Long-term potentiation in the optic tectum of rainbow trout

We examined synaptic plasticity in the optic tectum of rainbow trout by extracellular recordings. We found that the field-excitatory postsynaptic potential in the retinotectal synapses was potentiated by repetitive stimuli of 1.0 Hz for 20 s to the retinotectal afferents. The long-term potentiation (LTP) developed slowly, and was maintained for at least 2 h. Applications of an antagonist for N-methyl-D-aspartic acid (NMDA) receptors or Mg²⁺-free saline showed that activation of NMDA receptors was required to form the LTP beyond the induction period. The present findings indicate that presynaptic stimulation in the retinotectal synapses causes LTP mediated by NMDA receptors in the optic tectum of rainbow trout.     

Angiogenic endothelium-specific nestin expression is enhanced by the first intron of the nestin gene

Nestin is a member of intermediate filaments abundantly expressed in neural stem cells and glioblastomas. The nestin gene has four exons and three introns, and neural cell-specific expression is regulated by the second intron. We previously reported that nestin was invariably detected in the tumor endothelium in gliomas even though tumor cells were negative for nestin. In the present study, we further confirmed nestin immunostaining in tumor endothelium of a variety of common cancers, including lung, stomach, colon, and cervical carcinomas. We examined an endothelium-specific regulator using human umbilical vein endothelial cells (HUVECs) and human glioblastoma-derived U251 cells. In a luciferase reporter assay, the first intron plus 5' upstream promoter (5'UP) gave the highest activity, followed by 5'UP, and the second intron plus 5'UP. However, the assay values were much lower by HUVEC extracts than by U251 cell extracts. Although green fluorescent protein expression was positive over all U251 cells under either the first intron, second intron, or ubiquitously active CAG promoter, the fluorescence in HUVECs was limited to a few cells even under the first intron. This difference came from the growth feature of HUVECs which exhibit growth arrest by contact inhibition. We found that the nestin expression was specific to proliferative endothelium, by using proliferation markers in hemangioblastomas and in situ hybridization. Using an endothelial tube formation assay, tyrosine kinase domain-deleted VEGF receptor KDR effectively abolished the tube formation under the first intron. We suggest that the nestin expression in tumor endothelium is enhanced by the first intron.     

Depletion of mitochondrial DNA in HIV-1-infected patients and its amelioration by antiretroviral therapy

Mitochondrial DNA (mtDNA) of peripheral blood mononuclear cells (PBMCs) collected from Human immunodeficiency virus 1 (HIV-1)-infected patients and healthy controls were measured longitudinally using real-time polymerase chain reaction to evaluate the effects of antiretroviral agents on mtDNA synthesis in vivo and to assess the value of monitoring mtDNA in PBMCs to predict adverse events amongst these patients. MtDNA levels in PBMCs were significantly decreased in treatment-naive HIV-1-infected patients compared with healthy people. MtDNA levels were not only significantly correlated with CD4(+) T-cell count, but also inversely correlated with HIV-1 viral load. MtDNA levels in untreated patients and healthy controls were stable during the period of observation. On the other hand, amongst patients treated with regimens containing AZT/3TC or d4T/3TC, mtDNA increased during treatment and recovered to levels comparable to healthy controls. In contrast, mtDNA decreased immediately after the initiation of an AZT/ddC-containing regimen. We did not find a correlation between mtDNA levels and changes in clinical parameters. There was no significant difference in mtDNA levels between patients with and those without lipoatrophy. Furthermore, there was no obvious difference in mtDNA levels amongst those patients exhibiting signs and symptoms of peripheral neuropathy. In conclusion, the decrease in mtDNA levels in PBMCs amongst HIV-1-infected patients and its amelioration by antiretroviral therapy may suggest the influence of direct effects on mitochondria or mtDNA by HIV-1 infection. Further investigations are needed to elucidate the mechanisms contributing to decreased mtDNA and the value of mtDNA measurement in the care of HIV-1-infected individuals.     

Direct evidence for preferential multiplication ofBabesia gibsoni in young erythrocytes

To clarify the effect of the age of host erythrocytes on the multiplication ofBabesia parasites,B. gibsoni was cultured together with reticulocytes, immature erythrocytes, or mature erythrocytes from dogs. Parasitemia reached peak levels (34.1%±15.8%) at cultivation day 8 in immature-erythrocyte culture, whereas the highest parasitemia attained in mature-cell culture was only 3.6%±2.2% at day 5. These results clearly demonstrate thatB. gibsoni parasites preferentially invade and multiply in young erythrocytes rather than in mature cells.     

Effect of CYP2D6 genotypes on the metabolism of haloperidol in a Japanese psychiatric population.

We investigated the effect of CYP2D6 genotypes on plasma levels of haloperidol (HAL) and reduced haloperidol (RHAL) in 88 Japanese schizophrenic inpatients being treated with HAL. Some subjects carrying CYP2D6*5 allele (CYP2D6*1/CYP2D6*5, CYP2D6*5/CYP2D6*10) showed extremely high concentrations of both HAL and RHAL, and the groups with CYP2D6*5 allele seemed to have higher plasma concentrations of HAL (1.14+/-0.69 ng/ml/mg) and RHAL (1.10+/-1.05 ng/ml/mg) than the other groups. Among those without CYP2D6*5 allele, there were no significant differences in plasma concentrations of HAL and RHAL between those without CYP2D6*10 allele (HAL=0.68+/-0.31 ng/ml/mg, RHAL=0.28+/-0.37 ng/ml/mg), those with one CYP2D6*10 (HAL=0.70+/-0.23 ng/ml/mg, RHAL=0.31+/-0.16 ng/ml/mg) and those with two CYP2D6*10 alleles (HAL=0.69+/-0.14 ng/ml/mg, RHAL=0.40+/-0.09 ng/ml/mg), although there was a tendency of higher plasma concentration of RHAL in those with two CYP2D6*10 alleles. At a lower daily dosage of HAL (<10 mg/day), the subjects with two or one CYP2D6*10 allele(s) showed significantly higher plasma concentrations of RHAL (0.43+/-0.23 ng/ml/mg, 0.34+/-0.16 ng/ml/mg) than those without CYP2D6*10 allele (0.18+/-0.16 ng/ml/mg). The results of this study indicate that CYP2D6*10 allele plays significant but modest role in HAL metabolism in Japanese; nevertheless, we should not lump CYP2D6*10 allele with CYP2D6*5 allele because these two mutated alleles seem to have different impacts in the metabolism of HAL.     

Successful pregnancy after coronary artery bypass grafting for Kawasaki disease

Abstract A 13-year-old girl with a history of Kawasaki disease underwent coronary artery bypass grafting because of angina pectoris due to a giant coronary artery aneurysm on the left main trunk artery. Nine years after the operation, the patient had an uneventful pregnancy followed by a normal vaginal delivery. This is the first case of a successful pregnancy after coronary artery bypass grafting for Kawasaki coronary artery disease.     

Radioresponse of Thymomas Verified with Histologic Response

Patterns of radiologic response of 10 thymomas treated by preoperative radiotherapy (RT) (18-20 Gy/2 weeks) were determined in conjunction with histologic response. Changes in tumor volume were evaluated with CT scans obtained 5 to 36 days before and 14 to 24 days after the initiation of RT and before surgery. The extent of tumor volume reduction (TR) varied widely (40-78%), while the mean daily volume decrement expressed as a percentage of the pre-RT tumor volume correlated significantly with the pre-RT tumor volume. Histologically, the tumors, all of which were resected 17 to 33 days after RT initiation, generally consisted of predominant fibrous tissues, rare necrotic foci, and few epithelial cells. The TR did not correlate with pre-RT tumor volume, observation period, histologic subtype, or quantity of remaining epithelial cells. The TR of thymomas does not predict RT impact on tumor cells but does reflect the quantity of inherent tumor stroma.     

Mortality among persons with a history of Kawasaki disease in Japan: Can paediatricians safely discontinue follow-up of children with a history of the disease but without cardiac sequelae?

Aim: To clarify the question of whether patients with Kawasaki disease suffer a higher mortality rate after the incidence of the disease in comparison with age-matched healthy individuals. Methods: Between July 1982 and December 1992, 52 collaborating hospitals collected data on all patients having a new, definite diagnosis of Kawasaki disease. Patients were followed up until 31 December 2001 or their death. The expected number of deaths was calculated from Japanese vital statistics data and compared with the observed number. Results: Of 6576 patients enrolled, 29 (20 males and 9 females) died. The standardized mortality ratio (SMR: the observed number of deaths divided by the expected number of deaths based on the vital statistics in Japan) was 1.15 (95% CI: 0.77-1.66). In spite of the high SMRs during the acute phase, the mortality rate was not high after the acute phase for the entire group of patients. Although the SMR after the acute phase was 0.75 for those without cardiac sequelae, six males (but none of the females) with cardiac sequelae died during this period; and the SMR for the male group with cardiac sequelae was 1.95 (95% CI: 0.71-4.25). The mortality from congenital anomalies of the circulatory system was elevated, but no increase in cancer deaths was observed.

Conclusion: Although it was not statistically significant, the mortality rate among males with cardiac sequelae due to Kawasaki disease appeared to be higher than in the general population. On the other hand, the mortality rates for females with the sequelae and both males and females without sequelae were not elevated.