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1.
2.
P Rubinstein M Walker N Mollen C Carpenter S Beckerman N Suciu-Foca R McEvoy F Ginsberg-Fellner 《Diabetes》1990,39(9):1138-1143
The gene frequencies, haplotype relative risks, and zygotic assortments of HLA-DR in three ethnically defined samples of insulin-dependent diabetes mellitus (IDDM) patients were determined in a prospective family study. Although DR3 and DR4 were positively associated with IDDM in the probands of 123 northern European, 94 Ashkenazi Jewish, and 49 New York Hispanic families, significant excess of DR*3/4 heterozygotes was observed only among the probands from families of northern European ancestry. There was also a significant decrease in the frequency of Bw62,DR4 haplotypes derived by northern European patients from their mothers compared with their fathers. This difference, together with data reported in the literature, suggests that the expressivity of the susceptible genotype(s) in IDDM patients may be modified by protective maternal effects associated with Bw62,DR4 and probably other DR4 haplotypes. Samples of IDDM patients from populations with high frequencies of these modifiers should have different DR-gene frequencies contributed by fathers and mothers, capable of accounting for the observed Hardy-Weinberg disequilibrium. We postulate that, because the mechanism of action of these modifiers is distinct from that of the susceptibility gene, the difference must be considered in devising strategies for elucidation of the mode of inheritance of the disease and for understanding the molecular nature of the susceptibility. 相似文献
3.
The intravitreal penetration of ceftriaxone in man following systemic administration 总被引:1,自引:0,他引:1
M Sharir G Triester J Kneer E Rubinstein 《Investigative ophthalmology & visual science》1989,30(10):2179-2183
Seventeen patients who underwent vitreal surgery received ceftriaxone (Rocephin) 1-2 g intramuscularly at various time intervals before surgery. Specimens of serum and vitreous were assayed for ceftriaxone concentrations both by bioassay and high pressure liquid chromatography. All patients had detectable vitreous (and serum) ceftriaxone concentrations at all time periods. Vitreous ceftriaxone levels at the first 4.5 hr following the administration of the antibiotic ranged from 1.4-19.4 micrograms/ml and averaged 5.9 micrograms/ml. At 12-13 hr following ceftriaxone administration vitreous concentrations were 11.5 (+/- 9.0) micrograms/ml. Ceftriaxone in intramuscular administration could be used as prophylaxis against ceftriaxone-susceptible microorganisms in vitreal surgery. Ceftriaxone is the first antibiotic for which reliable penetration into the vitreous is demonstrable following intramuscular administration. 相似文献
4.
A method for coating native, non-derivatized, polysaccharide (PS) onto nitrocellulose (NC) for identifying PS-specific antibodies has been developed. The new feature of this method is that PS molecules are vacuum filtered onto NC in their native state by devices that can accommodate NC of different sizes and shapes. PS-coated NC disks were used to localize antibody secreting hybridoma cells cultured on filter paper disks. These were analyzed by blotting with size-matched PS-coated NC disks and specific antibodies secreted by individual colonies were detected by enzyme-linked immunoblot. In another application of this method, immune sera were separated by isoelectric focusing and the gels were blotted with PS-coated NC sheets. The spectrotype and isotype of antibodies that bound to the NC were examined using isotype specific enzyme-linked antibody. These immunoblots showed high resolution and specificity. The advantages of this method are that the PS used for coating does not need to be derivatized in order to bind the NC, and that smaller quantities of PS may be utilized by this coating method when compared to other techniques. This provides a useful tool to ask many questions regarding the immune response to PS. 相似文献
5.
G W Diamond J Kaufman A L Belman L Cohen H J Cohen A Rubinstein 《Archives of clinical neuropsychology》1987,2(3):245-256
The cognitive status of 12 clinically stable children with congenital HIV infection, nine of whom were neurologically impaired, age three to nine years, was assessed using the Kaufman ABC test. Seven of the children had ARC; five were diagnosed as having AIDS. The same children were evaluated by standard neurologic examinations with Characterization of tone and fine motor functioning. Two were diagnosed as being mildly retarded; six were borderline; and four tested as being of average intelligence. Visual-spatial perceptual based functioning was found to be more impaired than were abstract reasoning and verbally mediated skills in six (50%) of the patients. This pattern of impaired information processing was found irrespective of overall cognitive status. On neurological and physiatric examination abnormal developmental histories were obtained, or poor fine motor coordination, abnormal tone and gait, and impaired rapidly alternating movements were found in 9 of the 12 subjects. These findings suggest selective impairment in distinct areas of neurologic and neuropsychological functioning during stable phases of HIV infection in a select group of children. These patterns appear to persist over time. They differ from the clustering of impaired skills seen in children of comparable socio-cultural backgrounds without HIV infection. Similarities in functioning are noted between this subgroup of children with AIDS and ARC and comparable groups with cerebral palsy. 相似文献
6.
Excess of DR3/4 in type I diabetes. What does it portend? 总被引:1,自引:0,他引:1
The HLA-DR genotypes of 158 new type I diabetic probands from simplex families are compared with those of 43 multiply affected sibships. There were no significant differences in the gene frequencies of the insulin-dependent diabetes mellitus (IDDM)-associated alleles, DR3 and DR4, and whereas the DR3/4 heterozygotes were as frequent among simplex probands as among the first affected of multiplex sibships, subsequently affected sibs displayed lower frequencies of this genotype in this as well as in previously reported samples, indicating that the excessive risk associated with DR3/4 heterozygosity depends on the order of affection and thus on environmental factors. It is proposed that the penetrance of the susceptibility gene is enhanced by epistatic effects of this genotype and that this enhancement is strongest under conditions of low environmental liability. Thus, the excessive risk for DR3/4 individuals appears to depend on secondary interactions between DR and the environmental factors that trigger the onset of this disease and does not in itself indicate the existence of distinct susceptibility alleles in coupling with these genes, i.e., of genetic heterogeneity or overdominance. 相似文献
7.
Ninety-three women with FIGO stage II epithelial ovarian carcinoma underwent comprehensive surgical staging and were randomized prospectively to therapy consisting of either intraperitoneal radioactive phosphorus or oral melphalan. No patient had gross residual disease at the time of randomization. Ten of the forty-five women treated with melphalan experienced severe bone marrow depression at some time during therapy and two women expired from leukemia. Four of the forty-eight women treated with intraperitoneal phosphorus required surgical reexploration for intestinal obstruction or bowel injury. Twenty-one women died of their disease. Survival was not statistically different between the two treatment arms. The 5-year actuarial survival was 78%. 相似文献
8.
9.
Colonic Drug Delivery: Enhanced Release of Indomethacin from Cross-Linked Chondroitin Matrix in Rat Cecal Content 总被引:4,自引:0,他引:4
Pharmaceutical Research - 相似文献
10.
MGC Hendriks P Dogterom JT Ebels B Oosterhuis LR Geertsema T Hulot G Bianchetti and JHG Jonkman 《Fundamental & clinical pharmacology》1998,12(5):559-565
Summary— In the present study we have compared the steady state biopharmaceutic characteristics of four diltiazem once daily controlled release capsules: Mono-Tildiem LP 300® (300 mg), Adizem® XL (300 mg)1, Cardizem® (300 mg) and Dilacor® (240 mg). Sixteen healthy male volunteers (aged 22.9 ± 3.3 years, range 19–31 years) completed an open label, multiple oral dose, randomized, four-period crossover study without a washout period in between. The volunteers received each diltiazem formulation once daily for four days. Trough diltiazem and metabolites plasma concentrations were determined on days 3 and 4. The 24-h plasma concentration-time profiles were assessed after the dose on day 4 of each period. The following steady state pharmacokinetic parameters for diltiazem were calculated: the minimum plasma concentration (cmin), the maximum plasma concentration (cmax), the time to reach that concentration (tmax), the time interval during which the plasma concentration exceeds 50% of cmax (t50), the area under the plasma concentration-time curve (AUC72–96) and the peak-to-trough fluctuation (PTF). For the metabolites of diltiazem, N-mono-desmethyl-diltiazem (NDM) and desacetyldiltiazem (DAD), AUC72–96 (AUCNDM and AUCDAD) and the ratio metabolite/parent compound were calculated. Steady state was achieved on day 3. Except one, all controlled release formulations have satisfactory controlled release properties allowing once daily administration. However, significant (P < 0.05) differences were found between the pharmacokinetic characteristics which do not allow exchange of the various formulations. Concentrations well below 50 ng·mL-1 in the morning hours were observed for Dilacor® (240 mg) and Adizem® XL (300 mg), which could be a disadvantage of these formulations as it is well-known that ischaemic events occur at a higher rate during that part of the day. The plasma concentration profiles of NDM and DAD, the major circulating metabolites, parallel the plasma concentration profiles for the parent compound. From a clinical point of view, all treatments were well tolerated. 相似文献