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Biomedical subjects

J Schmitz

Publications and source records attributed to J Schmitz.

At least 73 records · Page 4Linked to original sources

Push enteroscopy in celiac sprue and refractory sprue.

BACKGROUND: The aim of this study was to determine in patients with sprue whether jejunal endoscopy improves the diagnostic yield or provides information that may modify management, when compared with evaluation limited to the duodenum. METHODS: From January 1994 to June 1998, a total of 31 patients (6 men, 25 women, mean age 41 years) were prospectively evaluated by push enteroscopy. They were divided into two groups: (1) celiac disease at different stages of activity (n = 23) and (2) refractory sprue (n = 8). The endoscopic and histologic findings in the duodenum and in the jejunum were compared. RESULTS: Celiac disease: In 19 patients, endoscopic and histologic findings in the duodenum and jejunum were similar; in four patients villous atrophy was more severe in the duodenum than in the jejunum. Refractory sprue: In 5 of 8 patients, enteroscopy revealed ulcerative jejunitis, whereas ulcerations were found in the duodenum in only one case. CONCLUSION: In refractory sprue, push enteroscopy with jejunal biopsies was of diagnostic value in 50% of cases demonstrating ulcerative jejunitis, whereas it did not modify the management of patients with responsive celiac disease.

Adult↗

Can NSAID/ASA-induced erosions of the gastric mucosa be identified at histology?

Studies in animals have shown that NSAID/ASA-induced erosions have an ischaemic pathogenesis. We therefore studied the question of whether such erosions in human gastric biopsy material can be identified on the basis of the ischaemic necrosis. Histological sections prepared from forceps biopsy material obtained from 122 patients with erosions (at least three biopsy specimens from the erosion and two from antrum and corpus each) were classified by a pathologist blinded to the endoscopic findings and the medication used by the patients. NSAID/ASA erosions were diagnosed when a homogeneous eosinophilic ischaemic necrosis blending into the adjoining lamina propria presented. Helicobacter pylori (Hp)-induced erosions were diagnosed when, in the presence of Hp gastritis, erosive defects were covered with a non-homogeneous fibrinoid necrosis containing granulocytes and cell debris. Finally, the histological classification was compared with data on medication usage. The histological diagnosis was Hp-induced erosions in 59 patients, NSAID/ASA-induced erosions with no Hp gastritis in 23, and NSAID/ASA-induced erosions with concomitant Hp gastritis in 40. A comparison of this histological classification with the data provided by the referring physicians on patient medication revealed that 70% of the patients with histological diagnosis of NSAID/ASA-induced erosions in the absence of Hp gastritis, and 65% of those diagnosed to have NSAID/ASA-induced erosions and concomitant Hp gastritis, had been taking such drugs. Among the erosions diagnosed as H. pylori-induced, 81% of the patients were reported not to take such medication. The sensitivity of the diagnosis of NSAID/ASA-induced erosions was 72.9%, and specificity 79.6%. The results of the present study show that a high percentage of the NSAID/ASA-induced erosions of the gastric mucosa can indeed be correctly diagnosed at histology.

Anti-Inflammatory Agents, Non-Steroidal↗

Use of monetary reinforcers by cocaine-dependent outpatients.

Monetary reinforcers have not been widely used as contingent reinforcers in the treatment of drug abuse, despite their demonstrated effectiveness. This is primarily due to concern that drug abusers will use monetary reinforcers to procure drugs. The present study addressed this concern by examining 48 cocaine-dependent outpatients' biweekly self-reports of how they used their earned reinforcers. For each subject, their reinforcement usage was classified into 12 higher-order categories and 34 subcategories. Usage proportions were calculated for each. Results indicated that monetary reinforcers were used very infrequently to acquire drugs or alcohol (2%). Reinforcers were used primarily for daily life activities (25%) (e.g., food and gas), money-related uses (18%) (e.g., savings and repaying debts), personal use (15%) (e.g., cosmetics and clothes), and household items (11%) (e.g., rent and bills). These findings challenge the concern that drug abusers use monetary reinforcers to purchase drugs and have important implications for the use of contingent monetary reinforcers in treatment settings.

Adult↗

[Anti-rotavirus vaccinations].

Rotavirus is the most common cause of severe acute diarrhea, responsible for 30 to 40 deaths of children each year in France. In order to decrease both mortality and morbidity, vaccines have been designed first from attenuated bovine strains, then from monovalent simian strains, and more recently from reassortant rhesus strains. The live tetravalent human-rhesus reassortant vaccine (RRT-TV) has been shown to be protective in the United States, Finland, and Venezuela despite different environments, in prospective double-blind studies. This vaccine, as the natural infection, decreases by 50% the risk of acute rotavirus diarrhea and by 70 to 100% the risk of severe diarrhea with dehydration. At the present time, its cost limits its use to developed countries. It was put on the market in the United States in October 1998. The challenge is now to make it available in developing countries.

Animals↗

Behavioral and emotional problems among children of cocaine- and opiate-dependent parents.

OBJECTIVE: To test associations between parental drug abuse and children's problems, children of cocaine- and opiate-dependent parents were compared with demographically matched referred and nonreferred children. METHOD: Cocaine- and opiate-dependent parents in treatment completed the Child Behavior Checklist for 410 children (218 boys, 192 girls) from ages 2 through 18 years (mean = 7.9 years). Children of drug abusers (CDAs) were demographically matched to referred (RCs) and nonreferred children (NRCs). RESULTS: RCs scored lower than CDAs and NRCs on most competence scales, and higher than CDAs and NRCs on all problem scales. CDAs scored lower than NRCs on most competence scales, and higher than NRCs on Withdrawn, Thought Problems, Delinquent Behavior, Aggressive Behavior, Internalizing, Externalizing, and Total Problems. Group status also predicted clinical range scores on most competence and all problem scales. CONCLUSIONS: CDAs showed more internalizing and externalizing psychopathology relative to matched NRCs, but they showed significantly less psychopathology than shown by matched RCs. CDAs are an important group to target for preventive interventions.

Adolescent↗

Multimodal convergence of presynaptic afferent inhibition in insect proprioceptors.

In the leg motor system of insects, several proprioceptive sense organs provide the CNS with information about posture and movement. Within one sensory organ, presynaptic inhibition shapes the inflow of sensory information to the CNS. We show here that also different proprioceptive sense organs can exert a presynaptic inhibition on each other. The afferents of one leg proprioceptor in the stick insect, either the position-sensitive femoral chordotonal organ or the load-sensitive campaniform sensilla, receive a primary afferent depolarization (PAD) from two other leg proprioceptors, the campaniform sensilla and/or the coxal hairplate. The reversal potential of this PAD is about -59 mV, and the PAD is associated with a conductance increase. The properties of this presynaptic input support the hypothesis that this PAD acts as presynaptic inhibition. The PAD reduces the amplitude of afferent action potentials and thus likely also afferent transmitter release and synaptic efficacy. These findings imply that PAD mechanisms of arthropod proprioceptors might be as complex as in vertebrates.

Afferent Pathways↗

Anderson's disease: exclusion of apolipoprotein and intracellular lipid transport genes.

Anderson's disease is a rare, hereditary hypocholesterolemic syndrome characterized by chronic diarrhea, steatorrhea, and failure to thrive associated with the absence of apo B48-containing lipoproteins. To further define the molecular basis of the disease, we studied 8 affected subjects in 7 unrelated families of North African origin after treatment with a low-fat diet. Lipid loading of intestinal biopsies persisted, but the pattern and extent of loading was variable among the patients. Electron microscopy showed lipoprotein-like particles in membrane-bound compartments, the densities (0.65 to 7.5 particles/mu(2)) and the mean diameters (169 to 580 nm) of which were, in general, significantly larger than in a normal fed subject (0.66 particles/mu(2), 209 nm mean diameter). There were also large lipid particles having diameters up to 7043 nm (average diameters from 368 to 2127 nm) that were not surrounded by a membrane. Rarely, lipoprotein-like particles 50 to 150 nm in diameter were observed in the intercellular spaces. Intestinal organ culture showed that apo B and apo AIV were synthesized with apparently normal molecular weights and that small amounts were secreted in lipid-bound forms (density <1.006 g/mL). Normal microsomal triglyceride transfer protein (MTP) and activity were also detected in intestinal biopsies. Segregation analyses of 4 families excluded, as a cause of the disease, significant regions of the genome surrounding the genes for apo AI, AIV, B, CI, CII, CIII, and E, as were the genes encoding 3 proteins involved in intracellular lipid transport, MTP, and fatty acid binding proteins 1 and 2. The results suggest that a factor other than apoproteins and MTP are important for human intestinal chylomicron assembly and secretion.

Adult↗

The relationship between leg stepping pattern and yaw torque oscillations in curve walking of two crayfish species

Curve walking in two species of crayfish, Procambarus clarkii and Astacus leptodactylus, was investigated to test whether the mechanism underlying curve walking is the synchronous action of a centrally pre-programmed leg tripod or whether it is the action of one principal leg that produces the main body yaw torque. Curve walking was induced by an optomotor visual stimulus, and the yaw torque produced by the tethered animals was measured in open-loop conditions. Our main results suggest that the yaw torque oscillations in both P. clarkii and A. leptodactylus are related to the movement of outer leg 4 (i.e. leg 4 on the outside of the turn). That is, the peaks in the yaw torque occur, on average, in synchrony with the power stroke of outer leg 4. When comparing the results of this open-loop experiment on P. clarkii with results previously obtained for curve walking in untethered individuals of the same species, we found a much higher variability in leg coordination in the open-loop situation. Similarly, here we did not find the same level of synchrony in the tripod (formed by outer leg 4 and inner legs 2 and 5) observed during untethered free walking. Therefore, we suggest that tethered conditions may diminish the need for stability and thus allow outer leg 4 to produce a body rotation regardless of the leg stepping configuration. The characteristics of leg 4 are in line with its major role in turning. According to previous studies, legs 4 provide the largest force and the largest step amplitude during walking, and their force includes both a pulling and a pushing component which can facilitate the control of turning. Although it is apparent that outer leg 4 is not the only leg that can produce an inward yaw torque, its major role in modulating the yaw torque suggests that there may be a specific, centrally generated control of outer leg 4 during curve walking in crayfish.

Journal Article↗

Activation of the protein tyrosine phosphatase SHP2 via the interleukin-6 signal transducing receptor protein gp130 requires tyrosine kinase Jak1 and limits acute-phase protein expression.

Stimulation of the interleukin-6 (IL-6) signalling pathway occurs via the IL-6 receptor-glycoprotein 130 (IL-6R-gp130) receptor complex and results in the regulation of acute-phase protein genes in liver cells. Ligand binding to the receptor complex leads to tyrosine phosphorylation and activation of Janus kinases (Jak), phosphorylation of the signal transducing subunit gp130, followed by recruitment and phosphorylation of the signal transducer and activator of transcription factors STAT3 and STAT1 and the src homology domain (SH2)-containing protein tyrosine phosphatase (SHP2). The tyrosine phosphorylated STAT factors dissociate from the receptor, dimerize and translocate to the nucleus where they bind to enhancer sequences of IL-6 target genes. Phosphorylated SHP2 is able to bind growth factor receptor bound protein (grb2) and thus might link the Jak/STAT pathway to the ras/raf/mitogen-activated protein kinase pathway. Here we present data on the dose-dependence, kinetics and kinase requirements for SHP2 phosphorylation after the activation of the signal transducer, gp130, of the IL-6-type family receptor complex. When human fibrosarcoma cell lines deficient in Jak1, Jak2 or tyrosine kinase 2 (Tyk2) were stimulated with IL-6-soluble IL-6R complexes it was found that only in Jak1-, but not in Jak 2- or Tyk2-deficient cells, SHP2 activation was greatly impaired. It is concluded that Jak1 is required for the tyrosine phosphorylation of SHP2. This phosphorylation depends on Tyr-759 in the cytoplasmatic domain of gp130, since a Tyr-759-->Phe exchange abrogates SHP2 activation and in turn leads to elevated and prolonged STAT3 and STAT1 activation as well as enhanced acute-phase protein gene induction. Therefore, SHP2 plays an important role in acute-phase gene regulation.

Antigens, CD↗

Commitment of individual Th1-like lymphocytes to expression of IFN-gamma versus IL-4 and IL-10: selective induction of IL-10 by sequential stimulation of naive Th cells with IL-12 and IL-4.

Commitment of Th lymphocytes to the Th1 phenotype, as characterized by the expression of the major proinflammatory cytokine IFN-gamma, may be critically involved in the establishment of chronic inflammation and inflammatory autoimmune disease. To date, it has been shown that in IL-12-stimulated murine Th cell lines containing a major fraction of Th1 cells, Th2 cells can be induced by IL-4 until about 2 wk after initial activation, but not later. Here we analyze, based on the magnetic isolation of viable Th1 cells according to their specific expression of IFN-gamma, the cytokine commitment of individual Th1 cells. After activation of naive Th cells with Ag and IL-12 for up to 5 wk, isolated IFN-gamma-producing cells were restimulated with Ag and IL-4. Within the first 3 to 4 wk of IL-12 stimulation, some IFN-gamma+ cells stopped expression of IFN-gamma when restimulated with IL-4. However, within only 1 to 2 wk of IL-12 stimulation, few IFN-gamma+ cells could be converted to produce IL-4. Others continued to express IFN-gamma and thus were already committed to a proinflammatory, Th1-like phenotype. Surprisingly, within 3 wk of IL-12 stimulation, many of the IFN-gamma-producing cells responded to IL-4 restimulation by expression of IL-10, but neither IFN-gamma nor IL-4, i.e., by conversion to a suppressive, anti-inflammatory phenotype.

Animals↗

Effects of nicotine on methadone self-administration in humans.

The effects of nicotine abstinence, ad libitum smoking, and 0, 2, and 4 mg nicotine gum on methadone self-administration were investigated. Five methadone-maintained patients with a history of smoking (18-30 cigarettes/day) were recruited as subjects. Upon arrival expired carbon monoxide levels were measured to confirm self-reported abstinence of 10-12 h. At 30 min prior to the methadone self-administration session, two response options were concurrently available. When a 64-button press requirement (FR64) was completed, 10 ml of 0.054 mg/ml methadone solution, or vehicle, was delivered. Immediately following, and 30, 60, 90, and 120 min after the self-administration session, expired carbon monoxide levels and typical symptoms of nicotine withdrawal were assessed. Relative to abstinence, subjects consumed more methadone following the 4-mg nicotine gum and ad libitum smoking conditions. Ratings of cigarette craving were significantly less following ad libitum smoking or administration of 4-mg nicotine gum, than following abstinence. Implications for understanding opioid and nicotine interactions are discussed.

Adult↗

Sequential production of IL-2, IFN-gamma and IL-10 by individual staphylococcal enterotoxin B-activated T helper lymphocytes.

Upon primary activation, T helper (Th) cell populations express different cytokines transiently and with different kinetics. Stimulation of naive murine splenic Th cells with the bacterial superantigen Staphylococcus aureus enterotoxin B (SEB) in vitro results in expression of IL-2, IFN-gamma and IL-10 with fast, intermediate and slow kinetics, respectively. This first report of a functional analysis of cells separated alive according to cytokine expression shows that these cytokines are not produced by different Th cell subpopulations, but can be expressed sequentially by individual Th cells. Th cells, activated with SEB for 1 day and isolated according to expression of IL-2, using the cellular affinity matrix technology, upon continued stimulation with SEB later secrete most of the IFN-gamma and IL-10. Likewise, after 2 days of SEB culture, cells expressing IFN-gamma, separated according to specific surface-associated IFN-gamma as detected by magnetofluorescent liposomes, 1 day later secrete IL-10. Thus, individual Th1 cells can contribute to the control of their own IFN-gamma expression by sequential expression of first IL-2, supporting their proliferation, and later IL-10, down-regulating the production of IFN-gamma-inducing monokines and limiting the pro-inflammatory effects of IFN-gamma.

Animals↗

Molecular phylogeny of Vespidae (Hymenoptera) and the evolution of sociality in wasps.

The oriental Stenogastrinae is a group in which there is considerable interest as regards the study of evolution of sociality in wasps, because they show broad diversity in social behavior. Using cladistic analysis on morphological and behavioral data, they have been grouped together with the social Vespinae and Polistinae in the family of Vespidae. This is not without dispute, because several other morphological and behavioral characters separate Stenogastrinae from the other Vespidae subfamilies. DNA sequences were obtained from nuclear 28S ribosomal DNA and the mitochondrial 16S ribosomal DNA of two Apis species and nine social and three solitary wasp species of the family Vespidae. Solitary wasps of the family Braconidae and Pteromalidae were used as outgroups. Parsimony, distance, and maximum-likelihood methods of both mitochondrial and nuclear DNA did not support the conventional phylogenetic position of Stenogastrinae. In all phylogenetic reconstructions, the solitary Eumeninae were a sister taxon to the Polistinae + Vespinae cluster. The analyzed sequences provide strong evidence that sociality has independently evolved twice in the Vespidae.

Animals↗

Sociality and the rate of rDNA sequence evolution in wasps (Vespidae) and honeybees (Apis).

Sequence data of mitochondrial 16S ribosomal DNA (mt-rDNA) and nuclear 28S ribosomal DNA (nuc-rDNA) were compared in two honeybee species (Apis mellifera and Apis dorsata) and a selection of 22 wasp species (Vespidae) with different levels of sociality. The averge substitution rates in mt-rDNA and nuc-rDNA were almost-equal in solitary species. In species with larger nests, however, the difference between the nuclear and the mitochondrial substitution rate significantly increased. The average substitution ratio, psi (nucleotide substitutions in mt-rDNA/nucleotide substitutions in nuc-rDNA) was 1.48 +/- 0.12 (SE) among the solitary Eumeninae, 3.70 +/- 0.15 among five primitive social Stenogastrinae species, 3.24 +/- 0.20 among five Polistinae species, 5.76 +/- 0.33 among nine highly eusocial Vespinae, and 12.7 in the two Apis species. The high egg-laying rate and the effective population size skew between the sexes may contribute to the rise of the substitution ratio in the highly eusocial species. Drift and bottleneck effects in the mitochondrial DNA pool during speciation events as well as polyandry may further enhance this phenomenon.

Animals↗

Syndrome of intractable diarrhoea with persistent villous atrophy in early childhood: a clinicopathological survey of 47 cases.

BACKGROUND: The syndrome of intractable diarrhoea of infancy is heterogeneous and includes several diseases with diverse aetiologies. This study determines whether diagnostic categories can be defined on the basis of clinicopathological analysis. METHODS: European Society of Paediatric Gastroenterology, Hepatology and Nutrition members were surveyed to identify cases of intractable diarrhoea with persisting small intestinal enteropathy. A retrospective clinicopathological analysis was performed on cases showing life-threatening diarrhoea within the first 24 mo of life and requiring total parenteral nutrition, which were characterized by persistent villous atrophy, and resistance to therapy. RESULTS: Forty-seven infants were identified with intractable diarrhoea. Villous atrophy was of varying degrees with (group I, n = 24) or without (group II, n = 18) lamina propria mononuclear cell infiltration. Group I presented later, had gut autoantibodies, and a higher prevalence of protein-losing enteropathy; a subset (group Ia, n = 12) also had extraintestinal symptoms of autoimmunity associated with a later onset of larger volume diarrhoea. Group II presented early; 8 cases (group IIa) had phenotypic abnormalities and a low birth weight; the remaining 10 (group IIb) showed mild-to-moderate villous atrophy, epithelial tufting, and abnormal crypts. Group III included five patients in whom no specific features were recognised. Twenty-one (45%) died at a median age of 24 months, 20 (43%) remained dependent on parenteral (n = 16) or enteral tube (n = 4) feeding, 4 (9%) received elimination diets plus other therapies, and 2 (4%) were lost to follow-up. CONCLUSIONS: Clinicopathological analysis allowed distinct disease groups to be identified, allowing a provisional classification to be made. This straightforward approach forms a basis for future research in this exceptionally difficult paediatric condition.

Atrophy↗

CTLA-4 gene polymorphism is associated with predisposition to coeliac disease.

BACKGROUND: Susceptibility to coeliac disease is strongly associated with particular HLA class II alleles. However, non-HLA genetic factors are likely to be required for the development of the disease. Among candidate genes is the CTLA-4 (cytotoxic T lymphocyte associated) gene located on chromosome 2q33 in humans, which encodes a cell surface molecule providing a negative signal for T cell activation. AIMS: To investigate CTLA-4 exon 1 polymorphism (position 49 A/G) in patients with coeliac disease. PATIENTS: 101 patients with coeliac disease and 130 healthy controls. METHODS: Allele specific hybridisation and restriction enzyme digestion of polymerase chain reaction amplified genomic DNA. RESULTS: The A allele of the CTLA-4 position 49 polymorphism was found on 82.2% of chromosomes in patients with coeliac disease compared with 65.8% in controls (p < 0.0001), mostly in the homozygous form (68.3% in patients versus 47.7% in controls; odds ratio (OR) 2.36, 95% confidence interval (CI) 1.37 to 4.06, p = 0.002). Four patients only had the G/G genotype compared with 21 controls (OR 0.21, CI 10.07 to 0.64, p = 0.002). These differences were maintained when subjects were stratified according to the HLA class II phenotype, in particular when patients and controls were matched for the presence of the predisposing HLA DQB1*02 (DQ2) allele or HLA-DQA1*0501/DQB1*02 heterodimer. CONCLUSION: The CTLA-4 gene polymorphism is a non-HLA determinant that predisposes to coeliac disease. Whether it directly contributes to disease susceptibility or represents a marker for a locus in linkage disequilibrium with CTLA-4 needs further investigation.

Abatacept↗