A novel G protein-coupled receptor kinase gene cloned from 4p16.3.

Within the Huntington's disease (HD) candidate region of 4p16.3, the D4S127 locus displays strong linkage disequilibrium with the defect and anchors a conserved haplotype found on many HD chromosomes. To isolate genes from this region we have applied the exon amplification technique to overlapping cosmids spanning D4S127. Here, we report the discovery of a new gene encoding a novel member of a family of protein kinases that specifically phosphorylate the activated forms of G protein-coupled receptors. Such kinases are thought to participate in desensitization of specific receptors, thereby blocking further signal transduction. This gene must now be carefully scrutinized to determine whether it might be involved in HD.     

Inhibitory effect of islet amyloid polypeptide of glucose-induced proinsulin biosynthesis in rat insulinoma cells.

Islet amyloid polypeptide (IAPP) has been recently identified as the principal constituent of amyloid deposits in pancreatic islets of patients with type 2 (non-insulin-dependent) diabetes mellitus and causes insulin resistance in some target cells. In addition, glucose-induced insulin secretion is inhibited by IAPP. We studied the effect of IAPP on proinsulin biosynthesis in rat insulinoma (RINr) cells. Glucose at concentrations of 0, 15, 30, 60, 100, and 300 mg/dl stimulated proinsulin biosynthesis in a dose-responsive and and actino-mycin D-inhibitable manner after 6 h of incubation. At a glucose concentration of 300 mg/dl, IAPP decreased the mean responses of proinsulin biosynthesis to 61.2 and 29% at concentrations of 0.1 and 1 microM, respectively, compared with the IAPP-free control. In conclusion, IAPP inhibits glucose-induced proinsulin biosynthesis in RINr cells. IAPP might play an important role in the pathogenesis of type 2 diabetes mellitus.     

Transurethral incision and posterior resection of prostate (TUI-PRP) for selected patients with benign obstructive prostatic disease.

Transurethral incision and posterior resection of the prostate (TUI-PRP) is described and used to overcome my three concerns in performing transurethral incision of the prostate (TUIP). The favorable result from TUI-PRP is presented.     

Immunopathological study on the uterine spiral arteries in pregnancy-induced hypertension]

The uterine spiral arteries were studied by the immunohistochemical ABC method in 30 cases of Pregnancy Induced Hypertension (PIH) and 10 cases of normal pregnant women. Depositions of IgM and/or C3 on the vessel wall were significantly observed only in PIH cases (15 cases, 50.0%; P < 0.05). Depositions of IgG were seen in 5 cases of PIH 16.7% showing significantly decrease. (P < 0.001), as compared with the normal pregnant women (9 cases, 90.0%). The results suggest that PIH is related to chronic rejection reaction resulting possibly from the decrease of local immunosuppression in pregnancy. Meanwhile the positive stain of IgG, IgM and C3 seen in the nuclei of decidual cells in some of PIH cases were discussed.     

Acute pseudo-obstruction of the colon following partial splenic artery embolization: report of a case.

This is a case of a 45-year-old woman suffering from liver cirrhosis with hypersplenism who received a partial splenic artery embolization with gelfoam pieces. Thrombocytopenia and leukopenia improved immediately after treatment. Marked abdominal distention, metallic bowel sounds and combined small and large bowel distension with air-fluid levels as shown on a plain abdominal X ray were noted on the fifth day after the embolization procedure. Laparotomy was performed. No mechanical obstruction was found during surgery. Acute pseudo-obstruction of the colon (Ogilvie's syndrome) was diagnosed. This condition was considered to be a complication of the partial splenic artery embolization and has not hitherto been reported.     

Pancreas divisum with early pancreatic cancer--presenting as chronic obstructive pancreatitis.

A 61-year-old man experienced four bouts of pancreatitis in 1 year. Detailed history taking and a series of examinations, including sonography, computed tomography scan, and endoscopic retrograde cholangiopancreatography (ERCP), revealed pancreas divisum on the first admission. He was treated conservatively. However, repeated ERCP on the fourth admission, 1 year later, showed a small filling defect in the tail of the pancreatic duct. A distal pancreatectomy was carried out. Pathological studies revealed a small papillary adenocarcinoma (1.5 x 1.0 x 0.5 cm) confined to the pancreatic duct grossly with minimal parenchymal invasion microscopically. He has been free from cancer and pancreatitis for 13 months since the operation.     

Rules for differentiating symptoms and signs of the heart-qi deficiency syndrome

344 cases of Heart-Qi Deficiency Syndrome (HQDS) including 19 Kinds of disease were observed to explore the rule of differentiation of symptoms and signs for HQDS. The results showed that the common symptoms of HQDS were weakness, shortness of breath, and palpitation, etc. According to with or without complicated cardiovascular diseases, the patients were divided into two groups: group A with cardiovascular diseases, group B without that. In group A, the symptoms and signs of HQDS were the most frequent and early clinical manifestations, the associated symptoms and signs were blood stasis and attack of water-evil, etc. In group B, in whom often associated with nervous and emotional symptoms such as insomnia, dreamfulness, and amnesia, etc., which was due to the disturbance of emotional activities of heart. In order to avoid diagnostic confusion, the authors suggest that the HQDS patients with cardiovascular diseases would be diagnosed as HQDS; on the other hand, the HQDS patients without cardiovascular diseases would be diagnosed as disturbance of emotional activities of heart.     

Coexistence of autonomic and somatic mechanisms in the pressor areas of medulla in cats.

The effects of electrical stimulation and microinjection of sodium glutamate (0.5 M) in the sympathetic pressor areas of the dorsal medulla (DM), ventrolateral medulla (VLM), and parvocellular nucleus (PVC) on the knee jerk, crossed extension, and evoked potential of the L5 ventral root produced by intermittent electrical stimulation were studied in 98 adult cats anesthetized with chloralose and urethane. During electrical and glutamate stimulation of these pressor areas, in addition to the rise of systemic arterial blood pressure marked inhibition of the spinal reflex was produced, indicating presence of neuronal perikarya responsible for these actions. Mild to moderate augmentation of spinal reflexes was also observed during brain stimulation but only in a few cases. The magnitude of the somatic effects among the pressor areas of the VLM, DM, and PVC subsequent to glutamate activation was about the same. Induced spinal reflex inhibition, independent from the baroreceptor and vagal influence, remained essentially unaltered after acute midcollicular decerebration. The inhibition was also observed in cats decerebellated 8-10 days in advance. The inhibition was not affected after bilateral electrolytic- or kainic-acid-induced lesions in the paramedian reticular nucleus (PRN). On the contrary, PRN-induced spinal reflex inhibition was attenuated after bilateral lesions in the DM or VLM. Data suggest that there coexists neuronal subpopulations in the VLM, DM, and PVC that can affect both the sympathetic pressor systems and spinal reflexes.     

Triflavin, an Arg-Gly-Asp containing snake venom peptide, inhibits aggregation of human platelets induced by human hepatoma cell line

Triflavin, an Arg-Gly-Asp (RGD)-containing peptide, purified from snake venom of Trimeresurus flavoviridis, inhibits human platelet aggregation through the blockade of fibrinogen binding to fibrinogen receptors associated with glycoprotein IIb/IIIa complex. In this report, we examined the effect of triflavin on tumor cells (human hepatoma J-5)-induced platelet aggregation (TCIPA) of heparinized platelet-rich plasma (PRP). ADP-scavenger agents, apyrase (10 U/ml) and creatine phosphate (5 mM)/creatine phosphokinase (5 U/ml) did not inhibit TCIPA while hirudin (5u/ml) completely inhibited it. J-5 cells initially induced platelet aggregation, then blood coagulation occurred. J-5 cells concentration-dependently shortened the recalcification time of normal as well as Factor VIII, IX-deficient human plasmas, while it was inactive at shortening the recalcification time of Factor VII-deficient plasma, suggesting J-5 cells induced platelet aggregation through activation of extrinsic pathway, leading to thrombin formation as evidenced by the amidolytic activity on S-2238 by expressing tissue factor-like activity. Triflavin inhibited TCIPA in a dose-dependent manner (IC₅₀, 0.02 μM). When compared on molar ratio, triflavin was approximately 30,000 times more potent than GRGDS (IC₅₀,0.58 mM). On the other hand, GRGES showed no significant effect on TCIPA, even its concentration was raised to 4 mM. Additionally, the monoclonal antibodies, raised against glycoprotein IIb/IIIa complex (i.e., 7E₃ and 10 E₅) inhibited J-5 TCIPA. In conclusion, we suggest the inhibitory effect of triflavin on J-5 TCIPA may be chiefly mediated by the binding of triflavin to the fibrinogen receptor associated with glycoprotein IIb/IIIa complex on platelet surface membrane.