Detection of novel rearrangement of the JC virus gene in a case of progressive multifocal leukoencephalopathy with adult T-cell leukemia]

A 53-year-old man with adult T-cell leukemia (ATL) developed progressive left hemiparesis and left homonymous hemianopsia. Magnetic resonance imaging (MRI) one month later showed multiple high-intensity lesions in the white matter of both occipital lobes, with predominance in the right side. Detection of JCV genome with polymerase chain reaction in his cerebrospinal fluid subsequently confirmed the diagnosis of progressive multifocal leukoencephalopathy (PML). He was admitted to our hospital. The serum level of soluble interleukin-2 receptor in the patient increased, and both edema and new Gd-enhanced lesions were observed in the cortex of the occipital lobe. He was treated with systemic administrations of Pirarubicin. Cyclophosphamide, and Prednisolone. as well as intrathecal injection of Methotrexate and Cytarabine. Although these treatments temporarily alleviated the symptoms of PML. the ATL spread to the liver and kidney. He died of multiple organ failure. Analysis of his JCV genes revealed that there were three types of rearrangements in the regulatory domains of the JCV genes. All three types lacked the domain B. and two had duplicate domain A. This is the first report of the simultaneous detection of three different types of rearrangements in JCV genes in a single patient. It has been reported that white-matter lesions caused by typical PML are not enhanced in Gd-MRI. However. the lesions seen in this patient were enhanced in Gd-MRI. Such enhancement might be attributable to the modification of the lesions through the direct invasion of ATL cells to the central nervous system.     

Intraosseous ganglion about to cause a fracture of the glenoid: a case report

Intraosseous ganglia of the glenoid are rare, and their etiology is unknown. This report describes a case of an intraosseous ganglion about to cause fracture of the glenoid. The patient was a 61-year-old woman with a painful left shoulder with a limited range of motion. Her symptoms did not improve after non-operative treatment. Arthroscopic examination showed a cartilage defect and erosion in the posteroinferior portion of the glenoid, behind which computed tomography (CT) showed a cystic lesion of the glenoid. There was no communication between the cyst and the joint space. The patient was treated by curettage and an autogenous cancellous bone graft from the iliac crest. Two years after the operation, the patient was almost free from pain, and CT showed good integration of the bone graft.     

Virtual endoscopic images by 3D FASE cisternography for neurovascular compression.

Three-dimensional fast asymmetric spin echo (3D FASE) cisternography provides high spatial resolution and excellent contrast as a water image acquisition technique. It is also useful for the evaluation of various anatomical regions. This study investigated the usefulness and limitations of virtual endoscopic images obtained by 3D FASE MR cisternography in the preoperative evaluation of patients with neurovascular compression. The study included 12 patients with neurovascular compression: 10 with hemifacial spasm and two with trigeminal neuralgia. The diagnosis was surgically confirmed in all patients. The virtual endoscopic images obtained were judged to be of acceptable quality for interpretation in all cases. The areas of compression identified in preoperative diagnosis with virtual endoscopic images showed good agreement with those observed from surgery, except in one case in which the common trunk of the anterior inferior cerebellar artery and posterior inferior cerebellar artery (AICA-PICA) bifurcated near the root exit zone of the facial nerve. The veins are displayed in some cases but not in others. The main advantage of generating virtual endoscopic images is that such images can be used for surgical simulation, allowing the neurosurgeon to perform surgical procedures with greater confidence.     

The influence of liver dysfunction on cyclosporine pharmacokinetics —A comparison between 70 per cent hepatectomy and complete bile duct ligation in dogs—

The influence of experimentally induced hepatic dysfunction on the pharmacokinetics of Cyclosporine A (CsA) was determined in dogs. The pharmacokinetics of oral (PO) and intravenous (IV) CsA were studied before and after 70 per cent hepatectomy or complete bile duct ligation (CBDL). Changes in liver function were monitored by serial measurements of serum bilirubin, and by the maximum removal rate (Rmax) and plasma disappearance rate (ICG-K) of indocyanine green (ICG). Concentrations of CsA in whole blood were measured by HPLC. Seventy per cent hepatectomy caused significant liver dysfunction: the ICG-Rmax decreased by 47.7±7.1 per cent (mean±SD) and the ICG-K decreased by 61.3±9.7 per cent during the first week after hepatectomy. At the same time, the systemic clearance (CLs) of IV-CsA decreased by 43.9±8.2 per cent, the area under the concentration curve (AUC) of IV-CsA increased by 35.4±20.8 per cent and the bioavailability of CsA decreased by 26.4±14.8 per cent. CBDL also induced significant liver dysfunction: the ICG-Rmax decreased by 39.1±12.8 per cent and the ICG-K decreased by 65.6±3.6 per cent in the second week after the operation. During the same period, the AUC of PO-CsA decreased by 69.9±10.7 per cent and the bioavailability of CsA also decreased markedly by 73.9±15.6 per cent. These data indicate that hepatic impairment significantly influences the pharmacokinetics of CsA, not only by the changes in intestinal absorption, but also by those in hepatic, metabolism. Dose adjustment is therefore necessary in the presence of hepatic dysfunction in order to maintain an adequate blood concentration of CsA without causing side effects. This research was performed in the Department of Surgery, University of Pittsburgh Health Center, University of Pittsburgh, USA     

gamma-Aminobutyric acid enhances the tone of human internal anal sphincter.

The effect of gamma-aminobutyric acid (GABA) on the human internal anal sphincter was investigated. Cumulative applications of GABA produced concentration-dependent contractions (10(-8)-10(-5) M) of the isolated human sphincter. Pretreatment with bicuculline (GABAA antagonist) turned them to relaxation. Muscimol, a GABAA agonist, induced concentration-dependent contractions (10(-8)-10(-5) M); however, baclofen (GABAB agonist, 10(-8)-10(-5) M) promoted concentration-dependent relaxation of the strips. These results suggested that both excitatory GABAA receptors and inhibitory GABAB receptors exist in the internal anal sphincter. Oral administration of sodium valproate (1600 mg/day), a GABA transaminase inhibitor, enhanced the anal canal resting pressure in 10 normal volunteers. Anal manometry showed a significant elevation in tonus without affecting amplitudes or frequencies. These results indicated that endogenous GABA, which was increased by sodium valproate, produced elevations in the anal canal resting pressure through its specific receptors in the human internal anal sphincter.     

Competitiveness in sports activities of the psychiatrically disabled]

In 2002, psychiatrically disabled athletes joined an historic first open game of volleyball at the national sports games for the disabled. Compared to the competitive sports and Paralympic Games that physically and intellectually disabled athletes have participated in, activities for the psychiatrically disabled have not been well-organized. In this paper, we examine a number of problems that have arisen when the psychiatrically disabled joined competitive sports games. We identify two major characteristics of the psychiatrically disabled of particular relevance when organizing competitive sports activities. First, all psychiatrically disabled athletes need treatment of their individual diseases. For example, psychiatric symptoms fluctuate markedly over time, unlike physical or intellectual disabilities, whose symptoms are much more stable. Exacerbations of psychiatric illness are also likely to occur due to the stresses of competitiveness. Second, psychiatric disabilities are manifestations of disorders in the central nervous system, which makes the classification of psychiatric disabilities less straightforward than classification of the physically disabled. These two characteristics require special attention when organizing competitive athletic challenges that include the psychiatrically disabled. However, promoting sports activities that include the psychiatrically disabled would be expected to reduce the prejudice toward and subsequent social disadvantages experienced by psychiatric patients. Thus, with careful planning to successfully integrate psychiatrically disabled athletes, we expect increased promotion of such sports activities in the future.     

An immunohistochemical study of MAP2 and clathrin in gerbil hippocampus after cerebral ischemia

Changes in MAP2 and clathrin immunoreactivity were studied in gerbil hippocampus after transient cerebral ischemia. MAP2 immuno-reactivity decreased significantly by 1 h in the subiculum-CA1 and CA2 areas which correspond to reactive change, while no decrease was observed in CA1 until day 4. Before the initiation of delayed neuronal death, MAP2 immunoreactivity was not changed in CA1. On the other hand clathrin immunoreactivity increased in the pyramidal cell layer of CA1 by 3 h after ischemia and remained high for 2 days. Clathrin immunoreactivity in the pyramidal cell layer of CA1 diminished after delayed neuronal death. The transient change of clathrin was noted especially in CA1 in the period prior to delayed neuronal death. These results imply an abnormal change in clathrin turnover after ischemia, which may participate in the pathogenesis of delayed neuronal death.     

Ketamine Suppresses Platelet Aggregation Possibly by Suppressed Inositol Triphosphate Formation and Subsequent Suppression of Cytosolic Calcium Increase

Background: Ketamine has been shown to suppress platelet aggregation, but its mechanisms of action have not been defined. The purpose of the current study is to clarify the effects of ketamine on human platelet aggregation and to elucidate the underlying mechanisms of its action.

Methods: Platelet aggregation was measured using an eight-channel aggregometer, and cytosolic free calcium concentration was measured in Fura-2/AM-loaded platelets using a fluorometer. Inositol 1,4,5-triphosphate (IP3) was measured with use of a commercially available IP3 assay kit. To estimate thromboxane A2 (TXA2) receptor binding affinity and expression, Scatchard analysis was performed using [3H]S145, a specific TXA2 receptor antagonist. TXA2 agonist binding assay was also performed. The membrane-bound guanosine 5'-triphosphatase activity was determined using [[gamma]-32P]guanosine triphosphate by liquid scintillation analyzer.

Results: Ketamine (500 [mu]m) suppressed aggregation induced by adenosine diphosphate (0.5 [mu]m), epinephrine (1 [mu]m), (+)-9,11-epithia-11,12-methano-TXA2 (STA2) (0.5 [mu]m), and thrombin (0.02 U/ml) to 39.1 +/- 30.9, 46.3 +/- 4.3, -2.0 +/- 16.8, and 86.6 +/- 1.4% of zero-control, respectively. Ketamine (250 [mu]m-1 mm) also suppressed thrombin- and STA2-induced cytosolic free calcium concentration increase dose dependently. Although ketamine (2 mm) had no effect on TXA2 receptor expression and its binding affinity, it (1 mm) suppressed intracellular peak IP3 concentrations induced by thrombin and STA2 from 6.60 +/- 1.82 and 4.39 +/- 2.41 to 2.41 +/- 0.98 and 1.90 +/- 0.86 pmol/109 platelets, respectively, and it suppressed guanosine triphosphate hydrolysis induced by thrombin (0.02 units/ml) and STA2 (0.5 [mu]m) to 50.3 +/- 3.2 and 67.5 +/- 5.5%versus zero-control, respectively.     

Alternative Expression of a Chitosanase Gene Produces Two Different Proteins in Cells Infected withChlorellaVirus CVK2

SeveralChlorellavirus CVK2 proteins had chitosanase and/or chitinase activities. A gene coding for an ORF of 328 amino acids (aa) with a predicted molecular mass of 36,769 Da was cloned from the viral genome. The predicted amino acid sequence of an N′-portion (174 aa) of this gene product (vChta-1) showed 22 to 25% identity with various bacterial chitosanases. A glutathioneS-transferase (GST)–vChta-1 fusion protein had strong chitosanase activity. Western blot analysis with antisera raised against the vChta-1 protein identified two proteins of 37 and 65 kDa in virus-infectedChlorellacells beginning at 240 min postinfection and continuing until cell lysis. The larger protein was packaged in the virion, while the smaller one remained in the cell lysate. Both chitosanase proteins were produced from the single gene,vChta-1,by a mechanism of alternative gene expression.