The enhanced expression of the matrix metalloproteinase 9 in nasal NK/T-cell lymphoma

Background  

Nasal NK/T cell lymphoma is an aggressive disease and has a poor prognosis. Nasal NK/T cell lymphoma is refractory to conventional chemotherapy and has strong tendency of widespread relapse or dissemination into distant sites.     

Does operational diagnosis of schizophrenia significantly impact intellectual deficits in psychotic disorders?

Background Evidence suggests that, as a group, patients with schizophrenia have intellectual deficits that may precede the manifestation of psychotic symptoms; however, how successfully intelligence tests are able to discriminate schizophrenia from other psychotic disorders has yet to be investigated in detail. Methods Using Wechsler Adult Intelligence Scale – Revised (WAIS‐R) data for 55 inpatients with schizophrenia and 28 inpatients with non‐schizophrenic psychotic disorders (NSPD) (schizophreniform disorder, brief psychotic disorder, delusional disorder, psychotic disorder due to a general medical condition, and psychotic disorders not otherwise specified), intelligence performance was compared between schizophrenia and NSPD and among different subtypes of schizophrenia. Results There were no significant differences in intelligence quotient (IQ), verbal IQ (VIQ) and performance IQ (PIQ) discrepancy, and subtest scores of WAIS‐R between the patients with schizophrenia and those with NSPD. These diagnostic groups were not discriminated well by any WAIS‐R variables. Schizophrenia patients with prominent negative symptoms, on the other hand, had a significantly larger IQ discrepancy (VIQ > PIQ) than those without prominent negative symptoms and NSPD patients. Intelligence performance in schizophrenia did not differ with respect to diagnostic subtypes and longitudinal courses. Conclusions The current study failed to show diagnostic usefulness of WAIS‐R in discriminating schizophrenia and other psychoses. A diagnosis of schizophrenia does not significantly impact intellectual deficits in psychotic disorders.     

Haloperidol metabolism in psychiatric patients: importance of glucuronidation and carbonyl reduction.

In 39 patients who received haloperidol regularly we measured plasma concentrations of haloperidol glucuronide (HAL-GL), reduced haloperidol glucuronide (RHAL-GL), haloperidol (HAL), reduced haloperidol (RHAL), and HAL reductase activity in red blood cells. Plasma HAL-GL concentrations were significantly higher than HAL, RHAL, or RHAL-GL concentrations. Concentration ratios of total glucuronide to nonglucuronide and RHAL/HAL ratios were calculated as indices of glucuronidation and reduction capacity in each patient. The plasma glucuronidation ratios showed a significant negative correlation (r = -0.63, p less than 0.001) with the dose, while the reduction ratios showed a positive correlation (r = 0.75, p less than 0.001). No correlations were found between the HAL reductase activity in red blood cells and either the dose or RHAL/HAL. Based on these findings we suggest that glucuronidation of HAL is the major metabolic pathway of HAL in humans and its activity is important in determining steady-state plasma HAL concentrations. Glucuronidation may also be a major contributing factor in the interindividual variability of HAL metabolism.     

Glucose as regulator of glucose transport activity and glucose-transporter mRNA in hamster beta-cell line.

To investigate the role of glucose in regulating glucose transporters in pancreatic beta-cells, we studied the hamster clonal beta-cell line HIT-T15, which retains responsiveness to glucose. Northern blot analysis demonstrates that GLUT2 and GLUT1 mRNA are abundant in HIT cells. After a 24-h culture with various concentrations of glucose (0-22.2 mM [0-400 mg/dl]), the GLUT2 mRNA level in HIT cells increased by 40% at 22.2 mM (400 mg/dl) glucose compared with 11.1 mM (200 mg/dl) without a change in mRNA stability. It also decreased proportionally to the reduction of glucose concentration. Glucose deprivation resulted in a decrease of GLUT2 mRNA to an almost undetectable level, with a marked increase in the degradation rate of mRNA. In contrast, the GLUT1 mRNA was not affected by glucose. We show that glucose uptake is highest in HIT cells incubated at 2.8-5.5 mM (50-99 mg/dl) glucose for 24 h, and that levels in cells cultured at 0 mM (0 mg/dl) and 22.2 mM (400 mg/dl) glucose decrease to approximately 20% of the maximum level. This decrease is consistent with the effects of glucose on glucose-stimulated insulin secretion in HIT cells. Our results indicate that glucose is involved in regulating GLUT2 mRNA and glucose uptake activity and that the glucose responsiveness of the insulin secretion correlates with the glucose-induced change in glucose uptake activity in HIT cells.     

Human monoclonal anti-nuclear antibodies produced by human-mouse heterohybridomas

To obtain human monoclonal anticentromere antibodies, mouse myelomas were fused with unfractionated mononuclear cells from the peripheral blood of a patient diagnosed as having the CREST variant of scleroderma: with only anticentromere antibodies. After a single fusion an heterohybridoma secreting a human antibody specific for nuclear antigens, as detected by indirect immunofluorescence staining, was isolated. The monoclonal antibody secreted by the clone was of the human IgM class. Indirect immunofluorescence staining of the antibody on HEp-2 cells showed multiple nuclear dots or a discrete speckled pattern resembling that of an anticentromere antibody. Immunoblot analysis showed antibody binding to a 33 kD antigen derived from the nuclear protein fraction. Enzyme-immunoassay results clearly showed that the antibody reacted with the chromosomal protein fraction and not calf thymus DNA.     

Neonatal impact of leukemia inhibitory factor on neurobehavioral development in rats

Cytokines have been implicated in the etiology or pathology of various psychiatric diseases of developmental origin such as autism and schizophrenia. Leukemia inhibitory factor (LIF) is induced by a variety of brain insults and known to have many influences on mature and immature nervous system. Here, we assessed the neurobehavioral and pathological consequences of peripheral administration of LIF in newborn rats. Subcutaneous LIF injection induced STAT3 phosphorylation in many brain regions and increased glial fibrillary acidic protein (GFAP) immunoreactivity in the neocortex, suggesting that LIF had direct effects in the central nervous system. The LIF-treated rats displayed decreased motor activity during juvenile stages, and developed abnormal prepulse inhibition in the acoustic startle test during and after adolescence. They displayed normal learning ability in active avoidance test, however. Brain neuronal structures and startle responses were grossly normal, except for the cortical astrogliosis during neonatal LIF administration. These results indicate that LIF induction in the periphery of the infant has a significant, but discrete impact on neurobehavioral development.     

Momentary changes in the cardiovascular autonomic system during mental loading in patients with panic disorder: a new physiological index "rho(max)"

BACKGROUND: Although panic disorder (PD) is suggestive of autonomic nervous system dysfunction, especially in the cardiovascular autonomic system (CAS), the results in many previous studies are still controversial. Using a new physiological index which could well reflect emotional reaction to visual stimuli (Yoshizawa, M., Sugita, N., Tanaka, A., Abe, K., Yambe, T., Nitta, S., 2001. Quantiatative Physioligical Evaluation of Three Dimensional Images. The Seventh International Conference on Virtual Systems and Multumedia, 25-27.), we studied momentary changes in the CAS in patients with PD during audiovisual stimulation (AS) as mental loading. METHODS: During AS, exposed to a video of imaginary experiences such as driving a motor vehicle or diving into the sea, blood pressure (BP) and heart rate (HR) were measured in 12 remitted patients with PD and 19 age- and sex-matched normal controls (NC). We used the maximum cross-correlation coefficient (rho(max)) from the BP to the HR, whose frequency components were limited to around 0.1 Hz. RESULTS: The rho(max) was an available index which could detect the momentary changes in the CAS during AS in both groups. The two-way ANOVA disclosed significant group and time effects on the rho(max). The momentary response to emotional stimuli in the PD patients was slower than that in the NC subjects. LIMITATIONS: Antidepressants have a potential impact on the autonomic variables in this study. CONCLUSIONS: These findings suggest that there may be a dysfunction of the CAS in remitted PD patients and that the dysfunction may be one of the trait markers of PD. To confirm these findings, however, further studies with a large sample size are required.     

Serum cholesterol levels and panic symptoms in patients with panic disorder: a preliminary study

BACKGROUND: Although some previous research has focused on the relationship between panic disorder (PD) and a high total cholesterol (TC) level, it is still controversial. Recently, researchers have reported the heterogeneity of clinical symptoms in PD and the complexity of the correlations found among them. Therefore, the controversy on the TC level in PD may be due to the existence of clinical subgroups in PD. It is important to ascertain whether or not an elevated TC level in patients with PD is associated with specific panic symptoms. METHODS: In 104 drug-free patients with PD, we examined the relationship between TC level and each of several panic symptoms occurring at the time of panic attacks (PAs), which included anticipatory anxiety, agoraphobia, and 13 panic symptoms based on the DSM-III-R. RESULTS: Stepwise regression analysis revealed a significant effect of the presence of the symptom 'fear of dying' on TC levels. Patients with a fear of dying had a significantly higher TC level than those without it. LIMITATIONS: The relatively small sample size may limit the generalizability of our findings. DISCUSSION: These data suggest that TC level may be associated with panic symptoms in patients with PD.     

Favorable efficacy of long-term lamivudine therapy in patients with chronic hepatitis B: an 8-year follow-up study

The long-term efficacy of lamivudine therapy in patients with hepatitis B virus (HBV) infection is still not clear. In this study, 20 non-cirrhotic Japanese patients infected with HBV received lamivudine therapy for more than 1 year and were followed for a median period of 8.5 years (range, 6.7-8.7 years). The rates of HBe antigen (HbeAg) negative, HBV-DNA undetectable, and alanine aminotransferase (ALT) normal level at the start of lamivudine were 55%, 25%, and 20% and 85%, 80%, and were 80%, respectively, at the last visit, including patients who received additional treatment. The values at the last visit tended to and were significantly higher than those at the start. The values improved at the last visit regardless of the emergence of YMDD motif mutant and continuation of lamivudine. YMDD mutant and biochemical relapse with mutant virus (breakthrough hepatitis) appeared in 65% and 45% during follow-up, respectively, but severe breakthrough hepatitis occurred in only 5%. Furthermore, 80% of patients who received additional treatment for breakthrough hepatitis, regardless of continuation of lamivudine, were ALT normal level at the last visit, in contrast to 25% untreated. HBsAg clearance occurred in two patients of the discontinuous lamivudine group with non-vertical transmission, who were relatively young. One was infected with HBV genotype C with breakthrough hepatitis and the other had no YMDD mutant and was infected with genotype D, a rare type in Japan. None developed cirrhosis or hepatocellular carcinoma (HCC) during follow-up. Our results suggest that long-term lamivudine therapy improves long-term prognosis, especially when additional treatment for breakthrough hepatitis is used.     

Autosomal linkage analysis of a Japanese single multiplex schizophrenia pedigree reveals two candidate loci on chromosomes 4q and 3q.

We analyzed a large multiplex schizophrenia pedigree collected in mid-eastern Japan using 322 microsatellite markers distributed throughout the whole autosome. Under an autosomal-dominant inheritance model, the highest pairwise LOD score (LOD = 1.69) was found at 4q (D4S2431: theta = 0.0), and LOD scores at two other loci 3q (ATA34G06) and 8q (D8S1128) were 1.62 and 1.46, respectively. In multipoint analysis, LOD scores of the regions on 4q and 3q remained at a similar level; however, the LOD score of the region on 8q apparently decreased. Additional dense map analysis revealed haplotypes on 4q and 3q regions shared by affected individuals. On chromosome 4q, the haplotype spanning about 8 centiMorgans (cM) was shared by four of six genotyped individuals with schizophrenia and one affected individual whose haplotype was estimated. On 3q, the haplotype spanning about 20 cM was shared by five genotyped individuals with schizophrenia. We obtained two candidate regions of major susceptibility loci for schizophrenia on chromosomes 3q and 4q.