A survey of undergraduate pediatric education. Progress in the 1980s?
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Clinical Clerkship↗
Biomedical subjects
K G Nelson
Publications and source records attributed to K G Nelson.
Flow cytometric analysis of human uterine sarcomas and cell lines.
Flow cytometric techniques were used to characterize multiple human uterine sarcomas and cell lines derived from some of these tumors. Analysis of DNA content showed that 9 of the 11 uterine sarcomas investigated were composed of at least one aneuploid population as well as a distinct diploid population. These data indicate that aneuploidy, as measured by flow cytometry, is a characteristic more common to uterine sarcomas than that previously reported for uterine adenocarcinomas. Unlike the original tumors, the cell lines established from three of the sarcomas contained predominantly diploid populations with only minor aneuploid populations. Treatment of one of the sarcoma cultures with tumor promoters did not result in an increase in the aneuploid populations. Tumors which arose in nude mice upon transplantation of two of the sarcomas did not contain the same distribution of tumor subpopulations as found in the original sarcomas. Apparently, the in vitro culture and and in vivo nude mouse conditions were not appropriate for maintaining the original equilibrium between the aneuploid and diploid subpopulations but instead provided a selective environment that resulted in the preferential growth of only certain tumor populations. Dual-parameter analysis of DNA content and alkaline phosphatase levels of one of the sarcomas were useful for distinguishing the aneuploid from the diploid population coexisting in this tumor. Our data suggest that flow cytometry is a valuable tool to analyze the characteristics of the tumor populations residing in primary uterine sarcomas as well as to determine which of these tumor subpopulations survive in culture and transplantation to nude mice.
Alkaline Phosphatase↗
Mass transport in dissolution kinetics. I: Convective diffusion to assess the role of fluid viscosity under forced flow conditions.
The quantitative influence of viscosity on dissolution kinetics is assessed under laminar flow conditions by utilizing a convective diffusion model for drug dissolution. Functional dependency of three types of viscosity inducing agents is established with respect to the parameters of fluid flow rate, diffusivity, and solubility. Studies of aqueous solutions of sucrose and of glycerol demonstrate that the decrease in dissolution rate of ethyl p-aminobenzoate is related to the decrease in solute diffusivity in these solutions, whereas the solubility change in the glycerol solutions has an additional independent simultaneous effect. Dissolution in hydroxypropyl cellulose solutions remains constant under fixed fluid flow conditions because of the negligible effect of the polymer upon the drug diffusivity. A change in fluid flow rate, however, alters the dissolution rate and correlates quantitatively with the rate of shear in the convective diffusion model. The interpretation of the effect of viscosity on dissolution kinetics with the convective diffusion model explains these phenomena quantitatively in terms of the fundamental mass transport processes.
Cellulose↗
Mass transport in dissolution kinetics. II: Convective diffusion to assess role of viscosity under conditions of gravitational flow.
Dissolution kinetics was studied in a laminar flow cell, through which aqueous solutions of increasing viscosity flowed under the force of gravity, in order to help elucidate the mechanism of drug dissolution. The viscosity was varied by addition of either hydroxypropyl cellulose, sucrose, or glycerin. The dissolution data were evaluated quantitatively in terms of a convective diffusion model for dissolution. It was demonstrated that the decrease in dissolution rate of a test compound due to viscosity in the polymer solution occurs primarily because of a decrease in the rate of shear over the dissolving surface. In solutions of sucrose or glycerin, the decrease in dissolution rate due to viscosity results because of a decrease in the diffusivity of the solute in addition to the decreased rate of shear. Also, the model accounts for the increase in solubility in the glycerin solution. Thus, the influence of viscosity on dissolution depends on whether the viscosity-inducing agent primarily affects only the flow properties of the liquid, or whether it affects diffusivity (i.e., a "micro" viscosity effect, in addition to the flow properties).
Cellulose↗
Placental markers of human exposure to polychlorinated biphenyls and polychlorinated dibenzofurans.
Our studies have evaluated biochemical changes in placentae from humans exposed to rice oil contaminated with polychlorinated biphenyls (PCBs) and polychlorinated dibenzofurans (PCDFs) in Taiwan. Placentae were obtained from nonsmoking women 4 to 5 years after the exposure had occurred. The exposed individuals ingested approximately 1 to 3 g PCBs and 5 mg PCDFs, and many exhibited symptoms characteristic of PCB poisoning. This disease was termed "Yu-Cheng" in Chinese. Based on data from experimental animal models, we examined a number of parameters in placentae from control and exposed women, including arylhydrocarbon hydroxylase (AHH) activity, cytochrome P-450 isozymes, epidermal growth factor (EGF) receptor binding properties and actions, and Ah receptor. We also quantified concentrations of various PCB and PCDF congeners known to be present in the contaminated rice oil. Our results revealed a dramatic elevation in placental AHH activity in samples from PCB/PCDF-exposed women. This increase in enzyme activity was associated with a parallel increase in placental microsomal protein immunochemically related to cytochrome P-450 form 6 [derived from 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD)-induced rabbit lung]. No other cytochrome P-450 isozyme was detected in placental preparations, and the form 6 homolog was found only in placentae from exposed women. EGF receptor-mediated autophosphorylation capacity was significantly diminished in PCB/PCDF placentae, but this effect was not associated with changes in plasma membrane EGF receptor binding properties (Kd and Bmax). The EGF receptor autophosphorylation effect correlated well with the decrease in birthweight observed in offspring of exposed women, suggesting that this biochemical event might provide a good marker of effect for the toxic halogenated aromatics.
Adolescent↗
Decreased human birth weights after in utero exposure to PCBs and PCDFs are associated with decreased placental EGF-stimulated receptor autophosphorylation capacity.
Yucheng (oil disease) is a clinical and metabolic syndrome reported in Taiwanese who consumed rice oil contaminated with large amounts of various polychlorinated biphenyls (PCBs) and polychlorinated dibenzofurans (PCDFs), including the 2,3,4,7,8- and 1,2,3,4,7,8-PCDF congeners which are similar in structure and toxicity to 2,3,7,8-tetrachlorodibenzo-p-dioxin. A well known characteristic of Yucheng is the marked decrease in birth weights, although the underlying mechanism of this effect is unclear. Placental epidermal growth factor (EGF) receptor binding and autophosphorylation studies were done using tissue samples taken from Yucheng and unexposed control patients. EGF-stimulated receptor autophosphorylation of the human placental EGF receptor in the Yucheng subjects was decreased more than 60% of control levels, 4-5 years after the exposure had occurred. The decrease in EGF receptor phosphorylation was significantly correlated with decrease in birth weights. Nonlinear regression analysis of the 125I-EGF receptor binding data revealed that there were two distinct EGF receptor binding isotherms representing the high affinity-low capacity (HALC) and the low affinity-high capacity (LAHC) binding sites. In contrast to the placental EGF-stimulated phosphorylation data described above, the binding kinetics of the EGF receptor were not significantly altered in the control [HALC site Kd = 0.10 +/- 0.02 (SE) nM, Bmax = 788 +/- 255 fmol/mg of protein; LAHC site Kd = 17.4 +/- 8.2 nM, Bmax = 62 +/- 32 pmol/mg) compared to the Yucheng subjects (HALC site Kd = 0.11 +/- 0.02 nM, Bmax = 784 +/- 305 fmol/mg; LAHC site Kd = 49.5 +/- 24.7 nM, Bmax = 147 +/- 80 pmol/mg). GC-MS analysis of placental specimens showed elevated levels of selected PCB and PCDF congeners in the Yucheng compared to control individuals. Total PCB levels were 0.5 +/- 0.2 ppb and 20.0 +/- 4.8 ppb for the control and Yucheng subjects, respectively. A significant dose-response relationship was observed between the placental EGF receptor phosphorylation levels and the PCB concentrations (total or concentrations of 2,2',4,4',5,5'-hexa- and 2,2'3,3'4,4',5-heptachlorobiphenyls). In contrast, no significant relationship was found between the EGF receptor phosphorylation activity and the 2,3,4,7,8- or 1,2,3,4,7,8-PCDF congeners, which were at nondetectable levels in the control and between 104 and 374 parts per trillion in the Yucheng subjects. In summary, our data reveal that decreased placental EGF receptor phosphorylation capacity is associated with decreased birth weight. Furthermore, PCB tissue concentrations might be a better predictor of effects than are PCDF concentrations.
Benzofurans↗
Fetal deaths in Alabama, 1974-1983: a birth weight-specific analysis.
Birth weight-specific fetal death rates were evaluated for Alabama for the years 1974-1983. The fetal death rate for the total low birth weight group improved less than 20% during the decade, whereas the fetal death rate for the 2500-3999-g birth weight group improved 40%, and the fetal death rate for the group of 4000 g or more improved 71%. By 1983, 76% of all stillbirths weighed less than 2500 g, compared with 66% in 1974. In contrast, in both years, only about 7% of live births weighed less than 2500 g. This study suggests that increased reporting of stillbirths of less than 500 g has contributed to the recent apparent lack of improvement in stillbirth rates in Alabama.
Alabama↗
Epidermal growth factor (EGF) stimulates EGF receptor synthesis.
Epidermal growth factor (EGF) binds to the extracellular domain of a specific 170,000-dalton transmembrane glycoprotein; this results in rapid removal of both ligand and receptor from the cell surface. In WB cells, a rat hepatic epithelial cell line, ligand-directed receptor internalization leads to receptor degradation. We tested whether the EGF receptor was replenished at a constitutive or enhanced rate following EGF binding by immunoprecipitating biosynthetically labeled EGF receptor from cells cultured with [35S]methionine. EGF stimulated receptor synthesis within 2 h in a dose-dependent manner; this was particularly evident when examining the nascent form of the receptor. To determine the site of EGF action, total WB cell RNA was transferred to nitrocellulose paper after electrophoresis and was hybridized to cDNA probes from both the external and cytoplasmic coding regions of the human EGF receptor. EGF increased receptor mRNA by 3-5-fold. Therefore, at least in some cells, the surface action of EGF that leads to EGF receptor degradation is counterbalanced by a positive effect on receptor synthesis.
Animals↗
Endometrial stromal cells in culture: an attempt to understand the genesis and biologic activity of uterine sarcomas.
The genesis of uterine sarcomas in vivo has been difficult to elucidate. The reasons are multifactorial and are compounded by the rarity of these tumors. In an effort to understand the biologic activity of this disease, normal endometrial tissue was subjected to tissue culture, histochemical study, and hormonal manipulation. Protein markers were used to differentiate endometrial epithelium from endometrial stromal cells in culture. The endometrial stromal cells grew rapidly following subculturing and were responsive to hormonal manipulation. When the stromal cells in culture were treated with the carcinogen N-methyl-N'-nitro-N-nitrosoguanidine (MNNG), the resultant morphologic changes mimicked uterine sarcomas grown in culture. These changes appeared to occur in a sequential manner, somewhat analogous to changes occurring in the endometrial epithelium as it undergoes transformation to endometrial adenocarcinoma. These studies, therefore, may serve as a model system in understanding the genesis and biologic activity of uterine sarcomas.
Alkaline Phosphatase↗
Low birth weight, intrauterine growth retardation, and preterm delivery.
The relationship between low birth weight, intrauterine growth retardation, and preterm delivery in infants born at a perinatal center is described. Between 20% and 30% of infants born weighing 500 to 2000 gm and nearly 50% of infants born weighing 2001 to 2750 gm had intrauterine growth retardation. For infants within the same low-birth weight group, infants with intrauterine growth retardation had one half to one sixth of the neonatal mortality rate of non-growth-retarded infants. However, only in the 501 to 1000 gm group did the difference in mortality between infants with and without intrauterine growth retardation substantially influence the composition of the group of survivors.
Birth Weight↗
Neonatal mortality in infants born weighing 501 to 1000 grams. The influence of changes in birth weight distribution and birth weight-specific mortality rates on neonatal survival.
We analyzed changes over time in neonatal mortality rates for infants born weighing 501 to 1000 gm. The decline in total mortality in this weight group due to improved small-group, birth weight-specific mortality was contrasted to the increase in mortality caused by changes in the birth weight distribution resulting from the care of smaller infants. Had the birth weight distribution remained unchanged, the total improvement in neonatal mortality for the entire 501 to 1000 gm group would have been substantially greater.
Alabama↗
Infant mortality: relationship between neonatal and postneonatal mortality during a period of increasing perinatal center utilization.
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Age Factors↗
Gestational age and the management of preterm labor in obstetric programs.
The gestational age at which obstetric training programs aggressively manage and attempt to salvage preterm vertex fetuses in distress was determined by survey. More than half the programs initiate fetal monitoring and perform cesarean section for certain cases of fetal distress by 26 weeks gestational age. By 28 weeks gestational age, most programs consistently perform a cesarean delivery for a vertex fetus in distress. Management practices in university training programs appear to be more aggressive than those in nonuniversity programs. Not all programs--either within or outside the university--try aggressively to salvage fetuses in distress at 28 weeks gestational age or more, however, despite the excellent chance for survival and normal development.
Cesarean Section↗
Analysis of isoenzymes in normal and carcinogen-treated human endometrial stromal cells in culture.
The isoenzyme patterns of lactate dehydrogenase (LDH), hexokinase, phosphofructokinase, and aldolase were investigated in cultured normal and carcinogen-treated human endometrial stromal cells. Both normal and carcinogen-treated cells had similar phosphofructokinase and aldolase isoenzymes. Distinctive changes in hexokinase and LDH isoenzyme patterns were found in the carcinogen-treated stromal cells. The LDH isoenzyme patterns of the carcinogen-treated stromal cells were shifted toward the muscle LDH forms. This is comparable to the alteration of LDH isoenzyme profiles observed in cell lines established from human uterine sarcomas. The two tissue culture media used affected the LDH isoenzyme patterns of endometrial stromal cells but differences between the LDH isoenzyme patterns of control and carcinogen-treated cells were detected regardless of the growth medium used. Total LDH activity was not significantly different in control and carcinogen-treated stromal cells. The hexokinase isoenzyme patterns expressed by the carcinogen-treated stromal cells were distinctly different from the normal hexokinase patterns. The treated stromal cells contained both hexokinase I and II, whereas the normal cells contained only hexokinase I. Hexokinase and LDH isoenzyme patterns may serve as markers with which to evaluate carcinogen-induced neoplastic changes in cultured endometrial stromal cells.
Cell Line↗
Promotion-like enhancement of transformed phenotypes in human endometrial stromal cells.
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Cell Transformation, Neoplastic↗
Clonal analysis of tumorigenicity and paratumorigenic phenotypes in rat liver epithelial cells chemically transformed in vitro.
Clonal subpopulations of a chemically induced tumorigenic rat liver epithelial cell line were analyzed for their cellular, biochemical, and in vitro growth properties and their tumorigenicity after injection into day-old newborn isogeneic rats. The phenotypic properties studied included DNA content; growth rate in culture; activities of gamma-glutamyl transpeptidase, NADH diaphorase, pyruvate kinase, glucose-6-phosphate dehydrogenase, and lactate dehydrogenase; ability to grow in calcium-poor medium; and ability to form colonies in soft agar. The results show that none of these phenotypes cosegregates with tumorigenicity and therefore is not reliable as a "marker" phenotype for neoplastic transformation in cultured rat liver epithelial cells. The poor correlations, either qualitatively or quantitatively, between paratumorigenic phenotypes and tumorigenicity suggest that neoplastic transformation in these cells involves a specific transforming gene locus or loci and that in vitro paratumorigenic phenotypes are merely epiphenomena of neoplastic transformation and progression. This study further reveals that the efficiency of the tumorigenicity assay of cultured rat liver epithelial cells in isogeneic newborn rats can be considerably improved by incubating the cells in medium containing only trace amounts of serum prior to transplantation into the host animals.
Animals↗
Phenotypic and karyotypic changes induced in cultured rat hepatic epithelial cells that express the "oval" cell phenotype by exposure to N-methyl-N'-nitro-N-nitrosoguanidine.
A diploid population of cultured rat hepatic epithelial cells that expresses the "oval" cell phenotype was exposed briefly and repetitively to N-methyl-N'-nitro-N-nitrosoguanidine (MNNG), and the effect on more than 20 phenotypic properties was evaluated during the neoplastic transformation of the population. MNNG treatments of this hepatic epithelial cell population resulted in a progressively increasing phenotypic alteration and heterogeneity including changes in specific activities of several cellular enzymes and expression of isozymes, synthetic functions, and various in vitro growth properties. Changes in phenotypic expression were clustered episodically and were associated with major karyotypic changes. The development of increasing phenotypic heterogeneity preceding and accompanying tumorigenicity in cultured liver epithelial cells in vitro and the specific phenotypes that occur resemble superficially the pattern of phenotypic changes that occur in hepatocytes during chemical hepatocarcinogenesis in vivo. The results of this study provide the basis for future investigations to further elucidate the mechanistic and linkage relationship between specific pretumorigenic and paratumorigenic phenotypes and tumorigenicity.
Animals↗
Apgar scores and umbilical arterial pH in preterm newborn infants.
One- and five-minute Apgar scores and umbilical cord arterial pH values were compared in preterm newborn infants of various gestational ages. The more premature the infant, the more likely the Apgar score was low in the presence of a pH greater than or equal to 7.25. Conversely, the closer to term, the more frequently an infant with a pH of less than 7.25 had an Apgar score of greater than or equal to 7. Therefore, in preterm infants, there is little congruity between the Apgar score and umbilical cord pH. Based on these findings, it is not appropriate to label preterm newborn infants as asphyxiated based on a low Apgar score.
Apgar Score↗