Decrease in insulin secretion in lactating rats.
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Biomedical subjects
Publications and source records attributed to T Imamichi.
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A male pseudohermaphrodite rat mutant showing a blind-ending vagina, small undescended testes, rudimentary male sex accessory organs and XY karyotype was investigated. Genetic analysis revealed an autosomal single recessive transmission of this defect and indicated that the gene action is restricted to males. Microscopic examination showed an absence of typical Leydig cells in testes of the mutant. Plasma concentrations of testosterone were extremely low and the values were comparable to those of castrated male rats and did not change after castration and/or after administration of hCG. Plasma concentrations of LH and FSH were remarkably high and the values were comparable to those of long-term castrated normal male rats which declined to basal levels after administration of exogenous testosterone. Weights of thymus and adrenal glands decreased and weights of preputial glands, kidneys and male accessory sex organs increased in response to exogenous testosterone. These results indicate that the primary defect in the mutant is an androgen deficiency probably due to a Leydig cell agenesis in the testes.
A new rat line (TS inbred rats) showing uni- or bilateral ectopic scrota in about 70% of the males was established. Ectopic scrota were elongated pouches of the thin muscle layer under the suprainguinal body skin, in which hypoplastic testes and epididymides were seen. Genetic analysis revealed that the ectopic scrotum was controlled by multiple genes. Groups of 5 normal, uni- and bilaterally affected rats were killed at 25 weeks of age. Histologically, ectopic testes of uni- and bilaterally affected rats showed arrest of spermatogenesis at the primary spermatocyte stage. Contralateral testes of unilaterally affected rats were normally descended and showed normal spermatogenesis. No abnormality was seen in the urinary system. Plasma concentrations of FSH were significantly elevated in bilaterally affected rats but plasma concentrations of testosterone and LH were unchanged in uni- and bilaterally affected rats. Pituitary contents of LH and FSH were significantly elevated in bilaterally affected rats. The endocrinological status of TS inbred rats was therefore similar to that of experimentally induced cryptorchid rats.
The lordosis behavior in female rats following removal of the vomeronasal organ (VNO) was observed for a period of 14 hrs by means of a video camera monitor. Although the VNO-ablated female rats received a large number of mounts (96 to 204 times) by sexually active males, they showed only low scores (8 to 22) of lordosis quotients (number of lordosis behavior displayed/number of mounts X 100). In contrast, sham-operated females showed the highest lordosis quotients of 100 as was expected.
The vomeronasal organ (VNO) in most mammalian species consists of a bilaterally paired tubular structure lying on either side at the base of the nasal septum. Functionally, the VNO receives chemosensory informations and conveys it to its parts of the hypothalamus thought to be important in the regulation of reproductive physiology and behavioral functions. Here the authors report an improvement of the VNO ablation in the rat. With the exception of restraint of a rat, this operation method is fundamentally similar to those reported by Saito and Mennella (1986). The rat was anesthetized and placed supine on a home-made operating board with some accessories, and its extremities and head were fixed. It should be emphasized that the restraint of its lower incisor and tongue to keep the mouth open was performed with home-made restraint devices. The above method enabled us to remove the VNO easily. In addition, it could be useful in this field of oral surgery in small animals.
To study the effects of SKF-525A, an inhibitor of cytochrome P-450, and of sodium phenobarbital (PB), a drug-metabolizing enzyme inducer, on the teratogenicity of thiabendazole (TBZ), pregnant mice were given ip either a single dose of 40 mg SKF-525A/kg 1 hr before oral dosing with 250 or 500 mg TBZ/kg or a dose of 75 mg PB/kg/day on three consecutive days before oral administration of a dose of 500 or 1000 mg TBZ/kg. In either case the TBZ dose was given on day 9 of gestation. All foetuses were removed from the uterus on day 18 of gestation, and were examined for external and skeletal anomalies. The spectrum of malformations in the groups of mice pretreated with SKF-525A or PB was similar to that in mice treated only with TBZ. In the group pretreated with SKF-525A, however, the incidence of resorbed foetuses was higher than in the group treated with TBZ alone and there was a tendency towards an increase in the number of foetuses with skeletal fusion and reduction deformity of the limbs, an anomaly characteristically induced by TBZ. On the other hand, in mice pretreated with PB, the incidence of resorbed foetuses tended to be lower, the numbers and body weights of live foetuses were higher and the incidence of external and skeletal malformations was lower than in the groups treated with TBZ only. No reduction deformity of the limbs was observed in the groups pretreated with PB. These results suggest that with TBZ the ultimate teratogen may be the parent compound rather than its metabolites.
The amylase (EC 3.4.21.4) and trypsin (EC 3.2.1.1) activities in the pancreas in rats during pregnancy, lactation and after the weaning period, and the secretory responses to a secretagogue (caerulein) in the exocrine pancreas of lactating rats were measured. Trypsin activity increased as lactation progressed and reached twice that of unmated rats in the second half of the lactation period. The amylase activity fell before parturition and failed to recover even after the start of lactation and was significantly decreased throughout the lactation period. The total amount of pancreatic juice produced in the lactating rats was significantly greater than that of unmated rats; the amylase output was significantly less than that of unmated rats. When the pups were removed, amylase activity in the pancreas returned to the value in unmated rats. Furthermore, the amylase activity in lactating rats receiving a daily injection of insulin significantly exceeded that of normal lactating rats. These results indicate that the decrease in amylase activity in lactating rats is due to the reduction of amylase synthesis and there is a possibility that insulin is required for normal or elevated rates of amylase synthesis in lactating rats.
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Sperm retention cysts were observed in the efferent duct of TE inbred rats at 15 weeks of age. Spermatozoa agglutinated in the efferent duct with destruction of the epithelium. Testicular weight increased or decreased. Diameter of the seminiferous tubules was enlarged in testes that increased in weight and germinal cells degenerated in the atrophied testes. After 30 weeks of age, the tubules of the efferent duct were sometimes replaced by scars and testicular atrophy became more frequent. In 3 out of 5 normal rats united by parabiosis with TE males for 25-27 days, cysts occurred in the efferent duct.
To determine whether pretraining with the water-filled straight channel affects learning acquisition, we studied the water filled multiple T-maze learning ability in 8-weeks-old SPF Wistar-Imamichi rats. The performance time for the straight channel was markedly shortened at the 2nd and 3rd trial compared to the time at the 1st trial on the 1st day. But at subsequent trials on days 2 and 3 it was longer than at the 3rd trial on day 1. At the 1st trial on day 1, the performance time of the group unexperienced in the straight channel was more than three times that of the experienced group. In subsequent trials, however, both groups showed similar performance times. More errors were observed in the unexperienced group than in the experienced group at the 1st trial on day 1. No difference was found between the two groups in subsequent trials. These results indicate that the learning acquisition was largely influenced by pretraining in the straight channel at the 1st trial on day 1.
Lymphocyte subpopulation as well as other hematological properties were compared between arterial and venous bloods of Wistar-Imamichi rats. Lymphocyte subsets were defined with four monoclonal antibodies which were specific to the respective cell surface glycoproteins. Using these monoclonal antibodies, subsets of B lymphocytes, T lymphocytes, helper T lymphocytes, and suppressor and cytotoxic T lymphocytes in the peripheral lymphocytes were identified. The blood samples were taken from aorta abdominalis and venae cava caudalis. The population of these subsets were enumerated by a laser flow-cytometry system. The result showed that there was no significant difference in hematological properties between the arterial and venous blood except in leukocyte count and hemoglobin concentration. The difference in leukocyte counts was thought to depend mainly on the fluctuation of the lymphocyte counts. However, no significant difference was recognized in the proportion of positive cells to each monoclonal antibody. It was concluded that the difference in leukocyte counts found between the arterial and venous bloods of the Wistar-Imamichi rat did not produce any effects on the proportion of the subpopulation in the peripheral lymphocytes, and the lymphocyte subpopulations in both arterial and venous bloods were substantially equivalent to each other.
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An outbreak of dermatophytosis by Trichophyton mentagrophytes infection was observed in a breeding stock of the Wistar-Imamichi rat. Typical cutaneous lesions such as alopecia and hyperkeratosis due to the fungus were observed in 10% and 44% of adult females, and males respectively. No infection was seen in infant, even in those fostered by infected females. By 3 repeated cultivations of the hair, T. mentagrophytes was isolated from 107 (90.7%) of 118 rats clinically diagnosed as dermatophytosis. In order to maintain the original stock, the usual wholesale slaughter program was avoided and the following control measures were taken. After sacrificing all rats with the cutaneous lesions, the breeding colony was transferred temporarily to a separate animal room. The resulting vacant room was then disinfected 3 times with 10% formalin, followed by spraying with 3% sodium propionate solution 3 month later. The progenies from the non-infected mothers were dipped into 3% sodium propionate solution and transferred back into the disinfected animal room for re-colonization. Frequent sterilization of all equipment with iodophor, balsam and formalin was carried out. The room sterilized monthly with iodophor and 70% alcohol. Daily observation of all rats and monthly screening by culture test was done thereafter. As a result, no infection has been detected 4 month after recolonization, except for the 3 rats which were sacrificed immediately after detection. On the basis of the culture test and clinical observation, no infection was observed in the treated rat colony for the next five following years. Therefore, the effectiveness of these procedures of the eradication of T. mentagrophytes infection from a rat colony was shown to be quite reliable.
In the TW inbred rat, about 50% of the males show bilateral or unilateral testicular hypoplasia with aplasia of the ipsilateral epididymis, ductus deferens and gland of the ductus deferens. To investigate the pathogenesis of the testicular abnormality in the TW rats, the weight and morphology of the testes on the aplastic and normal side were studied between one week and one year of age. The weight of the testes on the affected side was greater than those on the normal side at four and five weeks. However, it rose to a plateau at six weeks and then remained at about one half to one third the weight of a normal testis. As for the testicular histology, there were no obvious changes from one day to three weeks of age. The diameter of the seminiferous tubules became larger and the number of germ cells decreased at four and five weeks. At six weeks, degeneration and loss of germ cells were observed and many multinucleated giant cells appeared. Thereafter, the loss of germ cells became more severe, and they eventually disappeared with increasing age, but Sertoli's cells continued to exist. In the interstitial area, edematous changes and proliferation of Leydig's cells were observed. The efferent duct of another strain, with normal testes, was ligated at three weeks of age, and changes of the testis after the operation were examined to investigate whether or not these anomalies of the TW strain were due to the absence of the accessories, which may block the excretion of the testicular fluid.(ABSTRACT TRUNCATED AT 250 WORDS)
A simplified technique was established for the intravenous glucose tolerance test (ivGTT) in unanesthetized rats. In order to evaluate the relation between insulin secretion, glucose load and glucose disappearance rate, precatheterized rats were given glucose ranging in dose from 0.25 to 2.0 g/kg bw by intravenous injection. A highly linear correlation was observed in glucose disappearance rate during a period of 4-32 min. A glucose load greater than 0.5 g/kg ow induced a maximum response in insulin secretion. Small blood samples were collected using the orbital bleeding technique at 4, 16 and 28 minutes after a glucose load of 1.0 g/kg bw had been given and then T1/2, the time taken for the glucose level to fall by one half, was calculated. The mean T1/2 was significantly longer in alloxan- or cyproheptadin-diabetic rats than that in the intacts. These data indicate that a glucose load of 1.0 g/kg administered by intravenous injection with the T1/2 calculated between 4 and 32 minutes would provide an accurate means of assessing pancreatic endocrine function.
The number of delivered offspring, corpora lutea and implantation sites was observed in an SPF colony of Wistar-Imamichi rats bred in a barrier system free of specified microorganisms and parasites and was compared with that of rats bred under conventional conditions. The litter size of 6142 SPF rats ranged from 1 to 20, averaging 12.4 +/- 0.04, a value significantly higher (P less than 0.001) than that of conventionally bred rats (11.0 +/- 0.04). Although the number of corpora lutea was also higher in SPF rats than under conventional conditions, the number of post-implantation losses in SPF rats with less than 10 offspring showed a marked decrease compared with conventionally bred rats. These results show that the number of delivered offspring is higher in SPF rats than in conventionally bred rats and indicate that the increase in litter size is due to the increase in the number of corpora lutea and decrease in post-implantation loss of embryos of fetuses.
A testicular hypoplastic (T-H) rat strain, originating from the Wistar-Imamichi rat colony at the Institute for Animal Reproduction, has been maintained by full-sib matings since 1974 for eight filial generations. There were no abnormal signs in external features and growth patterns of the T-H strain. Testicular hypoplasia was detectable at about 8 weeks of age by palpation around the scrotum. Unilateral or bilateral testicular abnormalities were detected in 80 out of 391 males of this strain. The incidences were 32.5% for right side, 48.8% for left and 18.8% for both respectively. Reproductive performance of unilateral T-H males were not different from that of normal. While bilateral ones showed normal sexual behavior, they failed to produce their progenies. In adult T-H rats testicular weight was approximately two-fifth of the normal, and the accessory organs such as the seminal vesicles, epididymis and etc., especially located in the same side of the testicular hypoplasia, reduced their size and weight. Occasionally was seen lack or denaturation of the deferent duct or epididymis. At adult age, no spermatogenesis was observed in all hypoplastic testes with a few exception, and normal spermatogenesis in the testis of the normal side of unilateral T-H male.
The shortenings of intestinal strips isolated from narrow segments in the aganglionosis rat have been studied in response to stimulants and field stimulation. Relating to the action of nicotine, eserine and field stimulation, the number of exogenous nerve bundles observed between the longitudinal and circular muscle layer and the type of cells existing in the nerve bundles were examined by light and electron microscopes. Nicotine shortened in 16 out of 31 narrow segments and eserine 13 out of 14 preparations. In 6 out of 21 preparations, field stimulation produced weak contraction, which was abolished by pretreatment of atropine or TTX. The number of the nerve bundles was larger in the responded groups than in the non-responded. However, no ganglion cells were observed in the nerve bundle of the narrow segment of the aganglionosis rat. To acetylcholine, serotosine, prostaglandin E2, KCl and BaCl2, all narrow segments responded, though the response to these drugs particulary to KCl was extremely weaker than those in control. It is suggested that the nerve bundles of the narrow segment branched and formed nerve endings in the smooth muscle and the responsiveness of the receptor to the stimulants is maintained in the narrow segment, but contractility of the smooth muscle is small.