Extensive proliferation of T cell lineage-restricted progenitors in the thymus: an essential process for clonal expression of diverse T cell receptor beta chains

For clonal diversification of TCR, a large number of T cell progenitors are required in which highly diverse TCRbeta chains are accommodated individually. In the present study, we examined the proliferative potential of thymic progenitors that have been defined to be T cell lineage restricted. We show that the earliest fetal thymus (FT) cells from Rag2(-/-) mice, when cultured individually in a thymic organ culture system, produced 150-1,800 CD25(+) cells. Since differentiation and proliferation of Rag2(-/-) thymocytes are arrested at the stage of TCRbeta chain gene rearrangement, the observed proliferation was considered to represent the proliferative potential of progenitors prior to the TCRbeta rearrangement. A comparable level of proliferation was revealed to occur by analyzing the Dbeta-Jbeta rearrangement profiles of T cells generated from single progenitors in the earliest population of FT from normal mice. The proliferative potential of progenitors declined along with the progression of developmental stages. Such an extensive proliferation of progenitors after the restriction to the T cell lineage may be an essential process ensuring the clonal diversification of TCRbeta chains.     

Spectrotemporal window of integration of auditory information in the human brain

The human auditory system is adapted to integrate temporally successive sounds into meaningful entities, that is, acoustic information units. Hence, sound sequences falling within the temporal window of integration should be coded holistically as unitary representations in the human auditory cortex. Although it is well established that the auditory system operates in the frequency-temporal domain, many previous studies only focused on the temporal domain of the window of integration. Therefore, in the current study we investigated the relationship between the short-term temporal integration and the frequency integration. Event-related magnetic fields in response to infrequent omission of the second tone in repetitive tone pairs composed of two closely spaced tones of different frequencies were recorded. This omission elicited the magnetic counterpart (MMNm) of the electric mismatch negativity (MMN), a change-specific component mainly generated in the auditory cortex, when the interval between the two successive tones was extremely short or when the frequency difference between the two tones was small. These findings suggest that two stimuli presented in close succession might be represented in the auditory system as a unitary integrated event. In addition, as the distance between the two successive tones decreased in the spectrotemporal dimensions, the magnitude of the MMNm increased. Behavioral data also supported these neurophysiological phenomena. This work shows the first neurophysiological evidence that the two-dimensional (spectrotemporal) window of integration, which provides important constraints for the neural processing of the acoustic environment, exists in the human brain.     

Usefulness of proviral load measurement for monitoring of disease activity in individual patients with human T-lymphotropic virus type I-associated myelopathy/tropical spastic paraparesis

High human T-lymphotropic virus type I (HTLV-I) proviral load in peripheral blood mononuclear cells (PBMCs) has been reported in patients with HTLV-I-associated myelopathy/tropical spastic paraparesis (HAM/TSP) and the proviral load has been reported to fluctuate in individual patients during the course of the disease. Clinical symptoms usually became stable after a prolonged period of symptom progression. However, the authors have experienced having some patients whose clinical manifestations suddenly became worse during the course of the disease. To clarify the role of high proviral load and its fluctuation in the pathogenesis of HAM/TSP, the authors measured the proviral load of serially taken PBMCs as well as of cerebrospinal fluid (CSF) cells from patients with HAM/TSP on long-term follow-up and compared these with their clinical manifestations. There was a wide distribution of proviral load, from 0.3 to 37.8 copies/100 PBMCs; however, the proviral load in individual patients was relatively stable during the course of the disease. Eighty-three percent of the patients with clinical worsening showed an increase in proviral load at the time point when clinical worsening was recorded, or at the preceding time point. The proviral loads in CSF cells were higher than those in PBMCs in individual patients. The ratio of proviral loads in CSF cells/in PBMCs, but not the absolute load, in either compartment, was significantly associated with clinically progressive disease and with recent onset of HAM/TSP. These findings indicate that clinical progression of HAM/TSP is associated with increased proliferation or immigration of HTLV-I-infected lymphocytes in the central nervous system.     

Characterization of Klebsiella pneumoniae and Escherichia coli strains that produce CTX-M-2-type broad spectrum beta-lactamase isolated from a child with leukemia

An 8-year-old girl with acute leukemia had bacteremia caused by Klebsiella pneumoniae producing CTX-M-2-type broad spectrum beta-lactamase. K. pneumoniae and Escherichia coli strains producing the same enzyme and harboring identical conjugative plasmids were recovered from stoor culture. Patients with frequent episodes of neutropenia and prophylactic administration of beta-lactams are at risk of harboring colonizing strains that produce broad spectrum beta-lactamases.     

Role of hypomagnesemia in chronic cyclosporine nephropathy

BACKGROUND: Hypomagnesemia is a common finding of cyclosporine (CsA)-treated patients and has been proposed as both a cause and a consequence of CsA-induced nephrotoxicity. This experiment was conducted to elucidate the role of hypomagnesemia in the pathogenesis of chronic CsA nephropathy. METHODS: CsA (15 mg/kg/day subcutaneously) was administered to rats maintained on a low-sodium diet for 1, 2, and 4 weeks, and the effects of magnesium (Mg) supplementation on renal function, renal histology, and renal gene expression profile of fibrogenic molecules and vasoconstrictors was examined. RESULTS: CsA elicited hypomagnesemia and induced a progressive decline in glomerular filtration. At 28 day, renal tubular atrophy and cortical striped interstitial fibrosis were evident with CsA treatment. Dietary supplementation of Mg ameliorated CsA-induced hypomagnesemia and almost completely abolished CsA-induced chronic fibrotic lesions. Neither CsA nor Mg supplementation affected blood pressure. Renal cortical mRNA of transforming growth factor beta, plasminogen activator inhibitor (PAI)-1, and extracellular matrix started to increase at 14 days and elevated further at 28 days. In contrast, the increase in mRNA of tissue inhibitor of matrix metalloproteinase-1 and renin was evident early at 7 days and reached peak at 14 days. These mRNA increases, except that of renin, were almost abolished when hypomagnesemia was corrected. Magnesium supplementation also improved glomerular dysfunction, at least in part, through inhibition of up-regulated mRNA of endothelin-1. CONCLUSION: CsA-induced hypomagnesemia contributes to chronic renal fibrotic lesions seen during CsA treatment through up-regulation of fibrogenic molecules, most notably early activation of tissue inhibitor of matrix metalloproteinase-1 expression.     

Prognostic Factors in Synovial Sarcoma: A Clinicopathologic Study of 18 Cases

The prognostic factors for synovial sarcoma were analyzed retrospectivelyin 18 patients. Variables evaluated for their use in predictingsurvival included the location of the primary tumor, tumor size,local recurrence, completeness of surgical resection, and histologicsubtype. Chemotherapy was not evaluated because the patientsreceived various regimens and/or inadequate doses. Tumor sizewas the most significant prognostic factor, and a diameter ofmore than 10 cm was associated with a significantly worse prognosis(risk ratio: 5.38) (P=0.012).We conclude that complete surgicalresection of tumors less than 5 cm in maximum diameter may becurative and that adjuvant chemotherapy may not be necessaryfor such patients, because the value of chemotherapy for synovialsarcoma is still controversial.     

Antitumor activity of cis-diamminedichloroplatinum (II) depends on its time × concentration product against human gastric cancer cell lines in vitro

A pharmacodynamic study of cisplatin (DDP) was conducted using the gastric cancer cell lines MKN-45 and MKN-74 in vitro. Ten thousand tumor cells were incubated with 0.4–500 μg/ml DDP for 1–25 h, followed by recovery culture for a further 48 h. At the end of incubation, cell viability was detected by the MTT end-point, and the inhibition rate was compared in relation to the incubation time, DDP concentration, and the time × concentration product (area under the curve in vitro: AUC vitro). In both of the cell lines, the IC50 and IC90 values decreased as the exposure time increased, going a linear curve with a slope of almost — 1, and showing a typical log-log AUC vitro-dependent curve. These results indicate that the antitumor activity of DDP is dependent on its AUC vitro, suggesting the clinical usefulness of this drug when administered daily in small divided doses. © 1995 Wiley-Liss, Inc.     

Approach for drainage of descending necrotizing mediastinitis on the basis of the extending progression from deep neck infection to mediastinitis

BACKGROUND: Although epidemiologic studies of the general population have demonstrated a deficit of blood group O among patients with deep venous thrombosis (DVT), few studies have evaluated the importance of blood group in high-risk patients. The purpose of this study was to evaluate the importance of ABO blood group as a thrombotic risk factor in injured patients. METHODS: Injured patients with a discharge diagnosis of DVT were identified from an institutional trauma registry and compared with control patients matched for age and Injury Severity Score. ABO blood types of patients and controls were obtained from the regional blood center database. RESULTS: Three hundred forty-three case-control pairs were identified from a total of 401 consecutive cases of DVT. Blunt injury was the predominant mechanism of injury, accounting for 90.4% of cases. Chest (p = 0.01) and extremity (p < 0.001) Abbreviated Injury Scale scores were independent predictors of DVT. However, there was no significant difference in blood group distribution or the A to O ratio between patients with and without DVT. For non-type O patients, the odds ratio for developing DVT was 1.1 (95% confidence interval, 0.8-1.5; p = 0.5) in comparison with type O patients. CONCLUSION: These data do not support a clinically relevant association between blood type and DVT in trauma patients. Injury-associated derangements of coagulation may be more important than any hypercoagulability related to blood type in this population.