Behavioral treatment for chronic insomnia]

The efficacy of non-pharmacological intervention for chronic insomnia has been proven by several meta-analytic reviews, an NIH report, an American Academy of Sleep Medicine review, and numerous clinical trials. Behavior therapy for chronic insomnia consists of relaxation, stimulus control, sleep restriction, cognitive restructuring and sleep hygiene education, which has produced reliable and durable changes in total sleep time, sleep onset latency, number and duration of awakening. These studies also showed that the post-treatment effect of behavior therapy is equal to that of hypnotic therapy, and that these effects were maintained for 6 months on follow-up assessment. Elderly insomniac patients would gain considerable benefit from behavioral treatments because there are no adverse physical effects as there are from pharmacological therapy. The authors present the basic theory, techniques of behavior therapy for insomnia, and the results of two important key meta-analytic reviews. Any behavioral approach such as convenient education, self-care enhancement by bibliotherapy, and individual face-to-face counseling, seem to be fruitful not only for American but also Japanese insomnia patients. Nonetheless, there are no currently actual intervention studies using behavior therapy in Japan. We have discussed the methodology of intervention study and published a behavioral self-help manual for people with sleep problems. Development of a behavioral approach to chronic insomnia seemed to be very beneficial and a useful contribution to mental health services.     

Big mitogen-activated protein kinase 1 (BMK1)/extracellular signal regulated kinase 5 (ERK5) is involved in platelet-derived growth factor (PDGF)-induced vascular smooth muscle cell migration

Big mitogen-activated protein kinase 1 (BMK1), also known as extracellular signal-regulated kinase 5 (ERK5), is a newly identified member of the mitogen-activated protein (MAP) kinase family. Recently, several studies have suggested that BMK1 plays an important role in the pathogenesis of cardiovascular disease. To clarify the pathophysiological significance of BMK1 in the process of vascular remodeling, we explored the molecular mechanisms of BMK1 activation in vascular smooth muscle cells (VSMCs). From the results of co-immunoprecipitation and immunoblotting analyses, it was found that platelet-derived growth factor (PDGF), a known potent mitogen, activated BMK1 and triggered the Gab1-SHP-2 interaction in rat aortic smooth muscle cells (RASMCs). The abrogation of SHP-2 phosphatase activity by transfection of the SHP-2-C/S mutant suppressed PDGF-stimulated BMK1 activation. Infection with an adenoviral vector expressing dominant-negative MEK5alpha, which can suppress PDGF-stimulated BMK1 activation to the control level, inhibited PDGF-induced RASMC migration. Moreover, we observed an increase of BMK1 activation in injured mouse femoral arteries. From these findings, it is suggested that BMK1 activation leads to VSMC migration induced by PDGF via Gab1-SHP-2 interaction, and that BMK1-mediated VSMC migration may play a role in the pathogenesis of vascular remodeling.     

Histochemical studies on hyaluronic acid in the developing human retina

Changes in the distribution of hyaluronic acid in the developing human retina were investigated histochemically with alcian blue staining and theStreptomyces hyaluronidase digestion method using 56 human embryos and fetuses ranging from 5 to 41 weeks of gestational age. Hyaluronic acid was first detected in the inner layer of the retina at 12 weeks. The site of accumulation extended towards the outer layer by 20 weeks. At the neonatal stage, longitudinal fibers, possibly the processes of Müller cells, were proved to contain hyaluronic acid. These findings suggest that Müller cells produce hyaluronic acid transiently from 12 weeks’ gestation to the neonatal stage.     

A case of idiopathic bronchiolitis obliterans accompanied with pneumothorax and pulmonary atypical mycobacteriosis]

A 22-year-old man was urgently admitted for pneumothorax. He continued complaining of exertional dyspnea and dry cough after the pneumothorax healed. About three months later, an atypical pulmonary mycobacteriosis by mycobacterium kansasii was identified. Exertional dyspnea increased after chemotherapy was administered, and the patient was readmitted because of difficulty in daily life activities. Chest radiographs and CT scans showed bilateral pulmonary hyperinflation and a narrowed heart shadow. There was also marked combined ventilatory impairment, as identified by a respiratory function test. Furthermore, the histological findings of surgically removed lung tissue revealed accumulation of lymphocytes in the wall of a small bronchus. Idiopathic bronchiolitis obliterans was diagnosed from the clinical course and clinical findings. The patient is now being monitored and is awaiting lung transplantation.     

Adhesion molecules and transplantation.

OBJECTIVE: Accessory adhesion molecules are thought to influence the first interaction between host leukocytes and graft vascular endothelial cells. Their role in transplantation is reviewed. SUMMARY: Adhesion molecules have been divided into three major families: the selectins, the integrins, and the immunoglobulin superfamily. Selectins are small proteins that mediate the first contact between stimulated endothelial cells and leukocytes. Integrins interact with cytoskeletal components of cells, presumably coordinating extracellular stimuli with cytoskeleton dependent actions, such as motility, shape change, and phagocytic responses. Members of the immunoglobulin superfamily are structurally homologous, although they do not necessarily share similar functions. They are involved in T-cell proliferation and intracellular events. METHODS: Various groups of investigators have studied the influence and expression of adhesion molecules following transplantation. The authors of this article have reviewed and summarized the available literature. RESULTS: Many different adhesion molecules are up-regulated during the rejection event. Treatment of transplant recipients with monoclonal antibodies against accessory molecules, such as leukocyte function associated antigen 1 (LFA-1) and intercellular adhesion molecule 1 (ICAM-1), has resulted in either a prolongation of transplant survival or the induction of tolerance in some models. Other interventions are under study. CONCLUSION: By mediating the initial leukocyte/endothelial cell interactions, adhesion molecules may play an important role in graft rejection, mediation of infiltration into the graft, and dissemination of the antigenic message to the lymphoid tissues of the host. Future studies will have to deal not only with conceptualizing their function and mechanisms of action, but also with manipulating their interrelationships to the benefit of the graft recipient.