Search PubMed⌕ Search

Biomedical subjects

K Shiota

Publications and source records attributed to K Shiota.

At least 181 records · Page 10Linked to original sources

Effects of prenatal heat stress on postnatal growth, behavior and learning capacity in mice.

Pregnant ICR mice were immersed in water at 42 or 43 degrees C for 10 min once or twice daily on days 12 through 15 of gestation and the postnatal development of their offspring was observed. Postnatal weight gain of the offspring and their brain weight at 11 weeks of age were smaller than the values for control animals. As compared with controls, prenatally heated mice were less active in an open field and learned slower in a water-filled multiple T-maze and in a shuttle box. Thus, prenatal brief hyperthermia in mice was shown to suppress the body and brain growth during the postnatal period and adversely affect their emotionality and learning capacity.

Aging↗

Significance of germ cells for the expression of testicular endocrine function in rats.

Germ-cell depletion was induced in rats by busulphan administration during the fetal period (Group B). Although a sigmoidal increase of serum testosterone concentration was observed 1 h after the administration of graded doses of hCG (0.3-15.0 i.u./100 g body weight) in intact rats and those in Group B, a shift in the dose-response curve to the right was observed in the latter, suggesting that the sensitivity of testicular response to gonadotrophin was lower in germ cell-depleted rats. However, since the sensitivity was almost identical for both groups of rats for isolated Leydig cells incubated in vitro for 3 h with hCG (0.5-312.5 i.u./ml), the intrinsic nature of the cells was not affected in Group B rats. When the responses of testicular tissue blocks were examined in the in-vitro incubation system, reduced sensitivity reappeared for those from Group B rats, and the presence of testicular tissue components including seminiferous tubules was considered to be responsible for the difference in Leydig cell sensitivity between intact rats and those exposed to busulphan. By the combination of in-vivo and in-vitro experiments, we have demonstrated that germ cells are involved in the endocrine function of the testis.

Animals↗

Calcium metabolism, serum thyroid-stimulating hormone, prolactin, and growth hormone in spontaneously hypercholesterolemic rats.

We have shown previously that spontaneously hypercholesterolemic (SHC) rats exhibit abnormal bone metabolism with advanced bone resorption, which develops with age. In this study, we measured serum levels of growth hormone, thyroid-stimulating hormone, and prolactin in addition to several parameters of calcium metabolism and renal function in young (6-week) and old (24-week) SHC rats and compared these with age-matched Sprague-Dawley rats. In young SHC rats, urinary excretion of hydroxyproline and serum levels of calcium were significantly elevated and excretion of protein into urine and urea nitrogen in the serum were normal, suggesting that calcium metabolism was abnormal without kidney dysfunction at this age. Serum growth hormone and thyroid-stimulating hormone levels were markedly higher (20- to 30-fold and 4- to 5-fold, respectively) in young and old SHC rats, whereas serum prolactin levels were similar. A high level of serum thyroid-stimulating hormone was associated with elevated levels of thyroxine and triiodothyronine in young SHC rats, but not old ones. These results demonstrate that the rat exhibits abnormalities in endocrine function as well as calcium metabolism preceding the occurrence of renal dysfunction.

Animals↗

Induction of neural tube defects and skeletal malformations in mice following brief hyperthermia in utero.

Hyperthermia was induced in ICR mice on day 8.5 of gestation by immersing them in hot water. Control mice were immersed in water at 38 degrees C for 15 min. In dams exposed to 42 degrees C for 12.5-15 min or to 43 degrees C for 7.5-10 min, externally malformed fetuses increased significantly and in a dose-related manner. Anterior neural tube defects (exencephaly, anencephaly, encephalocele, and cranial neural tube defect with facial cleft) were induced most frequently. Embryonic and fetal death and skeletal malformations also increased following heat stress. At intervals after heat exposure, sections of embryonic prosencephalon were prepared for light microscopy. At 2 h after heat stress, mitotic figures disappeared almost completely in embryonic tissues. Mitotic activity was inhibited for at least 3 h. At 6 h, there was a burst of new mitotic activity. Some damaged cells became pyknotic and abnormal cells were encountered in the neuroepithelial tissue after 3-12 h. Thus, neural tube defects in mouse embryos following maternal hyperthermia may result from a temporary cessation of cell proliferation and partial necrosis of the embryonic neuroepithelium.

Animals↗

Involvement of splenocytes in the control of corpus luteum function in the rat.

We previously found that splenectomy caused a 1-day delay in ovulation in cycling rats. In the present study, the role of the spleen or splenocytes in corpus luteum function was investigated by comparing long-term splenectomized (SPX) rats with intact controls. When the rats were cervically stimulated on the day of proestrus, both SPX and control rats showed prolonged diestrus for 16 days associated with an increase in serum progesterone (P). However, in SPX rats, 20 alpha-dihydroprogesterone (20 alpha-OHP) concentrations were double those of controls throughout the period of pseudopregnancy. The concentration of total progestin (P plus 20 alpha-OHP) was also higher in SPX rats. All of these phenomena were normalized by injecting the animals with splenocytes. Taken together with our previous findings, these results indicate that splenocytes are involved in the control of ovarian function.

20-alpha-Dihydroprogesterone↗

Multiple fistulae of coronary arteries to both ventricles.

A 74 year old man was found at necropsy to have multiple coronary arteriosystemic fistulae involving all three major coronary arteries and both ventricles. This is the second such case reported. All terminal branches of the coronary arteries entered the myocardium and numerous tiny vessels opened into the cardiac chambers. No coronary veins or coronary sinus were recognized. This vascular anomaly is considered to result from the abnormal persistence of intertrabecular spaces within the embryonic myocardium.

Aged↗

Teratogenic interaction of ethanol and hyperthermia in mice.

Alcohol and maternal hyperthermia have been implicated in human birth defects. Both ethanol and heat can induce neural tube defects (NTDs) and other developmental abnormalities in mice when large doses are given during pregnancy. To explore the teratogenic interaction of both agents, pregnant ICR mice were injected with a single dose of 25% ethanol and/or were heat-stressed in a water bath at 42 degrees C on the morning of Day 8 of gestation. Combined treatment with ethanol (0.01-0.02 ml/g) and heat (10 min), when they were given concurrently or 1 hr apart, resulted in a significant increase of resorptions and externally malformed fetuses. Skeletal malformations and visceral variations also increased significantly following a concurrent exposure to both agents. These results indicate that ethanol and heat can be synergistically teratogenic in mice when the doses of each agent are below the teratogenic threshold. It was also suggested that pretreatment with a small dose of ethanol may not enhance the teratogenicity of heat when the hyperthermic stress is strong enough and teratogenic by itself.

Animals↗

Single central maxillary incisor and holoprosencephaly.

A holoprosencephalic child was born to a mother with a single central maxillary incisor. The infant had a median cleft lip, a flat nose with a single nostril, hypotelorism, and normal chromosomes. The head was brachycephalic and small, and computed tomography (CT) of the brain showed semilobar holoprosencephaly. The mother had mild hypotelorism but no anosmia, and her brain CT was normal. She was of normal intelligence and stature. Other relatives did not have single central maxillary incisors, hypotelorism, or oral clefts. Whether the mother's anomaly was a new mutation or had been inherited is unknown. We show the significance of a single central maxillary incisor as an indicator or potential holoprosencephaly in the next generation, even if other relatives are apparently normal.

Abnormalities, Multiple↗

High prevalence of defective human embryos at the early postimplantation period.

Thirty-seven cases of human embryos at the early postimplantation period were procured after induced abortion and examined histologically. Their developmental stages ranged from Carnegie stages 6 to 11, and their standard ages ranged from 14 to 24 days after fertilization. Five cases (13.5%) were grossly abnormal, and seven (18.9%) were degenerating partially or in toto. Gross abnormalities included distorted embryonic disc, disorganized neural groove or tube, and neural tube dysraphism. The high prevalence rate of defective embryos at the early postimplantation period supports the clinical finding that a substantial proportion of human conceptions are eliminated from an early stage of pregnancy, often without the knowledge of the mother. The fate of undifferentiated pathological embryos is uncertain and remains to be determined.

Abortion, Induced↗

Joint study on the teratogenic sensitivity of the Pika (Ochotona rufescens rufescens) to selected drugs.

A collaborative study was conducted to investigate the teratological susceptibility of the Pika (Ochotona rufescens rufescens) to selected teratogenic chemicals: cyclophosphamide, 6-mercaptopurine, 5-fluorouracil, 6-aminonicotinamide, actinomycin D, ethylurethan, ampicillin, tetracycline, thalidomide, diphenylhydantoin, hypervitaminosis A, aspirin, dexamethasone, betamethasone and bredinin. Some of the chemicals were shown to be teratogenic in the Pika, but this animal was generally more resistant to their teratogenicity than the rabbit and rodents. In the Pika, thalidomide did not induce any typical limb defects, which have been produced in the rabbit. Pikas reproduce well and appear to have no substantial disadvantages as an animal species for teratological studies. Thus, the Pika may be useful as a new non-rodent species for teratological testings.

6-Aminonicotinamide↗

Distinct effects of transforming growth factor-beta on EGF receptors and EGF-induced DNA synthesis in primary cultured rat hepatocytes.

Previous studies showed that transforming growth factor-beta (TGF-beta, 1 ng/ml) strongly inhibited DNA synthesis induced by epidermal growth factor (EGF) in primary cultures of adult rat hepatocytes. This paper reports that TGF-beta (4 ng/ml) caused marked increase of EGF-binding to cultured rat hepatocytes. The binding increased biphasically with time to a maximum after treatment with TGF-beta for 12 h. Scatchard analysis showed that adult rat hepatocytes had a single class of non-cooperative binding sites with a Kd of 1.5 nM, that there were 1.4 X 10(5) binding sites/cell, and that TGF-beta increased the number of binding sites without changing the Kd value. The increase in EGF binding sites by TGF-beta was dose-dependent and the dose that elicited the maximum increase was about 10 times that which inhibited DNA synthesis stimulated by EGF. These findings suggest that the effect of TGF-beta in modulating the EGF receptor is not directly related to that in inhibiting DNA synthesis in adult rat hepatocytes.

Animals↗