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Biomedical subjects

T Iguchi

Publications and source records attributed to T Iguchi.

At least 163 records · Page 9Linked to original sources

Frequent occurrence of polyovular follicles in ovaries of mice exposed neonatally to diethylstilbestrol.

The occurrence of polyovular follicles (PF) was examined at 10-34 days of age in the ovaries of BALB/cCrgl female mice given five daily injections of 0.1 microgram diethylstilbestrol (DES), 2 micrograms DES, 100 micrograms progesterone (P), 137 micrograms 17 alpha-hydroxyprogesterone caproate (HPC), 20 micrograms testosterone (T), 20 micrograms 5 alpha-dihydrotestosterone (5 alpha-DHT), or oil vehicle alone starting on the day of birth, and of C57BL/Tw females given five neonatal injections of 1 microgram DES, 20 micrograms 17 beta-estradiol (E2), 50 micrograms 5 alpha-DHT, 50 micrograms 5 beta-DHT, or the vehicle alone. Ovaries of 30-day-old C57BL mice given five daily injections of 1 microgram DES starting at 3-25 days of age were also examined. PF incidence (% of PF per ovary) and PF frequency (% of mice with PF) were significantly greater in BALB/c mice receiving injections of DES, P, HPC, and T than in the controls. In DES-treated mice at 34 days, PF incidence (2-13 oocytes/follicle) was 120-340 times higher than in the controls. BALB/c mice treated with T, P, and HPC showed PF incidence (two to four oocytes/follicle) three- to six-fold higher than in the controls. In 30-day-old C57BL mice treated with T, E2, and DES, PF incidence also increased by two- to 50-fold. 5 alpha-DHT and 5 beta-DHT failed to increase PF incidence. PF incidence was significantly increased only when neonatal DES treatment was begun on days 0 to 3, but was reduced when started at days 10-25.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Polyovular follicles in the ovary of immature mice exposed prenatally to diethylstilbestrol.

Polyovular follicles (PF) occur in the ovary of 30-day-old offspring of ICR/JCL mice given 4 daily subcutaneous injections of 20-2,000 micrograms diethylstilbestrol (DES)/day from days 15 to 18 of gestation. PF containing 2-9 oocytes per follicle in the prenatally DES-exposed mice are increased 33- to 112-fold as compared to controls. In 5- to 25-day-old offspring of mothers given injections of 2,000 micrograms DES/day, PF are observed 17-65 times more frequent than in controls.

Aging↗

Estrogen participation in induction of cervicovaginal adenosis-like lesions in immature mice exposed prenatally to diethylstilbestrol.

A high incidence of vaginal adenosis-like lesions (ADL, 67%) was found in 30-day-old offspring of ICR/JCL mice given 4 daily subcutaneous injections of 2,000 micrograms diethylstilbestrol (DES) on days 15-18 of gestation. The prenatally DES-exposed mice and the controls ovariectomized at 10 days of age were given 5 daily subcutaneous injections of 10(-4), 10(-3), 10(-2), 10(-1), or 1 micrograms 17 beta-estradiol (E2), respectively, starting at 25 days of age. ADL was never observed in the age-matched controls given prepubertal injections of any E2 dose. In contrast, high incidences of ADL (63-100%) were found in the vaginal fornix and upper vagina of 30-day-old DES mice receiving prepubertal injections of 10(-3)-1 micrograms E2/day, whereas in DES mice given prepubertal injections of the vehicle alone and a lower daily dose of 10(-4) micrograms E2, incidences were nil and 25%, respectively. Mitotic figures were found in the columnar epithelium with ADL, although the rate was lower than in the ADL-freed stratified epithelium. It is suggested, therefore, that an ovarian hormone (probably estrogen) participates in the prepubertal induction of ADL in DES mice.

Animals↗

Electron microscopic study of rheumatoid synovial vasculature. Intimate relationship between tall endothelium and lymphoid aggregation.

The relationship between (a) "tallness" and (b) cross-sectional area of the endothelial cells (EC) of postcapillary venules (PCV) and capillaries and the cellular composition of adjacent perivascular mononuclear cell infiltrates in rheumatoid (RA) synovial membrane has been examined by electron microscopy. "Tallness" of the EC was measured as the ratio of the height of the EC to its base (H/B). H/B showed a strong positive correlation with the number and percent of perivascular lymphocytes, i.e., the denser the lymphoid aggregation, the taller the EC. In contrast, H/B showed negative correlations with percent perivascular plasma cells, macrophages, and fibroblast(cyte)s. No such correlations were observed with pericapillary infiltrates. A computer-based morphometric technique yielded similar relationships between the cross-sectional area of the EC and the composition of the perivascular infiltrates. These results indicate that the EC of PCV in lymphocyte-rich areas of synovium tend to be tall and to occupy an increased fraction of the cross-sectional area of the vessel. In contrast, in areas rich in macrophages and plasma cells, EC tend to be flat and to occupy a smaller fraction of the cross-sectional area. PCV in uninfiltrated interstitial areas and in normal synovium had flat EC, and capillaries had flat EC regardless of the character of the surrounding infiltrate. Finally, PCV in lymphocyte-rich areas closely resembled those of tonsil in appearance. Our findings indicate that the PCV of the RA synovial membrane from which lymphocytes emigrate to form perivascular lymphoid aggregates resemble those of lymphoid tissue. They suggest that chronic inflammatory tissue and normal lymphoid tissue share mechanisms of lymphocyte emigration.

Arthritis, Rheumatoid↗

Development of vaginal adenosis-like lesions and uterine epithelial stratification in mice exposed perinatally to diethylstilbestrol.

Pregnant ICR/JCL mice were given either four daily subcutaneous injections of 20-2000 micrograms diethylstilbestrol (DES)/day or a 4-day intravenous infusion of 20-200 micrograms DES/day starting on Day 15 of gestation. Female mice were injected with 0.01-50 micrograms DES/day for 5 days starting on the day of birth. Females given oil injections during the neonatal period and offspring of mothers given injections of an infusion of respective vehicles alone served as controls when corresponding ages were attained. Incidence of adenosis-like lesions (ADL) in the vaginal epithelium and stratification of the uterine epithelium (UST) were determined in both offspring and neonatally exposed mice at 30 days of age. Injections of 0.1-50 micrograms DES/day during the neonatal period induced ADL in the fornical epithelium of vagina (36-70%), but not UST. A high incidence of ADL (80-88%) was found in the fornical and upper-vaginal epithelia in offspring of mothers given injections of 200-2000 micrograms DES/day, and UST was encountered in 38-70% of these mice. Offspring of mothers given an infusion of 20 micrograms DES/day had low incidences of ADL (11%) and UST (22%), whereas offspring of mothers infused with 200 micrograms DES/day exhibited high incidences of ADL (71%) and UST (86%). In offspring of mothers given injections of 2000 micrograms DES/day, ADL appeared in the fornical and upper-vaginal epithelial as early as 15 days of age. Thus, the present study revealed that ADL and UST occur at a high incidence in infantile mice exposed prenatally to high doses of DES. Previous studies failed to detect such effects perhaps due to the strain of mice, methods, duration, and/or dose of DES used.

Animals↗

Prevention by vitamin A of the occurrence of permanent vaginal and uterine changes in ovariectomized adult mice treated neonatally with diethylstibestrol and its nullification in the presence of ovaries.

Permanent proliferation and cornification of the vaginal epithelium occurred in adult ovariectomized (OVX) mice which had received neonatal injections of 5 micrograms diethylstilbestrol (DES). Occurrence of the permanent epithelial proliferation was prevented by injections of 200 IU vitamin A acetate (VA) given simultaneously with neonatal DES-treatment in mice when OVX at 30 days of age, but not in those OVX at 270 days. For the suppression of the permanent vaginal changes, however, more than one month were required after DES plus VA-treatment. In DES plus VA-treated OVX (at 30 days) mice, the vaginal epithelium indicated a lower mitotic rate than in DES-treated OVX mice. Clear cells were found in the degenerating vaginal epithelium in 63% of DES plus VA-treated OVX mice, while in the proliferated epithelium, this type of cells appeared only in 10% of DES-treated OVX mice. In 40% of 180-day-old, DES-treated OVX (at 30 days) mice, permanent stratification took place in the uterine epithelium, while it was inhibited in the age-matched DES plus VA-treated OVX mice. However, the uterine change was not prevented in 310-day-old, DES plus VA-treated mice when OVX at 270 days. This findings suggests that the relatively long-term presence of ovaries nullifys the inhibitory effect by VA on the occurrence of permanent changes in the utero-vaginal epithelium induced by neonatal DES treatment.

Animals↗

Changes in gonads of male and female offspring of mice receiving a continuous intravenous infusion of human chorionic gonadotropin during gestation.

In male offspring of mice given a continuous intravenous infusion of 24 IU/day hCG from days 15 to 19 of gestation (hCG-primed mice), the number of Leydig cells/testis at 15 days of age was similar to the value at 10 days, whereas the cells were decreased in number in the controls at 15 days. Mitotic rate of the interstitial tissue in 30-day-old, hCG-primed mice was lower than in the controls. In seminiferous tubules of hCG-primed mice, intratubular spaces were formed at 15 days, while the spaces in the controls were observed at 30 days. Various disorganization of the germinal epithelium occurred in some tubules of hCG-primed mice at 30-90 days. Spermatogenesis was impaired in the damaged tubules. Female hCG-primed mice showed a slightly longer estrus (24 IU/day), a higher frequency of estrus and larger number of total estrus days (120 IU/day) than those in the controls. Ovaries of 160-day-old, hCG-primed mice (24 IU/day) contained normal follicles more than those in the controls. Corpora lutea decreased in number in both groups of hCG-primed mice, showing a lower corpus-luteum occupancy. These findings suggest the occurrence of a slight degree of persistent-estrus syndrome in hCG-primed female mice.

Animals↗

Induction of abnormal epithelial changes by estrogen in neonatal mouse vaginal transplants.

Adenosis occurred in transplanted C57BL and BALB/c mice Müllerian-derived reproductive tract regions, cervix, and/or fornix (FX), and middle vagina but never in the urogenital sinus-derived portion of the vagina, after a 1-mo exposure to endogenous ovarian hormones or exogenous estradiol (E2). Grafts in ovariectomized hosts did not exhibit adenosis, confirming its dependence on estrogen. C57BL FX and midvaginal transplants from 1-, 3-, and 5-day-old donors but not from 7- or 10-day-old donors developed adenosis, indicating a critical period before day 6. Prolonged E2 exposure (to 2 mo) decreased the adenosis incidence observed in the C57BL FX group but not in midvaginal transplants. Progesterone added during the second half of transplantation to continuing exogenous E2 prevented this reduction in the FX group; however, adenosis incidence in the similarly treated middle vagina group was less than that observed after 1 or 2 mo of E2 treatment alone. Progesterone present throughout the 2-mo transplantation period did not significantly affect adenosis incidence induced by 2-mo exposure of midvaginal or FX grafts to E2 alone. Changes suggestive of squamous cell carcinoma were found in a few BALB/c midvaginal grafts after E2 exposure for 1 mo and in some C57BL midvaginal and FX grafts after E2 and progesterone exposure for 2 mo.

Animals↗

Comparative study of blocking effects of various retinoids on the occurrence of permanent proliferation of vaginal epithelium in mice treated neonatally with estrogen.

Neonatal injections of 20 micrograms 17 beta-estradiol (E2) induced persistent proliferation and cornification of the vaginal epithelium in adult ovariectomized C57 Black/Tw mice. However, permanent vaginal changes were prevented by various retinoids when, simultaneously with E2 treatment, the animals were given injections of 100 micrograms daily dose of retinol, retinol acetate, retinal or of 200 micrograms daily dose of retinol palmitate (RoP). Neonatal injections of a 100 micrograms daily dose of RoP had no preventive effect on the occurrence of E2-induced permanent vaginal changes. This finding suggests that the preventive effect of RoP is weaker than that of other retinoids showing approximately the same degree of prevention. Combined treatment with E2 plus retinoic acid (even a small dose of 20 micrograms) had such a toxic effect on newborn mice that they died within 7 days after birth, while the animals given neonatal injections of 20 micrograms retinoic acid alone survived until the termination of the experiment.

Animals↗

Origin of permanently altered epithelial cells of the vagina in neonatally estrogen-treated mice.

In adult mice, neonatal injections of estrogen induce persistent, estrogen-independent cornification of the vaginal epithelium. Since the occurrence of nodules composed of affected epithelial cells (B cells) is a prodromic phenomenon of the irreversible vaginal alterations, the relationship between the occurrence of B-cell nodules and the time of DNA synthesis in the vaginal epithelial cells was examined by means of the techniques of serial mapping and autoradiography. B-cell nodules appeared in the epithelium of mullerian vagina 3-5 days after the initiation of neonatal estrogen treatment, without spatial continuity to cuboidal epithelial cells of the sinus vagina. The time of DNA synthesis was different in B cells from that in both columnar mullerian and cuboidal sinus cells, suggesting that the mother cells of B cells might be a population of still unidentified, undifferentiated cells.

Animals↗

Growth of normal mouse vaginal epithelial cells in and on collagen gels.

Sustained growth in primary culture of vaginal epithelial cells from ovariectomized adult BALB/cCrgl mice embedded within or seeded on collagen gel matrix was achieved in a serum-free medium composed of Ham's F-12 medium/Dulbecco's modified Eagle's medium, 1:1 (vol/vol), supplemented with insulin, bovine serum albumin fraction V, epidermal growth factor, cholera toxin, and transferrin. Three-dimensional growth of vaginal epithelial cells occurred inside the collagen gel matrix. Cell numbers increased 4- to 8-fold in collagen gel and about 4-fold on collagen gel after 9-10 days in culture. The effect of 17 beta-estradiol (0.00018-180 nM in gel or 0.018-180 nM on gel) and diethylstilbestrol (DES; 0.0186-186 nM in gel) on the growth of vaginal epithelial cells was examined. The addition of estrogen did not enhance the growth of vaginal epithelial cells during this time period either in the complete medium or in a suboptimal medium. Cultures on floating collagen gels in the serum-free medium are composed of 1-3 cell layers with superficial cornification. Estrogen does not appear to be a direct mitogen for vaginal epithelial cells, at least in this system.

Animals↗

Antitumor activity of 2-keto-3-deoxyoctonate-free lipopolysaccharide of Vibrio anguillarum in mice.

The antitumor activity of a marine bacterium, Vibrio anguillarum, against Ehrlich carcinoma cells in ddY mice was investigated. The aqueous layer obtained by the hot phenol-water procedure exhibited more antitumor activity than did the middle layer or the phenol layer. This finding indicates that lipopolysaccharide (LPS) derived from V. anguillarum exhibits significant antitumor activity. In fact, mice injected with LPS obtained by ultracentrifugation and treatment with RNase had a longer mean survival period than the control mice. V. anguillarum LPS also inhibited the growth of syngeneic fibrosarcoma induced by 3-methylcholanthrene in C57BL/6 mice. V. anguillarum LPS possesses no 2-keto-3-deoxyoctonate, a regular sugar component of the core region of most gram-negative bacterial LPS, suggesting that 2-keto-3-deoxyoctonate is unnecessary for the antitumor activity of LPS.

Animals↗