The present study investigated the effect of pretreatment with 2,3-dihydroxy-6-nitro-7-sulfamoyl-benzo(f)quinoxaline (NBQX), an alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor antagonist, on behavioral sensitization induced by methamphetamine (METH) and cocaine at doses that are transitional relative to the induction of an acute response of locomotion and interrupting episodes of sniffing and head movement. Male Sprague-Dawley rats were randomly assigned to four groups that received daily either 20 mg/kg NBQX + 3 mg/kg METH, 40 mg/kg NBQX + 3 mg/kg METH, vehicle + 3 mg/kg METH, or vehicle + saline daily for 10 days. In another experiment, rats of four groups received daily either 20 mg/kg NBQX + 15 mg/kg cocaine, 40 mg/kg NBQX + 15 mg/kg cocaine, vehicle + 15 mg/kg cocaine, or vehicle + saline daily for 10 days. NBQX did not attenuate activity/stereotypy induced by acute administration of either psychostimulant. Pretreatment with NBQX did not affect augmentation of activity/stereotypy scores by repeated administration of METH or cocaine. There was no significant difference in the intensity of activity/stereotypy between the NBQX + METH and vehicle + METH groups and between the NBQX + cocaine and vehicle + cocaine groups following a challenge injection with 2 mg/kg METH alone or 15 mg/kg cocaine alone, respectively, given 7 days after the last dose of repeated treatment session. Pretreatment with NBQX alone for 10 days (20 mg/kg for 5 days and 40 mg/kg for subsequent 5 days) did not affect the intensity of activity/stereotypy induced by a challenge injection with 2 mg/kg METH given 7 days after the last dose of repeated injection session. NBQX at 40 mg/kg had no apparent effect on acute METH (3 mg/kg)-induced dopamine release in the striatum. These results suggest tht AMPA receptors are unlikely to be involved in induction of behavioral sensitization that is manifested as augmented activity/stereotypy following repeated administration of METH or cocaine.

Animals↗

PubMed1998

Translocation (3;16)(q27;p11) in a patient with diffuse large B-cell lymphoma associated with the BCL-6 gene rearrangement.

A patient with B-cell lineage diffuse large-cell lymphoma carrying the t(3;16)(q27;p11) and BCL-6 rearrangement is described. Cytogenetic studies showed 46,XY,t(3;16)(q27;p11.2)[.11]/46,idem,add(18)(q21)[7]/46,XY[2]. The chromosomal translocation involving the 3q27 locus was associated with the BCL-6 gene rearrangement identified by Southern blot analysis. This case involved systemic lymph nodes, as large as 3 cm in diameter, bilaterally in neck, axilla, and inguinal regions. The patient obtained complete remission with chemotherapy.

Antigens, CD↗

PubMed1998

Peak negative myocardial velocity gradient in early diastole as a noninvasive indicator of left ventricular diastolic function: comparison with transmitral flow velocity indices.

OBJECTIVES: We sought to assess the clinical significance of peak negative myocardial velocity gradient (MVG) in early diastole as a noninvasive indicator of left ventricular (LV) diastolic function. BACKGROUND: Peak systolic MVG has been shown useful for the quantitative assessment of regional wall motion abnormalities, but limited data exist regarding the diastolic MVG as an indicator of LV diastolic function. METHODS: Peak negative MVG was obtained from M-mode tissue Doppler imaging (TDI) in 43 subjects with or without impairment of systolic and diastolic performance: 12 normal subjects, 12 patients with hypertensive heart disease (HHD) with normal systolic performance and 19 patients with dilated cardiomyopathy (DCM), and was compared with standard Doppler transmitral flow velocity indices. In a subgroup of 30 patients, effects of preload increase on these indices were assessed by performing passive leg lifting. In an additional 11 patients with congestive heart failure at the initial examination, the measurements were repeated after 26+/-16 days of volume-reducing therapy. RESULTS: Peak negative MVG was significantly depressed both in HHD (-3.9+/-1.3/s, p < 0.01 vs. normal=-7.7+/-1.5/s) and DCM (-4.4+/-1.4/s, p < 0.01 vs. normal). In contrast, transmitral flow indices failed to distinguish DCM from normal due to the pseudonormalization. Transmitral flow velocity indices were significantly altered (peak early/late diastolic filling velocity [E/A]=1.1+/-0.5 to 1.5+/-0.7, p < 0.01; E deceleration time=181+/-41 to 153+/-38 ms, p < 0.01), while peak negative MVG remained unchanged (-5.3+/-2.2 to -5.3+/-2.0/s, NS) by leg lifting. Volume-reducing therapy resulted in the apparent worsening of the transmitral flow velocity pattern toward abnormal relaxation, as opposed to peak negative MVG, which improved by the therapy (p < 0.05). CONCLUSIONS: Peak negative MVG derived from TDI may be a noninvasive indicator of LV diastolic function that is less affected by preload alterations than the transmitral flow velocity indices, and thereby could be used for the follow-up of patients with nonischemic LV dysfunction presenting congestive heart failure.

Adult↗

PubMed1998

Mycoplasma pneumoniae meningoencephalitis and cerebellitis with antiganglioside antibodies.

A male patient with acute meningoencephalitis and cerebellitis associated with Mycoplasma pneumoniae infection is described. T2-weighted MRI demonstrated a high-intensity lesion involving the deep white matter of the right cerebellar hemisphere, which was not enhanced on injection of gadolinium. Brain perfusion scintigraphy revealed hypoperfusion in the bilateral cerebellar hemisphere. Polymerase chain reaction analysis using M. pneumoniae-specific primers failed to reveal the existence of the M. pneumoniae genome in cerebrospinal fluid. Conversely, serum antibodies to gangliosides (GM1, GM2, and GT1b) were detected, suggesting a mycoplasma-related neurologic disorder mediated by an immunologic mechanism. These findings support the hypothesis that vasculopathy and demyelination caused by an immunologic mechanism play an important role in the pathogeneses of neurologic disorders associated with M. pneumoniae infection.

Autoantibodies↗

PubMed1998

The number of metastatic lymph nodes: a promising prognostic determinant for gastric carcinoma in the latest edition of the TNM classification.

BACKGROUND: The number of metastatic regional lymph nodes determines the new pN categories in the 5th edition of the TNM classification. STUDY DESIGN: Our retrospective study was conducted to compare the new method of defining lymph node status with the conventional classification, consisting of the anatomic extent of lymph node metastases, a well-established prognostic factor. The study was based on clinical data for 493 patients with gastric carcinomas who underwent potentially curative operations and had histologically confirmed nodal metastases. These patients were stratified into 1) n categories according to the Japanese Classification of Gastric Carcinoma, 2) the new pN categories, and 3) the pN categories determined by the number of metastatic perigastric nodes resected by standard D1 gastrectomy. Survival data were analyzed for each group. RESULTS: The number of metastatic nodes after D2 lymphadenectomy reflected prognosis well and was shown by multivariate analysis to be a strong independent prognostic factor. When the classification was performed limited to the metastatic perigastric nodes, stage migration was evident, but the variable remained competent as a prognostic indicator. CONCLUSIONS: The number of metastatic nodes is a promising determinant in the new international stage classification.

Adult↗

PubMed1998

Effect of steroid pretreatment on contrast media-induced potassium release.

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Adult↗

PubMed1998

Mite antigen-induced IL-4 and IL-13 production by basophils derived from atopic asthma patients.

BACKGROUND: There is increasing evidence for the role of basophils in the pathogenesis of atopic diseases such as bronchial asthma, atopic dermatitis and atopic rhinitis. Recently, it has been reported that basophils derived from healthy donors produce the immunoregulatory cytokines interleukin (IL)-4 and IL-13 after cross-linking of cell surface IgE. In addition to well-known inflammatory mediators, such as histamine and leukotriene C4. these cytokines produced by basophils are also considered to be associated with atopic diseases. OBJECTIVE: Our first objective was to determine whether or not mite-sensitive atopic asthmatic basophils produce IL-4 and IL-13 in response to mite antigens. Our second objective was to investigate the relationship between antigen-specific or nonspecific IgE in the serum and the production of these cytokines in order to determine the association of basophil-derived cytokines with the pathogenesis of atopic asthma. Our final objective was to study how production of these cytokines could be regulated by some anti-asthma drugs. METHODS: Basophils were purified from peripheral venous blood of 67 atopic asthma patients with elevated RAST for the house dust mite. Cells were stimulated with mite antigens for 6 hours and then IL-4 and IL-13 levels in the supernatants were measured by enzyme-linked immunosorbent assay (ELISA). RESULTS: Mite-sensitive asthmatic basophils produced IL-4 and IL-13 when stimulated with mite antigens. Mite-induced IL-4 production peaked at 6 hours after the stimulation. whereas IL-13 production continued up to 24 hours. The higher the concentration of mite-specific IgE but not total IgE released in the serum, the more IL-4 and IL-13 were produced by basophils in response to mite antigens. The production of these cytokines was significantly suppressed by the anti-asthma drugs theophylline (IL-4, p<0.001, n=6; IL-13, p<0.001, n=10) and dexamethasone (IL-4, p<0.001, n=15; IL-13, p<0.001, n=10). CONCLUSION: Mite-antigen-induced IL-4 and IL-13 production by basophils derived from mite-sensitive asthma patients was associated with the concentration of mite-specific IgE and may play an important role in the pathogenesis of atopic asthma. The inhibitory effect of dexamethasone and theophylline on allergic inflammation may be due to the inhibition of IL-4 and IL-13 production not only by T cells but also by basophils.

Administration, Topical↗

PubMed1998

Allopurinol hypersensitivity syndrome: hypersensitivity to oxypurinol but not allopurinol.

Allopurinol is a xanthine oxidase inhibitor widely used to control plasma uric acid levels. Episodes of hypersensitivity to the drug are not rare. A severe form of this with a generalized exanthem, fever and liver involvement has been termed the allopurinol hypersensitivity syndrome (AHS). Patch testing and lymphocyte stimulation testing (LST) are not helpful in confirming this sensitivity. Allopurinol works as a substrate of xanthine oxidase, and is rapidly oxidized into oxypurinol in vivo. Therefore, the biological half-life of oxypurinol is markedly longer than that of allopurinol. In addition, conspicuous pre-existing renal impairment has been noted in many AHS patients. Thus, it is possible that AHS is a manifestation of hypersensitivity to oxy-, not allopurinol. Here, we now report three cases of AHS in which there were significant lymphoproliferative reactions to oxypurinol but not allopurinol.

Adult↗

PubMed1998

Skin surgery in patients 90 years of age and over.

BACKGROUND: The number of aged people is increasing. It is conceivable that we will be treating considerably more aged patients with more surgical risk factors in the very near future. METHODS: During the period between 1976 and 1996, 212 patients of 80 years of age and older underwent skin surgery at the Mie University Hospital, Japan. Among them, 25 patients of 90 years of age and over were studied. RESULTS: Fourteen patients (56.0%) have undergone skin surgery in the past 5 years; 22 patients (88.0%) had skin tumors on the face and ears; squamous cell carcinoma was found in 17 patients (68.0%), while basal cell carcinoma was seen in four patients (16.0%). Despite their advanced ages, half of the patients had no medical contraindications to performing surgery. CONCLUSIONS: Careful preoperative management may allow more cutaneous surgery to be carried out in aged people.

Aged↗

PubMed1998

Cyclic AMP-elevating agents prevent oligodendroglial excitotoxicity.

Previously, we have demonstrated that cells of the oligodendroglial lineage express non-NMDA glutamate receptor genes and are damaged by kainate-induced Ca2+ influx via non-NMDA glutamate receptor channels, representing oligodendroglial excitotoxicity. We find in the present study that agents that elevate intracellular cyclic AMP prevent oligodendroglial excitotoxicity. After oligodendrocyte-like cells, differentiated from the CG-4 cell line established from rat oligodendrocyte type-2 astrocyte progenitor cells, were exposed to 2 mM kainate for 24 h, cell death was evaluated by measuring activity of lactate dehydrogenase released into the culture medium. Released lactate dehydrogenase increased about threefold when exposed to 2 mM kainate. Kainate-induced cell death was prevented by one of the following agents: adenylate cyclase activator (forskolin), cyclic AMP analogues (dibutyryl cyclic AMP and 8-bromo-cyclic AMP), and cyclic AMP phosphodiesterase inhibitors (3-isobutyl-1-methylxanthine, pentoxifylline, propentofylline, and ibudilast). Simultaneous addition of both forskolin and phosphodiesterase inhibitors prevented the kainate-induced cell death in an additive manner. A remarkable increase in Ca2+ influx (approximately 5.5-fold) also was induced by kainate. The cyclic AMP-elevating agents caused a partial suppression of the kainate-induced increase in Ca2+ influx, leading to a less prominent response of intracellular Ca2+ concentration to kainate. The suppressing effect of forskolin on the kainate-induced Ca2+ influx was partially reversed by H-89, an inhibitor of cyclic AMP-dependent protein kinase. In contrast to this, okadaic acid, an inhibitor of protein phosphatases 1 and 2A, brought about a decrease in the kainate-induced Ca2+ influx. We therefore concluded that cyclic AMP-elevating agents prevented oligodendroglial excitotoxicity by cyclic AMP-dependent protein kinase-dependent protein phosphorylation, resulting in decreased kainate-induced Ca2+ influx.

Animals↗

PubMed1998

Dhh1p, a putative RNA helicase, associates with the general transcription factors Pop2p and Ccr4p from Saccharomyces cerevisiae.

The POP2 (Caf1) protein in Saccharomyces cerevisiae affects a variety of transcriptional processes and is a component of the Ccr4p complex. We have isolated five multicopy suppressor genes of a pop2 deletion mutation: CCR4, DHH1 (a putative RNA helicase), PKC1, STM1, and MPT5 (multicopy suppressor of pop two). Overexpression of either the CCR4 or DHH1 genes effectively suppressed phenotypes associated with pop2 mutant cells; overexpression of PKC1, STM1, or MPT5 genes produced only partial suppression. Disruption of the CCR4 or DHH1 genes resulted in phenotypes similar to those observed for pop2 cells. In addition, overexpression of the DHH1 gene also suppressed the ccr4 mutation, suggesting a close relationship between the POP2, CCR4, and DHH1 genes. Two-hybrid analysis and coimmunoprecipitation experiments revealed that Pop2p and Dhh1p interact physically, and these and other data suggest that Dhh1p is also a component of the Ccr4p complex. Finally, we investigated the genetic interaction between factors associated with POP2 and the PKC1 pathway. The temperature-sensitive growth defect of dhh1 or mpt5 cells was suppressed by overexpression of PKC1, and the defect of mpk1 cells was suppressed by overexpression of MPT5. These results and phenotypic analysis of double mutants from the POP2 and PKC1 pathways suggested that the POP2 and the PKC1 pathways are independent but have some overlapping functions.

Bacterial Proteins↗