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31.
The immunolocalization of cathepsins B(CB), H and L and cystatins(C) and(C) were examined in the hippocampus of cases of sporadic Alzheimer's disease (12 cases), parkinsonism-dementia complex on Guam (eight cases), senile dementia of Alzheimer type (two cases), aged subjects with marked senile change (one case) and controls (12 cases, including six normal subjects). CB was lower in most nerve cells in patients than in controls, but markedly increased at the sites of intracellular neurofibrillary tangles (NFTs) and degenerative neurites and/or dendrites in and outside senile plaques (SPs), indicating its close involvement in the metabolisms of various proteins in NFT and SPs. Abundant C and C were demonstrated in SP amyloid, suggesting that they are amyloid constituents or co-exist with amyloid. The present study indicated that CB, C and C are closely involved in abnormal protein metabolism in NFTs and SP amyloid and suggested that degeneration or denaturation of intracellular proteins, including substrates for proteases and lysosomes, from some acquired cause, results in absolute and/or relative overload for these proteolytic systems, including their inhibitors. This results in incomplete and/or abnormal proteolysis related to NFT and/or amyloid formation.  相似文献   
32.
Summary This report concerns the postnatal expression of calcineurin (CaN) in rat striatum. For this purpose an immunohistochemical procedure was used. In neonatal striatum CaN immunoreactivity was found in discrete patches composed of many immature cells. With development there was an increase in staining intensity and in the proportion of positively reacting cells. CaN expression and localization in the striatum of 22–25 day old rats were similar to those of adult animals.  相似文献   
33.
Polymeric conjugates of adriamycin (ADR) ( 2 ) or daunomycin (DM) ( 3 ) were synthesized by reaction of the drugs with the copolymer of divinyl ether and maleic anyhdride (DIVEMA) ( 1 ). The content of ADR moieties in the DIVEMA conjugate ( 4 ) could be varied depending on the reaction conditions up to 35,8 wt.-%. Considering the low toxicity and the high possibility of renal excretion, DIVEMA with M?w of 7000 and M?w/M?n = 1,6 was used for the conjugation. The rate of drug release from the conjugate was determined under physiological conditions by reversed phase HPLC. Within 14 days only 15% of the attached ADR was released from conjugate 4 . The antitumor activity of the conjugates was tested in vitro and in vivo against mouse P388 leukemia. Conjugate 4 proved to be 28 times less active than ADR in vitro, which could be explained from the slow drug-release. On the contrary 50% of the leukemic mice treated by 4 survived more than 60 days, whereas no mice given ADR alone or the admixture of ADR and DIVEMA survived 30 days. An antitumor activity of the polymeric conjugate better than that of the free drug was also observed in vivo with DM. Such a polymeric effect can be attributed either to the change in body distribution, the difference in pharmacokinetics, or the slow drugrelease.  相似文献   
34.
The genomes of class II avian sarcoma viruses PRCII, PRCII-p, PRCIV, and Fujinami sarcoma virus (FSV), were studied by oligonucleotide fingerprinting, heteroduplex mapping, and nucleic acid hybridization. All of these viruses are genetically defective and have a small RNA genome between 4.5 and 6.1 kilobases (kb) in length. They contain helper-related sequences at both the 5′- and 3′-ends, but most of the retroviral sequences in the middle of the genome are deleted. In place of this deleted information, a contiguous stretch of transformation-specific sequences, termed fps, is found. These putative oncogenic sequences are about 1.2 kb in PRCII, and those in PRCII-p and PRCIV are roughly 2.9 kb. From the analysis of oligonucleotides, it appears that the fps sequences of PRCII represent a subset of those of PRCII-p. Most of the additional sequences present in PRCII-p but absent from PRCII are at the 5′-half of fps. The helper-related sequences in PRCII and PRCII-p are almost indistinguishable, except that PRCII-p contains slightly more retroviral information at the 3′-end of the genome. Therefore, it is possible that PRCII has been derived by deletion from PRCII-p. By contrast, PRCII-p and PRCIV were found to contain identical fps sequences, but their helper-related sequences have diverged substantially. These two sarcoma viruses either represent two independent isolates or, if derived from a single isolate, they have undergone extensive mutation and recombination with diverse avian retroviruses. FSV was found to differ to a greater extent from other class II sarcoma viruses in both helper-related and fps sequences. The difference in fps sequences is localized in the 5′-half of that region. Considering the variation in fps among all members of class II avian sarcoma viruses, it appears that the 3′-half of that genetic region is more conserved than the 5′-half.  相似文献   
35.
Following horseradish peroxidase (HRP) injection into the cephalopharyngeal muscle (CeP), the hyopharyngeal muscle (HP), the thyropharyngeal muscle (TP), the cricopharyngeal muscle (CP) and the cervical esophagus muscle (CE) of the cat, labeled neurons were identified in the nucleus retrofacialis and the rostral part of the nucleus ambiguus ipsilaterally. The rostral end of the labeled cell column was located more rostrally for CeP and HP than for TP, CP and CE. No difference was noted within the former two or within the latter three. The level of the caudal end of the labeled cell column became more caudal in the order of CeP, HP, TP and CP. The caudal end was located more rostral for CE than for TP. The neurons for CE were located more ventro-laterally than those for the other muscles.  相似文献   
36.
The stereochemistry of the copolymerization of optically active phenylepoxyethane ( 5 ) with carbon dioxide using a diethylzinc/water system as catalyst was investigated. The optically active copolymer, poly(oxycarbonyloxy-2-phenylethylene) ( 1 ), was hydrolyzed and the oxy-2-phenylethylene unit was isolated in the form of 1,2-bis(trimethylsilyloxy)-1-phenylethane ( 3 ). The determination of the optical activity of this ether led to the conclusion that the ring opening of 5 takes place predominantly at the methineoxygen linkage accompanying an inversion in the copolymerization. This fact is in sharp contrast with the stereochemistry of the copolymerization of carbon dioxide with 1,2-epoxypropane in which the ring opening takes place at the methylene-oxygen linkage.  相似文献   
37.
Sequential treatment with lamivudine and interferon (IFN) has induced sustained biochemical and virologic responses in the majority of patients with chronic hepatitis B in France. However, the efficacy of sequential treatment in patients with chronic hepatitis B virus (HBV) genotype C infection has not been evaluated. Twenty-four HBe antigen-positive patients were treated with 100 mg lamivudine alone for 16-32 weeks, then with both 6 MU IFN-beta and lamivudine for 4 weeks, and lastly with IFN-beta alone for 20 weeks. Sustained response was achieved in 7 (29%) patients 24 weeks after the end of therapy. No lamivudine-resistant variants emerged in any patient. Hepatitis flare occurred in 3 patients after the withdrawal of lamivudine, but none had decompensation. The patients with sustained response were significantly younger at baseline (p = 0.033) and had a significantly lower HBV DNA level at the start of IFN (p = 0.020) than those without sustained response. In conclusion, the rate of response to sequential therapy with lamivudine and IFN in HBe antigen-positive patients with HBV genotype C infection was lower than the rate reported previously. Patients who were young or who had a favorable virologic response to lamivudine were more likely to have a sustained response.  相似文献   
38.
Using cDNA microarray technology, the expression of chemokine genes in the elicitation site of 2,4,6-trinitrochlorobenzene-induced contact hypersensitivity (CHS) was examined in mice. Of the 33 genes analyzed, levels of 11 gene expressions changed, and these can be assigned to four groups based on their kinetic patterns; (1) LARC/CCL20 whose mRNA level increased rapidly at 3 h post-challenge and then gradually decreased, (2) JE/CCL2, MARC/CCL7, MIP-1gamma/CCL9, monocyte chemoattractant protein (MCP)-5/CCL12, ELC/CCL19 and BRAK/CXCL14 whose mRNA levels increased with time and reached the maximum at 6-9 h post-challenge, (3) LIX/CXCL5, Mig/CXCL9 and IP-10/CXCL10 whose mRNA levels increased gradually at least up to 12 h post challenge, and (4) SLC/CCL21 whose mRNA level decreased gradually with time after challenge. The findings suggest that sequential expression of chemokine genes is essential for orientating non-specific skin response to hapten-specific CHS response through the recruitment of inflammatory cells such as neutrophils, monocytes/macrophages and T-cells from the circulation into the tissue site.  相似文献   
39.
In order to improve 8-hydroxyguanine (8-OH-Gua) detection in DNA, we digested isolated DNA with nuclease P1 and analyzed for 8-hydroxydeoxyguanosine 5'-monophosphate (8-OH-dGMP) using a high-performance liquid chromatography system equipped with an electrochemical detector (HPLC-ECD). The amount of 8-OH-Gua in the DNA was expressed as the ratio of 8-OH-dGMP to deoxycytidine monophosphate (dCMP). Using this analysis, the background level of 8-OH-Gua in DNA from human lung carcinoma cells (A549) was several-fold lower than that obtained by a previous method. A549 cells were exposed to 20-60 Gy of gamma-radiation and an increase in 8-OH-Gua concentration was observed with increasing gamma-ray dose (0.3 residues per 10(7) dCMP per Gy). Moreover, by an immunohistochemical procedure using a commercial FITC-kit, 8-OH-Gua was clearly detected in A549 cells and the fluorescence intensity of cells with oxidative DNA damage increased with the doses of gamma-irradiation. Using an endonuclease nicking assay, we also found that gamma-rays decreased 8-OH-Gua repair activity. The results indicate that 8-OH-dGMP is a useful and sensitive marker for estimating oxidative damage in DNA.  相似文献   
40.
Early-onset ataxia with ocular motor apraxia and hypoalbuminemia (EAOH)/ataxia with oculomotor apraxia type 1 (AOA1) is caused by mutations in the gene encoding aprataxin (APTX). Although several in vitro findings proposed that impaired enzymatic activities of APTX are responsible for EAOH/AOA1, potential instability of mutant proteins has also been suggested as the pathogenesis based on in vivo finding that mutant proteins are almost undetectable in EAOH/AOA1 tissues or cells. The present study aimed to experimentally prove instability of mutant proteins in neuronal cells, the cell type preferentially affected by this disease. Results of pulse-chase experiments demonstrated that all of the disease-associated mutants had extremely shorter half-lives than the WT. We further found that mutants were targeted for rapid proteasome-mediated degradation. These results help establish pathogenic and physiological protein characteristics of APTX in neuronal cells.  相似文献   
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