Inhibition of PAF-induced eosinophil accumulation in pulmonary airways of guinea pigs by anti-asthma drugs

Intraperitoneal (i.p.) injection of platelet activating factor (PAF) in guinea pigs caused a dose-related increase in the number of eosinophils recovered from bronchoalveolar lavage fluid (BALF). The prevalence of eosinophils in BALF had significantly increased within 1 hr of i.p. injection of PAF (10 micrograms/animal) and was maximal after 24 hr. Subcutaneous osmotic mini-pumps were used to administer drugs for 5 days prior to i.p. injection of PAF (10 micrograms/animal) and for the subsequent 24 hr. The percentage increase of eosinophils in BALF, due to PAF, was inhibited in animals treated with dexamethasone, aminophylline, cromoglycate, tranilast or ketotifen, but not in animals treated with oxatomide, azelastine, amlexanox, ibudilast or AA-861. These results suggest that inhibition of pulmonary eosinophilia may be a necessary property of prophylactic anti-asthma drugs and provide indirect evidence favoring a role for PAF in eosinophilia of asthma.     

Reappraisal of projection levels of the corticospinal fibers in the cat, with special reference to the fibers descending through the dorsal funiculus: a WGA-HRP study

The precise course and termination levels of the corticospinal tract (CST) in the cat were studied using the anterograde transport of wheat germ agglutinin-conjugated horseradish peroxidase (WGA-HRP). Following injection of WGA-HRP into the pericruciate (sensorimotor) cortex on one side, we observed the precise caudal termination levels of the CST fibers in the lateral and ventral funiculi. Simultaneously, the bilateral CSTs descending through the dorsal funiculus of the spinal cord were identified. Anterogradely labeled CST fibers within the lateral and ventral funiculi were observed bilaterally to reach the level of the third sacral (S3) spinal segment, which is lower than that ever described. The lowest level of the CST fibers within the dorsal funiculus, however, reached the level of the first sacral (S1) spinal segment. In conclusion, this study demonstrates that, in the cat, there exist 6 different CSTs (crossed and uncrossed lateral, ventral, dorsal) and that the termination levels of the lateral and ventral CSTs are much lower than those described in previous reports.     

Cytoplasmic loop of beta-adrenergic receptors: synaptic and intracellular localization and relation to catecholaminergic neurons in the nuclei of the solitary tracts

Pharmacological studies suggest that beta-adrenergic receptors (beta AR) in the medial nuclei of the solitary tracts (m-NTS) facilitate presynaptic release of catecholamines and also function at postsynaptic sites. We have localized the antigenic sites for a monoclonal antibody against a peptide corresponding to amino acids 226-239 of beta AR in the m-NTS of rat brain. By light microscopy, immunoperoxidase labeling for this antibody was detected in somata and proximal processes of many small cells that were distributed throughout the rostrocaudal extent of the m-NTS. Electron microscopy confirmed the cytoplasmic localization of beta AR in perikarya and proximal dendrites of neurons. Immunoreactivity occurred as discrete patches associated with cytoplasmic surfaces of plasma membrane and with irregularly-shaped saccules with clear lumen in the immediate vicinity. Select regions of nuclear envelopes, mitochondrial membranes, and rough endoplasmic reticulum were also immunoreactive along their cytoplasmic surfaces. In contrast, the Golgi apparatus was labeled, but infrequently. Immunoreactivity was also detected at numerous post- and occasional presynaptic membrane specializations of select axodendritic junctions. Dual labeling for the beta AR-antibody by the immunoperoxidase method and for a rabbit antiserum against the catecholamine-synthesizing enzyme, tyrosine hydroxylase (TH), by the immunoautoradiographic method within the same sections, further established the precise cellular relations between beta AR and catecholaminergic neurons. Immunoreactivity for beta AR was detected in numerous perikarya and proximal dendrites that did not show detectable levels of TH. However, a few cells were dually labeled for both antigens, as seen by both light and electron microscopy. The TH-labeled terminals formed synapses at junctions both with and without beta AR-like immunoreactivity. These results from the single and dual labeling studies: (1) confirm biochemical predictions that amino acids 226-239 of beta AR protein reside intracellularly; (2) provide the first ultrastructural evidence for beta AR localization within both pre- and postsynaptic membrane specializations of a subset of catecholaminergic synapses; and (3) suggest select intracellular sites that may be involved with synthesis and/or internalization and degradation of the receptor protein.     

School-refusal and social-withdrawal in the clinical setting at a psychiatric medical institution]

Fifty two outpatients, who showed signs of school-refusal-withdrawal at the Shiga Prefectural Psychiatric Institution have been analyzed according to their age, gender, ICD-10 diagnosis, medical evolution, and total number of consultations. A total of 61.5% of the population were male, and they showed a higher average and a wider range of age than female patients. According to the ICD-10 diagnosis, 67.3% were in the group of F40-48 neurotic, stress-related and somatoform disorders, and 11.5% were in the group of F30-39 mood [affective] disorders. Twenty five % of the patients were assumed to have show medical improvement, and 42.3% of the patients continued to have further consultations. This article discusses the possible role of psychiatric medical institutions in supporting cases of school-refusal and social-withdrawal.     

Case of severe ulcerative colitis successfully treated with intravenous cyclosporine without high dose corticosteroid]

A 44-year-old women developed marked myopathy one year earlier, when she was treated with intravenous prednisolone for acute severe exacerbation of ulcerative colitis. When she was admitted to our hospital for another severe exacerbation, intravenous cyclosporine A was administered as monotherapy because she could not tolerate corticosteroid. The treatment was successful and she obtained complete remission. Cyclosporine A monotherapy is considered to be a valuable alternative to proctocolectomy for severe ulcerative colitis patients who cannot tolerate corticosteroid.     

Characteristics and course of bone mineral densities among fast bone losers in a rural Japanese community: the Miyama Study

The aim of this study was to clarify and compare the temporal course of bone mineral density (BMD) between fast bone losers and normal residents in Miyama Village, a rural Japanese community. BMD was measured over a 10-year period in a cohort study in Miyama Village, Wakayama Prefecture, Japan, to provide information on rate of bone loss in the mature and elderly population. Subjects (n=400) were selected by sex and age stratum from the full list of residents born in 1910–1949, with 50 men and 50 women in each age decade. Baseline BMD of the lumbar spine and proximal femur was measured using dual energy X-ray absorptiometry in 1990, 1993, 1997 and 2000. In the cohort, 171 men and 189 women completed the follow-up survey performed in 1993. After calculating the rate of bone loss between 1990 and 1993, the greatest tertile from the distribution of bone loss was categorized as fast bone losers, with the remainder considered as normal subjects. Changes in BMD were compared between normal subjects and fast bone losers over the 10-year period. Mean rate of change for BMD at both lumbar spine and femoral neck in fast bone losers recovered to levels similar to those in normal subjects over 7 years of observation. By contrast, BMD at the lumbar spine and femoral neck decreased steeply over the 10-year period in both groups, and mean BMD for fast bone losers was significantly lower than that of normal subjects (P<0.05). These differences were apparent only at the lumbar spine in both men and women, even after adjusting for age. These results indicate that fast bone loss is a transient phenomenon rather than a fixed status, although individuals who have been categorized as fast bone losers at some stage continue to display low BMD in the lumbar spine.     

Effect of non-enzymatic glycosylation and heating on browning of human stratum corneum and nail.

The purpose of the present study was to examine the effect of non-enzymatic glycosylation and subsequent heating on the browning of the plantar stratum corneum and the finger-nail, and to elucidate the pathogenesis of the yellow skin and the yellow nail seen in diabetic subjects. We incubated stratum corneum and nail from non-diabetics in 0 (control), 10 (only nail), 20 (only nail), 100 and 250 mM glucose buffer at 37 degrees C for 5 days. These glycosylated samples were dialysed against distilled water for 96 h. Distilled water was changed every 24 h. Then samples were dried for 24 h. The extent of non-enzymatic glycosylation was measured by furosine content. Each 5 mg of sample was hydrolysed by 6 N HCl and processed for measurement of furosine by high-performance liquid chromatography. The rest of each sample was stored at 37, 42 (only nail), 47 and 52 degrees C for 14 days. Browning of the stratum corneum was assessed macroscopically, and that of the nail by spectrophotometry. Based on their spectrophotometric reflectances. Munsell's scores (H = hue score, V = lightness score, C = saturation score) and (H + C)/V were calculated for objective evaluation of browning. Incubation of the stratum corneum and nail with glucose buffer increased their non-enzymatic glycosylation (furosine) dose dependently. Macroscopically, the browning of the stratum corneum was enhanced in proportion to the glucose concentration and storage temperature. However, samples incubated in 10 and 20 mM glucose and stored at 42 degrees C did not show visible browning. Munsell's score of the nail samples treated by glycosylation and heating showed increased hue and saturation but reduced lightness. (H + C)/V values of these nail samples were significantly higher than those of the control. We could not detect any fluorescence with Wood light in the browned samples. The present in vitro study demonstrated that the browning of the stratum corneum and the nail depended on the extent of both non-enzymatic glycosylation and storage temperature. We suggested a hypothesis that the non-enzymatic glycosylation and the storage temperature of the stratum corneum and the nail might be a contributory factor in the development of yellow skin and yellow nail in diabetic patients.     

Benzodiazepine ([3H]flunitrazepam) binding in cat visual cortex: ontogenesis of normal characteristics and the effects of dark rearing

[3H]Flunitrazepam (FNZ) binding sites were characterized in homogenates of cat visual cortex during normal postnatal development and following dark rearing from birth. In parallel experiments, the distribution and density of [3H]FNZ binding sites were examined by in vitro autoradiographic or 'scrape' methods. In homogenates, Bmax measurements showed low early values, rising to a peak in receptor density at about 60 days postnatal, followed by a decline in adulthood. At all ages, gamma-aminobutyric acid (GABA) altered the Kd, but not the Bmax of [3H]FNZ binding sites. Kd values showed a general increase with age, parallelled by an increased sensitivity to GABA. Receptor autoradiography revealed that the highest density of [3H]FNZ binding sites was in layer IV of cats of all ages. Deafferentation of extrinsic inputs to the visual cortex by surgical undercutting did not alter this pattern of laminar distribution, indicating that the receptors were associated with intrinsic cortical elements rather than subcortical inputs. Dark rearing had no effect on [3H]FNZ laminar distribution in the visual cortex. The Bmax was higher at 30 days postnatal, but did not differ significantly thereafter. Modulation by GABA was concomitantly higher at 30 days, but lower than normal in dark-reared animals at ages greater than 30 days postnatal. The results are discussed in relation to the normal and abnormal development of GABA receptors in the cat visual cortex.