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Biomedical subjects

M N Runner

Publications and source records attributed to M N Runner.

At least 19 recordsLinked to original sources
PubMed1986

Epigenetically regulated genomic expressions for shortened stature and cleft palate are regionally specific in the 11-day mouse embryo.

Chronokinetic synergism, a holistic and extremely sensitive experimental design, has shown in the mouse embryo that site-specific epigenetic forces differentially regulate genesis of the palate (cleft palate) and limb bud organogenesis (shortened stature). Acute exposures of 11-day pregnant mice to minimally effective doses of thymidine or ethanol followed 5 or 8 hr later by minimal exposure to retinoic acid have enabled quantitative and qualitative assay for genomic-epigenetic interactions. These site-specific morphogenetic regulations occurred during palatal genesis from the maxillary prominence of the first pharyngeal arch and during limb bud prechondrogenesis. Thymidine is presumed to induce its response by inhibition of DNA polymerase and hence by transitory cytostatic block. (Embryo size was not detectably changed). Ethanol is interpreted, guilt by associated response, indirectly to interfere with histone regulation of transcription. Two central findings have demonstrated the coordinated regulation of genomic and epigenetic positional information. First, thymidine or ethanol as epigenetic probes for limb prechondrogenesis and palatal precursor cells have activated distinctive site-specific responses. Second, responses to chronokinetic synergisms have indicated that epigenetic regulators for limb and palate dysmorphogenesis may affect distinctly different phases of the cell division cycle and hence induce differential DNA expressions. Although each of palate and limb is concurrently susceptible to epigenetic regulation, their differential intrinsic genomic capabilities appear to have been uncoupled. The putative homeostatic balance of genomic expressions in the palate precursor and the prechondrogenic limb bud cells of the 11-day mouse embryo has been characterized as epigenetically regulated, alternatively expressed, and positionally restricted. We propose that the chronokinetic synergisms have disclosed the existence of distinctive palate-determining genes and stature-determining genes.

Abnormalities, Drug-Induced↗
PubMed1985

Tissue interactions and prostatic growth: II. Morphological and biochemical characterization of adult mouse prostatic hyperplasia induced by fetal urogenital sinus implants.

Current hypotheses regarding the causes of human benign prostatic hyperplasia have implicated both steroid hormone imbalance and tissue interactions. To examine the role of the latter we have further investigated the phenomenon of urogenital sinus-induced hyperplasia of the adult mouse ventral prostate. Urogenital sinuses (UGS) or purified urogenital mesenchyme (UGM) from C3H mice were implanted into the ventral prostates or coagulating glands of 50- to 90-day-old BALB/c-nu/nu hosts. The animals were sacrificed at 15, 30, and 180 days postimplantation to establish time dependence. Wet weight and DNA content were used as measures of net growth. Glucose phosphate isomerase (GPI) isozyme analysis was used to determine the relative contributions of C3H and BALB/c cells to the enlarged chimeric ventral prostates. It was determined that the induced growth is time-dependent and that the UGS induces 2- to 4-fold more growth than UGM. GPI analysis shows that UGM-induced growth was composed primarily of host-derived cells whereas the UGS is composed nearly equally of host- and implant-derived cells. Histologic analysis reveals that the UGS implants induce marked epithelial proliferation. The proliferating glands occur in clusters, and the epithelium within the glands appears cribriform. Foci of postobstructive cystic atrophy are also found. Remnants of the implanted UGS are still present even at 180 days postimplantation. UGM-induced growth is of a more subtle nature and appears morphologically similar to the sham-operated controls. In view of the morphologic similarity with human disease, as well as the time and hormonal dependence of UGS-induced ventral prostatic hyperplasia, this model represents the basis for a unified hypothesis regarding the roles of tissue interaction and hormonal milieu in human benign prostatic hyperplasia.

Animals↗
PubMed1984

Mitochondrial reorganization during resumption of arrested meiosis in the mouse oocyte.

Correlated nuclear and cytoplasmic reorganizations during the 14 hr of reactivated meiosis in vivo and in vitro were examined in the laboratory mouse. Observations of living oocytes by differential interference contrast microscopy, and by fluorescent microscopy with nontoxic mitochondrial and DNA-specific probes, enabled us to determine that the major cytoplasmic reorganization involved two mitochondrial translocations associated with two stages of nuclear maturation. These observations were confirmed at the fine structural level by parallel transmission electron microscopy. Mitochondria translocate to the perinuclear region during formation of the first metaphase spindle and subsequently disperse during abstriction of the first polar body. Determinations of frequency of maturation in more than 2,900 normal oocytes, and in more than 1,100 oocytes in which germinal vesicle breakdown was reversibly inhibited, indicated that mitochondrial redistributions are a normal and probably necessary feature of reactivated meiosis in the laboratory mouse. We suggest that these two rapid translocations serve to concentrate mitochondria for localized activities that require elevated levels of adenosine triphosphate.

Animals↗
PubMed1984

New evidence for monozygotic twins in the mouse: twinning initiated in the late blastocyst can account for mirror image asymmetries.

The 11.5-day twin mice reported here support one of the classically described mechanisms for mammalian monozygotic twinning: subdivision of the blastocyst inner cell mass at the stage of proamnion cavitation. This particular method for monozygotic twinning has the attraction of providing a hypothesis for mirror image translocation of asymmetric traits. Monozygotic twins in laboratory rodents at or near parturition have not been identified and only two prior descriptions, for 7.5- and 9.5-day mouse embryos, have been found in the literature. Experimentally induced twins having identical heredity, i.e., clones, would enable study of heritable and environmental regulation of the components of discordance. A set of twin mouse embryos at 11.5 days of gestation within a common yolk sac, and with shared vitelline and allantoic circulations, provides direct evidence that monozygotic twin mice can survive rotation within the common yolk sac and suggests a reasonable probability that they can survive to term.

Animals↗
PubMed1984

Identification and characterization of glycoproteins secreted by the skin of the day 16 fetal mouse.

The secretion of tissue-specific proteins during mouse skin development, was investigated by incubating day 16 fetal skin explants in the presence of [35S]methionine and analyzing the medium electrophoretically. The medium was found to contain five proteins, which could be classified into two groups according to molecular weight. The kinetics of release of these proteins indicated that they were specifically secreted and not released by cytolysis. Mapping of the proteins by partial proteolytic digestion revealed that although the digestion patterns between the two molecular weight groups were different, within each group similar patterns were seen, suggesting that they were structurally related. Incubation in the presence of tunicamycin resulted in the decrease in molecular weight of the secreted proteins, indicating that the proteins were glycosylated. The results suggest that the two groups of structurally related glycoproteins were secreted by the peridermal layer of the fetal skin.

Animals↗
PubMed1984

Tissue interactions and prostatic growth. I. Induction of adult mouse prostatic hyperplasia by fetal urogenital sinus implants.

A homologous chimeric prostate was produced by implantation of intact fetal urogenital sinus(es) (UGS) into the ventral prostate gland (VP) of an adult athymic mouse. A 10- to 20-fold overgrowth of the chimeric lobe of ventral prostate gland, as measured by glandular wet weight and by DNA content, was observed 4 to 9 wk following UGS implantation. The overgrowth was prostate-like as indicated by histologic composition and by responses to endogenous androgen, and was composed of both host and donor cells in about equal proportions as shown by glucose phosphate isomerase isozymic profiles. Unlike the canine model for prostatic hyperplasia, the mouse prostatic overgrowth occurred in the complete absence of exogenous sex steroids. The histoarchitecture of the chimeric VP and the isozymic detection of the contribution to the overgrowth by host cells have provided strong evidence that adult prostatic cells have been recruited to respond proliferatively by cellular interactions with fetal UGS. The demonstration of cellular interactions followed by reactivation of the fetal growth potential provides direct experimental evidence in support of McNeal's hypothesis that the reactivation of fetal growth potential may account for the development of human benign prostatic hyperplasia (BPH).

Androgens↗
PubMed1984

A new mouse model for prostatic hyperplasia: induction of adult prostatic overgrowth by fetal urogenital sinus implants.

A new mouse model for human BPH has been established. This model was developed on the basis that fetal and adult prostatic cells interact to induce the proliferation of adult prostatic cells. A 10- to 20-fold overgrowth of the adult mouse prostate gland can be induced by implantation of fetal UGS into the adult prostate gland. Components of UGS, fetal UGM, and fetal UGE may be involved in the regulation of adult prostatic overgrowth. The androgen dependency and the specificity (donor tissue, site of implantation, and strain and species) of UGS-induced adult prostatic overgrowth have also been established. The question remains whether the prostatic hyperplasia seen in this mouse model may be representative of human BPH. The observation that fetal UGS implants induce adult prostatic overgrowth in the complete absence of exogenous sex steroids support the hypothesis of McNeal that human BPH may develop as a result of the reactivation of fetal growth potential in the periurethral area of the adult prostate gland. The present mouse model may be used as a test system for the future development of anti-BPH drugs.

Androgens↗
PubMed1982

The patterns of protein synthesis during foetal and neonatal organ development in the mouse are remarkably similar.

The extent to which differential gene expressions can be correlated with organ development was examined at the level of protein synthesis during pre- and postnatal development in the mouse. High resolution, equilibrium, two-dimensional polyacrylamide gel electrophoresis detected, for each of five to ten successive stages for each of seven organ systems, between 850 and 1000 separate newly synthesized proteins. The possibility that the 1000 detectable proteins synthesized at any one time during organ development represent a sampling bias was contra-indicated (a) because a different and larger population of [14C]amino acid-incorporating protein syntheses gave similar results and (b) because nonequilibrium isoelectric focusing, electrophoresis, isoelectric points between pH 5.5 and 8.7 confirmed the results from yet a different population of protein syntheses. Within limits of the sampling of protein syntheses, the entire period of organ development examined proceeds with altered expression of small proportion of the total proteins being synthesized. While all protein changes were stage specific, approximately three organ-specific protein syntheses were detected per organ system. One family of five protein syntheses seen in 16-day foetuses had homologous primary structures and presumably are keratins derived from a single genomic expression. These selected stage-specific protein syntheses examined by electrophoresis of partial proteolytic digests disclosed a programme for post-translational changes in protein syntheses. The current observations indicate that the examined pre- and postnatal organ development of the seven organs occurs in the presence of greater than 99% similarity among proteins synthesized in the same and different organ systems. Functional differentiation during organogenesis, therefore, occurs in the presence of less than 1% change in qualitative or quantitative switch in protein syntheses. Evidence is presented to indicate that even this remarkably small number of changes in protein syntheses during functional organ differentiation may be derived from an even smaller subset of gene expressions. Collectively, the data suggest that explanatory mechanisms for molecular organogenesis must encompass both selective gene expressions along with post-translational programmed events.

Amino Acids↗
PubMed1978

Tissue specificity for incorporation of [3H]thymidine by the 10- to 12-somite mouse embryo: alteration by acute exposure to hydroxyurea.

Radioautograms from 10- to 12-somite mouse embryos labeled for 30 min in vitro with [3H]thymidine were examined for frequency and intensity of incorporation. Results from ten tissues showed that values ranged from 82% of nuclei with a mean of 16.6 grains for visceral yolk sac to 17% of nuclei labeled with a mean of 4.4 grains for epithelium of the anterior gut tube. Labeling in the ten tissues indicated (1) a tissue-specific spectrum of incorporation of [3H]thymidine, (2) close correlation between frequency and intensity of labeling within a tissue and (3) asymmetrical quantities of incorporation between right and left somatopleure. Treatment with hydroxyurea in vitro reduced the frequency of labeled nuclei by 85% to 12% of control values. Mean numbers of grains over treated nuclei, 3.3-4.6 grains, were well above background but were clustered below the low end of the control range. Tissues exposed to hydroxyurea showed (1) labeling of significant numbers of nuclei, (2) inhibition of labeling in selected tissues and (3) equalization of bilateral asymmetry in quantity (frequency and intensity) of incorporation in somatopleure. The selective reduction of thymidine incorporation and equalization of asymmetrical rates of proliferation may constitute mechanisms by which hydroxyurea causes abnormal morphogenesis.

Animals↗
PubMed1976

The fine structural development of preimplantation mouse parthenotes.

The normality of the preimplantation development of 2-cell to expanded blastocyst stage mouse parthenotes, derived from oocytes activated in vivo, or in vitro, has been assessed at the fine structural level. Major changes in the organization of the cellular organelles, i.e., nucleoli, mitochondria, ribosomes, RER and junctional complexes, follow the same developmental sequences observed in embryos obtained from normally fertilized oocytes. One difference between parthenotes and controls is the scarcity of crystalloid bodies in parthenotes at the blastocyst stage. Because the embryos examined in this study had been cultured in vitro, in a simple salt and albumin medium in the absence of maternal influences, our observations on parthenotes indicate that developmental, preimplantation changes in the subcellular organization of the embryo do not require the continued presence of "maternal" factors or the participation of the paternal genome.

Animals↗