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Gastric mucosal blood flow and oxygen tension in the corporal mucosa gradually declined after water immersion in the control animals. Neither cimetidine nor prostaglandin E2 had any influence on the decrease of the corporal mucosal blood flow or mucosal oxygen tension during seven hours of stress loading. The stress ulceration began to occur starting three hours after cold immersion in the control rats, and the deficit of energy metabolism was attributed to reduced oxidative phosphorylation from tissue hypoxia resulting from lowered blood flow and oxygen tension under stress. Cimetidine (4 mg/kg) maintained aerobic glycolysis, continued to produce high-energy phosphates and kept the energy charge unchanged in the gastric mucosa. In addition, PG E2-Me (100 micrograms/kg) showed similar, but less marked and shorter-lived effects on aerobic glycolysis and ATP production, whereas the energy charge of the adenosine pool decreased significantly from that produced by cimetidine. These results indicated that cimetidine significantly reduced energy requirements as compared with the control and PG E2 groups due to marked inhibition of gastric secretion and produced inhibition of mucosal ulceration by water immersion. On the other hand, increased energy requirements due to the rise of cytoprotective mucoprotein production and a resultant decrease of the energy charge were seen with PG E2 as compared with cimetidine.

Population dynamics of Japanese monkeys (Macaca fuscata) have been studied at Mt. Ryozen, central Japan, between 1969 and 1980. The troop had been artificially fed until August 1973 and, since then, has been living in its natural habitat without artificial feeding. Increase in body weight, primiparous age, age-specific natality, survivorship and mortality, population and biomass growth rate, and age of disappearance of young males were compared between the two study periods, with and without artificial feeding. Comparison of population parameters in each study period was also done between social classes, central and peripheral. As shown, in table VII, it was revealed that artificial feeding was an important factor in population growth and, furthermore, that this effect was mainly on the kin-groups of the central class of the troop. In the natural habitat without artificial feeding most of the population parameters showed almost the same figure for kin-groups of central and peripheral classes.

Bacteriophage T7 0.3 mRNA synthesised and processed in vitro has been purified starting from the DNA of T7+ as well as from that of two initiation mutants of T7 (CR17 with a U----C transition in the initiation codon and CR35b whose potential Shine and Dalgarno (S-D) interaction is interrupted by a G----A transition). These mRNAs were used as templates to direct the binding of fMet-tRNA and the synthesis of 0.3 protein in both E. coli and wheat germ cell-free systems. The initiation codon mutant displayed approximately 50% inhibition of fMet-tRNA binding and 0.3 protein synthesis in both systems. The S-D sequence mutant, on the other hand, was found to be less affected than the initiation triplet mutant (20%-40% inhibition) in both fMet-tRNA binding and template activity in the E. coli system. In the wheat germ system, which does not make use of the S-D interaction, however, this mutant displayed normal template activity suggesting that the inhibition obtained in the E. coli system, albeit slight, is due to the impairment of the S-D interaction and not to an alteration of the mRNA secondary or tertiary structure caused by the base substitution.

Serum secretory IgA was measured to elucidate the significance of secretory IgA in patients with IgA nephropathy. The levels of serum secretory IgA and IgA were, respectively, 6.8 +/- 3.5 micrograms/ml and 231.0 +/- 69.2 mg/dl in the controls and 11.8 +/- 3.2 micrograms/ml and 385.3 +/- 78.7 mg/dl in the patients. The levels of serum secretory IgA and IgA in the patients were significantly higher than those in controls (p less than 0.01). Elevated serum secretory IgA may reflect the excessive state of the IgA-secreting system in IgA nephropathy patients.

We had reported the fundamental study on the utility of a new cephem antibiotic, cefmetazole (CMZ). On the basis of the results we administered CMZ to patients to investigate its clinical utility in this study. 1. CMZ was administered to 53 patients including 4 infants. They consisted of 30 cases of acute tonsillitis, 10 of peritonsillar abscess, 10 of laryngitis or pharyngitis, and 3 of sinusitis. 2. One of 2 g CMZ was administered to an adult patient except for l case and 0.5 g to an infant patient once or twice daily for at least 3 days. The method of administration was one shot intravenous injection, intravenous drip infusion or intramuscular injection. 3. The strict criteria for evaluating the efficacy of a drug were made and used for judging the efficacy of CMZ. 4. CMZ was clinically effective in 100% of patients with acute tonsillitis, 100% of those with peritonsillar abscess, 90% of those with laryngitis or pharyngitis, and 67% of those with sinusitis. 5. Bacteriologically, a single sort of bacterium was isolated in most cases of acute tonsillitis, laryngitis and pharyngitis and in the half of cases of peritonsillar abscess. Two and more sorts of bacteria were isolated in the other cases. The main bacteria isolated were beta-Streptococcus, S. pneumoniae and H. influenzae. Anaerobic bacteria, mostly Peptococcus spp. and Peptostreptococcus spp., were detected in peritonsillar abscess. 6. The clinical results agreed with the clinicobacteriological results. All the bacteria detected before treatment of CMZ disappeared. CMZ also acted effectively in cases in which H. influenzae was suspected to be a causative organism. 7. The present results of CMZ treatment were similar to those of cefazolin (CEZ) treatment published so far. 8. Thus, CMZ was confirmed fundamentally and clinically to be a very useful drug for infection of the upper respiratory tract.

In order to elucidate the mechanism of left ventricular eccentric hypertrophy in conditions of volume overload, Tl-201 myocardial scintigraphy was performed patients with aortic valve regurgitation and mitral valve regurgitation. There was a good relationship between the severity of Tl-defects, as determined by Tl-201 myocardial scintigraphy, and the changes in the T wave on the ECG on the one hand and the NYHA functional classification of heart diseases. In 17 of 18 patients where LVDd increased with increasing severity of Tl-defects and the defects were moderate to severe, LVDd was 65 mm or larger. There was a significant negative correlation between the washout rate for the whole circumference of the left ventricle, as determined by exercise Tl-201 SPECT, and LVDd (r = -0.603, p less than 0.01). The phenomenon of redistribution as determined by exercise Tl-201 myocardial scintigraphy was observed relatively early. Our results suggest that mechanical volume overload and ischemic changes are involved in left ventricular wall damage in left ventricular eccentric hypertrophy. For patients with moderate to severe Tl-defects valve replacement is indicated, no matter whether they may have heart failure or arrhythmia.

Water intoxication occurs almost exclusively in many patients with chronic psychiatric disorder. To elucidate the mechanism of this syndrome, we undertook the following animal experiments and clinical study. Twelve rabbits were given neuroleptics for eight weeks. From measurement of arginine vasopressin (AVP) secretion response to osmotic stimuli (fluid deprivation, partaking ad lib. and water loading), we found that chronic neuroleptic administration might raise the sensitivity of AVP escretion response. Then we investigated the manners of AVP secretion during ad lib. drinking in seventeen schizophrenic patients with hyponatremia and sixteen schizophrenic patients without hyponatremia. Normal range of plasma AVP was obtained from healthy volunteers by water loading. Only in both schizophrenic groups was plasma AVP detected below 270 mOsm/kg osmolality. We observed that sensitivity of AVP secretion response to osmolality was decreased in schizophrenic patients, regardless of the presence of hyponatremia. We hypothesize that the primary low sensitivity of AVP secretion response to osmo-receptor and the secondary renal hypersensitivity of AVP receptor may play the major role in the occurrence of water intoxication, linked to SIADH, in schizophrenic patients.

We investigated insulin secretion and inositol phosphate formation in intact and permeabilized rat pancreatic islets, the objective being to elucidate mechanisms of activation of phospholipase-C in pancreatic islets. The intact islets prelabeled with myo-[3H]inositol were incubated in Krebs-Ringer bicarbonate buffer containing 10 mM LiCl and 1 mM myoinositol. Glucose, alpha-ketoisocaproate (KIC), and sulfated cholecystokinin (CCK8S) increased insulin secretion and formation of [3H]inositol phosphate, [3H]inositol bisphosphate, and [3H] inositol trisphosphate. Mannoheptulose, a glucokinase inhibitor, inhibited glucose-induced insulin secretion and [3H]inositol phosphate formation; however, it did not inhibit KIC- and CCK8S-induced secretion and formation. Both glucose- and KIC-induced insulin secretion and [3H]inositol phosphate formation were blocked by 2,4-dinitrophenol, an uncoupler of oxidative phosphorylation in the mitochondria. The islets prelabeled with myo-[3H]inositol were permeabilized by digitonin and then incubated in intracellular mimicking medium containing 1 microM Ca2+ and 2.5 mM ATP. Glucose had no effect on [3H]inositol phosphate formation in the permeabilized islets, and CCK8S increased the formation of [3H]inositol phosphates. Thus, phospholipase-C in pancreatic islets is activated not only via ligand-receptor interaction in the plasma membrane in the case of hormone stimulation, but also by metabolic product(s) in the case of fuel stimulation.

Recently colposcopy has come to be increasing used in the diagnosis of the early cervical cancer. We studied colposcopic findings (epithelial, vascular and glandular findings) of dysplasia, carcinoma in situ and microinvasive cancer of the uterine cervix. The results were as follows. We could classify the cases without white epithelium into microinvasive cancer and carcinoma in situ according to elevation or hollowness and roughness and the cases with I grade white epithelium (thin white epithelium) into severe dysplasia and mild or moderate dysplasia according to the existence of elevation, roughness, II type vessels and elevation of gland opening. Among the cases with II grade white epithelium (thick white epithelium) those without roughness, II type vessels and increased gland opening were mild or moderate dysplasia and most case with III or IV type vessels were microinvasive cancer. We concluded that more than half of the cases without III or IV type vessels spread to transverse pollution of white epithelium and lack or indefiniteness of gland opening, severe dysplasia with 0 finding, carcinoma in situ with 1 or 2 finding and microinvasive cancer with 3 findings. With these criteria, we were able to obtain high (93.4% with mean) correct diagnostic ratios.

Islet amyloid polypeptide has 37 amino acids and is a major component of amyloid deposition in pancreatic islets of patients with type 2 diabetes mellitus. To determine whether the peptide is involved in the impaired insulin secretion in this type of diabetes mellitus, we synthesized islet amyloid polypeptide and its fragments and examined its effect on insulin secretion. Islet amyloid polypeptide inhibited the glucose-stimulated insulin secretion from isolated rat pancreatic islets, as calcitonin gene-related peptide did, but the fragments failed to inhibit the secretion. Thus, we propose that amyloid deposition may be an important factor in the impairment of insulin secretion in type 2 diabetes mellitus.