Mitsuo Kodama

Effect of rice and salty rice diets on the structure of mouse stomach

The effect of rice and salty rice diets on stomach morphology was investigated in Swiss/ICR mice. Mice were fed rice, salty rice, or standard pellet diets for 3-12 months, starting when the mice were 4 weeks of age. Long-term maintenance on the rice or salty rice diet increased the dimension and wet weight of the forestomach and decreased the same parameters of the glandular stomach. Similar bidirectional changes of the forestomach (hypertrophy) and glandular stomach (atrophy) were produced by hydrocortisone treatment. Histological study showed that a reduction in the parietal cell population accounted for the regression of the glandular stomach in both cases. Evidence is presented to suggest that an excess of carbohydrate and sodium chloride combined with a deficiency of fat and protein produced steroidal disorders that in turn gave rise to hyperplasia of the forestomach and atrophy of the glandular stomach of the mice. Possible impact of the above findings on the genesis of human gastric cancer is discussed in relation to the metabolic competence of the host animals to synthesize vitamin C.

Hormonal status of gastric cancer. II. Abnormal constitution of urinary steroids in gastric cancer patients

We undertook a case-control study regarding the excretions of 14 urinary steroids in gastric cancer (GC) patients. The results are as follows: the levels of androgens, progestins, and two corticosteroids were, relative to tetrahydrocortisol, significantly depressed in GC patients of both sexes compared with the corresponding normal controls. The deviation profile of urinary steroids was not affected by radical gastrectomy. Evidence indicated that observed changes of GC urines were the steroidal expression of a decrease of endogenous testosterone combined with an increase of endogenous hydrocortisone; there was also evidence that the hormonal environment of our GC patients was endocrinologically homologous to that of rice-fed or salty rice-fed mice. Epidemiological inquiry revealed that GC patients having more access to rice-rich or salt-rich diets were taller and less obese than were rural healthy controls. In agreement with the anthropometric data of those cancer patients is the finding that the specific death rate of GC (as calculated for each of 15 prefectures of northern Japan) was positively correlated for each sex with the mean heights, but not with the mean weights, of 14-year-old youths of those areas. This paper discusses the possible relevancy of the hormonal and epidemiological aspects of GC patients to gastrocarcinogenesis in light of steroid physiology.

Hormonal status of gastric cancer. I. Effect of rice and salty rice diets on the constitution of urinary steroids in mice.

We investigated the effect of rice and salty rice diets on the physical growth and on the constitution of urinary steroids in Swiss/ICR mice. The following three kinds of diets were employed in the feeding experiment: 1) standard diet; 2) rice diet; and 3) salty rice diet. Long-term maintenance of mice on both rice and salty rice diets led to a relative increase of tetrahydrocortisol associated with a concomitant decrease of androgen, progestin, and cholesterol in urine. Evidence was presented to indicate that the activity of endogenous hydrocortisone in mice could be augmented by an increased intake of sodium chloride alone; there was also evidence that the glandular stomach of a young mouse drinking physiological saline is highly sensitive to a suppressive action of hydrocortisone. We concluded that the two experimental diets produced a state of catabolic glucocorticoid excess combined with a deficiency of anabolic androgen and progestin. Mineralocorticoid status was not examined. In the salty rice diet, a markedly lower weight gain was observed, whereas in the rice diet, in general, no significant weight changes were observed.

Relation Between Steroid Metabolism of the Host and Genesis of Cancers of the Breast, Uterine Cervix, and Endometrium

Publisher Summary This chapter describes the relation between the steroid metabolism of the host and the genesis of three female cancers—breast cancer, cervical cancer, and endometrial cancer—from the breast and uterus, organs which are known to be subjected to steroidal influences during their developmental stage. Relevant information from epidemiology, endocrinology, and molecular biology is exploited in an effort to extract common principles operating in the production of these three cancers. An attempt was made to investigate comparatively the epidemiological and endocrinological aspects of cancers of the breast, uterine cervix, and endometrium to construct a unifying theory about the genesis of three sex-related neoplasias. Epidemiological studies demonstrated that the risks for breast and cervical cancers were conditioned by specified combinations of three factors—climate, diet, and sex life; an increased risk for breast cancer was associated with a cold climate, a fatty diet, and a delay of, or abstention from, sexual experience, whereas an increased risk for cervical cancer was accompanied by just the reverse in each of the three factors. The chapter presents an evidence to indicate that a patient with endometrial cancer is smaller in stature, less fertile, and more disposed to a fatty diet than a healthy control. It also suggests that the risk of endometrial cancer could be augmented in a stressful environment. In addition, migration studies indicate that the risks for each of the three cancers are subjected to a change through emigration.

Effect of a rice-rich diet on the therapeutic efficacy of cyclophosphamide with special reference to the enhancement of transplantation immunity

The present study investigated the problem of whether the therapeutic efficacy of cyclophosphamide in the in vivo Ehrlich ascites tumor system can be improved by adjuvant use of hydrocortisone or of dietary hydrocortisone mobilizers. In the chemotherapy experiment, female ICR mice each received an inoculum of 1 × 106 cells of Ehrlich ascites tumor ip followed by 2 ip injections of cyclophosphamide 36 and 37 hr later (2.4 mg/mouse for the 1st injection, and 1.0 mg/mouse for the 2nd injection). The effects of both cyclophosphamide and adjuvant treatments were assessed in terms of either survival rate or cure rate in the 1‐month experiment. The results obtained were as follows. 1) Prolonged use of hydrocortisone as an adjuvant can improve the survival of cyclophosphamide‐treated mice. 2) Adjuvant use of a rice‐rich diet for maintenance increased the rates of both survival and cure in the cyclophosphamide‐treated mice. 3) The same maintenance of mice on a rice‐rich diet increased transplantation immunity on the one hand, and induced a set of steroidal changes including hydrocortisone excess on the other hand. 4) Evidence is presented to indicate that the beneficial influence of a rice‐rich diet on the drug effect is related to an increase of transplantation immunity in the host, and that there could be a causal relationship between hormonal and immunological changes in rice‐saturated mice.

The value of urinary steroid analysis in chorionic neoplasia.

The profile of urinary neutral steroids was investigated in normal pregnancy and chorionic neoplasia by gas-liquid chromatography. The whole chramatogram was divided into three metabolically distinct fractions. The excretion of fraction 2, including four menstruation-dependent steroids (11-hydroxyandrosterone, 11-hydroxyetiocholanolone, pregnanediol, and pregnanetrial), was remarkably increased in normal pregnancy as compared with that in nonpregnant controls. But the same parameter was differentially reduced in hydatidiform mole (HM) and chorioadenoma destruens (CA) as compared with normal pregnancy, and the ratio of fraction 2 to fraction 1 (11-deoxy-17-ketosteroids) was found useful in separating normal pregnancy, HM, and CA from each other. In choriocarcinoma (CC), reduced excretion was observed in both fraction 1 and fraction 2 steroids. The linear relationship between the logarithm of fraction 2-fraction 1 ratio and that of pregnanediol excretion, as observed in the reproductive cycle of a healthy woman, was not detectable in women with CA, whose urine revealed a low value of log (fraction 2/fraction 1) in spite of an abundant HCG content. It is indicated that the above findings reflect the deficiency of ovarian steroidogenesis under the influence of abnormal HCG from tumors.

General survey of intertumor linkages that connect the chronological changes of age-adjusted incidence rates of 13 neoplasia types from l975 to l993 in Japan

We attempted a stochastic study of cancer risk change in time using the follow-up data of the age-adjusted incidence rate (AAIR) of cancer in Japan, which covered 13 neoplasia types of both sexes in scope, and ranged from 1975 to 1993 in time. The purpose of our study was to test whether or not there was any mathematical regularity that was to condition cancer risk changes in time in all the 13 human neoplasia types. We investigated the relation between 2 neoplasias as regards log AAIR changes in time by the direct successive elimination method of Gauss, a fitness test of a given pair data to an equilibrium model. The fitness test was repeated in each of 156 tumor pairs [P(13.2)] in both sexes, in each of 3 (x, y) coordinates - the original (x, y) coordinates, the rect- (x, y) coordinates and the para- (x, y) coordinates. Total number of fitness test in this study was estimated to be 156x2x3=936. The rect- (x, y) coordinates and the para- (x, y) coordinates were defined each as an (x, y) framework with its x axis crossed at a right angle to the regression line of the original log AAIR data, and as another framework with its x axis run in parallel with the regression line of the original log AAIR data. The fitness of a given tumor to an equilibrium system was assessed in terms of the correlation coefficient value r within the range of -1.000 (the oncogene-type equilibrium system) to +1.000 (the tumor suppressor gene-type equilibrium system). Results obtained are given as follows: i) the positivity rates of the fitness test to the oncogene-type equilibrium system and the tumor suppressor gene-type system in the male all-cancer population were each 95.5% (149/156 tumor pairs) and 79.5% (124/156 tumor pairs), and those in the female all-cancer population were each 91.0% (142/156 tumor pairs) and 83.3% (130/156 tumor pairs). Evidence was available to indicate that all of the 13 human neoplasia types of both sexes was associated with both oncogene activation and tumor suppressor gene inactivation at the level of individual tumors. In other words, clearance of both oncogene activation and tumor suppressor gene inactivation was the sine qua non premise of carcinogenesis. ii) The positivity score profiles of a given tumor (profile-like presentation of positivity score for each tumor), for each of 2 cancer genes and for each sex, was highly specific for each of the 26 tumor units (13 tumors of both sexes). The presence of a highly specific positivity score pattern might be taken as another expression of complex interaction of 2 cancer genes in carcinogenesis. iii) Evidence was presented to suggest that specified interactions of the oncogene-tumor suppressor gene complexes of both sexes might be causally related to the emergence of sex discrimination of cancer risk, as testified in a set of tumors with both male dominance of cancer risk and female dominance of cancer risk. iv) The significance of one tumor pair that failed to show fitness to both the oncogene-type equilibrium system and the tumor suppressor gene-type equilibrium system was discussed in terms of spacially restricted dissociation of the power center of the oncogene-type equilibrium system from that of the tumor suppressor gene-type equilibrium system in a given tumor pair.

Dissociation of chorioadenoma destruens from hydatidiform mole by urinary steroid analysis

Dissociation between hydatidiform mole (HM) and chorioadenoma destruens (CA) was attempted by gas chromatographic analysis of urinary steroids. In the chromatogram, fraction 2 (F2) including four pregnane steroids (17-hydroxypregnanolone, pregnanolone, pregnanediol, and pregnanetriol) reflected the biologic activity of molar human chorionic gonadotropin (hCG), and the ratio of F2 to fraction 1 (F1) (17-ketosteroids) was found useful in monitoring secondary growth of trophoblastic tumor: Urinary log F2/F1 after curettage declined quickly and unidirectionally in HM, but the same parameter exhibited a temporal rise in CA at 11 to 20 days after curettage because of the molar hCG from residual tumor tissue. The resolution between HM and CA at that stage (11 to 20 curettage days) was of the order of diagnostic use and superior to that with immunoreacive hCG. The data obtained are discussed in the light of pathophysiology of CA.