Occurrence of the African subgroup (Ia) of BK polyomavirus in younger Japanese children.

BK polyomavirus (BKV) is ubiquitous among humans, usually infecting them asymptomatically during childhood. BKV persists in renal tissue of individuals and their progeny are excreted in urine, particularly in immunocompromised patients. JC virus, another human polyomavirus, has been considered to be transmitted from parents to children during prolonged cohabitation. However, BKV has been supposed to be transmitted not only within but also outside the family. In the present study, to clarify this possibility, we analyzed phylogenetically 35 BKV which were excreted in the urine by Japanese children and adults undergoing stem cell transplantation. Subtypes I, III and IV were detected in 15, two and one children and in 15, one and one adults, respectively. Among 15 subtype I isolates from children, three, four and eight belonged to subgroups Ia, Ib-1 and Ic, respectively. All the three children from whom Ia was detected were less than 9 years old. In contrast in the adults, three subtype I belonged to Ib-1 and the other 12 to Ic. These findings may reflect the recent transmission of BKV Ia strains to Japanese children.

Quantification of BK polyoma viruria in Japanese children and adults with hemorrhagic cystitis complicating stem cell transplantation.

Polyoma BK virus (BKV) is frequently found in the urine of stem cell transplantation (SCT) patients with hemorrhagic cystitis (HC), but also occurs in SCT patients without HC. How BK viruria relates to the development of HC in SCT patients, especially in children, has not yet been fully evaluated. In the present study, we analyzed the relationship of several factors including urinary BKV load to HC development in children and adults undergoing SCT. We employed a quantitative PCR assay and evaluated 37 patients (aged 9 months-62 years) of whom 12 developed HC and 25 did not. Older age was a risk factor for the development of HC; however, other factors such as sex, primary disease, type of SCT, conditioning regimen and aGVHD were not. Peak urinary BKV values in HC patients were not higher than those in non-HC patients. Severity of HC also did not correlate with urinary BKV loads. However, in some patients who secreted higher urinary BKV loads, the peak loads were closely related with the onset of HC. Higher BKV loads may be a risk factor for the development of HC in conjunction with other coexisting factors.

Probing the molecular mechanisms of neuronal degeneration: importance of mitochondrial dysfunction and calcineurin activation.

Cerebral injury is a critical aspect of the management of patients in intensive care. Pathological conditions induced by cerebral ischemia, hypoxia, head trauma, and seizure activity can result in marked residual impairment of cerebral function. We have investigated the potential mechanisms leading to neuronal cell death in pathological conditions, with the aim of discovering therapeutic targets and methods to minimize neuronal damage resulting from insults directed at the central nervous system (CNS). Over the years, deeper understanding of the mechanisms of neuronal cell death has indeed evolved, enabling clinical critical care management to salvage neurons that are at the brink of degeneration and to support recovery of brain function. However, no substantial breakthrough has been achieved in the quest to develop effective pharmacological neuroprotective therapy directed at tissues of the CNS. The current situation is unacceptable, and preservation of function and protection of the brain from terminal impairment will be a vital medical issue in the twenty-first century. To achieve this goal, it is critical to clarify the key mechanisms leading to neuronal cell death. Here, we discuss the importance of the calcineurin/immunophilin signal transduction pathway and mitochondrial involvement in the detrimental chain of events leading to neuronal degeneration.

Quantification of adenovirus species B and C viremia by real-time PCR in adults and children undergoing stem cell transplantation.

Adenovirus infection during stem cell transplantation is associated with high morbidity and mortality. Adenovirus species B and C have been the main causes for these infections; however, epidemiological details about the species are still unclear. To clarify the contributions of species B and C adenovirus, the DNA was tested serially by quantitative real-time PCR in peripheral blood, stool and urine of 32 patients (16 adults and 16 children) undergoing stem cell transplantation. Adenovirus species B viremia was detected in 10 of 16 adult and 6 of 16 pediatric transplant recipients. Adenovirus species C viremia was also detected simultaneously in five adult and three pediatric recipients. The stool and urine of patients with adenovirus viremia were also positive for the same adenovirus species as in blood. In contrast, in none of 50 healthy adult controls was adenovirus species B or C viremia detected. Among patients who developed adenovirus viremia, one adult recipient developed disseminated disease and died from multiple organ failure. The remaining patients experienced fever of several degrees and/or diarrhea during the period of adenovirus viremia; however, they all recovered without antiviral therapy. The results indicated that stem cell transplantation was frequently associated with adenovirus species B or C viremia, although it did not always cause serious infectious complications.

[Effective combination therapy of bortezomib and dexamethasone for two patients with refractory multiple myeloma].

We describe 2 cases of conventional therapy-resistant multiple myeloma (MM) that responded to bortezomib and dexamethasone therapy. Case 1: A 62-year-old woman with MM (IgG, kappa-type, stage IIIA) resistant to DMVM-IFN (dexamethasone, ranimustine, vincristine, melphalan, interferon-a), VAD (vincristine, doxorubicin, dexamethasone), high-dose melphalan with autologous peripheral blood stem cell transplantation (PBSCT) and thalidomide, received 2 courses of bortezomib treatment. In the first course, bortezomib alone was administered and then in the second course bortezomib was given in combination with dexamethasone. The patient's serum IgG level decreased from 8040 to 1020 mg/dl and the level of plasma cells in bone marrow was 1.2% after the treatments. Adverse reactions including rash, anemia, and thrombocytopenia occurred in the first course; however, they were milder in the second course combined with dexamethasone. Case 2: A 43-year-old man with MM (IgD, gamma-type, stage IIA) resistant to conventional and high-dose chemotherapy with PBSCT as well as thalidomide therapy, received treatment with bortezomib alone and then in combination with dexamethasone. His serum IgD level decreased from 2140 to 623 mg/dl. He suffered adverse reactions such as fatigue, anemia, and thrombocytopenia in the first course, which were relieved in the second course. These results indicate that the combination of bortezomib and dexamethasone is effective in the treatment of refractory MM and that dexamethasone can reduce the adverse reactions of bortezomib.