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PubMed2002

Effect of smoking on tear proteins.

PURPOSE: Cigarette smoking is a serious risk factor for many diseases, e.g., cardiovascular and pulmonary diseases. It is also a risk factor in several eye diseases, including macula degeneration, glaucoma, and cataract. Ischemic, toxic, and oxidative effects of cigarettes are thought to play an important role in damaging ocular tissue. Furthermore, smoking can cause symptoms of dry-eye disease. The aim of this study was to analyze and compare electrophoretic patterns in tears of smokers (SP), severs smokers (SSP), and nonsmokers (CTRL). METHODS: We examined 105 eyes (SP: n=29, SSP: n=26, CTRL: n=50). Each patient was asked for subjective symptoms such as burning, itching, and foreign-body sensation. Tear proteins were separated by Sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE). Digital image analysis was performed by BioDocAnalyze (Biometra, Göttingen, Germany), with densitometric data files being created for each electrophoretic lane. Data was analyzed by multivariate statistical techniques. RESULTS: Tear protein patterns in SP ( P<0.05) and SSP ( P<0.05) were different from those of CTRL. There were significantly more protein peaks in the SSP group ( P<0.005) than in CTRL. CONCLUSION: Electrophoretic analysis of tear protein patterns could detect changes in tear proteins of smokers in comparison to nonsmokers. These changes were correlated with an increase of dry-eye-related subjective symptoms in smokers. Thus, electrophoretic analysis of tear proteins provided greater insight into the pathogenesis of smoking-induced ocular surface diseases.

Control Groups↗
PubMed2006

Analysis of IgG antibody patterns against retinal antigens and antibodies to alpha-crystallin, GFAP, and alpha-enolase in sera of patients with "wet" age-related macular degeneration.

BACKGROUND: The aim of this study was to compare the IgG antibody patterns against retinal antigens in sera of patients with age-related macular degeneration (AMD) and healthy subjects to learn more about possible immunological aspects of this disease and to identify some of the most important antigens. METHODS: Sera of 140 patients were analyzed: healthy volunteers (CO, n=101) and patients with "wet" age-related macular degeneration (AMD, n=39). The sera were tested against western blots of bovine retinal antigens. The IgG antibody patterns were analyzed by multivariate statistical techniques and some antigens were identified via LC-MS/MS. RESULTS: All patients showed complex patterns of IgG antibodies against retinal antigens. The discriminant analysis revealed a statistical significant difference between the antibody profiles of the AMD and the CO group (P=0.000023). Not only up-regulations of antigen-antibody-reactivities in the AMD group at some molecular weight ranges, e.g. at 46 and 52 kDa, could be seen, but also down-regulations, e.g. at 18 and 36 kDa. The 18 kDa antigen band was identified as alphaB-crystallin, the band at 46 kDa as alpha-enolase, and one at 52 kDa as glial fibrillary acidic protein. CONCLUSIONS: We could demonstrate that both groups (wet AMD and CO) show complex IgG antibody patterns against retinal antigens, which are highly specific for each group. This provides further hints for the immunological basis of the disease. These changes in the antibody profiles in "wet" AMD could represent a secondary response to retinal damage or can play a causative role in the disease.

Adult↗
PubMed2003

Vascular diffusion density and survival of patients with primary lung carcinomas.

AIM: To investigate the clinical significance of tumour vascularisation in operated lung cancer patients. MATERIALS AND METHODS: Histological slides obtained from 498 patients with potentially curative operated lung carcinomas in two different institutions of thoracic surgery were immunohistochemically stained with an anti-CD34 antibody and subjected to quantitative image analysis. Syntactic structure analysis measured the absolute and relative features of vessels, including the numerical tumour cells densities relative to their nearest neighbouring vessel. These data are associated with tumour volume, post-surgical TNM stage, and each patient's survival. RESULTS: The clinical data, including sex distribution, age of patients, pTNM stages and survival, did not differ between the two institutions. The tumour vascularisation (volume fraction, Vv) amounted to 7% in lung carcinomas, was independent from cell type and increased in advanced tumour stages (pT4, pN3). Advanced tumour stages presented with a higher numerical vascular density and with maintained minimum diameter and circumference of vessels. Each patient's survival was closely associated with the pN stage, tumour volume, cell type and numerical density of tumour cells within a distance less than 20 micro m from the nearest neighbouring vessel due to multivariate statistical analysis. CONCLUSION: Vascularisation of lung tumours becomes altered in advanced tumour stages. Of prognostic significance is the distribution of tumour cells in relation to the nearest neighbouring vessel only.

Adenocarcinoma↗
PubMed2005

The macaque inferior parietal lobule: cytoarchitecture and distribution pattern of serotonin 5-HT1A binding sites.

The inferior parietal lobule (IPL) of the macaque monkey integrates sensory information as a prerequisite for reaching and grasping movements. Electrophysiological data suggest that the convexity of the IPL is heterogeneous along its rostro-caudal axis. Cytoarchitecture reflects this functional diversity. However, various parcellations have been proposed so far, ranging from one homogeneous region to four areas. In order to obtain a more valid anatomical map of the IPL, we studied the distribution pattern of serotonin 5-HT1A binding sites (i.e., the domain of synaptic transmission and cortical information processing) and cytoarchitecture with an observer-independent technique (thus avoiding the subjectivity inherent in visually guided microstructural parcellations). We cut with a cryostat microtome four unfixed macaque hemispheres and processed sections for 5-HT1A binding sites with [3H]8-OH-DPAT receptor autoradiography or for cell bodies with a modified silver stain. We digitized the autoradiographs and the histological sections and extracted from the cortex of the IPL equidistant density profiles oriented vertically to the cortical layers. We then compared groups of neighboring profiles with multivariate statistics expecting to see a significant difference in profile shape at the interface between two cortical areas. These positions were compared between 5-HT1A autoradiographs (neurochemical borders) and adjacent histological sections (cytoarchitectonic borders). Neurochemical and cytoarchitectonic borders showed a good topographical correspondence and revealed three areas arranged in a rostro-caudal sequence along the convexity of the IPL. Dorsally, the areas extend approximately 1 mm into the depth of the lateral bank of the intraparietal sulcus. Their ventral border lies on the convexity of the IPL close to the shoulder of the lateral sulcus. The three areas are in close agreement with areas PF, PFG, and PG as defined by Pandya and Seltzer (J Comp Neurol 204:196-210, 1982) and Gregoriou et al. (Program No. 919.5, Abstract Viewer/Itinerary Planner, Washington, Society for Neuroscience, 2003). The neurochemical and cytoarchitectonic data show that a complex structural framework underlies the functional heterogeneity along the rostro-caudal axis of the IPL, e.g., the representation of different types of arm and hand actions in different sectors of the monkey's workspace.

Animals↗
PubMed2004

DNA diversity of human populations from Eastern Europe and Siberia studied by multilocus DNA fingerprinting.

We used DNA fingerprinting with M13 phage DNA as a probe to estimate the degree of genomic variability and genetic relationships in a heterogeneous group of 13 populations from Eastern Europe and Siberia. The popultaions belong to three language families: Indo-European (Slavonic: Russians, Byelorussians), Uralic (Finno-Ugric: Maris, Mordvinians, Udmurts), and Altaic (Turkic: Bashkirs, Tatars, Chuvashes, Yakuts). Multivariate statistical analyses were used (multidimensional scaling, cluster, and multiple correspondence analyses), and coefficients of gene differentiation ( Gst') were evaluated. The level of interpopulation subdivision in the various ethnic groups appeared to be different: the Byelorussian populations revealed no regional differences, in contrast to the Bashkir populations, which formed a heterogeneous group. The populations subdivided into three general clusters: Slavonic populations formed a separate tight cluster characterized by a minimal level of interpopulation diversity, Bashkir and Yakut populations formed the second cluster, and the Finno-Ugric and several populations of the Turkic linguistic groups formed the third cluster. The robustness of these results obtained by different statistical data treatments reveals that multilocus DNA fingerprinting can be reliably used for population studies.

Bacteriophage M13↗
PubMed2005

Genetic dissection of gene expression observed in whole blood samples of elderly Danish twins.

The microarray technique is an important tool in gene expression analysis to study the activities of thousands of genes measured by their transcript levels under disease or laboratory controlled experimental conditions. Recent studies have suggested a genetic component in the variations of gene expression thus indicating the important role of genetic control over gene activities. In this study, we analyze and report the twin correlation on gene expression in whole blood samples of six female Danish twin pairs aged from 81 to 85 years. We studied the expression phenotype by treating the measured gene expression as a quantitative trait and introducing analytical approaches including the traditional twin methods in population genetics and the multivariate statistical methods. Using this combinatory approach, we were able to estimate and compare the twin correlation on the expression phenotype while accounting for systematic influence in microarray experiments. Analyses on our twin data detected a significant correlation on the expression levels of the actively regulated genes in both monozygotic and dizygotic twins, which is more pronounced in monozygotic twins. Gene ontology analysis has shown that these actively regulated genes are predominantly involved in defense and immune responses against antigenic stimulus. In conclusion, the correlation patterns revealed in our twin data provide evidence of the existence of a heritable mechanism in gene expression regulation persistently functioning even in aged subjects.

Aged↗
PubMed2004

Effects of plant diversity, community composition and environmental parameters on productivity in montane European grasslands.

In the past years, a number of studies have used experimental plant communities to test if biodiversity influences ecosystem functioning such as productivity. It has been argued, however, that the results achieved in experimental studies may have little predictive value for species loss in natural ecosystems. Studies in natural ecosystems have been equivocal, mainly because in natural ecosystems differences in diversity are often confounded with differences in land use history or abiotic parameters. In this study, we investigated the effect of plant diversity on ecosystem functioning in semi-natural grasslands. In an area of 10x20 km, we selected 78 sites and tested the effects of various measures of diversity and plant community composition on productivity. We separated the effects of plant diversity on ecosystem functioning from potentially confounding effects of community composition, management or environmental parameters, using multivariate statistical analyses. In the investigated grasslands, simple measures of biodiversity were insignificant predictors of productivity. However, plant community composition explained productivity very well (R2=0.31) and was a better predictor than environmental variables (soil and site characteristics) or management regime. Thus, complex measures such as community composition and structure are important drivers for ecosystem functions in semi-natural grasslands. Furthermore, our data show that it is difficult to extrapolate results from experimental studies to semi-natural ecosystems, although there is a need to investigate natural ecosystems to fully understand the relationship of biodiversity and ecosystem functioning.

Biodiversity↗
PubMed2006

Effects of climate-driven temperature changes on the diversity of freshwater macroinvertebrates.

Increasing temperatures due to climate change were found to influence abundance and timing of species in numerous ways. Whereas many studies have investigated climate-induced effects on the phenology and abundance of single species, less is known about climate-driven shifts in the diversity and composition of entire communities. Analyses of long-term data sets provide the potential to reveal such relationships. We analysed time series of entire communities of macrozoobenthos in lakes and streams in Northern Europe. There were no direct linear effects of temperature and climate indices (North Atlantic Oscillation index) on species composition and diversity, but using multivariate statistics we were able to show that trends in average temperature have already had profound impacts on species composition in lakes. These significant temperature signals on species composition were evident even though we analysed comparatively short time periods of 10-15 years. Future climate shifts may thus induce strong variance in community composition.

Animals↗
PubMed2001

Are the favorable outcomes of splenectomy predictable inpatients with idiopathic thrombocytopenic purpura (ITP)?

BACKGROUND: Historically, splenectomy has been an accepted procedure in the management of immune thrombocytopenic purpura (ITP). However, it is also true that the response to splenectomy in patients with ITP seems to be unpredictable. Therefore, the purpose of this study was to identify clinical variables that might predict a favorable response to splenectomy in patients with ITP. METHODS: Data were collected retrospectively for 40 adult patients with ITP who underwent laparoscopic (LS) and open (OS) splenectomy at Emory University Hospital between 1992 and 1999. Demographics and outcomes were recorded. Age, sex, disease duration, comorbidities (ASA > 2), previous response to steroids and/or other medications, and preoperative platelet count were analyzed by univariate (t-test, Fisher's exact test) and multivariate statistical methods. RESULTS: Of the 20 patients in each group, improved platelet counts were noted in 18 patients (90%) in the LS group and 20 patients (100%) in the OS group. Follow-up (16 +/- 3 months) was obtained in 19 LS patients (95%) and 16 OS patients (80%), with 84% and 87.5% sustained response rates, respectively. After univariate analysis, two variables (age and disease duration) were found to be significantly related to the outcome of splenectomy (p <lt; 0.01). However, after multiple logistic regression analysis, only disease duration (relative risk = 1.083; CI, 1.004-1.167) was an independent prognostic factor for a sustained response to splenectomy. CONCLUSION: These results suggest that the response to splenectomy (laparoscopic and open) in patients with ITP cannot be adequately predicted on the basis of presplenectomy clinical variables. However, disease duration and patient age should be taken into consideration when selecting patients for splenectomy.

Adult↗
PubMed2006

A synoptic climatology of pollen concentrations during the six warmest months in Sydney, Australia.

This paper takes an air mass approach to investigating the influence of weather on pollen concentrations in the atmosphere in Sydney, Australia, by producing a synoptic classification of pollen concentrations measured in the Sydney Basin. This synoptic classification has been produced using multivariate statistical techniques including principal component analysis and cluster analysis, to assign days into meteorologically homogenous categories. Surface and upper air meteorological data for warm months (October-March) over a 10-year period were used as input into the statistical analyses. Eleven synoptic categories were found in Sydney during the warm months. Pollen concentrations for the total pollen load and five individual families measured over a 3.5-year period have been investigated for each of the synoptic categories. High pollen concentrations during the warm months in Sydney are found to be influenced by the presence of a region of low surface pressure located to the south of the continent, bringing fast dry westerly gradient winds to Sydney. It is envisaged that these results will be important from a pollen forecast and associated public health perspective.

Air Pollutants↗
PubMed1999

Etiology and natural history of primary sclerosing cholangitis.

The etiology of primary sclerosing cholangitis remains unknown. Bacteria, toxins, viral infections, and immunological and genetic factors have all been proposed as etiological agents. Portal bacteremia, toxins absorbed from the diseased colon in inflammatory bowel disease, and cytomegalovirus and reovirus infections have been implicated by various investigators but there is little evidence to support these hypotheses. The close association between primary sclerosing cholangitis and various human leukocyte antigen haplotypes is now well established and lends support to the theory that immunologic and genetic mechanisms may be involved in its pathogenesis. Patients with primary sclerosing cholangitis may have elevated levels of circulating immune complexes, immunoglobulins, and non-organ specific autoantibodies. The association between ulcerative colitis and primary sclerosing cholangitis remains unexplained and both groups of patients have a high prevalence of antibodies to the perinuclear cytoplasmic antigen. The long-term prognosis in primary sclerosing cholangitis is tempered by the development of cholangiocarcinoma in 6%-30% of patients when followed over long periods of time. Detecting cholangiocarcinoma early in a patient with primary sclerosing cholangitis is one of the most frustrating problems faced by a clinician while caring for these patients. The long-term outlook for patients with primary sclerosing cholangitis and cholangiocarcinoma remains dismal, whatever the treatment modality employed. However, the development of a multivariate statistical survival model from long-term survival data from the Mayo Clinic and other centers has been a major step in identifying individual primary sclerosing cholangitis patients at low, moderate, and high risk of dying. Such models have been useful for stratifying patients in therapeutic trials, for in patient counseling, and in patient selection and timing of liver transplantation.

Cholangitis, Sclerosing↗
PubMed2005

DDAVP use in patients undergoing transsphenoidal surgery for pituitary adenomas.

BACKGROUND: Disorders of fluid and sodium regulation, often termed "diabetes insipidus," are a frequent occurrence following surgery for pituitary adenomas. The present study was undertaken to identify the incidence of diabetes insipidus after pituitary surgery and its associated factors. METHODS: A retrospective review of the medical records 300 patients who underwent transsphenoidal surgery for pituitary adenoma was undertaken. Information regarding patient gender, perioperative serum sodium levels and urinary output volumes, tumor size, previous pituitary surgery, tumor subtype, and the use of DDAVP was gathered. A multivariate statistical analysis was performed. FINDINGS: Follow-up data were available on 288 patients. During the inpatient postoperative hospital stay, DDAVP was administered to 19% of all patients and 16% of patients not taking DDAVP preoperatively. Of patients with normal fluid/sodium regulation preoperatively, DDAVP was prescribed for 9% at discharge and 4% at 6 weeks postoperatively. Only 1.4% of patients were taking vasopressing replacement at the time of last follow-up. Significant correlations were found between gender, previous surgery, serum sodium levels, and urine volumes at various time points. Immunohistochemical type of tumor and tumor size were not related to DDAVP requirement. CONCLUSIONS: Transient hypotonic polyuria is frequently encountered after pituitary surgery. However, only a small number of patients will develop a long-term requiring for ongoing medical treatment. Previous surgery, female gender, and elevated serum sodium and urine volumes in perioperative period were associated with DDAVP requirement.

Adenoma↗
PubMed2002

Description of women's personality traits and psychological vulnerability prior to choosing hormone replacement therapy.

INTRODUCTION: Data suggest that women using hormone replacement therapy (HRT) represent a special subgroup of the general population regarding, for instance, cardiovascular risk factors and education. OBJECTIVE: To analyse if women who choose HRT are characterised a priori by high neuroticism score or by psychological vulnerability. DESIGN: A prospective population-based study was initiated in 1976 with follow-ups in 1981, 1987 and 1996. The population comprises a random sample of 621 women born in 1936 and living in the county of Copenhagen. STUDY METHODS: The analyses are based on data on two sub-cohorts of 268 and 235 women from the large population-based study. These subgroups consist of the women participating in both baselines at 40 and 45 years respectively and at follow-up in 1996. At the age of 40 the women participated in a comprehensive examination, which apart from baseline characteristics included Eysencks personality questionnaire concerning intro/extroversion and neuroticism. At the age of 45, the re-examination of the women included a test for psychological vulnerability. The participants reported whether or not they used HRT at the age of 40, 45, 51 and 60 years. The analyses comprised "never users" of HRT and "future users", defined as women who started HRT subsequent to baseline registration during the observation period. The groups were compared by multivariate statistical methods to adjust for confounding factors. RESULTS: Women with high neuroticism score at the age of 40 were more likely to become users of HRT in the future compared to women with low neuroticism score. At the age of 45, psychologically vulnerable women were more likely to become users of HRT in the future compared to non-vulnerable women. The associations became insignificant when correcting for potential confounders. The study suggests that selection bias among women choosing HRT may also include personality traits.

Adult↗
PubMed2002

Ab initio structure of human seminal plasma prostatic inhibin gives significant insight into its biological functions.

Human seminal plasma prostatic inhibin (HSPI) is a protein isolated from the human prostate gland. Despite its profound biomedical and biotechnological importance, the 3D structure of this protein of 94 amino acids remains undeciphered. The difficulties in extracting it in pure form and crystallizing it have restrained the determination of its structure experimentally. The homology-based computational methods are also not applicable, as HSPI lacks sufficient sequence homology with known structures in the protein data banks. We have predicted the structure of HSPI by a knowledge-based method using nonparametric multivariate statistical techniques. Stereochemical and other standard validation tests confirm this to be a well-refined structure. The biophysical properties exhibited by this structure are in good agreement with the NMR experimental observations. Docking and other computational studies on this structure provide significant explanation and insight into its binding activities and related biological and immunogenic functions and offer new directions for its potential applications.

Binding Sites↗
PubMed2005

Structure prediction of a multi-domain EF-hand Ca2+ binding protein by PROPAINOR.

PROPAINOR is a new algorithm developed for ab initio prediction of the 3D structures of proteins using knowledge-based nonparametric multivariate statistical methods. This algorithm is found to be most efficient in terms of computational simplicity and prediction accuracy for single-domain proteins as compared to other ab initio methods. In this paper, we have used the algorithm for the atomic structure prediction of a multi-domain (two-domain) calcium-binding protein, whose solution structure has been deposited in the PDB recently (PDB ID: 1JFK). We have studied the sensitivity of the predicted structure to NMR distance restraints with their incorporation as an additional input. Further, we have compared the predicted structures in both these cases with the NMR derived solution structure reported earlier. We have also validated the refined structure for proper stereochemistry and favorable packing environment with good results and elucidated the role of the central linker.

Animals↗
PubMed2006

Structure-olfactive threshold relationships for pyrazine derivatives.

Structure-olfactive threshold relationships for 40 pyrazine derivatives have been studied by multivariate statistical analysis. Variable descriptors used to describe the molecules studied were obtained using molecular-mechanics software. A correlation coefficient of 0.82 was obtained when all the molecules were included in the model. When the model was established for closely related subsets of molecules, the correlation coefficients obtained were higher and the established models were bilinear. Such models allow the identification of optimal structures corresponding to low olfactive thresholds for the subsets studied. Surprisingly, we find that the optimum structures are included in the set of 40 molecules. The efficiency of the models was supported by the cross-validation technique, where the correlation coefficients were found to be good with respect to the precision of the values of the olfactive thresholds.

Pyrazines↗
PubMed2005

Severe chronic venous insufficiency: magnitude of the problem and consequences.

The aim of this study was to characterize patients requiring hospitalization for severe chronic venous insufficiency (CVI) at the local and national levels and to analyze factors related to primary amputation. An administrative database (Nationwide Inpatient Sample, 1988-2000) and a single institution (1992-2000) were reviewed using the International Classification of Diseases, 9th ed., Clinical Modification, codes for CVI, excluding phlegmasia and concomitant peripheral vascular occlusive disease codes. Demographics, clinical course, and outcomes were assessed. Descriptive, univariate, and multivariate statistical analyses were used; p < 0.05 was considered significant. Nationally, CVI occurred with a mean incidence of 92/100,000 admissions, of which 55% were women, having a mean age of 65 years and a median length of stay of 7 days. Mean hospital charges were $13,900 and did not change significantly over time. Acute deep vein thrombosis affected 1.3%, amputation was performed in 1.2%, and in-hospital mortality was 1.6% The local cohort included 67 patients with a mean age of 51 years; a majority were men (60%), and 85% were C6 (of Clinical-Etiologic-Anatomic-Pathophysiology [CEAP]). Patients averaged 23 clinic visits and a median of one hospitalization for CVI care over a 44-month follow-up. Twelve patients (18%) underwent a CVI-related amputation (one transmetatarsal amputation, nine below-knee amputations, and two above-knee amputations). They had fourfold more CVI-related hospitalizations, greater preoperative chronic narcotic use than nonamputee patients (85% vs. 58%), but less ongoing wound care needs (25% vs. 89%) (all p values < 0.05). However, no significant difference in long-term mortality, number of clinic visits, duration of symptoms, antibiotic courses, or prior venous-related surgeries was found. In those with amputation, ambulatory status was maintained in 75% at 15-month follow-up. The physiological and economic costs of severe CVI are significant and have not decreased over more than a decade. Amputation for CVI-related nonhealing wounds has a reasonable outcome. Future therapy must focus on prevention of CVI sequelae.

Aged↗
PubMed2000

Novel approach to acoustical voice analysis using artificial neural networks.

Perceptual rating scales are widely used for the assessment of voice quality. These ratings may be influenced by the individual experience of the listener. Thus, researchers have turned to acoustical measures which may eventually correlate with voice quality. In this study we tested whether multivariate statistics, combined with artificial neural networks, could identify patterns of acoustic voice parameters corresponding to a widely used perceptual rating scale. In a multicenter study with 31 raters, voice samples of 117 individuals with or without voice disorders were perceptually rated. The RBH index, consisting of a 4-point scale of roughness, breathiness, and hoarseness, was used. Voice samples were then analyzed with an acoustical feature extraction and classified using amultivariate regression tree analysis with the perceptual ratings as a priori information. Artificial neural networks were trained to selected acoustic parameters having high "relative importance" in the regression trees. Mean classification accuracies were around 30% with topographic feature maps (trained with Learning Vector Quantization algorithm) and 65-85% with feedforward networks (trained with RProp algorithm). Based on the best-fitting results with feedforward networks, a classification system (computer program) consisting of 50 simultaneous working networks was developed. Using this program, the classification matched 40% of the a prori values in both R and B domains. In 65% they matched at least in one domain. These accuracies are within the range reported by other authors using artificial neural networks in biology and clinical medicine. Thus, the results encourage further research of feedforward networks for acoustic voice analysis.

Humans↗