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101.
James L. Kennedy Elizabeth A. Billett Fabio M. Macciardi Massimiliano Verga Thomas J. Parsons Herbert Y. Meltzer Jeffery Lieberman Janet A. Buchanan 《American journal of medical genetics. Part A》1995,60(6):558-562
Several groups have reported an association between schizophrenia and the MscI polymorphism in the first exon of the dopamine D3 receptor gene (DRD3). We studied this polymorphism using a North American sample (117 patients plus 188 controls) and an Italian sample (97 patients plus 64 controls). In the first part of the study, we compared allele frequencies of schizophrenia patients and unmatched controls and observed a significant difference in the total sample (P = 0.01). The second part of the study involved a case control approach in which each schizophrenia patient was matched to a control of the same sex, and of similar age and ethnic background. The DRD3 allele frequencies of patients and controls revealed no significant difference between the two groups in the Italian (N = 53) or the North American (N = 54) matched populations; however, when these two matched samples were combined, a significant difference was observed (P = 0.026). Our results suggest that the MscI polymorphism may be associated with schizophrenia in the populations studied. © 1995 Wiley-Liss, Inc. 相似文献
102.
103.
Pato CN Macedo A Ambrosio A Vincent JB Bauer A Schindler K Xu J Coelho I Dourado A Valente J Azevedo MH Kennedy JL Pato MT 《American journal of medical genetics》2000,96(6):854-857
We have studied 24 families with multiple affected members with bipolar disorder to test the hypothesis that in those families clinically showing genetic anticipation [Macedo et al., 1999] we would find large repeat expansions. The families meeting inclusion criteria had a minimum of two affected members over two generations and showed marked anticipation both in terms of age of onset and disease severity. We used the repeat expansion detection (RED) method to test patients (n = 24) and controls from these families and unrelated controls (n = 53). We also genotyped patients and family members from two families with large expansions at the known expansion loci on chromosomes 13, 17, and 18. The RED method revealed a higher number of large expansions in patients compared with controls (t-test; P < 0.0055: Mann-Whitney U; P = 0.02). The patients with the largest expansions were typed at the specific loci on chromosomes 13, 17, and 18 and the chromosome 18 expansion locus segregated with disease in one family, and a second family showed segregation with the expansion located at the SCA8 locus on chromosome 13. Genetic anticipation had been analyzed in this cohort of families, with correction for potential ascertainment bias, possible proband effects, cohort effects, regression to the mean, gender effects, and maternal vs. paternal transmission. None of these potential confounds appeared to account for the observed anticipation. We also identified that the presence of large expansions in affected family members derives primarily from two families from the genetically isolated Azores population. One family shows segregation with the chromosome 18 locus, whereas the other family segregates with expansions at the SCA8 locus. Am. J. Med. Genet. (Neuropsychiatr. Genet.) 96:854-857, 2000. 相似文献
104.
In vitro studies with recombinant Plasmodium falciparum apical membrane antigen 1 (AMA1): production and activity of an AMA1 vaccine and generation of a multiallelic response 总被引:5,自引:0,他引:5
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Kennedy MC Wang J Zhang Y Miles AP Chitsaz F Saul A Long CA Miller LH Stowers AW 《Infection and immunity》2002,70(12):6948-6960
Apical membrane antigen 1 (AMA1) is regarded as a leading malaria blood-stage vaccine candidate. While the overall structure of AMA1 is conserved in Plasmodium spp., numerous AMA1 allelic variants of P. falciparum have been described. The effect of AMA1 allelic diversity on the ability of a recombinant AMA1 vaccine to protect against human infection by different P. falciparum strains is unknown. We characterize two allelic forms of AMA1 that were both produced in Pichia pastoris at a sufficient economy of scale to be usable for clinical vaccine studies. Both proteins were used to immunize rabbits, singly and in combination, in order to evaluate their immunogenicity and the ability of elicited antibodies to block the growth of different P. falciparum clones. Both antigens, when used alone, elicited high homologous anti-AMA1 titers, with reduced strain cross-reactivity. Similarly, sera from rabbits immunized with a single antigen were capable of blocking the growth of homologous parasite strains at levels theoretically sufficient to clear parasite infections. However, heterologous inhibition was significantly reduced, providing experimental evidence that AMA1 allelic diversity is a result of immune pressure. Encouragingly, rabbits immunized with a combination of both antigens exhibited titers and levels of parasite inhibition as good as those of the single-antigen-immunized rabbits for each of the homologous parasite lines, and consequently exhibited a broadening of allelic diversity coverage. 相似文献
105.
Otoniel Martínez-Maza Dewey J. Moody Ali R. Rezal George W. Ellison Lawrence W. Myers Wallace W. Tourtellotte John L. Fahey 《Journal of clinical immunology》1987,7(2):107-113
Spontaneous immunoglobulin (Ig) secretion by cells from multiple sclerosis (MS) patients (in the progressive phase) treated with monthly pulse doses of cyclophosphamide (CY) (1000–1600 mg/M2) was measured using the protein A plaque assay, to evaluate the effect of CY treatment on B-cell function. Surprisingly, an increase, rather than a decrease, in Ig-secreting cells was seen following CY treatment. CY-treated MS patients averaged 1380±535 spontaneous total (IgM+G+A) Ig plaque-forming cells (PFC) per 1×106 peripheral blood mononuclear cells (MNC), measured at 15–22 days after monthly CY administration, while healthy adults had 280±47 Ig PFC/106 MNC, and MS patients not treated with CY had 300±43 Ig PFC/106 MNC. The observed increase was due to an increase in IgG and IgA PFC. PFC levels remained elevated for 4 weeks following CY treatment, decreasing to control levels by 7–8 weeks post-CY. A small increase in serum IgG level was noted after >12 months of pulse CY therapy; no increase was seen in CSF IgG levels. A preferential decrease in the number of CD4+ T cells was also seen in the CY-treated MS patients. We propose that the observed increase in the number of spontaneous Ig PFC was due to the CY-induced disruption of the CD4+ T cell-mediated control ofin vivo activated B cells. 相似文献
106.
Relation between gastric histology and gastric juice pH and nitrite and N-nitroso compound concentrations in the stomach after surgery for duodenal ulcer
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P C Watt J M Sloan J Donaldson G Campbell T L Kennedy 《Journal of clinical pathology》1984,37(5):511-515
Formation of N-nitroso compounds in gastric juice has been implicated in the pathogenesis of cancer in the stomach after operation. Gastric juice was aspirated from 85 subjects: 23 were controls, 51 had previously undergone vagotomy and gastrojejunostomy, and 11 had previously undergone vagotomy and pyloroplasty. The gastric juice samples were analysed for pH, nitrite, and total N-nitroso compounds. A significant correlation was found between pH and nitrite concentration (p less than 0.01). No significant correlation was found between pH and total N-nitroso compound concentration or between nitrite and N-nitroso compound concentration. The vagotomy and gastrojejunostomy patients had higher pH values and higher concentrations of nitrites and N-nitroso compounds than controls (p = 0.01 in all cases). The 51 vagotomy and gastrojejunostomy patients also underwent endoscopy and biopsy. They were divided into three groups: group 1 (21 patients) had no intestinal metaplasia and no more than mild dysplasia; group 2 (20 patients) had intestinal metaplasia; and group 3 (10 patients) had moderate or severe dysplasia. Groups 2 and 3 both had higher pH values and higher nitrite concentrations than group 1 (p = 0.01 in all cases). There was no significant difference, however, between either group 2 or 3 and group 1 for total N-nitroso compound concentration. Since there was no simple linear relation between pH and N-nitroso compound concentration, it was concluded that formation of N-nitroso compounds at high pH was unlikely to be involved in the pathogenesis of gastric cancer in the hypochlorhydric stomach after operation. The relation between nitrite and histological abnormality was not associated with a similar relation between N-nitroso compounds and histological abnormality. It therefore appears that there is no simple relation between N-nitroso compounds and the pathogenesis of premalignant gastric mucosal changes. 相似文献
107.
Bowen T Guy CA Cardno AG Vincent JB Kennedy JL Jones LA Gray M Sanders RD McCarthy G Murphy KC Owen MJ O'Donovan MC 《Psychiatric genetics》2000,10(1):33-37
A number of studies using the repeat expansion detection (RED) technique have suggested an association between unknown large CAG/CTG repeats and schizophrenia. The polymorphic CAG/CTG repeat loci CTG18.1 and ERDA1 have been reported to account for a high proportion (approximately 90%) of the large repeats detected by RED and may therefore be responsible for the cited association. The recently described locus TGC13-7a contains a highly polymorphic CTA/TAG and CAG/CTG composite repeat, and is thus another authentic candidate. In the present investigation, each locus was analysed for association with schizophrenia in a sample of 206 patients and 219 group-matched controls. No evidence for association of CTG18.1, ERDA1 and/or TGC13-7a with schizophrenia was found. The combined data accounted for only 54% of the CAG/CTG arrays of > 40 repeats found in our previous RED analysis. 相似文献
108.
Amy C. Fuchs Eric V. Granowitz Leland Shapiro Edouard Vannier Gerhard Lonnemann Jonathan B. Angel Jeffrey S. Kennedy Arthur R. Rabson Elaine Radwanski Melton B. Affrime David L. Cutler Paul C. Grint Charles A. Dinarello 《Journal of clinical immunology》1996,16(5):291-303
We conducted a double-blind, placebo-controlled study to investigate the safety, pharmacokinetics, and immunological properties of interleukin-10 (IL-10) administration in healthy humans. Volunteers received a single intravenous bolus injection of recombinant human IL-10 (1, 10, or 25g/kg) or placebo. Cytokine production in whole blood and peripheral blood mononuclear cells (PBMC) was assessed before and 3, 6, 24, and 48 hr after the injection. Peak serum concentrations of IL-10 (15±1.1, 208±20.1, and 505±22.3 ng/ml) occurred after 2–5 min for 1, 10, and 25g/kg IL-10, respectively. The terminal-phase half-life was 3.18 hr. A transient leukocytosis (24–63% above baseline) was observed 6 hr after injection, which coincided with a dose-dependent decrease (12–24%) in neutrophil superoxide generation. There was a marked inhibition (60–95%) of endotoxin-induced IL-6 production from whole blood in each group receiving IL-10. Production of IL-8 in endotoxin-stimulated blood was reduced in the 10g/kg group. In PBMC stimulated with phytohemagglutinin and phorbol ester, there was a decrease (72–87%) in interferon- (IFN) production 6 hr after IL-10 with a return to pre-IL-10 levels after 24 hr. This reduction was only partially associated with a decrease in the number of CD2-bearing cells. We conclude that IL-10 administration into humans is without significant side effects, and a single injection reducesex vivo production of IL-6, IL-8, and IFN. 相似文献
109.
John M. Boone Greg S. Hurlock J. Anthony Seibert Richard L. Kennedy 《Journal of digital imaging》2003,16(4):345-349
Images acquired in a two-view digital chest examination are frequently not electronically distinguishable. As a result the lateral and posterioanterio (PA) images are often improperly positioned on a PACS work station. A series of 1998 chest radiographs (999 lateral, 999 PA or AP) were used to develop a neural network classifier. The images were down-sampled to 16 × 16 matrices, and a feed-forward neural network was trained and tested using the leave-one-out method. Using five nodes in the hidden layer, the neural network correctly identified 987 of the 999 test cases (98.8%) (average of six runs). The simple architecture and speed of this technique suggests that it would be a useful addition to PACS work station software. The accumulated time saved by correctly positioning the lateral and PA chest images on the work station monitors in accordance with each radiologists hanging protocols was estimated to be about 1 week of radiologist time per year. 相似文献
110.
Kennedy CM Coutsoudis A Kuhn L Pillay K Mburu A Stein Z Coovadia H 《Journal of acquired immune deficiency syndromes (1999)》2000,24(1):37-44
OBJECTIVE: To determine whether low-cost treatment of HIV using vitamin A would be beneficial, we examined the effect of vitamin A supplementation on morbidity of HIV-1 infected women. METHODS: We conducted a randomized, double blind placebo-controlled trial at King Edward VIII Hospital, in Durban, South Africa. In total, 312 HIV-seropositive pregnant women between 28 and 32 weeks' gestation were recruited into this trial. Patients were randomized to receive placebo or 5,000 IU retinyl palmitate and 30 mg beta-carotene daily. At delivery of their children, patients received placebo or 200,000 IU retinyl palmitate. The main outcome measures were pre- and postnatal report of HIV-related symptoms. RESULTS: Vitamin A did not confer any significant beneficial effect on the report of either HIV or pregnancy-related symptoms during the pre- or postnatal period. CONCLUSION: In this study of HIV-infected pregnant women, vitamin A supplementation given in doses designed to decrease mother-to-infant transmission did not result in significant beneficial effect on reported symptoms pre- or postnatally. Further investigation with larger number of participants, tailoring supplementation for specific clinical conditions, outside the context of pregnancy, is required to help clarify the possible clinical benefits of vitamin A. 相似文献