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Biomedical subjects

M Sen

Publications and source records attributed to M Sen.

At least 19 recordsLinked to original sources
PubMed2005

Wnt signalling in rheumatoid arthritis.

Rheumatoid arthritis (RA) is a symmetrical polyarticular disease of unknown aetiology that affects primarily the diarthrodial joints. Characteristic features of RA pathogenesis are synovial hyperplasia and inflammation accompanied by cartilage loss and joint destruction. Synovial hyperplasia and inflammation are a consequence of an increase in the macrophage-like and fibroblast-like synoviocytes of the synovial intimal lining associated with infiltration of leucocytes into the subintimal space. Although therapeutic interventions are available, the disease persists despite therapy in a significant fraction of patients. Several lines of evidence have substantiated a crucial role of activated fibroblast-like synoviocytes (FLS) during RA pathogenesis. The hyperplastic FLS population potentially promotes leucocyte infiltration and retention. The rheumatoid synovium eventually transforms into a pannus that destroys articular cartilage and bone. There are no approved drugs that are known to target the FLS in RA, and the underlying mechanisms driving FLS activation remain unresolved. In this review, the importance of Wnt-frizzled (Fz)-mediated signalling in the autonomous activation of FLS is discussed. Anti-Wnt/anti-Fz antibodies, Fz receptor antagonists or small-molecule inhibitors of Wnt-Fz signalling might be useful for therapeutic interventions in refractory RA.

Arthritis, Rheumatoid↗
PubMed2004

Prognostic significance of EGF receptor expression in early glottic cancer.

OBJECTIVE: A positive relationship between epidermal growth factor receptor (EGFR) expression and radioresistance has been shown both in vitro and in vivo. In a group of 31 patients with early glottic cancer treated with definitive radiotherapy, the relationship of EGFR expression with patient and tumor related parameters were analyzed and the prognostic effect of EGFR expression on local control (LC) was assessed. MATERIAL AND METHOD: Between 1991 and 2001, 114 patients with early glottic (Tis-T2N0M0) squamous cell carcinoma were treated with radiotherapy at our institution. Among these, 31 patients whose pretreatment pathology specimens were available for immunohistochemical analysis formed the study population. Median age was 64 (46-77). Anterior commissure involvement was evident in 12 (38.7%) patients. Distribution according to T stage was as follows: Tis 6 (19.3%), T1 22 (71%), and T2 3 (9.7%). Histopathological grades of the 25 T1-2 tumors were 10/25 (40%) grade 1, 9/25 (36%) grade 2 and 6/25 (24%) grade 3. Our radiotherapy regimen was 66-70 Gy in 33-35 fractions over 6.5-7 weeks. The median follow-up period was 45 months (range, 5-116). Following immunohistochemical staining, quantitative immunohistochemistry (IHC) was performed by image analysis software and stained tumoral area percentage (STAP) was identified. The cut-off value was < or =5% versus >5%. The relationship of EGFR expression with patient (age) and tumor related (T stage, histopathological grade, and anterior commissure involvement) parameters was evaluated using chi-square test. Prognostic significance of EGFR expression, age, T stage, histopathological grade, and anterior commissure involvement on LC was assessed using log-rank test. RESULTS: No difference was found in EGFR content distribution in relation to age, T stage, histopathological grade, and anterior commissure involvement. In the univariate analysis including age (< or =60 versus >60), T stage (Tis and T1 versus T2), histopathological grade (grade 1 and 2 versus grade 3), anterior commissure involvement (present versus absent), and EGFR expression (high versus low), only T stage and EGFR expression were found to be significant prognostic factors affecting LC (P = 0.0006 and P = 0.03, respectively). CONCLUSION: The results of this series support that EGFR expression is an unfavorable prognostic factor in early glottic carcinomas. For this reason EGFR IHC may be considered for selecting patients for more aggressive therapies (radiotherapy with different fractionation schemes or surgery) or enrollment into trials targeting EGFR signaling pathways.

Aged↗
PubMed2004

Peripancreatic tuberculous lymphadenitis mimicking carcinoma: report of a case.

Peripancreatic tuberculous lymphadenitis is a rare clinical entity and it usually raises serious diagnostic problems. We report a case of a solitary abdominal tuberculoma. A 45-year old woman was admitted to hospital with obstructive jaundice. An exploratory laparotomy was performed. A conglomerated mass, penetrating into the pancreas was found. Since exact diagnosis could not be obtained by peroperative frozen sections, standard Whipple procedure, segmental portal vein resection and reconstruction with autogenous saphenous vein were performed. Histopathological examination of the resected specimen revealed tuberculous lymphadenitis. The patient was given an anti-tuberculous treatment and a good response was noted. Abdominal tuberculoma is often mistaken for a malignant neoplasm and a high grade of suspicion is neccessary in order to make the exact diagnosis and optimal medical treatment of this entity.

Diagnosis, Differential↗
PubMed2004

Isolated hepatic tuberculous pseudometastasis co-existent with adenocarcinoma of the stomach; report of a case.

A 10 x 9 mm metastasis-like lesion in segment V of the liver was detected, when a 70-year-old man was operated on for adenocarcinoma of the stomach. Since exact diagnosis of the hepatic lesion could not be made by frozen sections, the lesion was excised, considering it to be a metastasis of gastric adenocarcinoma. Bacteriologic and pathologic studies established a diagnosis of isolated tuberculosis of the liver. A good response to antituberculous drug therapy was noted.

Adenocarcinoma↗
PubMed2004

Our sigmoid colon volvulus experience and benefits of colonoscope in detortion process.

BACKGROUND/AIMS: The sigmoid colon is the most frequent site for a volvulus. In this report, we review our experience with sigmoid colon volvulus. METHODOLOGY: We present our experience of 81 cases of sigmoid volvulus admitted to our department. RESULTS: Preoperative endoscopic volvulus detortion was attempted in all patients, and in 39 of them the procedure was successful. The success rate of endoscopic detortion for sigmoid colon volvulus with a flexible colonoscope (60%) was higher than with a rigid rectosigmoidoscope (42%). In 19 of these 39 non-operatively devolvulated patients, sigmoid resection with primary anastomosis was performed within 7-10 days after reduction, but 20 patients did not accept the elective operation after a non-operative treatment. Among the 61 patients undergoing urgent or elective operation for sigmoid volvulus, there were 17 laparotomies with only detortion, 19 resections with elective anastomosis, 6 resections with primary anastomosis, and 19 resections with a Hartmann's pouch. There were 9 deaths (21%) among 42 patients who underwent an emergency operation, and one (5.2%) among the 19 patients who had elective surgery died because of a cerebral embolus. CONCLUSIONS: Initial therapy with endoscopy affords decompression and an adequate preparation of patients for surgical resection, and a flexible colonoscope has notable advantages over rigid instruments for the detortion process.

Adult↗
PubMed2003

The microbiological quality of washing-up water and the environment in domestic and commercial kitchens.

AIMS: To determine the microbiological quality of washing-up water and the environment in domestic and commercial kitchens. METHODS AND RESULTS: Chicken meals were prepared by people without food safety training in their own kitchen (n = 52) or by trained staff in a commercial kitchen (n = 10). Study participants then washed-up, cleaned the kitchen and completed a food hygiene questionnaire. The temperature and microbiological quality of the washing-up water, and the presence of pathogens in dishcloths, tea towels and other kitchen samples was determined. Of the raw chickens used in meal preparation, 96 and 13% were naturally contaminated with Campylobacter or Salmonella spp., respectively. In domestic kitchens, two of 45 sponges, dishcloths or scourers and one of 32 hand- or tea towels were contaminated with Campylobacter after washing-up and cleaning but none of the tap or sink swabs yielded pathogens. The mean washing-up water temperature in the domestic kitchens was 40.7 degrees C, whereas in the commercial kitchen it was 44.7 degrees C (P = 0.04). Study participants who used hotter water (>/=40 degrees C) had lower levels of bacteria in their washing-up water. The aerobic plate counts of the washing-up water samples in domestic homes were usually between 105 and 106 CFU ml-1 but those associated with the commercial kitchen were consistently lower (P = 0.01). Despite this, Campylobacter was detected in one of 10 washing-up water samples from the commercial kitchen but in none of the samples from domestic kitchens. CONCLUSIONS: Pathogenic microorganisms can be recovered relatively frequently from the kitchen environment. SIGNIFICANCE AND IMPACT OF STUDY: By identifying factors that affect the number of microorganisms in washing-up water and the kitchen environment, evidence-based recommendations on implementing domestic food hygiene can be made.

Animals↗
PubMed2001

Controlled release of antifungal drug terbinafine hydrochloride from poly(N-vinyl 2-pyrrolidone/itaconic acid) hydrogels.

Adsorption and controlled release of terbinafine hydrochloride (TER-HCl) to and from pH-sensitive poly(N-vinyl 2-pyrrolidone/itaconic acid) P(VP/IA) hydrogels were investigated. P(VP/IA) hydrogels were prepared by irradiating the ternary monomer mixtures of N-vinyl 2-pyrrolidone/itaconic acid/ethylene glycol dimethacrylate in aqueous solution by gamma-rays at ambient temperature. Hydrogels containing antifungal drug TER-HCl, at different drug-to-polymer ratios, were prepared by direct adsorption method. The influence of IA content in the gel on the adsorption capacities of hydrogels and the effect of pH on the releasing behavior of TER-HCl from the gel matrix were investigated. Terbinafine adsorption capacity of hydrogels was found to increase from 6 to 82 mg of TER-HCl per gram of dry gel with increasing drug concentration and amount of IA in the gel system. In-vitro drug-release studies in different buffer solutions showed that the basic parameters affecting the drug-release behavior of hydrogels are the pH of the solution and the IA content of the hydrogel.

Algorithms↗
PubMed2001

Blockade of Wnt-5A/frizzled 5 signaling inhibits rheumatoid synoviocyte activation.

OBJECTIVE: It is not understood why cultured fibroblast-like synoviocytes (FLS) from patients with rheumatoid arthritis (RA) often display a persistently activated phenotype, despite removal from an inflammatory environment. Previously, we found that these FLS expressed high levels of both Wnt-5A and Frizzled 5 (Fz5), a receptor-ligand pair implicated in both limb bud and bone marrow stem cell development. The objective of the present experiments was to determine whether Wnt-5A/FzS signaling contributes to FLS activation. METHODS: Wnt-5A expression in FLS was inhibited by transfection with both antisense and dominant negative (dn) vectors. Fz5 signaling was blocked with an antibody to the extracellular domain of the receptor. The effects of these treatments on the expression of the proinflammatory cytokines interleukin-6 (IL-6) and IL-15 and on the expression of receptor activator of nuclear factor kappaB ligand (RANKL) were assessed by reverse transcriptase-polymerase chain reaction and immunoblotting. RESULTS: Both antisense Wnt-5A and dnWnt-5A vectors, but not empty vector, diminished IL-6 and IL-15 expression in RA FLS. Anti-Fz5 antibody exerted similar effects and also reduced RANKL expression. CONCLUSION: Wnt-5A/Fz5 signaling may contribute to the activated state of FLS in RA. Receptor antagonists of Fz5 should be considered for the treatment of refractory synovitis.

Antibodies, Blocking↗
PubMed2001

Optimization in high dose rate brachytherapy for utero-vaginal applications.

BACKGROUND AND PURPOSE: High dose rate (HDR) remote afterloading intracavitary brachytherapy is an effective treatment modality which has some advantages over low dose rate (LDR) techniques for gynaecological cancer. Optimization is one of the possibilities of modern brachytherapy techniques, especially the stepping source technology. The use of the term 'optimization' implies achieving the desired optimum dose distribution by changing some parameters of the treatment. The aim of this study was to theoretically evaluate the optimization possibilities by modifying dwell times and dwell positions of the uterine and vaginal sources. MATERIALS AND METHODS: Working on a virtual utero-vaginal model, the dose distribution variations in the rectum, bladder, mean point B reference points and volume parameters were investigated whilst giving a standard dose to point A in the Manchester system. In this model, the intrauterine tandem consisted of 27 dwell positions for 2.5 mm steps and 14 dwell positions for 5 mm steps. Vaginal colpostats consisted of five dwell positions each for 2.5 mm steps. Using a Nucletron Plato treatment planning system and a Microselectron Ir-192 HDR stepping source unit, the dwell times of the intrauterine (T(u)) and vaginal sources (T(v)) were modified at the ratios of (T(u)/T(v)) 1:1; 1:2; 1:3; 1:4; 1:0.50; 1:0.33; and 1:0.25 for the two different dwell positions, 2.5 and 5 mm steps, of the intrauterine tandem. RESULTS: All evaluated parameters decreased with increasing dwell time ratios of uterine tandem to vaginal colpostats, with the greatest fall in the percentage of rectum reference dose (D(R) %), 23 and 28% for 2.5 and 5 mm dwell positions respectively; in addition, the reference isodose volume decreased by 14 and 17% for 2.5 and 5 mm dwell positions, respectively. All evaluated parameters increased with decreasing dwell time ratios of uterine tandem to vaginal colpostats for both dwell positions. The DR% of 1:1-1:4 (T(u)/T(v)) weightings showed an increase from 40.6 to 58.3 (44%) for 2.5 mm and from 49.2 to 67.5 (37%) for 5 mm dwell positions. The volume was increased by 27 and 37% for 2.5 and 5 mm dwell positions respectively. CONCLUSION: Modern brachytherapy techniques enable the individualization of treatments by optimization procedures in gynaecological brachytherapy applications. By altering the dwell time and position, some important changes in reference points, volume and treatment time can be achieved, whilst maintaining a standard dose to point A.

Brachytherapy↗
PubMed2001

Serum zinc levels and zinc binding capacity in thalassemia.

Recently, it has been reported that serum zinc binding capacity (ZnBC) is a very important criterion to evaluate body zinc (Zn) status. It has been shown that chronic Zn deficiency occur in the patients with thalassemia major (TM). Zn deficiency in TM may cause hyperzincuria, high ferritin levels, hepatic iron load, hepatic dysfunction. This study was undertaken to determine serum Zn levels and ZnBC in different thalassemia forms and sickle cell disease (SCD). The study has been carried out on 30 Thalassemia Major (TM), 34 Thalassemia Intermedia (TI), 31 Thalassemia Trait (TT) and 10 SCD. As control group,13 healthy children and 20 adults were included. Serum Zn and ZnBC were determined by atomic absorption, then saturation index (SI%: serum Zn/ZnBC x 100) was calculated. Serum Zn levels in all patients were lower than control (p < 0.01). Serum ZnBC was at a normal level in patients with TT and TI but it was found to be lower in TM and SCD than control (p < 0.01). While serum Zn levels decrease and ZnBC increase in nutritionaL Zn deficiency, serum Zn levels decrease but ZnBC doesn't increase in patients with thalassemia.

Adolescent↗
PubMed2001

Nutritional quality of sesame seed protein fraction extracted with isopropanol.

The nutritional effect of diet containing decorticated sesame seed extracted with isopropanol (DSS-Iso) was evaluated on growth performance, food efficiency ratio, plasma and tissue lipid profile, plasma protein content, and erythrocyte membrane lipid profile of rats on a comparative basis with diets containing casein (control), soybean meal, and decorticated sesame seed extracted with hexane (DSS-Hex). Rats fed a DSS-Iso-based diet showed body weight gain and food efficiency ratio similar to those of the control groups fed diets prepared with casein, soybean meal, and DSS-Hex. However, dietary proteins exerted a separate effect on plasma lipid concentrations of the rats. Rats fed a DSS-Iso-based diet showed significant decreases in plasma total cholesterol (p < 0.01), triglyceride (p < 0.01), and VLDL+LDL cholesterol (p < 0.01) concentrations in comparison to the rats fed diet containing casein. No significant differences in plasma lipid concentrations were observed for the rats fed diets prepared with soybean meal, DSS-Hex, and DSS-Iso. Rats fed the different dietary proteins did not show much variation in plasma proteins, liver lipids, and erythrocyte membrane lipid concentrations, which suggests that DSS-Iso could be a suitable edible protein like casein or soybean meal.

2-Propanol↗
PubMed2001

Use of anti-CD3 x anti-HER2/neu bispecific antibody for redirecting cytotoxicity of activated T cells toward HER2/neu+ tumors.

Relapse after adjuvant chemotherapy or high-dose chemotherapy with stem cell transplant for high-risk breast cancer remains high and new strategies that provide additional antitumor effects are needed. This report describes methods to generate highly effective HER2/neu-specific cytotoxic T cells by arming activated T cells with anti-CD3 x anti-HER2/neu bispecific antibody (BsAb). OKT3 and 9184 (anti-HER2) monoclonal antibodies (mAb) were conjugated and used to arm T cells that were subsequently tested in binding, cytotoxicity, and cytokine secretion assays. Armed T cells aggregated and specifically killed HER2/neu(+) breast cancer cells. Cytotoxicity emerged after 6 days of culture, was higher in armed T cells than unarmed T cells at all effector to target ratios (E/T) tested, and increased as the arming dose was increased. At an E/T of 20:1, the mean cytotoxicity of armed activated T cells (ATC) from 10 normal subjects increased by 59 +/- 11% (+/-SD) over that seen in unarmed ATC (p < 0.001) and the mean cytotoxicity of armed ATC from 6 cancer patients increased by 32 +/- 9% above that seen for unarmed ATC (p < 0.0004). After arming, the BsAb persisted on ATC up to 72 h and armed ATC continued to be cytotoxic up to 54 h. The amount of interferon-gamma (IFN-gamma), tumor necrosis factor-alpha (TNF-alpha), and granulocyte-macrophage colony-stimulating factor (GM-CSF) secreted was 1699, 922, and 3092 pg/ml/10(6) cells per 24 h, respectively, when armed T cells were exposed to a HER2/neu(+) breast carcinoma cell line. These studies show the feasibility and clinical adaptability of this approach for generating large numbers of anti-HER2-specific, cytotoxic T cells for clinical trials.

Antibodies, Bispecific↗
PubMed2001

Activated T-cell and bispecific antibody immunotherapy for high-risk breast cancer. Bench to bedside.

Nontoxic approaches are needed to improve overall survival (OS) and progression-free survival (PFS) for high-risk breast cancer. Combination immunotherapy (IT) consisting of activated T cells (ATC), interleukin-2 (IL-2), and CTL (GM-CSF) was given after peripheral blood stem cell transplant (PBSCT). There were no major toxicities and there appear to be improvements in OS and PFS over historical controls. In order to develop specific cytotoxic T lymphocytes (CTL), we combined ATC with the use of bispecific antibody (BiAb). By arming ATC with anti-CD3 x anti-HER2/neu BiAb (HER2BiAb), the approach converts nonspecific ATC into HER2/neu (HER2) specific CTL. ATC remain armed, kill tumor targets for days, and produce cytokines after binding to tumor. Arming ATC with BiAbs may prove to be effective for targeting a variety of tumors with and without high-dose chemotherapy.

Antibodies, Bispecific↗
PubMed2001

The role of palliative radiotherapy in locally advanced non-small cell lung cancer.

The aim of this study was to evaluate retrospectively the treatment results of non-small cell lung cancer (NSCLC) patients treated with palliative intent in Dokuz Eylul University Hospital, Radiation Oncology Department. One hundred and fifteen inoperable, non-metastatic and symptomatic NSCLC patients were treated with palliative radiotherapy (PRT) between July 1991 and May 2000. PRT was used in patients with low performance status, weight loss more than 10% within last 6 months, secondary malignancies, co-morbid diseases and socio-economic problems. Parallelly opposed isocentric antero-posterior fields including both the parenchymal and mediastinal masses were used. 10-55 Gy total doses were delivered in 1-23 fractions with a median of 30 Gy. Nineteen patients received systemic chemotherapy before PRT. Survival analysis was made from the treatment beginning date, and subjective palliation rates were assessed according to clinical improvements in symptomatology evaluated 1-6 weeks after PRT. The median follow-up time was 28 weeks (1-234 weeks). Totally, 245 disease-related symptoms were detected in 115 patients. Overall "improvement" in symptomatology was found to be 90% (221/245) with a "near-total response" rate of 46% (113/245). Hemoptysis was the best palliated symptom. Median survival time was 30 weeks. Karnofsky performance status (KPS) (p=0.015), weight loss (p=0.0015), histologic tumor type (p=0.0024) and tumor size (p=0.02) were found to effect overall survival rates significantly in uni-variant analysis. Multi-variant analysis revealed statistically significant effect with histological tumor type and weight loss status. Only 16% of patients (3/19) showed partial and 5% (1/19) complete response to systemic treatment. Median survival time was 46 weeks in this group. In conclusion, this retrospective study of patients with poor prognostic factors confirms that PRT is an effective treatment modality in symptomatic locally advanced NSCLC patients resulting in 90% symptomatic improvement rate and a median survival of 30 weeks.

Adult↗
PubMed2000

A methylthioadenosine phosphorylase (MTAP) fusion transcript identifies a new gene on chromosome 9p21 that is frequently deleted in cancer.

Homozygous deletions of human chromosome 9p21 occur frequently in malignant cell lines, and are also common in primary gliomas, lung cancers, and leukemias. Moving from the centromere to the telomere, this complex region encodes the tumor suppressor genes p15INK4B (CDKN2B), p14ARF, p16INK4A (CDKN2A), and the housekeeping gene methylthioadenosine phosphorylase (MTAP). However, not all chromosome 9p21 deletions in tumors include these tumor suppressor genes. Here we describe the partial sequence and the exact localization of a new gene on chromosome 9p21 centromeric of p15INK4B, that formed an in frame fusion transcript with MTAP in a glioma xenograft, and that is homozygously deleted in various malignant cell lines. Northern blot revealed corresponding 1.5 kb transcript in non-deleted cell lines as well as in normal lymphocytes. Using a RNA master blot membrane including 50 different tissues, we could show that this new transcript is expressed in all tissues of the adult but not or only at very low levels in most of the fetal tissues tested. The expression pattern is similar to that of p16INK4A. The localization as well as the deletion pattern makes this transcript a candidate for a new tumor suppressor gene.

Adult↗
PubMed2000

Controlled release of terbinafine hydrochloride from pH sensitive poly(acrylamide/maleic acid) hydrogels.

Adsorption and controlled release of terbinafine hydrochloride (TER-HCl) to and from pH sensitive poly(acrylamide/maleic acid) (P(AAm/MA)) hydrogels were investigated. P(AAm/MA) hydrogels were prepared by irradiating the ternary mixtures of AAm/MA/and water by gamma-rays at ambient temperature. Antifungal drug, TER-HCl containing hydrogels, at different drug to polymer ratios, was prepared by direct adsorption method. The influence of MA content in the gel on the adsorption capacities of hydrogel and the effect of pH on the releasing behavior of TER-HCl from gel matrix were investigated. Terbinafine adsorption capacity of hydrogels are found to increase from 2 to 38 mg TER-HCl per g dry gel with increasing amount of MA in the gel system. In vitro drug release studies in different buffer solutions show that the basic parameters affecting the drug release behavior of hydrogel are the pH of the solution and MA content of hydrogel.

Acrylic Resins↗
PubMed2000

Expression and function of wingless and frizzled homologs in rheumatoid arthritis.

Rheumatoid arthritis (RA) is accompanied by synovial inflammation, proliferation, and cartilage destruction. The reasons the activation of synovial fibroblasts often persists despite antiinflammatory therapy are not known. One possibility is that the synovial membrane becomes gradually repopulated with immature mesenchymal and bone marrow cells with altered properties. To explore this hypothesis, we have investigated the expression in RA synovial tissues of various embryonic growth factors from the wingless (wnt) and frizzled (fz) families, which have been implicated in cell-fate determination in both bone marrow progenitors and limb-bud mesenchyme. Reverse transcriptase-PCR analysis revealed expression of five wnt (wnt1, 5a, 10b, 11, and 13) and three fz (fz2, 5, and 7) isoforms in RA synovial tissues. Osteoarthritis synovial tissues expressed much less wnt5a and fz5. Northern blotting confirmed the overexpression of wnt5a and fz5 in RA synovial tissues, in comparison to a panel of normal adult tissues. Compared with normal synovial fibroblasts, cultured RA fibroblast-like synoviocytes expressed higher levels of IL-6, IL-8, and IL-15. Transfection of normal fibroblasts with a wnt5a expression vector reproduced this pattern of cytokine expression and stimulated IL-15 secretion. These results suggest that the unusual phenotypic properties of RA fibroblasts may be attributable partly to their replacement with primitive fibroblast-like synoviocytes with characteristics of immature bone marrow and mesenchymal cells. Clear delineation of the signaling pathway(s) initiated by the wnt5a/fz5 ligand-receptor pair in the RA synovium may yield new targets for therapeutic intervention.

Arthritis, Rheumatoid↗