Search PubMed⌕ Search

Biomedical subjects

S Kumar

Publications and source records attributed to S Kumar.

At least 919 records · Page 51Linked to original sources

Intralesional steroid injections for corrosive induced pyloric stenosis.

Gastric outlet obstruction is a well-recognized sequela of corrosive ingestion. Such patients are traditionally treated surgically. We have treated three such patients with intralesional steroid injections combined with through-the-scope balloon dilation. All three patients responded well and are asymptomatic after 12 months, 14 months and 3 years and 3 months of follow-up, respectively. Endoscopic balloon dilation combined with intralesional steroid may be an effective alternative to surgery in such patients.

Adolescent↗

Trunk strength in combined motions of rotation and flexion/extension in normal young adults.

Thirty-eight normal healthy young subjects (14 males, 24 females) with mean ages of 23 years (males) and 21 years (females), performed 36 functional rotational tasks of the trunk. The subject's lower extremities were stabilized in a stabilizing platform, allowing the entire motion of flexion-rotation and extension-rotation to take place in the trunk. Of these tasks, 18 were isometric and the other 18 were isokinetic. The isometric tasks consisted of flexion-rotation and extension-rotation from a 20 degrees, 40 degrees and 60 degrees flexed trunk in 20 degrees, 40 degrees and 60 degrees of axial rotation. The isokinetic activity consisted of flexion-rotation and extension-rotation from upright and flexed postures respectively in 20 degrees, 40 degrees and 60 degrees rotation planes at 15 degrees, 30 degrees and 60 degrees/s angular velocities. The results revealed that the males were significantly stronger than females (p < 0.01) and isometric activities produced significantly greater torque compared to isokinetic efforts (p < 0.01). The degree of trunk flexion was not significant; the angle of rotation, although significant, had only a small effect. The 60 degrees trunk rotation was significantly different from 20 degrees and 40 degrees of trunk rotation. The multiple regressions were all significant (p < 0.01); however, they predicted only 40 to 60% of the variations. Based on the results and analysis, it is suggested that the motion involved rather than the torque may have a consequential effect in the precipitation of back injuries.

Adult↗

Phase I/IIa safety, immunogenicity, and efficacy trial of NYVAC-Pf7, a pox-vectored, multiantigen, multistage vaccine candidate for Plasmodium falciparum malaria.

Candidate malaria vaccines have failed to elicit consistently protective immune responses against challenge with Plasmodium falciparum. NYVAC-Pf7, a highly attenuated vaccinia virus with 7 P. falciparum genes inserted into its genome, was tested in a phase I/IIa safety, immunogenicity, and efficacy vaccine trial in human volunteers. Malaria genes inserted into the NYVAC genome encoded proteins from all stages of the parasite's life cycle. Volunteers received three immunizations of two different dosages of NYVAC-Pf7. The vaccine was safe and well tolerated but variably immunogenic. While antibody responses were generally poor, cellular immune responses were detected in >90% of the volunteers. Of the 35 volunteers challenged with the bite of 5 P. falciparum-infected Anopheles mosquitoes, 1 was completely protected, and there was a significant delay in time to parasite patency in the groups of volunteers who received either the low or high dose of vaccine compared with control volunteers.

Adolescent↗

Serum levels of vascular endothelial growth factor (VEGF) are markedly elevated in patients with Wegener's granulomatosis.

OBJECTIVES: Necrotizing vasculitis and granuloma formation are the predominant features of Wegener's granulomatosis (WG). We have investigated the importance of vascular endothelial growth factor (VEGF) in monitoring disease activity in WG. METHODS: Serum VEGF levels were determined in 23 patients with active WG, 21 healthy controls and 25 patients with urinary infection, by ELISA using commercially available antibodies to VEGF. RESULTS: VEGF levels were enormously elevated in patients with WG compared to both controls and patients with urinary infection (P < 0.0001). Of the 23 patients, 21 (91.3%) had VEGF levels above the cut-off value (3.3 ng/ml, calculated as the mean of the controls + 2 S.D.). Further analysis of the data showed that VEGF levels did not correlate with age, sex, incidence of classic antineutrophil cytoplasmic antibodies (c-ANCA) or duration of the disease (P > 0.05), but there was correlation with disease activity (r = 0.51, P < 0.01). VEGF levels were higher in patients with major compared to those with minor disease activity (P < 0.01). However, there was no significant correlation between VEGF levels and the Birmingham scores for vascular activity and damage. CONCLUSION: VEGF levels are raised in WG patients compared to normal controls and may be a marker of disease activity. Further studies on serial blood samples from a large cohort of patients with WG and other systemic vasculitides are needed to evaluate the specificity and usefulness of VEGF levels in monitoring disease activity.

Antibodies, Antineutrophil Cytoplasmic↗

Malignant chondroid syringoma.

Malignant chondroid syringoma (MCS) is a rare tumor, of the sweat gland; only a few hundred such cases are reported in literature. A female presented with a subcutaneous swelling on the scalp with repeated recurrence and positive regional lymph nodes. Adequate planning for the treatment of this case was possible as preoperative diagnosis of MCS was documented by fine needle aspiration cytology (FNAC). The case was successfully managed with a multimodal approach, which included radical surgery and subsequent radiotherapy. The patient is symptom free after 25 months. The possibility of this type tumor should be entertained when multiple recurrences occur following adequate excision. FNAC has a definitive role in planning rational therapy.

Adult↗

Tongue papillae in goat: a scanning electron-microscopic study.

The tongue papillae of 6-9-month-old Jamunapari goats were studied by scanning electron-microscopy. The conical-shaped filiform papillae had 3-6 pointed projections and 6-8 secondary papillae at the free tip and the base of the dorsal surfaced of the tongue, respectively. The convex surfaced fungiform papillae were raised above the lingual mucosa. The vallate papilla was characterized by a papillary groove and an annular pad. The large conical papilla had a round base and a blunt tip without any projection. Two types of lenticular papillae could be distinguished. The irregular surface of all types of papillae revealed microplicae in the form of microridges and micropits. The fungiform papilla was studded with microvilli. The taste pores were oriented on the dorso-lateral surface of the vallate papilla.

Animals↗

Neoadjuvant chemotherapy in locally advanced cervical cancer: two randomised studies.

Between August 1990 and January 1992, 184 patients with squamous cell carcinoma of the cervix, FIGO stage II B IV A were randomised (study 1) to receive either two cycles of bleomycin, ifosfamide-mesna and cisplatin (BIP) chemotherapy (CT) followed by radiotherapy (RT) 'CT-RT Group' n = 94 or RT alone, RT Group n = 90. In the 'CT-RT Group', of evaluable 89 patients, 64 responded: complete response (CR) four (4.5%) and partial response (PR) 60 (67.5%). Of the remaining 25 patients 23 had stable disease and two progressed. Eighty of 89 patients completed RT as planned. Following RT 56 (70%) achieved CR, 19 (23.7%) had residual disease and five (6.3%) had progressed. Patients aged > 45 and those with Hb > 10 gm/dL had significantly better response to CT. Further, CT responders had a better response to RT; 83% (49/59) vs 33.3% (seven/21), p < 0.01. In the 'RT Group' 88 patients were evaluable; 61 (69.3%) patients achieved CR, 25 had residual disease and two progressed. The estimated overall survival at 48 months in the 'CT-RT Group' and the 'RT Group' is 38% +2.01 (SE) and 36% +1.85 (SE), p = 0.59 respectively. In a subsequent randomised study (study 2) 36 patients with stage III B cervical cancer received three cycles of BIP (as above) followed by RT vs 36 patients who received RT alone. In the 'CT-RT Group' 29 patients responded; CR-8 (22.2%), PR-21 (58.3%). Six patients had no response to CT and one patient died of CT toxicity. Following RT-24 of 35 (68-6%) patients achieved CR, eight had residual disease and three patients progressed while on RT. In the 'RT Group'-21 of 36 (58.4%) achieved CR, 12 had residual disease and three progressed. Estimated survival was 71% in the 'CT-RT Group' and 69% in the 'RT Group', p = ns. Nausea/vomiting, alopecia, grade I-II myelosuppression, diarrhoea and mucositis were the major side effects of CT. Three patients died of CT toxicity-two in study 1 and one in study 2. Cystitis, proctitis and local skin reaction after RT occurred equally in the two groups in both the studies. BIP CT prior to RT in patients with locally advanced cervical cancer results in a high response rate. Response to CT predicts response to RT. There is no increase in the toxicity to subsequent RT. Our studies have failed to demonstrate any significant difference in overall and disease-free survival when neoadjuvant CT is added prior to the standard RT regimen.

Adult↗

Single agent versus combination chemotherapy in recurrent cervical cancer.

OBJECTIVE: Cisplatin and ifosfamide are two most active agents in patients with recurrent and metastatic cervical cancer. Combination of bleomycin, ifosfamide and cisplatinum (BIP) was compared with cisplatinum alone. PATIENTS AND METHODS: One hundred and six patients with recurrent/persistent and metastatic cervical cancer received either a combination of bleomycin, ifosfamide and cisplatinum, (Group A, n = 50) or cisplatinum alone (Group B, n = 56) every 3 weeks for up to 6 courses. Ninety-seven patients were evaluable and were analysed for response and survival. RESULTS: Patients receiving BIP (Group A) had a higher response rate (complete and partial responses), 52.2% vs 29.4%, p < 0.01 with overall median survival, 8 months (1 to 92+ months) vs 6 months (1 to 40+ months), p = 0.18. Chemotherapy responders had a significantly higher survival in both groups compared to the non-responders (Group A: 17 vs 6 months, p < 0.001, Group B: 20.5 months vs 5 months, p < 0.001). Patients in good performance status (ECOG, 0-2) had a significantly higher response rate to chemotherapy (Group A: 70.3% vs 26.3%, p < 0.01, Group B: 38.2% vs 11.7%, p < 0.05). In Group A, patients with extrapelvic disease responded better compared to pelvic disease (83.3% vs 34.5%, p < 0.01). Chemotherapy side effects were mainly nausea/vomiting, alopecia, myelosuppression, reversible encephalopathy (in Group A), and impaired renal functions. Chemotherapy toxicity was higher for patients receiving BIP, 2 patients died of BIP toxicity. Currently, in 'Group A' 8 patients are alive, 7 disease-free and one with disease at a median interval of 51 months after chemotherapy treatment. While in Group B, 3 patients are alive, 2 disease-free and one with disease. CONCLUSIONS: Bleomycin, ifosfamide and cisplatin improved the response rate in recurrent and metastatic cervical cancer compared with cisplatinum alone. However, the toxicity was moderate and survival was not significantly improved. These results need to be confirmed in a phase III, randomized study in larger number of patients.

Adult↗

Pseudoaneurysm of the cystic artery: a rare cause of hemobilia.

Aneurysms are a rare cause of hemobilia, and usually involved are branches of the hepatic and gastro-duodenal arteries. A case of a patient with hemobilia secondary to a pseudoaneurysm of the cystic artery is presented. Fewer than 10 cases have been reported in the literature, and in all of them the condition was associated with inflammation of the gall bladder, as in our case. Selective hepatic angiography is the procedure of choice for diagnosis. Upper gastrointestinal endoscopy with side-viewing scopy can demonstrate bleeding from papilla. Color-Doppler ultrasonography also may prove to be useful in equivocal cases. Cholecystectomy and ligation of cystic artery with proximal control of the hepatic artery was done at laparotomy after diagnosis was made.

Adult↗

Selective regulation of apoptosis: the cytotoxic lymphocyte serpin proteinase inhibitor 9 protects against granzyme B-mediated apoptosis without perturbing the Fas cell death pathway.

Cytotoxic lymphocytes (CLs) induce caspase activation and apoptosis of target cells either through Fas activation or through release of granule cytotoxins, particularly granzyme B. CLs themselves resist granule-mediated apoptosis but are eventually cleared via Fas-mediated apoptosis. Here we show that the CL cytoplasmic serpin proteinase inhibitor 9 (PI-9) can protect transfected cells against apoptosis induced by either purified granzyme B and perforin or intact CLs. A PI-9 P1 mutant (Glu to Asp) is a 100-fold-less-efficient granzyme B inhibitor that no longer protects against granzyme B-mediated apoptosis. PI-9 is highly specific for granzyme B because it does not inhibit eight of the nine caspases tested or protect transfected cells against Fas-mediated apoptosis. In contrast, the P1(Asp) mutant is an effective caspase inhibitor that protects against Fas-mediated apoptosis. We propose that PI-9 shields CLs specifically against misdirected granzyme B to prevent autolysis or fratricide, but it does not interfere with homeostatic deletion via Fas-mediated apoptosis.

Amino Acid Sequence↗

Cloning, characterization, and gene organization of K-Cl cotransporter from pig and human kidney and C. elegans.

We isolated and characterized the cDNAs for the human, pig, and Caenorhabditis elegans K-Cl cotransporters. The pig and human homologs are 94% identical and contain 1,085 and 1,086 amino acids, respectively. The deduced protein of the C. elegans K-Cl cotransporter clone (CE-KCC1) contains 1,003 amino acids. The mammalian K-Cl cotransporters share approximately 45% similarity with CE-KCC1. Hydropathy analyses of the three clones indicate typical KCC topology patterns with 12 transmembrane segments, large extracellular loops between transmembrane domains 5 and 6 (unique to KCC), and large COOH-terminal domains. Human KCC1 is widely expressed among various tissues. This KCC1 gene spans 23 kb and is organized in 24 exons, whereas the CE-KCC1 gene spans 3.5 kb and contains 10 exons. Transiently and stably transfected human embryonic kidney cells (HEK-293) expressing the human, pig, and C. elegans K-Cl cotransporter fulfilled two (pig) or five (human and C. elegans) criteria for increased expression of the K-Cl cotransporter. The criteria employed were basal K-Cl cotransport; stimulation of cotransport by swelling, N-ethylmaleimide, staurosporine, and reduced cell Mg concentration; and secondary stimulation of Na-K-Cl cotransport.

Amino Acid Sequence↗

Kinetic properties of nitric oxide synthase in cerebral cortex and cerebellum of morphine tolerant mice.

The effects of chronic morphine administration on the kinetics of nitric oxide synthase (NOS) activity were determined in the mouse cerebral cortex and cerebellum. Male Swiss-Webster mice were implanted subcutaneously with morphine pellets each containing 25 mg of morphine base for 3 days. Mice implanted with placebo pellets served as controls. NOS activity was determined by measuring the rate of conversion of [3H]arginine to [3H]citrulline. Morphine pellet implantation increased NOS activity in the cerebral cortex and cerebellum. Analysis of the Eadie-Hofstee plot indicated that the Vmax of NOS in the cortex and cerebellum was 140 and 228 pmol [3H]citrulline formed/min/mg protein and the Km values were 9.3 and 10.1 mumol/l, respectively. Mice implanted with morphine pellets had higher Vmax values in both the cortex and cerebellum, but the Km values did not differ from those of control mice implanted with placebo pellets. It is concluded that chronic treatment with morphine increases NOS activity in the brain without modifying its substrate affinity.

Analgesics, Opioid↗

Phylogeny of Tamm-Horsfall protein.

The Tamm-Horsfall protein (THP, uromodulin) is urine's most abundant protein. The phylogenetic distribution of the gene for THP was examined in all the major vertebrate classes. Genomic DNA was obtaind from each vertebrate class and hybridized with a rat THP cDNA probe in a DNA hybridization assay. In separate experiments, a polymerase chain reaction assay was used to amplify segments of the THP gene using primers from a consensus sequence for THP among multiple mammalian species. Both methods revealed that the THP gene was present in all the vertebrate classes. These data demonstrate the evolutionary conservation of the THP gene among vertebrates and suggest a role for this protein that is common to the kidney of all vertebrates.

Actins↗

Development and characterization of monoclonal antibodies specific to the serotonin 5-HT2A receptor.

Serotonin (5-hydroxytryptamine, 5-HT) mediates many functions of the central and peripheral nervous systems by its interaction with specific neuronal and glial receptors. Fourteen serotonin receptors belonging to seven families have been identified through physiological, pharmacological, and molecular cloning studies. Monoclonal antibodies (MAbs) specific for each of these receptor subtypes are needed to characterize their expression, distribution, and function in embryonic, adult, and pathological tissues. In this article we report the development and characterization of MAbs specific to the serotonin 5-HT2A receptor. To generate MAbs against 5-HT2AR, mice were immunized with the N-terminal domain of the receptor. The antigens were produced as glutathionine S-transferase (GST) fusion proteins in insect cells using a Baculovirus expression system. The hybridomas were initially screened by ELISA against the GST-5-HT2AR recombinant proteins and subsequently against GST control proteins to eliminate clones with unwanted reactivity. They were further tested by Western blotting against recombinant GST-5-HT2AR, rat and human brain lysate, and lysate from cell lines transfected with 5-HT2AR cDNA. One of the MAbs G186-1117, which recognizes a portion of the 5-HT2AR N-terminus, was selected for further characterization. G186-1117 reacted with a band of molecular size 55 kD corresponding to the predicted size of 5-HT2AR in lysates from rat brain and a 5-HT2AR-transfected cell line. Its specificity was further confirmed by adsorption of immunoreactivity with recombinant 5-HT2AR but not with recombinant 5-HT2BR and 5-HT2CR. Rat brain sections and Schwann cell cultures were immunohistochemically labeled with this MAb. G186-1117 showed differential staining in various regions of the rat brain, varying from regions with no staining to regions of intense reactivity. In particular, staining of cell bodies and dendrites of the pyramidal neurons in the cortex was observed, which is in agreement with observations of electrophysiological studies.

Aged↗

Progesterone induces calcitonin gene expression in human endometrium within the putative window of implantation.

The human endometrium acquires the ability to implant the developing embryo within a specific time window that is thought to open between days 19-24 of the secretory phase of the menstrual cycle. During this period the endometrium undergoes pronounced structural and functional changes induced by the ovarian steroids, estrogen and progesterone, that prepare it to be receptive to invasion by the embryo. The identification of reliable biochemical markers to assess this critical receptive phase in the context of the natural cycle remains one of the major challenges in the study of human reproduction. Our previous studies in a rat model system demonstrated that the expression of calcitonin, a peptide hormone involved in calcium homeostasis, is transiently induced by progesterone in the glandular epithelium at the onset of implantation. Attenuation of calcitonin synthesis in the uterus during the preimplantation phase by administration of calcitonin antisense oligodeoxynucleotides severely impairs implantation of rat embryos, suggesting that this peptide hormone plays a critical role in uterine receptivity. To investigate whether calcitonin is also expressed in the human endometrium during implantation, we monitored the spatio-temporal expression of calcitonin on various days of the menstrual cycle. Our studies employing RT-PCR showed that calcitonin messenger ribonucleic acid is expressed in human endometrium during the postovulatory midsecretory phase (days 17-25) of the menstrual cycle, with maximal expression occurring between days 19-21. Very little calcitonin expression was detected in the endometrium in either the preovulatory proliferative (days 5-14) or the late secretory (days 26-28) phase. In situ hybridization and immunocytochemical analyses localized the calcitonin expression predominantly in the glandular epithelial cells of the endometrium. Our studies further showed that calcitonin expression in the human endometrium is under progesterone regulation. Treatment of women with an antiprogestin, mifepristone (RU-486), drastically reduced calcitonin expression in the endometrium. Collectively, these findings reveal that progesterone-induced expression of calcitonin in the secretory endometrium temporally coincides with the putative window of implantation in the human.

Adult↗