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Biomedical subjects

L K Johnson

Publications and source records attributed to L K Johnson.

At least 73 records · Page 4Linked to original sources

Maternal zinc, iron, folic acid, and protein nutriture and outcome of human pregnancy.

Four hundred fifty women were observed during pregnancy and postpartum. Forty-three variables including 12 laboratory indices of maternal nutrient status were assessed. Of the variance in fetal weight and head circumference 9.9 and 8.1%, respectively, were predictable by polynomial stepwise regression of laboratory indices of maternal nutriture. Maternal plasma zinc levels were inversely correlated with fetal weight. The occurrence of pregnancy complications in the highest and lowest quartiles of maternal plasma zinc, albumin, iron, and folic acid were compared. Using data only from the initial blood samples for which the trimester was identified precisely (n = 394), a significant association was found between the total occurrence of fetomaternal complications and zinc and albumin levels in the lowest quartile (zinc, p less than 0.02; albumin, p less than 0.02). Low zinc or low albumin were also associated with the specific complications of fetal distress (zinc, p less than 0.002; albumin p less than 0.002). High plasma folate was also associated with the total occurrence of complications (p less than 0.008) and with fetal distress (p less than 0.002). When all data (n = 713) including repeat blood samples and data from 56 mothers in whom the trimester could not be verified precisely were evaluated, associations between other complications and lowest quartile zinc and albumin and highest quartile folate were identified. Discriminant analysis of data from the initial blood samples revealed that plasma zinc was a discriminator for fetomaternal complications only in women in the lowest quartile for plasma zinc.

Adult↗

Zinc nutriture in type I diabetes mellitus: relationship to growth measures and metabolic control.

Zinc concentrations in plasma, hair, and urine from children and young adults with insulin-requiring or Type I diabetes mellitus were significantly correlated with height, weight, and age, as well as with indices of metabolic control, i.e., fasting serum glucose, percent glycosylated hemoglobin (HbA1), and 24-h urine glucose and insulin excretion. Urinary zinc excretion was greater in subjects than in controls (p less than 0.0001) and significantly correlated with urine glucose (p less than 0.004, r = 0.35) and volume (p less than 0.0007, r = 0.40). Urinary zinc and volume were not correlated in controls. Hyperzincuria in the subjects was not secondary to hyperinsulinuria, although zinc and insulin excretion were significantly correlated in controls (p less than 0.03, r = 0.63). Zinc in insulin preparations could not explain the excessive zinc excretion. Mean fasting plasma zinc was significantly higher than in controls, and positively correlated with height for age, while being inversely correlated with age, duration of diabetes, HbA1, urine volume, and glucose excretion. Both the mean and range of hair zinc concentration in the subjects were not different from controls. Male subjects with diabetes had a significantly lower hair concentration when compared with female subjects with diabetes (p less than 0.0009). Zinc homeostasis appears to be altered as a consequence of glucose intolerance in diabetes. Continued urinary zinc losses over time may result in a zinc deficiency state not demonstrable by altered zinc concentrations in plasma and hair.

Adolescent↗

Proliferative variability of endothelial clones derived from adult bovine aorta: influence of fibroblast growth factor and smooth muscle cell extracellular matrix.

Four endothelial cell clones derived from adult bovine aorta were examined with respect to their proliferative characteristics in vitro. Three of these clones, derived in the absence of fibroblast growth factor (FGF), displayed variable basal proliferative rates. One of these non-FGF derived clones grew at a maximal rate which could not be further enhanced with FGF. The other two clones grew at a suboptimal rate which was stimulated by low doses of FGF (10-50 ng/ml) and inhibited by higher doses (100-250 ng/ml). The fourth clone, derived in the presence of FGF, was stimulated by FGF in a dose-dependent manner (10-250 ng/ml) and was not growth inhibited at high FGF concentrations (250-1,000 ng/ml). Growth of all four clones on extracellular matrix (ECM) derived from bovine aortic smooth muscle (BASM) cells was optimal in the absence of FGF. ECM-coated dishes also significantly increased the sensitivity of all clones by at least fivefold to mitogenic stimulation by serum. The proliferative lifespans of the clones ranged between 60 and 120 generations with the most actively proliferating clones attaining the greatest lifespan. Continuous subculture of two of the endothelial clones in the presence of FGF or on ECM-coated dishes did not induce a dependence of the cells on either factor for subsequent growth in its absence. The results indicate that aortic endothelial cells display considerable clonal variability in ther basal proliferative rate and in their response to FGF. This clonal variability is not observed when the cells are maintained on ECM-coated dishes derived from vascular smooth muscle cells.

Animals↗

Effect of a moderate increase in dietary protein on the retention and excretion of Ca, Cu, Fe, Mg, P, and Zn by adult males.

Mineral utilization was studied by metabolic balance techniques in 10 healthy male volunteers fed diets containing 65 and 94 g protein. Both diets contained approximately 650 mg calcium, 1 mg copper, 16 mg iron, 250 mg magnesium 1000 mg phosphorus, and 7 mg zinc. The diet consisted of conventional foods; the additional 29 g protein was egg white protein mixed into a beverage and fed twice per day. Plasma mineral levels were not affected by the increase in dietary protein. When the diet provided 94 g of protein, urinary calcium and zinc were slightly, but significantly, increased by an average of 35 mg (p less than 0.05) and 0.15 mg (p less than 0.001), respectively. Apparent mineral absorption and balance were unchanged by this modest increase in dietary protein.

Absorption↗

Folate status of adult males living in a metabolic unit: possible relationships with iron nutriture.

Folate and iron status was monitored at monthly intervals in 40 adult males who were living in a metabolic unit for 2 to 8 months and consuming diets containing 150 to 250 micrograms of folate per day. There were significant (p less than 0.02) declines in hematocrit, serum folate, and serum ferritin. Men who participated in studies for 6 months or more or those with initial serum folate levels more than 10.5 ng/ml and erythrocyte folate levels more than 481 ng/ml also exhibited a highly significant (p less than 0.001) decline in red blood cell folate. Men with erythrocyte folate below 480 ng/ml or serum folate below 10 ng/ml and who participated in the studies for less than 5 months showed little or no change in folate status. The findings may reflect adjustments in body folate to reflect dietary intakes. Also a folate intake of 200 +/- 68 micrograms/day appeared to be adequate for maintenance of folate stores in adult males. A correlation between iron stores and folate status was also observed. However, this relationship may be coincidental.

Adult↗

The effect of interactions between dietary egg white protein and zinc on body weight, bone growth and tissue trace metals in the 30-day-old rat.

Nine groups of 30-day-old rats were fed different diets, which contained 8, 15 or 20% egg white (equivalent to 6.0, 11.3 and 15.0% protein, respectively) each at 3 levels of zinc (6, 12 and 18 ppm zinc) for 30 days. The rats consuming the 6.0% protein, regardless of zinc intake, gained less weight than the groups fed 11.3 or 15.0% protein. Plasma zinc was not influenced by dietary egg white protein content, whereas, plasma zinc levels were lower in the rats fed 6 ppm dietary zinc compared to those fed 12 or 18 ppm zinc. Of the liver trace metals measured, only iron appeared to be influenced by an egg white protein-zinc interaction. Increasing dietary egg white protein led to increased concentrations of liver zinc and magnesium. Dietary zinc levels had no effect on the concentration of these metals in the liver. Liver calcium and copper concentrations were not significantly influenced by either dietary zinc or egg white protein. Femur weights and lengths were lower in the rats fed 6.0% than in those fed 11.3 or 15.0% protein diet but were unaffected by dietary zinc. Femur width was related to dietary protein and zinc. Dietary protein and zinc were interrelated in their affect on femur zinc levels. Femur zinc concentrations increased with increasing dietary zinc levels. Also femur zinc levels decreased with increasing dietary protein content. Other femur metal (copper, iron and calcium) concentrations were higher in rats fed the low level versus the higher levels of protein, but were not influenced by dietary zinc. These results show that dietary zinc and egg white protein are interrelated with regard to their effect on body and femur growth and tissue trace metal content.

Animals↗

Altered adhesiveness of tumor cell surface variants with reduced metastasizing capacity--reduced adhesiveness to vascular wall components in culture.

Heterotypic adhesiveness of surface variant clones of B-16 melanoma cells exhibiting different metastasizing capacity was studied with respect to components of the vascular wall in culture including endothelial (E) and smooth muscle (SM) cells from adult bovine aorta, and the extracellular matrices laid down by them. The ricin-resistant cells (ricinR) and the wheat-germ agglutinin-resistant (WGAR) cells, both of which showed reduced hematogenous metastases in vivo, showed reduced adhesiveness specifically to endothelial cells and extracellular matrices. This reduced heterotypic adhesiveness is in contrast to the homotypic adhesive properties in which respect the ricinR cells had similar values to the parental cells, while the WGAR cells had much higher values than the latter. There appeared to be a positive correlation between metastasizing capacity and specific adhesiveness to E cells and the extracellular matrix surfaces.

Blood Vessels↗

Glucocorticoid influence on growth of vascular wall cells in culture.

Primary mass cultures and cloned strains of bovine aortic endothelial and smooth muscle cells were investigated with respect to their growth responses to glucocorticoid hormones. The growth of primary endothelial cells was not influenced by glucocorticoid treatment in the absence of fibroblast growth factor (FGF) but was inhibited by about 30% in the presence of FGF; with cloned endothelial cells, glucocorticoids were also growth inhibitory only in the presence of FGF. In contrast, smooth muscle cell growth was inhibited 30%-70% by glucocorticoid treatment in both primary cultures and in the cloned strains in the absence of FGF, and this inhibition was totally abolished by the addition of FGF for both cultures. The corticosteroid influences on cell growth were glucocorticoid specific, concentration dependent, and were observed to be independent of the serum concentration. The results indicate that glucocorticoid hormones have direct and pronounced growth inhibiting effects on aortic smooth muscle cells but only minimal effects on endothelial cells when these components of the vascular wall are analyzed under identical conditions in vitro.

Animals↗

Senescence of aortic endothelial cells in vitro: influence of culture conditions and preliminary characterization of the senescent phenotype.

The replicative lifespan of a cloned strain of adult bovine aortic endothelial cells has been examined by serial passage in culture using conditions where the cells were either dependent on fibroblast growth factor (FGF) for rapid growth or relatively independent on FGF for growth. In FGF-dependent cultures a replicative lifespan of 130 generations was attained with a phase III period which spanned approximately 20 generations. Withdrawal of FGF at generation 55 and repeated passage of such cultures in the absence of the growth factor resulted in the loss of proliferative potential within 15 generations. The morphological changes occurring upon FGF withdrawal were different than those that occurred when cultures senesced in the presence of FGF, FGF withdrawn cells showed a homogeneous increase in cell size and after several passages overgrew one another at confluency. Endothelial cells which senesced in the presence of FGF showed a very heterogeneous distribution of enlarged cells, many of which were binucleated but continued to form a confluent monolayer at high cell densities. Under FGF-independent conditions (begun at generation 48) a replicative lifespan of 105 generations was attained in the presence of the growth factor. FGF withdrawal under these conditions only decreased the replicative lifespan to 95 generations. Under these conditions the morphological changes occurring during phase III were identical in the presence and absence of FGF. Examination of the sensitivity of endothelial cells to FGF as they entered phase III showed that their dose-response characteristics were not qualitatively altered after the onset of phase III, although the number of cells responding to FGF progressively dropped. Comparison of the patterns of proteins synthesized in phase II and phase III cultures showed that phase III cultures even when plated at sparse densities continued to synthesize proteins which were normally observed in phase II confluent cultures. The results indicate that onset of the phase III period in aortic endothelial cells cloned and maintained in the presence of fibroblast growth factor can be delayed to a greated extent if the cells are maintained under conditions where they are made dependent on FGF for rapid growth in culture.

Aging↗

Differential regulation by glucocorticoids of proopiomelanocortin mRNA levels in the anterior and intermediate lobes of the rat pituitary.

Glucocorticoids negatively regulate de novo synthesis of proopiomelanocortin (POMC) and the steady state POMC mRNA levels in the rat pituitary anterior lobe. The POMC system of the intermediate lobe is far less sensitive to alterations in circulating glucocorticoid levels. Possible mechanisms for this differential regulation of POMC gene expression in the two tissues are discussed.

Adrenalectomy↗

Synthesis of growth hormone, prolactin, and proopiomelanocortin by intact adult ovine pituitary tissue in vitro.

Synthesis of GH, PRL, and proopiomelanocortin (POMC) by the adult ovine pituitary was examined by culturing intact tissue explants in vitro and analyzing newly synthesized proteins by two-dimensional gel electrophoresis. Spots on autoradiographs of two-dimensional gels were identified by comigration with known standards, by analysis of tryptic peptides, or both. GH and PRL are the predominant proteins synthesized in the adult ovine pituitary, but their syntheses could not be detected in the neurointermediate lobe of the pituitary, the cerebral cortex, hypothalamus, mammillary body, or placenta. As quantified by cell-free translation in rabbit reticulocyte lysate, 14% of female ovine pituitary mRNA encodes pre-GH and 30% encodes pre-PRL. As determined by sodium dodecyl sulfate-polyacrylamide gel electrophoresis, ovine pre-GH and pre-PRL have molecular weights of 24,500 and 26,000, respectively, indicating they contain leader peptides of 26-30 amino acids, as found in bovine, rat, and human pre-GH and pre-PRL. POMC, the precursor to corticotropin, endorphin, and other peptides, was synthesized primarily in the neurointermediate lobe of the pituitary, but synthesis was also detected in the anterior lobe. POMC synthesis was not detected in the hypothalamus, cerebral cortex, mammillary body, or placenta.

Animals↗

Synthesis and glycosylation of proopiomelanocortin by a Cushing tumor.

ACTH derives from a larger protein, proopiomelanocortin (POMC), which is also the precursor to lipotropin, endorphin, melanotropin, and other peptides. The sequence of steps by which POMC is processed to ACTH has been delineated in detail in cultured mouse tumor cells, but little is known about these steps in human pituitary adenomas. Synthesis and glycosylation of POMC were studied in a pituitary adenoma causing Cushing disease and in adjacent tissue by incubating intact tissue explants in medium containing [35S]methionine or [3H]glucosamine. Labeled tissue was analyzed by two-dimensional gel electrophoresis, and a spot cut from these gels was analyzed by paper electrophoresis of tryptic digests. The location of the spot and the patterns of its [35S]methionine-labeled tryptic fragments resembled those found previously in other ACTH-secreting tissues and hence this spot appears to be POMC. Both the tumor and the adjacent pituitary produced this POMC, although tumor production of POMC was greater. The electrophoretic patterns of the putative POMC tryptic peptides labeled with [35S]methionine from this tumor are similar to the patterns of POMC tryptic peptides from a Nelson tumor and an ectopic ACTH- producing tumor when analyzed by the same techniques. This suggests that the excess ACTH in all three diseases arises from the same precursor POMC molecule. Two-dimensional gel electrophoresis of [3H]glucosamine-labeled tumor suggests that the first proteolytic cleavage occurs between the alpha ACTH-(1-39) and beta-lipotropin sequences and that a subsequent cleavage occurs between the N-terminal region of POMC and ACTH. Paper electrophoresis of [3H]glucosamine-labeled tryptic glycopeptides reveals at least three radioactive peaks, suggesting that the two known glycosylation sites in human POMC may be variably glycosylated.

Adenoma↗

Differential radiation response of cultured endothelial cells and smooth myocytes.

In vivo observations have suggested that endothelial cells are the most radiosensitive elements of the vascular wall. To test whether this represents an intrinsic differential sensitivity, the response of bovine aortic endothelial cells and smooth myocytes was investigated in confluent cell cultures exposed to single doses of gamma radiation (250, 500, 1,000 or 2,000 rad). Both cell types showed a dose-dependent decrease in attachment efficiency when dissociated and replated at six hours after radiation. However, the attachment efficiency in both cell types was similar when a 72-hour postirradiation incubation period was used prior to dissociation of the cells. Growth inhibition was significantly greater (7- to 10-fold) in endothelial cells than in myocytes when examined four days after attachment. Confluent endothelial monolayers showed a dose-dependent, progressive cell loss during the 72-hour postirradiation period (70% after 1,000 rad); the myocyte cultures showed no radiation effect on the cell numbers. In spite of the reduction in number, the endothelial cells maintained the continuity of their monolayer by compensation with an increase in mean cell size. Endothelial cells developed multiple structural lesions, including an increase in the number and size of residual and lysosomal bodies, electron-lucent cytoplasmic defects, interruptions in the plasma membrane and irregular aggregation of chromatin, causing electron-lucent nuclei. These changes increased in severity with time and dose and were most pronounced 24 to 72 hours after 1,000 rad. No significant ultrastructural alterations were detected in myocytes four days after 2,000 rad.

Animals↗

Plasma zinc in hypertension/toxemia and other reproductive variables in adolescent pregnancy.

A study was conducted at Charity Hospital, New Orleans, among 272 adolescent pregnant women to ascertain the relationship of pregnancy outcome to plasma zinc level measured once at the time of enrollment. Regression analyses were performed on zinc status versus parameters concerning success of pregnancy corrected for gestational stage at specimen collection. Analysis of variance was performed on groups according to presence or absence of complications, with analyses of covariance used to analyze dichotomous groups. Low, though widely variable, plasma zinc levels were found (mean = 58 +/- 12.6 micrograms/dl). Zinc values differed significantly by gestational stage at collection, the regression coefficient indicating a decline of 0.07 micrograms/dl/day. Plasma zinc level correlated significantly with Hb, red blood cells, ferritin, and folic acid. As to course of pregnancy, women experiencing hypertension/toxemia were found to have significantly lower plasma zinc level. Among infants displaying congenital defects at birth those with undescended testes and metatarsus varus were delivered by mothers whose plasma zinc was well below the mean for the group. These findings indicate the need to investigate the influence of dietary patterns and zinc intake on maternal plasma zinc level and pregnancy outcome, further delineating the role of zinc in human reproduction, particularly hypertension of pregnancy.

Adolescent↗

Dietary fiber and personality factors as determinants of stool output.

We examined effects of fiber on stool output, since this is one of the primary mediating variables for the hypothesized relationship between fiber and disease. Total neutral detergent fiber in the dietary fiber source was predictive of stool weight but not frequency. Substantial individual differences in stool output remained when dietary factors were controlled. Personality measures were used to predict stool weight and frequency independently of diet, and accounted for about as much variance in stool output as did dietary fiber. These results suggest that personality factors predispose some persons to low stool output. These individuals may benefit particularly from dietary fiber.

Adolescent↗