Locomotor and oculomotor impairment associated with cerebellar dysgenesis in Zic3-deficient (Bent tail) mutant mice

We examined the adult neural phenotypes of the Bent tail mutant mouse. The Bent tail mutant mouse was recently shown to lack a submicroscopic part of the X chromosome containing the Zic3 gene, which encodes a zinc-finger protein controlling vertebrate neural development. While nearly one-fourth of hemizygous Bent tail (Bn/Y, Zic3-deficient) mice developed neural tube defects in their midbrain and hindbrain region, the other Bn/Y mice showed apparently normal behaviour in a C57BL/6 genetic background. A battery of behavioural and eye movement tests revealed impaired spontaneous locomotor activity, reduction of muscle tone and impairments of vestibuloocular and optokinetic eye movements in these mice. Morphological examination of the mutant brain showed a significant reduction in the cell numbers in the cerebellar anterior lobe and paraflocculus-flocculus complex. Our results indicate that the cerebellar dysgenesis characterized by subregional hypoplasia affects the locomotor activity, muscle tone and eye movement control of the mice. These findings may have some clinical implications in relation to disorders characterized by cerebellar dysgenesis, such as Joubert syndrome.     

An earlier component of face perception detected by seeing-as-face task

To investigate the time sequence of the neural processes underlying face perception, magnetoencephalography was performed using a seeing-as-face task, in which visual inputs were identical across two conditions, but subject perceptions differed: one being a non-specific pattern of geographical shapes, the other being a percept of a face. Subtraction between the two conditions revealed a response occurring 120 ms after stimulus onset in right occipital, approximately 50 ms earlier than previously reported response at a latency of 170 ms at the right fusiform gyrus. As our novel task completely excluded differences in low-level properties of visual stimuli between control and face conditions, these two responses were considered specific to face perception. The result supported the two-stage theory of face processing.     

Development of an implantable undulation type ventricular assist device for control of organ circulation

It is well known that a rotary blood pump (RP) is effective as a small ventricular assist device (VAD). It might be still more effective if pulsation was available. The undulation pump (UP), which is a type of small RP, can also produce pulsation. In Japan, a development project for an implantable type UP ventricular assist device (UPVAD) is now advanced. Six universities and some companies together have been in charge of the development project for 5 years. In this study, the influence which the UP under development has on circulation in internal organs was investigated. Goats with the same weight as an average Asian person were used for the experiment. The left chest cavity was opened after resection of the fourth rib and the heart was approached. A cannula was inserted in the left ventricle from the apex. An outflow cannula was inserted into the left descending aorta. Heart muscle was excised using a newly developed puncher. The UPVAD was implanted using a left-heart bypass system. The myocardial blood flow, carotid arterial blood flow, and the kidney blood flow were recorded together with an electrocardiogram, blood pressure, and the flow rate. In these animal experiments, the blood circulation dynamic state was stabilized and sufficient support of the left heart was observed. Myocardial blood flow, carotid arterial flow, and a kidney blood flow increase resulting from UPVAD support was observed. Often the problem of multiple organ failure is important at the time of clinical application of a ventricular assist device. Assisting circulation to internal organs is important for prevention of multiple organ failure. It was concluded that the UPVAD might be useful for prevention of multiple organ failure.     

Histochemical properties of vascular and sinusoidal endothelial cells in liver diseases

Liver biopsy specimens with or without liver diseases were examined immunohistochemically to determine the distribution of endothelial cell markers, factor VIII-related antigen (FVIII-RAg), Ulex europaeus agglutinin I (UEA-I) lectin and PAL-E. We also investigated the localization of laminin, a component of the basement membrane. In normal livers, FVIII-RAg, UEA-I and laminin were negative in sinusoidal endothelial cells, but positive in blood vascular endothelia of the portal area. The antigen detected by PAL-E was distributed in venous endothelial cells. PAL-E did not label endothelial cells of the artery. In the lobule, immunoreactivity with PAL-E was weakly detected only in some sinusoids of the periportal area. In chronic active hepatitis and liver cirrhosis, FVIII-RAg and UEA-I stained endothelial cells of neovasculatures in the enlarged portal areas of the fibrous septum surrounding pseudolobules. Some sinusoidal endothelial cells in cirrhotic livers were reactive to UEA-I and FVIII-RAg, whereas PAL-E-positive cells were found rarely in the pseudolobules. In carcinomatous sinusoidal endothelial cells, FVIII-RAg, UEA-I and PAL-E were strongly stained. Laminin underlay these carcinomatous sinusoids. These suggest capillarization of sinusoids in hepatocellular carcinoma. The histochemical approach using endothelial cell markers could be a practical tool in the diagnosis of hepatocellular carcinoma.     

Interleukin-4 gene polymorphism is not involved in the risk of recurrent pregnancy loss

PROBLEM: Enhanced secretion of type-2 T-helper (Th2) cytokine is a characteristic feature in normal physiological pregnancy. A study has demonstrated defective production of interleukine-4 (IL-4) and other Th2 cytokine in women with recurrent pregnancy loss (RPL). Several studies have suggested that IL-4 variable number of tandem repeat (VNTR) gene polymorphism is probably associated with different IL-4 production. METHODS OF STUDY: The IL-4 VNTR genotypes were assessed in 109 Japanese women with RPL and 210 ethnically matched women experiencing at least one live birth and no spontaneous abortion. RESULTS: No significant differences in IL-4 VNTR genotype frequencies were found between the RPL and the control [B1B1 genotype (reference); B1/B2 and B2/B2 genotypes, odds ratio, 0.91; 95% confidence interval, 0.58-1.45]. CONCLUSION: The present study suggests that the IL-4 VNTR allele is not a major genetic regulator in RPL.     

Combined chemotherapy with weekly Paclitaxel and doxifluridine for advanced and recurrent gastric cancers

We conducted combined therapy of weekly paclitaxel and doxifluridine (5'-DFUR) for 23 cases of advanced and recurrent gastric carcinomas to investigate their efficacy and safety. Subjects included 7 unresectable cases, 5 noncurative resection cases, and 11 recurrent cases. Twenty of the 23 subjects had a history of prior treatment with another anticancer drug. The treatment regime consisted of one course comprising 70 mg/m(2)of paclitaxel weekly for three consecutive weeks followed by one week rest, combined with 800 mg/day of 5'-DFUR orally. Results revealed a response rate of 17.6% (3/17), with 2 cases of CR, 1 case of PR, 10 cases of NC, and 4 cases of PD. One of the CR cases was an unresectable case involving a primary tumor, liver metastasis, and abdominal lymph node metastasis, while the other was a recurrent case involving abdominal lymph node metastasis. The median survival period was 387 days. The one-and two-year survival rates were 52% and 24%, respectively. In terms of adverse effects, there were only single cases of grade 3 leukopenia and grade 3 neutropenia, with no cases of grade 4 hemotoxicity. Both patients could be treated as outpatients. Combination therapy of weekly paclitaxel and 5'-DFUR can be an effective and safe therapy for advanced and recurrent gastric carcinomas.     

Efficacy of postoperative adjuvant therapy for resected non-small cell lung cancer--an evidence-based review

Efficacy of postoperative adjuvant therapy for non-small cell lung cancer (NSCLC) was examined based on recent evidence. In 2003, when a clinical guideline for lung cancer had been published, the efficacy of postoperative adjuvant therapy had not been established. However, results of randomized controlled studies and metaanalysis on the efficacy of postoperative chemotherapy, platinum-based chemotherapy or UFT, were presented at the annual meetings of the American Society of Clinical Oncology (ASCO) held in 2003-2005. Thus, postoperative adjuvant chemotherapy for completely resected NSCLC cases is now a standard care of therapy.     

Serum carcinoembryonic antigen as a predictive marker for sensitivity to gefitinib in advanced non-small cell lung cancer

Gefitinib is an inhibitor of epidermal growth factor receptor tyrosine kinase, which has a tumour reducing effect in non-small cell lung cancer (NSCLC). In this study, we retrospectively reviewed the clinical data from 105 patients with advanced NSCLC treated with gefitinib at our department between May 2002 and April 2004. The overall response rate was 27.8% and the median survival time was 9.3 months. Pretreatment characteristics suggested that those with no history of smoking or an elevated serum carcinoembryonic antigen (CEA) level were more likely to be sensitive to gefitinib (P = 0.009). A multivariate analysis indicated good PS (P < 0.0001) and elevated serum CEA level (P = 0.0027) to be independent prognostic factors. These data show that the serum CEA level can be a predictive factor for the efficacy of gefitinib treatment while it is also a prognostic factor for advanced NSCLC patients undergoing this treatment.