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Biomedical subjects

T Schulz

Publications and source records attributed to T Schulz.

At least 127 records · Page 7Linked to original sources

Incidence of inflammatory bowel disease in southeastern Norway: evaluation of methods after 1 year of registration. Southeastern Norway IBD Study Group of Gastroenterologists.

To assess the feasibility of a prospective incidence study of inflammatory bowel disease (IBD), the registration methods and incidence figures during 1990 were evaluated. The study was a collaboration between 14 hospitals in an area of close to one million inhabitants. Common diagnostic criteria for ulcerative colitis (UC), Crohn's disease (CD) and indeterminate colitis (IND) were established prior to the start of the study. There was an overall incidence rate for IBD of 19.3 per 10(5) inhabitants, with 10.6 for UC, 5.1 for CD and 3.6 for IND. The age-specific incidence rates showed a peak between 25 and 34 years for UC and between 15 and 25 for CD. There was a male predominance for UC and a female preponderance for CD. These results are comparable with the previous registrations in western and northern areas of Norway.

Adolescent↗

Immunoblastic transformation of a Sezary syndrome in a black Caribbean patient without evidence of HTLV-I.

We describe an unusual case of Sezary syndrome which transformed into a large T-cell non Hodgkin's lymphoma (immunoblastic) in a black man of Caribbean descent with negative HTLV-I serology and no evidence of HTLV-I infection by DNA analysis using sensitive techniques. The disease presented as a small-cell Sezary syndrome and transformed in an inguinal lymph node one year from diagnosis. Immunological markers in the small and large cells showed a mature T-cell phenotype CD4+, CD8- with expression of T-cell activation markers and a high proliferative rate. Ultrastructural analysis confirmed small Sezary cells with serpentine nucleus in the peripheral blood and immunoblasts in the lymph node. Cytogenetics demonstrated complex clonal chromosome abnormalities with involvement of 7q35, the locus for the beta chain of the T-cell receptor (TCR). Southern-blot analysis showed the same rearrangement of the TCR beta, gamma, delta chain genes in lymph node and peripheral blood cells. Antibodies to HTLV-I were not detected in the serum by ELISA and particle agglutination (PA) nor HTLV-I specific sequences were demonstrated by nested polymerase chain reaction with primers to the envelope proteins, LTR and tax/rex of HTLV-I in both tissues, blood and lymph node. The disease had an aggressive course and was refractory to therapy; the patient died of progressive disease 28 months from presentation. Two unusual features characterised this patient's illness: immunoblastic transformation of a Sezary syndrome in a patient of Afro-Caribbean origin without evidence of HTLV-I DNA sequences and negative HTLV-I serology and the atypical lymph node histology resembling ATLL.

Base Sequence↗

[Preoperative status of serum proteins in lung surgery patients].

The preoperative serum-protein-status of 91 patients was investigated with a laboratory-screening in order to find out the patients with a malnutrition and consequently with a high risk of postoperative complications. The diagnosis was the basis for the classification in groups. There were no significant differences between values of our patients and normal values of a control group in protein, albumin, prealbumin, transferrin, cholinesterase, alpha-1-antitrypsin and haemopexin. Nutrition parameters are of limited value of preoperative risk-screening in operable lung cancer patients.

Adenocarcinoma↗

Contribution of CYP1A1 and CYP1A2 to the activation of heterocyclic amines in monkeys and human.

The activation of heterocyclic amines to mutagenic products by hepatic microsomal fractions from cynomolgus monkey, marmoset monkey and man was compared with the respective levels of cytochrome P450 enzymes CYP1A1 and CYP1A2. The rate of activation of 2-amino-3,8-dimethylimidazo[4,5-f] quinoxaline (MeIQx), 2-amino-3-methylimidazo[4,5-f]quinoline (IQ) and 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) to mutagens by hepatic microsomal fraction from cynomolgus monkey was very low. This was associated with a lack of constitutive expression of CYP1A1 and CYP1A2. In contrast, human hepatic microsomal fraction readily activates these heterocyclic amines and this is associated with constitutive expression of CYP1A2. Treatment of cynomolgus monkey with 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) causes a very modest induction of CYP1A2, and a small increase in the activation of MeIQx and IQ. However, there was marked induction of CYP1A1 which was accompanied by > 10-fold increases in PhIP activation and 7-ethoxyresorufin O-deethylase (EROD), 7-methoxyresorufin O-demethylase (MROD) and aryl hydrocarbon hydroxylase activities. Following treatment of cynomolgus monkey with 3-methylcholanthrene, induction of CYP1A1, but not CYP1A2, was evident. In untreated marmoset monkey the activations of MeIQx and PhIP, as well as phenacetin O-deethylase, EROD, MROD and aryl hydrocarbon hydroxylase activities, are similar to those in man, although the activations of IQ and coumarin 7-hydroxylase activity are lower than in man. The presence of constitutive CYP1A2, and the absence of CYP1A1, in the liver of this species correspond to the situation in man. Treatment of marmoset monkey with TCDD results in increased CYP1A2 levels (4-fold), accompanied by proportional increases in the activation of MeIQx and IQ and phenacetin O-deethylase, EROD and MROD activities. The activation of PhIP is increased disproportionately, by 8-fold, most likely due to the activity of CYP1A1 which is also induced by TCDD in this species. Overall, the hepatic metabolism of heterocyclic amines by CYP1A enzymes in the untreated marmoset monkey resembles that in human more closely than that in the cynomolgus monkey. Therefore, marmoset monkey may be a more suitable model than the cynomolgus monkey for carcinogenicity studies involving MeIQx and PhIP, but not IQ.

Animals↗

Phylogenetic classification of human T cell leukaemia/lymphoma virus type I genotypes in five major molecular and geographical subtypes.

Proviral DNA was obtained from ex vivo peripheral blood mononuclear cells of 75 human T cell leukaemia/lymphoma virus type I (HTLV-I)-infected individuals who were either asymptomatic or had adult T cell leukaemia or tropical spastic paraparesis/HTLV-I-associated myelopathy. Amplified long terminal repeats (LTRs) were analysed for restriction fragment length polymorphisms (RFLPs). The results, together with previously published LTR data (a total of 180 specimens analysed), showed the presence of 12 different RFLP profiles with four major molecular subtypes. Furthermore, a fragment of 413 bp (nucleotides 22 to 434) of the U3/R region was sequenced for 12 new HTLV-I specimens originating from Central and West Africa (8 cases), Iran (1 case), Caribbean (2 cases) and Reunion Island (1 case). Phylogenetic analysis using three different techniques (maximum parsimony, neighbour-joining and UPGMA) comparing these 12 strains (including four new African HTLV-I variants) with the 30 published partial HTLV-I LTR sequences (nt 120 to 434) showed the existence of clusters of molecular variants in discrete geographical areas. The topology of the phylogenetic trees is thought to reflect HTLV-I evolution and the migrations of virally infected populations in the recent or distant past. Furthermore, there was a nearly perfect concordance between the clustering based on the LTR sequence homologies and the LTR RFLP subtypes suggesting that this rapid and simple technique is well suited to the investigation of HTLV-I molecular epidemiology. These results allow a new phylogenetic classification of HTLV-I genotypes into five major molecular subtypes: Cosmopolitan (C) subtype widespread all over the world, Japanese (J) subtype, West African (WA) subtype. Central African (CA) subtype and Melanesian (M) subtype.

Africa↗

Identification of human immunodeficiency virus type 1 glycoprotein gp120/gp41 interacting sites by the idiotypic mimicry of two monoclonal antibodies.

A sequence of four amino acid residues amino-terminal to the only intramolecular disulphide bond of the human immunodeficiency virus type 1 (HIV-1) transmembrane protein gp41 is recognized by an anti-idiotypic antibody (9G5A) raised against another monoclonal antibody (M38), which recognizes the C5 region of gp120. 9G5A is an Ab2 beta antibody (internal image of the M38 epitope) in that it inhibits the interaction of M38 to its antigen. The binding of 9G5A to gp41 can be inhibited by M38 showing that the two antibodies interact via their paratopes. 9G5A neutralizes HIV-1 infection and syncytia formation. Ab3 antibodies induced in mice and rabbits immunized with 9G5A also can neutralize virus in both assays. These data show that the M38-defined epitope of the carboxy-terminal region of gp120 interacts with the 9G5A-defined epitope of gp41, and that this interaction can be reproduced by the idiotypic mimicry of the two antibodies. The results are consistent with a proposed molecular model of the two env regions which predicts the presence, within the C5 region of gp120, of a large intramolecular pocket that is contacted by the gp41 cysteine loop.

Amino Acid Sequence↗

A microgenetic study of the Müller-Lyer illusion.

In two experiments a decomposed Müller-Lyer pattern was used to measure the time course of the illusion. A partial report procedure was used to prevent the subjects from focusing only on parts of the pattern and to maximize visual processing. The Müller-Lyer figure was decomposed into two parts, its angles and its line. A configuration of three pairs of angles, each corresponding to a row in the usual partial report arrangement, was used. A line that did or did not fit the gap was shown with a variable delay (interstimulus interval, ISI). By this procedure the relevant row (line gap) was cued. The subject had to decide whether the line fitted or was too short/long. Two exposure times for the angles were used, 50 or 200 ms in one experiment and 50 or 500 ms in the other. The result of the first experiment, with outward-pointing fins, was a stable illusion for all values of ISI (25-400 ms) and all exposure times, with one significant exception: exposure for 50 ms with an ISI of 50 ms yielded an illusion peak. It was shown that this was not caused by a reduction in length-discrimination performance. In the second experiment, with inward-pointing fins, no such peak occurred. There was only a tendency for the illusion to vanish with zero ISI. The results are discussed with respect to 'global to local' theories of visual processing.

Distance Perception↗

[Color-word interference in relation to comparative compatibility: evidence for two sources of interference].

In previous studies on colour-word interference ('Stroop-phenomenon') stimulus-response-compatibility (word-speech, colour-speech) and task mode (word reading, colour determining) have usually been confounded or not been crossed completely. An experiment is reported where these two factors were varied orthogonally (besides type of stimulus: incongruent, congruent and control). Compatibility was varied by using response keys with varying labelling of the keys (colours or words). The results show--contrary to traditional expectations--the usual pattern of interference in spite of the response key conditions. The existence of response delays of different magnitude indicates separate sources of interference. Encoding interference is found under conditions of high-compatible colour determining by coloured response keys (colour-colour key), recoding interference under conditions of low-compatible reading (word-colour key), both presented here in an isolated form. Both modes of interference should therefore contribute to the interference under conditions of low-compatible colour determining which is the traditional Stroop condition. In an attempt to predict this complete interference encoding interference was shown to be the more stable predictor. The same was true of interference as measured here in a list version.

Adult↗

Misoprostol treatment exacerbates abdominal discomfort in patients with non-ulcer dyspepsia and erosive prepyloric changes. A double-blind, placebo-controlled, multicentre study.

One hundred and thirty-seven consecutive outpatients with non-ulcer dyspepsia (NUD) and erosive prepyloric changes (EPC) were randomly allocated to double-blind treatment with 400-micrograms misoprostol tablets twice daily or placebo for 4 weeks. Misoprostol had a significant worsening effect on epigastric pain, nausea, meteorism, lower abdominal pain, and diarrhoea, as compared with placebo. The fact that symptoms in patients with NUD and EPC were exacerbated by an antisecretory dose of misoprostol indicates that the symptoms are largely unrelated to gastric acid.

Adolescent↗

Retrovirus-like sequences in Graves' disease: implications for human autoimmunity.

On Southern blotting of DNA extracted from thyroid glands of five patients with Graves' disease, two probes (720 bp and 942 bp) for gag human immunodeficiency virus type 1 (HIV-1) gave a positive hybridisation signal in all samples tested. DNAs from peripheral blood mononuclear cells hybridised with the 720 bp gag HIV-1 probe in three of the five patients, none of whom had antibodies to HIV-1. Negative results were obtained with DNA from normal thyroid glands, thyroid neoplasms, various unrelated normal tissues, and virus-infected human cell lines. The intensity of the signal and the pattern of bands observed with the DNA of Graves' patients were heterogeneous and, in general, were not the same in the thyroid glands and peripheral blood mononuclear cells of individual patients. Similarly, no correlation was found between the positive hybridisation signals and other genetic and immunological indices or the duration of anti-thyroid drug treatment at the time the patients were investigated. The findings suggest the presence of a novel retrovirus, and the retrovirus-like sequences seem to be closely associated with thyroid autoimmunity.

Adolescent↗

Partial report, visual matching, and search as a function of cue-delay.

Three experiments are reported where a cue that was varied in time indicated a letter pair (or pairs) in a circular display with six pairs. The S had either to report letters from a pair (Exp. 1) or to decide about the equality of the letter pair (Exp. 2) or to decide about the presence of a target letter given with various delays (Exp. 3). Exp. 1 shows a short-lived partial report superiority, the loss being primarily due to adjacency errors. In Exp. 2 a short loss in the correct same decisions, but almost no loss in the correct "differents" was observed. In spite of its search task character, Exp. 3 showed the same loss as Exp. 1, 2. In all experiments performance recovered with the latest ISI (1 sec). The results of Exp. 1 can be explained by post-categorical accounts of the partial report (PR-) effect (loss of positional information), those of Exp. 2 by visual confusion, i. e. a precategorical account, those of Exp. 3 by neither. The results suggest that the PR-effect might be due to non-visible persistence rather but to visible persistence. A theory of early visual processing which would also explain the PR-effect is still lacking.

Attention↗

Plasma clearance of bile acids in the rat: hepatic uptake under physiological conditions without countertransport.

Studies in rats by others indicated that sulfobromophthalein (BSP), bilirubin and indocyanine green are taken up by the liver and can be transported back to plasma against the prevailing concentration gradient (= countertransport). The present in vivo study was designed to determine whether the bile acids cholic acid and taurocholic acid under physiological conditions undergo appreciable countertransport as has been suggested by experiments in isolated hepatocytes. Experiments with BSP (controls) showed that injections of unlabeled BSP into rats five minutes after the administration of radiolabeled BSP was followed by a release of radioactivity into plasma (BSP-countertransport). In contrast bile acid countertransport could not be demonstrated, no matter whether it was tested 1, 5 or 8 minutes after the administration of radiolabeled cholic- or taurocholic acid.

Animals↗

Cytomegalovirus infection.

Interest has focused on cytomegalovirus (CMV) infections during recent years for two reasons: First, the number of immunocompromised patients with CMV infections has risen continuously and, secondly, recent advances in basic research have clarified some of the mechanisms of persistent and recurrent CMV infection. Three different clinical pictures can arise with CMV infection. In healthy individuals most of the CMV infections are not clinically apparent. In immunocompromised patients CMV causes a wide spectrum of diseases and is one of the predominant causes of death in AIDS patients and bone marrow transplant recipients. The most important problem for public health associated with CMV are connatal and perinatal CMV infections. Progress has been made with treatment of CMV infection in immunocompromised patients with inhibitors of viral replication.

Acquired Immunodeficiency Syndrome↗

CD5 and CD21 molecules are a functional unit in the cell/substrate adhesion of B-chronic lymphocytic leukemia cells.

The modulation of surface molecules on B-chronic lymphocytic leukemia (B-CLL) cells was studied in vitro by incubation with CD19, CD20, CD21, CD5 and anti-IgM antibodies. The cytoplasmic changes were evaluated by analyzing the organization of cytoskeletal F-actin and the adhesive properties of stimulated B-CLL cells. The following observations were made: (a) CD5 antigen is capped on the surface of B-CLL cells (but not on normal CD5+ B and T lymphocytes). (b) On B-CLL cells, CD5 and CD21, the receptors for the C3d fraction of complement, co-cap and co-modulate while surface IgM as well as CD19 and CD20 do not cap. (c) B-CLL cells, after capping of CD5 or CD21 surface molecules, fail to organize F-actin into podosomes. (d) The pre-incubation of B-CLL cells with either CD5 or CD21 antibodies prevents their binding to purified C3d protein used to coat coverslips. These data indicate that an intimate spatial relationship exists between CD5 and CD21 molecules on the B-CLL surface. The CD5-CD21 complex is involved in the redistribution of cytoskeletal proteins which may control the adhesive properties of these malignant B cells.

Actins↗

Activation of cyclophosphamide in mouse limb bud cultures using a reconstituted cytochrome P-450 system.

Purified phenobarbital-induced rat liver cytochrome P-450 was incorporated in a reconstituted system containing NADPH-cytochrome P-450 reductase, dilauroyl phosphatidyl choline and sodium cholate. This system was added to organ cultures of limb buds from mouse embryos on day 11 of gestation. Cyclophosphamide (100 micrograms per ml) was used as a "pre-teratogen" and activation was initiated by adding an NADPH-regenerating system. Due to extensive purification, toxicity of the enzyme preparations and residual solubilisation detergents could be greatly reduced. A reconstituted system containing 10-100 pmol cytochrome P-450 per ml without cyclophosphamide caused no noticeable interference with limb development. The same assay containing cyclophosphamide, however, resulted in a pronounced impairment of cartilage differentiation and in the formation of clearly abnormal structures, especially at the paw skeleton. The activity of the reconstituted system declined under the experimental conditions used, but some activating capacity towards cyclophosphamide was still demonstrable after about 2 h of incubation.

Animals↗