Presence of human papillomavirus type 16 genome in bladder carcinoma in situ of a patient with mild immunodeficiency.

Using blot hybridization, we analyzed 10 bladder tumors (1 transitional cell carcinoma in situ, 1 adenocarcinoma, and 8 papillary tumors) for the presence of human papillomavirus (HPV) DNA. We detected HPV 16 DNA in a transitional cell carcinoma in situ, whereas no HPV DNA was found in the other bladder tumors. The patient, a 40-year-old female, who harbored HPV 16 DNA in the bladder tumor, had mild immunodeficiency and recently suffered from the bladder tumor, common warts on the right hand, Bowen's disease of the vulva, and severe dysplasia of the vaginal wall. From each of these lesions, we detected the DNA of HPV 16 or an unclassified HPV. HPV DNAs existed in nonintegrated form in all lesions examined. To our knowledge, this is the first case in which a bladder tumor was shown to harbor HPV DNA. However, HPV does not seem to be regularly present in bladder tumor, because we could not detect HPV DNA from the most common bladder tumor, i.e., papillary tumor. Our demonstration of HPV 16 DNA in a transitional cell carcinoma in situ of the bladder suggests that HPV may be associated with some of the bladder tumors of this type.

Polyadenylate in the virion RNA of mouse hepatitis virus.

Mouse hepatitis (MH) virus was grown in SR-CDF1-DBT, a mouse cell line, and purified by ammonium sulfate precipitation and by density gradient centrifugation. Extraction of RNA from purified virions with 1% SDS and sedimentation analysis of the RNA revealed a major 50S component and two minor components. Treatment of virions with phenol/chloroform also produced the 50S component, although its yield was lower. MH virion RNA can bind to a poly(U)-fiberglass filter, indicating that MH virion RNA contains poly(A). A poly(A)-like fragment was isolated by digestion with ribonuclease A [EC 3.1.4.22] and T1 [EC 3.1.4.8] and by DEAE-Sephadex column chromatography. Analysis of the fragment for base composition showed it to be an adenine-rich material. Its chain length was about 90 nucleotides, as determined by ion-exchange chromatography and gel electrophoresis.

[Chronological changes of lacunar infarctions on fluid-attenuated inversion recovery magnetic resonance images].

In 26 patients with lacunar syndromes, emergence of new lacunar infarctions were identified within 13 days from onset by diffusion-weighted magnetic resonance images. The identified lacunar infarctions were repeatedly imaged using fluid-attenuated inversion recovery (FLAIR) sequence up to 600 days from onset. On FLAIR images taken by 23 days from onset, lacunar infarctions showed homogeneous hyperintensity. On the later FLAIR images beyond 25 days from onset they were observed as heterogeneously hyperintense lesions in half of the patients. In the other patients, lacunar infarctions were observed as hypointense areas with a hyperintense rim beyond 41 days from onset, which indicates cystic transformation with surrounding gliosis. These FLAIR images of lacunar infarction differ from those of dilated perivascular space which is observed as an area of simple hypointensity.

[Acquired immunodeficiency syndrome-associated progressive multifocal leukoencephalopathy treated with highly active anti-retroviral therapy].

We reported a patient with acquired immunodeficiency syndrome (AIDS)-associated progressive multifocal leukoencephalopathy (AIDS-PML), whose condition improved after highly active anti-retroviral therapy (HAART). A 70-year-old man was admitted to our hospital because of worsening left hemiplegia and disturbance of consciousness. During the past 30 years, he frequently traveled to the United States and southeast Asia. On neurological examination, he was somnolent and left hemiplegia with severe rigospasticity was present. The deep tendon reflexes showed hyper-reflexes with extensor plantar responses. Laboratory studies showed pancytopenia and positive HIV-1 antibodies. The CD4 cell count was 38/mm3 and his HIV viral RNA load in the blood was 9,500 copies/ml. T2-weighted magnetic resonance imaging (MRI) of the brain revealed asymmetrical high intensity white matter lesions in the right fronto-parietal, and left frontal regions and in the cerebellar hemisphere. The cerebrospinal fluid (CSF) protein elevated to 91 mg/dl with a normal cell count. The diagnosis of PML was confirmed by the detection of JC virus DNA in the CSF using a nested polymerase chain reaction assay. Three weeks after starting HAART with zidovudine, lamivudine, and indinavir, he was able to respond to simple commands. Two months later, the HIV viral RNA load decreased to less than 400 copies/mm3, and no JC virus DNA was detected in the CSF, with an increase of the CD4 cell count to 285/mm3 in the blood. A follow-up MRI of the brain showed a reduction in the cerebellar and cerebral white matter lesions. The recovering immune function by decreasing of the HIV load after HAART might suppress JC virus replication. It was suggested that HAART would become a beneficial treatment for patients with AIDS-PML.

[Progressive multifocal leukoencephalopathy (PML). Report of a case diagnosed by amplification of JC virus DNA from cerebrospinal fluid (CSF)].

We report a 54-year-old Japanese man who was diagnosed as progressive multifocal leukoencephalopathy (PML). He had been maintained on regular hemodialysis for 10 years. He was admitted to our hospital with chief complaints of visual disturbance and disorientation. On neurological examination, he was somnolent, and showed mild weakness in the right upper and lower limbs. Deep tendon reflexes were brisk on the right upper and bilateral lower limbs. Sensory examination revealed no abnormal findings. The cerebrospinal fluid (CSF) showed five mononuclear cells/mm3, protein 39 mg/dl and glucose 38 mg/dl. Brain MRI revealed multiple hyperintense lesions in T2-images, which were confined to the white matter of bilateral occipital and the left frontal lobes without an enhancement after gadolinium administration. Using polymerase chain reaction, we amplified the JCV regulatory region from the CSF of the patient. The amplified product contained a rearranged regulatory region that could have been generated from the archetype by deletion and amplification. PML was diagnosed on the basis of these findings. The patient died 7 months after onset of the symptoms. The diagnosis of PML was confirmed by the postmortem findings. The present case indicates that PCR of JCV from CSF is very useful for definitive diagnosis of PML.

[A case of progressive multifocal leukoencephalopathy with methionine uptake demonstrated by PET].

We report here a 55-year-old man with progressive multifocal leukoencephalopathy (PML) associated with chronic adult T cell leukemia (ATL). Neurological examination revealed mild dementia, right homonymous hemianopsia and visual agnosia. Serologically anti-HTLV-I antibody was positive. Peripheral blood analysis showed ATL cells up to 23% in white blood cells. Because he did not have symptoms or signs directly related to ATL, it was considered that he had chronic ATL. T2-weighted cranial MRI demonstrated multiple hyperintensity lesions confined to the white matter from the bilateral occipital to parietal lobes, without enhancement after gadolinium administration or mass effect. We performed stereotactic biopsy of the left occipitoparietal white matter. Histological examination of the biopsied specimens showed demyelinated lesions, containing foamy macrophages and bizarre astrocytes. Oligodendrocytes contained nuclear inclusions which reacted with an antibody against the JC virus (JCV) antigen. These findings were consistent with those of PML. The genomic analysis of JCV from the biopsied brain revealed deletions in the regulatory region. We investigated cerebral blood flow, glucose and amino acid metabolism in this patient using positron emission tomography, and obtained the following three characteristic findings in the lesions: 1) luxury perfusion state, 2) decreased fluorodeoxyglucose (FDG) uptake, and 3) increased methionine (Met) uptake. These findings resembled those of low grade tumors.

A study of physiological response during emotional imaging.

We inspected Lang's bio-informational theory and furthered the research. 24 subjects were divided into two groups, a stimulus group (S-group) and a response group (R-group) for scripts with Joy, Anger, and Neutral emotions. In the training session, the S-group was instructed to image the scripts as vividly as possible, while the R-group was instructed to concentrate on physiological and physical responses in addition to what was asked of the S-group. On the test day, subjects imaged two Neutral scripts, two standard emotional scripts, and two personally relevant emotional scripts. Indices were physiological response (blood pressure) and subjects' ratings for imaging. We confirmed that emotional scripts increased physiological responses more than nonemotional scripts did. The results suggested that the differences in the scripts' content affected blood pressure and subjects' ratings of imaging.

Judgments of emotion by nurses and students given double-bind information on a patient's tone of voice and message content.

We examined the communication process in a situation typical of the nursing setting by use of a double-bind communication. Our objective was to examine which of two cues in communications from a patient, tone of voice or verbal content, was more important in judging the speaker's emotional status and personality traits and in arousing the listening nurse's emotions. Subjects were 82 nurses who worked at the university hospital and 100 students who were studying at the Faculty of Nursing of the university. They were assigned into four groups at random, presented professionally tape-recorded scripts representing a patient's verbal report, and then completed a questionnaire concerning the speaker's emotional status as well as the listener's own emotional status. When the listeners judged the speaker's emotional status, they gave more attention to a negative emotional expression, and when the listeners formed an impression of the speaker's personality traits, they were influenced by the speaker's tone of voice rather than by the content of the speech.

[Bladder carcinoma in situ which harbored human papilloma virus. A case report].

Last year, we reported that human papilloma virus type 16 genome (HPV 16 genome) was detected in a case (S.Y.) of bladder carcinoma in situ (bladder CIS) (Cancer Res., 1988). Since then, a number of bladder tumors other than CIS were searched for HPV genome. However, no HPV genome was detected in the bladder tumors. From the results, we consider that HPV may not have a relation with all types of bladder tumor but with only a part of it. In the current report, the case (S.Y.) is presented more precisely than before, in particular on the characteristic bladder lesion. The patient was a 40-year-old female with immunodeficiency and anemia who was referred from a hospital with a complaint of asymptomatic pyuria. Cystoscopic examination revealed a bladder tumor, well-demarcated, white and velvety lesion with slight elevation. On November 25, 1987, she underwent total cystectomy, resection of the anterior vaginal wall and of a part of vulval skin, and ileal conduit formation. Postoperative course was stormy because of bleeding from the wounds and thrombophlebitis in the right femoral vein. In spite of the episodes, she eventually recovered and was discharged 2 months later. However she was readmitted 9 months later due to severe anemia which was ascribed to acute myelogenous leukemia. She is now on cancer chemotherapy for leukemia.

[Lung cancer obscured by aspergillus hyphae].

A 66-year-old man was referred to our hospital because of cough. Chest X-ray films showed complete atelectasis of the left lung. Serum CYFRA was elevated. Bronchoscopic examination disclosed a white polypoid lesion occluding the left main bronchus. A biopsy specimen from the lesion revealed numerous aspergillus hyphae. Oral itraconazole (100 mg) and weekly endobronchial instillation of fluconazole were administered. Three months later, on the 12th bronchoscopic examination, the tumor occluding the left main bronchus was detected after the removal of aspergillus, and the biopsy findings yielded a diagnosis of squamous cell carcinoma. Aspergillosis complicated by lung cancer without cavity formation is very rare, and compounded the difficulty of diagnosing lung cancer in this case.

Even distribution of BK polyomavirus subtypes and subgroups in the Japanese Archipelago.

BK polyomavirus (BKV) is ubiquitous among humans, infecting children asymptomatically and then persisting in renal tissue. BKV has four subtypes (I-IV) that can be identified by serological and genotyping methods. Subtypes I and IV are most prevalent in all countries examined to date. Based on nucleotide sequence variation, subtype I is further classified into four subgroups (Ia, Ib-1, Ib-2 and Ic), each of which have a close relationship to a particular human population. To clarify the relationships between BKV and human populations, we investigated the distribution patterns of BKV subtypes and subgroups in the modern Japanese population, which was formed from two distinct ethnic groups. Urine samples were collected from immunocompetent elderly patients in six regions along the Japanese Archipelago. The 287-bp VP1 region of the viral genome from these samples was amplified using the polymerase chain reaction. The amplified VP1 regions were sequenced and a neighbor-joining phylogenetic tree was reconstructed to classify the BKV isolates. We observed a similar pattern of subtype distribution throughout the Japanese Archipelago, with subtype I always detected at high rates (67-75%), followed by subtype IV (19-31%), with rare or no detection of subtypes II and III. Based on phylogenetic and single nucleotide polymorphism analyses, the subtype I isolates were divided into subgroups; the percentage of the Ic subgroup was high in all geographic regions (88-100%). These results suggest that BKV subtypes and subgroups are evenly distributed in the Japanese Archipelago. We discuss the implications of these findings for the relationships between BKV and human populations.

Subtype IV of the BK polyomavirus is prevalent in East Asia.

BK polyomavirus (BKV) is ubiquitous in human populations, infecting children asymptomatically and then persisting in the kidney. Using either serological or genotyping methods, BKV isolates have been classified into four subtypes (I-IV), with subtype I mainly detected in all countries studied so far. To elucidate the subtype of BKV prevalent in East Asia, we examined BKV-positive urine samples collected from immunocompetent elderly patients in Mongolia, Northeast China, Northwest China, Southeast China, Southwest China, Vietnam and Japan. The 287-bp typing region of the viral genome in each of these samples was PCR-amplified and sequenced, and a phylogenetic tree was constructed. According to the tree, BKV isolates in East Asia were unambiguously classified into subtype I or IV (subtypes II and III were not detected). In Japan, subtype I was mainly detected and subtype IV was rare, whereas in the other regions subtype IV was detected frequently, at rates ranging from 24 to 100%. Thus, East Asia (excluding Japan) is a region in which subtype-IV BKV is prevalent, a finding that requires the view of the geographic distribution of BKV subtypes to be revised. Furthermore, we present evidence that the immunological states of urine donors do not affect the pattern of BKV subtypes.