Genetic changes in JC virus possibly associated with progressive multifocal leukoencephalopathy]

Progressive multifocal leukoencephalopathy (PML) is a fetal demyelinating disease in the central nervous system. PML was once a rare disease, but it is now relatively common among AIDS (acquired immunodeficiency syndrome) patients. The immunological state of patients mainly contributes to the pathogenesis of PML. Genetic changes of the etiological agent, however, may also be involved in the development and progression of the disease. The major genetic changes possibly associated with PML include the regulatory region rearrangement and the VP1 loop mutation. Both changes have been identified as genetic changes usually occurring in JCV (JCvirus) DNAs from the brain and cerebrospinal fluid of PML patients. Although it remained to be clarified how these changes are involved in the pathogenesis of PML, accumulating evidence suggests that the VP1 loop mutation is associated with the progression of PML. Here we overview studies (mainly those performed by ourselves) on these genetic changes.     

Angiographic studies on the effects of a novel calcium antagonist AE0047 on cerebral arteries in dogs, with special reference to the preventive effects of AE0047 on cerebral vasoconstriction induced by endothelin

AE0047, a novel calcium antagonist, has mild and long-acting hypotensive effects. This drug also has more selective dilating action on cerebral arteries than on other systemic ones. We studied the cerebral vasodilatative effects of AE0047 by means of vertebral angiography in anesthetized dogs. Vertebral blood flow (VBF) was significantly increased by 91, 139 and 132% in 10, 30 and 60 min after intravenous administration of AE0047 at 30 micrograms/kg, respectively. No difference in vasodilating action was observed among basilar, posterior communicating, middle cerebral and internal carotid arteries. In basilar artery, the dilatative rate was about 30% between 10 and 60 min after injection of AE0047. Following intravertebral administration of endothelin at 100 pmol/kg, small vessels of the cerebral artery were constricted, and VBF was gradually decreased. AE0047 eliminated the vasoconstriction and increased VBF. Moreover, the vasoconstrictive effect of endothelin was prevented by pre-treatment of AE0047. These results indicate that AE0047 has potent vasodilating and spasmolytic actions on cerebral arteries.     

Chromosomal Mapping of Genetic Locus Associated with Thymus-size Enlargement in BUF/Mna Rats

The thymoma-prone rat of the BUF/Mna strain is a useful model for human thymoma. In this strain thymoma development is regulated by a single autosomal susceptible gene, Tsr-1. At pre-thymoma age, BUF/Mna rats have extremely large thyrauses, when compared to those of other strains of rats. Genetic studies in crosses between BUF/Mna rats with large thymuses and WKY/NCrj rats with small thymuses suggested the presence of a major autosomal gene, Ten-1 , which contributes to thymus enlargement in a backcross population. Linkage studies between Ten-1 and microsatellite markers in backcross rats of (WKY/NCrj×BUF/Mna)Fl×BUF/Mna have led to the localization of Ten-1 in chromosome 1. This result may provide an approach to clone Tsr-1 , which could be allelic to Ten-1.     

Expression of TGF-α, EGF and their common receptor in human fetal kidney

Summary: Transforming growth factor-α (TGF-α) and epidermal growth factor (EGF) are structurally related mitogenic polypeptides. They share the same receptor; EGF receptor. the EGF receptor is widely expressed in human fetal tissues including the kidney, but little is known about the role of TGF-α/EGF/EGF receptor system in human fetal kidney. the expression of TGF-α, EGF and their common receptor was investigated immunohistochemically in the human fetal kidneys. In the cortex, immunoreactivity for TGF-α was found in the differentiating proximal tubules. In contrast, immunoreactivity for EGF was present in the thick ascending limbs of the Henle's loop (TAL) and medullary collecting duct cells (CD). Immunoreactivity for their common receptor was present mainly in the TAL and medullary CD. These data support the assumption that the system of TGF-α, EGF and its receptor has an important role in the proliferation and differentiation of the TAL and medullary CD. the different localization of TGF-α and its receptor may indicate that TGF-α acts through a paracrine mechanism. the co-localization of EGF and its receptor in the TAL and medullary CD suggests that EGF may act as an autocrine growth factor.     

Aneurysm of the ductus diverticulum in adults The diagnostic value of three-dimensional computed tomographic scanning

Ductus arteriosus aneurysm is rare in adults and preoperative diagnosis has not been usually done. We report 2 cases of adult type ductus arteriosus aneurysm. In both cases, 3D computed tomographic scanning showed a saccular aneurysm originating from the distal aortic arch toward the left pulmonary artery, which had a notching in the orifice of the aortic side. They were successfully treated surgically though one was a ruptured aneurysm to the left pulmonary artery. In these cases, 3D-CT scan was of great value in the preoperative diagnosis of the ductus arteriosus aneurysm.     

Enhanced effect of intra-arterial adriamycin administration in combination with degradable starch microspheres on an intra-arterial chemotherapy model of nude rats transplanted of human gastric cancer

Enhancement of the antitumor effects of adriamycin (ADR) by concomitant use of degradable starch microspheres (DSM) and pharmacokinetics of ADR in combination with DSM was investigated. An intra-arterial chemotherapy model of the nude rats transplanted of human gastric cancer xenografts (H-154) in the hind-limbs was used for this study. Drug was administered through a catheter inserted into the carotid artery with the tip in the common iliac artery. In the pharmacological study, increase of regional uptake of ADR and decrease of systemic distribution of ADR were recognized in some degree. DSM 30 mg/kg, which caused temporary arrest of blood flow in the tumor, had an only weak effect on tumor growth. ADR 3 mg/kg mixed with DSM 30 mg/kg was more effective than ADR 3 mg/kg solution. Furthermore, mixture of ADR 2 mg/kg and DSM 30 mg/kg had a greater effect on tumor growth than ADR 2 mg/kg following DSM 30 mg/kg. It seems that embolization by DSM, retention of ADR in regional tissues and cytotoxic effect of ADR have contributed to such a strong effect of ADR mixed with DSM.     

Prognostic significance of prostate specific antigen in endocrine treatment for prostatic cancer.

The prognostic value of prostate specific antigen was evaluated to predict disease progression after endocrine therapy in patients with prostatic cancer. A total of 73 patients was studied (6 with stage B2, 16 with stage C, 9 with stage D1 and 42 with stage D2 disease). Endocrine therapy included bilateral orchiectomy, diethylstilbestrol diphosphate and luteinizing hormone-releasing hormone analogue. Pre-treatment serum prostate specific antigen levels were determined in all patients with an enzyme immunoassay kit. During a followup of 4 to 68 months (average 24 months) clinical disease progression occurred in 24 of the 73 patients. The pre-treatment prostate specific antigen level by itself did not predict disease progression. Changes in prostate specific antigen level with treatment were correlated with the interval to disease progression in the 44 patients who had prostate specific antigen determinations at regular intervals after endocrine therapy and whose initial level was greater than 10 ng./ml. Patients who had a decrease in the prostate specific antigen levels of 80% or more within 1 month after the beginning of therapy survived significantly longer free of disease progression (p less than 0.001). Patients whose prostate specific antigen level remained elevated for more than 3 months had a high risk of disease progression within 2 years. Our study suggests that patients with the more favorable prognosis can be identified early, after 1 to 3 months of endocrine therapy, by the rapid decrease in the prostate specific antigen levels.