Chronic renal disease: new therapies to delay kidney replacement

Several factors promote the progression of renal disease, including glomerular hypertension and hypertrophy, molecular factors such as cytokines and growth hormones, proteinuria, acidosis, and hyperlipidemia. Regardless of the underlying etiology, many patients with chronic renal insufficiency will ultimately require kidney replacement therapy. Your goal is to delay the progression of renal failure, mainly through aggressive control of blood pressure. Other possible interventions include protein restriction, bicarbonate therapy, and lipid-lowering drugs.     

Inhibition of microtubule assembly in tumor cells by 3-bromoacetylamino benzoylurea, a new cancericidal compound

We have synthesized a new compound, 3-bromoacetylamino benzoylurea (3-BAABU), which showed strong cancericidal activity by inducing irreversible mitotic arrest and subsequently apoptosis in human T cell leukemic cells (CEM), human biphenotypic leukemic cells (SP), a human prostate cancer cell line (PC-3), murine melanoma cells (B-16), and murine lymphoma/leukemia cells (EL4) in vitro with an ID50 in the range of 0.013-0.07 microg/ml (0.04-0.22 microM). Treatment of tumor cells for 12-24 h with 3-BAABU resulted in mitotic arrest at prometaphase/metaphase/anaphase, with separation and dispersion of chromosomes and with the absence of mitotic spindle apparatus in cytoplasm. Treatment with 3-BAABU had no cytotoxic and mitotic blocking effect in normal human lymphocytes, proliferating fibroblast cells (3T3), or proliferating myocardial cells (MOT). Cell cycle analyses showed that most treated leukemic cells accumulated at M phase 12 h after treatment. By the end of 48 h of treatment, the cells underwent apoptosis with DNA fragmentation. 3-BAABU inhibited the assembly of microtubules from tubulin but did not interfere with the disassembly of microtubules. The presence and the position of bromine and urea groups on the benzoic ring are the determining factors for its inhibition of microtubule assembly. Replacing bromine with chlorine yielded much less mitotic blocking activity and increased the ID50 40-fold. Substitution of the urea group with ethyl ester abrogated the activity of blocking mitosis but induced apoptosis. Moving the bromoacetylamino group from the 3-position to the 4-position removed blocking activity for mitosis but induced necrosis. These results suggest that 3-BAABU possesses a unique and functional structure and is a potential agent for cancer chemotherapy.     

Continuous cardiac output and mixed venous oxygen saturation monitoring

Continuous assessment of cardiac output and SVO2 in the critically ill may be helpful in both the monitoring variations in the patient's cardiovascular state and in determining the efficacy of therapy. Commercially available continuous cardiac output (CCO) monitoring systems are based on the pulsed warm thermodilution technique. In vitro validation studies have demonstrated that this method provides higher accuracy and greater resistance to thermal noise than standard bolus thermodilution techniques. Numerous clinical studies comparing bolus with continuous thermodilution techniques have shown this technique similarly accurate to track each other and to have negligible bias between them. The comparison between continuous thermal and other cardiac output methods also demonstrates good precision of the continuous thermal technique. Accuracy of continuous oximetry monitoring using reflectance oximetry via fiberoptics has been assessed both in vitro and in vivo. Most of the studies testing agreement between continuous SVO2 measurements and pulmonary arterial blood samples measured by standard oximetry have shown good correlation. Continuous SVO2 monitoring is often used in the management of critically ill patients. The most recently designed pulmonary artery catheters are now able to simultaneously measure either SVO2 and CCO or SVO2 and right ventricular ejection fraction. This ability to view simultaneous trends of SVO2 and right ventricular performance parameters will probably allow the clinician to graphically see the impact of volume loading or inotropic therapy over time, as well as the influence of multiple factors, including right ventricular dysfunction, on SVO2. However, the cost-effectiveness of new pulmonary artery catheters application remains still questionable because no established utility or therapeutic guidelines are available.     

Cervical lymphadenopathy revealing differentiated thyroid cancer. Review of the literature and therapeutic approach]

Well-differentiated thyroid cancer (i.e. papillary microcarcinoma) may be revealed by a clinically palpable cervical node, especially in young patients. Primary tumor specificity (small-sized, superior location, invasion, multifocality) and characteristics of cervical node involvement (with synchronous central and lateral multiple node spread) require appropriate treatment by a skilled surgeon. Contrary to the primary tumor treatment (total thyroidectomy), surgical management of the cervical node basins remains controversial. Only a special knowledge of the specificity of this disease and cervical lymphatic anatomy will ensure a good prognosis for the patient.     

Medullary thyroid carcinoma: genetic advances, treatment recommendations, and the approach to the patient with persistent hypercalcitoninemia

Medullary thyroid cancer is a tumor of the thyroid C cells that occurs in sporadic and hereditary clinical settings. Genetic testing of at-risk individuals is available and has been applied to patient management. Plasma calcitonin levels are a sensitive marker for the presence of disease. Surgery offers the best hope for cure and also is an effective modality for managing metastatic and recurrent disease.     

Studies of the neutralizing activity and avidity of anti-human immunodeficiency virus type 1 Env antibody elicited by DNA priming and protein boosting

DNA vaccination is an effective means of eliciting strong antibody responses to a number of viral antigens. However, DNA immunization alone has not generated persistent, high-titer antibody and neutralizing antibody responses to human immunodeficiency virus type 1 (HIV-1) envelope glycoprotein (Env). We have previously reported that DNA-primed anti-Env antibody responses can be augmented by boosting with Env-expressing recombinant vaccinia viruses. We report here that recombinant Env protein provides a more effective boost of DNA-initiated antibody responses. In rabbits primed with Env-expressing plasmids, protein boosting increased titer, persistence, neutralizing activity, and avidity of anti-Env responses. While titers increased rapidly after boosting, avidity and neutralizing activity matured more slowly over a 6-month period following protein boosting. DNA priming and protein immunization with HIV-1 HXB-2 Env elicited neutralizing antibody for T cell line-adapted, but not primary isolate, viruses. The most effective neutralizing antibody responses were observed after priming with plasmids which expressed noninfectious virus-like particles. In contrast to immunizations with HIV-1 Env, DNA immunizations with the influenza virus hemagglutinin glycoprotein did not require a protein boost to achieve high-titer antibody with good avidity and persistence.     

A new class of tobacco chitinases homologous to bacterial exo-chitinases displays antifungal activity

A novel chitinase gene of tobacco was isolated and characterized by DNA sequence analysis of a genomic clone and a cDNA clone. Comparative sequence analysis of both clones showed an identity of 94%. The proteins encoded by these sequences do not correspond to any of the previously characterized plant chitinases of classes I-IV and are designated as class V chitinases. Comparison of the chitinase class V peptide sequence with sequences in the Swiss Protein databank revealed significant sequence similarity with bacterial exo-chitinases from Bacillus circulans, Serratia marcescens and Streptomyces plicatus. It was demonstrated that class V chitinase gene expression is induced after treatment of tobacco with different forms of stress, like TMV-infection, ethylene treatment, wounding or ultraviolet irradiation. Two related chitinase class V proteins of 41 and 43 kDa were purified from Samsun NN tobacco leaves inoculated with tobacco mosaic virus. The proteins were purified by Chelating Superose chromatography and gel filtration. In vitro assays demonstrated that class V chitinases have endo-chitinase activity and exhibit antifungal activity toward Trichoderma viride and Alternaria radicina. In addition, it was shown that class V chitinase acts synergistically with tobacco class I beta-1,3-glucanase against Fusarium solani germlings.     

不锈钢表面超薄铜层的激光熔覆

采用ＣＯ２激光器在３１６Ｌ不锈钢表面获得了超薄的铜熔覆层,文中分析和讨论了激光熔覆工艺参数加激光功率,熔覆速度,离焦量以及送粉率等对熔覆层质量的影响,提出了熔覆工艺的优化方法,使铜层的熔覆厚度可控制在１００μｍ之内,稀释率小于１０％以及很小的热变形。     

Concerted evolution at the population level: pupfish HindIII satellite DNA sequences

The canonical monomers (approximately 170 bp) of an abundant (1.9 x 10(6) copies per diploid genome) satellite DNA sequence family in the genome of Cyprinodon variegatus, a "pupfish" that ranges along the Atlantic coast from Cape Cod to central Mexico, are divergent in base sequence in 10 of 12 samples collected from natural populations. The divergence involves substitutions, deletions, and insertions, is marked in scope (mean pairwise sequence similarity = 61.6%; range = 35-95.9%), is largely confined to the 3' half of the monomer, and is not correlated with the distance among collecting sites. Repetitive cloning and direct genomic sequencing experiments failed to detect intrapopulation and intraindividual variation, suggesting high levels of sequence homogeneity within populations. The satellite sequence has therefore undergone "concerted evolution," at the level of the local population. Concerted evolution has previously almost always been discussed in terms of the divergence of species or higher taxa; its intraspecific occurrence apparently has not been reported previously. The generality of the observation is difficult to evaluate, for although satellite DNAs from a large number of organisms have been studied in detail, there appear to be little or no other data on their sequence variation in natural populations. The relationship (if any) between concerted, population level, satellite DNA divergence and the extent of gene flow/genetic isolation among conspecific natural populations remains to be established.     

Genomewide search for dehydrated hereditary stomatocytosis (hereditary xerocytosis): mapping of locus to chromosome 16 (16q23-qter)

Dehydrated hereditary stomatocytosis, also known as "hereditary xerocytosis," is caused by a red blood cell-membrane defect characterized by stomatocytic morphology, increased mean corpuscular hemoglobin concentration, decreased osmotic fragility, increased permeability to the univalent cations Na+ and K+, and an increased proportion of phosphatidylcholine in the membrane. The clinical presentation is heterogeneous, ranging from mild to moderate hemolytic anemia associated with scleral icterus, splenomegaly, and choletithiasis. Iron overload may develop later in life. The disease is transmitted as an autosomal dominant trait. We recruited a large three-generation Irish family affected with DHS and comprising 23 members, of whom 14 were affected and 9 were healthy. Two additional, small families also were included in the study. The DNA samples from the family members were used in a genomewide search to identify, by linkage analysis, the DHS locus. After the exclusion of a portion of the human genome, we obtained conclusive evidence for linkage of DHS to microsatellite markers on the long arm of chromosome 16 (16q23-q24). A maximum two-point LOD score of 6.62 at recombination fraction .00 was obtained with marker D16S520. There are no recombination events defining the telomeric limit of the region, which therefore is quite large. No candidate genes map to this area.