Periodic alternating nystagmus and rebound nystagmus in spinocerebellar ataxia type 6.

We report on a family with ataxia type 6 (SCA6) showing peculiar oculomotor symptoms. The proband presented with periodic alternating nystagmus (PAN), and her 2 brothers had rebound nystagmus and gaze-evoked nystagmus. They carried the identical mutation (the number of expanded CAG repeat, 24) in the CACNA1A gene. The intrafamilial variability of oculomotor symptoms may be ascribed to factors other than CAG repeat expansion size in SCA6.     

Platelet activating factor (PAF) involvement in endotoxin-induced thrombocytopenia in rabbits: studies with FR-900452, a specific inhibitor of PAF

PAF (1 ug/kg) injected intravenously (i.v.) into anesthetized rabbits resulted in marked loss of circulating platelets and leukocytes. Administration of FR-900452 1-methyl-3-(1-(5-methylthiomethyl-6-oxo-3-(2-oxo-3-cyclopenten-1-y lidene)- 2-piperazinyl) ethyl)-2-indolinone, a specific PAF inhibitor, at a dose of 10 mg/kg i.v. with 10 min prior to the PAF injection significantly prevented both changes. On the other hand, PAF has been considered as a mediator of endotoxin shock. Therefore, in order to determine whether endogenous PAF contributes to the occurrence of thrombocytopenia or leukopenia in endotoxin shock, we assessed the effect of FR-900452 on the thrombocytopenia and the leukopenia following bolus i.v. injection of E.coli endotoxin (0.03 mg/kg) in rabbits. As a result, pretreatment with the compound (10 mg/kg, i.v.) significantly reduced the thrombocytopenia at 60 and 180 min after the endotoxin injection. In contrast, FR-900452 did not reduced the leukopenia at any time of after endotoxin. These results indicate that PAF might be involved in the occurrence of thrombocytopenia in rabbit endotoxemia and the contribution of PAF to the leukopenia is much less extent than that to the thrombocytopenia.     

Hemobilia: Review of Recent Experience with a Worldwide Problem

Between 1981 and 1985, the reported incidence of hemobilia increased for two major reasons. First, a more sophisticated and better-trained medical community could entertain the diagnosis readily in certain settings and had broader access to diagnostic methods that precisely defined the source of bleeding into the biliary tract. Second, there was wider use of percutaneous techniques of diagnosis and treatment of biliary diseases. Once the diagnosis of hemobilia was made by endoscopic or arteriographic means, physicians and surgeons were quicker to institute proper therapeutic measures. For this reason, the mortality associated with hemobilia decreased compared with that reported earlier. The medical community must be aware that modern treatments are now the most common cause of this problem. Since invasive diagnostic methods are increasingly used by nonsurgeons, it is imperative that these patients are studied in the context of complete consultation with surgeons who can use definitive treatments when required.     

Vav3 modulates B cell receptor responses by regulating phosphoinositide 3-kinase activation.

To elucidate the mechanism(s) by which Vav3, a new member of the Vav family proteins, participates in B cell antigen receptor (BCR) signaling, we have generated a B cell line deficient in Vav3. Here we report that Vav3 influences phosphoinositide 3-kinase (PI3K) function through Rac1 in that phosphatidylinositol-3,4,5-trisphosphate (PIP3) generation was attenuated by loss of Vav3 or by expression of a dominant negative form of Rac1. The functional interaction between PI3K and Rac1 was also demonstrated by increased PI3K activity in the presence of GTP-bound Rac1. In addition, we show that defects of calcium mobilization and c-Jun NH2-terminal kinase (JNK) activation in Vav3-deficient cells are relieved by deletion of a PIP3 hydrolyzing enzyme, SH2 domain-containing inositol polyphosphate 5'-phosphatase (SHIP). Hence, our results suggest a role for Vav3 in regulating the B cell responses by promoting the sustained production of PIP3 and thereby calcium flux.     

Localization of basic FGF-like immunoreactivity in the hypothalamo-hypophyseal neuroendocrine axis

We examined the localization of basic fibroblast growth factor (basic FGF) in the adult rat brain by immunohistochemical and Western blotting analysis using a specific antibody against a synthetic basic FGF fragment (N-terminal 12 residues). The antibody did not cross-react with acidic FGF. Basic FGF-like immunoreactivity was located exclusively in the neuronal elements and had very heterogenous distribution. Immunoreactive cell bodies were observed in the paraventricular, supraoptic and circular nuclei of the hypothalamus. Numerous immunoreactive neuronal processes originating from these basic FGF-positive cells extended lateroventrally and then caudally to the internal layer of the median eminence. In addition, the neurohypophysis contained a significant number of basic FGF-like immunoreactive fibers. Western-blotting analysis revealed that the hypothalamus and the hypophysis contained a main band of basic FGF immunoreactive with an apparent molecular weight of 17 kDa. These results show that the hypothalamo-hypophyseal neuroendocrine pathway contains basic FGF.     

Orthotopic allotransplantation of the canine liver; a simplified technic with hypothermia

A simplified technique of the liver transplantation under hypothermia has been studied in dog. An immersion hypothermia was used in both the donor and the recipient. The temperature of the graft at excision was lowered to 20 degrees C with supplemental use of topical cooling. The temperature of the recipient was lowered at 27 degrees C when the transplantation was attempted. Chlorpromazine and dopamine were employed beneficially in hypothermia. No perfusion or irrigation of the graft was performed. The use of heparin was avoided. Anastomoses were carried out in turn of the proximal vena cava, portal vein, distal vena cava and the hepatic artery with a stem shaped aorta. Reperfusion was established after the completion of anastomosis between the proximal vena cava and portal vein. The anhepatic phase of the recipient was uneventfully lasted without heparinization. All dogs, 5 out of 11 without early surgical troubles survived more than 5 days. Immunosuppressive therapy was not employed except one which died of pneumonia on the 19th postoperative day. Histologically, these dogs were free from ischemic injury and/or thrombotic lesion throughout transplantation procedure.     

The usefulness of CEA as an indicator for early detection and a guide to the treatment of recurrent gastric cancer

The usefulness of carcinoembryonic antigen (CEA) as an indicator for recurrence and a guide to the treatment was evaluated from a retrospective analysis of 88 patients with recurrent gastric cancer. Sixty-two of these patients (70.5 per cent), 25 of whom had a preoperative positive assay, and 37 a negative assay, had elevated levels of CEA after disease progression. Averaged CEA level in patients with liver metastasis was significantly higher (872 ng/ml) than in those with peritoneal metastasis (68 ng/ml), with lymph node metastasis (103 ng/ml) or with local metastasis (93 ng/ml) (p<0.01). An elevation of CEA was found prior to the clinical manifestation of recurrence, and the average lead time was 4 months. In 25 patients with a lead time of more than 4 months, survival time after CEA elevation was 13.3 months, which was longer than the 6.5 months of 28 patients with less than 4 months. Thirty-seven of the 88 patients were treated after recurrence. The average survival period after the detection of recurrence was 9.4 months in patients with surgical treatments followed by chemotherapy, 5.9 months in those with chemotherapy alone and 3.8 months in those with surgery alone. The average survival period of 26 patients with positive CEA assays in recurrence was 5.1 months longer than of patients with negative assays. This fact suggested that early detection of recurrence followed by various treatments, in the elevated CEA group, contributes to favorable results.