Familial cryptogenic fibrosing pleuritis with Fanconi's syndrome (renal tubular acidosis). A new syndrome

We describe two siblings with a progressive unrelenting and unique syndrome of bilateral fibrosing pleuritis of unknown cause occurring in association with Fanconi's syndrome (renal tubular acidosis). The parents of the siblings were second cousins. Both siblings had identical pleural histologic characteristics and identical urinary metabolic defects. This condition resulted in the development of severe respiratory failure in both patients and ultimately the death of the older sibling at the age of 21 years.     

The effects of small dosage inactivated BCG vaccine on cellular immune function of pulmonary chronic obstructive disease patients with deficiency of lung-qi

To investigate the effects of the small dosage inactivated BCG vaccine on the cellular immune function of the patients suffered from pulmonary chronic obstructive disease with deficiency of the Lung-Qi, the authors observed the patients' immune function before and after BCG treatment for half a year. RESULTS: The peripheral blood T lymphocytes subsefs (CD3, CD4, CD8, CD4/CD8) and the conversion ratio of lymphocyte of the patients both were significantly lower than those of the healthy people (P < 0.01). But after the treatment of the small dosage inactivated BCG vaccine for half a year, these parameters of the patients were improved (P < 0.01 or P < 0.05). It indicated that the small dosage inactivated BCG vaccine could improve the damaged cellular immune function.     

Regression of experimental brain tumors with 6-thioxanthine and Escherichia coli gpt gene therapy

The identification of transgenes with antitumor activity is critical to the development of gene therapy of cancer. Retrovirus-mediated transfer of the Escherichia coli gpt gene into rat C6 glioma cells without subsequent selection still inhibited the proliferation of this mixed polyclonal population upon addition of the prodrug, 6-thioxanthine, with an ID50 of 4.1 microM, whereas parental C6 cells were not affected at a concentration of 500 microM. In a time-course assay, effects of the prodrug on the mixed polyclonal cell proliferation required at least 10 days of exposure. In mixed co-cultures, a bystander effect was not present over the first 4 days of prodrug exposure, but required trypsinization of the co-cultures and replating at lower densities. This "modified" bystander assay thus revealed a 50% decrease in C6 cell proliferation, even when the initial ratio of gpt-expressing to parental C6 cells was as low as 1:19. In a nude mouse model of subcutaneous tumors, co-grafts of C6 glioma and gpt-retrovirus producer cells displayed retarded growth upon exposure to 6-thioxanthine (6-TX). In a nude mouse model of intracerebral tumors, grafting of the gpt-retrovirus producer cells leads to an 80% reduction in intracerebral tumor volumes after 6-TX treatment. This reduction results in a 28% increase in the mean time of survival of animals that harbor intracerebral tumors (p < 0.0005). These antitumor effects indicate that the gpt/6-TX enzyme/prodrug pair is a promising alternative to the thymidine kinase gene and ganciclovir combination in the gene therapy of cancer.     

智能手机"加油"记

坊间流传着一种半调侃的说法——要判断一款手机是不是智能手机,看三点：屏幕够大不？功能够多不？待机时间够短不？笔者就曾经在HTCDream（以下简称G1）身上深深地体会到这最后一条是何等’杯具’。在受够了走到哪儿就把充电器带到哪儿的无奈之后,我终于决定,为了给G1“加点油”,还是求助于万能的网络吧!     

A discrete three-amino acid segment (LVI) at the C-terminal end of kinase-impaired ErbB3 is required for transactivation of ErbB2

ErbB3 is unique among other members of the receptor tyrosine kinase family of growth factor receptors in that its kinase domain is enzymatically impaired. This renders it incapable of transducing a signal in response to ligand binding. However, in conjunction with ErbB2, ErbB3 is a potent mediator of signaling by the growth factor heregulin. Heregulin binding to ErbB3 induces formation of a heterodimeric complex with ErbB2, and this results in transactivation of the ErbB2 kinase. Although interaction between the extracellular domains of these receptors is an essential part of this process, it was not clear whether interaction between the cytoplasmic domains is also necessary for transactivation. By examining the abilities of a series of cytoplasmic domain mutants of ErbB3 to activate ErbB2, we have found a discrete sequence of three amino acid residues (LVI), located at the carboxyl-terminal end of the impaired ErbB3 kinase region, that is obligatory for transactivation. We conclude that formation of a functional ErbB2-ErbB3 signaling complex requires the presence of a specific structural feature within the ErbB3 cytoplasmic domain and suggest that ErbB2 transactivation results from a physical interaction between the cytoplasmic domains of these receptors.     

Effects of olive oil and its minor phenolic constituents on obesity-induced cardiac metabolic changes

Background

Olive oil and its minor constituents have been recommended as important dietary therapeutic interventions in preventive medicine. However, a question remains to be addressed: what are the effects of olive oil and its phenolic compounds on obesity-induced cardiac metabolic changes?

Methods

Male Wistar rats were divided into two groups (n = 24/group): (C) receiving standard-chow; (Ob) receiving hypercaloric-chow. After 21 days C and Ob groups were divided into four subgroups (n = 6/group):(C) standard-chow and saline; (C-Olive)standard-chow and olive-oil (3.0 g/kg.day); (C-Oleuropein)standard-chow and oleuropein (0.023 mg/kg/day); (C-Cafeic) standard-chow and cafeic-acid (2.66 mg/kg/day); (Ob)receiving hypercaloric-chow and saline;(Ob-Olive) hypercaloric-chow and olive-oil;(Ob-Oleuropein) hypercaloric-chow and oleuropein;(Ob-Cafeic) hypercaloric-chow and cafeic-acid. Treatments were given twice a week during 21 days.

Results

After 42 days, obesity was evidenced in Ob rats from enhanced body-weight, surface-area, and body-mass-index. Energy-expenditure, oxygen consumption(VO₂) and fat-oxidation were lower in Ob-group than in C. Despite no morphometric changes, Ob-Olive, Ob-Oleuropein and Ob-Cafeic groups had higher VO₂, fat-oxidation, myocardial beta-hydroxyacyl coenzyme-A dehydrogenase and lower respiratory-quotient than Ob. Citrate-synthase was highest in Ob-Olive group. Myocardial lipid-hydroperoxide(LH) and antioxidant enzymes were unaffected by olive-oil and its compounds in obesity condition, whereas LH was lower and total-antioxidant-substances were higher in C-Olive and C-Oleuropein than in C.

Conclusions

The present study demonstrated for the first time that olive-oil, oleuropein and cafeic-acid enhanced fat-oxidation and optimized cardiac energy metabolism in obesity conditions. Olive oil and its phenolic compounds improved myocardial oxidative stress in standard-fed conditions.

     

The relationship between vaccinia virus DNA replication and intermediate filaments

Various DNA components which were extracted with gentle cell fractionation from the HeLa cells after 4 h vaccinia virus infection were detected by dot hybridization technique. The virus DNA mainly exist in intermediate filament-lamina-nuclear matrix complex. With DGD embedment free technique and electron microscopic autoradiography, the newly synthesized virus DNA is found to be associated with intermediate filaments. The results of southwestern hybridization demonstrate that vaccinia virus DNA has specific affinity to intermediate filaments and some nuclear matrix proteins.     

Increased risk of mortality in Alzheimer's disease patients with more advanced educational and occupational attainment

A reserve hypothesis suggests that clinical symptoms of Alzheimer's disease (AD) begin earlier in individuals with less education. Therefore, patients with less education might survive longer after diagnosis than those with more education. Two hundred forty-six subjects with probable AD were followed for 1 to 4 years. There were 78 deaths; 30 deaths occurred in the 127 patients whose education was < or = 8 years, while 48 deaths occurred in the 119 patients with > 8 years of education. Cox proportional hazards models adjusted for age, gender, and clinical dementia rating (CDR) showed that patients with more education had increased mortality (continuous variable: RR = 1.06 for each year of education; 95% confidence interval [CI], 1.01-1.11; dichotomous variable at 8 yr: RR = 1.76; CI, 1.11-2.77). This observation might at first seem counterintuitive, since groups with lower socioeconomic status are often at greater mortality risk. It implies that at any level of assessed clinical severity, the underlying pathology of AD is more advanced in patients with more education, resulting in shorter duration of diagnosed disease before death. These findings suggest either that education systematically influences global ratings of disease severity or that education provides a reserve against the clinical manifestation of AD pathology.     

The influence of heregulins on human Schwann cell proliferation

The use of Schwann cell (SC) autotransplantation to influence neural repair in humans is dependent upon identifying mitogens that will effectively expand human Schwann cells (SCs) in culture. The recent purification and molecular cloning of glial growth factor (GGF), a potent mitogen for rat Schwann cells, has led to the recognition that a family of proteins (GGF/HRG/NDF/ARIA) are alternatively spliced products of a single gene. The heregulins (HRGs) have been characterized with respect to their influence on human breast cancer cell lines; here we examined whether the HRGs have mitogenic activity for human SCs. Using DNA synthesis assays and serial passaging of cells in culture, we demonstrate that HRG is an effective mitogen for human SCs and that, in the presence of agents that elevate cAMP, it is possible to expand these cells over multiple passages without overwhelming fibroblast contamination. One putative target for this family of proteins is p185erbB2, and EGF-like receptor tyrosine kinase that is encoded by the erbB2 protooncogene. In this report we also demonstrate that the erbB2/3/4 messages as well as the erbB2/3 receptor proteins are present within cultured human SCs. The addition of HRG to human SCs results in tyrosine phosphorylation of a 185 kDa protein. In the presence of stimulatory concentrations of HRG, a blocking monoclonal antibody (2C4) to p185erbB2 is capable of significantly inhibiting phosphorylation of a 185 kDa protein as well as the subsequent incorporation of 3H-thymidine within the human SC. These latter results implicate an important role for p185erbB2 in mediating the mitogenic response of human SCs to HRGs.