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PubMed1963

AN ADJUSTING AVOIDANCE PROCEDURE WITH MULTIPLE AUDITORY AND VISUAL WARNING STIMULI.

Male albino rats were trained on an adjusting avoidance schedule in which each lever press accumulated a given amount of shock-free time. Multiple auditory and visual stimuli were programmed for each discrete temporal distance from the shock in an effort to place the avoidance behavior under the control of the shock proximity. The effects of the stimuli were further examined by presenting part of them and then by removing them altogether. With the combined auditory and visual stimuli, the rat spent most of the time relatively close to the shock and usually started to respond only when the shock was near. With the visual stimuli only, the rat kept the shock at intermediate temporal distances and responded more variably. The behavior with the auditory stimuli alone was quite similar to that produced by the combined stimuli, thus indicating that the auditory stimuli exercised the greater control. When all stimuli were removed, the animal usually kept the shock as far away as the procedure permitted. When only a single pre-shock stimulus was presented, the rat remained quite close to the shock and started to respond predominantly in the pre-shock step.

Adaptation, Psychological↗
PubMed1997

Three-dimensional demonstration of melanocyte distribution of human hair follicles: special reference to the bulge area.

Melanocytes of human hair follicles were histochemically and immunohistochemically examined in two and three dimensions. EDTA-treated extracted anagen vellus and intermediate hair follicles showed that monoclonal murine antibody (MoAb) NKI/ beteb-reactive melanocytes were distributed from the infundibulum to the bulb. Melanocytes of the infundibulum and bulb were larger and more strongly stained with MoAb NKI/beteb than those of the middle portion below the sebaceous gland. Latter melanocytes showed less dendricity. Dendritic melanocytes were exclusively observed in the bulb as well as the bulge area of vellus and intermediate hair follicles, where they were variably melanized. In longitudinal and transverse sections of adult human scalp some keratinocytes of the outer root sheath of the bulge area were melanized compared to other parts. This phenomenon was independent of the hair cycle. These findings may be characteristic of bulge melanocytes and/or keratinocytes.

Adult↗
PubMed2006

[The natural history of multiple sclerosis].

The course of multiple sclerosis (MS) results from the interplay of two clinical processes, relapses and progression. Three main clinical forms may be identified as relapsing-remitting, secondary progressive and primary progressive. The disease appears on average at the age of 30 and follows a remitting or a progressive course in 85% and 15% of the cases, respectively. Initial symptoms are related to an isolated or combined disturbance(s) of the long tracts of the central nervous system, of the brainstem, or of the optic nerve in 70%, 20% and 25% of the cases, respectively. The relapse rate is one relapse on average every other year. After an exacerbating-remitting onset of MS, secondary progression appears after 19 years on average. The median time to reach the landmarks of irreversible disability are 8 years regarding limitation of ambulation, 20 years for walking with a stick, and 30 years for wheel-chair dependency. In fact, MS prognosis is highly variable depending on individuals. All the intermediate types do exist between malignant forms, possibly lethal, and benign forms (circa 30% of the cases) that allow normal daily life. The clinical and paraclinical predictive factors identified so far have been acknowledged statistically. They provide little help however, if any, when an individual is concerned. Recent research has showed that relapses have only a marginal effect, relatively to progression, on the accumulation of irreversible neurological disability. Furthermore, the age when reaching the landmarks of irreversible disability is essentially similar whatever the mode of onset of MS, be it exacerbating-remitting or progressive. In spite of the outstanding clinical polymorphism of MS, a unifying concept of the disease ("complexity vs heterogeneity") can be put forward.

Disease Progression↗
PubMed1991

An evaluation of waist to hip ratio measurement methods in relation to lipid and carbohydrate metabolism in men.

The purpose of this study was to determine which method of measuring waist to hip ratio (WHR) was the most effective in assessing decrements associated with an abdominal fat distribution in 46 non-obese, middle to older aged men (mean +/- s.e., age 52.8 +/- 0.88 years; body fat 19.7 +/- 0.72 percent). Circumferences were obtained at the following sites and WHR calculated (waist circumference/hip circumference): (1) minimal waist/maximal hip; (2) level of umbilicus/maximal hip; (3) level of umbilicus/level of greater trochanters; (4) level of umbilicus/level of superior iliac spine; and (5) level of 1/3 of the distance between the xiphiod process and umbilicus/level 4 cm below the superior iliac spine. Significant (P less than 0.05) associations were observed for measurement methods 1, 2 and 3 with indices of lipid and carbohydrate metabolism, body composition, and fitness level. Measurement method 5 was not related to any metabolic or physiological variables, while measurement method 4 was intermediate in terms of the strength of the associations. These findings suggest that the predictive strength of WHR can vary depending upon the measurement method used.

Anthropometry↗
PubMed1988

[Cytogenetic and virological characteristics of the initial line and clones of RH cells with various degrees of sensitivity to the tick-borne encephalitis virus].

Virological and cytogenetic characterization of line RH and its two clones (RHk-20 and RHk-13/6), having different sensitivity to the tick-borne encephalitis virus (TBE), has been made. The RHk-13/6-cells are 10,000 times more sensitive to cytopathic effect of the tick-borne encephalitis virus in comparison with the RHk-20-cells. By its sensitivity to the virus the base line is in the intermediate position. Cytogenetic analysis revealed the variability interval decrease as to the chromosome number at cloning, and showed the structural stability of the line and clone karyotypes. The line RH and its clone K-20 have modal number of chromosomes equal to 65; the cell population with the chromosome number equal to 66 dominated in RHk-13/6. The application of methods of chromosome differential (G, C) staining and these for the detection of active nucleolar organizers (NO) permitted identifying the marker chromosomes and determining the difference between the clones and the line as associated with the presence of an additional homologue of chromosome 8 in the sensitive clone.

Cell Line↗
PubMed1994

p21 Ras as a governor of global gene expression.

The molecular mechanisms for signaling by receptor serine/threonine kinases are incompletely understood. To test the potential involvement of p21 H-Ras proteins in signal transduction for type beta transforming growth factors (TGF beta), TGF beta-responsive and constitutive reporter genes were cotransfected into cardiac myocytes and mink lung epithelial cells, with dominant inhibitory (Asn-17) or activated (Arg-12) Ras expression vectors. Asn-17 Ras inhibited both TGF beta-dependent and basal expression of inducible promoters (skeletal alpha-actin and plasminogen activator inhibitor-1), with equivalent dose-response relations. All seven reporter constructs were comparably sensitive to down-regulation by Asn-17 Ras, including those driven by nominally constitutive viral control regions or a TATA-less initiator element. All constructs were up-regulated by Arg-12 Ras more variably. Wild-type Ras had intermediate effects and could rescue a minimal thymidine kinase promoter from inhibition by dominant negative Ras. Thus, a Ras-dependent event is required for efficient expression of an unexpectedly global or inclusive set of genes.

Amino Acid Sequence↗
PubMed1997

Role of interactions between psychological and clinical factors in determining 6-month mortality among patients with acute myocardial infarction. Application of recursive partitioning techniques to the GISSI-2 database. Gruppo Italiano per lo Studio della Sopravvivenza nell' Infarto Miocardico.

BACKGROUND: Clinical and epidemiological studies support the hypothesis that ischaemic cardiovascular diseases are consistently associated with psychological, social and behavioural factors. Nevertheless, the joint effect of clinical characteristics and psychological variables in determining the prognosis of acute myocardial infarction survivors has been seldom investigated. METHODS AND RESULTS: In the framework of the GISSI-2 trial, the impact of psychological factors on 6-month mortality and their interaction with clinical features was included as an ad hoc research project. Overall, 2449 patients were evaluated, 63 of whom died during the study period. All patients undertook a self-administered questionnaire (Cognitive Behavioural Assessment Hospital Form), investigating 16 psychological dimensions relative to three areas (state variables, vital exhaustion, trait variables). The impact of psychological variables on prognosis and their interaction with clinical variables were investigated by using a tree-growing technique (RECursive Partitioning and AMalgamation-RECPAM) applied to survival analysis. This statistical method allowed the identification of three separate classes, characterized by different prognoses: Class I (presence of vital exhaustion), Class II (concomitance of no vital exhaustion, depression and low levels of anxiety) and Class III (all other patients). After adjusting for the clinical variables, Class I was associated with an intermediate prognosis (hazard ratio [HR] = 2.2; 95% confidence intervals [CI], 1.2-4.0) and Class II to the worst (HR = 3.2; 95% CI = 1.6-6.2), as compared to Class III. High levels of neuroticism and extroversion were associated with a better prognosis. When clinical and psychological variables were simultaneously investigated by RECPAM, Type A behaviour was shown to be an important risk predictor among patients with better clinical conditions, i.e. those eligible for exercise test (HR = 2.6, 95% CI = 1.2-5.5). Finally, a striking difference in the impact of the most predictive clinical variables (exercise test ineligibility, late and early ventricular failure) was found among patients with and without vital exhaustion. CONCLUSIONS: This study shows that acute myocardial infarction survivors are heterogeneous with respect to 6-month mortality according to their psychological profile. More important, the impact of these variables appears comparable to that of very well known clinical risk predictors. The availability of a large study population, together with the use of innovative statistical techniques, allowed us to identify subgroups of patients for whom the joint action of clinical and psychological characteristics has been clearly documented. This suggests the need for incorporating psychological evaluation in the care of acute myocardial infarction patients.

Cohort Studies↗
PubMed1991

Determinants of 2-year outcome after coronary angioplasty in patients with multivessel disease on the basis of comprehensive preprocedural evaluation. Implications for patient selection. The Multivessel Angioplasty Prognosis Study Group.

BACKGROUND: To assess the likelihood of intermediate-term event-free survival (freedom from death, coronary artery bypass surgery, and myocardial infarction) in patients with multivessel coronary disease undergoing coronary angioplasty, 350 consecutive patients from four clinical sites were carefully evaluated and followed for 22 +/- 10 months. METHODS AND RESULTS: Eight clinical variables were evaluated at the clinical sites, and 23 angiographic variables describing the number, morphology, and topography of coronary stenoses were evaluated at a core angiographic laboratory. Most patients had Canadian Cardiovascular Society class III or IV angina (72%), two-vessel coronary disease (68%), and well-preserved left ventricular function (mean ejection fraction, 58 +/- 12%; range, 18-85%). Follow-up was complete in 99% of patients. At 2 years, event-free survival was 72%, overall survival was 96%, freedom from bypass surgery was 82%, and freedom from nonfatal myocardial infarction without surgery was 96%. Sequential Cox proportional hazards regression analyses allowing stepwise entry of variables prospectively coded as simple, as of intermediate complexity, or as complex found event-free survival to be independently predicted by low Canadian Cardiovascular Society angina class, no diabetes, no proximal left anterior descending stenoses, and the sum of stenosis simplified risk-territory scores of 15 or less. In the absence of class IV angina and these risk factors, 2-year event-free survival was 87% and overall survival was 100%. In the presence of two or more of these risk factors, event-free survival was less than 50%. CONCLUSIONS: Recognition of risk factors for poor long-term outcome in this setting may improve clinical decision making and provide a framework on which to base meaningful subgroup analyses in randomized trials assessing the efficacy of coronary angioplasty.

Angioplasty, Balloon, Coronary↗
PubMed2002

Modular interaction strengths in regulatory networks; an example.

Cellular networks composed of metabolic, signalling, and genetic subnetworks, comprise many distinct intermediates. However, only a subset of the latter, referred to as 'communicating intermediates', mediate cross-talk between individual modules. Here, this characteristic feature of modular networks is exploited to simplify the quantitative description of the responses of these networks to environmental changes, to a description solely in terms of the communicating intermediates. Such a strategy reduces the number of variables that need to be considered. It allows for the determination of the quantitative contribution of individual modular interactions to the regulation of concentrations of communicating intermediates. This is illustrated by a calculation for an example of a modular biochemical network.

Cell Physiological Phenomena↗
PubMed1993

Flow cytometric analysis of lymphomas and acute leukemias.

In summary, flow cytometry is highly applicable to the detection and classification of leukemias and lymphomas due to the ease with which single-cell suspensions may be made. Composite immunophenotypic analysis is essential for classifying leukemias once the disease is detected by traditional means. In contrast, in the detection of lymphoproliferative diseases, the composite immunophenotype is itself diagnostic of the disease process. Characterization of size, as measured by light scatter and by DNA ploidy and cell cycle analysis, contributes to the further subdivision of lymphoproliferative disorders. Specifically, small, monoclonal cells that are diploid with a synthetic fraction of 5% are characteristic of low-grade lymphomas. Admixtures of large and small cells wherein the large cells are monoclonal and the small cells are either monoclonal or heterogeneous may be seen in intermediate lymphomas. In this category, DNA ploidy is variable and the total synthetic fraction is usually between 5% and 15%. High-grade lymphomas, with the exception of the immunoblastic category, are usually of intermediate size, are diploid or near-diploid, and exhibit synthetic fractions greater than 15%. Interestingly, few reactive T cells are seen. Ongoing efforts to standardize procedures will eventually result in more widespread applicability together with improved understanding of the attributes and limitations of this technology. The most important consideration, however, is that the technology is useless in the absence of a working knowledge of the biology of the diseases to be characterized. Conversely, the complexity of flow cytometry is sufficient to warrant rigorous training of laboratory professionals in this field.

Acute Disease↗
PubMed2004

Call recognition in the bullfrog, Rana catesbeiana: generalization along the duration continuum.

Male bullfrogs emit multicroak, quasiharmonic advertisement calls that function in mate attraction and neighbor recognition. The degree of variability of acoustic features in these calls can influence perceptual decisions by conspecific receivers. Analysis of duration of individual croaks in spontaneous advertisement calls of a sample of males shows considerable intraindividual variability in this feature, even within short chorusing bouts. The influence of this intraindividual variability on behavior was examined in a series of evoked calling experiments. When presented with synthetic calls whose croak durations varied over the range of the natural variability in this feature, males responded similarly to intermediate and long duration croaks, but significantly less to short duration croaks. When presented with playbacks of calls with croak durations outside the natural range of variability, males again responded significantly less to shorter durations. The response gradient for duration is thus asymmetrical, with stimuli at the shorter end of the continuum evoking fewer responses than stimuli at the longer end. This asymmetry may be related to the biological demands of rejecting perception of heterospecific advertisement calls, and of mediating appropriate responses to conspecific aggressive calls. The shape of the response gradient for duration may reflect a process of stimulus generalization.

Analysis of Variance↗
PubMed2000

Alternative splice variant of gamma-calmodulin-dependent protein kinase II alters activation by calmodulin.

Calmodulin-dependent protein kinase II (CaMKII) is a ubiquitous, multifunctional enzyme family involved in the regulation of a variety of Ca(2+)-signaling pathways. These family members are expressed from four highly homologous genes (alpha, beta, gamma, and delta) with similar catalytic properties. Additional isoforms of each gene, created by alternative splicing of variable regions I-XI, are differentially expressed in various cell types. gammaB, gammaC, gammaD, gammaE, gammaF, gammaGs, and gammaH CaMKII isoforms are expressed in the biliary epithelium; however, little is known about their roles in these cells. We began our studies into the function of these variable regions by examining the effects of variable region I on kinase activation and calmodulin binding. Activities and calmodulin binding properties of gammaB and gammaGs, which differ only by the exclusion or inclusion of this region, were compared. The K(0.5) for calmodulin was 2.5-fold lower for gammaGs than gammaB. In contrast, gammaB bound calmodulin more tightly in a calmodulin overlay assay. Mutation of variable regions I's charged residue, gammaGs-R318E, resulted in an enzyme with intermediate activation properties but a calmodulin affinity similar to gammaB. Thus, variable region I appears to modulate calmodulin sensitivity, in part, through charge-charge interactions. This altered threshold of activation may modulate cellular responses to gradients of Ca(2+)/calmodulin in the biliary tract.

Alternative Splicing↗
PubMed1992

Nonmonotonic relation of autogynephilia and heterosexual attraction.

In this study I investigated the relation between normal heterosexual attraction and autogynephilia (a man's propensity to be sexually aroused by the thought or image of himself as a woman). The subjects were 427 adult male outpatients who reported histories of dressing in women's garments, of feeling like women, or both. The data were questionnaire measures of autogynephilia, heterosexual interest, and other psychosexual variables. As predicted, the highest levels of autogynephilia were observed at intermediate rather than high levels of heterosexual interest; that is, the function relating these variables took the form of an inverted U. This finding supports the hypothesis that autogynephilia is a misdirected type of heterosexual impulse, which arises in association with normal heterosexuality but also competes with it.

Adolescent↗
PubMedDate not supplied

The Nordic back pain subpopulation program: can patient reactions to the first chiropractic treatment predict early favorable treatment outcome in nonpersistent low back pain?

OBJECTIVE: To investigate whether 3 distinct patterns of reactions to chiropractic care can predict early favorable treatment outcome in patients with nonpersistent low back pain (LBP). DESIGN: Multicenter practice-based predictive validity study. STUDY SUBJECTS: Sixty private practice chiropractors in Sweden recruited a maximum of 20 consecutive patients with LBP each, with a duration of less than 2 weeks at the time of consultation and a maximum of 30 days totally over the past year. METHODS: Chiropractic management was decided on by the treating chiropractor. The outcome variable was self-reported "definite improvement" at the fourth visit. The predictor variables included 3 hypothesized prognostic groups (best, intermediate, and least favorable) on the basis of clinical information collected at baseline and at the second visit. The covariates included age, sex, pain intensity during the past 24 hours, description of disability, duration and pattern of pain during the present attack, and duration and pattern of pain during the past 12 months. The 3 predictor groups were cross-tabulated against the outcome variable and the other covariates. Backward stepwise logistic regression was performed to test for confounding or modification from relevant covariates. RESULTS: Information was provided on 708 patients, of which 674 questionnaires were valid. Of the 223 patients in the hypothesized best prognostic group, 91% (95% CI, 79-100) reported to be "definitely improved" by the fourth visit, vs 76% (72-80) of the 420 patients in the intermediate prognostic group, and 36% (19-53) of the 31 patients in the least favorable prognostic group. These results were not altered after controlling for the covariates. CONCLUSION: For chiropractic patients with nonpersistent LBP, these findings show that it is possible to predict already by the second visit which patients may or may not report improvement at the fourth visit.

Adult↗
PubMed2002

Using sensory weighting to model the influence of canal, otolith and visual cues on spatial orientation and eye movements.

The sensory weighting model is a general model of sensory integration that consists of three processing layers. First, each sensor provides the central nervous system (CNS) with information regarding a specific physical variable. Due to sensor dynamics, this measure is only reliable for the frequency range over which the sensor is accurate. Therefore, we hypothesize that the CNS improves on the reliability of the individual sensor outside this frequency range by using information from other sensors, a process referred to as "frequency completion." Frequency completion uses internal models of sensory dynamics. This "improved" sensory signal is designated as the "sensory estimate" of the physical variable. Second, before being combined, information with different physical meanings is first transformed into a common representation; sensory estimates are converted to intermediate estimates. This conversion uses internal models of body dynamics and physical relationships. Third, several sensory systems may provide information about the same physical variable (e.g., semicircular canals and vision both measure self-rotation). Therefore, we hypothesize that the "central estimate" of a physical variable is computed as a weighted sum of all available intermediate estimates of this physical variable, a process referred to as "multicue weighted averaging." The resulting central estimate is fed back to the first two layers. The sensory weighting model is applied to three-dimensional (3D) visual-vestibular interactions and their associated eye movements and perceptual responses. The model inputs are 3D angular and translational stimuli. The sensory inputs are the 3D sensory signals coming from the semicircular canals, otolith organs, and the visual system. The angular and translational components of visual movement are assumed to be available as separate stimuli measured by the visual system using retinal slip and image deformation. In addition, both tonic ("regular") and phasic ("irregular") otolithic afferents are implemented. Whereas neither tonic nor phasic otolithic afferents distinguish gravity from linear acceleration, the model uses tonic afferents to estimate gravity and phasic afferents to estimate linear acceleration. The model outputs are the internal estimates of physical motion variables and 3D slow-phase eye movements. The model also includes a smooth pursuit module. The model matches eye responses and perceptual effects measured during various motion paradigms in darkness (e.g., centered and eccentric yaw rotation about an earth-vertical axis, yaw rotation about an earth-horizontal axis) and with visual cues (e.g., stabilized visual stimulation or optokinetic stimulation).

Darkness↗
PubMed2005

Impact of supplemental external beam radiotherapy and/or androgen deprivation therapy on biochemical outcome after permanent prostate brachytherapy.

PURPOSE: To evaluate the impact of supplemental external beam radiotherapy (EBRT) and/or androgen deprivation therapy (ADT) on 8-year biochemical outcome after permanent prostate brachytherapy. METHODS AND MATERIALS: Between April 1995 and January 2001, 668 consecutive patients underwent brachytherapy using either (103)Pd or (125)I for clinical Stage T1b-T3aNxM0 (2002 American Joint Committee on Cancer) adenocarcinoma of the prostate gland. No patient underwent seminal vesicle biopsy or pathologic lymph node staging. The median follow-up was 58.6 months. Biochemical progression-free survival was defined by the American Society for Therapeutic Radiology and Oncology consensus definition. The clinical, treatment, and dosimetric parameters evaluated for biochemical progression-free survival included supplemental EBRT, ADT, patient age, clinical stage, Gleason score, preimplant prostate specific antigen (PSA), risk group, percentage of positive biopsies, isotope used, prostate volume, planning volume, percentage of target volume receiving 100%, 150%, and 200% of prescribed dose, minimal percentage of dose covering 90% of target volume, tobacco status, hypertension, and diabetes. RESULTS: For the entire group, the actuarial 8-year biochemical progression-free survival rate was 98.2%, 98.4%, and 88.2% for low-, intermediate-, and high-risk patients, respectively, with a median PSA level of <0.1 ng/mL for all risk groups and ADT and EBRT subgroups. At last follow-up, only 5 patients (0.8%) had died of metastatic prostate cancer. In multivariate analysis, Gleason score, percentage of positive biopsies, and ADT predicted for biochemical outcome in high-risk patients. In low- and intermediate-risk patients, none of the evaluated variables predicted for biochemical outcome. For the entire population, pretreatment PSA level, Gleason score, ADT, and clinical stage predicted for 8-year biochemical progression-free survival, with the percentage of positive biopsies approaching statistical significance. CONCLUSION: Prostate brachytherapy results in a high probability of 8-year biochemical progression-free survival for low-, intermediate-, and high-risk patients. Although the role of supplemental EBRT could not be adequately evaluated in high-risk patients, it did not improve biochemical outcome in low- and intermediate-risk patients. However, ADT resulted in a statistically significant improvement in progression-free survival for high-risk patients.

Aged↗
PubMed1985

The relationship between fetal activity and behavioral states and fetal breathing movements in normal and growth-retarded fetuses.

The incidence of fetal breathing was studied during the course of behavioral state observations on 28 low-risk fetuses between 32 and 40 weeks' gestational age and on 12 growth-retarded fetuses between 36 and 40 weeks. Real-time ultrasound scanners were used to detect fetal eye, body, and breathing movements, and the fetal heart rate was recorded continuously. The mean duration of the observation sessions was 110 minutes. The mean incidence of fetal breathing was greater during periods of fetal activity (body and eye movements present, greater heart rate variability) than during quiescence (body and eye movements absent, narrowed heart rate variability) at all gestational ages studied in both low-risk and growth-retarded fetuses. During periods when one of the state variables (body movements, eye movements, heart rate pattern) was in its active condition while the other two were quiet, or the reverse, the incidence of fetal breathing was intermediate between those found when all three state variables were in agreement. After behavioral states had developed, at 38 and 40 weeks, the mean incidence of fetal breathing in the low-risk fetuses was greater during active states than during the quiet state. There was no apparent increase in the degree of linkage between fetal breathing and other expressions of fetal activity after the emergence of behavioral states.

Eye Movements↗
PubMed1988

Synthesis and fate of keratins 8 and 18 in nonepithelial cells transfected with cDNA.

To study the assembly of intermediate filaments in vivo we have transfected fibroblast cell lines with the cDNAs coding for keratins 8 and 18 under the control of the promoter of the SV40 early region and followed keratin expression by RNA hybridization, two-dimensional gel electrophoresis, and immunofluorescence analysis. When expressed individually, keratins 8 and 18 failed to polymerize into intermediate filaments but formed granular aggregates of variable size distributed throughout the cytoplasm as seen by staining with specific antibodies. The expression of one of these two keratins did not induce the synthesis of its partner or of any other keratin. Coexpression of the two keratins produced filamentous structures, frequently perinuclear, indicating that the two types of polypeptides were able to assemble into intermediate filaments but could not form the cytoskeleton characteristic of epithelial cells. These results demonstrate that assembly in heterocomplexes stabilizes keratins against cellular degradation, helping to explain why excess pools of simple keratins have never been detected.

Animals↗