The first recognized patient withLegionella pneumophila serogroup 9 pneumonia in Japan

A 77-year-old female was admitted because of high fever, cough and sputum. She had been receiving corticosteroid therapy for 4 years for multiple myeloma and was immunosuppressed. A physical examination on admission showed coarse crackles in the right lower lung field, a chest radiograph showed consolidation in the right middle and lower lung fields, and a blood gas analysis revealed marked hypoxemia. The patient was diagnosed as having refractory pneumonia associated with acute respiratory failure and treated with intravenous cefmetazole followed by imipenem. On hospital day 5, erythromycin therapy was started because of a poor response to the previous antibiotics. The patient became afebrile on the tenth day and was in good health on day 15. A sputum culture on day 4 revealed aLegionella organism on Wadowsky-Yee-Okuda medium, which was subsequently confirmed to beLegionella pneumophila by a DNA hybridization test. This strain was identified at the Centers for Disease Control (Atlanta, GA, USA) by slide agglutination asL. pneumophila serogroup 9. Although our patient's symptoms are not apparently different from those caused by other serogroup strains ofL. pneumophila, this is the first recognized patient with culture-provenL. pneumophila serogroup 9 pneumonia in Japan. The clinical course of the disease and the diagnostic difficulties in identifying this type of pneumonia are discussed.     

Multiple system atrophy variant with severe hippocampal pathology

The striatonigral and olivopontocerebellar systems are known to be vulnerable in multiple system atrophy (MSA), showing neuronal loss, astrogliosis, and alpha-synuclein-immunoreactive inclusions. MSA patients who displayed abundant neuronal cytoplasmic inclusions (NCIs) in the regions other than the striatonigral or olivopontocerebellar system have occasionally been diagnosed with variants of MSA. In this study, we report clinical and pathologic findings of MSA patients characterized by prominent pathologic involvement of the hippocampus. We assessed 146 consecutively autopsied MSA patients. Semi-quantitative analysis of anti-alpha-synuclein immunohistochemistry revealed that 12 of 146 patients (8.2%) had severe NCIs in two or more of the following areas: the hippocampal granule cells, cornu ammonis areas, parahippocampal gyrus, and amygdala. In contrast, the remaining 134 patients did not show severe NCIs in any of these regions. Patients with severe hippocampal involvement showed a higher representation of women (nine women/three men; Fisher's exact test, p = 0.0324), longer disease duration (13.1 ± 5.9 years; Mann–Whitney U-test, p = 0.000157), higher prevalence of cognitive impairment (four patients; Fisher's exact test, p = 0.0222), and lower brain weight (1070.3 ± 168.6 g; Mann–Whitney U-test, p = 0.00911) than other patients. The hippocampal granule cells and cornu ammonis area 1/subiculum almost always showed severe NCIs. The NCIs appeared to be ring-shaped or neurofibrillary tangle-like, fibrous configurations. Three of 12 patients also had dense, round-shaped NCIs that were morphologically similar to pick bodies. The patients with Pick body-like inclusions showed more severe atrophy of the medial temporal lobes and broader spreading of NCIs than those without. Immunohistochemistry for hyperphosphorylated tau and phosphorylated TDP-43 revealed minimal aggregations in the hippocampus of the hippocampal MSA patients. Our observations suggest a pathological variant of MSA that is characterized by severe involvement of hippocampal neurons. This phenotype may reinforce the importance of neuronal alpha-synucleinopathy in the pathogenesis of MSA.     

Hyperdynamic circulation in the left gastric venous area in patients with portal hypertension: Angiological assessment

The time of appearance of the left gastric vein on serial celiac arteriograms in patients with portal hypertension and esophageal varices was compared with that of the portal vein to assess regional hemodynamics in the left venous portion of the stomach, an area located in close proximity to the varices. In two thirds of all the patients with cirrhosis or non-cirrhotic idiopathic portal hypertension (IPH), the left gastric vein was visualized earlier or simultaneously than or with the portal vein, while in all but one patient with prehepatic portal obstruction, there was a delayed opacification of the left gastric vein. These results suggest the presence of a hyperdynamic circulatory state which promotes venous hypertension in the left gastric venous area of the stomach of a considerable number of patients with cirrhosis or IPH. In such a hemodynamic state, selective decompression of varices can be achieved by a left gastric venous caval shunt.     

Neurotoxicity induced by tacrolimus after liver transplantation: relation to genetic polymorphisms of the ABCB1 (MDR1) gene

BACKGROUND: Tacrolimus is a substrate of P-glycoprotein (PGP) encoded by the multidrug resistant (MDR)1 gene (ABCB1). PGP, a multidrug efflux pump, restricts the distribution of tacrolimus in the brain. In this study, we investigate the correlation of ABCB1 gene polymorphism with tacrolimus-induced neurotoxicity in patients after liver transplantation. METHODS: The genotype of 6 patients with neurotoxic events and 11 patients without neurotoxic events was analyzed by polymerase chain reaction (PCR), and 8 mutations were detected. In addition to laboratory findings and patient characteristics, the contribution of mutations in the ABCB1 gene was evaluated with stepwise discriminant function analysis. RESULTS: High tacrolimus concentration, liver dysfunction, and mutation at position 2677 in exon 21 were demonstrated as positive predictors of tacrolimus-induced neurotoxicity. CONCLUSION: It is indicated that blood concentrations, liver function, graft weight, and polymorphism in the ABCB1 gene are important factors in tacrolimus-induced neurotoxicity.     

Solitary Fibrous Tumor in the Retroperitoneal Space: Report of a Case

Solitary fibrous tumors (SFTs) are spindle-cell neoplasms originally described in the pleura. It is now known that these tumors can develop in many sites. This report describes the case of a well-circumscribed tumor located around the superior mesenteric artery (SMA), which was initially thought to be either a superior SMA aneurysm, a lymphoma, or a neurogenic tumor. Histological examination demonstrated the tumor to be composed of a cellular proliferation of ovoid to spindle cells with a fine collagenous matrix in the short fascicles. Immunohistochemical staining was strongly positive for CD34 and negative for factor VIII, cytokeratin, desmin, and muscle-specific actin (HHF-35). These findings suggested a diagnosis of SFT in the retroperitoneal space. To our knowledge, this is the first report of an SFT located around the SMA. Based on the above findings, it is important to include SFT in the differential diagnosis of retroperitoneal tumors located around the SMA. Received: August 13, 2001 / Accepted: March 5, 2002 Reprint requests to: M. Kume     

Flow cytometric analysis of de novo acute lymphoblastic leukemia in childhood: report from the Japanese Pediatric Leukemia/Lymphoma Study Group

Although the antigen expression patterns of childhood acute lymphoblastic leukemia (ALL) are well known, little attention has been given to standardizing the diagnostic and classification criteria. We retrospectively analyzed the flow cytometric data from a large study of antigen expression in 1,774 children with newly diagnosed ALL in JPLSG. T- and B-lineage ALL accounted for 13 and 87% of childhood ALL cases, respectively. Cytoplasmic CD3 and CD7 antigens were positive in all T-ALL cases. More than 80% of T-ALL cases expressed CD2, CD5 and TdT. In B-lineage ALL, the frequencies of early pre-B, pre-B, transitional pre-B and B-ALL were 81, 15.5, 0.6 and 2.9%, respectively. More than 90% of early pre-B ALL cases expressed CD19, CD79a, CD22, CD10 and TdT. CD34 was expressed in three-fourths of early pre-B ALL cases. The frequencies of TdT and CD34 expression were lower in pre-B ALL than in early pre-B ALL. B-ALL showed less frequent expression of CD22, CD10, CD34 and TdT than other B-lineage ALL cases. Expression of CD13 and CD33, aberrant myeloid antigens, was significantly more frequently associated with B-lineage ALL than with T-ALL. Based on this retrospective study of antigen expression in 1,774 de novo childhood ALL cases in JPLSG, we propose standardized clinical guidelines for the immunophenotypic criteria for diagnosis and classification of pediatric ALL.     

Involvement of Sl00–related Calcium–binding Protein pEL98 (or mts1) in Cell Motility and Tumor Cell Invasion

We examined the relationship between cell motility and the expressions of pEL9S ( mtsl ) mRNA and protein in various imirine normal and transformed cells. The expression of pEL98 ( mtsl ) in v–Ha– ras –transformed NIH3T3 cells and in normal rat kidney cells transformed by either v–Ha– ras or v–src was increased over that in the corresponding parental cells at both mRNA and protein levels. The expression in normal rat fibroblasts (3Y1) transformed by v–Ha– ras was also increased compared with that in 3Y1 cells. However, the expression of pEL98 (mtsl) in 3Y1 cells transformed by v –src was increased in one clone (src 3Y1–K), but decreased in another clone (src 3Y1–H). The expression level of pEL98 (mtsl) correlated well with cell motility, which was examined by measuring cell tracks by phagokinesis. In order to test direct involvement of the pEL98 ( mtsl ) protein in cell motility, src 3Y1–H cells that showed low cell motility were transfected with pEL98 cDNA. The transfectants expressing large amounts of the pEL98 protein showed significantly higher cell motility than src 3Y1–H cells. The expression of pEL98 ( mtsl ) was also found to be correlated with motile and invasive abilities in various clones derived from Lewis lung carcinoma. These results suggest that the pEL98 ( mtsl ) protein plays a role in regulating cell motility and tumor cell invasiveness.