Formation of ozone by fireworks.
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Journal Article↗
Biomedical subjects
U Kumar
Publications and source records attributed to U Kumar.
A conserved alpha-helix at the amino terminus of prosomatostatin serves as a sorting signal for the regulated secretory pathway.
Mammalian prosomatostatin (PSST) contains the bioactive peptides SST-14 and SST-28 at the COOH-terminal end of the molecule and a putative sorting signal in the propeptide segment for targeting the precursor to the regulated secretory pathway. The NH(2)-terminal segment of PSST consists of an amphipathic alpha-helix, which has been totally conserved throughout vertebrate evolution. We have analyzed the PSST-(3--15) region for sorting function by alanine scanning and deletional mutagenesis. Mutants created were stably expressed in AtT-20 cells. Regulated secretion was studied by analyzing basal and stimulated release of SST-14 LI and by immunocytochemistry for staining of SST-14 LI in punctate granules. Deletion of the PSST-(3--15) segment blocked regulated secretion and rerouted PSST for constitutive secretion as unprocessed precursor. Alanine scanning mutagenesis identified the region Pro(5)--Gln(12) as being important in precursor targeting, with Leu(7) and Leu(11) being critical. Molecular modeling demonstrated that these two residues are located in close proximity on a hydrophobic surface of the alpha-helix. Disruption of the alpha-helix did not impair the ability of PSST to be processed at the COOH terminus to SST-14 and SST-28. Processing, however, was shifted to the early compartments of the secretory pathway rather than storage granules and was relatively inefficient.
Amino Acid Sequence↗
Neurodegeneration in Niemann-Pick type C disease mice.
Niemann-Pick disease type C (NP-C) is an inherited neurodegenerative disorder associated with intracellular cholesterol and glycolipid trafficking defects. Two separate genes, NPC1 and NPC2, have been linked to NP-C. NPC1 encodes a polytopic membrane-bound protein with a putative sterol-sensing domain. NPC2 has been recently identified as epididymal secretory glycoprotein 1. The NPC1 protein functions in the vesicular redistribution of endocytosed lysosomal cargo, but how its inactivation leads to neurodegeneration is not known. The neurological symptoms of NP-C typically appear after a period of normal early development and reflect progressive degeneration of widespread brain regions. Here we have delineated the pattern of neurodegeneration in NP-C mice, whose genetic defect has been shown to be an inactivating mutation of the mouse NPC1 gene. The results reveal a spatially and temporally specific pattern of degeneration of nerve fibers followed by degeneration of neuronal cell bodies beginning as early as day 9 and continuing throughout life. We have recently showed that in the primate brain, the NPC1 protein is localized predominantly within perisynaptic astrocytic processes. The present observations suggest that a functional disturbance in NPC1 could disrupt vesicular transport of cholesterol, glycolipids and possibly other endocytic cargo in glia, which is critical for maintaining the integrity of neurons.
Aging↗
Newer techniques in intracorporeal tissue approximation: suturing, tissue adhesives, and microclips.
Great strides have been made in the discovery of alternative tissue approximation techniques for use in laparoscopy. Although none of the techniques have eliminated the need for suturing laparoscopically, their potential in achieving this end is promising. When an ideal approximation technique is discovered that is easy to use, safe, and reliably able to hold tissue together laparoscopically, laparoscopic reconstructive surgery should become less formidable and more appealing to urologists.
Animals↗
Immunohistochemical detection of somatostatin receptor types 1-5 in medullary carcinoma of the thyroid.
BACKGROUND: We have analysed the distribution of the five somatostatin receptors (sst1-5) by immunohistochemistry in a large retrospective series of 51 medullary carcinoma of the thyroid (MCT) specimens and correlated the pattern of sst expression with expression of somatostatin (SRIF) peptide, tumour pathology and clinical outcome. MEASUREMENTS: Immunohistochemistry was performed with rabbit polyclonal antipeptide antibodies directed against the extracellular domains or cytoplasmic tail of human (h) sst1-5. SRIF immunoreactivity was investigated in parallel paraffin sections. RESULTS: Eighty-five percent of the tumours were positive for one or more sst, localized to both tumour cells as well as surrounding peritumoural structures, especially blood vessels. Forty-nine percent of the tumours were positive for sst1, 43% for sst2, 47% for sst3, 4% for sst4, and 57% for sst5. Fifty-one percent of tumours expressed one or two sst subtypes; 33% were positive for three or more sst isoforms. All five sst receptors were detected in only two cases. Tumours expressing octreotide sensitive subtypes (sst2,3,5) accounted for 75% of the series. 50% of the tumours co-expressed SRIF suggesting tumour cell regulation by endogenous SRIF via paracrine/autocrine circuits. There was no correlation between sst1-5 expression and age, sex, tumour size or stage, histological type or clinical outcome. Simultaneous analysis of primary tumour and lymph node metastases revealed a similar pattern of sst immunoreactivity indicating that sst expression is not modified in the course of disease progression. CONCLUSIONS: With the exception of sst4, medullary carcinoma of the thyroid display a rich but heterogeneous expression of sst subtypes. Immunohistochemical typing of sst receptor expression using specific antireceptor antibodies represents an ideal approach for characterizing sst subtype expression in medullary carcinoma of the thyroid for optimizing receptor targeted diagnosis and therapy with somatostatin analogs.
Adult↗
Somatostatin suppresses endothelin-1-induced rat hepatic stellate cell contraction via somatostatin receptor subtype 1.
BACKGROUND & AIMS: Hepatic stellate cells (HSCs) are considered therapeutic targets to decrease portal hypertension. To elucidate some of the hemodynamic effects of somatostatin (SST) on portal pressure, the presence and function of SST receptors (SSTRs) on HSCs were investigated. METHODS: SSTR messenger RNA expression, and SSTR presence was investigated using reverse-transcription polymerase chain reaction, real-time quantitative polymerase chain reaction, Western blotting, and immunohistochemistry. The function of SSTRs was studied by examining the effects of SST and specific SSTR agonists on endothelin-1(ET-1)-induced HSC contraction. RESULTS: Specific amplicons for SSTR subtypes 1, 2, and 3 were demonstrated in rat liver and in activated HSCs. The presence of SSTR subtypes 1, 2, and 3 was confirmed by Western blotting. With immunohistochemistry, a strong staining of HSCs was obtained for SSTR subtypes 1, 2, and 3 in CCl4-treated rats, but not in normal rat liver. Incubation of HSCs on collagen gels with buffer, 10(-8) mol/L SST, and 2 x 10(-8) mol/L ET-1 resulted in collagen surface area decreases of 5.5% +/- 3.3%, 6.8% +/- 4.4%, and 49.8% +/- 8.3%, respectively. Relative contraction of gels preincubated with 10(-8) mol/L SST followed by 2 x 10(-8) mol/L ET-1 or vice versa as compared with maximal contraction (100%) with 2 x 10(-8) mol/L ET-1 were 72.6% +/- 17.9% and 76.2% +/- 12.6%, respectively (P < 0.05). SSTR agonist 1, but not SSTR agonist 2 or 3, was able to counteract the contractile effect of ET-1. CONCLUSIONA: Activated rat HSCs bear SSTR subtypes 1, 2, and 3. SST causes significant partial inhibition of ET-1-induced contraction of activated HSCs, mainly by stimulation of SSTR subtype 1.
Animals↗
Laparoscopic approach to adrenal carcinoma.
There is general agreement on the suitability of the laparoscopic approach for benign adrenal lesions but controversy about using laparoscopy for suspected adrenal malignancy. This article reviews the literature on laparoscopic adrenalectomy for cancer: the operative techniques and indications and contraindications.
Adrenal Gland Neoplasms↗
Effects of fibrin glue on injured rabbit ureter.
BACKGROUND AND OBJECTIVE: Fibrin glue is used as a hemostatic agent, has potential as a tissue adhesive, and may promote tissue healing. The histologic effects of fibrin glue on the ureter have not yet been fully investigated. We studied the effect of fibrin glue on the thickness of various layers of injured and uninjured ureters and its effect on vessel density in the rabbit model. MATERIALS AND METHODS: Rabbits were divided into two groups. The ureters were exposed using a midline abdominal incision. In the study group, one of the ureters was crushed, and fibrin glue was instilled around both ureters. In the control group, one of the ureters was crushed, but no fibrin glue was instilled. The animals were sacrificed at 6 weeks and the ureters examined histologically. Using NIH Image Analysis solftware, the thickness of the urothelium, muscular, and adventitial layers and the cross-sectional area of the ureters were measured. The vessel density of the ureters was also assessed. RESULTS: Whereas the thickness of the epithelium was increased in the crushed ureters treated with fibrin glue (20.7 microm v 15.3 microm), the thickness was reduced in the uncrushed ureters treated with fibrin glue compared with controls (16.3 microm v 19.8 microm). There was no statistically significant difference in the thickness of the muscular or adventitial layers in the study and control groups. There was a reduction in the cross-sectional area of the uncrushed ureters treated with fibrin glue compared with controls (7,095 microm2 v 9,409 microm2). In addition, the vessel density in the crushed ureters was reduced in ureters treated with fibrin glue compared with controls (0.00067/microm2 v 0.00108/micro2). In the uncrushed ureters, the difference was not statistically significant. CONCLUSIONS: Fibrin glue has potential as an adhesive agent in the ureter and may promote healing. It may affect epithelial layer thickness and vessel density of the ureter, but these effects were variable. Fibrin glue does not appear to have significant effects on the ureteral muscular and adventitial layers or on the overall cross-sectional area of all three layers. These results indicate that fibrin glue does not appear to have a detrimental effect on the ureter.
Animals↗
Ureteric obstruction with mucocoele of the appendix due to endometriosis.
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Adult↗
Somatostatin is required for masculinization of growth hormone-regulated hepatic gene expression but not of somatic growth.
Pulsatile growth hormone (GH) secretion differs between males and females and regulates the sex-specific expression of cytochrome P450s in liver. Sex steroids influence the secretory dynamics of GH, but the neuroendocrine mechanisms have not been conclusively established. Because periventricular hypothalamic somatostatin (SST) expression is greater in males than in females, we generated knockout (Smst(-/-)) mice to investigate whether SST peptides are necessary for sexually differentiated GH secretion and action. Despite marked increases in nadir and median plasma GH levels in both sexes of Smst(-/-) compared with Smst(+/+) mice, the mutant mice had growth curves identical to their sibling controls and retained a normal sexual dimorphism in weight and length. In contrast, the liver of male Smst(-/-) mice was feminized, resulting in an identical profile of GH-regulated hepatic mRNAs between male and female mutants. Male Smst(-/-) mice show higher expression of two SST receptors in the hypothalamus and pituitary than do females. These data indicate that SST is required to masculinize the ultradian GH rhythm by suppressing interpulse GH levels. In the absence of SST, male and female mice exhibit similarly altered plasma GH profiles that eliminate sexually dimorphic liver function but do not affect dimorphic growth.
Animals↗
Inhibitory effect of 1-benzyl-5[(C)-2,6-dimethyl-1,5-heptadienyl] imidazole (KK-42) on desert locust, Schistocerca gregaria forsk.
Imidazole compound KK-42 was tested for its inhibitory effect on Schistocerca gregaria. The compound caused 80% mortality after 19 days of treatment with 100 microg of KK-42/insect. It also caused the production of deformed adults at even lower doses. Ecdysteroid content, when estimated by RIA, declined due to KK-42 treatment in both haemolymph and ovaries of the insect. Reduction in ecdysteroid titer was maximum at 100 microg of KK-42/insect. The value estimated by RIA was 0.34 ng/pL haemolymph as compared to 0.97 ng/microL in case of controls. Similarly,ecdysteroid content of ovaries detected was 0.48 ng/mg in treated ones as compared to 0.61 ng/mg in controls. Histological studies, however, revealed no alteration in the ovarian tissues due to KK-42 treatment.
Animals↗
Covert bacteriuria in nephrotic syndrome.
Prevalence of covert bacteriuria in patients of nephrotic syndrome admitted for kidney biopsy was studied in 205 patients. Age ranged from 10 years to 65 years. 148 patients were male and 57 were female. Prevalence of covert bacteriuria was found in 38 patients (18.53%). In bacteriuric patients 30 were male, 8 were female. Escherichia coli was the commonest organism grown in bacteriuric patients (30 or 78.9%). Serum albumin was low and 24-hour urinary protein excretion was high in bacteriuric patients in comparison to abacteriuric patients. In bacteriuric patients membranous nephropathy was the commonest histopathological finding present in 15 patients (39.47%).
Adolescent↗
Change in blood group phenotype.
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ABO Blood-Group System↗
Receptors for dopamine and somatostatin: formation of hetero-oligomers with enhanced functional activity.
Somatostatin and dopamine are two major neurotransmitter systems that share a number of structural and functional characteristics. Somatostatin receptors and dopamine receptors are colocalized in neuronal subgroups, and somatostatin is involved in modulating dopamine-mediated control of motor activity. However, the molecular basis for such interaction between the two systems is unclear. Here, we show that dopamine receptor D2R and somatostatin receptor SSTR5 interact physically through hetero-oligomerization to create a novel receptor with enhanced functional activity. Our results provide evidence that receptors from different G protein (heterotrimeric guanine nucleotide binding protein)-coupled receptor families interact through oligomerization. Such direct intramembrane association defines a new level of molecular crosstalk between related G protein-coupled receptor subfamilies.
Animals↗
Subtypes of the somatostatin receptor assemble as functional homo- and heterodimers.
The existence of receptor dimers has been proposed for several G protein-coupled receptors. However, the question of whether G protein-coupled receptor dimers are necessary for activating or modulating normal receptor function is unclear. We address this question with somatostatin receptors (SSTRs) of which there are five distinct subtypes. By using transfected mutant and wild type receptors, as well as endogenous receptors, we provide pharmacological, biochemical, and physical evidence, based on fluorescence resonance energy transfer analysis, that activation by ligand induces SSTR dimerization, both homo- and heterodimerization with other members of the SSTR family, and that dimerization alters the functional properties of the receptor such as ligand binding affinity and agonist-induced receptor internalization and up-regulation. Double label confocal fluorescence microscopy showed that when SSTR1 and SSTR5 subtypes were coexpressed in Chinese hamster ovary-K1 cells and treated with agonist they underwent internalization and were colocalized in cytoplasmic vesicles. SSTR5 formed heterodimers with SSTR1 but not with SSTR4 suggesting that heterodimerization is a specific process that is restricted to some but not all receptor subtype combinations. Direct protein interaction between different members of the SSTR subfamily defines a new level of molecular cross-talk between subtypes of the SSTR and possibly related receptor families.
Dimerization↗
Sequence, expression and reconstitution of an HCV genome from a British isolate derived from a single blood donation.
Morphological analysis of hepatitis C virus and development of antiviral drugs to eradicate this agent have been seriously hampered by the low viraemias observed during natural infection and the unavailability of a cell culture system for virus propagation. Recently a low-grade hepatitis has been reported in chimpanzees after intrahepatic transfection of full-length synthetic HCV RNA and successful infections shown to be critically dependent on the integrity and genetic homogeneity of the reconstituted clone. In this study we describe and characterize a full HCV RNA sequence derived from a case of chronic sporadic hepatitis. The genotype was shown to be 1a with a low level of intraclonal sequence heterogeneity, and processing of both structural and nonstructural proteins has been documented. The assembly of the full genome has also been achieved. The low level of intraclonal variation observed may reflect infection with a single isolate and the fact that cloning was performed on virus obtained from a single blood donation makes this clone a good candidate for future in vivo and in vitro transfection studies.
Animals↗
Simple nephrectomy: transperitoneal approach.
Transperitoneal laparoscopic nephrectomy is performed much as originally described by Clayman and associates, although preoperative embolization of the kidney is no longer routine. Some surgeons use a hand-assisted technique, especially in difficult cases or when the organ is being removed intact, as in live-donor nephrectomy.
Adult↗
Evaluation of tumour markers in carcinoma breast.
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Biomarkers, Tumor↗