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Biomedical subjects

S Kumar

Publications and source records attributed to S Kumar.

At least 775 records · Page 43Linked to original sources

Characterization of matrix metalloproteinases in human urine: alterations during adolescence.

Matrix metalloproteinases (MMPs) are a family of at least 14 zinc-dependent proteinases that have been implicated in matrix turnover under both normal and pathological conditions. Previous studies have shown that several MMPs are produced in various cell types in the kidney, suggesting that MMPs may be involved in renal morphogenesis and remodelling. Using a variety of techniques, including gelatin and casein zymography, gelatin affinity chromatography, immunoblotting, and immunoprecipitation, we have identified the major gelatinases in human urine as MMP-2 and MMP-9. Latent forms of both enzymes were detected in urine, as well as lower molecular mass species of each, consistent with activated forms of MMP-2 and MMP-9. MMP-2 and MMP-9 were also measured in individual human urine samples (n=40). No significant gender differences in MMP concentrations were detected. However, renal MMP expression appeared to be age dependent; the highest average amounts of urine MMP-2 were detected during adolescence, while the converse was true of urine MMP-9. Together, these findings indicate that under normal conditions, human urine contains MMP-2 and/or MMP-9, suggesting that these two MMPs are normally produced within the kidney, where they may regulate normal renal remodelling and matrix homeostasis in an age-specific manner.

Adolescent↗

EYA1 nonsense mutation in a Japanese branchio-oto-renal syndrome family.

Advances in molecular genetics have recently revealed that mutations in the EYA1 gene are responsible for branchio-oto-renal (BOR) syndrome in European and other populations. This is the first report confirming that an EYA1 gene mutation is also disease-causing in an Asian population. We have described one Japanese BOR syndrome family showing a novel mutation in exon 7 of the EYA1 gene. There was extensive variation of clinical phenotypes within this family. When the physician is confronted with a BOR family showing a wide variation in clinical expression, molecular genetic testing helps to achieve accurate diagnosis.

Audiometry↗

Transferrin is an essential factor for myelination.

It has been established that oligodendrocytes, the myelin forming cells, participate in iron homeostasis through the synthesis and secretion of transferrin. Here we investigated whether a correlation exists between myelination, the commonly studied function of oligodendrocytes, and that of transferrin synthesis and secretion. We used a proteolipid protein mutant, the myelin deficient rat, whose condition is characterized by severe hypomyelination. We compared the ontogenic profile for transferrin gene expression in mutants with that of unaffected rat pups through northern blot analysis and in situ hybridization. Surprisingly, transferrin synthesis was null in mutant oligodendrocytes. Next, we demonstrated that a single apo-transferrin intraparenchymal injection administered to P5 rat pups enabled mutant oligodendrocytes to synthesize myelin basic protein and to myelinate axons, indicating that transferrin effects mutant oligodendrocyte maturation regardless of its source. Thus, transferrin availability is essential for oligodendrocyte maturation and function, and oligodendrocytes are most vulnerable to transferrin deficiency during the premyelinating stage.

Animals↗

Composite low grade B-cell lymphomas with two immunophenotypically distinct cell populations are true biclonal lymphomas. A molecular analysis using laser capture microdissection.

Low grade B-cell lymphomas comprise several well defined, clinically and immunophenotypically distinct disease entities. Composite lymphomas showing phenotypic characteristics of more than one of these tumor subtypes in the same site are rare, and both common and separate clonal origins of the two tumor parts have been reported for cases studied by molecular methods. We describe the detailed immunohistochemical and molecular findings in three cases with features of composite low grade B-cell non-Hodgkin's lymphoma (B-NHL). All three neoplasms contained morphologically distinct but interwoven compartments of different cell types, which exhibited discordant expression of several markers, including CD5, CD10, CD43, and cyclin D1. According to their morphology and phenotypes, they were classified as mantle cell lymphoma and follicular lymphoma (Case 1), follicular lymphoma and small lymphocytic lymphoma (Case 2), and mantle cell lymphoma and chronic lymphocytic leukemia/small lymphocytic lymphoma (Case 3). PCR analysis of DNA obtained from whole tissue sections failed to reveal evidence for biclonality in any of the cases. We therefore isolated cell populations with different antigen expression patterns by laser capture microdissection and analyzed them by polymerase chain reaction amplification and sequencing of clonal immunoglobulin heavy chain gene rearrangements and oncogene rearrangements. Sequence analysis revealed unrelated clonal rearrangements in each of the two tumor parts in all three cases, suggesting distinct clonal origins. In addition, Case 1 showed a bcl-2 rearrangement present only in the follicular lymphoma part. Our findings suggest that low grade B-NHL with two distinct morphological and immunophenotypic patterns in the same anatomical site are frequently biclonal. This is in keeping with current classification schemes, which recognize subtypes of low grade B-NHL as separate disease entities. Furthermore, our analysis demonstrates the power of laser capture microdissection in revealing molecular microheterogeneity in complex neoplasms.

Aged↗

Intralesional steroids augment the effects of endoscopic dilation in corrosive esophageal strictures.

BACKGROUND: Intralesional corticosteroid injection has been shown to be effective in refractory esophageal strictures of various etiologies. The present study was conducted to determine the efficacy of intralesional triamcinolone in augmenting results of endoscopic dilation in corrosive esophageal strictures. METHODS: Seventeen patients with corrosive esophageal strictures were treated with endoscopic dilation together with injection of triamcinolone acetonide into the stricture. Fourteen patients were already undergoing dilation; 3 patients were newly recruited. The interval between dilations and frequency of dilation were calculated before and after corticosteroid injections, and periodic dilation index was calculated as number of dilations/number of months. RESULTS: The mean age of the 17 patients (8 men and 9 women) was 30+/-9.21 (range 13 to 52). Thirteen had strictures due to acid ingestion, four to alkali ingestion. There were 18 strictures in total, involving the upper (n = 2), middle (n = 10), and lower (n = 6) thirds of esophagus. Fourteen patients already on a dilation program had undergone 27.92+/-28.63 (range 6 to 92) dilations over a period of 22.92+/-30.73 months (range 2 to 96) before corticosteroid injections. Nine patients received a single injection of triamcinolone, whereas four each had two and three sessions. The dilation requirement after injections in these 14 patients was reduced to 3.57+/-2.90 (range 0 to 10) dilations over a period of 10.5+/-5.58 (range 4 to 21) months. The median total periodic dilation index irrespective of corticosteroid therapy was 0.33 (range 0.55 to 1.8). In 12 of the 14 patients, periodic dilation index before injections (range 0.91 to 3.0, median 1.67) was higher than the median total periodic dilation index and in all the 14 patients periodic dilation index after corticosteroid therapy (range 0 to 0.83, median 0.32) was less than the median of total periodic dilation index (p < 0.01). In addition three patients received intralesional corticosteroid injections at the time of first dilation. These three patients could be effectively dilated with 5, 3, and 3 dilations. CONCLUSIONS: Intralesional triamcinolone injections augment the effects of endoscopic dilation in patients with corrosive esophageal strictures.

Adult↗

Ultrasound guided aspiration of endometrioma--a new therapeutic modality to improve reproductive outcome.

OBJECTIVE: To evaluate the therapeutic efficacy and reproductive outcome following ultrasound guided aspiration (UGA) of endometrioma in infertile patients. METHOD: This is a prospective non-randomized clinical report of UGA in 22 infertile patients with endometrioma. The aspiration of endometriotic cysts was carried out transvaginally in nine and transabdominally in 13 patients. Following aspiration intranasal buserilin was given to eight and danazol to 14 patients. In the case of recurrence a reaspiration was done. Patients were allowed to conceive following medical therapy. Recurrence of endometrioma and conception rate was recorded and correlated with endometrioma size and volume aspirated. RESULT: A total of 47 aspirations were done. There were no procedure related complications. Reaspiration was required in six patients and one was operated (total recurrence 7/22--31.8%). During a mean follow-up of 20+/-8.4 months nine patients (40.9%) conceived and eight have already delivered at term. The recurrence risk and the conception rate was not affected by the cyst size or volume aspirated. CONCLUSION: UGA of endometrioma can be an effective and safe alternative therapeutic procedure in infertile patients with endometrioma to improve their reproductive outcome.

Adult↗

Short and long-term morbidity of thoracoabdominal incision for nephrectomy: a comparison with the flank approach.

PURPOSE: A thoracoabdominal incision provides optimal exposure for radical nephrectomy, especially for large tumors. Intuitively it is perceived that the morbidity of a thoracoabdominal incision far exceeds that of a flank incision. We compare the morbidity of thoracoabdominal and flank incisions, which to our knowledge has not been reported previously. MATERIALS AND METHODS: A questionnaire assessing postoperative pain, use of pain medications and return to activities was sent to the last 100 renal donors who underwent nephrectomy at our institution through the 11th rib (flank incision, group 1) and the last 100 patients who underwent radical nephrectomy through the 8th to 10th rib (thoracoabdominal incision, group 2). A total of 52 group 1 and 42 group 2 questionnaires were returned. Pain was assessed at 4 periods using a visual analog scale. RESULTS: Length of stay was the same in both groups. There were no differences between groups in terms of pain severity on postoperative day 1, on day of discharge home, 1 month postoperatively and at the time of study (p >0.05). There were no significant differences between groups in times following surgery when pain completely disappeared, when pain medications were discontinued, and when the patient returned to daily activities and work (p >0.05). CONCLUSIONS: Morbidity was comparable for thoracoabdominal and flank incisions in terms of incisional pain, analgesic requirements after discharge home and return to normal activities.

Abdomen↗

Detection of EWS-FLI-1 fusion in Ewing's sarcoma/peripheral primitive neuroectodermal tumor by fluorescence in situ hybridization using formalin-fixed paraffin-embedded tissue.

The balanced translocation t(11;22)(q24;q12) is specific for the Ewing's sarcoma/peripheral primitive neuroectodermal tumors (ES/PNETs) and results in the EWS/FLI-1 fusion transcript, which can be detected by reverse transcription polymerase chain reaction (RT-PCR). Recent studies also have used fluorescence in situ hybridization (FISH) to show the translocation; however, most of these have been performed on cell lines or touch preparations and short-term cultures of tumors. Moreover, the existing probes generally have shown only the break in the specific chromosomes rather than the translocation itself. We describe our findings with a new set of probes that localize to 22q12 (EWS) and 11q24 (FLI-1) and directly show the translocation as juxtaposed red-green signals on der(22) in nuclei extracted from formalin-fixed, paraffm-embedded tissues. After establishing the specificity of the probes (on metaphase spreads and interphase nuclei in two translocation-positive cell lines and normal peripheral blood lymphocytes), we evaluated 11 ES/PNETs and 10 other tumors (four alveolar rhabdomyosarcomas, three neuroblastomas, two lymphomas, one extramedullary myeloid tumor) using a two-color FISH assay. All 11 ES/PNETs showed fusion signals in 20% to 80% of evaluable nuclei. In two lymphoma cases, random overlapping signals were present in 2% and 4% of nuclei, whereas the remaining eight tumors were negative. The presence of t(11;22) was confirmed by RT-PCR in 10 of 11 ES/PNETs. We conclude that FISH analysis with this newly designed probe pair is a specific and sensitive method of detecting t(11;22) on routinely processed tissue and can be useful in the differential diagnosis of ES/PNETs from other small round blue cell tumors when only fixed tissue is available.

Adolescent↗

Absence of EWS/FLI1 fusion in olfactory neuroblastomas indicates these tumors do not belong to the Ewing's sarcoma family.

The balanced reciprocal translocation t(11;22)(q24;q12) is a specific molecular marker for the Ewing's sarcoma family of tumors (ESFT). Based on the detection of this translocation in some olfactory neuroblastomas (ONBs), it has been proposed that ONBs also belong to the ESFT. Others have challenged this hypothesis; however, the rarity of ONBs, as well as the lack of molecular techniques that work reliably on formalin fixed tissue, have precluded the molecular analysis of a significant number of cases. We evaluated the immunophenotypic and molecular features of 17 paranasal small round neuroectodermal tumors using routinely fixed tissue. Probes localizing to 22q12 (EWS) and 11q24 (FLI-1) were used in a standard 2-color fluorescence in situ hybridization (FISH) assay to evaluate EWS/FLI1 fusion on the der(22). Sixteen tumors were mic-2 negative, whereas 1 tumor was mic-2 positive, compatible with ONB and ESFT, respectively. Thirteen of 15 ONBs could be evaluated by FISH, and all 13 were negative for the EWS/FLI1 fusion. Distinct fusion signals were identified in the single paranasal ESFT. Our findings indicate that ONBs lack the EWS/FLI1 fusion and are unrelated to the ESFT; however, true ESFTs may rarely occur as primary sinonasal tumors.

Adolescent↗

Morbidity of flank incision for renal donors.

OBJECTIVES: To analyze the short and long-term morbidity of flank incision in renal donors. The flank incision has been widely used by urologists for decades, and its morbidity has always been an issue. METHODS: A questionnaire assessing the morbidity and quality of life was sent to the last 100 living donors at our institution. All operations had been performed through the flank approach. Fifty-two questionnaires were returned. The mean age was 45 years. The mean follow-up was 29.5 months (range 7 to 58). The questionnaire was composed of questions regarding pain, cosmesis of the incision, and quality-of-life issues after surgery. RESULTS: No patients had any major postoperative complications. Pain was described in the first postoperative day as severe, moderate, or mild by 36 (69.3%), 6 (11.5%), and 10 (19.2%) patients, respectively. On the day of discharge (mean 4 days), 17 patients (32.7%) reported severe pain. Pain was completely or somewhat controlled with analgesics after surgery in all but 3 patients. Most (81%) discontinued pain medication by the end of fourth postoperative week (54% by the end of second week). Only 3 patients (5.8%) related being very bothered by the incision at the time of the questionnaire. Bother relates to pain, location, length, and unsightliness of scar. In 43 patients (83%), the incision did not impact negatively on their self-esteem and quality of life, and 93% of patients in retrospect would undergo the same procedure without any reservation. CONCLUSIONS: The short and long-term morbidity of the flank incision for living donor nephrectomy is acceptable. Most patients are content after the kidney donation, and all would undergo the same procedure all over again, the vast majority without any reservation.

Adult↗

Sensitization to the locomotor stimulant effect of cocaine modifies the binding of [3H]MK-801 to brain regions and spinal cord of the mouse.

The effects of chronic administration of cocaine and its subsequent withdrawal on the binding of [3H]MK-801, an antagonist of the N-methyl-D-aspartate (NMDA) receptor, to brain regions and spinal cord of the mouse was determined. Chronic administration of cocaine (10 mg/kg, SC) twice a day for 7 days sensitized male Swiss-Weber mice to its locomotor activity, as evidenced by a greater locomotor activity in comparison with vehicle-injected controls. In nonwithdrawing mice, the binding of [3H]MK-801 was increased in the cerebellum and spinal cord but was decreased in the cortex and hypothalamus. On the other hand, during withdrawal from cocaine, a significant decrease in the binding of [3H]MK-801 was observed only in the cortex, but the changes in the cerebellum, spinal cord and hypothalamus were normalized. It is concluded that, in the mouse, sensitization to the locomotor activating action of cocaine is associated with differential changes in the NMDA receptors of the central nervous system.

Animals↗

Wide spectrum antibacterial and antifungal activities in the seeds of some coprophilous plants of north Indian plains.

In a survey at Lucknow, India, the seedlings of plant species which are prescribed in the Indian traditional system of medicine for a variety of infectious diseases were found to predominate on fresh or decomposing cattle dung, a harsh medium for plant growth due to high microbial load and other abiotic factors. Plants of most of the common species did not occur on the cattle dung heaps. It was hypothesized that plant species which are able to grow on cattle dung may have antimicrobial compounds in their seeds to protect them from microbial attack. In confirmation, the seeds of 15 of the coprophilous (kopros--dung, philein--to love) plant species, identified as occurring most frequently on fresh/decomposing cattle dung were directly tested against eight bacterial and three fungal strains. Interestingly, seeds of all the examined species exhibited antimicrobial activity. The seeds of the species found more frequently on the cattle dung heaps possessed higher levels of antimicrobial activities.

Animals↗

Nedd4-like proteins: an emerging family of ubiquitin-protein ligases implicated in diverse cellular functions.

The members of an emerging family of proteins similar to Nedd4 have a unique modular structure consisting of a Ca2+/lipid-binding domain, multiple protein-protein interaction modules and a ubiquitin-protein ligase domain. Although little is known about the physiological roles of these proteins, studies in both mammals and yeast are providing evidence that members of this family might be involved in diverse cellular functions, such as regulation of membrane channels and permeases, the cell cycle and transcription. This article attempts to bring together what is currently known about these evolutionarily conserved ubiquitin-protein ligases.

Animals↗

EMG spectral characteristics of spinal muscles during isometric axial rotation.

The objective of this study was to determine the frequency profile, median frequency (MF) and mean power frequency (MPF) of trunk muscles in an isometric graded maximal voluntary contraction (MVC) in isometric axial trunk rotation from a neutral upright seated posture. Twelve young healthy subjects (seven males, five females) were instrumented with surface electrodes on their external obliques, internal obliques, rectus abdominis, pectoralis, latissimus dorsi and erector spinae at T10 and L3 levels bilaterally. These subjects were stabilized in seated posture in an axial rotation tester (AROT) and asked to perform a graded isometric contraction of their maximal value to both right and left directions from a neutral posture within a period of 10s. EMG from all 14 channels were sampled at 1 kHz at 10% intervals of MVC from 10% to MVC. These samples were subjected to fast Fourier transform analysis. The frequency profile plots demonstrated the power of muscles involved in agonistic and antagonistic activity. However, the frequency composition showed little difference between them. The MF was higher in agonists of the same muscle. The MPF was always higher than MF. Both values were generally insignificantly different between different levels of contraction. However, with increasing level of contraction there was increase in power.

Adult↗

Diphenhydramine disposition in the sheep maternal-placental-fetal unit: determinants of plasma drug concentrations in the mother and the fetus.

The objective of this study was to identify the important factors that determine plasma concentrations of diphenhydramine (DPHM) in the mother and the fetus after maternal as well as fetal steady-state drug administration. Inter-relationships were evaluated between maternal and fetal placental and nonplacental clearances, plasma protein binding, and steady-state plasma concentrations of DPHM among data obtained from 18 pregnant sheep during late gestation. The major determinant of plasma DPHM concentrations in the mother after maternal as well as fetal administration appears to be maternal plasma protein binding and maternal nonplacental clearance. In contrast, the major determinant of fetal plasma DPHM concentrations after maternal drug administration was the extent of fetal first-pass hepatic drug uptake from the umbilical vein. However, after fetal drug administration, the fetal plasma concentrations were related to the extent of fetal plasma protein binding and fetal placental and nonplacental clearances. The index of fetal-to-maternal placental drug transfer after fetal drug administration (steady-state maternal-to-fetal plasma concentration ratio) was related to steady-state fetal plasma unbound fraction and fetal placental and nonplacental clearance. However, this index was not related to the magnitude of the factors operating on the maternal side of the placenta such as maternal plasma protein binding and maternal nonplacental clearance. This might indicate a lack of complete equilibration of the unbound drug concentrations on the two sides of the placenta at the exchange site.

Animals↗