Mechanisms of inhibitory noradrenergic transmission in the rabbit facial vein

In isolated buccal segment of the rabbit facial vein, electrical responses produced by perivascular nerve stimulation and exogenously applied noradrenaline (NA) were recorded from the smooth muscle cells using microelectrode. Perivascular nerve stimulation hyperpolarized the smooth muscle cell membrane. The hyperpolarization was converted to depolarization after application of the -adrenoceptor antagonist, propranolol, and the depolarization was blocked by ₂ antagonists, yohimbine. These responses elicited by nerve stimulation were blocked by tetrodotoxin or guanethidine, but not by atropine. Exogenously applied NA mimicked the responses elicited by nerve stimulation. The amplitude of the -adrenoceptor-mediated hyperpolarization was increased in low potassium solution, decreased in high potassium solution, but unaltered by low sodium or low chloride solution, i.e., the hyperpolarization may be generated by an increase in potassium conductance of the membrane. An involvement of the apamin-sensitive (Ca-dependent) potassium channel or sodium-potassium ATPase in the hyperpolarization was ruled out.     

c-fos overexpression in splenic B cells augments development of marginal zone B cells

Marginal zone (MZ)-B cells participate in very early immune responses and play a pivotal role in the first-line of defense against blood-borne Ags including bacterial LPS. Since splenic B cells from c-fos transgenic (H2-c-fos) mice are hyper-sensitive to LPS stimulation, we examined LPS-sensitivity of MZ-B cells in the spleen of H2-c-fos mice. Here, we show that proliferation of MZ-B cells from H2-c-fos mice stimulated with LPS was larger than that from control mice. Proliferation and IgM production of the H2-c-fos MZ-B cells were also larger than those of splenic follicular (FO)-B cells from the H2-c-fos mice, suggesting that c-fos overexpression augments LPS-sensitivity of MZ-B cells more than that of FO-B cells. Furthermore, the number of MZ-B cells but not that of FO-B cells in the spleen of H2-c-fos mice was two- to three-fold larger than that in control littermates. The number of transitional type II (T2)-B cells in H2-c-fos mice was also larger than that of control littermates. However, the number of transitional type I (T1)-B cells in the spleen of H2-c-fos mice was not larger than that of control mice. Moreover, this c-fos effect on differentiation of MZ-B cells was intrinsic in B cells by the competitive repopulation assay with hematopoietic stem cells of H2-c-fos and control mice. These results suggest that c-fos overexpression in B cells augments differentiation and accumulation of MZ-B cells.     

Alterations in the INK4a/ARF locus and their effects on the growth of human osteosarcoma cell lines

Two different proteins, p16(INK4a) and p14(ARF), encoded by the INK4a/ARF locus play important roles in the RB and p53 pathways, respectively. This study was performed to determine genetic and epigenetic alterations in the INK4a/ARF locus and their effects on the growth of osteosarcoma. Among six cell lines examined, both p16(INK4a) and p14(ARF) exons were homozygously deleted in two cell lines, MG63 and HOS, and both p16(INK4a) and p14(ARF) promoters were methylated in one cell line, U2OS. Wild-type mRNA and proteins for p16(INK4a) and p14(ARF) were expressed in three other cell lines, SaOS2, HuO9, and G292. Transfection studies were performed using two cell lines, U2OS and MG63. Both the RB and p53 genes were wild types in U2OS, whereas p53 but not RB was mutated in MG63. Both p16(INK4a) and p14(ARF) suppressed the growth of U2OS, whereas p16(INK4a) but not p14(ARF) suppressed the growth of MG63. p53 only did not suppress the growth of MG63 either; however, coexpression of p14(ARF) with p53 increased the fraction of the G0/G1 phase in MG63 cells. The data presented here demonstrate the importance of genetic and epigenetic alterations in the INK4a/ARF locus for the growth of osteosarcoma and thus will be useful to further understand the biologic behavior of osteosarcoma in association with the defects in the p53 and RB pathways.     

A study of comparison between the nationwide epidemiological survey in 1991 and previous surveys on behçet’s disease in Japan

The 4th nationwide epidemiological survey on Behçet disease (BD), which included all patients with BD at 1,200 hospitals selected at random from 10,081 hospitals in Japan, was carried out by the BD Research Committee of the Ministry of Health and Welfare in 1991 to examine the epidemiological features of BD in Japan by comparing with previous surveys. 3,938 patients from these hospitals were examined by the Japanese diagnostic criteria of BD (JCBD) revised in 1987 and the International criteria for classification of BD (ICBD). Among these 3,938 patients, 622 patients were only suspected of having BD or clinical signs of the disease were unknown, and most of these patients were incompatible with the ICBD. So these patients were excluded from the study of epidemiological features. The average patients age has risen 7–8 years over the last 20 years and the average age of onset in both sexes increased by about 3 years from 1972 to 1991. While a decrease in the sex ratio was seen in the complete-type and the incomplete-type BD without ocular symptoms, a sustained high sex ratio was shown in incomplete-type BD with ocular symptoms. The positive rate of HLA-B51 antigen was 54.9% (men: 56.9%, women: 52.2%) significantly higher than die 15–16% in healthy subjects but it might have been gradually decreasing. Also the clinical course of BD has become too mild for prognosis. According to diese epidemiological features of BD, the clinical manifestation of BD in Japan might have become the Western type of BD.     

Efficacy of Epinastine Hydrochloride for Antigen-Provoked Nasal Symptoms in Subjects with Orchard Grass Pollinosis

BackgroundAmong the gramineae species, orchard grass is a typical causative pollen that provokes seasonal rhinitis. The purpose of this study was to examine the protective efficacy of epinastine hydrochloride for signs and symptoms caused by repeated nasal provocation with discs containing orchard grass pollen.MethodsA single-dose, placebo-controlled, double-blind, crossover clinical study was conducted in subjects with orchard grass pollinosis. The pollen challenge was conducted with the use of provocation discs containing orchard grass pollen.ResultsEpinastine hydrochloride suppressed nasal symptoms caused by nasal provocation tests using orchard grass pollen discs. Among the nasal symptoms, the number of sneezing was significantly inhibited 30 minutes and 60 minutes after the administration of epinastine hydrochloride, as compared with placebo. There were no adverse reactions to the study drugs.ConclusionsOur results suggest that nasal provocation tests with discs containing orchard grass pollen is a useful method for evaluating the onset of action of antiallergic drugs. As compared with placebo, epinastine hydrochloride decreased early-phase sneezing and the total nasal symptom score after repeated nasal provocations with orchard grass pollen discs.     

Lessons on health promotion from Japanese early childhood development

Early childhood development (ECD) has received increasing attention in both developed and developing countries since the 1990s. In Japan, ECD facilities have pursued integrated practices of education and health care to provide appropriate services to promote children’s welfare. This ECD approach appears to embody objectives of health promotion in young children. Therefore, information about Japanese practices may help to support ECD in other countries, especially developing countries. In this context, the present study discussed the potential application of health‐related ECD practices in Japan for developing countries by reviewing an outline of Japanese ECD, along with a case study describing practices in ECD facilities in Japan. We identified four main points: (i) distinct legal grounds including a legal basis for allocating health specialists; (ii) outlines of activities based on national standards and flexible practices at the facility level; (iii) teachers’ attitudes that respect children’s initiative, and explicit and independent activities embedded in children’s daily lives that reflect the child’s developmental status; and (iv) various useful practices to enhance the effect of health‐related activities, such as cooperation with parents, lesson study and hoiku‐ (teachers) conference. As these practices are based on the Japanese context, it is essential to consider both the Japanese context and potential risks of transplanting such concepts, to enable optimum use of these lessons in other countries.     

Oncolytic Virus Therapy with HSV-1 for Hematological Malignancies

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Possible roles of 5-HT in vein graft failure due to intimal hyperplasia 5-HT, nitric oxide and vein graft

For vascular occlusive disease, an autologous vein graft is the most suitable conduit for arterial reconstruction. Intimal hyperplasia, resulting from the migration and proliferation of vascular smooth muscle cells, is a major obstacle to patency after vein grafting. The degree to which the function of nitric oxide (NO) in the vein graft is preserved has been reported to be associated with the magnitude of intimal hyperplasia. Serotonin (5-HT) is released from platelets in the vascular system and plays physiological roles in controlling the vascular tone. The subtype receptors contributing to the 5-HT-induced mechanical responses vary by vessel type (artery and vein) and among species (dogs, rabbits, rats, and so on). Recent studies have demonstrated that 5-HT induces vasoconstriction through the activation of 5-HT_2A receptors in smooth muscle cells or vasodilatation through the activation of endothelial 5-HT_1B receptors in arteries from various animals. However, the effects of 5-HT have not been clarified in grafted veins. We herein demonstrate the responses to 5-HT in un-operated veins and then autogenous vein grafts. Next, we describe the effects of chronic in vivo administration of Rho-kinase inhibitors and 5-HT_2A receptor antagonists, both of which reduce the 5-HT-induced contraction and intimal hyperplasia in vein grafts. Further studies targeting 5-HT are required to evaluate its possible benefits for autologous vein grafts with respect to vasospasm, function, and patency.     

Assessment of the viability and treatment response of bone metastases in patients with metastatic castration-resistant prostate cancer using choline PET/CT

This study aimed to evaluate the clinical use of choline-PET/CT for discriminating viable progressive osteoblastic bone metastasis from benign osteoblastic change induced by the treatment effect and evaluating the response of bone metastasis to treatment in metastatic castration-resistant prostate cancer (mCRPC) patients. Thirty patients with mCRPC underwent a total of 56 ¹¹C-choline-PET/CT scans for restaging, because 4 patients received 1 scan and 26 had 2 scans. Using 2 (pre- and post-treatment) ¹¹C-choline-PET/CT examinations per patient, treatment response was assessed according to European Organization for Research and Treatment of Cancer (EORTC) criteria in 20 situations, in which only bony metastases were observed on ¹¹C-choline-PET/CT scans. Viable bone metastases and osteoblastic change induced by the treatment effect were identified in 53 (94.6%) and 29 (51.8%) of 56 ¹¹C-choline-PET/CT scans, respectively. In 27 cases (48.2%), ¹¹C-choline-PET/CT scans could discriminate the 2 entities. The mean SUVmax of the metastatic bony lesions was 5.82 ± 3.21, 5.95 ± 3.96, 6.73 ± 5.04, and 7.91 ± 3.25 for the osteoblastic, osteolytic, mixed, and invisible types, respectively. Of the 20 situations analyzed, CMR, PMR, SMD, and PMD, as determined by the EORTC, were seen in 1, 2, 3, and 14 cases, respectively. Of the 13 patients with increasing PSA trend, all 13 showed PMD. Of the 2 patients with PSA response of <50%, both 2 showed SMD. Of the 5 patients with PSA response of ≥50%, 1 showed CMR, 2 showed PMR, 1 showed SMD, and 1 showed PMD. Choline-PET/CT is very useful to discriminate viable progressive osteoblastic bone metastasis from osteoblastic change, and assess treatment response of bone metastases in mCRPC.