node analysis: a multicenter phase II trial.

PURPOSE: Approximately 30% of patients with American Joint Committee on Cancer stage I or II colorectal cancer (CRC) develop systemic disease. We hypothesized that multimarker reverse transcriptase-polymerase chain reaction (RT-PCR) analysis of sentinel lymph nodes (SNs) draining a primary CRC could detect micrometastases not detected by conventional histopathologic analysis. PATIENTS AND METHODS: In a multi-institutional study, 40 patients with primary CRC underwent dye-directed lymphatic mapping at the time of colon resection. Each dye-stained SN was tagged, and the tumor and regional nodes were resected en bloc. All lymph nodes were examined by conventional hematoxylin and eosin (HE) staining. In addition, each SN was cut into multiple sections for cytokeratin immunohistochemical (CK-IHC) staining and for RT-PCR and electrochemiluminescent detection of three markers: beta-chain human chorionic gonadotropin, hepatocyte growth factor receptor, and universal melanoma-associated antigen. Whenever possible, RT-PCR assay was also performed on primary tumor tissue. The detection sensitivity of individual markers was 10(-3) to 10(-4) microg of RNA and one to five tumor cells in 10(7) lymphocytes of healthy donors. RESULTS: One to three SNs were identified in each patient. An average of 15 nodes were removed from each CRC specimen. No nonsentinel (untagged) node contained evidence of tumor if all tagged (sentinel) nodes in the same specimen were histopathology tumor-negative. HE staining of SNs identified tumor in 10 patients (25%), and CK-IHC of SNs identified occult micrometastases in four patients (10%) whose SNs were negative by HE. Of the remaining 26 patients with no evidence of SN involvement by HE or CK-IHC, 12 (46%) had positive RT-PCR results. The number of markers expressed in each SN correlated (P <.04) with the T stage of the primary tumor. There was 79% concordance in marker expression for the respective pairs (n = 38) of primary tumor and histopathologically positive SNs, and 86% (12 of 14) concordance between RT-PCR positive and histopathologically positive SNs. CONCLUSION: Identification and focused examination of the SN is a novel method of staging CRC. CK-IHC and RT-PCR identified occult micrometastases in 53% of patients whose SNs were negative by conventional staging techniques. These ultrasensitive assays of the SN can identify patients who may be at high risk for recurrence of CRC and therefore are more likely to benefit from systemic adjuvant therapy.

Antigens, Neoplasm↗
PubMed2001

Photochemical E (trans)-->Z (cis) isomerization in substituted 1-naphthylacrylates.

Substituted naphthylacrylates, 1-3, not showing rotamerism have been synthesized with a view to study photochemical E (trans)-->Z (cis) isomerization. Photostationary state composition of the isomers upon direct excitation, triplet sensitized isomerization, quantum yield of isomerization, and steady state and time-resolved fluorescence behavior have been studied for these naphthylacrylates. The direct excitations of the compounds yield high Z (approximately 80%) isomer composition, whereas the triplet sensitization results in less Z (approximately 20%) isomer composition. This indicates that the singlet pathway is very efficient in converting the E isomer to the Z isomer. The naphthylacrylates 1 and 2 exhibit structured fluorescence at room temperature in hexane and upon changing the solvent to CH3CN; the structure of the fluorescence is lost, indicating that the singlet excited-state develops a polar character in a polar environment. The polar nature of the singlet excited state becomes more clear in the case of 3 from its fluorescence solvatochromism. The naphthylacrylates did not exhibit excitation wavelength-dependent fluorescence at room temperature suggesting that the ground state conformers (rotamers) are not involved. Fluorescence lifetimes measured for these compounds displayed biexponential behavior, which is explained using a two-state model.

Journal Article↗
PubMed2001

Adverse effects of early dexamethasone treatment in extremely-low-birth-weight infants. National Institute of Child Health and Human Development Neonatal Research Network.

BACKGROUND: Early administration of high doses of dexamethasone may reduce the risk of chronic lung disease in premature infants but can cause complications. Whether moderate doses would be as effective but safer is not known. METHODS: We randomly assigned 220 infants with a birth weight of 501 to 1000 g who were treated with mechanical ventilation within 12 hours after birth to receive dexamethasone or placebo with either routine ventilatory support or permissive hypercapnia. The dexamethasone was administered within 24 hours after birth at a dose of 0.15 mg per kilogram of body weight per day for three days, followed by a tapering of the dose over a period of seven days. The primary outcome was death or chronic lung disease at 36 weeks' postmenstrual age. RESULTS: The relative risk of death or chronic lung disease in the dexamethasone-treated infants, as compared with those who received placebo, was 0.9 (95 percent confidence interval, 0.8 to 1.1). Since the effect of dexamethasone treatment did not vary according to the ventilatory approach, the two dexamethasone groups and the two placebo groups were combined. The infants in the dexamethasone group were less likely than those in the placebo group to be receiving oxygen supplementation 28 days after birth (P=0.004) or open-label dexamethasone (P=0.01), were more likely to have hypertension (P<0.001), and were more likely to be receiving insulin treatment for hyperglycemia (P=0.02). During the first 14 days, spontaneous gastrointestinal perforation occurred in a larger proportion of infants in the dexamethasone group (13 percent, vs. 4 percent in the placebo group; P=0.02). The dexamethasone-treated infants had a lower weight (P=0.02) and a smaller head circumference (P=0.04) at 36 weeks' postmenstrual age. CONCLUSIONS: In preterm infants, early administration of dexamethasone at a moderate dose has no effect on death or chronic lung disease and is associated with gastrointestinal perforation and decreased growth.

Anti-Inflammatory Agents↗
PubMed2001

Gamma-aminobutyric acid receptor (GABA(A)) subunits in rat nucleus tractus solitarii (NTS) revealed by polymerase chain reaction (PCR) and immunohistochemistry.

Expression of mRNAs encoding seven GABA(A) receptor subunits (alpha1, alpha2, alpha3, alpha5, beta2, beta3, gamma2) in the nucleus tractus solitarii (NTS) of rat medulla oblongata was examined by reverse transcription-polymerase chain reaction (RT-PCR). All subunit mRNAs, except alpha5, were clearly detected. Band densities produced by alpha1, alpha3, beta3, and gamma2 subunits were greater than those corresponding to beta2 and alpha2 transcripts. The localization of these subunits in tissue sections through NTS was examined by immunohistochemistry. The differential patterns of immunoreactivity in neuronal somata and dendrites of NTS neurons were generally in agreement with the PCR results, confirming that mRNA expression is correlated with receptor protein synthesis. At ultrastructural level, alpha1, alpha3, beta2/3, and gamma2 subunits were localized in both cytoplasmic and subsynaptic sites, the latter often apposed to GABA immunoreactive synapses. These results suggest that ionotropic receptors comprising the alpha1, alpha3, beta2/3, and gamma2 may mediate inhibitory GABA responses in the NTS.

Animals↗
PubMed2001

Clinical appraisal of Ascaris lumbricoides, with special reference to surgical complications.

Over a period of 4 years (January 1993-December 1997), 509 patients were treated for abdominal colic with or without intestinal obstruction and a history of passage of adult roundworms either in the stool or in vomitus. All patients were below the age of 10 years, the youngest 6 months old, and were treated successfully with antispasmodics and normal saline enemas. When the pain subsided, an anthelminthic drug was given. Of 209 patients admitted to the hospital, 105 responded to conservative management and 104 (50%) required surgical intervention. The procedures included squeezing out of worms, resection and anastomosis, and treatment of other pathologies like acute appendicitis, tubercular stricture of the small intenstine, etc. Five patients died in the postoperative period due to various complications. There were no deaths among those treated by conservative management. Early recognition of the condition can prevent serious surgical complications and morbidity.

Animals↗
PubMed2001

Validation of lymphatic mapping in colorectal cancer: in vivo, ex vivo, and laparoscopic techniques.

BACKGROUND: The use of lymphatic mapping (LM) is being investigated to improve the staging of colorectal cancer (CRC) and thereby identify patients who might benefit from adjuvant chemotherapy. This study evaluated in vivo, laparoscopic, and ex vivo approaches for the ultrastaging of CRC. METHODS: Seventy-five CRC patients were enrolled in a study of LM with peritumoral injection of isosulfan blue dye. LM was undertaken during open colon resection (OCR) in 64 patients, during laparoscopic colon resection (LCR) in 9 patients, and after specimen removal (ex vivo) in 2 patients. Ex vivo LM was also undertaken in 6 patients after unsuccessful in vivo LM. All nodes were examined by hematoxylin and eosin (H&E) staining; in addition, sentinel lymph nodes (SNs) were multisectioned and examined by immunohistochemical staining with cytokeratin (CK-IHC). RESULTS: At least one SN was identified in 72 patients (96%). In vivo LM identified SNs in 56 of 64 (88%) patients undergoing OCR and in 9 of 9 (100%) patients undergoing LCR. Ex vivo LM was undertaken as the initial mapping procedure in 2 cases of intraperitoneal colon cancer and after in vivo LM had failed in 6 cases of extraperitoneal rectal carcinoma; an SN was identified in 7 of the 8 cases. Focused examination of the SN correctly predicted nodal status in 53 of 56 OCR cases, 9 of 9 LCR cases, and 6 of 7 ex vivo cases. Multiple sections and CK-IHC identified occult micrometastases in 13 patients (17%), representing 10 OCR, 1 LCR, and 2 ex vivo cases. CONCLUSIONS: LM of drainage from a primary CRC can be accurately performed in vivo during OCR or LCR. Ex vivo LM can be applied when in vivo techniques are unsuccessful and may be useful for rectal tumors. During LCR, colonoscopic injection can be used to mark the primary tumor and define the lymphatic drainage so that adequate resection margins are obtained. These LM techniques improve staging accuracy in CRC.

Adult↗
PubMed2001

A three-dimensional mathematical model of temporomandibular joint loading.

OBJECTIVE: A mathematical model of the temporomandibular joint was developed to study the magnitude and direction of the compressive loading experienced at the temporomandibular joint during clenching. DESIGN: The model was based on the principles of static equilibrium in three dimensions. BACKGROUND: Direct measurement of temporomandibular joint loading in humans is extremely difficult. Animal models have provided an alternative in the past. However, evidence suggests that primates are not the most accurate human analogues for temporomandibular joint studies. A mathematical model was used as an alternative to direct measurement. METHODS: The EMG activity of two masticatory muscles was combined with their cross-sectional areas to calculate the force exerted by each muscle. Experimentally determined forces were implemented into a quadratic programming model to solve for the compressive forces on the joint. Two objective functions were chosen and their ability to predict muscle and joint forces was evaluated. RESULTS: The maximum bite forces for normal men, normal women, and women with temporomandibular joint disorders were 300 N (SD 102 N), 210 N (SD 57.7 N), and 120 N (SD 77.1 N), respectively. The calculated joint force for normal males was 260 N (SD 84.1 N). Normal females and female temporomandibular joint disorder patients produced temporomandibular joint forces of 172 N (SD 37.5 N) and 152 N (SD 44.2 N), respectively.

Electromyography↗
PubMed2001

The art and science of incorporating cost effectiveness into evidence-based recommendations for clinical preventive services.

As medical technology continues to expand and the cost of using all effective clinical services exceeds available resources, decisions about health care delivery may increasingly rely on assessing the cost-effectiveness of medical services. Cost-effectiveness is particularly relevant for decisions about how to implement preventive services, because these decisions typically represent major investments in the future health of large populations. As such, decisions regarding the implementation of preventive services frequently involve, implicitly if not explicitly, consideration of costs. Cost-effectiveness analysis summarizes the expected benefits, harms, and costs of alternative strategies to improve health and has become an important tool for explicitly incorporating economic considerations into clinical decision making. Acknowledging the usefulness of this tool, the third U.S. Preventive Services Task Force (USPSTF) has initiated a process for systematically reviewing cost-effectiveness analyses as an aid in making recommendations about clinical preventive services. In this paper, we provide an overview and examples of roles for using cost-effectiveness analyses to inform preventive services recommendations, discuss limitations of cost-effectiveness data in shaping evidence-based preventive health care policies, outline the USPSTF approach to using cost-effectiveness analyses, and discuss the methods the USPSTF is developing to assess the quality and results of cost-effectiveness studies. While this paper focuses on clinical preventive services (i.e., screening, counseling, immunizations, and chemoprevention), the framework we have developed should be broadly portable to other health care services.

Advisory Committees↗
PubMed2001

Solution structure of the LDL receptor EGF-AB pair: a paradigm for the assembly of tandem calcium binding EGF domains.

BACKGROUND: From the observed structure and sequence of a pair of calcium binding (cb) epidermal growth factor-like (EGF) domains from human fibrillin-1, we proposed that many tandem cbEGF domains adopt a conserved relative conformation. The low-density lipoprotein receptor (LDLR), which is functionally unrelated to fibrillin-1, contains a single pair of EGF domains that was chosen for study in the validation of this hypothesis. The LDLR is the protein that is defective in familial hypercholesterolaemia, a common genetic disorder that predisposes individuals to cardiovascular complications and premature death. RESULTS: Here, we present the solution structure of the first two EGF domains from the LDL receptor, determined using conventional NMR restraints and residual dipolar couplings. The cbEGF domains have an elongated, rod-like arrangement, as predicted. The new structure allows a detailed assessment of the consequences of mutations associated with familial hypercholesterolaemia to be made. CONCLUSIONS: The validation of the conserved arrangement of EGF domains in functionally distinct proteins has important implications for structural genomics, since multiple tandem cbEGF pairs have been identified in many essential proteins that are implicated in human disease. Our results provide the means to use homology modeling to probe structure-function relationships in this diverse family of proteins and may hold the potential for the design of novel diagnostics and therapies in the future.

Amino Acid Sequence↗
PubMed2001

Coronary artery bypass grafting in Native Americans: a higher risk of death compared to other ethnic groups?

BACKGROUND: While the efficacy and safety of coronary artery bypass grafting (CABG) has been established in several clinical trials, little is known about its outcomes in Native Americans. MEASUREMENTS AND MAIN RESULTS: We assessed clinical outcomes associated with CABG in 155 Native Americans using a national database of 18,061 patients from 25 nongovernmental, not-for-profit U.S. health care facilities. Patients were classified into five groups: 1) Native American, 2) white, 3) African American, 4) Hispanic, and 5) Asian. We evaluated for ethnic differences in in-hospital mortality and length of stay, and after adjusting for age, gender, surgical priority, case-mix severity, insurance status, and facility characteristics (volume, location, and teaching status). Overall, we found the adjusted risk for in-hospital death to be higher in Native Americans when compared to whites (odds ratio [OR], 3.8; 95% confidence interval [CI], 1.5 to 9.8), African Americans (OR, 3.4; 95% CI, 1.1 to 9.9), Hispanics (OR, 7.1; 95% CI, 2.5 to 20.3), and Asians (OR, 2.8; 95% CI, 1.1 to 7.0). No significant differences were found in length of stay after adjustment across ethnic groups. CONCLUSIONS: The risk of in-hospital death following CABG may be higher in Native Americans than in other ethnic groups. Given the small number of Native Americans in the database (n = 155), however, further research will be needed to confirm these findings.

Black or African American↗
PubMed2001

Stenting for localised arterial stenoses in the aorto-iliac segment.

OBJECTIVE: to determine complications and patency following angioplasty (PTA) and stenting of aorto-iliac stenoses. SETTING: District General Hospital in U.K. DESIGN: prospective observational study. PATIENTS AND METHODS: between December 1994 and June 2000, 50 patients (38 men), median age 64 (41-89) years underwent aorto-iliac stenting. A total of 61 stents were placed. Indications were intermittent claudication in 38 and rest pain, ulceration or gangrene in 12. Sites stented were aorta 11, common iliac artery 32, external iliac artery 14, common and external iliac arteries two. Bilateral iliac procedures were carried out in nine. Two stents were used to correct residual stenoses after aortic stenting. Some 11 recurrent stenoses were treated. The other reasons for stenting were residual stenoses greater than 30% after PTA, tight calcified stenoses or when a stenosed iliac artery was being used as a donor prior to crossover or femoropopliteal bypass. RESULTS: two immediate technical failures occurred due to malposition. Residual stenoses were corrected by PTA. Two further patients sustained minor complications. None of the aortic stents occluded through two required secondary procedures. Primary-assisted patency was thus 100% at three years. Primary patency following iliac stenting for claudication and critical ischaemia were 97% and 86% at three years respectively. CONCLUSION: PTA and stenting of aorto-iliac stenoses can be safely achieved with durable results.

Adult↗
PubMed2001

The National Center for Health Statistics reference and the growth of Indian adolescent boys.

BACKGROUND: Few studies describing the growth of adolescents exist because of the difficulties in interpreting anthropometric data in this age group. OBJECTIVE: We describe the growth of adolescent boys from West Bengal, India, and assess the adequacy of using the National Center for Health Statistics (NCHS) reference data. DESIGN: A cross-sectional anthropometric survey was conducted in 818 Bengali boys from middle-class families. Anthropometric measurements were taken on each subject's birthday (+/-3 d) by use of standard measuring techniques. The NCHS reference data on height and body mass index (BMI) were used to estimate age-specific prevalences of stunting, thinness, and overweight. BMI was also assessed by using British, Dutch, and French reference data. The biological parameters of the adolescent growth spurt were estimated by using the Preece-Baines growth model. RESULTS: With use of the 5th percentile of the NCHS reference data, the prevalence of thinness was approximately 5 times (50.5%) that of stunting (11.2%). The median curves of the 3 European references lay between the Indian and NCHS samples and also yielded high prevalences of thinness when applied to the study sample. The prevalence of being at risk of overweight was low (4.2%). Mean age at peak height velocity was 13.0 y and peak height velocity was 7.0 cm/y. CONCLUSIONS: The NCHS reference data seem inadequate for this sample. Consideration should be given to developing appropriate reference data based on healthy adolescent populations from different ethnic groups. Issues of maturation-related variation in assessing growth during adolescence should be given particular attention.

Adolescent↗