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O Taguchi

Publications and source records attributed to O Taguchi.

At least 127 records · Page 7Linked to original sources
PubMed1988

[Analysis of experimental autoimmune oophoritis as a model of premature ovarian failure].

Neonatal thymectomy in mice at 3 days of age (Tx-3) can induce autoimmune oophoritis and results in complete loss of oocyte at young adult age. We examined endocrinological and immunological abnormalities in Tx-3 (C3H/He X A/J)F1 female mice to find some similarities to premature ovarian failure (POF) in humans. The majority of the Tx-3 mice showed irregular estrous cycles during 7 to 9 weeks of age then fell into continuous diestrous. Endocrinological analysis of Tx and sham-Tx mice revealed that serum gonadotropin levels (LH and FSH) of Tx-3 mice rapidly increased from 8 weeks of age and serum estradiol levels significantly decreased from 10 weeks of age (P less than 0.05). In contrast with estradiol, serum androstenedione levels significantly increased from 10 weeks of age (P less than 0.01). In the mice with oophoritis, circulating autoantibodies against ooplasm and/or zona pellucida determined by immunoperoxidase method could be detected from 6 weeks of age, became high titer from one or two weeks later, but resulted in low titer or negative test from about 4 months of age. Acute loss of oocyte with massive mononuclear cell infiltration coincident with the appearance of these autoantibodies were progressed, and then atrophic ovaries with complete destruction of follicles were seen at 3 months of age. This experimental model of autoimmune oophoritis abounds in suggestion for the understanding of one of the possible etiology of POF in women.

Androstenediols↗
PubMed1988

Rapid induction of ovarian granulosa cell tumors by 7,12-dimethylbenz(a)anthracene in neonatally estrogenized mice.

Groups of female C3H/HeMs x 129/J F1 mice were given injections of either 20 micrograms of 17 beta-estradiol or sesame oil (vehicle) for the first 5 days after birth. Half of each group was then given gastric intubations of 20 mg/kg of 7,12-dimethylbenz(a)anthracene (DMBA) at 70, 77, and 84 days of age. The other half of each group was given sesame oil. Thus, this design yielded four experimental groups: oil + oil; 17 beta-estradiol + oil; oil + DMBA; and 17 beta-estradiol + DMBA. They were sacrificed at approximately 144 days of age (Experiment 1) or the day of palpable ovarian tumor detection or 360 days of age (Experiment 2). In Experiment 1, the total number of oocytes (follicles) per ovary in mice of the 17 beta-estradiol + oil group was maintained at the same level as mice of the oil + oil group. A significant reduction of oocytes, however, was observed in mice of the 17 beta-estradiol + DMBA group in comparison with mice of the oil + DMBA group (P less than 0.01), and neoplastic nodules of the granulosa cell type developed in the unilateral ovary in 10 of 17 mice of the 17 beta-estradiol + DMBA group. No tumors were detected in the mice of the other groups. The plasma levels of both follicle-stimulating and luteinizing hormones as determined by radioimmunoassay were significantly higher (P less than 0.01) in mice of the 17 beta-estradiol + oil group than in mice of the oil + oil group. In Experiment 2, more ovarian tumors of the granulosa cell type were detected before 360 days of age in mice of the 17 beta-estradiol + DMBA group (14 of 18) than in mice of the oil + DMBA group (5 of 15) (P less than 0.05). No tumors developed in mice of the other two groups. These results strongly indicate that an abnormal endocrine milieu caused by neonatal treatment with estrogen may induce a high frequency of transformation of some ovarian tissues and rapid growth of the ovarian tumors after DMBA treatment.

9,10-Dimethyl-1,2-benzanthracene↗
PubMed1988

Possible site of bronchodilation due to inhaled procaterol aerosol in asthmatic patients.

We studied the effective site of an inhaled aerosol of procaterol, a beta 2-selective adrenergic bronchodilator, in 8 asthmatic patients whose basal lung functions are almost within the normal range in both slow vital capacity (VC) and forced expiratory volume in one second (FEV1.0), and are free from asthmatic attack. In patients who had received procaterol 30 min after inhalation of aerosol, there was no significant change in VC, although FEV1.0, maximal expiratory flow at 50% VC (V50), maximal expiratory flow at 25% VC (V25) and maximal expiratory flow at 30% VC of partial maximal expiratory flow volume curve (V30p) improved significantly. On the other hand, in those who had received placebo, none of the parameters changed. Furthermore, R1 decreased and C0.5 increased significantly during the first 5 min after inhalation of procaterol aerosol. After an interval of 5 min, R1 did not change any further, while C0.5 continued to improve until 30 min after inhalation of procaterol. These results suggest that procaterol may first dilate the large airway and then may gradually dilate the small airway in bronchial asthma.

Adult↗
PubMed1988

Acute oocyte loss in experimental autoimmune oophoritis as a possible model of premature ovarian failure.

A high incidence of autoimmune oophoritis can be induced in (C57BL/6Cr x A/J)F1 mice that were thymectomized at 3 days of age. The vaginal opening day was significantly delayed (thymectomized mice [n = 35], 38.1 +/- 5.8 days [mean +/- SD] versus sham thymectomized mice [n = 26], 34.0 +/- 5.2 days; p less than 0.02). Most of the thymectomized mice showed irregular estrous cycles during the first several weeks and then fell into continuous diestrus. Local infiltration of mononuclear and plasma cells inside and around growing follicles was a prominent feature in the early stage of oophoritis. This abnormal feature was first noticed at 24 days of age and progressed in the follicular units. Acute loss of oocytes, especially of growing follicles, with massive mononuclear cell infiltration rapidly progressed after puberty, and atrophic ovaries with complete destruction of both primordial and growing follicles were then seen for 1 to 2 months after puberty. In mice with oophoritis, circulating autoantibodies against, ooplasm, zona pellucida, or steroid-producing cells were constantly detected by immunohistochemical assay. Autoimmune thyroiditis and gastritis accompanied by specific circulating antibodies were also detected in mice thymectomized at 3 days of age. This experimental model may serve as a tool for studying premature ovarian failure in humans.

Animals↗
PubMed1988

Hormonal characterization of female SL/Ni mice: a small thymus gland strain exhibiting ovarian dysgenesis.

Female SL/Ni mice have a small thymus gland and show accelerated aging of the reproductive system characterized by an early loss of the follicular apparatus and early onset of ovarian tumors. At 9 months of age, circulating levels of luteinizing hormone (LH) and follicle-stimulating hormone (FSH) were higher in the SL/Ni animals than in controls while prolactin (PRL) was lower in the SL/Ni mice. The trends of these hormones are consistent with the loss of the follicular apparatus which is responsible for estradiol production. The high levels of gonadotropins which precede the onset of the tumors confirm the hypothesis that prolonged stimulation by gonadotropins can be a cause of ovarian tumorigenesis. Further, these data suggest that aging of the reproductive system may be a thymus-dependent phenomenon.

Aging↗
PubMed1988

Absence of teratogenic effects of progesterone on the developing genital tract of the human female fetus.

It has been questioned whether prenatal exposure to progesterone, like exposure to diethylstilbestrol (DES), results in teratogenic abnormalities of the upper and lower genital tract in human females. Through the use of a recently described model in which human fetal reproductive tracts can be transplanted and grown in vivo for extended periods in athymic nude mice, genital tracts from human female fetuses, ages 7 to 18 weeks postovulation, were grafted into castrated murine hosts and grown for 4 to 10 weeks in the presence or absence of continuous exposure to progesterone. Substantial growth was observed. For all specimens, the morphogenetic process proceeded normally, resulting in the harmonious organization of a complete, well differentiated genital tract composed of fallopian tubes, uterine corpus, and cervix and vagina. The fallopian tubes were highly convoluted and disclosed fimbria. The uterine corpus was lined by a simple columnar epithelium; two layers of stroma in the wall were distinctly separated from each other. In the older specimens, the outer layer of stroma had assumed microscopic properties diagnostic of smooth muscle (myometrium). In the majority of specimens the region of the cervix/vagina disclosed the development of a fornix-like evagination at which point or slightly cranially there was a gradual but defined transition from columnar epithelium to squamous epithelium. The inner layer of endometrial stroma tapered and disappeared at or close to the squamocolumnar junction. The vaginal stroma was a single homogeneous layer and was continuous with the myometrium of the uterine corpus. In the context of this model system, prenatal exposure of the developing human female genital tract of progesterone was not associated with any obvious teratogenic effects.

Animals↗
PubMed1988

Low tumorigenic response to 3,2'-dimethyl-4-aminobiphenyl administration in the prostate of rats castrated at birth.

Six-week-old rats which had been orchiectomized at birth were given 3,2'-dimethyl-4-aminobiphenyl (DMAB) at various doses combined with a stimulus to prostate epithelial cell proliferation in the form of oral administration of methyltestosterone (MT) for 4 weeks. Thereafter MT treatment was continued or the animals received subcutaneous implants of testosterone propionate (TP) and were maintained until sacrifice at week 60. Although prostatitis and prostatic enlargement were frequently observed, especially in the TP group, numbers of atypical hyperplastic lesions were low and only one prostatic carcinoma in situ developed. Thus, despite the presence of proliferation, castration brought about a significant reduction in susceptibility to DMAB.

Aminobiphenyl Compounds↗
PubMed1988

Immunological abnormalities in human interleukin-2 or interleukin-2/interleukin-2 receptor L chain transgenic mice.

We constructed two strains of transgenic mice that carry the cDNA of either human interleukin-2 (IL-2) or the L chain of its receptor under the control of the H-2Kd promoter. The IL-2 transgenic mice expressed human IL-2 mRNA in the thymus, spleen, bone marrow, lung, muscle, and skin. Human IL-2 protein was also detected in their sera. The IL-2 transgenic mice suffered from dermatitis and pneumonia. Immune responses of their spleen cells against antigens were significantly impaired whereas their spleen cells responded well to polyclonal lymphocyte activators, suggesting that constitutive expression of IL-2 might have affected the repertoire formation of T cells in the mice. The IL-2 receptor (IL-2R) transgenic mice were healthy. We crossed the IL-2 and IL-2R transgenic mice to yield hybrid mice expressing both the ligand and the receptor constitutively. The life span of the hybrid mice was remarkably shortened. In addition to several abnormalities found in the IL-2 transgenic mice, spleen cells of the hybrid mice showed the strong natural killer activity which was ascribed to a large number (18%) of Thy-1+/CD3-cells unique to their spleen.

Animals↗
PubMed1987

Self tolerance and localized autoimmunity. Mouse models of autoimmune disease that suggest tissue-specific suppressor T cells are involved in self tolerance.

Autoimmune diseases appeared frequently in adults in the prostate and stomach of C3.129 mice after thymectomy on day 3 (Tx-3) without any additional treatment. Lesions of both organs could be completely prevented by a single i.p. injection of spleen cells from syngeneic adult mouse on day 4. For prevention of prostatis, the most effective cell source was normal males (4 X 10(6); normal females or Orx-0 males were less effective as the cell source, and higher doses of cells (4 X 10(7)) were needed. In contrast, spleen cells (4 X 10(6)) from these three donors had equivalent capacity for the prevention of gastritis. Similar autoimmune prostatis developed at very high frequency when spleen cells (4 X 10(6)) from normal females or Orx-0 males, but not from normal males, were injected i.p. into C3.129 nu/nu mice at 4 d. However, no sign of prostatis was found in nu/+ recipients. Injection of a larger dose (4 X 10(7)) from the same donors was not effective for induction of prostatis. Gastritis could not be induced in nu/nu mice by this procedure. Injection of spleen cells from Tx-3 males or females was effective for induction of both prostatis and gastritis in nu/nu recipients. It was also shown that a T cell population (Thy-1.2+, Ig-) had the capacity to prevent and to induce autoimmune diseases. These results together strongly suggest a role for active tissue-specific suppressor T cells in self tolerance, and elimination of such T cell populations causes autoimmunity.

Animals↗
PubMed1987

Teratogenic effects of clomiphene, tamoxifen, and diethylstilbestrol on the developing human female genital tract.

The potential estrogenicity and teratogenicity of triphenylethylene antiestrogens were examined in 54 genital tracts isolated from 4- to 19-week-old human female fetuses and grown for 1 to 2 months in untreated athymic nude mice or host mice treated by subcutaneous pellet with the antiestrogens clomiphene and tamoxifen or the synthetic estrogen diethylstilbestrol (DES). In specimens grown to a gestational age equivalent of 15 weeks or less, the vagina and urogenital sinus were lined by an immature squamous epithelium, which were similar in both drug-treated and untreated specimens. Proliferation and maturation of the squamous vaginal epithelium were observed in specimens treated with clomiphene, tamoxifen, or DES only when grown to a gestational age equivalent of 16 weeks or more. Formation of endometrial and cervical glands proceeded in 87 per cent (13 of 15) of control specimens grown to a gestational age equivalent of 13 weeks or more in untreated hosts. By contrast, age-matched drug-treated specimens contained glands in only 44 per cent (12 of 27) of specimens. In the developing uterine corpus of untreated controls, the uterine mesenchyme segregated into inner (endometrial stroma) and outer (myometrial) layers; whereas in drug-treated specimens, condensation and segregation of the mesenchyme were greatly impaired. The fallopian tube was also affected by clomiphene and tamoxifen (and to a lesser extent by DES) in that its epithelium was hyperplastic and disorganized. The complex mucosal plications characteristic of the fallopian tube were also distorted in drug-treated specimens. These results emphasize the heretofore unrecognized estrogenicity and potential teratogenicity of triphenylethylene antiestrogens on the developing human genital tract and emphasize the need for caution to prevent inadvertent exposure of the developing fetus to these compounds.

Abnormalities, Drug-Induced↗
PubMed1987

Reproductive tract lesions in male mice treated neonatally with tamoxifen.

Male mice of the NMRI/Tg strain were treated with tamoxifen for the first 3 days after birth. The affected mice were sterile, with multiple reproductive tract lesions. These lesions included testicular hypoplasia, intraabdominal testes, epididymal cysts, and squamous metaplasia of accessory glands.

Animals↗
PubMed1987

Thymic epithelial reticular cell subpopulations in mice defined by monoclonal antibodies.

Thymic epithelial reticular cells (TER) are heterogeneous cell populations. Of 14 rat monoclonal antibodies (moAbs) raised against established cell lines of mouse thymic stromal cells (TSC), two were found to recognize TER subpopulations that exhibited distinct intrathymic distributions. MoAb B6TS-1 (IgG2a) recognized the cell-surface determinant mB6TS-1 on TSC in the subcapsular zone, cortico-medullary junction, and medulla. Double staining with antikeratin antiserum showed that, except in the cortex, the distribution of mB6TS-1 bearing cells highly corresponded with that of keratin-positive TER indicating that mB6TS-1 within the thymus was selectively expressed in a particular subpopulation of epithelial cells. Immunoelectronmicroscopy revealed clear polarity in the expression of mB6TS-1 on TER. In the subcapsular zone. TER adherent to fibrous capsule expressed mB6TS-1 on the cell surface that faced the lymphocytes. In the cortico-medullary junction, mB6TS-1 also was found on the side of the TER closely associated with the small blood vessels. The mB6TS-1-bearing cells in the medulla characteristically had cytoplasmic infoldings containing collagen fibrils and amorphous material but did not exhibit the polarity of mB6TS-1-bearing cells. The mB6TS-1-bearing TER were interconnected by desmosomes and tonofilaments, therefore, were easily distinguished from macrophages, dendritic cells, and other components of thymic stroma. In contrast, another moAb AKTS-1 (IgM) stained the keratin-positive TER localized in the subcapsular zone and cortex forming a fine meshwork but did not stain those in the medulla. MoAb B6TS-1 stained thymic nurse cells but not the central cells of thymic rosettes, whereas moAB AKTS-1 did neither. Formation of lymphoid-stromal cell complexes in vitro was not affected by either antibody.

Animals↗
PubMed1987

Reorganization of thymic microenvironments during development and lymphomagenesis.

Modulation of thymic microenvironments during ontogeny and lymphomagenesis in mice was studied with two rat monoclonal antibodies (moAb) which recognized distinct subpopulations of thymic epithelial reticular cells (TER). In adult thymus, the TER subpopulation stained by moAb B6TS-1 was localized in the subcapsular zone, cortico-medullary junction, and medulla. In fetal thymus, it was initially distributed throughout the rudiment, but after day 16 of gestation, it was rapidly redistributed to the locations seen in adult thymus. From an early stage of thymic lymphomagenesis, the TER bearing mB6TS-1 (epitope defined by moAb B6TS-1) in the cortico-medullary junction, in particular those associating with small blood vessels, proliferated and formed a characteristic network throughout the thymus, in which numerous growing lymphoma cells were entrapped. On the other hand, moAb AKTS-1 stained another TER subpopulation that was localized in the cortex in both fetal and adult thymus. Unlike mB6TS-1+ TER, mAKTS-1+ TER became increasingly sparser during lymphomagenesis. Selective proliferation of the mB6TS-1+ TER subpopulation in the cortico-medullary junction was seen in spontaneous, radiation-induced, and chemical-induced mouse thymic lymphomas. The possible biological significance of such modulation of thymic microenvironments in the natural history of lymphomagenesis is discussed.

Animals↗
PubMed1986

Development of multiple organ-localized autoimmune diseases in nude mice after reconstitution of T cell function by rat fetal thymus graft.

Restoration of T cell function of athymic BALB/c nu/nu mice was investigated after transplantation of xenogeneic thymic rudiments from 15-d-old embryonic rats into kidney subcapsule. The rudiments developed well and formed a proper thymus structure composed of donor epithelia and host lymphocytes. Examination of antibody responses to SRBC revealed that approximately half the normal number of indirect PFCs were observed. Skin grafts from syngeneic BALB/c mice and thymic donor rat strains were accepted, whereas those from allogeneic mice and the rats of other than donor strains were vigorously rejected. Thymus-grafted nude mice under a conventional environment survived without any evident infectious diseases. Histological and immunofluorescence studies, however, showed a high incidence of multiple organ-localized autoimmune diseases in thyroid, salivary gland, stomach, adrenal, prostate, ovary, and testis in mice that produced the corresponding autoantibodies. These results together suggested that rat thymic grafts reconstituted T cell functions of nu/nu mice to a considerable degree, but that organ-localized autoimmune diseases developed, probably because certain auto-antigens of the recipients were recognized by the newly reconstituted host immunity.

Animals↗
PubMed1986

Expression of nuclear estrogen-binding sites within developing human fetal vagina and urogenital sinus.

An autoradiographic study of nuclear estrogen binding was performed in developing human urogenital sinuses and vaginas derived from first and second trimester specimens. Nuclear estrogen binding was detected in all specimens greater than or equal to 10 weeks of gestation within mesenchymal cells. Nuclear labelling within epithelium was observed only in those specimens whose development and differentiation was advanced. Thus, mesenchyme appears to be the initial estrogen target tissue within the developing human vagina and may play a fundamental role in estrogen-induced teratogenesis of the human genital tract.

Autoradiography↗