Overview of nuclides for bone pain palliation

Currently, six distinct types of hepatitis virus have been identified: A, B, C, D, E, and G. Hepatitis A virus infection does not cause a chronic carrier state, and perinatal transmission is extremely uncommon. Hepatitis B can be transmitted perinatally, but immunization of the newborn with hepatitis B immune globulin and hepatitis B vaccine markedly reduces the risk of neonatal infection. Hepatitis D virus is dependent on coinfection with the hepatitis B virus for replication. Immunoprophylaxis against hepatitis B also is effective against hepatitis D. Hepatitis C virus is primarily transmitted by the parenteral route and is particularly likely to cause chronic liver disease. Perinatal transmission of hepatitis C principally occurs in women who have high titers of HCV-RNA or who are coinfected with human immunodeficiency virus. At this time, no immunoprophylaxis for hepatitis C is available. Hepatitis G, a recently described organism, is related to hepatitis C. Its clinical significance remains undetermined. Hepatitis E is transmitted in a manner similar to hepatitis A. Perinatal transmission is unusual, but maternal disease is often severe.     

Investigation of human urine for genomic sequences of the primate polyomaviruses simian virus 40, BK virus, and JC virus

Recent reports of the detection of simian virus 40 (SV40) nucleotide sequences in ependymomas, choroid plexus tumors, osteosarcomas, and mesotheliomas have raised the possibility that SV40, which naturally infects Asian macaques, is circulating among humans. This possibility was examined by performing polymerase chain reaction assays on urine samples of 166 homosexual men, 88 of them human immunodeficiency virus (HIV)-seropositive, for genomic sequences of SV40 as well as of human polyomaviruses BK virus (BKV) and JC virus (JCV). Tests with masked urine specimens spiked with SV40-transformed cells were included to monitor the SV40 assay. SV40, BKV, and JCV sequences were identified, respectively, in 0, 14%, and 34% of the urine specimens. JCV viruria was far more common (37%) than BKV viruria (5%) in HIV-seronegative persons. HIV infection and more severe immunosuppression were associated with a higher frequency of BKV viruria. In summary, SV40 viruria was not detected among homosexual men who shed human polyomaviruses at a high frequency.     

The role of endothelin in regulation of vascular tone in physiology and pathology

JC virus (JCV) with an archetypal regulatory region (archetype) has been cloned from urines of a healthy individual. It has been suggested that the regulatory region of prototype JC virus (PML type) isolated from brain of PML patient was derived from that of the archetype by deletion and duplication. Biological characteristics of archetypal JCV, however, have not been fully studied. In the present study we examined the infectivity of archetypal JCV (CY), PML-type JCV (Mad-1) and Chimera JCV (Mad-1/CR-CY), in which the regulatory region is composed of CY and the other region Mad-1. DNAs from the three JCV types were transfected into COS-7 (monkey kidney cells transformed with SV40 T) and IMR-32 (human neuroblastoma cell). COS-7 was permissive for all three types, but IMR-32 was only infected with Mad-1. Infected DNAs were confirmed by Southern blotting, and the constancy of the regulatory regions before and after transmission was verified by DNA sequencing. The results showed that the viral regulatory region was related to viral cell tropism and that PML type regulatory region would be necessary for IMR-32 to propagate. The fact that COS-7 was susceptible for all three types may be explained by the function of SV40 T protein. In addition, we first succeeded in the propagation of CY in COS-7, which would provide a useful system to analyze the mechanism of persistent infection of archetypal JCV.     

The morphological diagnosis of Helicobacter pylori in the gastric mucosa in chronic gastritis]

JC virus (JCV), a human polyomavirus, is the agent of the demyelinating disease progressive multifocal leukoencephalopathy (PML). JCV exists in four main genotypes in the USA. Type 1, including subtypes Type 1A and Type 1B, makes up about 64% of strains in the USA and is thought to be of European origin. Type 2 is found in Asia, and Type 3 in Africa. A fourth type is found only in the USA. In general, these genotypes differ in 1-2.5% of their DNA sequence. Thirty MS patients and 30 paired controls from Budapest were studied. The clinical course of MS was mainly secondary progressive, and patients were stable at the time of testing. Most of the controls were relatives of the probands: a spouse, parent, or child. Overall, 25 of 60 (42%) of the urines tested positive for JCV by PCR. These included 13 of 30 MS patients, and 12 of 30 controls. Genotyping in the VPI gene showed all 25 JCV strains to be Type 1. Among the MS patients, seven were Type 1A and six were Type 1B. Among the controls, nine were Type 1A and three were Type 1B. In five pairs of MS patients and controls, both were positive for JCV by PCR. Two of these were husband/wife pairs of which one pair was matched for subtype (both Type 1A), and the other was not. Two of them were mother/daughter pairs, and both were matched for subtype (both Type 1B). These findings demonstrate that JCV Type 1 predominates among Hungarians, and suggest that parent/child pairs can be used to trace JCV transmission within the MS family.     

Composite polytetrafluroethylene/vein bypass grafts: conventional distal vein segment or vein cuff?

Faecal samples from asymptomatic dairy cows and calves from a farm on the Island Falster, Denmark, were examined by a sucrose gradient flotation technique. Giardia cysts were found in 7.6% of the 92 samples, and estimated cyst excretion rates ranged from 50-200 cysts per gram faeces. Given that Giardia has the potential to cause clinical disease in cattle and to be transmitted to other animal species and humans, finding the parasite in cattle may be of major epidemiological significance. Future work should focus on elucidating the pathogenicity, transmission patterns and the genetic structure of Giardia populations in cattle in Denmark.     

The elimination of hepatitis B virus infection: changing seroepidemiology of hepatitis A and B virus infection in Okinawa, Japan over a 26-year period

Serial changes in hepatitis A virus (HAV) and B virus (HBV) markers were determined from 1970 to 1996 in healthy Japanese residents of a rural area of Okinawa, Japan. All 190 serum samples taken in 1970, 791 in 1980, 708 in 1988, and 523 in 1996 from residents 0 to more than 60 years of age were tested for antibody to HAV (anti-HAV), antibody to hepatitis B core antigen (anti-HBc), and hepatitis B surface antigen (HBsAg). The age-adjusted prevalences of anti-HAV and anti-HBc decreased significantly from 83.9% and 74.9%, respectively, in 1970 to 39.7% and 36.6%, respectively, in 1996. In residents < or = 29 years of age, the prevalences of anti-HAV and anti-HBc decreased significantly from 65.3% and 83.8%, respectively, in 1970 to 0.7% and 8.2%, respectively, in 1996. The age-adjusted HBsAg prevalence decreased significantly from 8.2% in 1980 to 4.1% in 1988. These results indicate that exposure to HAV and HBV infections among Okinawa residents less than 29 years of age is decreasing, probably because of improvements in socioeconomic conditions since 1970. Infection with HBV may be eliminated there in the near future.     

Prevalence of liver abnormalities in the general population of Okinawa, Japan

A total of 2,825 Japanese over 20 years of age living in the Yaeyama District of Okinawa, Japan were investigated in 1983 and 1984 to determine the prevalence and risk factors of liver abnormalities. Obesity index, hepatitis B virus markers, hepatitis C virus marker and serum transaminase were measured and the history of alcohol intake was recorded. People with elevated transaminase levels were assumed to have abnormalities of the liver. The overall prevalence of liver abnormalities was 3.6% and was significantly higher in men than in women (p < 0.001). Logistic regression analysis showed that the strongest predictors of liver abnormalities were alcohol for the men and obesity for the women. Hepatitis B virus was the second most prevalent risk factor in both sexes.     

Influenza infection in humans and pigs in southeastern China

The three last pandemic strains of influenza A virus-Asian/57, Hong Kong/68 and Russian/77-are believed to have originated in China. The strains responsible for the 1957 and 1968 human pandemics were reassortants incorporating both human and avian influenza viruses, which may have arisen in pigs. We therefore undertook a population-based study in the Nanchang region of Central China to establish the prevalence, types and seasonal pattern of human influenza infection and to screen serum samples from animals and humans for evidence of interspecies transmission of influenza viruses. Two definite influenza seasons were demonstrated, one extending from November to March and the other July to September. The profile of antibodies to commonly circulating human influenza viruses was no different in Nanchang and neighboring rural communities than in Memphis, Tennessee, USA. In particular, Chinese women who raised pigs in their homes were no more likely to have been exposed to influenza virus than were subjects who seldom or never had contact with pigs. However, we did obtain evidence using isolated H7 protein in an enzyme-linked immunoabsorbent assay for infection of pig farmers by an avian H7 influenza virus suggesting that influenza. A viruses may have been transmitted directly from ducks to humans. The results of the serological survey also indicated that pigs in or near Nanchang were infected by human H1N1 and H3N2 influenza viruses, but not with typical swine viruses. We found no serological evidence for H2 influenza viruses in humans after 1968.     

Review: JC virus infection of lymphocytes--revisited

JC virus (JCV), the causative agent of the fatal human demyelinating disease progressive multifocal leukoencephalopathy (PML), is an opportunistic papovavirus that infects and destroys oligodendrocytes, the myelin-producing cells of the central nervous system. Since its isolation from the brain of a PML patient, JCV has long been classed as a neurotropic virus. Many studies, however, have demonstrated that JCV can infect various other cell types, including immune system cells. Moreover, several recent studies have focused specifically on lymphocytes as a target of JCV. This review chronicles the association of JCV with lymphocytes, including cell type localization, molecular regulation, and viral sequences, and discusses clinical implications of these findings.     

Restriction endonuclease analysis of plasmid DNA of Yersinia pseudotuberculosis infections in Shimane Prefecture, Japan

The epidemiology of Yersinia pseudotuberculosis infections in a limited area of Shimane Prefecture, Japan, was examined by serotyping and restriction endonuclease analysis of virulence plasmid DNA of Y. pseudotuberculosis strains isolated from humans, wildlife animals and river water. Almost all isolates from three sources belonged to serotype 1b REAP pattern D and serotype 4b REAP patterns B, G and L. The identity of the distribution of serotype and REAP patterns among isolates from humans, wildlife animals and river water shows that Y. pseudotuberculosis is transmitted to humans through environmental substances contaminated by wildlife animals infected with this species.     

Detection of alcohol misusing patients in accident and emergency departments: the Paddington alcohol test (PAT)

The list of hepatitis viruses is increasing over the years. Now the viruses range from A to G. Hepatitis A virus is a short incubation RNA virus which is transmitted oro-faecally. It does not cause chronic illness but may be fatal in a few cases especially in pregnancy. It can now be prevented by vaccination. Hepatitis B virus is a long incubation DNA virus which is transmitted mainly through blood and blood products. It causes chronic illness and can lead to liver cancer in some cases. It can be prevented by vaccination and WHO is now recommending global vaccination of all infants irrespective of endemicity of hepatitis B virus. Hepatitis C virus is an RNA virus which used to be known as parenterally transmitted non A non-B virus. It leads to chronic illness and can lead to liver cancer. It is now responsible for most cases of post transfusion hepatitis in Europe, North America and Asia. Hepatitis Delta virus is a defective virus which requires hepatitis B virus for its existence. Thus it affects only those who have hepatitis B virus. Hepatitis E virus used to be known as the enterically transmitted non-A non-B virus. It is transmitted oro-faecally and seems not to lead to chronic illness. It is endemic in some areas like Middle East and parts of Africa. Hepatitis G virus is just being described. More information about it will soon be available.     

Seroprevalence of human herpesvirus 8 in human immunodeficiency virus 1-positive and human immunodeficiency virus 1-negative populations in Japan

To determine the seroprevalence of human herpesvirus 8 (HHV8) among human immunodeficiency virus 1 (HIV-1)-positive (HIV-1+) and HIV-1-negative (HIV-1-) populations in Japan, 276 HIV-1+ patients and 1,000 HIV-1- blood donors were enrolled in this study. Antibodies against HHV8 latency-associated nuclear antigen (LANA) were examined through indirect immunofluorescent assay by using a B-cell line that was infected latently with HHV8 (body cavity-based lymphoma 1). An HHV8- and Epstein-Barr virus-negative B-cell line (Ramos) was used as a control. Thirty-two seropositive cases against LANA (anti-LANA+) were identified among the 276 HIV-1+ patients who were studied. Five cases were foreigners living in Japan. The risk factor of all 27 Japanese cases was unprotected sexual intercourse, and the great majority of these cases (23 in 27; 85%) reported homosexual/bisexual behavior. Anti-LANA+ status correlated with the presence of sexually transmitted diseases, such as amoeba and HBV infection, further suggesting male homosexual behavior as the main route of HHV8 transmission in Japan. Only two LANA+ cases were identified among 1,000 HIV- blood donors in Japan; thus, seroprevalence of HHV8 identified by LANA was estimated to be 0.2% among HIV-1- populations in this country.     

Differences in the p53 gene mutational spectra of prostate cancers between Japan and Western countries

Mutations of the p53 gene are related to development of human cancers and their frequencies and spectra, the latter representing fingerprints left by carcinogens, provide information about the molecular epidemiology of the disease. Prostate cancer is the most common neoplasm in American males and although its incidence is still relatively low in Japanese people, it has recently been increasing with the westernization of life style. To assess the frequency and spectrum of p53 gene mutations in Japanese prostate cancers, we examined a series of 90 lesions using polymerase chain reaction (PCR)-single-strand conformation polymorphism (SSCP) analysis. The patients' mean age was 69.3 years (range 57-87). Of the total, six were well-, 34 moderately- and 50 poorly-differentiated adenocarcinomas, and the median Gleason score was 7.9. Eleven of the 90 cases (12%) had mutations in exons 2-11 of the p53 gene: none of the five clinical-stage A, one of 25 stage B (4%), three of 35 stage C (9%) and seven of 25 stage D (28%) cancers. The correlation with an advanced stage was statistically significant. One insertion and 10 base pair substitutions were encountered, comprising six transversions (55%) and four transitions (36%). Two of the latter involved methylated cytosine-guanine (CpG). These 11 mutations were combined with 18 other mutations in previous reports concerning Japanese prostate cancers to facilitate comparison of the p53 gene mutational spectrum with those reported for American and European prostate cancers. In the latter, 61% were transitions and 33% were transversions. The greater proportion of transversions in the Japanese population suggests that there are different factors responsible for carcinogenesis of the prostate glands in the various countries.     

Use of risk projection models for the comparison of mortality from radiation-induced breast cancer in various populations

The aim of our study is to compare lifetime risk estimates for radiation-induced breast cancer between various populations. Some epidemiological studies, mainly on Japanese A-bomb survivors, but also on North American populations irradiated for medical reasons, provide risk coefficients for excess mortality from breast cancer after exposure to ionizing radiation. For this comparative study, these risk coefficients have been transferred into the Japanese, American, and French populations, using demographic data, risk projection models, and assuming an individual acute exposure. The lifetime risk estimates are similar in the three populations when the additive projection model is used because of the similarity of the life tables of the three countries. However, using the multiplicative model, large differences appear due to the discrepancies in the baseline breast cancer rates between the Japanese and Occidental populations. It is for this reason that transfer of risk coefficients fitted on the Japanese population data must be considered with caution when applied to an Occidental population. Lifetime risk estimates for a given population, the French population for example, are largely dependent on the risk coefficients considered from various epidemiological studies. Nevertheless, for each source of data, they are higher with the multiplicative model than with the additive one. Moreover, it should be noted that data from medical irradiation lead to higher risk estimates when using the additive model, whereas studies of the A-bomb survivors lead to higher risk estimates with the multiplicative model. This comparative study points out the variations of the lifetime risk calculations according to the baseline breast cancer mortality rates of the three populations and with the use of different mathematical projection models.     

Radiation-associated lung cancer: a comparison of the histology of lung cancers in uranium miners and survivors of the atomic bombings of Hiroshima and Nagasaki

A binational panel of Japanese and American pulmonary pathologists reviewed tissue slides of lung cancer cases diagnosed among Japanese A-bomb survivors and American uranium miners and classified the cases according to histological subtype. Blind reviews were completed on slides from 92 uranium miners and 108 A-bomb survivors, without knowledge of population, sex, age, smoking history, or level of radiation exposure. Consensus diagnoses were obtained with respect to principal subtype, including squamous-cell cancer, small-cell cancer, adenocarcinoma, and less frequent subtypes. The results were analyzed in terms of population, radiation dose, and smoking history. As expected, the proportion of squamous-cell cancer was positively related to smoking history in both populations. The relative frequencies of small-cell cancer and adenocarcinoma were very different in the two populations, but this difference was accounted for adequately by differences in radiation dose or, more specifically, dose-based relative risk estimates based on published data. Radiation-induced cancers appeared more likely to be of the small-cell subtype, and less likely to be adenocarcinomas, in both populations. The data appeared to require no additional explanation in terms of radiation quality (alpha particles vs gamma rays), uniform or local irradiation, inhaled vs external radiation source, or other population difference.     

Simultaneous progressive multifocal leukoencephalopathy, Epstein-Barr virus (EBV) latent infection and cerebral parenchymal infiltration during chronic lymphocytic leukemia

We report a non-HIV patient who had B chronic lymphocytic leukemia (CLL) with progressive multifocal leukoencephalopathy (PML) and diffuse cerebral leukemic parenchymal infiltration in the presence of JC virus and Epstein-Barr virus (EBV) cerebral co-infection. Multiple subcortical hypodensities lining the cortico-subcortical junction were present within the white matter on computerized tomography (CT) scan, with large areas of high signal intensity on T2-weighted sequences on magnetic resonance imaging (MRI). JCV DNA was identified in peripheral blood nuclear cells and cerebrospinal fluid polymerase chain reaction (PCR) DNA/DNA hybridization plus Southern blot analysis. Frontal stereotactic biopsy confirmed the diagnosis of PML by immunocytochemistry, in situ hybridization (ISH) with JC Enzo probe and electron microscopy. Leukemic B cells with the same phenotype as leukemic blood cells were disseminated in the demyelinated areas. They were labeled by anti-latent membrane protein and by BamHl W EBV probe after ISH. Adhesion and activation molecules were positive for CD23. Autopsy showed diffuse visceral leukemic infiltration without acutization. EBV-transformed B lymphocytes would favour JCV penetration and/or intracerebral reactivation of previously latent JCV infection with further development of simultaneous PML and cerebral CLL infiltration in an immunosuppressed patient.