Distribution of JC virus DNA in peripheral blood lymphocytes of hematological disease cases.

OBJECTIVE: The distribution of JC virus DNA in peripheral blood was surveyed by the polymerase chain reaction using the late genes as markers. RESULTS: Six out of 52 cases of hematological diseases and one systemic lupus erythematosus case out of 17 cases were positive for JCV DNA. After separation into B and T lymphocytes by a cell sorter, JCV DNA was found in both cell types prepared from adult T cell leukemia and PML patients. CONCLUSION: Only 1 or 2 copies of JCV genome were calculated to exist in a cell based on the time course analysis of PCR. Only B lymphocytes and glial brain cells are known to produce nuclear factors which support the growth of the virus. The result that B lymphocytes contained a copy number of JCV genome similar to T lymphocytes suggests that there is some barrier to viral growth in susceptible B lymphocytes, and that the growth of JCV is different from that of other virulent viruses.

[Epstein-Barr virus-associated hemophagocytic syndrome during mid-term pregnancy successfully treated with combined methylprednisolone and intravenous immunoglobulin].

A 32-year-old woman in the 16th week of pregnancy was admitted to our hospital because of high fever. Laboratory findings disclosed pancytopenia and extremely elevated serum LDH and ferritin levels. Coagulation tests showed disseminated intravascular coagulation. Serum soluble interleukin-2 receptor, tumor necrosis factor-alpha, and interleukin-6 levels were high, but serum interferon-gamma was below the detectable limit. Reactive Epstein-Barr virus (EBV) infection was diagnosed on the basis of a high titer of IgG antibodies to the EBV capsid antigen and early antigen. EBV was demonstrated in the peripheral blood and bone marrow cells by polymerase chain reaction. Mature histiocytosis and hemophagocytosis were detected in the bone marrow. A diagnosis of EBV-associated hemophagocytic syndrome (EBV-AHS) was made. Neither prednisolone (PSL 30 mg/day, P.O.) nor methylprednisolone (m-PSL) pulse therapy (1,000 mg/day for 3 days) induced a response. Thereafter, treatment with m-PSL pulse therapy (1,000 mg/day for 3 days) and i.v. administrations of high-dose immunoglobulin (20 g/day for 3 days) in combination with acyclovir (750 mg/day) and gabexate mesilate (2 g/day) induced remission of the disease. Maintenance therapy consisted of PSL (5 mg/day, P.O.) and camostat mesilate (600 mg/day, P.O.). The patient delivered a healthy male infant in the 35th week of pregnancy via natural birth. Reports of pregnant women with EBV-AHS are rare, and the choice of therapy has not yet been established. The present case study suggested the above combination treatment is useful and safe, and capable of changing the fulminant course of EBV-AHS during pregnancy without the use of anticancer drugs.

[Pulmonary thromboembolism that developed during an airplane flight "economy-class syndrome"].

The occurrence of thromboembolic phenomena during long-duration airplane flights is called "economy-class syndrome". Recently it has become more popular for Japanese to go abroad by airplane, and an increase in the prevalence of pulmonary thromboembolism should be expected. However, there are few reports of the economy-class syndrome in Japan. A 52-year-old woman was admitted to our hospital because of chest discomfort and dyspnea that developed during an airplane flight. We suspected pulmonary thromboembolism, on the basis of a chest X-ray film and on electrocardiogram. A ventilation-perfusion lung scan disclosed mismatching between ventilation and perfusion in the right upper lung field. Pulmonary thromboembolism was confirmed by pulmonary arteriography. The patient was treated with heparin and urokinase. A phlebogram of the legs showed no significant findings. There was no history of thromboembolic disease or of consumption of oral contraceptives. We conclude that the pulmonary thromboembolism might have been caused by stasis of blood in the lower limb veins during the airplane flight. We emphasize the importance of including pulmonary thromboembolism in the differential diagnosis of patients with chest discomfort and dyspnea that develop during airplane flights. No noninvasive test can lead to a definitive diagnosis of pulmonary thromboembolism. Early pulmonary angiography should be recommended when pulmonary thromboembolism is suspected.

[A case of erythroleukemia found after multiple cerebral hemorrhage].

A 61-year-old man without hypertension was admitted for unconsciousness. Brain CT showed multiple cerebral hemorrhage of the left frontal lobe and right occipital lobe. The hemoglobin was 7.0 g/dl, the platelet count 7,000, the white-cell count 7,600 with erythroblasts, and the fibrinogen 327 mg/dl. No disseminated intravascular coagulation was found. Bone marrow examination demonstrated 69.2% erythroblasts including abnormal types of nucleus, 12.8% myeloblasts, 12.8% neutrophils, 0.8% monocytes, 4% lymphocytes, and 0.4% reticulocytes. Chromosomal examination showed 7 of 20 bone marrow cells were variously abnormal. A diagnosis of erythroleukemia with major karyotype aberrations (MAKA) was made. The patient died 5 days after admission. Histologically, cerebral hemorrhagic lesions showed complete necrosis, but neither invasion of leukemic cells nor amyloid angiopathy. We suspected that the cause of cerebral hemorrhage was severe loss of platelets. This is a rare case of erythroleukemia found after multiple cerebral hemorrhage. As a cause of cerebral hemorrhage in an old man without hypertension, one should consider not only cerebral amyloid angiopathy but also leukemia.

[Hemodynamic TIA associated with severe anemia--a case report].

A 62-year-old man developed recurrent TIAs presenting as mild unconsciousness, dysarthria and weakness of the right upper extremity lasting for 15 to 20 minutes. He was found to have severe iron deficiency anemia (hemoglobin: 5.5-5.9g/dl; hematocrit: 18.4-19.5%) which insidiously developed through the chronic bleeding from the gastric ulcer. He had slight hypertension (184/86mmHg), but no orthostatic hypotension. DSA and MR angiography showed severe stenosis at the origin of the bilateral internal carotid arteries and of the left vertebral artery. There was also hypoplasia of the right vertebral artery. Blood circulation detected by 123I-IMP-SPECT was markedly decreased in the whole brain and in the right hemisphere of the cerebellum. TIA was, however, completely disappeared following to the recovery of anemia. The present case suggested that the presence of severe anemia accelerated the occurrence of hemodynamic TIA (regional cerebral anemic hypoxia), which is probably the consequence of the reduced oxygen-transporting capacity of the blood.

Phylogenetic comparison between archetypal and disease-associated JC virus isolates in Japan.

We examined the phylogenetical correlation between two types of JC virus (JCV) isolates, archetypes derived from the urine of nonimmunocompromised individuals and PML-types derived from the brain of patients with progressive multifocal leukoencephalopathy (PML) in Japan. A phylogenetic tree was constructed for eight JCV isolates, five PML-types obtained in this and previous studies and three representative archetypes, from DNA sequence data on the VP1 (major capsid protein) gene. The eight isolates were divided into two major groups, named subtypes MY and CY after the representative archetypal isolates. Four of five PML-type isolates belonged to subtype MY, and the other one to subtype CY. Isolates belonging to subtype MY were further divided into two groups; one group containing archetype MY and three PML-types and the other one containing archetype YI and a PML-type. These findings, together with those in our previous study that correlated various JCV isolates in the world provide evidence for the hypothesis that JCVs associated with PML may have been generated from archetypal JCVs persisting in the patients.

[Comparative trial of granisetron versus granisetron plus methylprednisolone for the prevention of nausea and vomiting induced by cancer chemotherapy].

Preclinical and clinical studies have demonstrated the effectiveness of granisetron in preventing emesis induced by antineoplastic chemotherapy. This comparative study was undertaken to investigate the efficacy and safety of granisetron (40 micrograms/kg) and granisetron plus methylprednisolone (MPL; 10 mg/kg). Sixty-eight patients were given granisetron 170 times and thirty-nine patients were given a combination of granisetron and MPL 81 times. Sixty-one patients received the treatment in crossover fashion during the same chemotherapy regimens. The emetic and nausea episodes were counted during the 24 hours following each chemotherapy treatment. Complete response, no emesis or less than two episodes, were obtained in 75.3% (128/170 times) of patients receiving granisetron alone compared to 85.2% (69/81 times) of patients receiving the combination of granisetron plus MPL. There were no significant differences in complete responses between the two groups, male and female, and each age group. However, 11 of eighteen patients receiving granisetron alone who responded mildly, if at all, with respect to nausea and vomiting, showed a complete or major response when MPL was added to granisetron. There were two patients who developed temporal paresthesia of the both hands as an adverse effect, but there was spontaneous recovery after 3 hours. Our data suggested that granisetron plus MPL was slightly more effective than granisetron alone and a safe antiemetic drug.

[A case of smoldering ATLL in high risk family and familial double infection of HTLV-1 and HBV].

A 35-year-old male from Kagoshima prefecture developed nodules with asymptomatic erythema on both upper eyelids, both hands and upper right leg in April 1986. On April 10, 1987, biopsy of skin lesions revealed numerous atypical CD4 positive lymphocytes which had invaded the dermis around the vessels. Analysis of serum showed positive antibody titer (X40) against the human T lymphotropic virus type I (HTLV-I) with some flower cells evident in peripheral blood; however, no infiltration into bone marrow or lymph nodes could be seen. Lymphocytes from peripheral blood and from the skin lesion of the right leg showed monoclonal integration of HTLV-I proviral DNA. Chronic active hepatitis B virus (HBV) was also a complicating factor. Familial study revealed all three family members to be infected with HTLV-1 as well as HBV. Proviral integration of HTLV-I was the intermediate type in two out of the three. From the results, a diagnosis of smoldering adult T cell leukemia-lymphoma (ATLL) was made in this patient with high risk to family members. Herein we discuss the development of ATLL in this case and infection among family members.

Production of interleukin-2 by YAC-1 cells stimulated with interleukin-1 and its augmentation of the natural killer activity.

The production of interleukin-2 (IL-2) by YAC-1 cells stimulated with interleukin-1 (IL-1) was examined in the in vitro culture system. The IL-2 activity was detectable in the culture supernatant of YAC-1 cells stimulated with either a mouse IL-1 preparation or human purified IL-1. This activity could be detected 1 h after stimulation with IL-1. The addition of monoclonal antibody reactive with mouse IL-2 receptor completely blocked the IL-2 activity in the culture supernatant of IL-1-stimulated YAC-1 cells. Further, the culture supernatant of IL-1-stimulated YAC-1 cells augmented the NK activity in mouse spleen cells. The role of the IL-2 activity in the culture supernatant of IL-1-stimulated YAC-1 cells on augmentation of the NK activity is discussed.