Central cyanosis in a young man.
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Adult↗
Biomedical subjects
U Kumar
Publications and source records attributed to U Kumar.
Subtype-selective expression of the five somatostatin receptors (hSSTR1-5) in human pancreatic islet cells: a quantitative double-label immunohistochemical analysis.
We have developed a panel of rabbit polyclonal antipeptide antibodies against the five human somatostatin receptor subtypes (hSSTR1-5) and used them to analyze the pattern of expression of hSSTR1-5 in normal human islet cells by quantitative double-label confocal fluorescence immunocytochemistry. All five hSSTR subtypes were variably expressed in islets. The number of SSTR immunopositive cells showed a rank order of SSTR1 > SSTR5 > SSTR2 > SSTR3 > SSTR4. SSTR1 was strongly colocalized with insulin in all beta-cells. SSTR5 was also an abundant isotype, being colocalized in 87% of beta-cells. SSTR2 was found in 46% of beta-cells, whereas SSTR3 and SSTR4 were relatively poorly expressed. SSTR2 was strongly colocalized with glucagon in 89% of alpha-cells, whereas SSTR5 and SSTR1 colocalized with glucagon in 35 and 26% of alpha-cells, respectively. SSTR3 was detected in occasional alpha-cells, and SSTR4 was absent. SSTR5 was preferentially expressed in 75% of SST-positive cells and was the principal delta-cell SSTR subtype, whereas SSTR1-3 were colocalized in only a few delta-cells, and SSTR4 was absent. These studies reveal predominant expression of SSTR1, SSTR2, and SSTR5 in human islets. Beta-cells, alpha-cells, and delta-cells each express multiple SSTR isoforms, beta-cells being rich in SSTR1 and SSTR5, alpha-cells in SSTR2, and delta-cells in SSTR5. Although there is no absolute specificity of any SSTR for an islet cell type, SSTR1 is beta-cell selective, and SSTR2 is alpha-cell selective. SSTR5 is well expressed in beta-cells and delta-cells and moderately well expressed in alpha-cells, and thereby it lacks the islet cell selectivity displayed by SSTR1 and SSTR2. Subtype-selective SSTR expression in islet cells could be the basis for preferential insulin suppression by SSTR1-specific ligands and of glucagon inhibition by SSTR2-selective compounds.
Animals↗
Absorbable mesh envelope facilitates handling of pediatric en bloc kidneys during transplantation.
There is increasing evidence to favor the use of pediatric en bloc kidneys in renal transplantation. However, from a technical standpoint, pediatric en bloc renal transplantation is more complex because of difficulty in optimal intraoperative handling and positioning, as well as a higher potential for vascular complications. We describe our experience with a technique that has helped us to minimize the technical difficulties associated with the surgical procedure. Use of a tailored absorbable mesh envelope improves handling of the en bloc pediatric kidneys during performance of the vascular anastomoses and reduces the risk of torsion of renal pedicles.
Absorbable Implants↗
Evaluation of thyroid hormones in chronic renal failure.
When chronic renal failure becomes advanced, the serum levels of most hormones are altered because of several interplaying mechanisms. This study was carried out to evaluate the level of total thyroxine (T4), triiodothyronine (T3) and thyrotropin (TSH) in 96 clinically euthyriod patient with chronic renal failure and 25 healthy individual as control. The patients were grouped into two groups, 62 patient on conservative management and 34 patients on chronic haemodialysis. The patient of both groups showed significant decrease in total T3 and T4 level as compared to normal control. Serum TSH level were similar in both groups as well as in control and were with in normal limit except 3 patients on conservative management which showed TSH level above normal chronic haemodialysis did not have positive effect in alteration of serum T3, T4 and TSH level.
Adult↗
Hemoglobin levels and concomitant intestinal parasitoses among children in and around Patna.
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Child↗
Hepatitis C--a transfusion associated hepatitis.
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Child↗
The cytoplasmic tail of the human somatostatin receptor type 5 is crucial for interaction with adenylyl cyclase and in mediating desensitization and internalization.
We have investigated the role of the cytoplasmic tail (C-tail) of the human somatostatin receptor type 5 (hSSTR5) in regulating receptor coupling to adenylyl cyclase (AC) and in mediating agonist-dependent desensitization and internalization responses. Mutant receptors with progressive C-tail truncation (Delta347, Delta338, Delta328, Delta318), Cys320 --> Ala substitution (to block palmitoylation), or Tyr304 --> Ala substitution of a putative NPXXY internalization motif were stably expressed in Chinese hamster ovary K1 cells. Except for the Tyr304 --> Ala mutant, which showed no binding, all other mutant receptors exhibited binding characteristics (Kd and Bmax) and G protein coupling comparable with wild type (wt) hSSTR5. The C-tail truncation mutants displayed progressive reduction in coupling to AC, with the Delta318 mutant showing complete loss of effector coupling. Agonist pretreatment of wt hSSTR5 led to uncoupling of AC inhibition, whereas the desensitization response of the C-tail deletion mutants was variably impaired. Compared with internalization (66% at 60 min) of wt hSSTR5, truncation of the C-tail to 318, 328, and 338 residues reduced receptor internalization to 46, 46, and 23%, respectively, whereas truncation to 347 residues slightly improved internalization (72%). Mutation of Cys320 --> Ala induced a reduction in AC coupling, desensitization, and internalization. These studies show that the C-tail of hSSTR5 serves a multifunctional role in mediating effector coupling, desensitization, and internalization. Whereas coupling to AC is dependent on the length of the C-tail, desensitization and internalization require specific structural domains. Furthermore, internalization is regulated through both positive and negative molecular signals in the C-tail and can be dissociated from the signaling and acute desensitization responses of the receptor.
Adenylyl Cyclases↗
Expression of somatostatin receptor subtypes in human brain tumors.
Expression of mRNA for the 5 somatostatin receptors (sst1-5) was characterized by Northern blot and RT-PCR analysis in 20 meningioma and 9 glioma samples. sst1 mRNA was detectable by Northern blots of poly-A+ RNA in meningiomas but not gliomas. In contrast, sst2 mRNA was readily detected by Northern blots of total RNA as a major 2.3 kb transcript and 2 minor 4.3 kb and 8 kb transcripts in all meningiomas and 6 out of 9 gliomas. Quantitation of the 2.3 kb sst2 mRNA showed that 15 out of 20 tumors expressed 1.3- to 33-fold higher levels than control normal human brain. Mean sst2 mRNA for the 20 meningioma samples was 978% that of normal brain. Three gliomas showed 7- to 14-fold higher sst2 mRNA than normal brain whereas the remaining samples displayed very low or undetectable levels. Immunocytochemistry of meningioma and glioma samples, with a sst2-specific antibody revealed immunoreactivity in tumor cells and peritumoral tissue, with prominent expression in blood vessels. mRNA for sst3,4,5 could not be detected by Northern blots in any of the tumors. RT-PCR analysis of meningiomas and gliomas revealed the following percent of tumors positive for a given sst mRNA: sst1 (86%), sst2 (100%), sst3 (60%), sst4 (58%), and sst5 (67%); 85% of tumors expressed 3 of the 5 subtypes. No correlation was found between the pattern of expression of sst mRNA and tumor type, location, and histology for either the meningiomas or gliomas. Our results show that meningiomas and gliomas are all positive for at least one sst subtype, the majority expressing multiple subtypes. sst2 is the most abundant isoform with a rich expression in both tumor and peritumoral tissue especially blood vessels.
Adult↗
Comparison of the rate of sequence variation in the hypervariable region of E2/NS1 region of hepatitis C virus in normal and hypogammaglobulinemic patients.
The hypervariable region (HVR) of the E2/NS1 region of hepatitis C virus (HCV) varies greatly between viral isolates with high rates of genomic change reported during the course of chronic infection. The HVR is thought to encode a structurally unconstrained envelope protein containing several linear B cell epitopes recognized by neutralizing antibody. It has been postulated that amino acid changes in the HVR could result from humoral immune pressure leading to the selection of escape mutants. The aim of this study was to compare the rates of nucleotide and amino acid variation in the HVR of control patients to patients with common variable immunodeficiency (CVID) where the effect of the humoral immune system is reduced. Five controls and four patients with CVID were studied. Serum samples were taken over periods of between 1 and 6 years. HCV was detected by polymerase chain reaction (PCR) with primers derived from conserved flanking regions of the HVR. PCR products were cloned into a plasmid vector and recombinant clones identified by restriction enzyme digestion. Purified DNA from at least three individual clones from each time point was sequenced by the dideoxynucleotide chain-termination method. Consensus sequences were extracted from the three clones, and the DNA and deduced protein sequences were compared. Control patients had a mean rate of nucleotide change of 6.954 nucleotide substitutions per year, compared with patients with CVID with a rate of 0.415 nucleotide substitutions per year (P < .02). The corresponding rates for amino acid variation were 3.868 amino acid substitutions per year for the control patients compared with 0.185 amino acid substitutions per year for the patients with CVID. These findings suggest that in the absence of humoral immune selective pressure, the frequency of occurrence of genetic variation in the major viral species is reduced. The mutations occur, but in the absence of immune selection remain as minor species. The evolution of viral mutants capable of evading the host's immune system may contribute to the ability of HCV to establish chronic infection.
Adult↗
Testicular dislocation after scrotal trauma.
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Accidents, Traffic↗
Diminished expression of renal dopamine D1A receptors in the kidney inner medulla of the spontaneously hypertensive rat.
BACKGROUND: Dysfunctional dopamine neurotransmission and greater than normal retention of salt have been found for renal proximal tubules of the spontaneously hypertensive rat OBJECTIVE: To determine whether there are differences between kidney D1A dopamine receptor distributions of spontaneously hypertensive rats and Wistar-Kyoto rats. METHODS: We examined the expression of D1A dopamine receptors in kidneys of spontaneously hypertensive rats and the normotensive Wistar-Kyoto rat through Western blots and immunocytochemistry, using highly specific antipeptide antibodies directed against the receptor. RESULTS: The specificity of the antisera was demonstrated by Western blot studies, using proximal tubules, from Wistar-Kyoto rats. The antiserum recognized a major polypeptide with Mr of 72 kDa and a minor protein of Mr 66 kDa, which were not detected either by antigen-adsorbed or by preimmune sera. In renal cortex of both Wistar-Kyoto rats and spontaneously hypertensive rats, D1A receptors were expressed at equivalent levels. In the inner medulla of Wistar-Kyoto rat, there was diminished (by 60%) expression of D1A receptors compared with that of the renal cortex. However, the expression of D1A receptors in the inner medulla in the spontaneously hypertensive rat was even more diminished (by 83%) relative to levels found in spontaneously hypertensive rat renal cortex. Immunocytochemical studies localized the D1A receptor protein in renal cortex primarily to epithelia of tubules. Relative to renal cortex, there was an overall decrease in staining intensity in the inner medulla both of Wistar-Kyoto rats and of spontaneously hypertensive rats. Compared with that of Wistar-Kyoto rat, the intensity of staining of D1A receptors in the inner medulla of spontaneously hypertensive rats was greatly diminished, confirming the Western blot analyses. The less than normal expression of D1A receptors in the inner medulla of spontaneously hypertensive rats might be of physiologic importance in the etiology of greater than normal retention of salt and hypertension in spontaneously hypertensive rats.
Animals↗
Audit of clinical judgements and actions in an audiological investigation of school entrant children screened positive for hearing loss.
Of 117 children attending an aural clinic after screening positive by one or both of two tests for hearing loss at school entry, 43 (36.8%) were either seen again for review or listed for surgery. Clinical findings which were significantly associated with either being reviewed or listed for surgery, as opposed to being discharged, were the presence of conductive or sensory neural hearing loss, pronounced negative pressure, reduced compliance volume or absent stapedial reflexes on impedance testing and the presence of an abnormal tympanic membrane associated with effusion on otoscopy. This population of children were then followed up through their school medical records over 4 y to determine what proportion of those discharged from the clinic had subsequently required some form of surgical intervention due to a hearing problem. Note was also taken of all those actually receiving surgery or long term review for sensory neural hearing loss, these cases being designated as true positives in the aural clinic assessment process. This assessment, albeit of a 'high-risk group', gave rise to a sensitivity of 88.9% and a specificity of 68.0%.
Audiometry, Pure-Tone↗
Distribution of protein inhibitor of neuronal nitric oxide synthase in rat brain.
In neuronal cells, nitric oxide (NO) is synthesized by neuronal nitric oxide synthase (nNOS) and performs various functions including neurotransmission, modulation of nociception and long-term potentiation and memory. Recently, a novel 89-amino acid protein, designated PIN, has been shown to interact specifically with nNOS and inhibit nNOS dimerization. In this report, we investigated the distribution and the correlation of PIN with that of nNOS in various brain regions of rats. Amplified PIN cDNA from brain tissues revealed an open reading frame which is identical to that of human PIN. Northern blotting of brain RNA with PIN cDNA produced two transcripts, a major 0.9 kb and a minor 2.5 kb. Expression of PIN cDNA as a fusion protein in E. coli produced a 10 kDa protein which interacted specifically with pure nNOS in an overlay assay. Immunoblotting of rat brain regions with nNOS antibody demonstrated strong expression in the cerebellum, moderate expression in the cerebral cortex, midbrain, medulla and hippocampus with only weak expression in the spinal cord. By comparison, PIN expression was stronger in the cerebral cortex, midbrain, hippocampus and medulla compared with that of cerebellum and spinal cord. We conclude that PIN interacts strongly with nNOS and is constitutively expressed in various brain regions. The dissimilarity between nNOS and PIN expressions in various brain regions may explain the well known differences in NOS activity between these regions. Our results also suggest that PIN may serve other functions other than nNOS inhibition.
Amino Acid Sequence↗
The traE gene of plasmid RP4 encodes a homologue of Escherichia coli DNA topoisomerase III.
The polypeptide encoded by the plasmid RP4 traE gene shows extensive protein sequence similarity to Escherichia coli topB, the gene encoding DNA topoisomerase III (Topo III). The traE gene product has been cloned into a bacteriophage T7-based transient expression system, and the polypeptide has been expressed and purified. The TraE protein exhibits topoisomerase activity similar to that of Topo III. Relaxation is stimulated by high temperature and low concentrations of Mg2+. In addition, similar to E. coli Topo III, the TraE protein is a potent decatenase and can substitute for Topo III activity in vivo. The biochemical properties of the TraE protein in vitro suggest that the protein may be involved in the resolution of plasmid DNA replication intermediates either during vegetative replication or in conjugative DNA transfer. Putative homologues of Topo III have been found to be encoded by other broad host range, conjugative plasmids isolated from both Gram-negative and Gram-positive organisms, suggesting that Topo III-like polypeptides may have an essential role in the propagation of many promiscuous plasmids.
Amino Acid Sequence↗
Expression, purification, and partial characterization of HCV RNA polymerase.
The product of the NS5B gene of Hepatitis C Virus (HCV) has been expressed in Escherichia Coli both as a fusion protein with glutathione-S-transferase (GST) of molecular weight 91 KDa and at high level as a single protein of molecular weight 65 KDa. The protein was sequestered within inclusion bodies and a variety of procedures designed to minimize inclusion body formation proved unsuccessful. The method finally adopted involved the purification of inclusion bodies followed by the solubilization, purification, and refolding of the expressed protein. A good recovery and protein purity of the order of 80-90% were achieved. The purified protein was shown to possess RNA polymerase activity in an assay using polyA/oligoU as template. The enzymatic activity is rifampicin resistant, poly A dependent, and requires Mg++. The availability of purified HCV RNA polymerase will allow the study of viral replication and constitute the basis for testing new anti-viral drugs.
Cloning, Molecular↗
Expression of NMDA receptor-1 (NR1) and huntingtin in striatal neurons which colocalize somatostatin, neuropeptide Y, and NADPH diaphorase: a double-label histochemical and immunohistochemical study.
The subset of striatal neurons which colocalize SS/NPY/NADPH-d are selectively resistant to neurodegeneration in Huntington's Disease (HD) and to excitotoxic cell death induced experimentally with NMDA receptor (NMDAR) agonists. Here we have analyzed the expression of immunoreactive NMDAR-1 (NR1) subunit (as an index of NMDAR protein) and of huntingtin (the normal product of the HD gene) in primary cultures of rat striatum to see if differential expression of the two antigens in the subset of SS/NPY/NADPH-d and other striatal neurons can explain their selective resistance or vulnerability. Double-label histochemical and immunocytochemical studies were carried out using conventional and confocal laser scanning microscopy to characterize the cellular and subcellular expression of NR1 and SS, or NPY or bNOS, together with NADPH-d histochemistry. The percentages of cultured striatal neurons that were positive for NADPH-d, SS, NPY, bNOS, and NRI were, respectively, 3.8, 8.4, 10.2, 5.1, and 80%. The majority of striatal NADPH-d neurons coexpressed SS and NPY; 17% of SS-producing neurons were strongly positive for NR1; the remaining cells (approximately 80%) exhibited only weak NR1 expression. Comparable data were obtained for NPY-positive neurons, 15% of which colocalized NR1 strongly and 70-80% weakly. By double-label immunofluorescence, huntingtin was nonselectively expressed in virtually all striatal neurons including SS/NPY/NADPH-d neurons. These results show that the majority of striatal SS/NPY/NADPH-d neurons express NR1. The relative abundance of NR1 in SS/NPY/NADPH-d neurons, however, varies between a small subset of neurons that are receptor rich and the remainder that express low levels only and may determine susceptibility to NMDAR-mediated neurotoxicity. Huntingtin is nonselectively expressed in virtually all striatal neurons and does not appear to be a determinant of the selective resistance of normal striatal SS/NPY/NADPH-d neurons to NMDA toxicity.
Animals↗
Is there a relationship between proximity to industry and the occurrence of otitis media with effusion in school entrant children?
In a study of the relationship between the prevalence of persistent otitis media with effusion (OME) in school entrant children in Redcar and Cleveland and the distance of the homes of these children from known industrial emission points, 1156 school entrant children were screened for the presence of persistent OME. The social disadvantage scores and map references were determined from the postcode area of each of the study entrants and map references were also obtained of known industrial emission points in the locality. Analyses were conducted on the association between the presence of OME and distance from emission sources and between the presence of OME and disadvantage score. A significantly greater proportion of study entrants with OME lived within 1000 meters of an industrial emission point than further away. However, there was no trend established between the proportion of study entrants with OME and increasing distance from an emissions source, nor was there any significant relationship established between the social disadvantage score of the areas of residence of the study entrants and the presence of OME. Further research is required to establish the effect of confounding variables on this relationship.
Air Pollution↗
A randomized cross-over study comparing the use of a catheter valve and a leg-bag in urethrally catheterized male patients.
OBJECTIVES: To evaluate the use of a catheter valve (CV) and a leg-bag (LB) in men with urethral catheters and to determine the preferred modality. PATIENTS AND METHODS: Eighteen men (mean age 71.4 years, SD 3.4, range 63-76) presenting in acute retention and catheterized urethrally were enrolled in a 6-week randomized cross-over study comparing the CV with the LB (3 weeks with each modality). The outcome was assessed using a questionnaire which quantified the incidence of bladder spasms, nocturnal frequency, the extent of any by-passing episodes and the degree of discomfort. At the end of the study, the patients were asked to express a preference (using a subjective scoring scale) for either the CV or the LB and to give the reasons why. RESULTS: There was no difference in the reported incidence of bladder spasms or discomfort and no difference in positive urine cultures with each modality. However, with the CV, there was a slightly higher incidence in nocturnal frequency and by-passing episodes. Thirteen patients preferred the CV whilst five preferred the LB. With the subjective scoring scale (range 0-10), the CV scored significantly higher than the LB (7.2, SD 3.1 and 5.2, SD 2.8, P < 0.05: paired t-test). CONCLUSIONS: Most patients preferred to use the CV, reporting that it felt more comfortable and discreet, and many patients did not like the sensation of urine 'sloshing about' when using the leg-bag. Some patients using the CV were troubled by nocturnal frequency. In these patients we suggest that a combination of a valve during the day and an overnight bag may be the ideal solution.
Acute Disease↗