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101.
A novel synthetic foot-and-mouth disease virus (FMDV) peptide vaccine consisting of a synthetic B-cell and macrophage activator covalently linked to an amphiphilic alpha-helical T-cell epitope was developed. The low molecular weight vaccine of 3400 daltons is composed of virus VP1 antigenic determinant and the immunologically active lipotripeptide tripalmitoyl-S-glyceryl-cysteinyl-seryl-serine (P3CSS) as built-in adjuvant. The vaccine, tripalmitoyl-S-glyceryl-cysteinyl-seryl-seryl-FMDV-VP1 (VP1 = serotype O1K 135-154) induces protection against homologous challenge and serotype-specific virus neutralizing antibodies in guinea pigs after single administration without further adjuvants or carriers. A P3CSS conjugate with the FMDV-VP1 segment 135-154 of strain O Wuppertal produced only poor cross-protection against challenge with O1K virus. The antigenic determinant VP1(135-154) is an amphiphilic alpha-helix, as shown by CD. Molecular dynamics simulations (MDS) carried out using the highly homologous alpha-helical alcohol dehydrogenase (ADH) segment H3 as starting conformation for VP1(138-149) suggest that the FMDV segment 138-149 may adopt alpha-helical conformation during binding to its T-cell receptor, and that the development of the system during MDS may be considered as the dissociation step of the complex. 相似文献
102.
A cdc2-3w weel-50 double mutant of fission yeast displays a temperature-sensitive lethal phenotype that is associated with gross abnormalities of chromosome segregation and has been termed mitotic catastrophe. In order to identify new genetic elements that might interact with the cdc2 protein kinase in the regulation of mitosis, we have isolated revertants of the lethal double mutant. The suppressor mutations define six mcs genes (mcs: mitotic catastrophe suppressor) that are not allelic to any of the following mitotic control genes: cdc2, wee 1, cdc13, cdc25, suc1 or nim1. Each mcs mutation is recessive with respect to wild-type in its ability to suppress mitotic catastrophe. None confer a lethal phenotype as a single mutant but few of the mutants are expected to be nulls. A diverse range of genetic interactions between the mcs mutants and other mitotic regulators were uncovered, including the following examples. First, mcs2 cdc2w or mcs6 cdc2w double mutants display a cell cycle defect dependent on the specific wee allele of cdc2. Second, both mcs1 cdc25-22 or mcs4 cdc25-22 double mutants are nonconditionally lethal, even at a temperature normally permissive for cdc25-22. Finally, the characteristic suppression of the cdc25 phenotype by a loss-of-function wee1 mutation is reversed in a mcs3 mutant background. The mcs genes define new mitotic elements that might be activators or substrates of the cdc2 protein kinase. 相似文献
103.
A lethally malformed neonate with mosaic tetrasomy 12p is presented. This is the third reported case of mosaic tetrasomy 12p to have died in the neonatal period. These three babies have shown a consistent phenotype characterized by dysmorphic facies and large diaphragmatic hernia. Mosaic tetrasomy 12p is usually not detectable from lymphocyte investigation, indicating that chromosome studies from cultured fibroblasts should be undertaken in neonates with multiple malformations which include a diaphragmatic defect. 相似文献
104.
A J Ping A E Reeve D J Law M R Young M Boehnke A P Feinberg 《American journal of human genetics》1989,44(5):720-723
Beckwith-Wiedemann syndrome (BWS), characterized by multiorgan developmental abnormalities and predisposition to cancer, usually occurs sporadically, but small apparently dominant pedigrees have been described. Since rare patients show varying karyotypic abnormalities on the short arm of chromosome 11, it has been suggested that BWS may be related to the Wilms tumor gene on 11p13 or, alternatively, to growth factor genes on 11p15. We performed genetic linkage analysis on two BWS kindreds, using RFLPs for loci on 11p. BWS was linked to the insulin gene (11p15.5), with an overall maximum lod score of 3.60 (recombination fraction = .00). Linkage to D11S16 (11p13) could be excluded for recombination fractions less than or equal to .03. These results suggest that BWS defines a tumor-predisposition gene on 11p15. 相似文献
105.
Differential susceptibility of type III erythrocytes of paroxysmal nocturnal hemoglobinuria to lysis mediated by complement and perforin 总被引:1,自引:0,他引:1
S Jiang P M Persechini W F Rosse B Perussia J D Young 《Biochemical and biophysical research communications》1989,162(1):316-325
Previous reports have suggested that a 65 kDa membrane protein, termed homologous restriction factor (HRF), in addition to protecting erythrocytes (E) against lysis by homologous complement (C), may also be involved in protecting cytolytic lymphocytes against lysis mediated by a pore-forming protein (PFP/perforin), one of their own lytic mediators. Here, we used HRF-deficient type III E of patients with paroxysmal nocturnal hemoglobinuria (PNH) to study their susceptibility to lysis mediated by homologous C and perforin, and compared it with lysis of HRF-bearing control or PNH type I E. We show that type III E of PNH patients are indeed more susceptible to lysis mediated by homologous C than control or type I E, but they are as susceptible to perforin-mediated lysis as type I E. In addition, all human E (type I or III) tested here are equally susceptible to lysis mediated by either human (homologous) or murine (heterologous) perforin. By immunoblot analysis, we confirm that type III E, in contrast to type I E, were deficient in the 65 kDa HRF. These results support the notion that homologous species restriction is seen in the C- but not in the lymphocyte perforin-system and argue against an active participation of HRF in protecting cells from perforin-mediated lysis. 相似文献
106.
New mutations fts-36, lts-33, and ftsW clustered in the mra region of the Escherichia coli chromosome induce thermosensitive cell growth and division. 总被引:11,自引:7,他引:4 下载免费PDF全文
F Ishino H K Jung M Ikeda M Doi M Wachi M Matsuhashi 《Journal of bacteriology》1989,171(10):5523-5530
Three new mutants of Escherichia coli showing thermosensitive cell growth and division were isolated, and the mutations were mapped to the mra region at 2 min on the E. coli chromosome map distal to leuA. Two mutations were mapped closely upstream of ftsI (also called pbpB), in a region of 600 bases; the fts-36 mutant showed thermosensitive growth and formed filamentous cells at 42 degrees C, whereas the lts-33 mutant lysed at 42 degrees C without forming filamentous cells. The mutation in the third new thermosensitive, filament-forming mutant, named ftsW, was mapped between murF and murG. By isolation of these three mutants, about 90% of the 17-kilobase region from fts-36-lts-33 to envA could be filled with genes for cell division and growth, and the genes could be aligned. 相似文献
107.
108.
We are using molecular genetic techniques to identify sites of interaction of beta-tubulin with benzimidizole anti-microtubule agents. We have developed a marker-rescue technique for cloning mutant alleles of the benA, beta-tubulin gene of Aspergillus nidulans and have used the technique to clone two mutant benA alleles, benA16 and benA19. These are the only A. nidulans alleles known to confer resistance to the benzimidazole antimicrotubule agent thiabendazole and supersensitivity to other benzimidazole antimicrotubule agents including benomyl and its active breakdown product, carbendazim. benA16 has been shown, moreover, to reduce thiabendazole binding to beta-tubulin. We have sequenced the two mutant alleles and have found that they carry different nucleotide changes that cause the same single amino acid substitution, valine for alanine at amino acid 165. Since thiabendazole and carbendazim differ at only one side chain, the R2 group, we conclude that the region around amino acid 165 is involved in the binding of the R2 group of benzimidazole antimicrotubule agents to beta-tubulin. 相似文献
109.
Summary Electron microscopic studies revealed that major cytological changes in the cortical cells of poplar (Populus euramericana cv. gelrica) began to occur in early September in conjunction with the metabolic transition from the growing to the wintering stage. During this transition, the cells became temporarily rich in endoplasmic reticulum, polysomes and vesicles. As the conspicuous formation of organelles progressed, the large vacuoles became smaller and filled with osmiophilic materials. Undefined organelles (protein-lipid bodies) also increased in number. From late October until March, organelles involved in protein synthesis were sparsely distributed in the cells, indicating that the number of these organelles is probably linked to the seasonal cycle of protein synthesis. In early February, after release from dormancy, fusion of vacuoles proceeded in the cells. The inclusion of organelles and a gradual decrease in the amount of osmiophilic materials in the vacuoles occurred at this stage. Subsequently, the structure of the cells continued to undergo changes to accommodate growth, which occurred in early May. 相似文献
110.
R Taylor L Lovelock W M Tunbridge K G Alberti R G Brackenridge P Stephenson E Young 《BMJ (Clinical research ed.)》1990,301(6763):1243-1247
OBJECTIVE--To determine whether non-mydriatic Polaroid retinal photography was comparable to ophthalmoscopy with mydriasis in routine clinic screening for early, treatable diabetic retinopathy. DESIGN--Prospective study of ophthalmoscopic findings according to retinal camera screening and ophthalmoscopy and outcome of referral to ophthalmologist. SETTING--Outpatient diabetic clinics of three teaching hospitals and three district general hospitals. PATIENTS--2159 Adults selected randomly from the diabetic clinics, excluding only those registered as blind or those in wheelchairs and unable to enter the screening vehicle. MAIN OUTCOME MEASURES--Numbers of patients and eyes correctly identified by each technique as requiring referral with potentially treatable retinopathy (new vessel formation and maculopathy) and congruence in numbers of microaneurysms, haemorrhages, and exudates reported. RESULTS--Camera screening missed two cases of new vessel formation and did not identify a further 12 but indicated a need for referral. Ophthalmoscopy missed five cases of new vessel formation and indicated a need for referral in another four for other reasons. Maculopathy was reported in 147 eyes with camera screening alone and 95 eyes by ophthalmoscopy only (chi 2 = 11.2; p less than 0.001), in 66 and 29 of which respectively maculopathy was subsequently confirmed. Overall, 38 eyes received laser treatment for maculopathy after detection by camera screening compared with 17 after ophthalmoscopic detection (chi 2 = 8.0; p less than 0.01). Camera screening underestimated numbers of microaneurysms (chi 2 = 12.9; p less than 0.001) and haemorrhages (chi 2 = 7.4; p less than 0.01) and ophthalmoscopy underestimated hard exudates (chi 2 = 48.2; p less than 0.001). CONCLUSIONS--Non-mydriatic Polaroid retinal photography is at least as good as ophthalmoscopy with mydriasis in routine diabetic clinics in identifying new vessel formation and absence of retinopathy and is significantly better in detecting exudative maculopathy. 相似文献