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PubMed1998

Three-dimensional reconstruction of metal replicas of the Helicobacter pylori vacuolating cytotoxin.

The Helicobacter pylori vacuolating cytotoxin (VacA) forms high molecular weight homooligomers which contain either six or seven copies of a 95-kDa polypeptide. Electron microscope visualization of carbon platinum replicas of quick-freeze, deepetched, preparations of VacA has revealed that the oligomers are arranged in flower-like structures with six- or sevenfold radial symmetry, depending on the number of 95-kDa oligomers that they contain. Each monomer is structured in two subunits of 37 and 58 kDa connected by an exposed loop which is a site for proteolytic cleavage. In preparations of VacA which had undergone extensive cleavage at the exposed loop, oligomers of both six- and seven-fold symmetry which appeared flatter were observed; these latter were interpreted as molecules which had lost a complete set of one of the subunits. We exploited a 3D reconstruction of metal replicas of quick-freeze, deep-etched, oligomers, representing the four types of molecules described. All the molecules appear to adhere with the same face toward the mica. Images of rotary shadowed oligomers were processed by multivariate statistical analysis to evidence clusters of equivalent and homogeneous oligomers. 3D reconstructions of the replicas so classified were performed by random conical tilt tomography. In the case of intact molecules (not cleaved) the reconstructions represent both the outer and the inner surfaces of the mold; the latter gives a reasonably accurate sense of the upper surface of the VacA oligomers. These data support the hypothesis that VacA is an AB type toxin and suggest a model in which the smaller of the two subunits is arranged in a uniform ring on the surface of the molecule in such a way as to contribute to the overall stability of the molecule.

Bacterial Proteins↗

PubMedDate not supplied

Single-particle approaches in the analysis of small 2D crystals of the mitochondrial channel VDAC.

It has been difficult to obtain better than moderate resolution in analysis of electron microscopic images of small, 2D crystals with variable lattice parameters, e.g., crystals of the channel VDAC generated by phospholipase treatment of outer mitochondrial membranes. We demonstrate that applying single-particle analysis methods to correlation-averaged images can lead to significant improvements in the attainable resolution. Application of a soft-edged fitted mask passing only the central unit cell, and excluding the positionally variable adjacent unit cells, allows improved alignment and more sensitive multivariate statistical analysis, needed to guide intelligent merging of data from different crystals.

Cryoelectron Microscopy↗

PubMed1997

Characterizing the response of PET and fMRI data using multivariate linear models.

This paper presents a new method for characterizing brain responses in both PET and fMRI data. The aim is to capture the correlations between the scans of an experiment and a set of external predictor variables that are thought to affect the scans, such as type, intensity, or shape of stimulus response. Its main feature is a Canonical Variates Analysis (CVA) of the estimated effects of the predictors from a multivariate linear model (MLM). The advantage of this over current methods is that temporal correlations can be incorporated into the model, making the MLM method suitable for fMRI as well as PET data. Moreover, tests for the presence of any correlation, and inference about the number of canonical variates needed to capture that correlation, can be based on standard multivariate statistics, rather than simulations. When applied to an fMRI data set previously analyzed by another CVA method, the MLM method reveals a pattern of responses that is closer to that detected in an earlier non-CVA analysis.

Analysis of Variance↗

PubMed1999

Areas 3a, 3b, and 1 of human primary somatosensory cortex.

This study defines cytoarchitectonic areas 3a, 3b, and 1 of the human primary somatosensory cortex by objective delineation of cytoarchitectonic borders and ensuing cytoarchitectonic classification. This avoids subjective evaluation of microstructural differences which has so far been the only way to structurally define cortical areas. Ten brains were fixed in formalin or Bodian's fixative, embedded in paraffin, sectioned as a whole in the coronal plane at 20 microm, and cell stained. Cell bodies were segmented from the background by adaptive thresholding. Equidistant density profiles (125 microm wide, spacing 300 or 150 microm) were extracted perpendicularly to the pial surface across cortical layers II-VI and processed with multivariate statistical procedures. Positions of significant differences in shape between adjacent groups of profiles were correlated with the cytoarchitectonic pattern. Statistically significant borders can be reproduced at corresponding positions across a series of nearby sections. They match visible changes in cytoarchitecture in the cell-stained sections. Area 3a lies in the fundus of the central sulcus, and area 3b in the rostral bank of the postcentral gyrus. Area 1 lies on its crown and reaches down into the postcentral sulcus. Interareal borders, however, do not match macrostructural landmarks of the postcentral gyrus, and they considerably vary in their positions relative to these landmarks across different brains. Hence, only genuine microstructural analysis can define the borders between these cortical areas. Additional significant borders which do not correlate with visible changes in cytoarchitecture can be found within areas 3b and 1. They may represent somatotopy and/or cortical representations of different somatosensory receptors.

Adult↗

PubMed1999

Detecting structural changes in whole brain based on nonlinear deformations-application to schizophrenia research.

This paper describes a new method for detecting structural brain differences based on the analysis of deformation fields. Deformations are obtained by an intensity-based nonlinear registration routine that transforms one brain onto another one. We present a general multivariate statistical approach to analyze deformation fields in different subjects. This method was applied to the brains of 85 schizophrenic patients and 75 healthy volunteers to examine whether low frequency deformations are sufficiently sensitive to detect regional deviations in the brains of both groups. We observed significant changes caused by volume reduction in brains of schizophrenics bilaterally in the thalamus and in the superior temporal gyrus. On the left side, the superior frontal gyrus and precentral gyrus are found to be changed, while on the right side, the middle frontal gyrus was altered. In addition, there were significant changes in the occipital lobe (left lingual gyrus) and in the left cerebellum. Volume enlargement in brains of schizophrenics was observed in the right putamen and in the adjacent white matter of the thalamic region. Our data suggest a disturbance in the nodes of a prefrontal-thalamic-cerebellar circuitry. This provides further support for the model of "cognitive dysmetria," which postulates a disruption in these nodes. We have demonstrated the application of deformation-based morphometry by detecting structural changes in the whole brain. This technique is fully automatic, thus allowing for the inclusion of large samples, with no user bias or a priori-defined regions of interest.

Adult↗

PubMed1995

Surgical risk factors for severe postoperative proliferative vitreoretinopathy (PVR) in retinal detachment with grade B PVR.

BACKGROUND: Previous studies have shown that grade B proliferate vitreoretinopathy (PVR) is a considerable risk factor for the development of severe postoperative PVR. We conducted a prospective study to elucidate which surgical procedures used in retinal detachment management may stimulate the PVR process in such eyes. MATERIALS AND METHODS: The study included 156 eyes of 152 consecutive patients with rhegmatogenous retinal detachment complicated by grade B PVR referred before any failed surgery and operated on between 1983 and 1993. The parameters evaluated by multivariate statistical analysis included the cumulative circumferential extent of the retinal tears, the extent of the scleral buckle, gas injection, vitrectomy, the method used for retinopexy, and the time of surgical management during the period of the study. RESULTS: The incidence of severe postoperative PVR was 25.8% in eyes managed with cryotreatment versus 2.2% in eyes managed with argon laser photocoagulation (P = 0.001). The rate of severe postoperative PVR was not influenced by the other surgical variables. CONCLUSION: We conclude that cryotherapy may be a risk factor for the development of severe postoperative PVR in retinal detachments associated with grade B PVR.

Adolescent↗

PubMed1996

Cryopexy in primary rhegmatogenous retinal detachment: a risk factor for postoperative proliferative vitreoretinopathy?

PURPOSE: To evaluate the role of cryopexy in the stimulation of postoperative proliferative vitreoretinopathy (PVR) in primary rhegmatogenous retinal detachment. MATERIALS AND METHODS: A series of 595 eyes of 554 patients with primary rhegmatogenous retinal detachment, referred before any failed surgery, were prospectively evaluated. Univariate and multivariate statistical analyses of the data were conducted. RESULTS: The incidence of postoperative PVR in relation to the methods used for retinopexy was dependent on the types and anatomy of retinal breaks associated with retinal detachment. The incidence of postoperative PVR was nil in retinal detachments due to atrophic holes in lattice, oral dialyses, and macular holes, regardless of the retinopexy methods. Postoperative PVR occurred solely in retinal detachments due to horseshoe tears (incidence 4.42%), paravascular tears of the postequatorial region (18.18%), and giant tears (24.6%) (P < 0.00001). The incidence of postoperative PVR was 0.5% in eyes with horseshoe tears with mobile posterior edges vs 9.72% in eyes with horseshoe tears with curled posterior edges, regardless of the retinopexy methods (P < 0.00001). In retinal detachments due to horseshoe tears with mobile posterior edges the incidence of postoperative PVR (0.5%) was not influenced by the retinopexy methods. In contrast, in retinal detachments due to horseshoe tears with curled posterior edges the incidence of postoperative PVR was higher in eyes managed with cryopexy (14.77%) than in eyes managed with laser retinopexy (1.78%) (P < 0.02). In retinal detachments due to giant tears the incidence of postoperative PVR was not statistically significantly greater in eyes managed with cryopexy (33.3%) than in eyes managed with laser retinopexy (15.6%). In tears 180 degrees and over in size, however, the incidence of postoperative PVR was significantly higher in eyes managed with cryopexy (9/11 eyes) than in eyes managed with laser retinopexy (5/17 eyes) (P = 0.006). CONCLUSIONS: Cryopexy is not a stimulating factor for postoperative PVR in primary rhegmatogenous retinal detachments due to atrophic holes in lattice, oral dialyses, macular holes, or horseshoe tears with mobile posterior edges. In contrast, cryopexy probably is a stimulating factor for postoperative PVR in retinal detachments due to horseshoe tears with curled posterior edges or to retinal tears 180 degrees and over.

Adolescent↗

PubMed1995

Cytogenetic biomonitoring of styrene-exposed plastic boat builders.

Earlier studies have produced evidence for an association between work-related styrene exposure and cytogenetic damage, while more recent studies have failed to show such an association. In the present study, chromosome aberrations (CA) and sister chromatid exchanges (SCE) were measured in peripheral blood lymphocytes of 46 male workers employed in a fiber-reinforced plastic boat building factory and exposed to styrene. Two groups of 23 workers each, characterized by different exposure levels (ranges: 2-120 mg/m3 and 86-1389 mg/m3 ambient air) were studied, fifty-one controls matched by sex, age and smoking habits were included. Randomized blood samples were analyzed for cytogenetic damage separately in two laboratories. Interlaboratory differences in the scoring of CA and SCE were noted. However, increases of the considered cytogenetic endpoints in exposed vs control groups were consistently observed in both laboratories. Multivariate statistical analysis of pooled data revealed increases of CA ranging between 19% (RR = 1.19; 95% C.I., 0.80-1.78; chromatid-type aberrations, low exposure group) and 144% (RR = 2.44; 95% C.I., 1.26-4.70; chromosome-type aberrations, high exposure group). Parallel excess of SCE in styrene exposed workers was also observed, although at a lesser extent (RR = 1.22; 95% C.I., 1.05-1.43, low exposure group; RR = 1.26; 95% C.I., 1.07-1.47, high exposure group). These findings suggest the presence of a causal association between occupational exposure to styrene and cytogenetic damage in the plastic boat building factory that was the object of the study.

Adult↗

PubMed1987

On the mode of action of six putative dopamine receptor agonists on suppression of exploratory behaviour in rats.

The effects of six putative dopamine receptor agonists on exploratory behaviour in rats were assessed: pergolide, (+)- and (-)-3-PPP, bromocriptine, mesulergine and CQ 32-084. Behaviour was automatically recorded in a holeboard apparatus and the data were analysed by the novel multivariate statistical method of partial least squares. All six substances suppressed exploratory behaviour at low doses. Pergolide and (+)-3-PPP-induced stereo-typed behaviour at higher doses. The suppression of exploration induced by pergolide was completely antagonised by sulpiride, partly antagonised by metoclopramide and weakly affected by haloperidol pretreatment. The effects of a low dose of (+)-3-PPP, bromocriptine or CQ 32-084, but not (-)-3-PPP or mesulergine, were antagonised by sulpiride. These findings support the hypotheses that pergolide, (+)-3-PPP, bromocriptine and CQ 32-084 inhibit exploration via stimulation of dopamine receptors. The present data do not substantiate the hypothesis that the suppression of exploration induced by (-)-3-PPP is mediated by stimulation of dopamine autoreceptors. A detailed analysis of the dose curves for pergolide and (+)-3-PPP indicates that the latter compound may have effects in addition to those of a dopamine receptor agonist.

Animals↗

PubMed1987

The staging of soft-tissue sarcomas.

We have assessed the ability of the American Joint Committee System, the Hajdu and the Surgical Staging System to separate different prognostic groups of patients with soft-tissue sarcoma. There were 122 patients with nonmetastatic tumours of the locomotor system. All were operated on with a wide, or radical, surgical margin. None of the staging systems could identify more than two groups with significantly different overall survival. A plea is made for the use of statistical multivariate analysis of prognostic factors when constructing staging systems for soft-tissue sarcoma.

Adolescent↗

PubMed1991

Codon usage in Aspergillus nidulans.

Synonymous codon usage in genes from the ascomycete (filamentous) fungus Aspergillus nidulans has been investigated. A total of 45 gene sequences has been analysed. Multivariate statistical analysis has been used to identify a single major trend among genes. At one end of this trend are lowly expressed genes, whereas at the other extreme lie genes known or expected to be highly expressed. The major trend is from nearly random codon usage (in the lowly expressed genes) to codon usage that is highly biased towards a set of 19-20 "optimal" codons. The G + C content of the A. nidulans genome is close to 50%, indicating little overall mutational bias, and so the codon usage of lowly expressed genes is as expected in the absence of selection pressure at silent sites. Most of the optimal codons are C- or G- ending, making highly expressed genes more G + C-rich at silent sites.

Aspergillus nidulans↗

PubMed1985

Biological potency of porcine, bovine and human insulins in the rabbit bioassay system.

Potency determination of porcine, bovine and human insulins relative to the International Standard in the pharmacopoeial rabbit bioassay system requires that the log-dose response curves are parallel. Furthermore, the same relative potency should be obtained independent of how the hypoglycaemic response is defined. The results of 508 rabbit blood glucose assays have been analyzed by new multivariate statistical methods. No deviations from parallelism of the log-dose response curves were detected. However, the potencies showed significant variation depending on the blood sampling times. Pure porcine and human (semisynthetic and biosynthetic) insulin potencies decreased by 12% and 18%, respectively, from the 30-min to the 2.5-h response, whereas bovine insulin potencies increased by 9%. Since the standard is a 52:48 mixture of bovine and porcine insulins, these results could be due to porcine and human insulins having a quicker onset and shorter duration of hypoglycaemic effect than bovine insulin. This was confirmed in assays of bovine relative to porcine insulin and by direct comparison of mean blood glucose curves. It is concluded that there is a response time-dependent variation in potency when the test and standard insulin have a different species composition. Hence, pure species insulin standards - a porcine, a bovine and a human standard - are needed for assay of the three insulins.

Animals↗

PubMed1990

Psychometric intelligence after infantile hydrocephalus. A critical review and reinterpretation.

Methodological issues in research concerning intellectual sequelae of infantile hydrocephalus are reviewed, and a multivariate statistical approach to this problem is proposed and exemplified. The significance of a variety of medical history variables with regard to psychometric intelligence was assessed in a sample of 5- to 8-year-old children who had been shunted in the 1st year of life. Stepwise discriminant analyses revealed that many medical history variables were neutral with regard to intellectual outcome (as assessed by performance on psychometric tests). The presence of additional medical problems in infancy, as well as current ocular defects, were the most significant variables that were associated with a high likelihood of mental retardation. Implications for further research are discussed.

Cerebrospinal Fluid Shunts↗

PubMed1992

Quantitative morphology of stimulation-induced damage in rabbit fast-twitch skeletal muscles.

The purpose of this study was to examine the contention that stimulation-induced damage, resulting in degeneration with subsequent regeneration, plays a major role in the transformation of fibre type brought about by chronic electrical stimulation. Data from histological and histochemical sections of 9-day-stimulated rabbit fast-twitch muscles were analysed with multivariate statistical techniques. Fibre degeneration and regeneration varied non-systematically between sample areas at any given cross-sectional level. In the extensor digitorum longus muscle, but not in the tibialis anterior, there was more degeneration in proximal than in distal portions of the muscle. The extensor digitorum longus muscle consistently showed more degeneration than the tibialis anterior muscle. Degeneration was less extensive for an intermittent pattern of stimulation that delivered half the aggregate number of impulses of continuous stimulation. Degeneration and regeneration varied markedly between individual rabbits in each of the groups. Sections that revealed the most degeneration and regeneration also had more fibres that reacted positively with an anti-neonatal antibody. Rigorous analysis of different sources of variation has helped to explain apparent conflicts in the literature. The incidence of muscle fibre damage in the stimulated tibialis anterior muscle is low, showing that the contribution of degenerative-regenerative phenomena to fibre type conversion in this muscle is insignificant.

Animals↗

PubMed1982

[Principle factors and symptom complexes in delirium tremens, factor and a group analytic study].

Before treatment 80 unselected patients suffering from delirium tremens were examined with regard to 13 psychopathological criteria. For the data a matrix of correlation was computed and it was factor analyzed according to the principal-component method. In consideration of the course of the value-curve two factors were interpreted. The result, however, is an undetailed classification. In addition to that, the data were cluster-analyzed according Ward. The results of the multivariate statistical analysis admit the assumption of two great, though heterogenous groups of symptoms (hallucination/vigilance). Factor I comprises the symptoms, disorder of orientation and consciousness, sweating, agitation and tremor on its positive pole, the duration of the delirant state on its negative pole. Factor II combines paranoid-hallucinatory symptoms, fearful affects and suggestibility on its positive pole, while on its negative, there are happy affect and grand-mal seizures. The bipolarity of this factor and additional diagnoses show that paranoid-hallucinatory symptoms without disorder of consciousness and grand-mal seizures mutually exclude each other. From this a differential therapy treating patients suffering from paranoid-hallucinatory symptoms with neuroleptics (e.g. Haloperidol) can be deduced, while the danger of grand-mal seizures has to be considered when disorders of consciousness appear.

Alcohol Withdrawal Delirium↗

PubMed1978

The measurement of change in endogenous affective disorders.

Psychopathological syndromes, as originally revealed by clinical observation, can also be detected by multivariate statistical analyses of symptom ratings. Changes in the course of psychiatric syndromes may be rated simply by improvement scales or by consecutive quantifications of symptoms and their comparison in chronological order. For the latter approach, which is less liable to bias, clinical ratings of psychopathology by staff members, self-ratings by the patients, analyses of patients' overt behavior (including video and speech records), or objective measurements of psychological and/or physiological variables can be used. Advantages and limitations of these different methods are discussed and illustrated by examples from ongoing clinical research in affective disorders. Generally, the combined use of different rating procedures is recommended. Self-ratings are economical, but they may represent aspects of psychopathology other than clinical ratings. In endogenous depression, mood scales are valid (supplementary) tools for the quantification of long-term as well as short-term changes, including diurnal variations. In severe conditions of mania, however, clinical rating has been--until now--the only valid basis for quantifying the degree of psychopathology and its changes with time. Precise evaluation of changes in psychopathology is essential in longitudinal investigations of endogenous affective disorders, since psychopathology up to now seems to have been the most sensitive and the most specific indicator of the hypothetical underlying abnormalities of cerebral functioning.

Affect↗

PubMed1990

A seroepidemiological study on bluetongue virus in dairy cattle in the central valley of California.

A seroepidemiological study on bluetongue virus (BTV) infection in California dairy cattle was conducted to estimate the prevalence and distribution by age and season of BTV group-reactive antibodies and to look for possible associations between the presence of antibodies and cattle age or breed and farm. Between December 1985 and March 1987, a sample of cattle was tested at approximately two-month intervals for BTV group-reactive antibodies using an enzyme-linked immunosorbent assay (ELISA). Data taken during the month of December 1986 were used to evaluate possible associations between a positive antibody test and certain intrinsic (age, breed) and extrinsic (farm) factors. Univariate and multivariate statistical analyses using the chi-square test for associations and multiple logistic regression, respectively, were carried out for possible associations between positive antibody tests to BTV and each factor of interest. The strengths of the associations were determined using estimates of the odds ratio. Of the 3774 serum samples tested, 238 (6.3%) were from calves, 1045 (27.6%) were from heifers and 2492 (66.0%) were from cows. Seroprevalence varied from nil in calves on two occasions to over 90% on several occasions in cows. Cows consistently had higher prevalence rates than heifers or calves across all test dates (p less than 0.05). The seroprevalence of BTV group-reactive antibodies also showed a seasonal fluctuation, with the highest rates occurring during the warmer months of the year. These highest prevalence rates coincided with heavy activity of the known vector of BTV, Culicoides spp. Breed and farm effects were not statistically significant (p greater than 0.05). With the exception of one farm, all cattle were of the Holstein breed, which reduced confidence in assessing any breed effect in this study. Relative estimates of the sensitivity and specificity of BTV ELISA were 87% and 100% respectively, compared to the standard agar gel immunodiffusion (AGID) test. The observations support previous findings of seasonal distribution of BTV antibodies and suggest an age relationship, whereby older cattle are more likely to be positive to BTV group-reactive antibodies than younger cattle.

Age Factors↗

PubMed1992

Shiftwork: its impact on the length and quality of sleep among nurses of the Valencian region in Spain.

Previous research has shown the repercussions of shiftwork for workers' sleep. The objective of the present work is to evaluate the impact of shiftwork on the length and quality of sleep among nurses and on the intake of psychotropic drugs. A cross-sectional epidemiological study was carried out in 606 female nurses and 367 male nurses selected at random from the public hospitals in the Valencian region. Information was collected by means of a questionnaire. Univariate and multivariate statistical analysis techniques were used. For both female and male nurses, shiftwork led to a reduction in the length of sleep (by 2 h in those permanently on night shifts and by 30 min in those on a rotating night shift system) and an alteration in the quality of sleep (difficulty in sleeping, intermittent sleep, early waking, etc. occurred 10% more frequently), but it did not lead to an increase in the consumption of psychotropic drugs.

Cross-Sectional Studies↗