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Biomedical subjects

N Katz

Publications and source records attributed to N Katz.

At least 37 records · Page 2Linked to original sources

Fuzzy logic-based tumor marker profiles improved sensitivity of the detection of progression in small-cell lung cancer patients.

Tumor markers were used for disease monitoring in small-cell lung cancer patients. The aim of this study was to improve diagnostic efficiency in the detection of tumor progression in small-cell lung cancer patients by using fuzzy logic modeling in combination with a tumor marker panel (NSE, ProGRP, Tumor M2-PK, CYFRA 21-1, and CEA). Thirty-three consecutive small-cell lung cancer patients were included in a prospective study. The changes in blood levels of tumor markers and their analysis by fuzzy logic modeling were compared with the clinical evaluation of response versus non-response to therapy. Clinical monitoring was performed according to the standard criteria of the WHO. Tumor M2-PK was measured in plasma with an ELISA, all other markers were measured in sera. At 90% specificity, clinically detected tumor progression was found by the best single marker, NSE, in 32% of all cases. A fuzzy logic rule-based system employing a tumor marker panel increased the sensitivity significantly (P>0.0001) in small-cell carcinomas to 67% with the threemarker combination NSE/ProGRP/Tumor M2-PK and to 56% with the best two-marker combination ProGRP/Tumor M2-PK, respectively. An improvement of sensitivity was also observed using the two-marker combination of ProGRP/NSE (sensitivity 49%) or NSE/Tumor M2-PK (sensitivity 52%). The fuzzy classifier was able to detect a higher rate of progression in small-cell lung cancer patients compared with the multiple logistic regression analysis using the marker combination NSE/ProGRP/Tumor M2-PK (sensitivity 44%; AUC=0.76). With the fuzzy logic method and different tumor marker panels (NSE, ProGRP and Tumor M2-PK), a new diagnostic tool for the detection of progression in patients with small-cell lung cancer is available.

Aged↗

Endothelin-1 and vasopressin plasma levels are not associated with the insertion/deletion polymorphism of the human angiotensin I-converting enzyme gene in patients with coronary artery disease.

The objective was to investigate whether the renin-angiotensin (RA) system and related peptides endothelin-1 (ET-1) and vasopressin (VP) influence the development of coronary artery disease (CAD). Angiotensin I-converting enzyme (ACE) insertion/deletion (I/D) gene polymorphism has been associated with the risk of CAD. The ACE I/D polymorphism determines ACE activity, but plasma levels of other RA system components remain unchanged. However, ET-1 and VP production could be increased by RA system-dependent stimulation, continually promoted by paracrine stimulation and sustained by neointimal growth. ET-1 and VP have not been associated with the ACE I/D polymorphism so far. The present study investigated the association of the ACE I/D polymorphism with plasma concentrations of ET-1 and VP, as well as with renin, angiotensin-II (AT-II) and ACE activity in 98 Caucasian individuals with CAD. ACE I/D polymorphism showed no association with plasma levels of VP, ET-1, AT-II or renin. These parameters were also not associated taking into consideration different patient variables, such as diabetes mellitus, hypertension or severity of CAD. Only plasma ACE activity was associated with the D allele. In conclusion, the ACE I/D polymorphism could not be related to plasma concentrations of VP, ET-1, renin or AT-II, but as previously demonstrated, it could only be related to ACE activity in patients with CAD. Differences in ACE activity between ACE I/D genotype subgroups are probably compensated within the RA system itself or within non-ACE pathways, so that plasma concentrations of the related peptides ET-1 and VP remain unaffected.

Adult↗

Beliaev damping of quasiparticles in a Bose-Einstein condensate.

We report a measurement of the suppression of collisions of quasiparticles with ground state atoms within a Bose-Einstein condensate at low momentum. These collisions correspond to Beliaev damping of the excitations, in the previously unexplored regime of the continuous quasiparticle energy spectrum. We use a hydrodynamic simulation of the expansion dynamics, with the Beliaev damping cross section, in order to confirm the assumptions of our analysis.

Journal Article↗

Exploring the subsite specificity of Schistosoma mansoni aspartyl hemoglobinase through comparative molecular modelling.

Blood flukes of the genus Schistosoma currently infect millions of people in tropical and subtropical countries. An enzyme playing a major role in hemoglobin (Hb) degradation by Schistosoma mansoni has been cloned and shown to be highly similar to the human cathepsin D aspartyl proteinase, although presenting a distinct substrate specificity from the latter. Investigating the structural features responsible for this difference has a major application in the design of selective anti-schistosomal drugs. In order to achieve this goal a homology model for the S. mansoni aspartyl hemoglobinase was constructed and then used to simulate the complexes formed with two transition state analogues of Hb-derived octapeptide substrates. Comparison with human cathepsin D showed that different pocket volumes and surface electrostatic potentials arise from substitutions in residues comprising the S4, S3, S2 and S3' subsites. Since the primary specificity of the S. mansoni enzyme resembles that of HIV-1 protease, we have discussed the applicability of current retroviral protease inhibitors as leads for the design of new anti-schistosomal drugs.

Animals↗

Excitation spectrum of a Bose-Einstein condensate.

We report a measurement of the excitation spectrum omega(k) and the static structure factor S(k) of a Bose-Einstein condensate. The excitation spectrum displays a linear phonon regime, as well as a parabolic single-particle regime. The linear regime provides an upper limit for the superfluid critical velocity, by the Landau criterion. The excitation spectrum agrees well with the Bogoliubov spectrum in the local density approximation, even close to the long-wavelength limit of the region of applicability. Feynman's relation between omega(k) and S(k) is verified, within an overall constant.

Journal Article↗

Epidemic West Nile encephalitis, New York, 1999: results of a household-based seroepidemiological survey.

BACKGROUND: In the summer of 1999, West Nile virus was recognised in the western hemisphere for the first time when it caused an epidemic of encephalitis and meningitis in the metropolitan area of New York City, NY, USA. Intensive hospital-based surveillance identified 59 cases, including seven deaths in the region. We did a household-based seroepidemiological survey to assess more clearly the public-health impact of the epidemic, its range of illness, and risk factors associated with infection. METHODS: We used cluster sampling to select a representative sample of households in an area of about 7.3 km(2) at the outbreak epicentre. All individuals aged 5 years or older were eligible for interviews and phlebotomy. Serum samples were tested for IgM and IgG antibodies specific for West Nile virus. FINDINGS: 677 individuals from 459 households participated. 19 were seropositive (weighted seroprevalence 2.6% [95% CI 1.2-4.1). Six (32%) of the seropositive individuals reported a recent febrile illness compared with 70 of 648 (11%) seronegative participants (difference 21% [0-47]). A febrile syndrome with fatigue, headache, myalgia, and arthralgia was highly associated with seropositivity (prevalence ratio 7.4 [1.5-36.6]). By extrapolation from the 59 diagnosed meningoencephalitis cases, we conservatively estimated that the New York outbreak consisted of 8200 (range 3500-13000) West Nile viral infections, including about 1700 febrile infections. INTERPRETATION: During the 1999 West Nile virus outbreak, thousands of symptomless and symptomatic West Nile viral infections probably occurred, with fewer than 1% resulting in severe neurological disease.

Adolescent↗

Abnormal thermoregulation in drug-free male schizophrenia patients.

Schizophrenia patients may develop various thermoregulatory disturbances. We hypothesized that a standardized exercise-heat tolerance test [two 50-min bouts of walking a motor-driven treadmill at 40 degrees C (relative humidity=40%)] would reveal abnormal thermoregulation in drug-free schizophrenia patients. Six drug-free schizophrenia outpatients and seven healthy comparison subjects participated in this study. The schizophrenia patients exhibited significantly higher baseline and exertion-related rectal temperature. The relevance of these findings to the pathophysiology of schizophrenia-related thermoregulatory disorders is as yet unclear.

Adult↗

Giessen Wholesome Nutrition Study: relation between a health-conscious diet and blood lipids.

OBJECTIVE: To study in humans the relationship between a diet consistent with most of the current recommendations for the prevention of nutrition-related diseases (Wholesome Nutrition) and the blood lipid profile (total cholesterol, LDL-, HDL-cholesterol, LDL/HDL-ratio, triglycerides). DESIGN: Cross-sectional study with two diet groups. SETTING: Former West Germany. SUBJECTS: Healthy women (n=243, aged 25-65 y) adhering to Wholesome Nutrition for at least 5 y (subdivided into 111 ovo-lacto vegetarians and 132 low-meat eaters) and an according control group of 175 women eating an average German mixed diet. They were all recruited through an advertisement campaign and selected on the basis of their food consumption. RESULTS: Considering potential confounders, the Wholesome Nutrition subgroups had higher HDL-cholesterol levels than the control group. No differences were observed for total cholesterol and LDL-cholesterol. For LDL/HDL-ratio and triglycerides the effect of diet was dependent on interaction terms. With increasing risk factors (age or body mass index (BMI)) the Wholesome Nutrition subgroups showed more favourable blood lipids. CONCLUSIONS: Women eating a preventive diet on a long-term basis exhibit more favourable blood lipid profiles than women consuming an average mixed diet. This is particularly obvious for HDL-cholesterol in the presence of certain risk factors and when an ovo-lacto vegetarian version is practised. SPONSORSHIP: Eden Foundation, Bad Soden, Germany.

Adult↗

Anosognosia for hemiplegia in stroke rehabilitation.

OBJECTIVE: The purpose of this study was to investigate anosognosia for hemiplegia (AHP) in the rehabilitation phase after onset of stroke. METHODS: Forty-six hemiplegic stroke patients, 29 with right hemisphere damage (RHD) and 17 with left hemisphere damage (LHD) were evaluated approximately 1 month after onset of stroke. Anosognosia was evaluated with an implicit measure designed to assess anosognosic behaviors (choosing between unimanual and bimanual tasks), in addition to a traditional explicit verbal measure. RESULTS: AHP was found in 28% of the RHD and 24% of the LHD group. The majority of patients with AHP in the RHD group had large lesions involving the frontal, parietal, or temporal lobes and had coexisting sensory deficits and unilateral spatial neglect, whereas the LHD patients with AHP had predominantly small subcortical lesions and no sensory or attentional deficits. The functional outcomes of AHP patients in both hemisphere groups revealed their inability to retain safety measures at discharge from rehabilitation (p < 0.036) and their need for assistance in basic and instrumental activities of daily living at follow-up. CONCLUSIONS: AHP presents a significant risk for negative functional outcome in stroke rehabilitation. The underlying mechanisms of AHP may be different for left and right hemisphere patients, therefore requiring different intervention approaches.

Activities of Daily Living↗

Effectiveness of dynamic cognitive intervention in rehabilitation of clients with schizophrenia.

OBJECTIVE: To examine the efficacy of dynamic cognitive treatment in rehabilitation of schizophrenic clients. SUBJECTS: Fifty-eight schizophrenic clients that were matched equally into two groups: a study group (n = 29) (treated by Instrumental Enrichment) and a control group (treated with traditional occupational therapy methods). SETTING: The subjects were treated in a day rehabilitation centre in the community. STUDY DESIGN: The programme lasted one year, the same schedule was provided for both groups. Subjects were randomly assigned and assessed before and after intervention with the same battery and at a follow-up six months later, work and residence status were evaluated. MAIN OUTCOME MEASURES: Instruments included: (1) memory and thought processes, measured by a battery of structured tests from the Learning Potential Assessment Device (LPAD), Raven Progressive Matrices and General Aptitude Test Battery (GATB); (2) functional outcomes, instrumental activities of daily living (IADL), measured by a questionnaire; work and residence status; (3) self-concept measured with Fitts questionnaire. RESULTS: Results showed significant differences between the groups on almost all the cognitive tests (MANOVA revealed significant differences between the two groups for both memory and thought process (F(2.52) = 13.75, p < 0.001; and F(1.46) = 7.28, p < 0.001, respectively) as well as in work (chi2 = 14.30, p < 0.001), and residence (chi2 = 3.86, p < 0.05) status. There were no significant differences in IADL questionnaire or the self-concept scale. CONCLUSIONS: The successful outcome points to the importance of including long-term cognitive intervention in rehabilitation of schizophrenic clients. This work suggests that the classic view of schizophrenia as a progressive irreversible decline that cannot be altered may be wrong.

Activities of Daily Living↗

Detection limit, cut-off and specificity of an improved rapid assay for cardiac troponin T.

The performance of an improved version of the troponin T rapid test TROPT Sensitive was investigated in a multicentre evaluation at twelve centres. The detection limit and the cut-off were determined in a method comparison with Elecsys Troponin T using a total of 365 samples from patients with suspected acute coronary syndromes and 91 samples from healthy blood donors or non-cardiological patients. The analytical specificity was determined by measuring 1271 blood samples from blood donors without any myocardial injury. The test cut-off (90% of results positive) is 0.08 microg/L, and the detection limit is about 0.05 microg/L. The analytical specificity of the test is between 99.7 and 99.9%. With its small area of undefined significance between positive and negative results and its high sensitivity and specificity, TROPT Sensitive is very well suited to the reliable detection of troponin T positive patients with acute coronary syndromes.

Biomarkers↗

Simulating the Effects of Intergalactic Gray Dust.

Using a high-resolution cosmological hydrodynamic simulation, we present a method to constrain extinction due to intergalactic gray dust based on the observed magnitudes of distant Type Ia supernovae. We apply several simple prescriptions to relate the intergalactic dust density to the gas density in the simulation, thereby obtaining dust extinctions that may be directly compared with the observed distribution of supernova magnitudes. Our analysis is sensitive to the spatial distribution of gray dust but is not dependent on its intrinsic properties, such as its opacity or grain size. We present an application of our technique to the supernova data of Perlmutter et al., who find that their high-redshift sample is approximately 0.2 mag fainter than the expectation for a nonaccelerating, low-density universe. We find that for gray dust to be responsible, it must be distributed quite smoothly (e.g., tracing intergalactic gas). More realistic dust distributions, such as dust tracing the metal density, are inconsistent with observations at the 1.5-2 sigma level. Upcoming observations and improved modeling of the dust distribution should lead to stronger constraints on intergalactic gray dust extinction.

Journal Article↗

The paraoxonase Leu-Met54 and Gln-Arg191 gene polymorphisms are not associated with the risk of coronary heart disease.

BACKGROUND: Evidence has been presented that gene polymorphisms (PON54 L/M, PON191 Q/R) of paraoxonase are risk factors of coronary heart disease. RESULTS: We determined both PON genotypes in 535 male individuals who were free of vascular disease and in 2249 male subjects who underwent coronary angiography, and analysed the relation of both gene variations to CAD and MI. Both gene polymorphisms were in linkage disequilibrium (P<0.0001). Coronary artery disease: the PON54 gene polymorphism was not associated with an increased risk of CAD. In the total sample and also in younger subjects, an association of the PON191 gene variation with the risk of CAD was not detected when the control group of individuals without coronary heart disease was compared with patients with at least one diseased vessel (verified by coronary angiography). In individuals younger than 62 years, a moderate increase in the relative risk of CAD associated with the PON191 R allele (1.45 (1. 08-1.95); P=0.015) were found, when subjects without vessel disease (verified by coronary angiography) were compared with CAD patients. Myocardial infarction: an association of the PON54 gene variation with MI was not detected when the control group of individuals without coronary heart disease were compared with patients with at least one MI. A marginal increase in the risk of MI associated with the PON54 LL genotype (OR 1.27 (1.05-1.51); P=0.011) were detected when patients without MI but with coronary angiography were compared with MI positive patients. Subgroup analyses of low- and high-risk populations did not reveal any association of both PON gene polymorphisms with CAD or MI. CONCLUSION: The present findings do not strengthen the hypothesis that the paraoxonase gene polymorphisms are independently associated with coronary heart disease indicating that these gene variations are of little usefulness as genetic markers of cardiovascular disease.

Amino Acid Substitution↗

Beta-endorphin (1-31) in the plasma of male volunteers undergoing physical exercise.

beta-Endorphin is an opioid peptide representing the C-terminal 31 amino acid residue fragment of proopiomelanocortin (POMC). The release of beta-endorphin from the pituitary into the cardiovascular compartment under physical or emotional stress has been frequently reported. However, besides beta-endorphin (1-31), nine acetylated or non-acetylated beta-endorphin analogues exist - in addition to N-terminally elongated beta-endorphin derivatives such as beta-lipotropin (beta-LPH). Since conventional radioimmunoassays (RIAs) and even commercially available two site-RIAs pick up at least some of those beta-endorphin derivatives, only "beta-endorphin immunoreactive materials" and not authentic beta-endorphin have been determined in those studies. We have developed a highly specific two site-RIA for beta-endorphin (1-31), which does not cross-react with all beta-endorphin derivatives known to occur as yet. Using this RIA as well as further assays for determination of beta-endorphin (1-31), beta-endorphin immunoreactive material (IRM), ACTH and Cortisol in the plasma of 14 volunteers upon intensive physical exercise, we found authentic beta-endorphin only in about 50% of the plasma samples, representing therein only a minor portion of the beta-endorphin IRM.

Adrenocorticotropic Hormone↗

beta-Endorphin immunoreactive material and authentic beta-endorphin in the plasma of males undergoing anaerobic exercise on a rowing ergometer.

Adrenocorticotropic hormone (ACTH), beta-endorphin immunoreactive material (beta-endorphin IRM), and authentic beta-endorphin (1 -31) have been determined in the plasma of 23 volunteers undergoing anaerobic exercise on a rowing ergometer. The volunteers had different histories of training from occasional physical activities up to intensive preparation for international rowing competitions. ACTH and beta-endorphin-IRM were determined using commercially available immunometric assays; for determination of beta-endorphin (1-31) a highly specific two-site fluid phase immunoprecipitation radioimmunoassay was developed, which did not cross-react with any beta-endorphin derivative or any other opioid peptide tested. In agreement with reports from the literature ACTH and beta-endorphin-IRM concentrations in the plasma rose upon anaerobic exercise in all 23 subjects; this increase in the ACTH and beta-endorphin IRM levels was significantly correlated with the increase of lactate levels observed upon anaerobic exercise. Authentic beta-endorphin (1-31) was only found in two plasma samples containing minor concentrations of the peptide. We conclude that the beta-endorphin immunoreactive material released into blood under anaerobic exercise is identical with authentic beta-endorphin (1-31) only to a minor extent and thus should not be called "beta-endorphin". The major part of the material in fact released into the blood upon anaerobic exercise is probably identical with beta-lipotropin and further components so far unknown.

Adrenocorticotropic Hormone↗

Neuropathic pain in cancer and AIDS.

Neuropathic pain is highly prevalent in patients with cancer and patients with AIDS, has profound effects on ability to function and quality of life, and is undertreated. Multiple obstacles to the adequate treatment of pain in patients with cancer and AIDS have been identified. Specific factors relevant to neuropathic pain, as well as the prevalence of substance abuse disorders in the AIDS population, contribute heavily to the undertreatment of pain in these patients. The differential diagnosis of neuropathic pain in these settings is broad, and a methodical diagnostic approach is required to achieve the primary objective of effective primary therapy. The parallel objective of providing optimal analgesic treatment also requires an aggressive and systematic approach. The presence of comorbid substance abuse issues requires special considerations that ordinarily do not compromise analgesic approaches. This review summarized the neuropathic pain syndromes seen in cancer and in AIDS, presents principles of pain assessment, highlights treatment options, and addresses the issue of pain and chemical dependency.

Acquired Immunodeficiency Syndrome↗

Transcriptional induction of heme oxygenase-1 gene expression by okadaic acid in primary rat hepatocyte cultures.

Heme oxygenase (HO) catalyzes the rate-limiting enzymatic step of heme degradation and regulates the cellular heme content. The gene expression of the inducible isoform of HO, HO-1, is up-regulated in response to various agents causing oxidative stress. To investigate the regulatory role of protein phosphatases in the hepatic regulation of HO-1 gene expression, primary cultures of rat hepatocytes were treated with okadaic acid (OA), which specifically inhibits the serine threonine protein phosphatases 1 and 2A. Both protein synthesis and mRNA expression of HO-1 were induced by OA in cultured hepatocytes, but not in cultured tissue macrophages of rat liver. The HO-1 mRNA induction by OA occurred in a time- and concentration-dependent manner. Simultaneous treatment with OA plus dibutyryl cAMP caused a synergistic up-regulation of steady-state levels of HO-1 mRNA, and the specific protein kinase A inhibitor KT5720 markedly reduced the OA-dependent HO-1 mRNA induction. In contrast, the dibutyryl cAMP-dependent induction of the phosphoenolpyruvate carboxykinase mRNA expression and enzyme activity was inhibited by simultaneous treatment with OA in hepatocytes. The induction of the HO-1 gene expression by OA was transcriptional as determined by studies with actinomycin D, nuclear run-off assay, and measurement of the half-life of HO-1 mRNA. Luciferase reporter constructs containing DNA sequences of the rat HO-1 promoter 5'-flanking region were up-regulated by OA in transiently transfected hepatocytes. Mutation of the cAMP response element/activator protein-1 (-665/-654) site obliterated the OA-dependent induction, suggesting that this element is involved in the transcriptional induction of the rat HO-1 gene by OA.

Animals↗