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PubMed2001

Per capita alcohol consumption and all-cause mortality in 14 European countries.

AIMS: (1) To estimate the relationship between per capita alcohol consumption and male all-cause mortality in 14 European countries. (2) To compare the estimates with predictions from the U-shaped curve at the aggregate level. DATA AND METHOD: The outcome measures comprised annual data, after 1950, on male mortality (all-cause mortality and mortality from diseases) for the following age groups: 15+, 15-29, 30-49, 50-69 and 70+ years. Female mortality was included as a control variable. Alcohol sales were used as proxy for per capita consumption. The data were analysed using the Box-Jenkins technique. The estimated alcohol effects were pooled within low-, medium- and high-consumption countries. RESULTS: For all-cause mortality (15+), the effect estimates were significantly positive in eight of the 14 countries. The effect on mortality of a 1-litre increase in consumption tended to be stronger in low-consumption countries (3% per litre) than in medium- and high-consumption countries (1%). This pattern deviates from that predicted from the U-shaped curve. No significant impact of alcohol was found in the youngest age group when mortality from diseases was used as the outcome. CONCLUSIONS: Increases in overall consumption seem to be associated with increases in total mortality. Differences in drinking patterns are discussed as a possible explanation for the variation between country groups in alcohol effect.

Adolescent↗
PubMed2000

Surface characteristics of Azospirillum brasilense in relation to cell aggregation and attachment to plant roots.

The free-living bacteria of the genus Azospirillum live in close association with plant roots and represent one of the best-characterized plant growth promoting rhizobacteria (PGPR). The attachment of Azospirillum to the roots is essential for the establishment of an efficient association with the host plant. Azospirillum cells are able to aggregate under certain environmental conditions, leading to the formation of bacterial flocs. The bacterial surface plays an important role in the establishment of the bacteria-plant association as well as in the bacterial aggregation and data suggesting the involvement of extracellular polysaccharides and proteins in these phenomena have been published. This review summarizes the current knowledge on the involvement of surface components in the adhesion processes of Azospirillum. Emphasis is placed on A. brasilense, the species that has been the subject of most studies in the Azospirillum genus.

Azospirillum brasilense↗
PubMed2000

Interaction of bacterial flagellum filaments with skeletal muscle myosin.

Interaction of isolated bacterial flagellum filaments (BFF) and intact flagella from E. coli MS 1350 and B. brevis G.-B.p+ with rabbit skeletal myosin was studied. BFF were shown to coprecipitate with myosin (but not with isolated myosin rod) at low ionic strength, that is, under conditions of myosin aggregation. The data of electron microscopy indicate that filaments of intact bacterial flagella interact with isolated myosin heads (myosin subfragment 1, S1), and this interaction is fully prevented by addition of Mg2+ -ATP. Addition of BFF inhibited both K+ -EDTA- and Ca2+ -ATPase activity of skeletal muscle myosin, but had no effect on its Mg2+ -ATPase activity. Monomeric flagellin did not coprecipitate with myosin and had no effect on its ATPase activities. BFF were shown to compete with F-actin in myosin binding. It is concluded that BFF interact with myosin heads and affect their ATPase activity. Thus, BFF composed of a single protein flagellin are in many respects similar to actin filaments. Common origin of actin and flagellin may be a reason for this similarity.

Actin Cytoskeleton↗
PubMed1997

Tyrosine residue in exon 14 of the cytoplasmic domain of platelet endothelial cell adhesion molecule-1 (PECAM-1/CD31) regulates ligand binding specificity.

Platelet/endothelial cell adhesion molecule (PECAM-1) is a cell adhesion molecule of the immunoglobulin superfamily that plays a role in a number of vascular processes including leukocyte transmigration through endothelium. The presence of a specific 19- amino acid exon within the cytoplasmic domain of PECAM-1 regulates the binding specificity of the molecule; specifically, isoforms containing exon 14 mediate heterophilic cell-cell aggregation while those variants missing exon 14 mediate homophilic cell-cell aggregation. To more precisely identify the region of exon 14 responsible for ligand specificity, a series of deletion mutants were created in which smaller regions of exon 14 were removed. After transfection into L cells, they were tested for their ability to mediate aggregation. For heterophilic aggregation to occur, a conserved 5-amino acid region (VYSEI in the murine sequence or VYSEV in the human sequence) in the mid-portion of the exon was required. A final construct, in which this tyrosine was mutated into a phenylalanine, aggregated in a homophilic manner when transfected into L cells. Inhibition of phosphatase activity by exposure of cells expressing wild type or mutant forms of PECAM-1 to sodium orthovanadate resulted in high levels of cytoplasmic tyrosine phosphorylation and led to a switch from heterophilic to homophilic aggregation. Our data thus indicate either loss of this tyrosine from exon 14 or its phosphorylation results in a change in ligand specificity from heterophilic to homophilic binding. Vascular cells could thus determine whether PECAM-1 functions as a heterophilic or homophilic adhesion molecule by processes such as alternative splicing or by regulation of the balance between tyrosine phosphorylation or dephosphorylation. Defining the conditions under which these changes occur will be important in understanding the biology of PECAM-1 in transmigration, angiogenesis, development, and other processes in which this molecule plays a role.

Alternative Splicing↗
PubMed2004

AIDS-defining cancers in Western Europe, 1994-2001.

To determine the recent trends in AIDS-defining cancers in Western Europe, we analyzed the June 2002 European Non-Aggregate AIDS Data Set. We obtained the percentage of people with AIDS aged 15 years or older (n = 125,691; males, 99,560, females, 26,131) who had cancers as the initial AIDS-defining illness in 17 European countries. Overall, from 1994 through 2001, declines were noted in the number of people with AIDS (25,324 to 8929), the proportion of people with AIDS who were homosexual/bisexuals (38.8% to 26.6%) or intravenous drug users (male, 41.7% to 34.8%; female, 50.2% to 26.4%). Among males, between 1994 and 2001, the percentage with any AIDS-defining, cancers declined (14.4% to 13.1%, p for trend = 0.091) because of a decline in Kaposi's sarcoma (KS; 10.7% to 7.9%) mostly among homosexual/bisexual men (22.7% to 18.8%) (p for trends < 0.05). Between 1994 and 2001, the percentage of males with all types of lymphomas increased (3.8% to 5.2%, p for trend = 0.012). Among females, AIDS-defining cancers increased (7.3% to 8.5%) due to increase in lymphomas (all types, 2.6% to 4.0%) (p for trend = 0.05). Cervical cancer remained the most common cancer among females, the percentage of which declined between 1994 and 2001 (2.8% to 2.0%, p for trend = 0.37) mostly among women who were 15 to 29 years old, most of whom acquired HIV heterosexually. In summary, declines were noted for the two leading AIDS-defining cancers at initial AIDS diagnosis among certain population groups. KS declined among men who had sexually transmitted HIV infection. Cervical cancer declined among young females and heterosexuals.

AIDS-Related Opportunistic Infections↗
PubMed1995

Picture imperfect: hidden problems among Asian Pacific islander elderly.

Asian Pacific Islander (API) elderly represent the fastest growing group of ethnic elderly in the United States, yet their social and health needs remain little understood in the field of ethnogerontology. Existing literature generally portrays API elderly as in equal or better health compared to whites. However, aggregate API data cloud the bimodal distribution in socioeconomic and health status. We review existing literature on API elderly, and examine selected national data to illustrate the effects of a bimodal distribution on our understanding of API elderly socioeconomic and health status. Implications for research and policy are discussed.

Activities of Daily Living↗
PubMed2003

Suppression of polyglutamine-induced protein aggregation in Caenorhabditis elegans by torsin proteins.

Torsion dystonia is an autosomal dominant movement disorder characterized by involuntary, repetitive muscle contractions and twisted postures. The most severe early-onset form of dystonia has been linked to mutations in the human DYT1 (TOR1A) gene encoding a protein termed torsinA. While causative genetic alterations have been identified, the function of torsin proteins and the molecular mechanism underlying dystonia remain unknown. Phylogenetic analysis of the torsin protein family indicates these proteins share distant sequence similarity with the large and diverse family of AAA+ proteins. We have established the nematode, Caenorhabditis elegans, as a model system for examining torsin activity. Using an in vivo assay for polyglutamine repeat-induced protein aggregation in living animals, we have determined that ectopic overexpression of both human and C. elegans torsin proteins results in a dramatic reduction of polyglutamine-dependent protein aggregation in a manner similar to that previously reported for molecular chaperones. The suppressive effects of torsin overexpression persisted as animals aged, whereas a mutant nematode torsin protein was incapable of ameliorating aggregate formation. Antibody staining of transgenic animals indicated that both the C. elegans torsin-related protein TOR-2 and ubiquitin were localized to sites of protein aggregation. These data represent the first functional evidence of a role for torsins in effectively managing protein folding and suggest that possible breakdown in a neuroprotective mechanism that is, in part, mediated by torsins may be responsible for the neuronal dysfunction associated with dystonia.

Aging↗
PubMed1994

Sex differences in measles mortality: a world review.

BACKGROUND: In general females have a lower mortality than males at all ages. Excess female mortality has been documented in certain high mortality situations, in particular in South Asia. However, females may have a higher mortality for certain causes of death. One of the causes of death for which excess female mortality is suspected is measles. METHOD: Sex differences in measles mortality are investigated using all national data on causes of death published by WHO since 1950. An index of excess mortality is used: the geometric mean of the female sex ratios of age-specific deaths rates from measles, from age 0 to 44 years. RESULTS AND CONCLUSIONS: When pooled together, the results show an excess of female mortality from birth until age 50 years. The excess female mortality appears small at age 0-4 (+4.2%), larger at age 5-14 (+10.9%) and peaks during the female reproductive period, at age 15-44 (+42.6%). This pattern of excess female mortality occurs in all the major regions of the world: Europe, North and South America, Far-East Asia, the Middle East and South Asia. The only noticeable exceptions are the Philippines and Thailand. The validity of the finding is extensively reviewed. Emphasis lies on the statistical power to prove that sex differences in measles mortality do exist, on the critical analysis of a case study in England and Wales, on the comparison with the overall pattern of sex differences and on available data on sex differences in incidence. Possible explanations are reviewed.

Adolescent↗
PubMed1999

Classification differences and maternal mortality: a European study. MOMS Group. MOthers' Mortality and Severe morbidity.

OBJECTIVES: To compare the ways maternal deaths are classified in national statistical offices in Europe and to evaluate the ways classification affects published rates. METHODS: Data on pregnancy-associated deaths were collected in 13 European countries. Cases were classified by a European panel of experts into obstetric or non-obstetric causes. An ICD-9 code (International Classification of Diseases) was attributed to each case. These were compared to the codes given in each country. Correction indices were calculated, giving new estimates of maternal mortality rates. SUBJECTS: There were sufficient data to complete reclassification of 359 or 82% of the 437 cases for which data were collected. RESULTS: Compared with the statistical offices, the European panel attributed more deaths to obstetric causes. The overall number of deaths attributed to obstetric causes increased from 229 to 260. This change was substantial in three countries (P < 0.05) where statistical offices appeared to attribute fewer deaths to obstetric causes. In the other countries, no differences were detected. According to official published data, the aggregated maternal mortality rate for participating countries was 7.7 per 100,000 live births, but it increased to 8.7 after classification by the European panel (P < 0.001). CONCLUSION: The classification of pregnancy-associated deaths differs between European countries. These differences in coding contribute to variations in the reported numbers of maternal deaths and consequently affect maternal mortality rates. Differences in classification of death must be taken into account when comparing maternal mortality rates, as well as differences in obstetric care, underreporting of maternal deaths and other factors such as the age distribution of mothers.

Cause of Death↗
PubMed1980

A comparison of trends of coronary heart disease mortality in Australia, USA and England and Wales with reference to three major risk factors-hypertension, cigarette smoking and diet.

A comparison has been made of the recent changes in coronary heart disease mortality in Australia, the USA, and in the United Kingdom (England and Wales). Sharp declines in mortality dating from 1966 in Australia and from 1968 in the USA in both sexes contrast with a persistent increase in men in England and Wales until 1972 (after which a sight fall occurred) and a consistent slight fall in women since 1950. An investigation has been made of changes in 3 major risk factors-hypertension, cigarette smoking and diet in the 3 countries in an attempt to determine to what extent such changes might correlate with the different patterns of mortality. There has been a progressive and similar fall in mortality due to hypertension in both sexes in all 3 countries since 1950. There was a rise in cigarette smoking in all 3 countries from 1947 followed by a fall in the USA from 1963 and a more recent fall in men in Australia. There has been a levelling off of smoking in the United Kingdom in middle-aged and older men but not in women where smoking rates have increased from 1950 since when there has been a progressive slight fall in overall coronary heart disease mortality (although there is evidence of a recent rise in younger women.) Changes in dietary constituents (meat, eggs, milk and cheese, butter or margarine) have been examined by reference to aggregate consumption data. In Australia and the USA increases in vegetable fat consumption have occurred since 1950 with a reduction in animal fat in Australia but not in the USA. In the United Kingdom increases in vegetable fat have not been observed while there has been some increase in animal fat. It is concluded that the different patterns of coronary heart disease mortality in the 3 countries do correlate to some extent with changes in diet and cigarette smoking.

Adult↗
PubMed2003

Changes in child survival are strongly associated with changes in malnutrition in developing countries.

Considerable evidence suggests that malnutrition affects human performance, health and survival, including physical growth, morbidity, mortality, cognitive development, reproduction, physical work capacity and risks for several adult-onset chronic diseases. In recent decades, development agencies and governments have emphasized selective interventions to improve health and nutritional status, such as immunizations, oral rehydration, antibiotics and micronutrients, with child survival as a major motivation and justification. Although the efficacy of these approaches for improving child survival has been amenable to study, providing some of the rationale for using these approaches, it has not been possible to test directly the effects of improvements in general malnutrition. The present study quantified the effects of changes in general malnutrition, as measured by child weight-for-age (WA), on changes in child survival in 59 developing countries, using aggregate, longitudinal data at national and subnational levels from 1966 to 1996. Mixed model analysis (in SAS) was used, to take advantage of the multilevel and longitudinal nature of these data sets. Changes in WA have a statistically significant effect on changes in child mortality, independent of socioeconomic and policy changes represented by the secular trend. The secular trend in mortality began earlier and leveled off at higher mortality rates in populations with a higher prevalence of malnutrition. Gaps in coverage of selective interventions are more likely and more serious in the more malnourished populations. Continued reduction in mortality will require improved targeting of selective interventions and general nutritional improvement to the most marginal populations.

Child, Preschool↗
PubMed1998

Acute nephrotoxic serum nephritis in complement knockout mice: relative roles of the classical and alternate pathways in neutrophil recruitment and proteinuria.

BACKGROUND: The importance of complement in the pathophysiology of renal disease is still being appreciated. To further address the role of this mediator system, we evaluated the influence of absolute deficiency of C3 and C4 on acute nephrotoxic serum nephritis (NSN). METHODS: Selective 'knockout' of C3 and C4 was routinely confirmed in null mice by ELISA. NSN was induced by intravenous injection of a sheep anti-rat nephrotoxic serum that cross-reacts with murine glomerular antigens. Deposition of heterologous immunoglobulin in wild-type glomeruli was associated with rapid complement deposition and neutrophil infiltration, and followed by the development of proteinuria. RESULTS: Neutrophil infiltration was markedly inhibited in C3-deficient mice indicating a role for complement in PMN recruitment. In contrast, C3 deficiency afforded only partial protection against proteinuria. NSN was studied further in C4 null mice to probe the relative roles of the classical and alternate pathway in disease pathophysiology. C3 and C4 deficiency were associated with equivalent inhibition of PMN recruitment and proteinuria. CONCLUSIONS: In aggregate, the data support a major role for complement in PMN recruitment in this model and point to complement-independent mechanisms of proteinuria in antibody-mediated glomerulonephritis. These 'knockout' mice should prove valuable for defining the complement-activated mediator systems that regulate leukocyte recruitment and tissue injury in renal diseases.

Acute Disease↗
PubMed2005

Cyclosporine A induced epithelial-mesenchymal transition in human renal proximal tubular epithelial cells.

BACKGROUND: Tubulointerstitial fibrosis is a relatively common and sinister complication of cyclosporine A (CsA) therapy that limits its clinical use. CsA may have direct effects on renal tubular epithelial cells by promoting epithelial-mesenchymal transition (EMT). EMT plays an important role in embryonic development and tumourigenesis and has been described in organ remodelling during fibrogenesis. In this study, we investigated the effects of CsA on a human renal cell line as a model system to test the hypothesis that CsA can induce renal EMT. METHODS: Human renal proximal tubular cells were treated with CsA (0.42-42 microm) for periods up to 72 h. Viability was assessed by the Alamar Blue assay. Morphological changes were assessed by phase contrast microscopy. The effects on epithelial adherens molecule, beta-catenin and stress fibre protein, F-actin were analysed by indirect immunofluorescence. Reverse transcription--polymerse chain reaction was performed to measure the mRNA levels of extracellular matrix components. Expression of transforming growth factor-beta was measured by western blotting. Expression and activity of matrix metalloproteinases were measured by gelatin zymography. RESULTS: CsA induced striking morphological changes in epithelial cells, including changes in cellular morphology, F-actin stress fibre formation, delocalization of the adherens junction protein beta-catenin and increased levels of collagen IV and fibronectin. In addition, CsA-induced EMT was associated with increased TGF-beta1 protein levels and EMT was markedly attenuated in the presence of anti-TGF-beta1 antibody. CsA-induced EMT was also associated with increased expression of connective tissue growth factor (CTGF) suggesting that this molecule may serve as downstream mediator of TGF-beta1 pro-fibrotic activity in this setting. CONCLUSIONS: In aggregate, these data suggest that CsA is a direct stimulus for EMT in renal tubule epithelial cells and implicate TGF-beta1 and CTGF as mediators of this response. The further delineation of the molecular components of this pro-fibrogenic response may suggest novel strategies through which to prevent CsA-induced tubulo-interstitial fibrosis in vivo.

Actins↗
PubMed1999

Reliability and validity of the EuroQol in patients with osteoarthritis of the knee.

OBJECTIVE: To assess the reliability and validity of the EuroQol (EQ-5D) for osteoarthritis of the knee (OA knee). METHODS: Eighty-two patients with OA knee were asked to complete on two occasions, separated by 1 week, the EQ-5D, the Western Ontario and McMaster Universities (WOMAC) Osteoarthritis Index and the 36-item short form of the Medical Outcomes Study (SF-36). RESULTS: In this patient population, < 10% of the 243 EQ-5D health states were active. The EQ-5D demonstrated a non-Gaussian distribution. Reliability [intraclass correlation coefficient (ICC) = 0.70] is acceptable for aggregate level data. There were significant rank correlations with both the WOMAC and SF-36. CONCLUSIONS: This study provides some evidence of EQ-5D construct validity and reliability. However, the restricted and non-normal distribution of scores, the marked difference between patients' self evaluation and derived societal utility tariffs, as well as the lack of discriminative ability for patients with 'moderate' morbidity within each of the five EQ-5D dimensions, are of concern.

Aged↗
PubMed2001

Evidence for inadequate construct validity of the Disease Repercussions Profile in people with rheumatoid arthritis.

OBJECTIVE: To re-evaluate the construct validity of the Disease Repercussions Profile (DRP), a measure of handicap in arthritis populations. METHODS: We used the multitrait-multimethod approach to determine convergent and discriminant validity in a postal survey of randomly selected patients with rheumatoid arthritis who had attended the Wellington Regional Rheumatology Unit since 1988. Respondents (n=142) completed the following self-report instruments: Disease Repercussions Profile, EuroQol EQ-5D, Health Assessment Questionnaire, London Handicap Scale and WHOQOL-BREV. RESULTS AND CONCLUSIONS: The pattern of correlation supported the construct validity of the dichotomous response question (DRP domain affected or not) for the activity and relationships domain, provided ambiguous support for the appearance and emotion domain and no support for the social and financial domains. There was no support for construct validity of any of the domains on the importance rating part of the DRP. We suggest that the DRP be interpreted cautiously in aggregated group data.

Arthritis, Rheumatoid↗
PubMed1988

The cells of giant cell tumor of tendon sheath resemble osteoclasts.

To determine whether the mononuclear cells (MC) and multinucleated giant cells (GC) of giant cell tumor of tendon sheath (GCTTS) exhibit evidence of monocyte/macrophage lineage, we studied their antigenic features (seven cases, paraffin sections; two cases, frozen sections) and enzymatic features in situ (four cases, plastic sections). Both MC and GC expressed a monocyte/macrophage phenotype: HLA-A,B,C+, HLA-DR+, T200+ (leukocyte common antigen), Leu-M3+ and Leu-3+. MC and GC also expressed similar enzymatic phenotypes which resembled that of osteoclasts. Both were rich in acid phosphatase and contained smaller, variable amounts of ATPase, beta-glucuronidase, alpha-naphthyl acetate esterase, and 5'-nucleotidase. Both lacked alkaline phosphatase. Reactive osteoclasts in plastic and paraffin sections were also T200+, a finding strongly supporting their bone marrow derivation and leukocytic differentiation. In plastic sections, osteoclasts were additionally reactive with macrophage antigen EBM11. In aggregate, these data suggest that GCTTS is a true histiocytic lesion of monocyte/macrophage lineage composed of phenotypically similar MC and GC that most closely resemble osteoclasts. We found no evidence that GCTTS cells resemble osteoblasts, fibroblasts, or synovial sarcoma cells. Furthermore, expression of the Ki-67 nuclear antigen by 1-2% of MC but not by GC suggests that the proliferating cells in GCTTS are restricted to its MC component.

Antibodies, Monoclonal↗
PubMed1996

Kaposi's sarcoma and non-Hodgkin's lymphomas in children and adolescents with AIDS.

OBJECTIVE: To assess the proportion of, and the characteristics associated with, Kaposi's sarcoma (KS) and non-Hodgkin's lymphomas (NHL) in children (0-12 years) and adolescents (13-19 years) at AIDS diagnosis, in Europe and in the United States (US). DESIGN: Comparison of the proportions of KS and NHL at AIDS diagnosis, according to various characteristics, by means of the European Non-Aggregate AIDS Data Set (4400 children and 764 adolescents) and the US AIDS Public Information Data Set (4710 children and 1064 adolescents) updated to June 1993. METHODS: Comparison of data was made using odds ratios (OR) and corresponding 95% confidence intervals. RESULTS: Between 0 and 19 years, the proportion of KS at AIDS diagnosis (0.5% in Europe and 0.9% in the US) increased with age, particularly in Europe, and was higher in males than in females. It decreased with time in the US but not in Europe. In the US, black children showed a nearly threefold excess of KS as compared with white children. Adolescents who reported homosexual intercourse with other males had significantly elevated risks of KS, both in Europe (OR, 6.3) and in the US (OR, 21.1). NHL was diagnosed in 0.9% of children in Europe and in 1.5% in the US. The proportion of NHL significantly increased with age (3.1% among adolescents in Europe and 3.0% in the US), and was higher in males than in females. In the US, NHL tended to decline in proportion with all AIDS cases over time and showed a nearly twofold higher frequency in white children. No association emerged between NHL and HIV transmission category. CONCLUSIONS: In agreement with incidence rates in the general paediatric population, but at variance with AIDS in adults, NHL turned out to be more common than KS in children and adolescents with AIDS. A strong excess of KS was already present in adolescents who reported homosexual intercourse.

Acquired Immunodeficiency Syndrome↗