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Biomedical subjects

K G Nelson

Publications and source records attributed to K G Nelson.

At least 73 records · Page 4Linked to original sources

Survival of infants with low birth weight and early gestational age, 1979 to 1981.

A chart for displaying neonatal survival data regarding low birth weight and early gestational age is presented. Survival data at two institutions for infants with low birth weight and early gestational age are compared. This format is useful for student and resident teaching, for counseling parents-to-be about potential outcomes, for consulting with out-of-hospital physicians who request advice about maternal-fetal transport, and most important, for helping to make the crucial decisions necessary during the management of labor and delivery of infants with low birth weight and early gestational age.

Black or African American↗

Biochemical effects of 12-O-tetradecanoylphorbol-13-acetate, retinoic acid, phenobarbital, and 5-azacytidine on a normal rat liver epithelial cell line.

The effects of 12-O-tetradecanoylphorbol-13-acetate (TPA), all trans-retinoic acid (RA), 5-azacytidine (5-AC), and phenobarbital (PB) on the activities of seven enzymes and/or isozymes of a diploid rat liver epithelial cell line have been studied. At 0.1 microgram/ml, TPA depressed the specific activities of lactate dehydrogenase and gamma-glutamyl transpeptidase, whereas 2 mM PB depressed gamma-glutamyl transpeptidase and alkaline phosphatase. At 0.01 microgram/ml, RA markedly depressed the activity of NADH-diaphorase and lactate dehydrogenase but enhanced the activity of alkaline phosphatase. Only 2 microM 5-AC caused the most significant shift of lactate dehydrogenase isozyme toward the "muscle"-type isozyme. Histochemical studies revealed that PB and 5-AC induced focal areas of cells with glycogen deposits, but no significant changes in either ultrastructure or alpha-fetoprotein and albumin immunohistochemical staining pattern were observed to suggest hepatocytic differentiation. Although none of the enzymatic changes could be consistently correlated with the effects of these biological modifiers on the cellular growth rate, the effect of RA on NADH-diaphorase, lactate dehydrogenase, and alkaline phosphatase activities was the opposite of the changes observed during carcinogenesis of these rat liver epithelial cells by multiple treatments with N-methyl-N'-nitro-N-nitrosoguanidine. The depression of gamma-glutamyl transpeptidase activity by PB is contradictory to that observed histochemically in hepatocytes in vivo, but such discrepancy may be related to the differences in cell type, growth conditions, or duration of exposure.

Animals↗

Menogaril: a new anthracycline agent entering clinical trials.

Menogaril [menogarol, 7(R)-O-methylnogarol, 7-OMEN] is a new anthracycline agent which was chosen for clinical trials based on: broad spectrum activity against a panel of murine tumors, lower cardiotoxicity than doxorubicin in the chronic rabbit model, differences in biochemical effects from other anthracyclines suggesting a possible difference in mechanism of action, murine antitumor activity by oral as well as parenteral routes. Biochemical studies indicated that, in comparison to doxorubicin, menogaril is bound weakly to DNA, inhibits RNA synthesis less, and has different cell cycle phase-specific cytotoxicity. Pharmacology studies in the mouse and dog using HPLC analytical methodology have shown multiexponential clearance from plasma and metabolism of menogaril to a material which co-chromatographs with N-demethylmenogaril in addition to at least two other metabolites of unknown structure. Oral bioavailability studies in the mouse showed significant absorption of menogaril from the gastrointestinal tract followed by first-pass metabolism. In acute toxicity studies in the rat, the dog, and the monkey, dose-related myelosuppression and gastrointestinal toxicity predominated. Phase I clinical trails on menogaril are currently in progress on a variety of schedules.

Administration, Oral↗

Histochemical identification of cultured cells from human endometrium.

Histochemical techniques have been applied to the identification of cell types cultured from human endometrium. Previous work from this laboratory characterized two principal cell types found in cultures of endometrium: a mature epithelial cell and another cell which was classified as the endometrial stromal cell based on light and electron microscopy. In this report we compare the histochemical staining of endometrial tissue in frozen sections to that of cultured cells. These results confirm the epithelial and stromal nature of the respective cell types. Several markers were found that could distinguish between cells of epithelial and stromal origin. The enzymes alkaline phosphatase, gamma-glutamyltranspeptidase, peroxidase, and beta-glucuronidase were localized in glandular and surface epithelia in frozen sections and in colonies of epithelial cells in culture. Stroma in frozen sections and cultured stromal cells contained leucine aminopeptidase and fibronectin. Epithelia in sections and in culture could also be distinguished from cells of stromal origin by preferential binding of lotus and peanut lectin. Several other markers were found in both endometrial epithelium and stroma.

Alkaline Phosphatase↗

A diploid epithelial cell line from normal adult rat liver with phenotypic properties of 'oval' cells.

A diploid epithelial cell line (termed WB-F344) was isolated from the liver of an adult male Fischer-344 rat and the phenotypic characteristics of the cells were studied. These cells measure approximately two-fifths the volume of freshly isolated hepatocytes. They are histochemically negative for glucose-6-phosphatase and weakly positive for gamma-glutamyl transpeptidase. They produce extensive intercellular reticulin fibers which stain immunocytochemically for fibronectin, and they synthesize both alpha-fetoprotein and albumin, but they do not accumulate glycogen particles. Ultrastructurally, they are polygonal cells with numerous intercellular desmosomes and nexus junctions, and they are partially surrounded by basement membrane-like material. Cytoplasmic organelles include few, but sometimes dilated profiles of rough endoplasmic reticulum, lysosomes, abundant free ribosomes, sparse smooth endoplasmic reticulum and Golgi membranes, microbodies, and small, pleomorphic mitochondria. They express A and C isozymes of aldolase, K isozyme of pyruvate kinase, LDH2 to LDH5 isozymes of lactate dehydrogenase, and 'fetal liver'-type alkaline phosphatase isozyme. When compared with the phenotypes of isolated and purified normal hepatocytes, biliary epithelial (ductular) cells and 'oval' cells isolated from livers treated with chemical carcinogens, the phenotypic properties of the liver epithelial cell line in culture most resemble those of the 'oval' cells.

Animals↗

Promotional effect of diethylstilbestrol on human endometrial stromal cells pretreated with a direct-acting carcinogen.

Chronic treatment with 0.1 microM diethylstilbestrol (DES) increased the expression of phenotypic alterations in human endometrial stromal cells pretreated with the direct-acting carcinogen N-methyl-N'-nitro-N-nitrosoguanidine (MNNG). Abnormal morphology, expression of gamma-glutamyltranspeptidase, and the ability to form colonies under restrictive conditions were more pronounced after combined treatment with carcinogen and DES compared to carcinogen or DES alone. This effect did not appear to be due simply to growth enhancement by DES, because acute treatment with DES did not alter colony formation, growth rate or thymidine incorporation into DNA in stromal cell cultures. Neither did the presence of DES after the toxicity of MNNG. DES did cause shifts in the isoenzyme distribution of lactate dehydrogenase which could be indicative of a hormonal response. The results suggest that DES may act as a tumor promoter or cocarcinogen in human cells through a mechanism other than simply stimulating cell proliferation, but that other estrogenic effects may contribute to the promotional process.

Carcinogens↗

The unanticipated breech presentation in labor.

In summary, the obstetrician often cannot anticipate the appearance of a woman with a breech fetus in labor, and, in the majority of instances, a woman will be in labor before the diagnosis is made. To obtain the best outcome with both preterm and term breech fetuses, the appropriate data must be obtained rapidly, and a plan of management based on this data must be developed. Management protocols outlined in this article, although not ensuring a good outcome in every instance, most often will result in the delivery of a healthy newborn. We should emphasize again that if the information described above is not available, then the safest course in most instances is delivery by cesarean section.

Body Weight↗

Delay in delivery: influence of gestational age and the duration of delay on perinatal outcome.

The potential benefits to be gained in neonatal survival and freedom from serious morbidity by delaying delivery at various gestational ages was explored by examining the results of studies of neonatal mortality and subsequent morbidity published from 1978 and 1984. The major benefits were found to occur between 24 and 27 weeks' gestational age. In general, little benefit was found in delaying delivery after 34 weeks' gestational age.

Birth Weight↗

The heterogeneity of LDH isoenzyme patterns of human uterine sarcomas and cultured sarcoma cell lines.

Both the tissue lactate dehydrogenase (LDH) isoenzyme pattern and total LDH activity were investigated in a series of human uterine sarcomas and cell lines derived from these tumors. Abnormal LDH isoenzyme patterns characterized by shifts toward the muscle isoenzyme forms (LDH4 and 5) were found in some, but not all, of the sarcomas. The tumors containing rhabdomyosarcomatous elements usually had normal or only slightly altered LDH isoenzyme patterns. The LDH isoenzyme patterns expressed by cultured cell lines established from the uterine sarcomas, in general, resembled those found in the primary tumors. These results suggest that the normal or near normal LDH isoenzyme distributions found in uterine sarcomas with rhabdomyosarcomatous differentiation may be a potential characteristic which may be used for distinguishing these tumors from other uterine sarcomas.

Adult↗

Fractionation and characterization of DNA at sites of replication from rat liver nuclei.

Regenerating rat liver nuclei when sonicated and centrifuged in a Cs2SO4 gradient were fractionated into three distinct bands. These bands were designated as light band (LB), middle band (MB), and heavy band (HB) according to their density. LB and MB were shown to consist of large granular particles with varying electron densities, but LB also contained remnants of nuclear membrane. When analysed by gel electrophoresis, LB and MB displayed more than 35 bands of proteins. The third fraction, HB, consisted largely of small chromatin fibers and its proteins were predominantly the four histones of the nucleosomal core particle. Following short pulses with [3H]thymidine in vivo, the specific activity of DNA in LB and MB was significantly higher than that of bulk DNA contained in HB. DNA in all three fractions became equally labelled as the duration of the labelling interval increased beyond 30 min. Newly synthesized DNA was characterized by electrophoresis on analytical 1.7% acrylamide -0.5% agarose composite gels. After a 1-min labelling interval in vivo, 17% of the rapidly labelled DNA from LB and MB was stationary at the gel origin like replication forks from E. coli, but only 3% of HB DNA had zero mobility. Electron microscopy confirmed the presence of DNA replication forks in LB, MB, and HB. With increasing time of synthesis the proportion of labelled DNA exhibiting zero mobility decreased in all three fractions. Denaturation of DNA or digestion of single-stranded DNA with S1 nuclease released newly synthesized DNA from the gel origin. Ribonuclease was without effect. DNA recovered from LB and MB also had a higher molecular weight than the HB DNA. Together these results indicate (1) that LB and MB are enriched in newly replicated DNA; (2) that an increased proportion of newly replicated DNA in LB and MB is associated with DNA replication forks; and (3) that the replicating DNA recovered in LB and MB may be associated with other nuclear constituents in situ because this DNA appears to be protected from the more frequent chain breaks introduced into the bulk of chromatin (HB) by sonication.

Animals↗

Characterization of a pure heterologous sarcoma of the uterus: rhabdomyosarcoma of the corpus.

A case of a pure heterologous sarcoma of the uterine corpus composed exclusively of rhabdomyosarcomatous elements has been studied by multiple morphologic and biochemical techniques. The neoplasm filled the endometrial cavity and protruded out the cervical os, but the myometrium was only superficially invaded. The tumor did not extend outside the corpus. The pathologic features are discussed in detail. Evidence of striated muscle differentiation could be identified on light microscopic and ultrastructural examination. Immunoperoxidase staining of tumor cells with antibodies to myoglobin were positive. Histochemical preparations for lactate dehydrogenase, succinic dehydrogenase, and acid phosphatase were also positive in neoplastic cells. Other stains gave equivocal or negative results. These findings are discussed in comparison with previous reports.

Acid Phosphatase↗

Simultaneous appearance of keratin modifications and gamma-glutamyltransferase activity as indicators of tumor progression in mouse skin papillomas.

gamma-Glutamyltransferase (GGT), an enzyme not found in normal adult epidermis, was detected in most skin papillomas larger than 13 mm in diameter and in all squamous carcinomas induced by 7,12-dimethylbenz[a]anthracene initiation and 12-O-tetradecanoylphorbol 13-acetate promotion in noninbred Sencar mice. Furthermore, these GGT-positive lesions were also characterized by a marked decrease or absence of high-molecular-weight components of epidermal keratin. Since these characteristics are common to both carcinomas and large papillomas but are practically undetectable in normal epidermis and small papillomas, GGT activity and lack of high-molecular-weight keratin components seem to be good indicators of tumor progression, i.e., from papilloma to squamous carcinoma.

9,10-Dimethyl-1,2-benzanthracene↗

The variability of viability: the effect of physicians' perceptions of viability on the survival of very low--birth weight infants.

Physicians who deliver babies in Alabama were surveyed to determine their level of knowledge about the survival of low--birth weight/early gestational age infants. These estimates of neonatal survival were compared to the actual neonatal survival rates at local hospitals and at the regional perinatal centers in Alabama. In addition, the physicians' knowledge of survival rates was correlated with their management decisions in hypothetical cases of premature labor. Our findings indicate that physicians who perform deliveries tended to underestimate the potential for neonatal survival in premature infants. Equally as important, the range of responses varied markedly. In the hypothetical cases, management decisions often appeared to be based on incorrect information about neonatal survival. These decisions, including not electronically monitoring fetuses, not performing a cesarean section for fetal distress, and not transferring women in premature labor to a perinatal center, if made in actual cases, would result in potentially viable fetuses receiving less than optimal management.

Adult↗

The teen-tot clinic: an alternative to traditional care for infants of teenaged mothers.

A comprehensive interdisciplinary clinic was established to provide health care for teenaged mothers less than 16 years old and their infants. Thirty-five mother-infants pairs using this clinic were matched with 70 mother-infant pairs who used "traditional" health care facilities. Significant differences in infant outcomes of immunization status at 6 months (91% versus 46% completed), and weight (97% versus 83% within "normal" range) and maternal outcomes of contraceptive use (91% versus 63%), enrollment in educational programs (86% versus 66%), and repeat pregnancy rate (16% versus 38%) were found between Teen-Tot Clinic participants and the control group. Coordination and consolidation of services for teenaged mothers and their infants appears to favorably influence their short-term outcomes.

Adolescent↗

Effects of inhibitors of tumor promotion on 12-O-tetradecanoylphorbol-13-acetate-induced keratin modification in mouse epidermis.

In order to investigate the role that hyperplasia plays in the induction of the keratin modifications by the tumor promoter 12-O-tetradecanoylphorbol-13-acetate (TPA), the effects of several inhibitors of tumor promotion and cycloheximide on the TPA-induced protein changes were studied. The antiinflammatory steroid fluocinolone acetonide and cycloheximide, which prevent the induction of hyperplasia, were found to prevent the appearance of the TPA-induced keratin modifications. Retinoic acid and tosylphenylalanylchloromethyl ketone, which have minor influence on hyperplasia, were found to have essentially no effect on these protein changes. These results provided further evidence that the TPA-induced epidermal keratin changes were associated with the induction of hyperplasia by TPA and not necessarily related to promoting ability.

Animals↗