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Biomedical subjects

R Padmanabhan

Publications and source records attributed to R Padmanabhan.

At least 127 records · Page 7Linked to original sources
PubMed1986

MDBK nuclear factor-binding site of various serotypes of adenovirus DNA.

A fraction with the ability to bind the terminal fragment of equine adenovirus (EAd) DNA was prepared from MDBK cell nuclei. The fraction (MDBK nuclear factor) bound to the terminal fragment of all human and animal adenovirus DNAs examined except avian adenovirus EDS-76. However, the terminal fragments of two animal adenoviruses, EAd and bovine adenovirus type 3 (BAd3), showed higher affinity for the nuclear factor than the others. The MDBK nuclear factor-binding site determined by footprinting analysis was the sequence located between nucleotides 22 and 46 in EAd, between 36 and 53 in canine adenovirus type 2, and between 20 and 46 in BAd3, counting from the terminus. The respective binding site contained a sequence resembling the consensus sequence. The binding site of Ad4 DNA was not within the inverted terminal repetition, but was located at least 550 base pairs apart from the terminus.

Adenoviridae↗
PubMed1986

The talar facets of the calcaneus--an anatomical note.

The number and extent of articular facets for the talus on the superior surface of the calcaneus were studied in 272 Indian specimens. These included 66 pairs of male, 39 pairs of female, 29 unpaired male, 4 unpaired female and 29 unsexed bones. The results indicated that there were only 2 major types of calcanei, as far as the number of these facets were concerned: type A (3 facets, 35%) and type B (2 facets, 65%). There was no single case of type C (1 facet) of BUNNING and BARNETT (1965). The frequency of incidence has no association with sex and side.

Calcaneus↗
PubMed1986

Exencephaly and axial skeletal dysmorphogenesis induced by maternal exposure to cadmium in the mouse.

To investigate the axial skeletal dysmorphogenesis associated with exencephaly and facial abnormalities, two doses of cadmium chloride (4 mg/kg and 6 mg/kg) were administered subcutaneously to MF1 mice on day 7 of gestation (sperm-positive day = day 0). Fetuses were collected on day 18. Gross examination revealed a very high incidence of cranioschisis aperta with exencephaly, maxillary and mandibular hypoplasia, low-set microtia, edema, and growth retardation of fetuses in both treatment groups. Alizarin red S-stained and cleared skeletal preparations of these embryos revealed hypoplasia of the premaxilla, maxilla, nasal bone, zygoma, and mandible of the facial skeleton. The orbital plate represented the frontal bone. The vault of the skull was conspicuously absent. In cranioschisis, the exoccipitals had splayed and fused with the atlas. The basicranial bones were hypoplastic and crowded, thus reducing the cranial cavity. The vertebral bodies were more affected than the arches. Hemivertebrae and longitudinal fusion of centra and arches were also noted. The ribs were usually rudimentary. Agenesis, fusion, and forking of ribs were frequently observed. The sternebrae were rudimentary, bipartite, or longitudinally fused. These data clearly establish the association between neural tube and axial mesodermal abnormalities and emphasize the interdependence of the neurectoderm and mesoderm in normal morphogenesis.

Animals↗
PubMed1985

Malformations of the axial skeleton in cranioschisis aperta and exencephaly in rat fetuses induced after neural tube closure.

Single doses of cyclophosphamide were administered (IP) to groups of Wistar rats, on different days of gestation after neural tube closure (days 12-15) and fetuses were collected on day 20. A very large number of the fetuses treated during days 12-14 exhibited cranioschisis and exencephaly. Ethanol fixed, alizarin red stained specimens were observed for axial skeletal abnormalities. The exencephalic ones lacked ossified skulls. The basicranial bones were either under ossified or had undergone extensive fusion resulting in reduction in cranial volume. The basicraniovertebral angle was obtuse. The vertebral bodies and arches showed varying degrees of hypoplasia, fusion and/or agenesis. The development of ribs and sternebrae was also extensively affected. Treatment on day 15 did not induce exencephaly but the axial skeleton was hypoplastic. Wavy ribs were a remarkable feature of these fetuses. All exencephalic fetuses had subcutaneous haemorrhages; many of them were obviously oedematous. These data indicate that the susceptible period for induction of these anomalies does not stop at neuropore closure.

Abnormalities, Drug-Induced↗
PubMed1985

Exencephaly and axial skeletal dysmorphogenesis induced by acute doses of ethanol in mouse fetuses.

Administration of single doses (0.02 ml and 0.03 ml/g body wt.) of a solution of absolute alcohol (25%, v/v) in saline to MF1 mice on day 8 of gestation resulted in significant fetal mortality, growth retardation and gross malformations of the fetuses at term. The malformations included cranioschisis with exencephaly, maxillary hypoplasia, exophthalmia and various digital anomalies. The exencephalic fetuses, cleared in KOH and stained with alizarin red revealed the absence of the skull vault and hypoplasia of the facial bones. The skull base indicated under ossification and overcrowding of the constituent bones resulting in severe reduction in the cranial volume and asymmetry of cranial base. These cranial skeletal malformations were accompanied by abnormalities of the vertebral bodies, arches, ribs and sternum. It is concluded that acute doses of alcohol during critical stages of neural tube development is deleterious to both the central nervous system (CNS) and axial skeleton in the mouse.

Abnormalities, Drug-Induced↗
PubMed1985

Histological and histochemical changes of the placenta in fetal alcohol syndrome due to maternal administration of acute doses of ethanol in the mouse.

In both clinical and experimental research on the fetal alcohol syndrome (FAS) the possible involvement of the placenta has not been considered. In an attempt to investigate the effects of alcohol on the placenta, single doses of 0.02 ml and 0.03 ml/g body weight of freshly prepared solutions (25%, v/v) of absolute alcohol in saline were administered to MF1 mice on day 8 of gestation. Controls were saline treated or/and pair fed and pair watered. Fetuses and placentas were collected on day 18, weighed individually, observed for malformations and fixed. Paraffin sections of placentas of control and of fetuses with FAS were stained with hematoxylin and eosin, Best's carmine and PAS with and without diastase (saliva). The experimental fetuses and placentas were lighter in weight than the controls. The decidua basalis of placentas of FAS cases were occasionally vacuolated and infiltrated by lymphocytes. The glycogen and mucopolysaccharide content in the basal zone was reduced. In most situations the glycogen cells had degenerated and were replaced by an acidophilic mass. The cytoarchitecture of the labyrinthine zone had been altered. Large cysts filled most parts of the placenta; besides fibrinoid accumulation, extensive vacuolisation was also clearly visible. The overall width of this zone and arborisation of fetal vasculature were also reduced. The consistent association of these placental abnormalities with FAS in this mouse model is suggestive of placental mechanisms in FAS.

Animals↗
PubMed1985

Quantification of expression of linked cloned genes in a simian virus 40-transformed xeroderma pigmentosum cell line.

We wished to determine whether simian virus 40 (SV40)-transformed xeroderma pigmentosum cells, despite their defective DNA repair, were suitable for DNA-mediated gene transfer experiments with linked genes. Expression of a nonselectable gene (cat, coding for chloramphenicol acetyltransferase [CAT]) linked to a selectable gene (gpt, coding for xanthine-guanine phosphoribosyltransferase [XPRT]) in the plasmid pSV2catSVgpt was quantified after transfection of SV40-transformed xeroderma pigmentosum [XP20s(SV40)] and normal human [GM0637(SV40)] fibroblast cell lines. A novel autoradiographic assay with [3H]xanthine incorporation showed 0.5 to 0.7% phenotypic expression of XPRT in both cell lines. Without selection, transient CAT activity was 20 times greater in the GM0637(SV40) than in the XP20s(SV40) cells, and transient XPRT activity was 5 times greater. Both of these transient activities were increased and equalized in both cell lines by transfection with pRSVcat or pRSVgpt. Genotypic transformation to gpt+ occurred at a frequency of 2 X 10(-4) to 4 X 10(-4) in both cell lines with pSV2catSVgpt. After 2 to 3 months in selective medium, stable expression of the (nonselected) cat gene was found in 11 (92%) of 12 gpt-containing clones derived from GM0637(SV40) cells and in 13 (81%) of 16 gpt-containing clones from XP20s(SV40) cells. However, the levels of CAT activity did not correlate with those of XPRT activity, and both of these activities varied more than 100-fold among different clones. Copies (1 to 4) of the gpt gene were integrated in four clones of the GM0637(SV40) cells having an XPRT activity of 1 to 5 nmol/min per mg, but 5 to 80 copies were integrated in four XP20s(SV40) clones with an XPRT activity of 0.8 to 1.8 nmol/min per mg. This study shows that XP20s(SV40) is as suitable for gene transfer experiments as the normal human line GM0637(SV40).

Acetyltransferases↗
PubMed1984

Effect of acetaldehyde on skeletogenesis in rats.

Acetaldehyde (ACH), the metabolite of ethanol was administered to pregnant CF rats intraperitoneally (50 mg/kg) from day 8 through 15 of gestation and fetuses from different mothers were collected from day 16 through 21 of gestation. Fetuses were processed for alizarin skeletal staining. There was significant delay in ossification besides certain skeletal malformations such as wavy ribs. The delay in ossification may be one of the reasons for reduced birth weight and increased postnatal mortality and growth.

Acetaldehyde↗
PubMed1984

Effects of acute doses of ethanol on pre- and postnatal development in the mouse.

Investigators on fetal alcohol syndrome (FAS) both clinical and experimental, have generally concentrated attention on chronic alcoholism. In an attempt to elucidate the effects of binge drinking on pre- and postnatal development, single doses of 0.01, 0.02 and 0.03 ml/g body weight of alcohol solutions (25% v/v of ethanol in saline) were administered intraperitoneally to groups of mice on days 8-12 of gestation. Controls were untreated or starved for 6 h. Fetuses collected on day 18 revealed retardation, fetal mortality and craniofacial and digital malformations. While growth retardation and fetal mortality were dose-dependent, malformations were stage-dependent. The 0.01-ml group exhibited only postaxial polydactyly of the forepaw. The reduction in fetal weight of 0.03-ml groups corresponded well with that of umbilical cord length. Following administration of single doses of 0.01 ml/g of ethanol solution on days 8-12, groups of mice were allowed to deliver. Controls were untreated or pairfed and pair watered. Pups were reared by the respective mothers and their survival and growth were observed till postconception day 71 and thereafter brother/sister matings were carried out. At least one pup in each litter remained extremely stunted and failed to reproduce. No significant differences in mortality, growth rates and reproductive capacity of the rest of the pups were observed. It is concluded that single but heavy doses of ethanol during organogenesis leads to a situation reminiscent of human FAS.

Animals↗
PubMed1984

Implication of the placenta in acetaldehyde-induced intrauterine growth retardation.

Acetaldehyde (AcH) the proximal metabolite of ethanol was administered to pregnant CF rats intraperitoneally in single and triple doses (50, 75 and 100 mg/kg) on days 10, 11 and 12 of gestation and fetuses along with placentae were collected on day 21. Placentae were subjected to histological sectioning and the volume fractions of various zones of placenta were calculated using Weibels point counting techniques. There was no correlation between fetal weight and placental weight, but the fetal weight showed a positive correlationship with the percentage volume fraction of the labyrinthine zone suggesting that the reduction in the labyrinthine zone volume is probably responsible for intrauterine growth retardation following acetaldehyde maternal treatment.

Acetaldehyde↗
PubMed1984

Rat growth hormone expression in cell hybrids.

Extinction of rat growth hormone (rGH) gene expression occurs in somatic cell hybrids of GH3 cells (rat pituitary adenoma) and L cells (mouse transformed fibroblast). We have suggested that this is due to transacting factors contributed directly or indirectly by the L cells. To study this in more detail, the cloned rGH gene was introduced into clones of these hybrid cells by microinjection or calcium phosphate transfection. GH peptides were detected 24 hr later in the microinjected cells by immunofluorescence. Production of rGH gene transcripts in the stably transformed hybrid cells was also detected by Northern hybridization. Although the overall patterns of transcripts differed from those present in GH3 cells, normal-sized rGH mRNA species were detected, whereas these had not been observed in previous studies in which the GH gene was transfected into L cells and other mouse fibroblasts. No more than one or two extra GH gene copies per cell were required to restore GH gene expression in the hybrids. Whereas GH gene expression in the hybrid cells transfected with the GH gene might reflect activation of the endogenous GH gene, this was not the case in at least one transfected hybrid cell line which had lost the endogenous gene. These results suggest: (i) the putative transactive repressors of GH gene expression in the hybrid cells do not recognize the transfected genes; and (ii) elements in the hybrid cells, unlike the case with L cells, allow for the production of normal-sized GH mRNA that can also produce GH peptides.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1984

Congenital anomalies of the ear resulting from cyclophosphamide treatment in the rat.

A single dose of cyclophosphamide (20 mg/kg) administered on day 12 of gestation to CF rats resulted in microtia in 97.5% of fetuses at term. The ears of affected fetuses were low set and dorsally placed. Histological examination revealed persistence of meatal plug, branching of the primordium of external acoustic meatus, periotic hemorrhages, narrowing of tympanic cavity, presence of only one to two primordia of middle ear ossicles, hypoplasia of stapedial artery, a maximum of two turns of cochlea and under differentiation of the organ of Corti and the semicircular ducts. Hemorrhages in and around the region of the ear were extensive. Bilaterally symmetrical distribution of microtia and consistency of associated anomalies suggest that this is a good animal model for further investigation into the pathogenetic mechanisms of these ear anomalies.

Animals↗
PubMed1984

Characterization of the effector cells mediating an "innocent bystander" cytotoxicity reaction induced by a syngeneic mammary adenocarcinoma in mice.

Spleen cells from BALB/c mice bearing a syngeneic mammary adenocarcinoma nonspecifically destroy xenogeneic targets following in vitro induction with mammary tumor-associated antigens. Studies were undertaken to characterize the effector cell population(s) mediating this "innocent bystander" cytotoxicity reaction. Fractionation experiments using phagocyte-depleted spleen cells revealed that the effector population was adherent to nylon wool columns. Flow cytometric analysis of the nylon-adherent cells revealed the presence of a minor population of Thy 1.2+ cells. Following treatment of the nylon-adherent cells with anti-Thy 1.2 and complement, the cytotoxic activity was abolished. Furthermore, when those cells expressing the Thy 1.2 antigen were positively selected by cell sorting, they were able to mediate the cytotoxic reaction. In contrast, nylon-adherent Thy 1.2-negative cells were unable to mediate the reaction following selection by cell sorting. Depletion studies with anti-Lyt 1 or anti-Lyt 2 and complement also abolished this cytotoxic response. Additional studies demonstrated that nylon-adherent spleen cells from mammary tumor-bearing mice were not able to lyse natural killer cell-sensitive targets. These data suggest that the cells which effect tumor antigen-induced "innocent bystander" cytotoxicity, or their activated precursors, are nylon-adherent Thy 1.2+, Lyt 1+2+ T-cells.

Adenocarcinoma↗