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Although glucocorticoid hormones have important roles in the development of neurotransmitter systems in cells derived from the neural crest, it is not known whether they have parallel effects on neuronal development in the brain. To address this issue, we have established an in vitro system of fetal medulla oblongata (MO) to follow development of the epinephrine-synthesizing enzyme, phenylethanolamine N-methyltransferase (PNMT). Embryonic MO was explanted from E13 or E18 embryos and maintained for up to 3 weeks. Successful culture of adrenergic neurons was possible only in explants taken from young embryos, since E18 explants failed to develop. In E13 explants, immunoreactivity to both PNMT and tyrosine hydroxylase, the rate limiting enzyme in catecholamine synthesis, was observed. PNMT catalytic activity which was barely detectable at the time of explanation increased markedly during the first week in vitro. To study the effects of glucocorticoids on PNMT development in central neurons, MO explants were grown in glucocorticoid deficient medium in which rat serum from adrenalectomized rats was substituted for human placental serum. Addition of natural glucocorticoids, cortisol or corticosterone, or the mineralcorticoid, deoxycorticosterone, during the third culture week had no effect on PNMT activity. Dexamethasone (DEX), a synthetic glucocorticoid, also had no effect on PNMT during the first or second weeks in culture. However, addition of DEX during the third culture week resulted in a doubling of PNMT activity. However, attempts to block the DEX effect during the third week or to block the increase in PNMT activity during the first week in control cultures with the glucocorticoid receptor antagonist, dexamethasone 21-mesylate, were unsuccessful. These results suggest that PNMT in central neurons does not require glucocorticoids for ontogeny during the embryonic period. This is in contrast to PNMT in adrenal medulla which requires glucocorticoids for normal development during both the embryonic and postnatal periods. More generally, these studies suggest that development of the same neurotransmitter phenotype in brain and periphery may be differentially regulated. 相似文献
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Non-clastogenicity in mouse bone marrow of fructose/lysine and other sugar/amino acid browning products with in vitro genotoxicity 总被引:1,自引:0,他引:1
J T MacGregor J D Tucker I I Ziderman C M Wehr R E Wilson M Friedman 《Food and chemical toxicology》1989,27(11):715-721
Heated sugar/amino acid reaction mixtures, known to contain products that are clastogenic and/or mutagenic to cells in vitro, were evaluated for clastogenic activity in mouse bone marrow using the erythrocyte micronucleus assay. Heated (i.e. browned) fructose/lysine reaction mixtures were also evaluated in the Salmonella his-reversion assay and the Chinese hamster ovary (CHO) cell chromosomal aberration assay to confirm and extend previous in vitro observations. Significant mutagenicity of fructose/lysine mixtures was observed in Salmonella typhimurium strains TA100, TA2637, TA98 and TA102, with greater activity in mixtures heated at pH 10 than at pH 7. S-9 decreased the activity in strains TA100, TA2637 and TA98, but increased the activity in strain TA102. Both pH 7 and pH 10 reaction mixtures of the fructose/lysine browning reaction were highly clastogenic in CHO cells. Heated mixtures of fructose and lysine, and of glucose or ribose with lysine, histidine, tryptophan or cysteine, did not increase the frequency of micronucleated erythrocytes in mice when administered by the oral route. This indicates the absence of chromosomal aberrations in erythrocyte precursor cells, and indicates that the genotoxic components of the browned mixtures are not absorbed and distributed to bone marrow cells in amounts sufficient to induce micronuclei when given orally. Because sugar/amino acid browning reactions occur commonly in heated foods, it is important to evaluate further the in vivo genotoxicity of browning products in cell populations other than bone marrow. 相似文献
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S. Friedman R. Komorowski W. Maillet H. Q. Nguyen C. D. Torneck 《Dental traumatology》1998,14(5):225-231
Abstract— NdYAG laser-induced modification of the root surface may inhibit development of external inflammatory resorption in replanted teeth. This study tested this hypothesis in vivo. The pulp chambers of six mandibular premolars in each of two dogs were accessed, inoculated with plaque, and sealed (Groups 1, 2). Two additional premolars in each dog were endodontically treated without inoculation (Groups 3, 4). After 2 weeks, teeth were hemisected and extracted. Each root had a 2times3 mm surface area denuded of cementum on the buccal and lingual surface. In Groups 1 (n= 12 roots) and 3 (n=4), the denuded surfaces were wiped with 15% EDTA, coated with black ink, and irradiated with Nd:YAG laser (0.75 W, 15 ppc, 300 pm tip, 20 s). In Groups 2 (n= 12) and 4 (n= 4), the surfaces were wiped with 15% EDTA, and rinsed with sterile saline for 20 s. Roots were replanted within 5 min. The dogs were perfwion-euthanised 10 weeks after replantation. Block specimens were removed, decalcified, embedded and horizontally sectioned (6 pm) at 180-pm intervals, resulting in 10 to 14 cross-sections of each root. From these, the middle five consecutive sections were stained with hematoxylin and eosin, and observed by light microscopy for occurrence of surface, inflammatory and replacement resorption on the denuded surfaces. No obvious differences were noted between the laser-irradiated and non-irradiated surfaces. Inflammatory resorption was frequent in Groups 1 and 2, and absent in Groups 3 and 4. Replacement resorption was minimal in Groups 1 and 2, and frequent in Groups 3 and 4. Differences between Groups 1 and 2, and between Groups 3 and 4 were not significant, whereas the differences between the two pairs of groups were statistically significant (chi-square and two-way ANOVA, P>0.006). These results did not support the hypothesis, and questioned the clinical validity of the surface modification in NdYAG laser-irradiated den-tin. Therefore, the clinical application of NdYAG laser to the root surfaces of replanted teeth is not warranted. 相似文献
27.
We report a series of 33 consecutive hospitalized geriatric diabetic patients who were referred for evaluation of diabetic nephropathy, defined as proteinuria greater than or equal to 1 g/d (1,000 mg/24 h) or a serum creatinine concentration greater than or equal to 177 mumol/d (greater than or equal to 2 mg/dL). The study population was 60 years old or older (mean age, 68 +/- 6 years), was comprised mainly of women (24 of 33, 72.7%), and was predominantly black (25 of 33, 75.8%). All patients had type II diabetes. A family history of diabetes in parent or sibling was elicited in 24 (72.7%) patients. There were eight patients undergoing maintenance hemodialysis and 25 with less severe nephropathy (mean proteinuria, 2.7 g/d [2,700 mg/24 h]; mean creatinine clearance, 0.57 mL-s [34 mL/min]). Cardiac disorders were noted in the majority of patients: congestive failure in 20 (60.6%), myocardial infarction in eight (24.2%), and active angina in five (15.2%). Other comorbid diseases were present in both hemodialysis patients and the subset of nondialyzed azotemic-proteinuric patients, and consisted of peripheral neuropathy in 31 (93.9%), gastroparesis in 16 (48.5%), retinopathy in 28 (84.8%), and legal blindness in 11 (33%). We conclude that geriatric diabetic nephropathy in type II diabetes is similar in presentation and severity of comorbid extrarenal complications to the syndrome described in younger adults. This inference must be tempered by both the small size and the limitation imposed by the demographics of the study population, which is predominantly composed of black patients receiving treatment at inner city hospitals. 相似文献
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Clinical findings and common symptoms in retinitis pigmentosa 总被引:3,自引:0,他引:3
J R Heckenlively S L Yoser L H Friedman J J Oversier 《American journal of ophthalmology》1988,105(5):504-511
Data analysis was performed in a prospective study of clinical symptoms and findings in 500 patients with retinitis pigmentosa. The symptoms and findings in these patients met the usual definitions of the disease. At initial examination the patients were questioned in a standardized manner; symptoms and associated health problems were reviewed. Some patients were unable to answer all of the questions. Of the patients 274 (55%) were men and 226 (45%) were women, with a race distribution of 21 (4%) black, 47 (9%) Hispanic, 26 (5%) Oriental, three (1%) American Indian, and 403 (81%) white. Sixty-nine patients reported no symptoms of night blindness and 116 patients claimed no visual field changes; 90 stated that they saw better at dusk. The most common problem noted by 263 (53.3%) was headaches, 31 on a daily basis, 42 at least weekly, 124 infrequently, and the remainder nonspecifically. Numbness or tingling, mainly in extremities, was reported by 99 patients. The second most common problem affecting 170 patients (34.6%) was light flashes; since eight patients had retinal detachments, light flashes cannot be totally discounted. Of 143 patients who had been pregnant, 14 had visual changes. 相似文献
30.
CM Reid M. Nelson P. Beckinsale P. Ryan LMH Wing LJ Beilin MA Brown GLR Jennings CI Johnston J. Marley JJ McNeil TO Morgan J. Shaw ID Steven MJ West 《Clinical and experimental pharmacology & physiology》1997,24(5):370-373
1. The present study aimed to determine the feasibility of conducting a 5 year cardiovascular outcome trial of the treatment of 6000 elderly hypertensive patients in Australian general practices. 2. General practitioners (GPs) were invited to participate by mail and personal follow-up. Patient records were reviewed to identify subjects for a blood pressure (BP) screening programme. Blood pressure was measured on three occasions and eligible subjects were included if the average BP was 160 mmHg systolic or 90 mmHg diastolic if systolic BP was 140 mmHg. 3. Seven hundred and forty-one GPs were approached and 89 were enrolled in the study (12% of mail invites and 75% of those receiving a personal contact). In 16 practices where screening was completed, 82 000 records were reviewed to identify 4% patients eligible for screening. Twenty-two per cent of eligible subjects attended screening. Of 1938 subjects screened, 180 (9%) had BP 5=160/90 mmHg. Forty-seven percent of subjects (n = 916) were receiving antihypertensive therapy and 184 (20%) were withdrawn from therapy. One hundred and sixteen (63%) of these subjects had BP return to study entry levels within 6 weeks. Fifty-seven newly diagnosed and 81 previously treated subjects were randomized (7% of the screened population). 4. Based on the high participation rate of GPs, the response rate of patients to attend a BP screening programme and the 7% randomization to screening ratio for entry into the study, the ANBP2 pilot study has demonstrated that it is feasible to recruit subjects from Australian general practices to a cardiovascular outcome trial. 相似文献