Different corticostriatal projections from two parts of the cortical masticatory area in the rabbit

The cortical masticatory area (CMA) elicits rhythmic jaw movements in response to repetitive stimulation and is involved in the control of mastication. Based on jaw movement patterns, the CMA is divided into two parts. One is the part of the CMA in which a T-pattern similar to jaw movements during food transport in natural mastication is evoked by electrical stimulation. The other is more dorsomedially located, and during chewing a C-pattern similar to jaw movements can be induced. However, it is still not known which region of the putamen receives projections from the CMA and whether projections originate from both parts of the CMA. In this study, electrophysiological and histological experiments were undertaken in rabbits to investigate projections from the CMA to the putamen. Both experiments showed that the ventral region of the putamen received projections from the CMA. The density of the projections from the CMA area inducing the T-pattern seemed to be higher than that from the area inducing the C-pattern. Furthermore, the peak latency of the evoked potentials from stimulation of the CMA area inducing the T-pattern was shorter than that from stimulation of the area inducing the C-pattern. The data obtained from the present study indicate the functional role of the ventral region of the putamen in the regulation of mastication, and further suggest that the corticostriatal pathway is involved in the transition between behavioral jaw movement patterns.     

Diversity of Hepatitis G Virus within a Single Infected Individual

The extent of population diversity among GB virus C (GBV-C)/hepatitis G virus (HGV) within a persistently infected individual (Iw) was investigated by sequence analysis of multiple clones generated from polymerase chain reaction (PCR)-amplified products of cDNA analogous to fragments of 5 non-coding region (5NC), envelope region 1/2 (E1/E2) and non-structural region 3 (NS3) of viral genome. Although nucleotide substitutions were more common in coding regions than in the 5NC region, there was no region corresponding to the hypervariable region of hepatitis C virus in the E1/E2 region. Transition substitution exceeded transversion by 7 to 12-fold, and 79.4% of substitutions were synonymous. This bias against substitutions producing amino acid replacements and the use of Pfu DNA polymerase with an error rate 10 times lower than the observed frequency of substitution, suggests that most substitutions were not artefactual. This data suggests that individual genomes of HGV within an infected individual may differ from each other at 0.23–0.84% nucleotide position and at 0.42–0.61% amino acid position.     

Intravesical chemotherapy with 4′-epi-Adriamycin in patients with superficial bladder tumors

Summary We evaluated the effects of 4-epi-Adriamycin (EPI), a derivative of Adriamycin (ADR), in intravesical instillation chemotherapy. The patients received two courses of three daily instillations of 50–80 mg EPI dissolved in 30 ml physiological saline on 3 consecutive days, with an interval of 4 days between courses. Full evaluation was possible in 33 of 35 patients with superficial bladder tumors treated with EPI. Complete response was observed in 4 cases and partial response in 14 cases, giving a response rate of 55%. Side effects such as pollakiuria and pain on micturition occurred in 9 cases. EPI appears to be an effective agent for intravesical instillation chemotherapy in patients with superficial bladder tumors.     

Habitual Dietary Intake Affects the Altered Pattern of Gut Microbiome by Acarbose in Patients with Type 2 Diabetes

The aim of this research was to reveal the characteristics of gut microbiome altered by acarbose intervention in Japanese patients with type 2 diabetes (T2D) and its possible association with habitual dietary intake. Eighteen patients with T2D were administered acarbose for four weeks. The abundances of two major phyla, namely Actinobacteria and Bacteroidetes, were reciprocally changed accompanied by the acarbose intervention. There were also significant changes in the abundances of ten genera, including the greater abundance of Bifidobacterium, Eubacterium, and Lactobacillus and the lower abundance of Bacteroides in the group after the intervention than that before the intervention. Hierarchical clustering of habitual dietary intake was performed based on the pattern of changes in the gut microbiota and were classified into distinct three clusters. Cluster I consisted of sucrose, cluster II mainly included fat intake, and cluster III mainly included carbohydrate intake. Moreover, the amount of change in Faecalibacterium was positively correlated with the intake of rice, but negatively correlated with the intake of bread. The intake of potato was negatively correlated with the amount of change in Akkermansia and Subdoligranulum. Acarbose altered the composition of gut microbiome in Japanese patients with T2D, which might be linked to the habitual dietary intake.     

A cost-minimization analysis of measures against metallic dental restorations for head and neck radiotherapy

The aim of this study was to compare the estimated public medical care cost of measures to address metallic dental restorations (MDRs) for head and neck radiotherapy using high-energy mega-voltage X-rays. This was considered a first step to clarify which MDR measure was more cost-effective. We estimated the medical care cost of radiotherapy for two representative MDR measures: (i) with MDR removal or (ii) without MDR removal (non-MDR removal) using magnetic resonance imaging and a spacer. A total of 5520 patients received head and neck radiation therapy in 2018. The mean number of MDRs per person was 4.1 dental crowns and 1.3 dental bridges. The mean cost per person was estimated to be 121 720 yen for MDR removal and 54 940 yen for non-MDR removal. Therefore, the difference in total public medical care cost between MDR removal and non-MDR removal was estimated to be 303 268 800 yen. Our results suggested that non-MDR removal would be more cost-effective than MDR removal for head and neck radiotherapy. In the future, a national survey and cost-effectiveness analysis via a multicenter study are necessary; these investigations should include various outcomes such as the rate of local control, status of oral mucositis, frequency of hospital visits and efforts of the medical professionals.     

Cdc7 kinase is required for postnatal brain development

The evolutionally conserved Cdc7 kinase plays crucial roles in initiation of DNA replication as well as in other chromosomal events. To examine the roles of Cdc7 in brain development, we have generated mice carrying Cdc7 knockout in neural stem cells by using Nestin-Cre. The Cdc7^Fl/Fl Nestin^Cre mice were born, but exhibited severe growth retardation and impaired postnatal brain development. These mice exhibited motor dysfunction within 9 days after birth and did not survive for more than 19 days. The cerebral cortical layer formation was impaired, although the cortical cell numbers were not altered in the mutant. In the cerebellum undergoing hypoplasia, granule cells (CGC) decreased in number in Cdc7^{Fl/F l}Nestin^Cre mice compared to the control at E15-18, suggesting that Cdc7 is required for DNA replication and cell proliferation of CGC at mid embryonic stage (before embryonic day 15). On the other hand, the Purkinje cell numbers were not altered but its layer formation was impaired in the mutant. These results indicate differential roles of Cdc7 in DNA replication/cell proliferation in brain. Furthermore, the defects of layer formation suggest a possibility that Cdc7 may play an additional role in cell migration during neural development.     

Therapeutic effect of a CDDP-epirubicin-Lipiodol emulsion on advanced hepatocellular carcinoma

Prior injection of an anticancer agent and Lipiodol mixture is a key point for the treatment of hepatocellular carcinoma (HCC). We therefore prepared a new, improved emulsion of Lipiodol containing a high dose ofcis-diamminedichloroplatinum (CDDP) and epirubicin by replacing the ionic contrast medium (Urografin 67) with a nonionic contrast medium (Iopamidol; Iopamiron 300) and adding phosphatidyl choline. This CDDP-epirubicin-Lipiodol emulsion (CELE) was examined pharmacologically and chemically with the following results. The size of these particles is less than 10 m (diameter) for up to 24 h; the release of 28%–34% of the CDDP and 80%–90% of the epirubicin was estimated in the dissolution test, and 85% of the CDDP and 35% of the epirubicin was retained in the organs in the moment calculation. CELE was injected into 58 HCC patients via a celiac angiographic catheter. In 36 of these patients, the CELE injection was followed by transcatheter arterial embolization (TAE) therapy. Following the administration of CELE as one-shot injection therapy for stage IV HCC, the 1-year survival rate was 59% and the 2-year survival rate was 27%. Moreover, in patients (stage II, 12; stage III, 8; stage IV, 16) who received CELE and subsequently underwent TAE therapy, the 1-year survival rate was 90% and the 2-year survival rate was 67%. The nonionic contrast medium with Lipiodol forms finer emulsified particles, and these particles are more capable of penetrating into the tumor. In addition, the greater pharmacological stability of these particles provides a slow-release effect and prolonged stability of their shape. Finally, theoretically, the use of two major anticancer agents such as CDDP and epirubicin showed a greater clinical effect in the treatment of HCC than either our earlier suspension or a single anticancer agent.Work presented at the Third International Symposium on Treatment of Liver Cancer, Seoul, Korea, 12–13 February 1993     

A study on how a 6-month aerobic exercise program can modify coronary risk factors depending on their severity in middle-aged sedentary women

It is well known that physical exercise can reduce coronary risk factors. But how an aerobic exercise modifies coronary risk factors in relation to severity and physical fitness is still controversial. Fifty-four middle-aged women (mean age, 55 years) completed a 6-month on-site and home-based anaerobic threshold-level exercise program. The changes in coronary risk factor profiles were observed during the pre-intervention and intervention periods. Before the intervention (during control period), most coronary risk factors showed a rather unfavorable trend. After the program, their mean body weight decreased from 56.7 to 55.7 kg (p>0.05) and the proportion of body fat from 30.9 to 27.9% (p>0.05) without any reduction in lean body mass. Systolic blood pressure (SBP) decreased from 129.0 to 125.0 mm Hg (p>0.05) and diastolic blood pressure from 79.5 to 76.6 mm Hg (p>0.05). Fasting plasma glucose (FPG) declined from 109.6 to 103.4 mg/dl (p>0.05). Changes in SBP and FPG were most remarkable in their respective worst tertile. Serum lipids improved only modestly. Maximum oxygen uptake increased from 23.6 to 26.1 ml/kg/min (p>0.01). However, no significant correlations were found between changes in coronary risk factors and those in physical fitness. We conclude that the 6-month aerobic exercise program would modify women’s coronary risk factors depending on their initial values, probably independently of the changes in physical fitness.