Chronic toxicity of thiram in rats

The results of a chronic 2-years experiment of thiram on Wistar-rats are given. On the basis of clinical, biochemical and pathomorphological investigations a Noel of 5 mg/kg bw were proposed.     

Immunoenzymatic visualization of tetrodotoxin (TTX) in Cephalothrix species (Nemertea: Anopla: Palaeonemertea: Cephalotrichidae) and Planocera reticulata (Platyhelminthes: Turbellaria: Polycladida: Planoceridae).

Tetrodotoxin (TTX) was localized as brown color in different tissues of an undescribed species of the nemertean genus Cephalothrix (phylum Nemertea) and a turbellarian Planocera reticulata (phylum Platyhelminthes) on light microscopy by means of a monoclonal anti-TTX antibody. In the Cephalothrix sp., TTX was recognized in the vesicles apically arranged in the bacillary cells in the epidermis, basal lamina, the granular cells in the proboscis epithelium, rhynchocoel epithelium, and the vesicles in the basal portion of the intestinal wall near the blood vessels and rhynchocoel. The excretory system and the ovum also showed positive reaction of TTX antigen-antibody. On the other hand, the hermaphrodite flatworm P. reticulata exhibited TTX antigen-antibody complex only in their ovum. To our knowledge, this is the first experimental effort on micro-distribution of TTX in invertebrates.     

What determines the life satisfaction of the elderly? Comparative study of residential care home and community in Japan

Background:   Increasing lifespan has forced elderly persons and researchers alike to look at life and aging in a new way: at adding life to years rather than years to life. With increasing lifestyle choices for the elderly, the present study was undertaken to determine and compare the factors associated with life satisfaction in elderly living in a residential care home and in the community in Japan.
Methods:   This was a cross-sectional, self-reported, questionnaire-based study. Elderly persons from the residential care home in Kyoto City ( n  = 261, mean age ± SD = 79.6 ± 6.6 years, male : female = 1 : 3.1) and from the town of Urausu, Hokkaido ( n  = 733, mean age ± SD = 74.8 ± 6.8 years, male : female = 1 : 1.3), participated in the study. This represented 95.3% and 89.5% of all eligible elderly ≥ 65 years in the home and town, respectively. Activities of daily living, higher functions, medical and social history, geriatric depression scale and quality of life were studied. Using multiple logistic regression models, factors associated with high satisfaction of life were identified.
Results:   In community-dwelling elderly, relationship with friends, as opposed to relationship with family for elderly in residential care home, were factors related to life satisfaction.
Conclusions:   This study demonstrates the relative importance of social factors versus medical and functional factors as determinants of life of elderly. We have also shown how these factors differ for elderly living in different environments. Understanding these different as well as common determinants of life satisfaction from a whole array of diverse ones allows us to make effective strategy to improve the quality of life of elderly living in different conditions.     

Distribution of two types of infiltrating helper T cells among rat renal allografts, spleen, peripheral blood, and regional lymph node cells.

Cytokine production by graft-infiltrating cells (GIC) of helper T cell (Th) subtypes were investigated in rat kidney allograft compared to those infiltrating the spleen, those in peripheral blood, and in regional lymph nodes. The relative proportion of OX-22 positive cells (Th type 1) and the W3/25-positive cells (Th) of GIC was 49.4 +/- 2.1% on day 3 and 52.7 +/- 2.2% on day 6, whereas those in spleen cells was 80.3 +/- 4.1% (p less than 0.05) and 95.5 +/- 2.5% (p less than 0.01), respectively. GIC produced more B cell-stimulating factor 2 (BSF-2, 106.3 +/- 8.2 U/ml) when compared to spleen cells (15.9 +/- 4.6 U/ml; p less than 0.01), peripheral blood mononuclear cells (4.2 +/- 1.0 U/ml; p less than 0.01) or lymph node cells (24.9 +/- 4.0 U/ml; p less than 0.01) upon stimulation with donor BN lymphocytes in vitro. However, GIC produced less interleukin 2 (IL-2, less than 1.0 U/ml) and IL-3 (less than 1.0 U/ml) than produced by spleen cells (5.1 +/- 0.9 U/ml, p less than 0.05, and 10.5 +/- 2.3 U/ml, p less than 0.01, respectively) or lymph node cells (4.5 +/- 0.4 U/ml, p less than 0.01; 23.5 +/- 3.1 U/ml, p less than 0.01, respectively). These results demonstrate that the subtype of Th cells which produce BSF-2 migrates selectively to allografts.     

A Case of Early Gastric Cancer Manifesting as a Submucosal Tumor

Abstract: Gastric cancer manifesting as a submucosal tumor (SMT) is not common. A gastric barium meal and endoscopic studies performed on a 49-year-old male with epigastric pain, revealed an elevated lesion with bridging folds and central depression on the posterior wall of the lower body. An endoscopic ultrasonography (EUS) revealed a hypoechoic mass lesion within the submucosal layer. Due to an increase in the size of the tumor and its central depression during the subsequent year and a half, the patient was admitted for closer examination. Endoscopic biopsy material from the deeper layer, obtained by mucosal resection, revealed a poorly differentiated adenocarcinoma. Microscopic examination of the resected stomach showed a poorly differentiated adenocarcinoma within the submucosal layer, with considerable lymphocyte infiltration. Immunohistological examination disclosed marked T cell infiltration adjacent to the cancer cells. We suggest that considerable lymphocyte infiltration, particularly T cells, may have some role in the protective reaction against cancer cells. Our case was diagnosed as being cancer 18 months after the first endoscopic study. The biopsy material taken from the depression at the time of the first examination showed benign findings and a EUS revealed typical SMT. In the case of SMT shown by EUS to be a hypoechoic mass lesion in the submucosal layer, it is recommended that biopsy material be obtained from the deeper layer using methods available such as artificial ulcer formation.     

Role of UGT1A1 mutation in fasting hyperbilirubinemia

BACKGROUND AND AIM: Low-grade fasting hyperbilirubinemia is a common observation in healthy subjects (HS), whereas high-grade fasting hyperbilirubinemia is believed to be a characteristic finding of Gilbert's syndrome. This study was undertaken to assess the role of mutation in bilirubin UDP- glycosyltransferase gene (UGT1A1) on fasting hyperbilirubinemia. METHODS: Analysis of UGT1A1 and a caloric restriction test (400 kcal for 24 h) were performed in 56 healthy subjects (25 males, 31 females), and 28 patients with Gilbert's syndrome (18 males, 10 females). There were 29 healthy subjects with no mutation in UGT1A1, and 27 healthy subjects and 26 Gilbert's syndrome patients with mutations in the coding and/or promoter (TATA box) regions of UGT1A1. RESULTS: The mean increment of serum bilirubin (DeltaSB) was 7.6 micromol/L [corrected] (males) and 4.1 micromol/L (females) in subjects with no UGT1A1 mutation. Subjects with mutation in UGT1A1 showed higher levels of DeltaSB than individuals without mutation. Among healthy subjects, gender difference in DeltaSB values was observed only in individuals with the wild type of UGT1A1, but not in those with mutations in this gene. CONCLUSION: The results of the present study suggest that UGT1A1 mutation has a role in the development of high-grade fasting hyperbilirubinemia after caloric restriction.     

Follow-up for patients with obstructive sleep apnea syndrome using a portable recording device

A home screening device, LT-200, can record data on both breathing conditions and body positions during sleep for up to 3 consecutive days in patients with obstructive sleep apnea (OSAS). We investigated the usefulness of the LT-200 device for follow-up of OSAS. Eighteen patients (age 51.0 +/- 10.8 years, mean +/- SD) were enrolled in this study. Standard polysomnography (PSG) was performed on all patients. The number of apnea/hypopnea episodes per hour (apnea/hypopnea index: AHI), the total time that nocturnal oxygen saturation was < 90% (oxygen desaturation time: ODT), and the minimum oxygen saturation during sleep (lowest Spo2) were calculated. We used the LT-200 and PSG to evaluate any improvement in the data obtained after auto-continuous positive airway pressure (auto-CPAP) therapy. AHI was also measured using the LT-200 in three sleep positions to evaluate the efficacy of the lateral position. AHI, ODT, and lowest Spo2 values did not differ significantly between the PSG and LT-200 recordings on the control and therapy nights. The LT-200 recordings showed that AHI, ODT, and lowest Spo2 tended to be better on the second night of auto-CPAP therapy than on the first. AHI was significantly lower in the right and left lateral sleep positions than that in the supine position. Our findings suggest that since the LT-200 device provides important information about the severity of OSAS, the efficacy of auto-CPAP therapy, and body position under unattended conditions in the home. It may prove to be a useful tool for following up patients.     

Downregulation of extracellular matrix-related gene clusters during osteogenic differentiation of human bone marrow- and adipose tissue-derived stromal cells

Bone marrow- and adipose tissue-derived stromal cells (BMSCs and ASCs, respectively) exhibit a similar capacity for osteogenic differentiation in vitro, but it is unclear whether they share a common differentiation process, because they originate from different tissues. The aim of this study was to explore BMSC and ASC osteogenic differentiation by focusing on the expression of extracellular matrix-related genes (ECMGs), which play a crucial role in osteogenesis and bone tissue regeneration in vivo. We characterized the gene expression profiles of BMSCs and ASCs using a custom complementary deoxyribonucleic acid microarray containing 55 ECMGs. Undifferentiated BMSCs and ASCs actively expressed a wide range of ECMGs. Once BMSCs and ASCs were placed in an osteogenic differentiation medium, 24 and 17 ECMGs, respectively, underwent considerable downregulation over the course of the culture period. The remaining genes were maintained at a similar expression level to corresponding uninduced cell cultures. Although the suppression phenomenon was consistent irrespective of stromal cell origin, collagen (COL)2A1, COL6A1, COL9A1, parathyroid hormone receptor, integrin (INT)-beta3, and TenascinX genes were only downregulated in osteogenic BMSCs, whereas COL1A2, COL3A1, COL4A1, COL5A2, COL15A1, osteopontin, osteonectin, and INT-beta1 genes were only downregulated in osteogenic ASCs. During this time period, cell viability was sustained, suggesting that the observed downregulation did not occur by selection and elimination of unfit cells from the whole cell population. These data suggest that osteogenically differentiating BMSCs and ASCs transition away from a diverse gene expression pattern, reflecting their multipotency toward a configuration specifically meeting the requirements of the target lineage. This change may serve to normalize gene expression in mixed populations of stem cells derived from different tissues.     

Vitamin K2-induced cell growth inhibition via autophagy formation in cholangiocellular carcinoma cell lines

Vitamin K2 (MK4) has antitumor effects on various types of cancer cell lines in vitro, and its efficacy has also been reported in clinical applications for patients with leukemia, myelodysplastic syndrome, and hepatocellular carcinoma (HCC). However, details of the mechanism of the antitumor effects of MK4 remain unclear. In the present study, we examined the antitumor effects of MK4 on cholangiocellular carcinoma (CCC) cell lines and its mechanism of action using the HL-60 leukemia cell line that exerts MK4-induced cell growth inhibition via apoptosis induction and cell cycle arrest as a control. MK4 exerted dose-dependent antitumor effects on all three types of CCC cell lines. However, apoptosis occurred in a smaller percentage of cells and there was less cell cycle arrest compared with other cancer cell lines studied previously, which suggested slight MK4-induced cell growth inhibition via apoptosis induction and cell cycle arrest. On the contrary, histopathological fidings showed a large number of cells containing vacuoles in their cytoplasm, and electron microscopic findings showed a large number of cytoplasmic autophagosomes and autolysosomes. These findings suggested evidence of autophagy-related cell death. Fluorescence microscopy following acridine orange staining revealed an increase in the number of cytoplasmic acidic vesicular organelles characteristic of autophagy. Moreover, there were few cells forming autophagic vesicles in the control group, while the percentage of cells containing vacuoles in the MK4-treated group increased with the duration of culture. These results suggested that, unlike in leukemia, gastric cancer, HCC, and other cancer cells, the antitumor effects of MK4 on CCC cells are induced via autophagy formation.