PubMed HealthSearch

Biomedical subjects

S Tojo

Publications and source records attributed to S Tojo.

At least 163 records · Page 9Linked to original sources

A schematic approach to the work-up of amenorrhea.

Amenorrhea is a symptom having many possible causes. Since amenorrhea can result from disturbed function anywhere in the hypothalamic-pituitary-ovarian-uterine axis, a specific etiologic diagnosis must be made if treatment is to be effective. For this purpose, a diagnostic scheme for the differential diagnosis of the etiology of primary and secondary amenorrhea is proposed. This scheme includes a progestin test, a cyclic estrogen and progestin test, a luteinizing hormone-releasing hormone (LH-RH) loading test, and a gonadotropin (human menopausal gonadotropin and human chorionic gonadotropin) loading test. A specific pattern of responses to LH-RH and gonadotropins exists in patients with hypothalamic, pituitary, and ovarian amenorrheas, respectively, and the character of the response may facilitate the etiologic diagnosis of amenorrhea. The clinical usefulness and/or value of the scheme in the diagnosis and treatment of amenorrheas is discussed.

Adult

Immunochemical characterization and quantitation of the human glomerular basement membrane antigen from the urine of patients with glomerular diseases.

A soluble glomerular basement membrane (GBM) antigen was detected in the urines of patients with various glomerular diseases including chronic glomerulonephritis, nephrotic syndrome, chronic renal insufficiency, and lupus nephropathy. The urinary GBM antigen (u-GBM) was immunochemically distinct from other renal antigens and other serum components, but it was cross-reactive with trypsinized human GBM antigen (t-GBM). The molecular size of u-GBM was approximately the same as human serum albumin as estimated by elution patterns on Sephadex G-200. The concentration of u-GBM was estimated quantitatively by a single radial radioimmunodiffusion. Although differed from case to case, a rough correlation with the type and/or stage of nephrotic syndrom existed. It was also demonstrated that the amounts of u-GBM decreased in response to steroid therapy of nephrotic syndrome. It was further shown that in a case of membranoproliferative glomerulonephritis, anti-GBM antibody could be eluted from the kidney removed from the patient. These findings imply that the GBM antigen plays an important role in the pathogenesis of human renal diseases. The pathophysiological significance of urinary GBM excretion in renal diseases is also discussed here.

Antigens

Alpha-subunit of human chorionic gonadotropin in fluid of molar vesicles.

Sera and fluid in molar vesicles from 4 patients with hydatidiform mole were analyzed for hCG and its subunits. These samples were initially chromatographed through a standardized Sephadex G-100 upward column. Starting materials and each fraction on gel filtration were radioimmunoassay in homologous hCG, hCG-alpha and hCG-beta assays. The specimens obtained from 4 patients contained primarily hCG and little hCG-beta. Immunoreactive hCG-alpha was barely detectable in sera but was clearly demonstrated in vesicle fluid from molar patients. This immunoreactive hCG-alpha was combined with [125I]hCG-beta. The combined protein, [125I]hCG and [125I]hCG-beta recombined with urinary hCG-alpha were concentrated in the superovulated rat ovary in vivo. However, [125I]hCG-alpha and [125I]hCG-beta were not taken up by the ovaries. The biosynthesis of hCG-alpha are discussed.

Animals

Binding of LH and FSH to porcine granulosa cells during follicular maturation.

The uptake of 125I-labelled LH by equal numbers of granulosa cells from small, medium or large follicles was greater by cells from large follicles. In contrast, granulosa cells obtained from small follicles bound much more 125I-labelled FSH per cell than did cells obtained from medium and large follicles. Competition studies with unlabelled hormones indicated that porcine granulosa cells have specific receptors for LH and FSH. The addition of diethylstilboestrol enhanced the binding of 125I-labelled LH and inhibited the binding of 125I-labelled FSH to granulosa cells harvested from small and medium-sized follicles, but had no effect on those from large follicles.

Animals

Renal tubular dysfunction in Minamata disease. Detection of renal tubular antigen and beta-2-microglobin in the urine.

"Minamata disease" was found among the residents along Minamata bay contaminated with the effluent from an industrial plant using mercury. The patients were suffering from various neurologic disorders primarily due to organic mercury poisoning. Evidence is described of renal tubular dysfunction associated with this disease by the immunochemical demonstration or renal tubular epithelial antigen and beta-2-microglobulin in the urine. Nineteen patients with Minamata disease and 35 diseased and healthy control subjects were examined. The contents of urinary renal tubular epithelial antigen and beta-2-microglobulin, and the ratios of these proteins to albumin in individuals with Minamata disease were significantly different from the levels in healthy control subjects (P less than 0.05) were identical to those found in patients with tubular and the values, proteinuria. These results indicate that Minamata disease is associated with renal tubular dysfunction, and also suggest that these procedures would be useful for screening the nephrotoxicity in the environmental exposure of heavy metals.

Adult

Growth hormone, prolactin and chorionic somatomammotropin in normal and molar pregnancy.

Twenty patients with molar pregnancy, ten normal pregnant women and ten healthy non-pregnant women were given 30 g of arginine intravenously. The serum concentration of growth hormone, prolactin and chorionic somatomammotropin (CS) was determined by radioimmunoassay. In addition, serum 17beta-estradiol, estriol and progesterone were also measured. Arginine infusion induced a sharp rise of GH in patients with molar pregnancy and in nonpregnant subjects, but the response in normal pregnancy was blunted. The response of PRL was high in patients with molar pregnancy, blunted in normal pregnancy and very small in nonpregnant subjects. CS did not respond at all to arginine infusion both in normal pregnancy and molar pregnancy. The high response to argine of PRL, normal response of GH and low baseline secretion and no response of CS may be characteristic of molar pregnancy.

Arginine

Placento-thyroidal relationship in normal pregnancy.

Estimations of serum HCT, HTSH, T4, T3, PBI, ETR, Triosorb, TBG-binding capacity, BMR and urinary total estrogen were made simultaneously in 160 women in normal pregnancy. TRH stimulation tests were made in 20 cases in each trimester of pregnancy. HCT was detectable even in early pregnancy, tending to increase gradually toward the terminal stage of pregnancy as serum thyrotrophin bioactivity showed. On the other hand, serum TSH level measured by radio-immunoassay remained essentially the same throughout the course of pregnancy as in the nonpregnant state, moreover, it was suggested by the TRH stimulation test that pituitary TSH secreting function of pregnant women was similar to that of the non-pregnant. These findings suggest that thyroid hyperfunction during pregnancy which is shown by progressively increased T3, T4, and PBI may not be due to high estrogen-high TBG binding capacity-low free thyroxinenegative feed back-high TSH secretion but to HCT originating from placenta. In spite of thyroid hormone increase, it is true that the clinical picture of hyperthyroidism is not manifest among normal pregnant women, and ETR remained within the non-pregnant range throughout the course of pregnancy. We have also demonstrated that Triosorb decreased progressively. This may be interpreted to be due to the increase of TBG binding capacity which is increased progressively and binds more of free thyroxine during pregnancy. Such a change in TBG binding capacity is well known to be caused by the effect of estrogen which is progressively increased during pregnancy. In a word, it is possible to say that there is a placento-thyroidal system in pregnancy; HCT elevates thyroid function and TBG increased by estrogen carries thyroid hormone to target organ.

Estrogens

HCT and thyroid function in molar pregnancy.

HCT, TSH, T3, T4, PBI, T3-RSU, TBG binding capacity, BMR and thyroid uptake of radioiodine were measured simultaneously on the volunteers with hydatidiform mole and normal pregnancy. TRH stimulation tests were performed on the two groups. The serum HCT levels were higher in association with molar pregnancy than in normal pregnancy. TSH levels were within the nonpregnant range in the two groups. T3, T4, PBI, ETR, BMR and thyroid uptake of radioiodine suggested thyroid hyperfunction in molar pregnancy with a greater degree than that in normal pregnancy. TBG binding capacity and T3-RSU were similar in two groups. The peak TSH levels of TRH stimulation tests ranged widely in patients with molar pregnancies but were within the nonpregnant range in the subjects with normal pregnancies. These findings suggest thyroid hyperfunction in the molar pregnancy is due to a larger amount of HCT than in normal pregnancy.

Female

Cellular kinetics and histological changes in experimental cancer of the uterine cervix.

Carcinoma of the mouse uterine cervix was induced by the insertion of 20-methylcholanthrene (MC) thread into the uterine cavity. Through biweekly observations, it was seen that the histopathological carcinogenesis in the cervix was characterized by three distinct changes: normal epithelium, anaplastic epithelium, and carcinoma. The incidence rate of normal epithelium declined sharply in the first 4 weeks, followed by slight decline up to the 20th week of observation. Nevertheless, about 20% of MC-treated mice maintained histologically normal epithelium even at the 20th week. In contrast, the incidence rate of anaplastic epithelium increased sharply in the first 4 weeks and thereafter tended to decline. Carcinoma was first observed at the 4th week, and its incidence rate increased thereafter almost linearly, reaching about 50% of the MC-treated mice at the 20th week. Carcinoma was divided into two groups, the early invasive and the frank invasive types. The former was further subgrouped into epithelial bud, nodular growth, epithelial cord, and mixed type by the mode of stromal invasion. Studies using [3H]thymidine autoradiography on the cell proliferation kinetics in the process of carcinoma development showed that a labeling index became higher as the malignant changes of the epithelium advanced. Moreover, S-phase prolongation was observed with the malignant changes, and the cell cycle time did not differ markedly among normal epithelium (22.8 hr), anaplastic epithelium (23.0 hr), and frank invasive carcinoma (26.1 hr). However, the growth fraction was greatly varied; it was 28% for normal epithelium, 61% for anaplastic epithelium, 100% for early invasive carcinoma, and 100% for frank invasive carcinoma. These results indicate that the growth fraction increases as the malignant changes in the MC-treated mouse uterine cervix.

Animals

[Human growth hormone and prolactin during pregnancy (author's transl)].

In order to know the secretory behaviors of human growth hormone (hGH) and human prolactin (hPRL) during pregnancy, the following studies were undertaken. Twenty three normal pregnant women of every period of gestation, eighteen women of postpartum and five nonpregnant subjects volunteered for this study. After fasting overnight, these volunteers were placed at complete bed rest, and a fasting antecubital venous blood sample was drawn at 8:00 a.m. Then L-arginine, 30 g, was infused intravenously over a 30 minute period, and venous blood samples were drawn at 30, 45, 60, 90, 120, minutes after infusion. Serum hGH level was detected by hGH radioimmunoassay Kit (Dainabot) and serum hPRL concentration was measured by double-antibody radioimmunoassay system (NIH-NIAMDD). In addition, serum hCS level was measured by hCS-Kobe double-antibody radioimmunoassay system in comparison with the secretory behaviors of hGH and hPRL. 1. Serum hGH, hPRL and hCS concentrations during pregnancy. HGH concentration remained almost unchanged through the course of pregnancy, but hPRL and hCS concentrations increased with the programs of pregnancy. 2. Serum hGH and hPRL concentrations in puerperium. HGH level did not change as compared to that of nonpregnant or pregnant women. HPRL concentration maintained high level in 1-3 postpartum weeks. 3. Effect of arginine on the concentrations of serum hGH, hPRL and hCS during pregnancy. The hGH response decreased, but that of hPRL increased along with the progress of pregnancy. During the arginine loading test there was no significant change in hCS concentration. 4. Effect of arginine on the concentrations of serum hGH and hPRL in puerperium. The HGH response was suppressed at the first week of the postpartum. The response of hPRL was lower than that of late pregnancy. To summarize, hGH and hPRL have some similar biological characters, but there was a difference in secretion pattern of the two hormones during pregnancy. Reserve function of hGH secretion was suppressed, but that of hPRL secretion increased along with the progress of pregnancy. And in the third trimester of pregnancy, the difference of the secretory behavior and secretory reserve function between hGH and hPRL was prominent.

Arginine

Ovarian response to exogenously administered human gonadotropins during the postpartum period.

Eighteen normal puerperal women received a combined administration of human menopausal gonadotropin (HMG) and human chorionic gonadotropin (HCG) and the ovarian response to these human gonadotropins was evaluated by the daily estimation of the 24 hour urinary excretion of total estrogens. Fourteen of the 18 subjects studied were responsive to the exogenously administered gonadotropins with a rise in the urinary estrogen excretion. Moreover, plasma follicle-stimulating hormone (FSH) and luteinizing hormone (LH) levels during the postpartum period were low compared to normal cycle gonadotropin levels. Thus, it might be concluded that puerperal anovulation and amenorrhea during lactation might be due to hypophyseal gonadotropic dysfunction rather than to ovarian refractoriness.

Amenorrhea

Effect of pituitary gonadotrophins on tritiated thymidine uptake by rat ovary. An autoradiographic study.

The effect of follicle-stimulating hormone (FSH) and luteinizing hormone (LH) on the follicular growth in the ovary of the hypophysectomized rat was investigated using autoradiography. The numbers of DNA-synthesizing nuclei in the granulosa cell were measured by autoradiography after flashlabelling with tritiated (3-H) thymidine. The frequency of 3-H-thymidine labelled nuclei in the granulosa cell enhanced in the presence of FSH. In contrast, LH had no significant effect on thymidine uptake. The result suggests that FSH stimulates follicle cell division, whereas LH does not.

Animals

Pituitary responsiveness to synthetic luteinizing hormone releasing hormone (LH-RH) during the menstrual cycle and in female hypogonadism.

The pituitary responsiveness to synthetic luteinizing hormone releasing hormone (LH-RH) in female patients with primary and secondary hypogonadism was tested and compared with that in normal women with regular menstrual cycles. A 200 mug dose of synthetic LH-RH was injected intravenously into 15 normal menstruating women, 8 patients with primary hypogonadism and 5 patients with secondary hypogonadism and the serum luteinizing hormone (LH) and follicle stimulating hormone (FSH) response to LH-RH was investigated using double-antibody radioimmunoassay. In normal women, the LH response to LH-RH in the preovulatory phase was greater than that seen in the follicular (p less than 0-05) and luteal phases (p less than 0-05) of the menstrual cycle. In contrast, no significant difference in the FSH response was demonstrated among the three different phases of the cycle. The serum LH response to LH-RH in primary hypogonadism was greater than that in the follicular (p less than 0-01) and luteal phases (p less than 0-01) of the cycle. The serum FSH response in primary hypogonadism was markedly greater than that in the follicular (p less than 0-01), preovulatory (p less than 0-01) and luteal phases (p less than 0-01) of the menstrual cycle. Conversely, the LH levels after LH-RH administration in secondary hypogonadism were significantly lower than in the follicular (p less than 0-01), preovulatory (p less than 0-01) and luteal phases (p less than 0-01) of the cycle. The FSH response in secondary hypogonadism was slightly below that in the follicular phase (p less than 0-05). Thus, the FSH response to LH-RH in primary hypogonadism and the LH response in secondary hypogonadism seemed to be sufficiently characteristic to have diagnostic value.

Adolescent

Antibody avidity for native DNA in lupus nephritis.

To study the participation of the antibody avidity in the pathogenesis of lupus nephritis, we measured the antibody avidity to native DNA by the method of Minden and Farr (14) in patients with SLE. The avidity to native DNA was almost less than 40%. The avidity and the histological activity of lupus nephritis were well correlated; the antibody avidity of the active-group sera was higher than that of the inactive-group sera and the group without nephritis. In the group with antibodies of relatively high avidity, the complexes were deposited mainly in the subendothelial side of GBM and in the mesangium. On the other hand, in the group with low-avidity antibodies, the complexes were localized in the subepithelial side of GBM. On investigating the quality of the complexes, we noted that the complexes composed of high-avidity antibodies prepared in vitro were larger than those of low avidity and the former were larger than 19S. If the native-DNA-anti-native DNA system is the mechanism basic to lupus nephritis, the differences in immune response of the host, namely the degree of antibody avidity may greatly affect complex formation and influence the histological activity and nephritogenicity of lupus nephritis.

Adult

Lipolytic action of human chorionic somatomammotropin.

Human chorionic somatomammotropin extracted and purified from placenta at term was proved to have a lipolytic action in the epididymal fat pad of rats. The following mechanism appears to be involved in the lipolytic action of the hormone; human chorionic somatomammotropin activates adenyl cyclase, thereby increasing the concentration of cyclic AMP in the tissue, which, in turn, activates protein kinase to lead to the activation of hormone sensitive lipase.

Adenylyl Cyclases