The effects of change in the concentration of Ca++ on myocardial contractility depressed by thiamylal and halothane were studied in isolated dog heart muscle. The concentration of Ca++ in the bathing medium was increased stepwise from 1.9 to 20.9 mM. An increase in Ca++ concentration resulted in an increase both in net-shortening (Δ1) and in maximum velocity of shortening at 0.4 g preload (V'max) which reached the maximum values at 11.4 mM of Ca++. A further increase in Ca++ concentration rather decreased dl and V'max. The concentration-response relation curves in the presence of thiamylal (3.3 mg%) shifted to the right almost parallel to the control curve, with the peaks at 15.2 mM of Ca++. The result indicates that the depression of myocardial contractility produced by thiamylal is counteracted competitively by Ca++. However, the curves in the presence of halothane (5.0+ 0.4 mg%) were kept lower than those of the control, with the peaks at 7.6 mM of Ca++. The result shows that the counteraction of Ca++ to the depression of myocardial contractility was limited in the presence of halothane. A similar tendency was observed in maximum force of isometric contraction (Fm). Moreover, in the presence of halothane, the administration of higher concentrations of Ca++ almost always accompanied “after-contraction”. From the result obtained and the literature concerned it was suggested that the mechanism for producing the depression of myocardial contractility might be different between thiamylal and halothane in relation to Ca++ movements at the Ca++ storage sites within the myocardium.
The changes in the electrical activity of the antrum muscle fibers of the guinea pig stomach caused by ATP and its related compounds were compared with those caused by catecholamines. The antrum preparation exhibited spontaneous electrical activity and this was suppressed or inhibited by treatment with eatecholamines (adrenaline, noradrenaline and isoprenaline). The inhibitory actions of catecholamines were observed in the presence of tetrodotoxin or alpha-blockers (phentolamine or phenoxybenzamine) while the effects were antagonized by beta-blockers (propranolol or DCI). At higher concentrations than that of catecholamines, ATP or related nucleotides also produced the inhibitory effect on the spike activity and the generation of slow waves. The inhibitory actions of ATP and related substances were still observed in the presence of alpha- or beta-adrenergic blockers. Furthermore, the inhibition was present after treatment with tetrodotoxin. From these results, it is concluded that the inhibitory action of ATP and related compounds is due to a direct action on the antrum muscle and is not mediated via alpha- or beta-adrenoceptors.
The serum levels of estradiol, progesterone, LH and FSH were determined by radio immunoassay in post-menopausal and castrated women and the data obtained at the same periods after menopause and castration were compared. The serum levels of estradiol and progesterone in post-menopausal women within 1 year after menopause were higher than those of castrated women. The result suggested that ovarian function was indeed depressed in the postmenopausal women but was still preserved for I to 2 years after menopause. In the post-menopausal women, the levels of serum LH and FSH rose gradually to reach a peak at 1 to 3 years after menopause, when the production of ovarian sex steroid hormones presumably ceased. On the contrary, the serum LH and FSH levels of castrated women began to decrease gradually 4 to 9 years after castration. It is highly suggestive from these findings that a negative feedback mechanism is elicited by ageing.
Methylated salmon sperm deoxyrinbonucleic acid (Me-ssDNA) prepared by using dimethyl sulfate was used to elicit antibodies in rabbits. The antisera obtained reacted specifically with Me-ssDNA but not with thermally denatured Me-DNA, native DNA, thermally denatured DNA or ribonucleic acids (RNAs). Antibody activity was demonstrable in both IgG and IgM fractions which were obtained by Sephadex G-200 column chromatography. A single precipitating line was formed by either of IgG and IgM fractions in the double diffusion test with Me-ssDNA.
The effect of insulin treat-ment on the exocrine pancreas of streptozotocin-diabetes rats was investigated by light and electron microscopy. In the diabetic rats treated with daily lente insulin injection for four weeks, the islets became hyperplastic and proliferative, although degenerative and atrophic islets caused by streptozotocin remained if diabetic rats were not treated with insulin. Fibrosis and degeneration of the acinar cells were not found in all the diabetic rats by light microscopic examinations. Electron microscopic examinations showed that acinar cells of the exocrine pancreas of the diabetic rats without insulin treatment were characterized by irregular dilatation and prominent lamellar arrangement of rough endoplasmic reticulum and by nuclear pyknosis. After one hour of a single injection of regular insulin, rough endoplasmic retieulum of the acinar cells of the diabetic rats was rapidly activated and many intracisternal granules appeared. When the daily injection of insulin was continued, the acinar cells became to show regular arrangment of rough endoplasmic reticulum, much less vacuolarizations and less immature zymogen granules in comparison with those of the untreated diabetic rats. Exocrine pancreas of the insulin-treated rats revealed a lot of autophagic vacuoles which were supposed to derive from lysosomes. These results suggested that insulin had a repairing effect on the damaged acinar cells in diabetic state.
A 47-year-old man had diarrhea in 1965. Four years later, malabsorption syndrome was diagnosed and the patient was found to have mild lymphocytosis. Abdominal lymphoma was suspected, but exploratory laparotomy was normal except for partial villous atrophy of small intestine and slightly enlarged mesenteric lymphnodes which were normal microscopically. In vitro lymphocyte blastformation with phytohemagglutinin was depressed markedly throughout the course and the result predicted the developement of malignancy of the lymphocytic system. Infection of Isospora betli was found thereafter, and sul-famethoxazole was quite effective for diarrhea. In August, 1974, he noticed cervical lymphadenopathy for the first time and it was diagnosed as undifferentiated type of malignant lymphoma. He died in December, 1974. In this case diarrhea was most probably caused by the intestinal infection of Isospora belli without obvious lymphoma. The symptom was swept away by peroral sulfamethoxazole. In this patient coccidiosis was presumably induced and prolonged by suppression of cellular immunity which might have already begun to progress at the onset of diarrhea.
In this study a possibility was examined that the specific antigen might inhibit antibody forming cells in order to know whether a non-T-cell-dependent mechanism of selftolerance is present or not. If an autoantigen inhibits autoantibody forming cells, this inhibition may be one of the non-T- cell -dependent mechanisms of self-tolerance. Spleen cells from mice which were immunized with sheep red blood cells (SRBC) were incubated with SRBC and after an hour incubation erythrocytes added were removed. After 4 and 8 hr incubation, the plaques against SRBC were assayed by the plaque method. 1) After 8 hr incubation, SRBC reduced the plaque count to about 60% of the control aliquot incubating spleen cells with C3H mouse red blood cells. 2) This inhibition required 1% SRBC suspension, but despite increase in its concentration to more than l% the degree of the inhibition remained constant. 3) This inhibition seemed to require neither T cells, macrophages nor the cells which display the cytotoxic activity in the antibody dependent cell-mediated cytotoxicity.
Using the data reported previously by Moriya and Kanoh, the metabolic turnover of rat lung lecithins was calculated on the basis of the new assumption that the for-mation rate (V a ) of lecithins from diacylglycerols did not equal the disappearance rate (Vb) of lecithins because of the presence of precursors other than diacyl-glycerols. The ratio of Va/Vb was almost the same in dienoic lecithin as that for total lecithins, whereas a very low ratio was found in saturated and hexaenoic species. The turnover time of lung lecithins estimated was markedly shorter than those determined in much later experimental periods after administration of labeled precursors. The reason for this discrepancy was discussed.
As to the mechanism of the action of LH-RH on rat anterior pituitary, the participation of the adenylate cyclase system in gonadotropin release has been clarified. The authors previously reported that LH-RH increased the RNA synthesis in the rat anterior pituitary. In this study, the significance of the increase of RNA synthesis by LH-RH and the relationship between the adenylate cyclase system and the RNA synthesis system were investigated and the following results were obtained. (1) LH-RH induces not only the release of LH but also its synthesis in the rat anterior pituitary, and furthermore, RNA synthesis participates in LH synthesis. (2) The effects of LH-RH on RNA synthesis appeared to be independent from the effects on the adenylate cyclase system.
A water-soluble fraction was isolated from delipidated cells of Mycobacterium bovis strain BCG by extraction with hot water. Chemical analyses revealed that the above fraction presumably consisted of a peptidoglycan containing 5-10% of nucleic acids. When it was injected into guinea pigs with Freund's incomplete adjuvant plus egg white albumin as antigen, an increase of circulating antibody was observed as shown by the augmented titers of precipitin and hemagglutinin. The results of skin test and corneal reaction indicated that the fraction mentioned above induced delayed hypersensitivity to egg white albumin. Footpad reaction in mice demonstrated that the above fraction induced delayed hypersensitivity to sheep red blood cells. It was confirmed in addition that the adjuvant activity of this fraction was not due to the presence of nucleic acids. This adjuvant-active fraction was designated as HSA (hot-water soluble adjuvant).
To evaluate the role of insulin in familial hypertriglyceridemia, 34 relatives of the pedigrees of 3 index cases of endogenous hypertriglyceridemia and hepatic steatosis as well as 9 spouses were examined for plasma lipids and responses of blood glucose and and plasma insulin during oral glucose tolerance tests. The combined disorders of hypertriglyceridemia and hyperinsulinemia plus glucose intolerance - insulin resistance - were most commonly found among the relatives, which were often accompanied by an impaired liver function. Some relatives showed hyperin-sulinemia without hypertriglyceridemia. Obesity was frequent, but its incidence was similar to the controls. Thus, the observed form of familial hypertrigly-ceridemia was apparently coupled with insulin resistance; and hyperinsulinemia, or insulin resistance by itself, might be a basic genetical trait in this form of lipid disorder.
Effects of X-ray irradiation to the pituitary and transfrontal hypophysectomy were evaluated on the responsiveness of plasma growth hormone (GH) to exogenous stimuli in 8 patients with acromegaly. As exogenous stimuli, arginine, TRH, LH-RH and L-dopa were administered. In 2 out of 3 patients treated with Liniac irradiation, the responsiveness to arginine was essentially unchanged, while in the third patient positive response to arginine disappeared after therapy. Of 2 patients who received a combination of hypophysectomy and Liniac irradiation, the responsiveness to arginine, TRH, LH-RH and L-dopa did not change in 1 patient, but in the other it was observed that negative response to L-dopa became positive after the treatment, remaining the unchanged responsive-ness to arginine, TRH, and LH-RH. In 3 hypophysectomized patients, little change in responses to the above 4 stimuli was observed. In summary, out of 22 pairs of responses (pre- and post-therapy) examined 20 were not altered. In 11 pairs of responses (pre- and post-irradiation) particularly, 10 were essentially unchanged. It might be concluded that the responsiveness of GH to exogenous stimuli in acromegalics would not be affected by irradiation or transfrontal hypophysectomy.
Hemoglobin contamination in antiserum occurs frequently in immunohematology. The hemoglobin obscures the ring test for the observation of antigen-antibody reac-tion. A simple method to remove hemoglobin from antiserum is described in this paper. An appropriate amount of CM-Sephadex was added to antiserum contain-ing hemoglobin and the mixture was packed into a cellulose tube, followed by dialysing against 0.01 M monobasic sodium phosphate solution (pH approx. 6). Equilibrating with stirring, the hemoglobin was completely adsorbed with CM-Sephadex so that hemoglobin-free antiserum was prepared without dilution of the antiserum. This method is useful for immunohematology.