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Biomedical subjects

R M Shah

Publications and source records attributed to R M Shah.

At least 73 records · Page 4Linked to original sources

Ultrastructural and cytochemical observations on 5-fluorouracil-induced cleft-palate development in hamster.

Sequential alterations in 5-fluorouracil-treated hamster fetal palate were studied by light and electron microscopy and by acid phosphatase cytochemistry. At an early stage in 5-fluorouracil-treated fetuses, when the palatal shelves were vertical, lysosomes first appeared in cells of the prospective fusion epithelium and then in the cells of subjacent mesenchyme. In contrast to controls, increasing numbers of both the epithelial and mesenchymal cells of the vertical palate showed lysosomal injury in 5-fluorouracil-treated fetuses as development progressed. Subsequently, the basal lamina in the vertical palate showed alterations, characterized initially by disturbances in lamina lucida, by fingerlike extensions of lamina densa, and ultimately by its complete breakdown. At a later stage, when shelves became horizontal, the lysosomes were absent in both the epithelial and mesenchymal cells, and the basal lamina continuity was restored. Unlike controls, however, 5-fluorouracil-treated horizontal shelves never contacted one another. Instead, the epithelia of the horizontal shelves underwent stratification. It appears that premature formation of lysosomes in palatal epithelial and mesenchymal cells following 5-fluorouracil treatment disrupts normal cytodifferentiation and affects the integrity of the basal lamina; both effects are associated with cleft-palate development.

Acid Phosphatase↗

Differentiation of the avian secondary palate.

The avian secondary palate exhibits the unique feature of a midline cleft. Cryostat sections indicated that although extensive contact between homologous shelves was present, chick palatal medial edge epithelium (MEE) failed to fuse. The failure of fusion and subsequent clefting of the avian palate were correlated with continued proliferation of the avian MEE, a failure of selective MEE cell death, and an absence of elevated levels of intracellular cAMP. Moreover, immunohistochemical staining for cAMP and microspectrophotometric quantitation of staining intensity indicated that staining of chick MEE was significantly (p less than .01) less than murine MEE at comparable gestational ages. These data indicate that differentiation of the avian secondary palate is fundamentally different than reported for the mammalian palate in that many developmental events known to be associated with normal mammalian palate formation (cessation of MEE proliferation, MEE cell death, elevated levels of MEE cAMP) fail to occur in the chick. The developing avian secondary palate, with its midline cleft, thus provides an interesting and useful model system with which to compare mammalian palate formation where the palate is normally fused in the midline.

Animals↗

A35512, a complex of new antibacterial antibiotics produced by Streptomyces candidus. I. Isolation and characterization.

The new antibiotic complex A35512 produced by Streptomyces candidus was isolated from the filtered fermentation broth. The individual factors A, B, C, E, and H were separated and purified by column chromatography. A35512B, the major factor, was isolated as the dihydrochloride salt, a white crystalline compound with an approximate empirical formula of C90H101 N8O39Cl.2HCl. The A35512 antibiotics belong to the glycopeptide class of antibiotics and possess high in vitro and in vivo activity against Gram-positive bacteria.

Anti-Bacterial Agents↗

Morphological study of cleft palate development in 5-fluorouracil-treated hamster fetuses.

Morphogenesis of palate was studied in normal and 5-fluorouracil-treated hamster fetuses. The results showed that normal palatal development was completed between days 12 and 13 of gestation. In 5-fluorouracil-assaulted palate the reorientation of shelves from a vertical to horizontal plane was delayed. Crown-rump length, gestational age and fetal weight were reliable predictors of the stages of normal palatal development, whereas the morphological rating system was not. Following 5-fluorouracil treatment, however, crown-rump length, weight and morphological rating were poor indicators of the stage of palatal development.

Abnormalities, Drug-Induced↗

Developmental abnormalities induced by 6-mercaptopurine in the hamster.

Pregnant hamsters were given varying doses of 6-mercaptopurine (6MP) at various times during gestation. The fetuses were examined for both gross and histological malformations which showed that the toxic and teratogenic effects of 6MP were dose and time dependent. The most severe gross malformations induced by 6MP were cleft palate, micrognathia and agnathia, microglossia, short limbs, and gut herniation. Grossly normal appearing fetuses, greated during late gestation, showed malformations at the tissue and cellular level. The effects of 6MP in hamster was compared with other species, and with other growth-supressive agents, and it was deduced that the teratogenicity of 6MP is species and tissue specific. Also, it was recommended that histological observations be made an integral part of the teratological safety analysis.

Abnormalities, Drug-Induced↗

Teratogenic effects of diazepam in the hamster.

Pregnant hamsters were treated with different doses of oral and intravenous diazepam during the period of organogenesis. Teratogenic effects of diazepam were observed following oral treatment on days 8 and 10 and following intravenous treatment on day 11 of gestation. Types of malformations included cleft palate, exencephaly, limb anomalies, and hemorrhage. A dose-effect relationship was not observed. Comparison with reported literature seems to indicate that diazepam may be a mild teratogen in some species.

Abnormalities, Drug-Induced↗

The effects of nitrous oxide on the developing hamster embryos.

Pregnant hamsters were exposed to different concentrations of nitrous oxide during the period of organogenesis. Teratogenic effects were observed in a small but significant number of fetuses. Types of malformations included cleft palate, limb defects, gut herniation, and fetal edema. A dose-effect relationship was not observed. It is not clear from our observations whether the observed effect on the fetuses was due to the excess of nitrous oxide, hypoxia, or a combination of both. Comparison with published literature indicates that further studies on the effects of nitrous oxide in placental animals are needed.

Abnormalities, Drug-Induced↗

Light- and electron-microscopic observations on the closure of the secondary palate with the primary palate and the nasal septum.

Closure between the secondary palate and the primary palate and between the former and the nasal septum was studied in the Syrian golden hamster at light- and electron-microscopic level. Sequential changes in the epithelia before, during and after the closure of the primary and the secondary palate were described. A characteristic epithelial thickening was observed prior to epithelial fusion between the nasal septum and the secondary palatal shelf. Fusion of the opposing epithelia was characterized by formation of desmosomes. An unilateral or bilateral empty space was observed on each side of the epithelial seam, and it was suggested that this may represent the incisive foramen in the adult.

Animals↗

A cellular mechanism for the palatal shelf reorientation from a vertical to a horizontal plane in hamster: light and electron microscopic study.

Cellular and subcellular events during reorientation of the palatal shelf in hamster fetuses are described. An alteration in the morphology of the epithelial and the mesenchymal cells is observed during shelf realignment from a vertical to a horizontal plane. The mesenchymal cells elongate and subsequently appear to protrude in the medially bulging palatal shelf. Microtubules, microfilaments and close contacts are associated with elongation of the mesenchymal cells. The cells of the thickened epithelium may play a mechanical role in providing direction to the mesenchymal cells during palatal shelf reorientation. The altered morphology of the mesenchymal cells may be associated with the intrinsic shelf force implicit in Walker and Fraser's theory of palatal shelf reorientation.

Animals↗

Cleft palate development in hamster embryos following triamcinolone treatment.

Development of the palate was studied in normal and triamcionolone-treated hamster fetuses. The results demonstrated that normal palatogenesis was completed between days 12 and 13 of gestation. Following triamcinolone treatment the reorientation of the palatal shelves was delayed before there was any general retardation of fetal growth (as indicated by crown-rump length and body weight). Since triamcinolone affected palatogenesis at an earlier stage than hydrocortisone, the view that the former is a more potent teratogen was supported. Chronological age, fetal weight and crown-rump length were reliable predictors of normal palatogenesis in the hamster, whereas the numerical morphological rating systems were not. Neither measures of general fetal growth, nor numerical rating, were useful in predicting the stages of experimentally induced cleft palate, since triamcinolone appears to be site-specific, and the drug does not produce a general retardation of embryonic development.

Animals↗