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S Kagimoto

Publications and source records attributed to S Kagimoto.

25 records · Page 2Linked to original sources

Cloning, functional expression and pharmacological characterization of a fourth (hSSTR4) and a fifth (hSSTR5) human somatostatin receptor subtype.

Somatostatin exerts diverse effects in various tissues upon binding its specific membrane receptors. Recently, we have cloned three different somatostatin receptor subtypes. Here we report the sequence and functional expression of a fourth and a fifth human somatostatin receptor subtype, termed hSSTR4 and hSSTR5, respectively. The hSSTR4 encodes a protein of 388 amino acids and the hSSTR5 is a protein of 364 amino acids. There is 42-60% identity among the amino acid sequences of the five human somatostatin receptor subtypes identified to date. RNA blotting studies reveal that the hSSTR4 is expressed as a single transcript of 4.8 kb in MIA PaCa-2 cells, a cell line derived from human pancreatic cancer while the hSSTR5 is undetectable in the tissues examined. The hSSTR4 and hSSTR5 transiently expressed in COS1 cells exhibit specific binding to somatostatin-14 with IC50 values of 1.6 and 0.16 nM, respectively. We also have characterized the binding affinity of various somatostatin analogues to the hSSTR4 and hSSTR5. The rank of the potency of the analogues are: somatostatin-14 = somatostatin-28 >> RC-160 >> SMS201-995 for the hSSTR4 and somatostatin-28 > somatostatin-14 >> RC-160 > SMS201-995 for the hSSTR5. These results suggest that diverse actions of somatostatin are mediated by at least five somatostatin receptor subtypes with potentially different function.

Amino Acid Sequence↗

Duodenal findings on ultrasound in children with Schonlein-Henoch purpura and gastrointestinal symptoms.

Abdominal ultrasonic examination was performed in 14 patients with Schonlein-Henoch purpura (SHP). Thickening of the duodenal wall was observed in nine (82%) of the 11 with such gastrointestinal (GI) symptoms as severe abdominal pain or bleeding. The thickened duodenal wall showed a high echogenicity. Enlargement of the duodenal lumen was seen in seven (64%) patients with GI symptoms. These findings had been observed in four patients before SHP was diagnosed on the basis of the peculiar skin lesions. In three cases of SHP without GI symptoms, those changes were absent. Four cases of ulcerative colitis, three of bacterial enterocolitis (two Yersinia and one Klebsiella), and five without SHP and any GI problems did not exhibit such duodenal abnormalities. On subsequent endoscopic study, mucosal edema and multiple hemorrhagic erosions were seen, especially at the second portion of the duodenum in two cases of SHP. Biopsy specimens from the duodenum of those cases showed leukocytoclastic vasculitis, suggested by the ultrasound (US) findings. It is important to consider the duodenal changes carefully when US is performed in patients with severe GI symptoms of unknown origin. The characteristic duodenal findings described suggest the differential diagnosis of SHP, which usually requires no surgical intervention.

Adolescent↗

Somatostatin receptors, an expanding gene family: cloning and functional characterization of human SSTR3, a protein coupled to adenylyl cyclase.

We previously reported the cloning of two distinct somatostatin receptor (SSTR) subtypes, SSTR1 and SSTR2. Although both SSTR1 and SSTR2 bound somatostatin specifically and with high affinity, neither was coupled to adenylyl cyclase, a major cellular effector of somatostatin's actions. Here we report the cloning and functional characterization of a third member of the SSTR family. Human SSTR3 is a protein of 418 amino acids and has 45% and 46% identity with human SSTR1 and SSTR2, respectively. RNA blotting studies showed that SSTR3 mRNA could be readily detected in brain and pancreatic islets. The pharmacological properties of human SSTR3 were characterized by transiently expressing the human SSTR3 gene in COS-1 cells. Membranes from cells expressing human SSTR3 bound the somatostatin agonist [125I]CGP 23996 specifically and with high affinity, with a rank order of potency of somatostatin-28 = CGP 23996 > somatostatin-14 > SMS-201-995. Studies using cells transiently coexpressing the human dopamine D1 receptor and human SSTR3 showed that somatostatin was able to inhibit dopamine-stimulated cAMP formation in a dose-dependent manner, indicating that SSTR3 was functionally coupled to adenylyl cyclase. These results indicate that the diverse biological effects of somatostatin are mediated by a family of receptor with distinct, but overlapping, tissue distributions, unique pharmacological properties, and potentially different functions.

Adenylyl Cyclases↗

Changes of anti-HB core antibody in children with positive HB surface antigen.

To elucidate the clinical courses of children chronically infected with HB virus (HBV), RIA values of anti-HBc were surveyed in 88 cases with positive HBs antigen. Among 56 children with positive HBe antigen, 20 had negative, indefinite or low titers of anti-HBc, and 18 (90%) of them had no liver malfunction. Out of 30 cases with abnormal liver function tests, 28 (93%) had high titers of anti-HBc. Follow-up study for a period of over 12 months reveals that serum HBe antigen disappeared in 10 out of the 40 cases who were positive for this antigen. All of the 10 cases had liver malfunction and high levels of anti-HBc. Among 12 children with initially positive anti-HBe, five had high titers of anti-HBc. Out of 13 children who once had high levels of anti-HBc, 3 showed reduction in titers of anti-HBc during the follow-up period in accordance with decrease in activity of hepatitis. Four out of 16 who initially had HBe antigen and low titers of anti-HBc showed high titers of anti-HBc during the observation period, while only one of 33 who had HBeAg and a high titer of anti-HBc went to the low titer group of anti-HBc, though continuously positive for HBe antigen. We presume that high levels of anti-HBc indicate previous or current liver damage due to HBV infection, while low titers of anti-HBc indicate that HBV-derived liver damage has not yet occurred or that a long time has passed since the last episode of liver damage subsided.

Adolescent↗

Study to establish normal values for portal vein blood flow in children using a duplex ultrasound system.

Portal vein blood flow in healthy children was measured using a duplex ultrasound system consisting of a B mode linear scanner and a single Doppler transducer. Portal blood flow volume (PBFV) correlated with age, height, weight and body surface area. Increases in PBFV with age were greater in boys than girls. A correlation was noted between the diameter of the portal vein and PBFV (r = 0.89). However, the maximum portal blood flow velocity (Vmax) did not correlate with age, height, weight or body surface area. Increases in PBFV in accordance with physical development was thought to depend mainly on widening of the portal vein and not on acceleration of portal blood flow velocity. The formula for calculating PBFV by multivaliate statistical analysis is as follows: PBFV(ml/min) = 30.1 x age(yrs) - 1.07 x height(cm) = 3.31 x weight(kg). Portal vein flowmetry using a duplex ultrasound system may be useful for evaluation of the hepatic circulation in children.

Adolescent↗

Effect of diabetes on the free polyol pattern in cataractous lenses.

To obtain information about the effects of lenticular polyols on the prevention, initial stages, and development of diabetic cataracts, we identified and determined with gas-liquid chromatography or gas-liquid chromatography/mass spectrometry eight polyols in cataractous lenses of non-insulin-dependent diabetes mellitus patients and nondiabetic subjects. In the diabetics' lenses, the concentrations of polyols (e.g., sorbitol, fructose, mannitol, and adonitol) were higher than in the nondiabetics' lenses, whereas the concentration of 1-deoxyglucose was lower. The mean concentration of myo-inositol in lenses of diabetics was lower than that of nondiabetics, but this difference was statistically not significant. The total content of eight polyols in the diabetics' lenses did not differ significantly from that in the nondiabetics. In the lenses of diabetics, the content of glucose correlated positively with that of adonitol, fructose, and sorbitol. In the lenses of nondiabetics, the content of glucose correlated positively with that of mannitol and inversely with that of 1-deoxyglucose and myo-inositol. In diabetics, hemoglobin A1 (%) correlated positively with the concentration of adonitol in the lenses and inversely with the concentration of lens myo-inositol; however, it did not correlate with the concentration of glucose in lenses. Regulation of both the metabolism of lenticular polyols and the pattern of polyols in serum may be necessary for normalizing lenticular polyol content.

Aged↗