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Biomedical subjects

R S Tulsi

Publications and source records attributed to R S Tulsi.

At least 19 recordsLinked to original sources

The teratogenic effects of salicylic acid on the developing nervous system in rats in vitro.

Aspirin ingestion in humans and animals has been reported to lead to a range of undesirable outcomes, including fetal death, growth retardation, and congenital abnormalities. Rat embryos were cultured for 48 h in 100-300 micrograms/ml of salicylic acid, a metabolite of aspirin, days 9.5-11.5 of gestation. When compared to growth in control embryos, a significant dose-dependent decrease in crown-rump lengths, somite numbers, and yolk sac diameters was observed. There was also a significant increase in overall dysmorphology, including eye, brachial arch, and heart anomalies, and an absence of forelimb buds. The neural tube was especially vulnerable and had frequently failed to close. Cellular and ultrastructural examination revealed extensive cell death in the neuroepithelium, with a lesser effect on the mesenchymal cells. Large condensed blebs projected into the ventricular lumen, and cell membranes as well as the basal lamina were severely disrupted, with all cytoplasmic organelles affected in dying cells. It is likely that the extensive cell necrosis and blebbing in the developing neuroepithelium at the site of neural tube fusion may be involved in failed neurulation, while necrosis at other sites in the cranial neuroepithelium may be linked with previously reported intellectual and behavioural abnormalities.

Abnormalities, Multiple

A study of the angle of inclination and facet curvature of superior lumbar zygapophyseal facets.

The angle of inclination and depth of curvature of L1-L5 of the superior articular facets of both sexes were measured in 112 lumbar spines. In addition to standard statistical methods data were also analyzed to show various degrees of departure from the "normal." The L3 vertebra showed the least variation and L5 and L1 showed the most. The angle and depth of L1 to L5 showed a small, albeit statistically significant, difference between the two sexes but no laterality differences were apparent. At L1 12.5% of males and 10.4% of females revealed an asymmetry of angle exceeding 20, and at L5 3.1% of males and 1.7% of females showed such tendency. An asymmetry of the depth of curvature of the articular facets exceeding 1.5 mm was recorded in 12.5% of males and 8.3% of females at L1 and 6.5% of males and 2.1% females at L5. The expected values of depth of curvature were lowest at L1 and highest at L3 and L4. It is suggested that a more quantitative approach to the study of the zygapophyseal joint would enhance precision and facilitate meaningful interlaboratory comparisons of published data.

Adult

A quantitative and morphological study of ectodermal microvilli in ten areas in the control and experimental prenatal rat.

This study provides a baseline of mainly quantitative morphologic information in relation to the ectodermal microvilli in ten areas in the control and experimental prenatal rat with special reference to the period of neural tube closure. Embryos from six litters were used and ten areas were examined mainly with the scanning electron microscope. Statistical analysis showed no significant difference between litters nor between the ten areas examined. In the 376 hr (day 15.6) fetus only the ectodermal cells of the nostril region demonstrated a rich population of microvilli, a fact possibly associated with late maturation of that region. Some evidence is provided to show that there is an increase in the population of microvilli in the 276 hr (day 11.5) embryo following experimentally induced zinc deficiency and introduction of nicotine in the culture medium. The possible mechanisms underlying the increase in ectodermal microvilli are i) an attempt by ectodermal cells to absorb nutrients, ii) a reflection of cells under stress, iii) failure of early embryonic ectodermal cells to shed microvilli normally associated with developmental changes, and iv) a generalized developmental delay rather than some cellular response to a trace element nutritional deficiency and a teratogen.

Animals

Zinc deficiency in the 11 day rat embryo: a scanning and transmission electron microscope study.

Zinc deficient rat embryos were obtained on the 11th day of pregnancy and examined by scanning and transmission electron microscopy. Scanning electron microscopy revealed an increase in the number of deformed embryos, as well as embryonic growth retardation. In addition, the epithelium of zinc deficient embryos displayed a marked increase in surface microvilli, as well as the presence of blebbing. Transmission electron microscopy indicated extensive cell death in the neural epithelium which was apparently more severely damaged by zinc deficiency than were mesenchymal cells. Mitochondrial cristae were affected to a greater degree than any other membrane of the cell and cristael disintigration appeared to represent the principal cellular lesion preceding necrosis of neural cells and neural tube teratology.

Animals

A quantitative and qualitative study of craniofacial development in the rat embryo aged 302 hours to 374 hours (days 12.5 to 15.5).

One-hour mated Sprague-Dawley rats underwent a normal pregnancy, which was terminated at hours 302, 326, 350, and 374. After appropriate processing and scanning electron microscopy of the embryos, absolute measurements of the craniofacial area, especially of the snout, maxillary process, eye, lower face, and brain were taken in the 302- and 326-hr embryos. Additionally, growth ratios were established in all stages. The greatest growth and developmental changes occurred between 302 and 326 hr, when 1) the snout developed from the nasal anlagen and the maxillary process, 2) the eye lens replaced the eyepit, and 3) the hindlimb developed. Between 326 and 350 hr, the optic pit developed. The results of the present study can markedly enhance precision in interpretation of results of teratological studies in the rat. The detailed quantitative data established allow reporting of subtle departures from the normal hitherto impossible.

Animals

Maternal metabolism and teratogenesis in zinc-deficient rats.

Embryos removed at 11.5 days gestation from pregnant rats allowed a zinc-deficient diet from the time of mating showed a high frequency of malformations of all organ systems. There were, however, large differences between litters of individual dams. Comparison of the daily food intake of zinc-deficient dams with the appearance of the embryos suggested that fluctuations in the maternal serum zinc levels induced by feeding or fasting influenced the availability of zinc to the embryos. By cyclically feeding zinc-deficient dams to a predetermined schedule, low maternal serum zinc levels were induced at selected stages of development. This was accompanied by specific malformations of the organs developing at that time.

Abnormalities, Multiple

Cellular necrosis in zinc-deficient rat embryos.

Abnormal cellular necrosis was studied in 9.5-11.5-day embryos obtained from zinc-deficient rats. At periods of low maternal zinc status induced by a high intake of a zinc-deficient diet, cell death was observed in those regions of the embryo that were most sensitive to teratogenic insult at that time. As the maternal serum zinc level increased during the fasting phase of the feeding cycle, the degree of necrosis decreased, leaving the tissue histologically more normal even though the embryos were grossly malformed. The mitotic index of cells in the neural epithelium and limb buds of zinc-deficient, non-necrotic embryos was found to be elevated, but there was no evidence of blockage at any particular stage of mitosis. It can be hypothesised that during the early stages of organogenesis, periods of low maternal zinc status initiate unscheduled cell death by some as yet undefined mechanism that in turn, gives rise to the morphological anomalies observed later.

Animals

In vitro development of zinc-deficient and replete rat embryos.

The development of the zinc-deficient rat embryo has been studied in vitro using embryo culture techniques. Normal 9.5 day embryos cultured for 48 h in serum obtained from zinc-deficient rats grew and developed to the same extent as those cultured in zinc-replete serum. Embryos from dams which had been fed a zinc-deficient diet since mating were also removed for culture. Such zinc-deficient embryos fell into two broad morphological categories. One group appeared identical to the normal embryos, while the others had apparently normal visceral yolk sacs but small embryonic poles and retarded or abnormal embryonic development. Culture of the first group in either zinc-deficient or replete serum produced morphologically normal embryos; however, those which appeared abnormal at day 9.5 were grossly malformed after 48 h incubation in either sera. When embryos were cultured in the presence of 65Zinc, the most severely affected zinc-deficient embryos accumulated as much zinc as the zinc-replete and apparently unaffected zinc-deficient embryos, indicating that the malformations do not arise from an inability of the embryo or yolk sac to accumulate zinc from the surrounding fluid. The results from these studies suggest that the teratogenic effects of zinc deficiency cannot be induced by direct culture of zinc-replete embryos in zinc-deficient serum. Furthermore, it would appear that maternal zinc deficiency can exert its teratological influence prior to day 9.5 of gestation and that these effects are not readily reversible.

Abnormalities, Multiple

Persistent trigeminal artery: an anatomical study.

A detailed anatomical study of three persistent trigeminal arteries (PTA) is presented. In two cadavers the PTA linked the carotid and basilar systems by traversing the cavernous sinus and lying between the posterior clinoid process and the sensory root of the trigeminal nerve. In the third cadaver the PTA pierced the dorsum sellae and lay in the floor of the pituitary fossa. The potential clinical significance of the course and the possible pattern of blood flow in the vessels is discussed in the light of some recent clinical observations.

Aged

Neural elements associated with the subcommissural organ of the brush-tailed possum (Trichosurus vulpecula).

By means of various techniques and on the basis of a large sampling of the brush-tailed possum, Trichosurus vulpecula, a detailed description is given of the morphology of the neural elements associated with the subcommissural organ (SCO) and the leptomeninges on the dorsal surface of the midbrain. It is shown that the SCO of the possum is richly innervated, the nerves reaching the cerebral aqueduct by passing through the organ; there is, however, no evidence of a neural link between the SCO and the pineal gland. No typical axo-glandular synapses were found; however, many axo-glandular synaptoid junctions between axons and secretory cells of the SCO were demonstrable within the parenchyma of the SCO and on the aqueductal surface of the organ. The possible functional implications of the findings are: (1) The secretory activity of the SCO may be modified by nerves associated with it; this is in accord with some recently published experimental studies. (2) The nerves that innervate the SCO may also be responsible for ciliary activity on the aqueductal surface of the SCO, thus directing the apical secretory product of the SCO and debris flowing caudally in the cerebrospinal fluid into the poorly ciliated median groove where Reissner's fibre is found.

Animals

Architecture of the basal region of the subcommissural organ in the brush-tailed possum (Trichosurus vulpecula).

The architecture of the basal region of the subcommissural organ (SCO) and the subjacent neuropil was studied in the brush-tailed possum, Trichosurus vulpecula (Marsupialia). Several structural features suggest that the basal mode of SCO-secretion may be as prominent as the well-established apical secretion. Some of the features that speak in favour of basal secretion are: (1) the existence of deep processes of secretion-laden SCO cells which reach and surround the capillaries in the hypendyma and the subjacent neuropil; (2) the presence of perivascular spaces, some of which may contain a material that resembles the secretory product of the SCO; (3) positive staining by means of paraldehyde-fuchsin of secretory material in the pericapillary zone of vessels in the hypendyma and its corresponding neuropil; (4) presence of labyrinths of the basal lamina of capillaries and associated nerves. The presence of nerve and other cell processes adjacent to the perivascular space, labyrinths and capillary wall suggests discharge into the capillaries of material such as the basal secretory product of the SCO. However, the absence of fenestrae in capillary endothelium in the context of the foregoing observations is enigmatic and speaks against the possibility of a conventional release of secretion. Nevertheless, it is possible that a secretory product containing particles of low molecular weight combined with some specific features of the local capillary endothelium, which facilitate transport, may be critical factors making possible transfer of such product(s) from the SCO to the capillaries.

Animals

Reissner's fiber in the sacral cord and filum terminale of the possum Trichosurus vulpecula: a light, scanning, and electron microscopic study.

The ending of Reissner's fiber (RF) and structural features associated with gaps or fissures in the rostral part of the filum were investigated using light, scanning, and transmission microscopic techniques in young and mature possums of both sexes. To the best of the author's knowledge the report contains results of the first successful application of the SEM for a study of RF in the spinal cord. Some new observations suggest that while the bulk of RF is formed by the subcommissural organ and moved caudally, additional secretory products may be added by ependymal cells in the sacral and possibly other regions of the spinal cord. Evidence is provided in support of the view that RF may pass through gaps in the ependymal lining in the rostral part of the dorsal wall of the filum terminale and caudal end of the sacral cord to reach the periependymal loose tissue and possibly the subarachnoid space. The region of the gap shows the surface of the ependyma facing the lumen of the filum to be covered with microvilli and cilia, and to be in direct continuity with the external surface of the ependyma covered with basement membrane with glial processes and collagen fibers in close proximity. The present results confirm and extend observations reported by Wislocki et al. ('56).

Animals

Microsurgical reversal of the artificially induced hydrosalpinx in the rabbit - morphological studies.

Mechanical occlusion of the rabbit oviduct at 2 sites produces a hydrosalpinx which was found to be associated with a predictable degree of loss of cilia from the mucosal cells (deciliation). The morphological changes observed closely resemble the light and surface electron microscopic appearance of a human hydrosalpinx. Microsurgical reconstitution of the obstructed oviduct in oestrus rabbits produced almost complete reversal to normal mucosal morphology. This suggests that the morphological changes observed in the rabbit hydrosalpinx may be due to an increase in intraluminal pressure and that reduction of this pressure may effect a reversal to normal.

Animals

Epithelium of mouse yolk sac placenta lacks H-2 complex alloantigens.

The only fetal cell membrane exposed to the mother in the mouse yolk sac placenta is the apical membrane of the endodermal epithelial cells. In yolk sac preparations in vitro, this apical membrane was exposed to reagents or cells in the incubation medium. By using several techniques we were not able to detect fetal major histocompatibility complex (MHC) antigens in this membrane. Immunoferritin labeling with and without prefixation and after neurominidase and trypsin digestion indicated that the apical membrane could contain no more than approximately 1% of the H-2 complex antigens that were present on peritoneal macrophages. Incubation of yolk sac preparations in anti-H-2 complex antiserum and complement had no cytotoxic effect on the endodermal epithelium, nor did incubation in an excess of alloreactive lymphocytes. Dissociated preparations of prefixed yolk sac contained endodermal epithelial cells and vascular endothelial cells whose entire surface membranes were exposed to the medium. H-2-complex antigens were not detected by immunoferritin labeling in either the apical or the laterobasal membrane of the yolk sac endoderm, but they were present in low density on the vascular endothelium. Also, incubation of unfixed, dissociated cells in anti-H-2-complex serum and complement had no detectable cytotoxic effect on endodermal epithelial cells. These observations indicate that H-2 antigens are sparse or absent in both the apical and laterobasal membranes of endodermal epithelial cells. The deficiency of MHC antigens in the apical membrane may account for the failure of sensitized females to reject the yolk sac, whereas the composition of the laterobasal membrane is probably less important to maternal-fetal relations. The present observations are consistent with labeling studies of adult-lining epithelial cells, which indicate that self-marker MHC molecules are absent from the apical membranes oriented toward the outside world and variably expressed in the laterobasal self-side membranes. It is suggested that the corresponding exclusion of fetal self-marker molecules from the apical membranes of some kinds of placental epithelia would deprive the mother of target sites for an alloimmune reaction at the maternal-fetal interface.

Animals

Observations on the secretions of the subcommissural organ and the pineal in the adult brush-talled possum (Trichosurus vulpecula).

Secretory functions of the subcommissural organ (SCO) were investigated using mainly transmission and scanning electron microscopes, in 40 adult (19 males, 21 females) Trichosurus vulpecula which were caught in different seasons over several years. There is clear evidence of apical secretion, Reissner's fiber (RF), a presumptive basal secretory material with associated perivascular space and labyrinthine basal lamina. Secretory function does not appear to be related to the sex of the animal or to the season when they were investigated. Radioimmunoassay of blood, SCO and pineal gland (PIN) for melatonin (MEL) was carried out in 18 adult animals in summer and winter. Gonads were also histologically examined. The SCO showed very little MEL. Findings suggest that the PIN of this animal has a low capacity to store and secrete MEL. Further, there is no evidence for the increased storage or secretion of MEL during darkness, and more specifically at midnight. The present investigators support the view that other indoles such as methoxytryptophol or pineal peptides may elicit the physiological effects of PIN.

Animals

A scanning electron microscope study of the pineal recess of the adult brush-tailed possum (Trichosurus vulpecula).

The ventricular surface features of the pineal recess of 35 adult brush-tailed possums (Trichosurus vulpecula) were studied, mainly with the scanning microscope. The complex and interesting details observed have not been reported before. The pineal recess shows three distinct zones, and it is suggested that these be called: central, paracentral, and peripheral. The surface cells of the central zone show neither cilia nor microvilli, the paracentral zone shows microvilli (in a polygonal and homogeneous array), supraependymal cells and CSF-contacting nerve processes, while the peripheral zone is heavily ciliated. These features are consistent with the hypothesis that, in certain physiological states, the CSF from the pineal recess carrying pineal secretion is momentarily 'swept' forward in the direction of the median eminence to influence hypothalamic functions directly.

Age Factors

Some specific anatomical features of the atlas and axis: dens, epitransverse process and articular facets.

Metrical and morphological findings, based on 107 human vertebral columns, related to the variations of the dens are given, and differences in the depth of the superior articular facets of the atlas and specific pertinent details related to the os odontoideum and epitransverse process are also provided and their possible clinical relevance indicated. Findings reveal considerable variation in the height of the dens (11 to 18 mm), but remarkably little in its anteroposterior and transverse diameters at the root. The use of the term "hypoplasia" with reference to the dens is discussed, and a need for more rigid criterian in the use of this term stressed. It is also suggested that there may be sufficient radiological evidence in a lateral radiography to lead one to suspect the presence of an os odontoideum or a separate dens caused by trauma in the distant past.

Adult