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Biomedical subjects

G Koh

Publications and source records attributed to G Koh.

28 records · Page 2Linked to original sources

Degradation and conversion of somatostatin in normal and diabetic rats in vivo and in vitro.

Plasma somatostatin-like immunoreactivity in the portal and jugular veins of streptozotocin diabetic rats was compared with that in normal control rats. In the diabetic group, somatostatin levels in the portal (p less than 0.05) and jugular (p less than 0.01) veins were both elevated compared with those in the control group. Moreover, the degree of elevation was greater in the jugular vein than in the portal vein. To further investigate the role of the liver in the clearance of somatostatin-28 in vivo, 2 micrograms of somatostatin-28 was administered as a bolus into the external jugular vein of intact and functionally hepatectomized rats. The mean half-time of somatostatin-28 was significantly longer in intact diabetic rats than in controls (p less than 0.05). The functional hepatectomy did not cause a significant difference in the half-time in diabetic rats but made it longer in control rats. These results suggest that the longer half-time of somatostatin-28 in diabetic rats in vivo is due to its slower hepatic clearance. The hepatic clearance of somatostatin-28 and somatostatin-14 was further studied in vitro using a recirculating liver perfusion method. The hepatic clearance of 1.2 nM of either somatostatin-28 or somatostatin-14 was significantly lower in diabetic rats than in controls (p less than 0.01). This indicates that elevated plasma somatostatin levels in diabetic rats are caused at least in part by decreased hepatic clearance of somatostatin.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Sequence of an intestinal cDNA encoding human motilin precursor.

A cDNA clone encoding the human motilin precursor was isolated from an intestinal library using synthetic oligonucleotide probes. The predicted amino acid sequence indicates that the motilin precursor consists of 115 amino acids and includes a 25-residue N-terminal signal peptide followed by the 22-amino-acid motilin sequence and a long, 68-residue C-terminal peptide. The amino acid sequence of human motilin predicted from the cDNA sequence is identical to its porcine counterpart, which has been determined by protein sequencing. Proteolytic processing of promotilin to motilin occurs at the sequence, Lys-Lys, this being the first reported instance of processing occurring at a pair of Lys residues. In other precursors it occurs at Lys-Arg, Arg-Arg, Arg, or very rarely Lys.

Amino Acid Sequence↗

Effect of the alpha 2-blocker DG-5128 on insulin and somatostatin release from the isolated perfused rat pancreas.

2[2-(4.5-Dihydro-1H-imidazol-2-yl)-1-phenylethyl] pyridine dihydrochloride sesquihydrate (DG-5128) is an alpha 2-specific-adrenergic antagonist. We have studied the effect of DG-5128 on insulin and somatostatin release from the isolated perfused rat pancrease. DG-5128 stimulated somatostatin and insulin release not only at a low glucose concentration but also at a high glucose concentration. These findings suggest that an alpha 2-adrenergic receptor plays an important role in the regulation of insulin and somatostatin secretion.

Animals↗

Effects of oral glucose administration on preproinsulin mRNA in rats in vivo.

An experiment was performed to examine whether the acute increase in insulin release induced by oral glucose ingestion is associated with alterations in pancreatic preproinsulin mRNA (PImRNA) levels. Rats either fed ad libitum or after overnight fast were used. Fasted rats were administered glucose orally in a conscious, unrestrained state. Pancreatic RNA was extracted and the relative level of PImRNA was determined by dot blot analysis with a cloned rat preproinsulin I cDNA probe. In fasted animals PImRNA levels decreased compared with those of fed animals and showed no significant changes after acute glucose administration, while blood glucose and plasma insulin increased rapidly to maximum values at 15 min after glucose administration. Although the transcription rate was not directly measured in this experiment, it is possible that the rapid increase in insulin release from the beta cell under physiological conditions is controlled by post-transcriptional regulations.

Animals↗

Restriction fragment length polymorphism (RFLP) of the human insulin receptor gene in Japanese: its possible usefulness as a genetic marker.

Restriction fragment length polymorphism of the human insulin receptor gene was analyzed with a 4.2 Kb cDNA probe in Japanese normal subjects and Type 2 (non-insulin-dependent) diabetic patients. Restriction endonuclease Rsa I digestion showed polymorphism of the human insulin receptor gene, with a band at 6.7 Kb, 6.2 Kb or 3.6 Kb. The frequency of the 6.7 Kb band was less than that in Caucasians. Furthermore, 15% of all the Japanese subjects examined lacked a 3.6 Kb band, which is commonly found in Caucasians. We have also detected restriction fragment length polymorphism in the human insulin receptor gene by Pvu II or Stu I digestion. Although no significant association of restriction fragment length polymorphism with Type 2 diabetes was found in the present study, our results suggest that the restriction fragment length polymorphism in the human insulin receptor gene varies among ethnic groups, and that the restriction fragment length polymorphism linked to the human insulin receptor gene might be a useful marker for the linkage study of the genes located close to the human insulin receptor gene on chromosome 19.

Adult↗

The polymorphism linked to the human insulin gene: its lack of association with either IDDM or NIDDM in Japanese.

Polymorphism of 5' portion of the human insulin gene was examined in 188 unrelated Japanese subjects (49 normal, 71 with IDDM, and 68 with NIDDM) using restriction endonuclease analysis. Restriction fragments were classified according to the insertion size: Class 1 (600 base pairs), Class 2 (1300 base pairs), and Class 3 (2000 base pairs). We found a very high frequency of Class 1 alleles (96.8%) and a low frequency of both Class 2 (0.8%) and Class 3 alleles (2.4%) and that approximately 94% of the genotypes were Class 1/Class 1 homozygote. In addition, there was no correlation of allelic or genotypic frequency with NIDDM or IDDM. We conclude that length polymorphism of the human insulin gene cannot be a useful marker for diabetes in Japanese.

Diabetes Mellitus, Type 1↗

Epstein-Barr virus-associated hemophagocytic syndrome: virological and immunopathological studies.

The virus-associated hemophagocytic syndrome (VAHS) is a disorder characterized by a benign, generalized histiocytic proliferation, with marked hemophagocytosis associated with systemic viral infections. We have studied the virological and immunopathological events occurring in two children experiencing Epstein-Barr VAHS. Neither of the patients had an underlying immunodeficiency and both recovered from their disease and are completely well one year after follow-up. In each patient, evidence for primary Epstein-Barr virus (EBV) infection was documented with a typical humoral immune response, including IgM antibody directed against virus capsid antigen. EBV was demonstrated in lymphoreticular tissues by electron microscopy and molecular hybridization studies. Permissive EBV infection was suggested by the finding of mature virus particles and linear viral DNA in lymphoreticular tissues. Immunopathological studies demonstrated complete effacement of lymph node architecture by a marked proliferation of immunoblasts in patient 1 and infiltration and effacement of the lymph node architecture with benign-appearing histiocytes in patient 2. Atypical lymphocytes characteristic of acute EBV infection were notably absent in the peripheral blood of both patients and cytotoxic T cells, which normally lyse EBV-infected B cells, were also absent from the peripheral circulation. Our observations suggest that EBV-induced VAHS may be the result of an increased virus burden in the face of immunoregulatory cell imbalances.

Bone Marrow Examination↗

Coarctation of the aorta and renal artery stenosis in tuberous sclerosis.

Among neurocutaneous disorders, coarctation of the abdominal aorta and renal artery stenosis have traditionally been associated with neurofibromatosis. We report a 5-year-old girl who, during the evaluation of asymptomatic hypertension, was discovered to have bilateral renal artery stenosis, coarctation of the abdominal aorta, renal cysts and typical skin lesions of tuberous sclerosis. Renal vascular hypertension has not been reported previously in tuberous sclerosis. We conclude that the tuberous sclerosis complex should be expanded to include vascular malformations and that hypertension should not be assumed to be secondary to renal hamartomata or cysts in patients with tuberous sclerosis.

Aortic Coarctation↗

Cystic kidneys in a patient with oral-facial-digital syndrome type I.

A cystic renal lesion is described in a girl with oral-facial-digital syndrome, type I. Excretory urography was normal at 1 yr of age; however, flank masses, hypertension, and renal failure were discovered at 11 yr of age. Bilateral nephrectomies were performed prior to renal transplantation. The renal cortex was replaced by large cysts. The cysts were lined by flattened nondescript epithelium and many contained glomerular tufts. Twenty renal cysts were aspirated, and the cyst fluid analyzed for sodium, potassium, creatinine, and osmolality. The concentration of solutes in the cyst fluid was comparable to plasma values. The pathologic features and pattern of cyst solute concentration appear to distinguish the cystic renal lesion in oral-facial-digital syndrome from the more common adult-type polycystic kidney disease.

Abnormalities, Multiple↗