[Relationship between the level of plasma D-dimer and diabetic microangiopathy].

OBJECTIVE: To study the relationship between the level of plasma D-dimer and microangiopathy of the type 2 diabetes mellitus. METHODS: The level of plasma D-dimer and blood viscosity were measured in 52 cases with type 2 diabetes mellitus, and these patients were divided into three groups according to the level of urinary albumin excretion (UAE) together with 15 age-matched healthy volunteers as the control (NC group). RESULTS: In the cases with higher urinary albumin excretion rate, including 28 cases with trace albuminuria (EDN group) and 10 cases with clinical albuminuria (CDN group), plasma D-dimer and blood viscosity were increases than 14 cases without albuminuria (SDM group) and NC group. D-dimer was positively correlated with diabetic retinopathy, Serum insulin and diabetic durations, but not correlated with blood viscosity and fibrinogen. CONCLUSION: The type 2 diabetes mellitus complicated with microangiopathy had a higher level of plasma D-dimer. As a marker of thrombus formation, D-dimer may play an important role in the pathogenesis of diabetic microangiopathy.

Transforming growth factor-beta3 protection of epithelial cells from cycle-selective chemotherapy in vitro.

The transforming growth factor-beta (TGF-beta) family of regulatory growth factors can reversibly arrest cell division in the G1 phase of the cell cycle. Previously, TGF-beta3 was shown to protect epithelial cells and hematopoietic cells from cytotoxic damage in vitro and in vivo, and to reduce the severity and duration of oral mucositis induced by 5-fluorouracil (5-FU) in vivo. In the present study, we tested whether TGF-beta3 can protect epithelial cells from a range of chemotherapy drugs with differing mechanisms of action, using the CCL64 cell line as a model system. We report that preincubation of cells with TGF-beta3 for 24 hr resulted in enhanced clonogenicity following exposure to vinblastine, vincristine, etoposide, taxol, ara-C, methotrexate, or 5-FU. Protection was measured in colony-forming assays, which demonstrated that the protected cells could re-enter the cell cycle and undergo multiple rounds of cell division. At high cytotoxic drug concentrations, absolute colony counts were increased for the cultures prearrested by TGF-beta3, as compared with the proliferating control cultures. The effects of TGF-beta3 were reduced for cisplatin and doxorubicin, drugs that are toxic to cells throughout the cell cycle. Thus, TGF-beta3 can effectively reduce the cytotoxicity of anticancer drugs that act predominantly in S or M phase of the cell cycle.

Umbilical cord transforming growth factor-beta 3: isolation, comparison with recombinant TGF-beta 3 and cellular localization.

The transforming growth factor beta (TGF-beta) family of growth modulators play critical roles in tissue development and maintenance. Recent data suggest that individual TGF-beta isoforms (TGF-beta 1, -beta 2 and -beta 3) have overlapping yet distinct biological actions and target cell specificities, both in developing and adult tissues. The TGF-beta 3 isoform was purified to homogeneity from both natural and recombinant sources and characterized by laser desorption mass spectrometry, by protein sequencing, by amino acid analysis and by biological activity. TGF-beta 3 was the major TGF-beta isoform in umbilical cord (230 ng/g), and was physically and biologically indistinguishable from recombinant TGF-beta 3 and from the tumor growth inhibitory (TGI) protein found in umbilical cord. Immunohistochemistry using antipeptide TGF-beta 3 specific antibody showed TGF-beta 3 localization in perivascular smooth muscle.

Physical and biological characterization of a growth-inhibitory activity purified from the neuroepithelioma cell line A673.

Epithelial- and haematopoietic-cell growth-inhibitory activities have been identified in the conditioned medium of the human peripheral neuroepithelioma cell line A673. An A673-cell-derived growth-inhibitory activity was previously fractionated into two distinct components which inhibited the proliferation of human carcinoma and leukaemia cells in culture. One inhibitory activity was shown to comprise interleukin-1 alpha (IL-1 alpha). Here, we have purified to homogeneity a distinct activity which inhibited the growth of the epithelial cells in vitro. Using a combination of protein-sequence analysis and mass spectrometry, we demonstrated that biological activity can be assigned to a dimeric protein with a molecular mass of 25,576 (+/- 4) Da and an N-terminal sequence identical with that of transforming growth factor-beta 1 (TGF-beta 1). Further characterization of the growth inhibitor with TGF-beta-isoform-specific antibodies showed that > 90% of the bioactivity consists of TGF-beta 1 and not TGF-beta 2 or TGF-beta 3. Although A673 cells were growth-inhibited by exogenous TGF-beta 1, we showed that TGF-beta 1 in A673-cell-conditioned media was present in the latent, biologically inactive, form which did not act as an autocrine growth modulator of A673 cells in vitro.

The malignancy of dementia. Predictors of mortality in clinically diagnosed dementia in a population survey of Shanghai, China.

OBJECTIVE: To evaluate the effect of dementing illnesses on the risk of dying, taking into account other conditions that would shorten survival. DESIGN: Five-year follow-up of community survey of dementia. SETTING: Five-year data were obtained for the 3531 subjects, aged 65 years and older, who participated in the 1987 population survey of dementia in Shanghai, China. MAIN OUTCOME MEASURE: Time to death. Relative risks of dying were calculated for demographic variables, dementia diagnoses based on findings of clinical evaluations, and 15 reported prevalent medical conditions using the proportional hazards model. RESULTS: In those subjects aged 65 to 74 years, the mortality risk ratio was 5.4 (95% confidence interval, 2.0 to 14.6) for Alzheimer's disease and 7.2 (95% confidence interval, 3.6 to 14.4) for vascular dementia. The risk ratio for Alzheimer's disease was similar to the mortality risk ratio for cancer (5.6 [range, 2.9 to 10.9]). In this age group, dementing illnesses were uncommon, and few deaths were therefore attributable to the dementing illnesses. In those subjects aged 75 years and older, the mortality risk ratios were 2.8 (95% confidence interval, 2.1 to 3.6) for Alzheimer's disease, 3.5 (95% confidence interval, 2.4 to 5.1) for vascular dementia, and 3.6 (95% confidence interval, 2.0 to 6.7) for "other dementias." Because these dementing disorders were common in those subjects aged 75 years and older, 23.7% of the risk of death could be attributed to these disorders. CONCLUSIONS: Both Alzheimer's disease and vascular dementias are truly malignant and constitute major risk factors for death in persons older than 75 years.

Prevention of chemotherapy-induced ulcerative mucositis by transforming growth factor beta 3.

Mucositis is a common, dose-limiting complication in patients receiving cancer chemotherapy, which appears to be a consequence of the rate of epithelial proliferation. The beta transforming growth factors have been shown to be negative regulators of epithelial cell proliferation. Here we show that transforming growth factor beta 3 administration reduced proliferation of oral epithelium in vitro and in vivo. Topical application of transforming growth factor beta 3 to the oral mucosa of the Syrian golden hamster prior to chemotherapy significantly reduced the incidence, severity, and duration of oral mucositis, reduced chemotherapy-associated weight loss, and increased survival.

The prevalence of dementia and Alzheimer's disease in Shanghai, China: impact of age, gender, and education.

We report the prevalence rates for dementia and Alzheimer's disease (AD) obtained from a probability sample survey of 5,055 noninstitutionalized older persons in Shanghai, China. A two-stage procedure was used for case finding and case identification. A Chinese version of the Mini-Mental State Examination was used to determine cases of possible dementia. Three different cutoff points on this mental status test were used depending on the respondent's level of education. Clinical evaluations, based on functional assessments and psychiatric interview, medical and neurological examinations, three standardized mental status tests, and a selected group of psychometric tests, were made in the second stage of the study to ascertain the clinical diagnosis of dementia and AD utilizing the Diagnostic and Statistical Manual for Mental Disorders, edition 3 and National Institute of Neurological and Communicative Disorders and Stroke-Alzheimer's Disease and Related Disorders Association criteria, respectively. The prevalence rate of dementia in persons 65 years and older was 4.6%. Clinically diagnosed AD accounted for 65% of the subjects with dementia. These findings indicate that the prevalence of dementia in Shanghai is very much higher than figures published earlier for China and Japan, and at the lower part of the range of values reported for community residents in the United States and other Western countries, but less than half of that reported in the recently published survey of the elderly in East Boston. Increasing age, gender (female), and low education are each highly significant and independent risk factors for dementia. One hypothesis to explain the increased prevalence in elderly women who had received no formal education invokes the possibility of an effect of early deprivation, perhaps lowering brain "reserve," allowing the symptoms of dementia to appear at an earlier date during disease progression.

Cognitive impairment among elderly adults in Shanghai, China.

This study reports the methods and initial findings of the first longitudinal study of Alzheimer's disease and dementia in China. A probability sample of 5,055 noninstitutionalized elderly persons in Shanghai was tested directly during the first phase of the study using a Chinese version of the Mini-Mental State Examination (MMSE). Details of sampling design and data collection procedures are described. Overall, some 4.1 percent of adults 55 years or older may be classified as having severe cognitive impairment, and 14.4 percent are mild cases. The rates for females are higher than for males by a ratio of 3.75 in the severe category, and 2.6 in the mild group. Within each age group, cognitive impairment rates vary by education. Multiple logistic regression was used to examine, within each age group, the nature of the association between the presence of a cognitive impairment and educational level controlling for sex. The results showed that educational attainment has a highly significant inverse relationship with prevalence of cognitive impairments (severe vs others). On the other hand, when educational attainment was controlled for in the logistic regression model, sex was significantly associated with prevalence of cognitive disorders for the age groups 65-74 and 75 years or older, but not for the group 55-64 years. These findings suggest the impact that basic educational deficits have on human cognitive functioning as measured through tests like the MMSE. Cross-tabulations of impairment rates according to marital status, economic status, and health-related problems are also presented.