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.     

Evaluation of blood flow patterns of true and false lumens in dissecting aneurysms using MR phase-contrast techniques

The magnetic resonance phase-contrast technique for the measurement of flow velocity and volume in true and false lumens was studied in six patients with chronic dissecting aneurysms. Phase-contrast images were obtained at a level perpendicular to the dissecting aneurysms of the descending aorta. As the maximum diameter of aneurysms increased, the ratio of the cross-sectional area of the false to the true lumen increased and the peak average velocity in the true lumen during systole was decreased. This technique proved invaluable for determining prognosis and operability for this condition.     

Use of epr oximetry with india ink to measure the po2 in the liver in vivo in mice

The partial pressure of oxygen (pO₂) of the liver in vivo in unanesthetized mice was determined using electron paramagnetic resonance (EPR) oximetry with India ink. The EPR spectra were obtained using a low-frequency (1.2 GHz) EPR spectrometer with a loop gap cavity resonator. The line width of the India ink used in this experiment was reversibly broadened by oxygen and was particularly sensitive to pO₂ below 30 torr. After the administration of India ink into the tail vein, the India ink particles were taken up mainly by Kupffer cells in the liver and in part by phagocytes in the spleen. The pO₂ measured in the normal liver was about 14 torr and was constant for the 2-week experimental period. The pO₂ decreased when measured at 1, 2, and 6 days after treatment with a hepatotoxin (carbon tetrachloride (CCI₄)); within 2 weeks, it returned almost to the initial level. Measurements by EPR at sacrifice of controls and CCI₄-treated mice indicated that more than 90% of the India ink went to the liver; the spleen contained 4.7% of total amount in control mice and 8.8% in CCI₄-treated mice when measured 2 weeks after the treatment. These data indicate the usefulness of India ink for measuring the pO₂ of the liver in vivo and that the pO₂ in the Kupffer cells is decreased when the liver is damaged by CCI₄.     

Remote Connection to the Kyushu University Medical Center LAN Using Digital and Analog Telephone Lines

SOHO (Small Office/Home Office) has recently become popular, as it makes working at home possible. Computers or Local Area Networks(LAN) connected to the office network from home are necessary for the implementation of this concept. Kyushu University has begun a service connecting home computers to the campus LAN for researchers, staff and students of the Faculty of Medicine. We have two different telephone connection methods. One connects the campus LAN and the home computer LAN using routers through the Integrated Services Digital Network (ISDN). The other connects computers at home to the workstation in the university, using modems and the PPP (Point to Point Protocol) through a public telephone analog line. This paper outlines our university SOHO connection system and discusses the merits and demerits of using telephone line connections.     

Phase I study of cefixime, a new oral cephalosporin

The tolerance to and pharmacokinetics of cefixime, a new oral cephalosporin, were evaluated in healthy volunteers given the drug in single doses of 50, 100 and 200 mg and repeated doses of 200 mg bid for 14 days. In the repeated-dose study, there were mild and transient subjective symptoms such as soft stools, diarrhea, and anorexia, which disappeared without additional treatment during the dosing period. Slight increases in eosinophil and serum amylase levels were also observed. The serum concentrations of cefixime peaked at 0.71, 1.17, and 2.08 micrograms/mL on average, four to five hours after dosing with 50, 100, and 200 mg, respectively, and the half-lives were 2.54, 2.38, and 2.29 hours. Serum concentrations and urinary recoveries after dosing with 100 mg were little affected by food ingestion. There was no evidence of cefixime accumulation in the body by repeated dosing since mean serum concentrations and urinary recoveries were almost the same on the first, third, seventh, and 14th days of dosing.     

The efficacy of fluconazole in treating prosthetic valve endocarditis caused byCandida glabrata: Report of a case

A case of active prosthetic valve infective endocarditis (PVE) due toCandida glabrata was successfully treated by the systemic administration of fluconazole. A 66-year-old Japanese man with infective endocarditis of unknown etiology underwent aortic and mitral valve replacement to treat severe aortic and mitral regurgitation associated with multiple organ failure. Postsurgical cultures of arterial blood were repeatedly positive forC. glabrata, and therefore fluconazole was administered either intravenously or orally at a dose of 400 mg/day for 46 days. During that time the signs of inflammation including fever such as an elevated white blood cell count and the presence of C-reactive protein (CRP) all improved while the blood cultures became negative. Fluconazole is thus considered to be effective in treating PVE caused byC. glabrata. When administering this treatment, it is also important to monitor the patient's renal and liver function.     

Mass contents of inositol 1,4,5-trisphosphate and 1,2-diacylglycerol in human platelets stimulated with a thromboxane analogue and thrombin.

Mass contents of inositol 1,4,5-trisphosphate (IP3) and 1,2-diacylglycerol (DG) were measured in U46619-stimulated human platelets. 1 microM of U46619 induced maximum responses in aggregation, 5-hydroxytryptamine (5HT) secretion and increase in intracellular free Ca2+ concentration ([Ca2+]i). Aggregation was almost comparable to that induced by maximal dose (1 U/ml) of thrombin, while 5HT release was almost half. The initial [Ca2+]i peak in response to U46619 was about half of thrombin stimulation. Production of IP3 and DG was, however, less than one tenth of that seen in thrombin stimulation. The profile (time course and concentration-dependency) of IP3 formation did not correlate with that of [Ca2+]i, suggesting that U46619 stimulates IP3-dependent and -independent Ca2+ mobilization. DG production was small but sustained for more than 5 min. These findings support the recent hypothesis that aggregation is regulated by a delayed accumulation of DG. The low level of 5HT secretion could be explained by the low production of second messengers, IP3 and DG.     

Uveitis associated with human T-cell lymphotropic virus type I.

Seroepidemiologic, clinical, and virologic studies were performed to determine whether human T-cell lymphotropic virus type I was closely associated with uveitis in two hospitals. One hospital was in an endemic area of the virus (Miyakonojo, Miyazaki) and the other hospital was in a less endemic area (Kurume). In the endemic area, the seroprevalence of the virus in patients with uveitis without defined causes (35.4%, 62 of 175 patients) was significantly higher than that in patients with nonuveitic ocular diseases (16.1%, 42 of 261 patients), or in patients with uveitis with defined causes (10.3%, eight of 78 patients). The seroprevalence in younger patients (20 to 49 years of age) with uveitis without defined causes in the area was 44.8% (30 of 67 patients), whereas it was only 9.3% (ten of 107 patients) in the other two groups. A similar observation was recorded even in the less endemic area (Kurume). Because the seroprevalence of the virus in the general population is known to be low in younger patients and to increase with age, these findings were interpreted to indicate that the association of human T-cell lymphotropic virus type I with uveitis was significant. Most patients, particularly those aged 20 through 49 years, had an intermediate uveitis characterized by a moderate inflammation in the vitreous body accompanied by an iritis and retinal vasculitis. The ocular symptoms in the patients differed from those of other types of uveitis common in Japan (Beh?et's disease, Vogt-Koyanagi-Harada's disease, and toxoplasmosis, for example).(ABSTRACT TRUNCATED AT 250 WORDS)     

Media conditioned by smooth muscle cells cultured in a variety of hypoxic environments stimulates in vitro angiogenesis. A relationship to transforming growth factor-beta 1.

Conditioned media (CM) harvested from bovine smooth muscle cells (SMCs) of aortic media cultured under hypoxic conditions remarkably enhanced angiogenesis in vitro, that is, the tube formation of bovine capillary endothelial cells (BCEs) cultured on type I collagen gels. The extent of in vitro angiogenesis was assessed by the total length of tube structures formed by BCEs per area measured quantitatively with an image analyzer. The tube formation in CM obtained from the cultivation of SMCs at 1% O2 for 24 hours was enhanced by about 1.5 times and 3.4 times as compared with those at 5% O2 and 20% O2, respectively. This tube-forming activity was abrogated by the pretreatment of CM with anti-transforming growth factor (TGF)-beta 1 IgG, but not by anti-basic fibroblast growth factor IgG. The SMC-CM obtained from hypoxic cultivation (1% O2 for 24 hours) inhibited [3H] thymidine incorporation by BCEs, SMCs, and fibroblasts more than about 20% of control. Anti-TGF-beta 1 IgG thus significantly reduced the inhibitory effect of hypoxic SMC-CM on DNA synthesis of these cells. These results suggest that SMCs in a hypoxic state release active in vitro angiogenic factors into CM, and active TGF-beta 1 is closely related to the in vitro angiogenic enhancement of media conditioned by SMCs cultured in a hypoxic state.     

HTLV-I uveitis: a distinct clinical entity caused by HTLV-I.

Seroepidemiological, clinical and virological studies were carried out in an HTLV-I endemic area to find out if HTLV-I caused an intraocular inflammatory disorder, uveitis. The seroprevalence in patients with uveitis without defined etiologies (62/175, 35.4%) was significantly higher than that in patients with non-uveitic ocular diseases (42/261, 16.1%) or in patients with uveitis with defined etiologies (8/78, 10.3%). Moreover, the seroprevalence in young adults (20-49 years) with uveitis without defined etiologies was 30/67 (44.8%), whereas it was only 10/107 (9.3%) in the other two groups. The uveitis in HTLV-I carriers was characterized clinically by a moderate inflammation of the vitreous body accompanied by a mild iritis and retinal vasculitis. The proviral DNA of HTLV-I was detected by polymerase chain reaction from the inflammatory cells in the anterior chamber in 9 out of 9 seropositive patients with the uveitis, but not in any of the tested patients with other types of uveitis. These data, thus, indicate that HTLV-I causes a specific type of intraocular inflammation, uveitis.