Aversive taste stimuli increase CGRP levels in the gustatory insular cortex of the rat

Calcitonin gene-related peptide-like immunoreactivity (CGRP-IR) was surveyed immunohistochemically in the insular cortex of the rat, and the levels of insular cortical CGRP-IR were measured with the radioimmunoassay method following intraoral stimulation with various taste stimuli. CGRP-IR was localized in nerve fibers within the agranular and dysgranular insular cortices. The CGRP-IR levels in the rostral (gustatory) part of the insular cortex were increased significantly by strongly aversive taste stimuli such as quinine hydrochloride and conditioned taste stimuli (NaCl and sucrose) which animals had been taught to avoid. The results suggest that CGRP in the gustatory insular cortex is concerned with rejection or avoidance behaviors to aversive taste stimuli.     

Reduction of cell proliferative activities of gastric stump adenomatous hyperplasias after bile reflux diversion in rats

Previously we reported the majority of lesions induced by bilereflux, in the absence of chemical carcinogens, in the rat remnantstomach to consist primarily of gastric type and secondarilyof intestinal type cells, and that they are reversible afterdiversion of bile reflux. The present study was designed toevaluate changes in proliferative activities in cells of eachtype under these conditions. The frequency of adenomatous hyperplasia(AH) induced in the gastric stump mucosa by duodenal contentreflux after Billroth II partial gastrectomy (BII) increaseduntil the 54th week of the experiment. Roux-en-Y (RY) surgicalprocedure which prevents duodenal reflux performed at the 24thor 36th week after BII led to a decrease in AH. Cell contentof the lesions was analyzed using routine H&E staining,immunohistochemical staining for pepsinogen isoenzyme 1 andhistochemical procedures for mucins (paradoxical concanavalinA, galactose oxidase Schiff and sialidase galactose oxidaseSchiff reactions) and proliferation in each compartment evaluatedby an immunohistochemical method using bromodeoxyuridine (BrdU)and a monoclonal antibody against BrdU. At the 54th week thenumber of BrdU-labeled cells per normal pyloric column was significantly(P < 0.05) increased to 10.63/pit after the BII operation,while it diminished to 5.23/pit after RY diversion, this beingthe same level as with the RY procedure alone. AH maintaineda high rate of BrdU incorporation at 12.7% after BII operation,which was also significantly reduced (P < 0.01) to 7.0% bythe RY surgery. The intestinal type cell showed highest (22.2%),the surface mucous type cell showed the next (16.5%) and thepyloric gland type cell showed lowest (5.2%) BrdU labeling indicesafter BII operation. All the cell types in AH showed similarproportional decreases in BrdU incorporation after RY diversion.Thus surgical intervention reverses the cell proliferation causedby bile reflux in the gastric stump.     

The effect on the bones of condensed phosphate when used as food additives: Its Importance in Relation to Preventive Medicine

Based on the fact that chemical products such as binding agents are produced by mixing three kinds of phosphates with different ratios, we mixed metaphosphate, polyphosphate and pyrophosphate. Each was made to Na-phosphate, K-phosphate, and Ca-phosphate and each was mixed with commercial feeds so that the content of P would be approximately 0.1, 0.15, 0.3, 0.4, 0.6 and 1.0%. The prepared pellets were given to ICR, CF # 1 and AKR strains of mice at 29 days of age for 680 days and observations were made through this experimental period at different stages. The observations were also carried out on the mice administered with the experimental feeds for 1.5 months from 9 to 10.5 months of age. The observations were compared with those of the control group at all times. As a result, plasma 1 α, 25 (OH)₂ D₃ and P levels were always significantly higher in the phosphate administered groups relative to the control. Urine P and Fe increased while urine Ca decreased in the phosphate-treated groups. The effect of phosphates on the bones was studied taking soft X-ray pictures of hind legs and applying microdensitometry to them. Through these observations we recognized thinning of the cortex of bones, reduction of marrow trabecules and development of osteophyte. Histological observations disclosed that changes in knee joint tissues were apparent; that is, a decrease in or an irregular loss of the number of cells in superficial, intermediate, and radial strata of the joint cartilage, proliferation of subchondral bone, and the development of osteophytes were noted. As for muscles, diameters of musclar fibers became smaller; in particular, type II fibers showed greater shrinkage. Regarding kidneys, swelling and atrophy of glomerular capillaries, proliferation of mesangial cells, nephroselerosis, swelling, thinning, and loss of tubular epithelium, interstitial tissue inflammation, development of cylindruria, and deposition of calcium were observed. All these changes seem to be a particularly advanced aspect of the changes which are more pronounced with increasing dose and age. These changes were found even in the group administered with the feed containing 0.1% phosphorus, and, these changes were dependent on the concentration level of P. It was observed that administration to older subjects for a short term (1.5 months) produced effects stronger than those to younger subjects administered for a long term (10.5 months). The effects of condensed Ca-phosphate on bones were similar to those of condensed Na- and K-phosphates, and, hence, it was supposed that these effects were caused by phosphate radicals. An erratum to this article is available at .     

Cytosol and serum concentration of cytokeratin subunit-19 fragment (cyfra-21-1) in breast-cancer

Cytokeratin 19 is a subunit of cytokeratin intermediate filament. CYFRA 21-1 is a new tumor marker using monoclonal antibodies which recognize a fragment of cytokeratin 19. CYFRA 21-1 was measured in cytosol of breast cancer tissues or in sera of patients with breast cancer or benign breast diseases to study the significance of this protein as a tumor marker. The cytosol concentration of CYFRA 21-1 was elevated in cancerous tissue compared to that in adjacent noncancerous tissue, and correlated with the tumor stage or the estrogen receptor status. In the serum, the mean value and positive rate for CYFRA 21-1 (assuming 2.2 ng/ml as the cut-off value) were 0.61 ng/ml (0%) in benign breast diseases, 0.98 ng/ml (6.7%) in stage I/II primary breast cancer, 75.67 ng/ml (60.0%) in stage III/IV primary breast cancer, 45.28 ng/ml (60.0%) in recurrent breast cancer, and 0.64 ng/ml (2.6%) in those with no evidence of recurrence. From the above, we concluded that CYFRA 21-1 could be a tumor marker with high specificity in breast cancer.     

Complete nucleotide sequence of mouse mammary tumor virus from jyg chinese wild mice: Absence of bacterial insertion sequences in the cloned viral gag gene

Mammary tumors of a newly isolated strain of Chinese wild mouse (JYG mouse) harbor exogenous mouse mammary tumor virus (MMTV). The complete nucleotide sequence of exogenous JYG-MMTV was determined on the proviral 5' long terminal repeat (LTR)(partial)-gag-pol-env-3' LTR (partial) fragment cloned into a plasmid vector and the cDNA sequence from JYG-MMTV producing cells. Similarly to the other MMTV species the LTR of JYG-MMTV contains an open reading frame (ORF). The amino acid sequence of the JYG-MMTV ORF resembles that of SW-MMTV (92% identity) and endogenous Mtv-7 (93% identity) especially at the C-terminal region. Thus, a functional similarity in T-cell receptor V beta recognition as a superantigen is implicated among these MMTV species. Analysis of the viral gag nucleotide sequence revealed that this gene is not disrupted by the bacterial insertion sequence IS1 or IS2, which have been reported to be present in the majority of the plasmids containing the gag region. Comparison of amino acid sequences of JYG-MMTV with those of BR6-MMTV showed that over 96% of the amino acids of gag, pol, protease and env products are identical. These results suggest the intact nature of the nucleotide sequence of the near full-length MMTV genome cloned in the plasmid.     

Inhibitory effects of adhesion oligopeptides on the invasion of squamous carcinoma cells with special reference to implication of αv integrins

We studied invasion-related adhesion events in vitro using three squamous carcinoma cell lines (HSC-3, poorly differentiated type; OSC-19, well-differentiated type; and KB cells, undifferentiated type). An in vitro invasion assay through matrigel in the transwell chamber revealed that HSC-3 cells were most invasive, OSC-19 cells moderately invasive and KB cells least invasive. Inhibition assay of invasion using synthetic peptides RGD, RGDV, RGDS, RGDT, IKVAV and YIGSR, showed that invasion of the three cell lines was significantly inhibited by RGDV. There were other peptides that inhibited invasion significantly including IKVAV for HSC-3, and RGDS and YIGSR for OSC-19. HSC-3 cells and OSC-19 cells adhered to fibronectin, laminin, vitronectin, and type IV collagen, and KB cells did not adhere to laminin but did to fibronectin, vitronectin and collagen type IV. Pretreatment of cells with RGDV peptide in the attachment assay reduced the ability of these cells to bind to vitronectin and fibronectin more efficiently than pretreatment with RGDS. Anti-v antibodies inhibited adhesion of HSC-3, OSC-19 and KB cells to vitronectin, but anti-1 antibodies did not inhibit adhesion. Immunofluorescent microscopic examinations showed that all cell lines were positive for anti-5 and anti-v antibodies, and only HSC-3 cells were positive for anti-3 antibody. 51 was not clearly demonstrated in any of the cell lines. RGDV was the most effective inhibitor of squamous cell carcinoma invasion among the synthetic oligopeptides used in this experiment, and it is suggested that it affects v3-and/or v5-mediated carcinoma cell invasion.Abbreviations BSA bovine serum albumin - MEM Eagle's minimal essential medium - MTT 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide - PBS phosphatebuffered saline - FITC fluorescein isothiocyanate This work supported in part by a grant from the Osaka Cancer Research Foundation     

Pharmacological effects of concomitant administration of β-adrenoceptor blocker and agonist in normal subjects: characterization by heart rate response to exercise

The effects of a combination regimen of metoprolol and ₁-adrenoceptor agonist denopamine on resting and exercise heart rate have been studied in 10 normal volunteers. Maximal ramp upright bicycle exercise was performed three times at 1-week intervals. Two hours before each exercise test, 5 mg metoprolol plus 20 mg denopamine, 5 mg metoprolol plus a denopamine placebo, or two placebos were orally administered in a double-blind fashion.During exercise after placebo administration, heart rate increased in parallel with the exercise intensity. Compared to the placebo values, resting heart rate was significantly decreased by an average of 10 beats · min^–1 by 5 mg metoprolol, whereas it was not altered by the combination regimen. During exercise, however, both the combination regimen and metoprolol alone showed a significant negative chronotropic effect, decreasing peak exercise heart rate by an average of 14 and 21 beats · min^–1, respectively. Peak oxygen uptake was also significantly decreased by both regimens.We conclude that concomitant administration of 5 mg metoprolol and 20 mg denopamine exerts an effective -adrenoceptor blocking action during exercise but a minimal effect at rest in normal subjects. The combination regimen appears to have a favourable pharmacological profile for -adrenoceptor blocker therapy in patients with chronic heart failure.     

Poorer nutritional status of the older-generation in a Japanese farming village, as related to fewer types of food consumed

This study was carried out to determine whether the most recent nutritional improvements in Japanese farming villages were due to improvement in the diet of the young only or across all ages. Food duplicates for 24 h were collected. The number of food items and the adequacy of each nutrient level were compared between subgroups, by age of cooking and those eating meals. The older-generation used and ate fewer food items resulting in poorer nutrition. The most recent improvement in nutrition in the farming villages of Japan was found mainly to affect the younger-generation with the older-generations being more poorly nourished.     

The available period and kind of exercise for increasing osteo sono assessment index in women

PURPOSE: The purpose of this study is to determine the optimum period and kind of exercise which are more effective for increasing the calcaneus osteo sono assessment index (OSI) in adolescent women. METHODS: The subjects consisted of 600 female students aged from 19 to 21 studying at the Department of Food and Nutrition at Nakamura Gakuen University. The calcaneus OSI was measured by ultrasonic bone absorptiometry. The factors associated with an increased OSI were determined using piecewise linear regression analyses. RESULTS: Experience in performing impact-loading exercise either in junior high school or high school was found to be a significant predictive factor for increased calcaneus OSI after adjusting for age and weight. Regarding other exercise-related factors such as subjective intensity, frequency, hours at a time, and total duration of exercise, a piecewise liner regression analysis showed that a total duration of over 7 yr and a high subjective intensity of the impact-loading exercise during high school and junior high school periods caused a significant increase in the calcaneus OSI. However, the OSI decreased when the subjective intensity of the impact-loading exercise during the high school period was reported to be "very strenuous." CONCLUSIONS: Impact-loading exercise in junior high school and high school is important for increasing calcaneus OSI; however, impact-loading exercise in high school with a "very strenuous" subjective intensity was also found to possibly decrease the calcaneus OSI.     

Childhood multiple sclerosis and allied demyelinative diseases

We report five cases of multiple sclerosis (MS) and three cases of allied demyelinative diseases starting during childhood. Three of the MS patients presented with atypical initial symptoms, such as acute encephalitis or myelitis, making an early clinical diagnosis difficult. Ophthalmologic symptoms were noted in four of MS children, and in two with allied demyelinative diseases. Therefore, if a child shows ophthalmologic symptoms (i.e. optic neuritis, ophthalmoplegia), brain magnetic resonance imaging (MRI) should be conducted for the differential diagnosis of MS and other demyelinative diseases. Cerebrospinal fluid analysis is not useful for the initial diagnosis of MS, because pleocytosis and increase of oligoclonal IgG band in cerebrospinal fluid are seen in both MS and other demyelinative disorders. However, neuron specific enolase (NSE) is slightly higher in the latter than in the former. T2-weighted MRI of multiple sclerosis showed multiple high intensity areas in the white matter of the cerebrum and cerebellum, capsula interna, and crus cerebri etc. Most of these lesions were clinically silent, being characteristic of MS. In two MS cases, however, initial MRI revealed no abnormal findings. Thus, the diagnosis of MS can not be made by initial MRI only.