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Biomedical subjects

C Ritter

Publications and source records attributed to C Ritter.

At least 55 records · Page 3Linked to original sources
PubMed1994

Retinoic acid suppresses parathyroid hormone (PTH) secretion and PreproPTH mRNA levels in bovine parathyroid cell culture.

1,25-dihydroxyvitamin D3[1,25(OH)2D3] suppresses parathyroid hormone (PTH) gene transcription. Recent evidence suggests that retinoid X receptors are involved in 1,25(OH)2D3-mediated transcriptional events. However, little data exists for a role of retinoids in parathyroid function or in PTH expression. In the present study, we observed that all-trans- or 9-cis retinoic acid suppressed the release of PTH from bovine parathyroid cell cultures. Both retinoids were remarkably potent with significant decreases evident at 10(-10) M and a maximally suppressive effect (approximately 65%) at 10(-7) M. All-trans-retinol was considerably less potent in this system. The effect was not evident until 12 h, suggesting that retinoids did not affect the rapid secretion of preexisting PTH stores. PreproPTH mRNA levels were also suppressed by retinoic acid and the retinoid potencies were similar to those observed in the secretion studies. Combined treatment with 10(-6) M retinoic acid and 10(-8) M 1,25(OH)2D3 more effectively decreased PTH secretion and preproPTH mRNA than did either compound alone. These data indicate that retinoic acid: (a) elicits a bioresponse in bovine parathyroid cells; (b) attenuates PTH expression at the protein and mRNA levels, and (c) acts independently of 1,25(OH)2D3 in the control of PTH expression.

Animals↗
PubMed1993

The mechanism for the disparate actions of calcitriol and 22-oxacalcitriol in the intestine.

22-Oxacalcitriol (OCT) is one of several new analogs of vitamin D that retain many of the therapeutically useful properties of 1,25-dihydroxyvitamin D3 [1,25-(OH)2D3], but have much less calcemic activity. In the present study we examined the actions of OCT on intestinal calcium absorption and calbindin D9k mRNA in vitamin D-deficient rats. After ip injection of OCT (1 microgram/kg), calcium absorption increased significantly by 2 h and was maximal at 4 h (2.5-fold above control), but returned to pretreatment levels by 16 h. In contrast, the same dose of 1,25-(OH)2D3 caused a 3-fold increase in calcium absorption, which lasted more than 48 h. The transient effect of OCT on calcium absorption was also observed when the analog was infused at a dose of 1 micrograms/kg.day for 3 days. At the end of the infusion period, calcium absorption was 3-fold higher than that in vehicle-infused controls, but fell to pretreatment levels by 24 h after removing the minipumps. The time courses for induction of calbindin D9k mRNA were similar for OCT and 1,25-(OH)2D3, with no change observed until more than 4 h after injection. However, calbindin mRNA levels returned to pretreatment values more rapidly in the OCT-treated rats. Consistent with these findings, we observed that a 1 microgram/kg dose of [3H] OCT was completely cleared by 4-6 h after injection. This was paralleled by a loss of [3H]OCT associated with the intestinal vitamin D receptor. The rapid clearance of OCT is probably due to its low affinity for the serum vitamin D-binding protein. This low affinity would also be expected to allow greater accessibility to target cells. In support of this, we found that higher amounts of OCT than 1,25-(OH)2D3 were associated with the intestinal vitamin D receptor after the injection of several doses of these tritiated ligands. In summary, our results indicate that the pharmacokinetic properties of OCT are responsible at least in part for its low calcemic activity. Furthermore, comparison of the transient elevation of calcium absorption by OCT with its more prolonged effects on PTH and calbindin D9k indicates that each action of vitamin D compounds has a distinct biological half-life. The short circulating half-life of OCT can exploit these differences to provide a therapeutic advantage in the treatment of vitamin D-responsive diseases.

Animals↗
PubMed1993

Bayesian analysis of lamb survival using Monte Carlo numerical integration with importance sampling.

Approximate and exact Bayesian analyses of survival from birth to weaning measured as an "all or none" trait were conducted on 2,554 Rambouillet lambs using an asymptotic normal approximation and Monte Carlo numerical integration with importance sampling, respectively. A linear logistic model was used to assess the effects of year, age of dam, sex of lamb, and type of birth on the survival probability. A least squares analysis of the data, ignoring their discrete nature, was also performed. The Bayesian analyses were compared by plotting the marginal posterior distributions and by constructing 95% highest-posterior-density regions for some parameters of interest. The analyses were repeated for a reduced data set consisting of 300 observations selected at random from the original file. For all practical purposes, the Bayesian and non-Bayesian analyses yielded identical results despite their different interpretations. Also, the asymptotic normal approximations to the true posterior distributions were excellent. Undoubtedly, this is because the likelihood functions contained a large amount of information about the parameters. Four-year-old ewes produced lambs with greater survival rates than either younger or older ewes. Female and male lambs had similar rates, and single-born lambs had a 10% higher survival rate than multiple-born lambs.

Age Factors↗
PubMed1992

Metabolism of 22-oxacalcitriol by a vitamin D-inducible pathway in cultured parathyroid cells.

Catabolism of 22-oxacalcitriol (OCT) in parathyroid cells was compared to that of the parent hormone, 1,25-dihydroxyvitamin D3 [1,25-(OH)2D3]. Catabolism of both compounds was greatly accelerated by pretreatment of the cells with 1,25-(OH)2D3 or OCT. The rate of degradation of OCT was slightly greater than that of 1,25-(OH)2D3. Excess unlabeled OCT or 1,25-(OH)2D3 inhibited metabolism of both tritiated substrates. Ketoconazole, a cytochrome P450 inhibitor, blocked catabolism of both compounds. The major OCT metabolite appeared to be 1,20-dihydroxy-22,23,24,25,26,27-hexanor-vitamin D3 which was not active in suppressing PTH secretion. We conclude that OCT appears to be metabolized by the same vitamin D-inducible side chain oxidation pathway that catabolizes other vitamin D compounds and that its higher than expected suppression of PTH secretion is not due to slower cellular metabolism.

Animals↗
PubMed1992

Functional homologs of the Arabidopsis RPM1 disease resistance gene in bean and pea.

We showed that a bacterial avirulence (avr) gene function, avrPpiA1, from the pea pathogen Pseudomonas syringae pv pisi, is recognized by some, but not all, genotypes of Arabidopsis. Thus, an avr gene functionally defined on a crop species is also an avr gene on Arabidopsis. The activity of avrPpiA1 on a series of Arabidopsis genotypes is identical to that of the avrRpm1 gene from P.s. pv maculicola previously defined using Arabidopsis. The two avr genes are homologous and encode nearly identical predicted products. Moreover, this conserved avr function is also recognized by some bean and pea cultivars in what has been shown to be a gene-for-gene manner. We further demonstrated that the Arabidopsis disease resistance locus, RPM1, conditioning resistance to avrRpm1, also conditions resistance to bacterial strains carrying avrPpiA1. Therefore, bean, pea, and conceivably other crop species contain functional and potentially molecular homologs of RPM1.

Amino Acid Sequence↗
PubMed1992

Race differences in the effects of multiple roles on health: longitudinal evidence from a national sample of older men.

This paper examines race differences in the effects of social roles on physical health. Using data from the older men cohort of the National Longitudinal Surveys of Labor Market Experience, we examine the impact of employment, marriage, and being a supporter on health limitations and mortality. Employment has the most consistent health-protective effect, and the benefits of employment are more pronounced for Blacks than for Whites. Marriage affects health in conjunction with employment. These findings lend further support to the growing literature on the effects of roles on health. The results further illustrate the importance of ascribed statuses as structural determinants of the relationship between roles and health, highlighting the very real differences in the meanings and expectations of social roles for Blacks and Whites.

Black or African American↗
PubMed1991

IgE hidden in immune complexes with anti-IgE autoantibodies in children with asthma.

Serum levels of IgE, anti-IgE autoantibodies (Abs), and IgE/IgG anti-IgE immune complexes (ICs) were measured in 110 children with asthma and 90 healthy control children. Significantly enhanced levels of IgE/anti-IgE IC were detected in children with asthma. However, only a weak correlation was found between anti-IgE auto-Ab serum levels and the degree of lung function abnormalities in children with asthma. However, children with asthma with low serum IgE levels had elevated IC serum levels of IgE/anti-IgE auto-Abs, suggesting that IgE might be hidden within these ICs and is therefore not measurable in vitro. The significant elevation of IgE/anti-IgE IC serum levels raises the question whether IgE within ICs is neutralized or might still be involved in immunologic mechanisms responsible for clinical symptoms of bronchial asthma.

Adolescent↗
PubMed1991

Extrarenal production of calcitriol in normal and uremic humans.

We have previously reported low serum levels of 1,25-dihydroxyvitamin D3 [1,25-(OH)2D3] and increased 1,25-(OH)2D3 production after the administration of 25-hydryoxyvitamin D (25OHD) to anephric humans. Since normal alveolar macrophages are known to synthesize 1,25-(OH)2D3 when stimulated with gamma-interferon or lipopolysaccharide, we determined whether macrophages derived from peripheral blood monocytes could be an extrarenal source of 1,25-(OH)2D3. Our results demonstrated that macrophages from normal individuals synthesize 1,25-(OH)2D3. The apparent Km for 25OHD3 was 6.6 +/- 0.5 nM and the maximum velocity was 47.4 +/- 13.7 fmol 1,25-(OH)2D3/h.microgram DNA. The activity of this enzyme was reduced 37.2 +/- 3.1% by physiological concentrations (96 pmol/L) of 1,25-(OH)2D3 in the incubation medium. Normal macrophages further hydroxylated 1,25-(OH)2D3 to more polar metabolites, and this catabolic activity was significantly enhanced by physiological concentrations of 1,25-(OH)2D3. In chronic renal failure, peripheral macrophages exhibited an enhanced 1 alpha-hydroxylase activity (8.2 +/- 0.8 vs. 4.2 +/- 0.5 fmol 1,25-(OH)2D3/microgram DNA.h in controls) and a decreased capacity to degrade 1,25-(OH)2D3. Exogenous 1,25-(OH)2D3, in physiological concentrations, reduced 1,25-(OH)2D3 synthesis to a degree (23.6 +/- 8.5%) comparable to that observed in normal cells. 1,25-(OH)2D3 production by macrophages did not correlate with the severity of hyperparathyroidism. Moreover, human PTH-(1-34) in supraphysiological concentrations (20,000 and 100,000 ng/L) did not stimulate the 1 alpha-hydroxylase activity of macrophages from either normal or uremic subjects. These results demonstrate that 1) normal peripheral macrophages metabolize 25OHD3 and 1,25-(OH)2D3; 2) macrophages in uremia display higher rates of 1,25-(OH)2D3 synthesis and lower rates of catabolism than normal macrophages; and 3) 1,25-(OH)2D3 deficiency, but not hyperparathyroidism, may play a role in the stimulation of 1,25-(OH)2D3 production by macrophages in chronic renal failure.

25-Hydroxyvitamin D3 1-alpha-Hydroxylase↗
PubMed1990

[A heat gelatinized subdural hematoma in a burned cadaver as an indication of a vital accident].

The autopsy of a carbonized male cadaver revealed a subdural hematoma which permitted by absence of soot aspiration and carbon monoxid intoxication to think of a crime with following fire setting. This was confirmed later by detective investigations. The most impressive finding of this case was a heat-gelatinized subdural hematoma highly resembling to a postmortem epidural burn hematoma, which could easily lead to an error conclusion. The problems in the diagnosis of the causes of death in carbonized bodies are discussed and the taking into account of crimes is accentuated.

Adult↗
PubMed1990

The prevalence and self-reported consequences of cocaine use: an exploratory and descriptive analysis.

In this study, prevalence rates for cocaine use were estimated by sex and race, as well as for selected social role and lifestyle characteristics, including educational level, martial status, living arrangements, job type and employment status. Prevalence rates were based on an estimation procedure that made the age-race-sex distributions balanced to that of the nation as a whole. Data were gathered from a multi-site probability sample of adults interviewed in 1981-1984 as part of the National Institute of Mental Health Epidemiologic Catchment Area Program (ECA) (n = 14,333). In addition to prevalence of use, rates of self-reported consequences of cocaine use were generated, by level of cocaine use. Striking differences in prevalence were found by education and marital status, which remained after controlling for age of respondent. Respondents who were employed full-time had a higher prevalence of cocaine use than those who were not. Individuals residing in households at the time of interview had a 6.4% lifetime prevalence of cocaine use, vs. hospitalized respondents (22%) and incarcerated respondents (40%). Cocaine use consequence rates varied greatly across survey sites, with self-reported tolerance (28%-51%) and withdrawal sickness (8%-33%) figuring prominently among sustained daily users.

Adult↗
PubMed1990

Effects of high concentrations of glucose on PTH secretion in parathyroid cells.

We examined the effects of high concentrations of glucose on PTH secretion from cultured bovine parathyroid cells. Increasing medium concentration of glucose caused suppression of PTH secretion. A significant suppression of PTH secretion was found within 48 hours of incubation with as little as 15 mM glucose. The addition of choline chloride to the medium did not suppress PTH secretion, although the osmolality was the same as that of the medium containing 50 mM glucose. When cells previously exposed to 50 mM glucose were reincubated in the medium containing 5 mM glucose for another 48 hours, a complete recovery of PTH secretion was observed. In the cells exposed to 50 mM glucose, the magnitude of the response of PTH secretion to 10(-6) M isoproterenol was blunted. Acid-urea gel electrophoresis revealed that the pattern of intact PTH and fragments secreted from cells exposed to high concentration of glucose was similar to that from control cells. Removal of insulin from the medium resulted in a suppression of PTH secretion similar to changes observed with high concentrations of glucose. The suppressive effects of high concentrations of glucose and lack of insulin were additive. However, we cannot exclude from the present studies whether the suppressive effects of the lack of insulin on PTH secretion was secondary to the fact that insulin may be required for the maintenance of parathyroid cells. The present studies demonstrate that glucose directly modulates PTH secretion in primary parathyroid cell culture.

Animals↗
PubMed1990

Large-scale isolation of plasmid DNA using cetyltrimethylammonium bromide.

A rapid procedure for the large-scale isolation of plasmid DNA is described. The method utilizes cetyltrimethylammonium bromide to precipitate the plasmid following extraction of DNA by lysozyme digestion and boiling. The plasmid is then purified by passing through the spin column pZ523. The purity and yield of the plasmid obtained with this method is similar to that isolated by cesium chloride-ethidium bromide gradient centrifugation. The method does not involve any phenol-chloroform extractions and takes five to six hours for completion after growth of the bacterial cells. The plasmid obtained is amenable to digestion with various restriction endonucleases, can be used for cloning with high efficiency and is also suitable as template for dideoxy sequencing.

Centrifugation, Density Gradient↗
PubMed1990

Role of guanine nucleotide binding protein, cytosolic calcium and cAMP in fluoride-induced suppression of PTH secretion.

In the present studies, we used fluoride and pertussis toxin, potent modulators of guanine nucleotide binding proteins (G proteins), to examine the role of G proteins, cytosolic calcium ([Ca]i) and cAMP in the regulation of PTH secretion from dispersed bovine parathyroid cells. NaF suppressed PTH secretion and cAMP content and increased [Ca]i levels in a dose-dependent manner. Prior removal of extracellular calcium with EGTA completely blocked the NaF-induced increase in [Ca]i, but did not prevent the NaF-induced inhibition of PTH secretion and cAMP content. Pretreatment with 10(-5) M verapamil or 10(-4) M diltiazem blocked neither the NaF-induced suppression of PTH secretion and cAMP content nor the increase in [Ca]i. Manganese chloride (10(-4) M) significantly inhibited the NaF-induced increase in [Ca]i, but did not block the NaF-induced suppression of PTH secretion and cAMP content. Pertussis toxin blocked neither the NaF-induced increase in [Ca]i nor suppression of PTH secretion and cAMP content. Our data suggest that (1) NaF might stimulate a calcium channel resulting in the increase in [Ca]i by acting on a G protein in a manner resistant to the inhibition by pertussis toxin; (2) the NaF-induced increase in [Ca]i is not directly linked to the suppression of PTH secretion, and (3) the NaF-induced suppression of PTH secretion might be explained at least in part by the decrease in cell cAMP content.

Animals↗
PubMed1990

New active analogues of vitamin D with low calcemic activity.

In conclusion, a number vitamin D analogues have been developed that have very low calcemic activity but retain several other properties of 1,25-(OH)2D3, including the ability to differentiate leukemia and skin cells, to enhance the immune response, and to suppress parathyroid hormone levels. Although the mechanism of this selective activity is not yet clear, these analogues may provide new insights into the differences in action of 1,25-(OH)2D3 in various target tissues. Most importantly, the selective action of these analogues may be exploited for the treatment of diseases such as leukemia, psoriasis and hyperparathyroidism.

Animals↗
PubMed1989

Regulation of cytosolic pH in bovine parathyroid cells: effect of fluoride.

In the present investigation, sodium fluoride (NaF) was employed to explore the role of guanine nucleotide-binding proteins (G-proteins), protein kinase-C, or cytosolic calcium [( Ca]i) in the regulation of cytosolic pH [( pH]i) in dispersed bovine parathyroid cells, using the pH-sensitive fluorescent dye BCECF. When cells acidified by nigericin in Na-free medium were resuspended in Na-containing buffer, [pH]i returned to basal levels. This recovery was blocked by continued removal of Na+ or the addition of amiloride. NaF (10 mM) increased [32P]phosphate incorporation into phosphatidylinositol bisphosphate, suggesting an increase in phosphatidylinositol bisphosphate turnover. NaF caused an initial acidification, followed by an alkaline recovery in a dose-dependent manner (1-10 mM). Amiloride blocked the NaF-induced alkaline recovery. The protein kinase-C activator phorbol 12-myristate 13-acetate (10(-7) M) caused cytosolic alkalinization, while the protein kinase-C inhibitor H7 (6 x 10(-5) M) significantly inhibited the NaF-induced alkaline recovery. Pertussis toxin (1 microgram/ml) did not affect the NaF-induced changes in [pH]i. Removal of extracellular Ca2+ with EGTA blocked the NaF-induced increase in [Ca]i and alkaline recovery. Ionomycin (5 x 10(-7) M) caused cytosolic alkalinization, but pretreatment with EGTA inhibited the ionomycin-induced cytosolic alkalinization. The present studies clearly demonstrated the presence of an amiloride-sensitive Na+/H+ exchanger in parathyroid cells. Our findings suggest that the NaF-induced cytosolic alkaline recovery was via two complementing pathways: 1) activation of protein kinase-C, followed by stimulation of a Na+/H+ exchanger, and 2) existence of extracellular calcium and/or an increase in [Ca]i.

Amiloride↗