Lowered effectiveness of immunotherapy for cypress pollinosis by using Japanese cedar pollen extract]

BACKGROUND: Japanese cedar and cypress pollen share a common antigen. The cedar pollen season is followed by the cypress pollen season. However, both the clinical significance and involvement of cypress pollinosis in the treatment of the cedar pollinosis have not yet been clarified. METHODS: The clinical efficacy of sublingual immunotherapy with cedar pollen extract for cedar pollinosis was evaluated during the cypress pollen dispersal season in Japan. In addition, the change in cypress pollen specific IgE antibodies of the patients with cedar pollinosis was examined before and after the pollen season. RESULTS: Sublingual immunotherapy with cedar pollen extract did not improve the clinical symptoms of the cedar pollinosis patients combined with cypress pollinosis in the cypress pollen season. The cypress pollen specific IgE antibodies were found to demonstrate significant seasonal changes. CONCLUSION: The presence of cypress pollinosis should therefore be taken into consideration when planning the optimal treatment for cedar pollinosis. Sublingual immunotherapy with cedar pollen extract may not be effective for cypress pollinosis.     

Effects of nocturnal bright light on saliva melatonin, core body temperature and sleep propensity rhythms in human subjects

Nine healthy male volunteers (mean age of 24) participated in two experimental sessions of random crossover design: a bright light (5000 lux for 5 h from 00:00 to 05:00 h) session and a dim light (10 lux for 5 h from 00:00 to 05:00 h) session. Subsequently participants entered an ultra-short sleep-wake schedule for 26 h, in which a sleep-wake cycle consisting of 10-min sleep EEG recording on a bed and 20-min resting awake on a semi-upright chair were repeated. Saliva melatonin level and core body temperature was measured throughout the experiment. Bright light significantly delayed rhythms of melatonin secretion (01:58 h), core body temperature (01:12 h) and sleep propensity (02:00 h), compared as dim light session. Significant positive correlation was found between bright light-induced phase change in core body temperature and that in sleep propensity rhythm. Light-induced melatonin suppression significantly positively correlated with the phase change in core body temperature and that in sleep propensity rhythm. Assuming that light-induced melatonin suppression represents an acute impact of light on the circadian pacemaker, our results suggest that such an impact may be directly reflected in phase changes of sleep propensity and core body temperature rhythms rather than in melatonin rhythm.     

Multi-center study of seasonal affective disorders in Japan. A preliminary report

A multi-center study on seasonal affective disorder (SAD) was conducted from the autumn of 1988 to the spring of 1989 with the cooperation of 16 facilities in Japan. Forty-six SAD patients were identified among 1104 respondents to our advertisements in mass media, or patients seen at the outpatient clinics. Essentially similar findings to other previous reports were obtained in terms of onset age of the first episode, duration of episode, high proportion of depression in first-degree relatives and atypical vegetative symptoms. However, a nearly equal sex ratio, together with a high proportion of unipolar depression, is characteristic of the present study. Increased appetite and carbohydrate craving were predominant only in female patients, whereas hypersomnia was prominent in both sexes. Effective response to light therapy was found in 17 SAD patients. However, a controlled study on a large number of patients is required to allow final conclusions on the efficacy of light therapy in Japanese SAD patients.     

Possible role of vascular endothelial cells in immune responses in colonic mucosa examined immunocytochemically in subjects with and without ulcerative colitis

Phenotypic characteristics of vascular endothelial cells of the colonic mucosa in patients with ulcerative colitis and healthy controls were studied with immunoperoxidase staining by light and electron microscopy. The cells could be classified into two groups according to their phenotypes; one was positive for von Willebrand factor and the other had an antigen detected by a monoclonal antibody, OKM5. The endothelial cells positive for von Willebrand factor were usually in relatively large blood vessels, and OKM5-positive cells were mostly located in small capillaries along the glandular epithelium. OKM5-positive endothelial cells also expressed HLA-DR and interleukin-1 (IL-1). In patients with ulcerative colitis, OKM5-positive endothelial cells and spindle-shaped cells that might be precursors of endothelial cells were more numerous in the lamina propria than in the other subjects. Thus, OKM5-positive endothelial cells may be important as antigen-presenting cells and immunoregulatory cells in the intramucosal immune system. Furthermore, colonic epithelial cells in patients with ulcerative colitis synthesized HLA-DR and IL-1, and may have a close relation to immune responses, such as antigen processing and presentation to immunocompetent cells. It was suggested that these cells have a close relation to the pathogenesis of the impaired immune responses in situ in ulcerative colitis.     

Production of anti-peptide specific antibody in mice following immunization with peptides conjugated to mannan.

In order to investigate the usefulness of polysaccharides as carriers for the induction of antibody to synthetic peptides, peptides representing residues 139-147 of the surface antigen of hepatitis B and residues 129-140 of the pre-S2 region of the protein were coupled to mannan and dextran via an aminocaproic spacer molecule. Of the two conjugates studied, only mannan was useful as a carrier for the efficient production of anti-peptide antibodies.     

Effects of small dose of brotizolam on P300

Nine healthy men (mean age, 22.2 years) participated in two experimental sessions cross-overed randomly in a double blind manner; one with a placebo and the other with 0.125 mg of brotizolam (BTZ) administered in the morning. Resting electroencephalogram and event-related potential under oddball paradigm was recorded before and 1, 2, 4, 6 and 8 h after the administration. Mean 30-msec bin amplitude from 240 msec to 450 msec after the stimulus was compared between placebo and drug sessions in order to observe P300. Brotizolam reduced the amplitude of P300 at 6 h after administration. It was noted that the effects of BTZ were most marked at Fz.     

Sleep loss and daytime sleepiness in the general adult population of Japan

Presynaptic dopamine metabolism was studied in a group of patients with schizophrenia and in an age- and gender-matched normal control group using 6-[(18)F]fluoro-L-DOPA ((18)F-DOPA) and positron emission tomography (PET). Nineteen patients, nine drug-free, 10 on neuroleptics, and 13 normal control subjects underwent PET scans using (18)F-DOPA. The neuroleptic-treated patients were taking typical neuroleptics (N=4) or the atypical neuroleptic, clozapine (N=6). The ratio of specific/non-specific activity was calculated for eight cortical and subcortical regions of interest. Medication-free patients had a significant reduction in (18)F-DOPA uptake in the ventral striatum (P=0.04) and significantly increased uptake in the posterior cingulate (P=0.02) compared with normal control subjects. The 18F-DOPA PET technique proved to be useful and sensitive in detecting changes in dopamine metabolism in patients with schizophrenia in vivo. The results of this study provide evidence of an aberrant dopamine system in schizophrenia.     

Calpain inhibitor inhibits secretory granule maturation and secretion of GH

Clathrin- and AP-1-coated buds are present on immature secretory granules of endocrine cells that mature into clathrin-uncoated granules. The mechanism of clathrin and adaptor protein uncoating has remained obscure. Benzyloxycarbonyl-L-leucyl-L-leucinal (ZLLal), a calpain inhibitor, reduced growth hormone (GH) secretion with intracellular accumulation, in a GH-secreting rat pituitary tumor cell. Pulse and chase demonstrated that ZLLal retarded the turnover of clathrin (Clt.H) and adaptins. ZLLal-treatment co-immunoprecipitated the increased amounts of GH with Clt.H and adaptins compared to control cells, suggesting the intracellular accumulation of immature secretory granules. Clt.H and adaptins were limited-proteolyzed by m-calpain in vitro, indicating that calpain may be involved partly in the maturation of secretory granules in endocrine cells via the process of clathrin uncoating.