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S Kumar

Publications and source records attributed to S Kumar.

At least 901 records · Page 50Linked to original sources
PubMed1998

Geometrical and sequence characteristics of alpha-helices in globular proteins.

Understanding the sequence-structure relationships in globular proteins is important for reliable protein structure prediction and de novo design. Using a database of 1131 alpha-helices with nonidentical sequences from 205 nonhomologous globular protein chains, we have analyzed structural and sequence characteristics of alpha-helices. We find that geometries of more than 99% of all the alpha-helices can be simply characterised as being linear, curved, or kinked. Only a small number of alpha-helices ( approximately 4%) show sharp localized bends in their middle regions, and thus are classified as kinked. Approximately three-fourths (approximately 73%) of the alpha-helices in globular proteins show varying degrees of smooth curvature, with a mean radius of curvature of 65 +/- 33 A; longer helices are less curved. Computation of helix accessibility to the solvent indicates that nearly two-thirds of the helices ( approximately 66%) are largely buried in the protein core, and the length and geometry of the helices are not correlated with their location in the protein globule. However, the amino acid compositions and propensities of individual amino acids to occur in alpha-helices vary with their location in the protein globule, their geometries, and their lengths. In particular, Gln, Glu, Lys, and Arg are found more often in helices near the surface of globular proteins. Interestingly, kinks often seem to occur in regions where amino acids with low helix propensities (e.g., beta-branched and aromatic residues) cluster together, in addition to those associated with the occurrence of proline residues. Hence the propensities of individual amino acids to occur in a given secondary structure depend not only on conformation but also on its length, geometry, and location in the protein globule.

Amino Acid Sequence↗
PubMed1998

Effects of chocolate cyst fluid on endometrioma cell growth in culture.

OBJECTIVE: To evaluate the effect of chocolate cyst fluid on the proliferation of cultured human endometrioma cells and to assay the concentration of transforming growth factor-B1 in this fluid. DESIGN: Controlled in vitro study. SETTING: Department of Obstetrics and Gynecology, State University of New York Health Science Center. PATIENT(S): Five women with ovarian endometriomas. INTERVENTION(S): Endometrioma tissue and chocolate fluid from five different patients were entered in this study. MAIN OUTCOME MEASURE(S): Endometrioma cell proliferation in culture with and without chocolate cyst fluid. RESULT(S): Chocolate cyst fluid increased the proliferation of endometrioma cells compared with controls. Also, high concentrations of transforming growth factor-B1 were found in cysts' fluid. CONCLUSIONS: Chocolate cyst fluid has a growth-enhancing effect on endometrioma cells. One promoting growth factor is transforming growth factor-B1.

Cell Count↗
PubMed1998

Awareness of diagnosis and psychiatric morbidity among cancer patients--a study from South India.

Awareness regarding cancer diagnosis and its relationship to psychiatric morbidity was studied in 294 newly admitted cancer patients at an oncology center in South India. Fifty-four percent of patients were aware that they had cancer and were able to discuss their diagnosis; 46% of patients reported nonawareness of diagnosis. Discriminant function analysis revealed that oral cancers and relatives' awareness of the cancer was more prevalent in the group aware of diagnosis. More patients in the "unaware" group refused treatment for psychological distress. There was no difference between the two groups in patterns and prevalence of psychiatric morbidity. The study emphasizes the complexities in assessing awareness in cancer patients and a need to study its various components and relationship to psychological distress.

Adaptation, Psychological↗
PubMed1998

Subcutaneous panniculitic T-cell lymphoma is a tumor of cytotoxic T lymphocytes.

Subcutaneous panniculitic T cell lymphoma (SCPTCL) is characterized by primary involvement of the subcutaneous fat in a manner mimicking panniculitis. We studied 16 cases of this lymphoma to define its immunophenotypical profile as well as cellular origin. Involvement of the subcutaneous fat in a lacelike pattern with neoplastic cells rimming individual fat spaces was present in all cases. All 16 cases were of T cell phenotype. Thirteen of the 16 cases were CD8+, whereas three were negative for both CD4 and CD8. Twelve cases were stained for betaF1; of these, eight were betaF1+ and four were betaF1-. Focal staining for CD56 and CD30 was seen in 2 of 13 and two of eight cases, respectively. Intense diffuse positivity for the cytotoxic granular proteins T cell intracellular antigen-1 (TIA-1) and perforin was present in all cases, indicating an origin from cytotoxic T lymphocytes. Ten cases studied for Epstein-Barr viral sequences were negative. Eight of 9 cases with amplifiable DNA showed a clonal TCR gamma gene rearrangement by polymerase chain reaction. Controls included seven cases of benign panniculitis and seven other peripheral T cell lymphomas involving the skin and subcutaneous tissues: two peripheral T cell lymphomas, not otherwise specified (PTL,NOS), four anaplastic large cell lymphomas (ALCL), one T/NK cell lymphoma. The seven cases of panniculitis lacked cytological atypia and were characterized by an admixture of CD4+ and CD8+ cells with interspersed aggregates of L26+ B cells. Only infrequent cells showed staining for TIA-1 and perforin. In the control cases of T cell lymphoma, the infiltrate had a tendency for dermal and sometimes even epidermal involvement, with sheeting out of malignant cells, in contrast to the characteristic subcutaneous localization and rimming of fat spaces noted in SCPTCL. The two PTL, NOS were CD4+ and negative for both TIA-1 and perforin. Although the remaining controls expressed TIA-1 and perforin, in keeping with their cytotoxic T or natural killer (NK) cell origin, histological and other immunophenotypical features allowed distinction from SCPTCL. Five cases of SCPTCL were also stained for apoptosis using a tdt-mediated end labeling kit. All cases showed numerous positive apoptotic bodies, suggesting apoptosis as the mechanism of cell death in these tumors. Our study indicates that SCPTCL constitutes a distinctive clinicopathological entity derived from cytotoxic T lymphocytes and should be differentiated from other benign and malignant lymphoid infiltrates involving the subcutis. The apoptosis seen in these tumors may be mediated by release of cytotoxic granular proteins.

Adult↗
PubMed1998

Partial nephrectomy: alternative treatment for selected patients with renal cell carcinoma.

OBJECTIVES: To analyze the experience and the results of partial nephrectomy in a single institution over the last 10 years in order to optimize patient selection and minimize morbidity. METHODS: This is a retrospective chart review of 64 patients (mean age 56.6 years, range 18 to 88; 43 men, 21 women) who underwent 66 partial nephrectomies at the Brigham and Women's Hospital between 1987 and 1997. Preoperatively, 62% of the patients had no symptoms, whereas 38% had pain and/or hematuria. The indications were elective in 23 patients, solitary kidney in 28 (14 with bilateral asynchronous tumor), bilateral synchronous tumor in 7, von Hippel-Lindau disease with normal contralateral kidney in 3, lymphoma in 3, and other indications in 2 patients. Surgery was performed for solid or indeterminate renal mass suspected of being renal cell carcinoma in 58 patients. RESULTS: The most common final pathologic diagnosis was renal cell carcinoma in 47 procedures. One or more complications occurred after 18 procedures (15 with solitary kidney and 3 in patients with normal contralateral kidney) or 27% of the patients. The most common complication was an increased creatinine level (two times the baseline), occurring in 10 procedures (15.1%). Transfusion was necessary in 37 of 66 procedures (56%), and the mean blood loss was 836 cc (range 100 to 3200). Regarding renal function, 85% of the patients had a minimal increase in creatinine of less than 0.5 mg/dL after surgery (all patients with a normal contralateral kidney are in this group); 3 patients required either temporary (n = 1) or permanent (n = 2) dialysis. Other complications are also described. The mean length of stay among 65 patients was 6.5 days (range 3 to 14). The differences between length of stay, blood loss, and tumor size were statistically significant between the solitary kidney group and the elective indications group (P < 0.001). CONCLUSIONS: Nephron sparing surgery is feasible and relatively safe in patients with a normal contralateral kidney. Awareness of potential complications should aid in the selection of appropriate patients for this procedure.

Adolescent↗
PubMed1998

Relationship of elevated urinary albumin excretion to components of the metabolic syndrome in non-insulin-dependent diabetes mellitus.

Microalbuminuria is associated with increased morbidity and early mortality in non-insulin-dependent diabetes mellitus (NIDDM), mostly due to cardiovascular disease. This association may be due to a higher prevalence of known cardiovascular risk factors in those with microalbuminuria. We examined the relationship of microalbuminuria to components of the metabolic syndrome in 98 NIDDM patients with elevated urinary albumin excretion rate (UAER) (> 10.5 micrograms/min) (high UAER) and 102 normoalbuminuric NIDDM patients. Patients with high UAER were older than normoalbuminuric patients (P < 0.05), but they did not differ with respect to duration of diabetes, total cholesterol, body mass index (BMI) or the prevalence of smoking. A total of 58 (60%) patients with elevated UAER had two or more of hypertension, ischaemic heart disease (IHD), hypertriglyceridaemia and obesity compared with 41 (40%) in the normoalbuminuric group, (P < 0.05). Only nine (9.2%) high UAER patients had none of the above risk factors compared with 26 (25.5%) in the normoalbuminuric group (P < 0.01). The prevalence of hypertension (blood pressure (BP) > 160/95) was significantly higher in high UAER patients; 61/98 (62%) versus 39/102 (38%) in normoalbuminuric group, (P < 0.05). Elevated UAER was also associated with a higher risk of macrovascular disease (P < 0.01). The high UAER group included 50 Caucasian, 30 Asian and 18 Afro-Caribbean. The three groups did not differ with respect to total cholesterol, glycosylated haemoglobin (HbA1c) or prevalence of smoking. Asians had a lower BMI, a lower BP and a lower prevalence of peripheral vascular disease (PVD), but had a higher serum triglyceride (P < 0.01 for all) compared with Caucasian. Patients of Afro-Caribbean origin had a lower prevalence of IHD (0%) compared with both Asians (16%) and Caucasians (22%). Elevated UAER in NIDDM is closely associated with components of the metabolic syndrome and an increased risk of IHD and PVD. There are however, significant ethnic differences in this association.

Age Factors↗
PubMed1998

Prevention of cyclophosphamide-induced micronucleus formation in mouse bone marrow by indole-3-carbinol.

Indole-3-carbinol (I3C) is a glucobrassicin derivative isolated from cruciferous vegetables. In this study, the protective effect of 13C is reported against cyclophosphamide (CP)-induced micronuclei formation in mouse bone marrow cells. The three test doses, namely 500, 250 and 125 mg/kg body weight of 13C provided protection when given 48 hr prior to the single ip administration of cyclophosphamide (50 mg/kg). The efficacy of the test doses of 13C was also evaluated using a lower dose of CP (25 mg/kg body weight). A significant inhibition in micronuclei formation was noticed with 13C at 250 and 125 mg/kg body weight dose. 13C could not induce micronuclei formation at the test doses 500 and 250 mg/kg body weight. 13C, therefore seems to have a preventive potential against CP-induced micronuclei formation in Swiss mouse bone marrow cells.

Animals↗
PubMed1998

A non-randomized comparison of two radiotherapy protocols in inoperable squamous cell carcinoma of the oesophagus.

We report an audit of two different telebrachytherapy schedules in inoperable carcinoma of the oesophagus. Between October 1990 and December 1996, 108 patients with a Karnofsky performance status > or = 50 were selected from our database on the basis of intention to treat by telebrachytherapy. Teletherapy in the low dose group L (55 patients) consisted of 35 Gy in 15 fractions over 3 weeks, while that in the high dose group H (53 patients) consisted of 50 Gy in 25 fractions over 5 weeks. The choice of teletherapy dose was based on physician preference. The high dose rate intraluminal radiotherapy that followed 2 weeks later was identical in both groups and consisted of two applications of 6 Gy, a week apart. The pretreatment disease characteristics of the patients in both arms were similar. Relief of dysphagia was obtained in 49% of the patients in group L and in 75% of those in group H (chi2: P = 0.004). The median dysphagia-free interval was 0 and 7 months in groups L and H respectively (log-rank: P = 0.06), while the median overall survival was identical at 8 months (log-rank: P = 0.21) for both groups. The probability of survival at 1, 2 and 5 years was 34.8% versus 35.8%, 14.5% versus 13.9% and 0% versus 10% for groups L and H respectively. Morbidity in the form of ulcers, strictures and fistulae were observed in 9%, 7% and 5% of patients in group L compared with 8%, 8% and 13% in groups H respectively. This audit suggests that the protocol used in group H, when compared with group L, results in a greater proportion of patients being rendered dysphagia free, with a statistical trend towards a greater sustainment of dysphagia relief on follow-up.

Aged↗
PubMed1998

Partial transmission block for optimization of anterior supraclavicular-posterior axillary boost in the radiation therapy of carcinoma breast.

Radiation therapy of breast often involves an anterior supraclavicular-axillary (SC-AX) portal to irradiate the supraclavicular and axillary contents. However, the fall-off of the dose in this region leads to an inhomogeneity that could result either during the use of a single anterior SC-AX field or even with the concomitant use of a posterior axillary boost. An attempt has been made to circumvent this inhomogeneity by the use of a partial transmission block that could be placed in the anterior SC-AX portal corresponding to the posterior axillary boost field. The details of the quantum of partial transmission block to be used for different axillary separations and the reference depths of the dose prescription has been evaluated and presented.

Axilla↗
PubMed1998

Electromyographic response of the trunk muscles to postural perturbation in sitting subjects.

Electromyographic (EMG) patterns of the trunk muscles were investigated during balance perturbations in a sitting position. Five healthy subjects (two females and three males, mean age 24.4 yr) were seated on a platform allowing rotational perturbations in the frontal and sagittal planes. Each of the forward, backward, right and left perturbations were delivered with and without expectation at the velocities 8 degrees s-1 (SD +/- 4 degrees s-1) and 26 degrees s-1 (SD +/- 6 degrees s-1). The fast expected and unexpected perturbations were compared in blindfolded subjects. In the slow perturbations the effect of a blindfold on the balance reactions was tested. The root mean square (RMS) EMG signals from 12 trunk muscles were recorded and analysed to determine the EMG magnitudes. During the forward and backward rotations there was always a symmetrical EMG pattern between corresponding muscles on the right and left sides. A reciprocal phasic EMG activity between the left and right back muscles was found during frontal rotations. No reciprocal phasic activity was found in the abdominal muscles. Neither verbal instruction about the upcoming perturbation nor the blindfold changed the activation patterns.

Abdominal Muscles↗
PubMed1998

An electromyographic study of upper limb adduction force with varying shoulder and elbow postures.

The purpose of this study was to study the electromyographic (EMG) activity of shoulder and arm muscles during force generation in different shoulder and elbow positions when performing an isometric adduction. EMG from four pairs of muscles (biceps, anterior deltoid, pectoralis and flexor carpi radialis) were recorded bilaterally in 10 healthy young males who performed a two-handed maximal adduction against the lateral sides of the force measuring device. Descriptive statistical analysis and analysis of variance were carried out for average and maximal force. Multivariate analyses were performed to explore the relationship between force and EMG at intervals of 20% of the maximal voluntary force (contraction). The results showed that the EMG activity was significantly affected by posture (P < 0.001) but not by symmetry. The Pearson correlation coefficients were low, especially for the flexor carpi radialis and deltoid. The results revealed that the EMG activity increased with the increase in forward flexion of the shoulder, whereas the forces decreased.

Adult↗
PubMed1998

p300/MDM2 complexes participate in MDM2-mediated p53 degradation.

Control of p53 turnover is critical to p53 function. E1A binding to p300/CBP translates into enhanced p53 stability, implying that these coactivator proteins normally operate in p53 turnover control. In this regard, the p300 C/H1 region serves as a specific in vivo binding site for both p53 and MDM2, a naturally occurring p53 destabilizer. Moreover, most of the endogenous MDM2 is bound to p300, and genetic analysis implies that specific interactions of p53 and MDM2 with p300 C/H1 are important steps in the MDM2-directed turnover of p53. A specific role for p300 in endogenous p53 degradation is underscored by the p53-stabilizing effect of overproducing the p300 C/H1 domain. Taken together, the data indicate that specific interactions between p300/CBP C/H1, p53, and MDM2 are intimately involved in the MDM2-mediated control of p53 abundance.

Cell Line↗
PubMed1998

Calpain activation is upstream of caspases in radiation-induced apoptosis.

The molecular events involved in apoptosis induced by ionizing radiation remain unresolved. In this paper we show that the cleavage of fodrin to a 150 kDa fragment is an early proteolytic event in radiation-induced apoptosis in the Burkitts' Lymphoma cell line BL30A and requires 100 microM zVAD-fmk for inhibition. Caspases-1, -3, -6 and -7 were shown to cleave fodrin to the 150 kDa fragment in vitro and all were inhibited by 10 microM zVAD-fmk. We also show that the in vitro cleavage of fodrin by calpain is inhibited by 100 microM zVAD-fmk as was the calpain-mediated hydrolysis of casein. We demonstrate that calpain is activated within 15 min after radiation exposure, concomitant with the cleavage of fodrin to the 150 kDa fragment whereas caspase-3 is activated at 2 h correlating with the cleavage of fodrin to the 120 kDa fragment. These results support a role for calpain in the early phases of the radiation-induced apoptosis pathway, upstream of the caspases.

Amino Acid Chloromethyl Ketones↗
PubMed1998

Definition of T cell epitopes within the 19 kDa carboxylterminal fragment of Plasmodium yoelii merozoite surface protein 1 (MSP1(19)) and their role in immunity to malaria.

MSP1(19) is one of the leading malaria vaccine candidates. However, the mechanism of protection is not clear. To determine whether MSP1(19)-specific effector T cells can control parasitaemia, we analysed the specificity of T cells induced following immunization with recombinant forms of P. yoelii MSP1(19) and asked whether they could protect mice. There was no evidence that effector T cells were capable of protecting since: (1) immunization of mice with yMSP1(19), but not defined epitopes, was able to induce protection; and (2) long term MSP1(19)-specific CD4+ T cell lines were incapable of adoptively transferring protection. In contrast, priming mice with the T cell epitopes resulted in a rapid anamnestic antibody response to MSP1(19) after either challenge with MSP1(19) or parasite. Thus, MSP1(19) contains multiple T cell epitopes but such epitopes are the targets of helper T cells for antibody response but not of identified effector T cells capable of controlling parasitaemia.

Adoptive Transfer↗
PubMed1998

The relative contribution of antibody production and CD8+ T cell function to immune control of Trypanosoma cruzi.

The life cycle of the protozoan parasite Trypanosoma cruzi in mammalian hosts includes both non-dividing trypomastigote forms which circulate in the blood and replicating intracellular amastigotes which reside within the cytoplasm of a variety of host cells. In this study we have used mice with induced mutations in genes responsible for either antibody production or cytolytic T lymphocyte (CTL) function to examine the relative contributions of these effector mechanisms to control of T. cruzi. Mice deficient in the production of antibodies exhibited a delay in the rise in acute phase parasitaemia and an extended time to death relative to mice lacking CD8+ T cells. Nevertheless, B cell deficient mice eventually succumbed to the infection. Prior infection with an avirulent strain of T. cruzi failed to protect either CD8+ T cell-deficient mice or B cell deficient mice from challenge infection with virulent parasites. In contrast, mice with disruptions in the genes controlling perforin- or granzyme B-mediated cytolytic pathways had parasitaemia and mortality rates similar to wild-type mice and were protected from secondary infection by prior exposure to avirulent parasites. These results 1) confirm that antibody production, although secondary in importance to cellular responses, is nevertheless absolutely required and 2) perforin- or granzyme B-mediated lytic pathways are not required for control of T. cruzi infection.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1998

Cerebriform sebaceous nevus.

A 20-year-old man presented with a well-defined, soft to firm, freely mobile pinkish-yellow plaque of 9.5 cm over the right parieto-occipital region with a typical cerebriform appearance. In total, nine folds were present with short black terminal hair in the sulci area. There was no follicular plugging. Skeletal survey and neurologic and ophthalmologic assessments were normal. Skin biopsy was compatible with sebaceous nevus showing mature sebaceous glands in the upper dermis and mature apocrine glands in the lower dermis with malformed hair germ.

Adult↗