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Biomedical subjects

J Schmitz

Publications and source records attributed to J Schmitz.

At least 127 records · Page 7Linked to original sources
PubMed1994

Follicular dendritic cells retain HIV-1 particles on their plasma membrane, but are not productively infected in asymptomatic patients with follicular hyperplasia.

During HIV-1 infection, extensive alterations can be observed in the germinal centers (GCs) of lymphatic tissue. The initial hyperplasia of GCs is followed by disintegration and involution of these structures. The process is accompanied by progressive destruction of the network of follicular dendritic cells (FDCs). We investigated whether or not the destruction of GCs is caused by HIV-1 infection of FDCs in vivo. FDCs were purified by FACS or magnetic cell sorter (MACS) from enlarged lymph nodes (LNs) of four asymptomatic HIV-1-infected patients with persistent generalized lymphadenopathy. In situ hybridization demonstrated positive signals for HIV-1 RNA on the cell membrane of FDCs. Virus particles attached to the dendritic network could be demonstrated by electron microscopy, but budding was not seen. Furthermore, proviral DNA was detected by nested PCR (NPCR) in limiting dilution assays of FACS-purified FDCs (up to 1.0 x 10(4) cells) in only one cell fraction. In comparison, proviral DNA could be found in 5.0 x 10(3) to 2.5 x 10(5) FACS-purified Th cells obtained from peripheral blood and in 7.5 x 10(5) to 2.5 x 10(4) Th cells from LN of the same patients. In conclusion, FDCs retain HIV-1 particles on their cell membrane during HIV-1 infection, but the progressive destruction of FDC in vivo is probably not caused by a productive infection of FDCs with HIV-1.

Cell Membrane↗
PubMed1994

Induction of interleukin 4 (IL-4) expression in T helper (Th) cells is not dependent on IL-4 from non-Th cells.

Interleukin 4 (IL-4) is essential for the induction of immunoglobulin E (IgE) responses in mice. Recent in vitro studies have suggested that IL-4 derived from non T helper (Th) cells, in particular from mast cells and basophils, may be essential for triggering of IL-4 expression in Th cells and may directly contribute to IgE isotype switch induction. Here, we have generated mice carrying a functional IL-4 gene only in Th cells or non-Th cells, respectively, by reconstitution of IL-4-deficient mice (IL-4T mice) with CD4+ or CD4- spleen cells from congenic wild-type animals. In mice in which only CD4+ cells are able to express IL-4, antigen-specific IgE is produced in a T cell-dependent immune response. Thus, induction of IL-4 expression in Th cells can occur in the absence of IL-4 from non-Th cells, which suggests that at least some Th cells can express IL-4 in response to another signal which has yet to be identified. No IgE is detectable, however, in mice in which only CD4- cells can express IL-4, suggesting that Th cells are the primary, if not the only source of IL-4 for initial induction of IgE synthesis.

Animals↗
PubMed1994

Flow cytometric determination of cytokines in activated murine T helper lymphocytes: expression of interleukin-10 in interferon-gamma and in interleukin-4-expressing cells.

In an immune response, effector functions are controlled by T helper (Th) 1 cytokines [interferon-gamma (IFN-gamma), interleukin (IL)-2 and tumor necrosis factor-beta] and Th2 cytokines (IL-4, IL-5 and IL-10). Here we analyze by multiparameter immunofluorescence to what extent IL-2, IL-4, IL-5, IL-10 and IFN-gamma are co-expressed in individual normal murine Th cells upon activation in vitro with the bacterial superantigen Staphylococcus aureus enterotoxin B, presented in the context of major histocompatibility complex class II. IL-2 and IFN-gamma are co-expressed by some, but not by other Th cells. Expression of IL-4 and IFN-gamma is exclusive. IL-10 is co-expressed in individual cells either with IL-4 or with IFN-gamma. No IL-5-expressing cells are detected. While IL-10- and IL-4-co-expressing Th cells correspond to classical Th 2 cells, cells co-expressing IL-10 and IFN-gamma could be involved in negative-feedback regulation of a Th1 response. Apart from such functional implications, our results show that IL-2, IL-4, IL-5, IL-10 and IFN-gamma are expressed independently of each other in individual murine Th cells.

Animals↗
PubMed1994

Deletion of the mitochondrial DNA in a case of de Toni-Debré-Fanconi syndrome and Pearson syndrome.

We report a patient with Pearson syndrome with failure to thrive, exocrine pancreas insufficiency, growth hormone deficiency and severe tubular dysfunction. The patient had no signs of liver involvement. Normal respiratory chain enzyme activity was found in the lymphocytes, but a mitochondrial DNA deletion was demonstrated in lymphocytes and in the kidney. Polymerase chain reaction amplification and sequence analysis revealed the presence of the 4,977 base pair "common" deletion in the mitochondrial genome. Our findings support the view that tubulopathies of unknown origin may be related to mitochondrial respiratory chain deficiency.

Base Sequence↗
PubMed1994

Polymorphism of antigen processing (TAP, LMP) and HLA class II genes in celiac disease.

Susceptibility to CD is strongly associated with particular HLA class II molecules. However, additive genetic factors are likely to be required for the development of the disease. The polymorphic TAP and LMP genes, located within the HLA class II region, are involved in the antigen presentation pathway and thus represent candidate susceptibility genes. HLA class II DRB1, DRB3, DQA1, DQB1, and DPB1 as well as TAP1, TAP2, and LMP2 polymorphism was studied in 80 Caucasian CD patients and 213 normal controls by DNA oligotyping. The DQB1*0201 allele was found in 96.3% of CD patients and provided the highest risk (RR = 50), whereas only 89% of CD patients carried the DQ alpha 501/beta 201 heterodimer (RR = 30). The participation of the DRB3 and DPB1 locus was ruled out as it was attributed to a linkage disequilibrium on the DR3 haplotype. TAP1 and LMP2 allelic distribution was not significantly different among CD patients and controls. The TAP2-C allele was completely absent from the CD population, while it was found in 22.5% of controls. Although linkage disequilibrium between TAP2 and class II loci clearly exists in some haplotypes, TAP could act as additional susceptibility genes.

Adolescent↗
PubMed1994

A new cause of progressive intrahepatic cholestasis: 3 beta-hydroxy-C27-steroid dehydrogenase/isomerase deficiency.

There have been a few reports of infants with severe neonatal cholestasis related to a defect in primary bile acid synthesis. To assess the importance of such deficiency among children with progressive intrahepatic cholestasis (Byler disease), screening for inborn errors in bile acid synthesis was performed by fast atom bombardment ionization-mass spectrometry of urine samples from 30 affected children. Bile acid analysis revealed a specific fast atom bombardment ionization-mass spectrometry profile for 3 beta-hydroxy-C27 steroid dehydrogenase/isomerase deficiency in five children who had jaundice, hepatosplenomegaly, and fatty stools beginning at ages ranging from 4 to 46 months. None of them had pruritus. Liver function tests showed persistently normal serum gamma-glutamyltransferase activity, low serum cholesterol and vitamin E levels, normal serum bile acid concentrations despite raised serum bilirubin levels, and decreased prothrombin time and clotting factor V. In four of the cases a similar disease was observed in siblings. Liver function returned to normal after oral ursodeoxycholic acid therapy. We conclude that 3 beta-hydroxy-C27-steroid dehydrogenase/isomerase deficiency should be considered when idiopathic cholestatic liver disease with clinical features akin to Byler disease is characterized by the association of normal serum gamma-glutamyltransferase activity, normal serum bile acid concentration, absence of pruritus, and a return to normal liver function during ursodeoxycholic acid therapy. Early identification of these children is essential because they benefit from bile acid therapy and might thus avoid the need for liver transplantation.

Alanine Transaminase↗
PubMed1994

Mitochondrial DNA rearrangements with onset as chronic diarrhea with villous atrophy.

We report two unrelated children with onset of chronic diarrhea and villous atrophy in the first years of life. Elevated plasma lactate concentrations and lactate/pyruvate and ketone body molar ratios suggested a genetic defect of oxidative phosphorylation. Analysis of the mitochondrial respiratory chain showed a complex III deficiency in muscle of both patients. Southern blot analysis provided evidence of heteroplasmic mitochondrial DNA rearrangements that involve deletion and deletion-duplication. Directly repeated sequences (10 and 11 base pairs, respectively) were present in the wild type of mitochondrial genome at the boundaries of the deletion. Neither parent of either patient had rearranged molecules in their circulating lymphocytes. It appears that a mitochondrial disorder can have chronic diarrhea and villous atrophy as the initial clinical feature. On the basis of these observations, we suggest that genetic defects of mitochondrial energy supply be considered in elucidating the origin of unexplained chronic diarrheas, especially when other, unrelated symptoms occur in the course of the disease.

Atrophy↗
PubMed1994

Detection of Mycobacterium paratuberculosis by polymerase chain reaction in children with Crohn's disease.

Mycobacterium paratuberculosis, the causative agent of Johne's disease (a chronic enteritis in ruminants), has been suspected to be involved in Crohn's disease. In this study, polymerase chain reaction was used to detect the presence of IS900 DNA sequences specific to M. paratuberculosis genomes in biopsies and surgical resections from 53 children with various gastrointestinal diseases and disorders. IS900 sequences were found in 13 of 18 samples from patients with Crohn's disease (72%; P < .01 vs. samples from patients without Crohn's disease), in 1 of 5 with ulcerative colitis, in 2 of 6 with severe unclassified colitis, and in 7 of 24 with other gastrointestinal illnesses. These results appear to support the hypothesis that M. paratuberculosis is involved in the pathogenesis of Crohn's disease.

Child, Preschool↗
PubMed1994

Recovery of T-lymphocytes for adoptive immunotherapy by lymphapheresis of HIV-infected patients without alterations of virological, immunological or clinical parameters.

We performed repeated continuous flow cytaphereses (CFC) on 13 asymptomatic HIV-1-infected patients to study the feasibility of cell separation procedures to recover high yields of peripheral blood T-lymphocytes for adoptive immunotherapy in HIV-infected patients and to determine immunological and virological alterations following such procedures. A mean yield of 6.23 x 10(9) lymphocytes could be obtained by each cytapheresis, containing 1.82 x 10(9) CD4+, 3.23 x 10(9) CD8+ T-lymphocytes and 8.39 x 10(6) CD34+ peripheral progenitor cells. The CD4/CD8 ratio (mean 0.53, SD +/- 0.15) in the cell samples reflected the distribution of the lymphocyte subsets in vivo. Absolute lymphocyte counts decreased at a mean of 404/mm3 (25%) immediately after CFC but were replaced from the extravascular pool within 1 h. The CD4/CD8 ratios, p24-antigenaemia, HLA-DR expression and neopterin levels did not change significantly after cell separation. No alteration of the number of T-cells with integrated proviral DNA copies (1/10(3) to 1/10(6)) could be detected in peripheral T-helper cells by PCR after lymphapheresis. We conclude that high yields of peripheral T-lymphocytes can be obtained by continuous flow lymphapheresis for cell-mediated immunotherapy, without deterioration of virological or immunological parameters in HIV-infected patients. The separated T-cells are fully replaced from extravascular pools after 1 h.

CD4-CD8 Ratio↗
PubMed1994

Sequence analysis of the D1 and D2 regions of 28S rDNA in the hornet (Vespa crabro) (Hymenoptera, Vespinae).

The two variable domains D1 and D2 near the 5' end of the 28S ribosomal RNA gene (large subunit rRNA) have been sequenced for Vespa crabro. The sequence was aligned to corresponding rDNA regions of the wasp species Nasonia vitripennis, Melittobia digitata and the fruit fly Drosophila melanogaster. We analysed the nucleotide composition and sequence similarity for the different regions of the investigated sequences and present the inferred secondary structure of Vespa crabro.

Animals↗
PubMed1994

Follicular dendritic cells in non-Hodgkin's lymphomas.

Follicular dendritic cells (FDC) are restricted to the B-cell regions of secondary lymphoid tissue and to non-Hodgkin's lymphomas derived from the follicular center or the mantle zone. With their cytoplasmic ramifications they form a dense network which contains the B-lymphocytes. In situ, FDC are only detectable at the ultrastructural level or when stained with anti FDC-reagents. On the surface of their dendritic extensions they express transferrin receptors (CD71), the B-cell epitope CD20, class II antigens, the myelomonocytic molecule CD14, the glycoprotein gp50 (CD40), and several receptors for components of the complement system (CD11b, CD21, CD35). Subsequent to an antigen challenge, FDC trap and retain immune-complexes for a long period of time. In vitro FDC and neoplastic lymphocytes spontaneously form small cellular aggregates. This adhesion is mediated by the LFA-1-alpha/beta = ICAM-1, the VLA-4 = VCAM-1, and the ICAM-1 = C3bi- receptor ligand pathways on B-cells and on FDC, respectively. The loss of LFA-1- alpha/beta and ICAM-1 molecules may enable neoplastic lymphocytes to detach from FDC. The monoclonal B-cells now invade new compartments. In vitro, FDC have the capacity to activate resting B-cells and to save them from dying by apoptosis. Signals involved in this activation include cell-surface immunoglobulin and CD40. Immunocytochemistry and autoradiography with single cell suspensions of neoplastic B cells suggest that FDC also provide signals leading to the continued stimulation of lymphoma lymphocytes. During the early stage of HIV infection lymph nodes show an immense follicular hyperplasia, with a massive increase of the dendritic network of FDC. In the later stage of the disease, the continuous involution of the germinal centers is associated with a progressive destruction of FDC.

Antigen Presentation↗
PubMed1994

[Psychological treatment approaches in pain. A comparative study of therapies in patients with chronic polyarthritis].

The efficacy of psychological treatment to reduce pain has recently been shown in a number of studies. They are considered to enhance or even replace medical approaches in pain management, especially in chronic pain-states. The study reported here aimed to test two established (multimodal pain management, relaxation training) and one newly designed approach (visualization techniques) in comparison with a control group (medical treatment alone). The study was conducted with in-patients (N = 46; rheumatoid arthritis). Medical and pain data were gathered before and after treatment. Patients also filled out questionnaires in the beginning and at the end of the study assessing pain-experience, emotional states and capability to cope with pain. Patients participating in the multimodal pain management group and the visualization group profited from participation (especially in pain reduction) only if they gained substantially extents in the capability to cope with pain. Simply taking part in the groups and not reaching acceptable measures to cope with pain had no or negative effects. Both approaches were clearly above the control- and the relaxation-condition (relaxation participants were hardly better than the controls). The range of efficacy was broadest in the multimodal group (in addition to pain-reduction, substantial improvements in emotional states were obtained). However, visualization techniques, which were tested empirically for the first time here, can also be recommended as pain management therapy.

Adult↗
PubMed1994

[A rare cause of rectal hemorrhage in children: rectal angiodysplasia].

BACKGROUND: Parietal vascular malformations of the intestinal tract are rare and their diagnosis is often difficult. CASE REPORT: A 2 year-old boy had suffered from intermittent rectal bleeding since the age of one year. Endoscopic examination showed unspecific congestive changes and biopsy showed features of chronic inflammatory changes in the rectum. Barium enema was normal. The patient was operated on, but surgery failed to find any cause for these hemorrhages. Rectal bleedings recurred, some of them resulting in severe anemia. Two further endoscopic examination were grossly negative as was inferior mesenteric arteriography. Spontaneous rectal prolapsus occurred when the boy was 4 years old. This allowed resection of all the submucosal veins of the anal canal; it was followed by complete cessation of rectal bleeding with a follow-up of 36 months. Histological examination showed several ectasias of the capillaries and veins in the submucosa and muscular layers. CONCLUSION: Angiectases can occur in a small part of the intestinal tract, and can escape detection by repeated specialized investigation.

Arteriovenous Malformations↗
PubMed1994

[Antigliadin, antireticulin, antiendomysium antibodies: value in the diagnosis and follow-up of celiac disease in children].

In recent years, the clinical spectrum of coeliac disease has changed and forms with mild aspecific symptoms are today frequent. Therefore many infants are submitted to jejunal biopsy in order to exclude coeliac disease or to allow an early diagnosis. This has led to a search for a simple and reliable diagnostic test of coeliac disease in order to limit the use of jejunal biopsy. Recent data suggest that the study of serum antigliadin, antireticulin and antiendomysium antibodies may possibly play the role. In this paper the working group on coeliac disease of the Groupe Francophone de Gastroentérologie et Nutrition Pédiatriques expresses its view on the place of the dosages of these antibodies in the diagnosis and follow up procedures of coeliac disease in infants and children. At the present time, although it allows a simplification of the procedures, these dosages are presently not sufficiently reliable to serve as a substitute of jejunal biopsy.

Autoantibodies↗
PubMed1993

Structural and functional requirements for the chromatin transition at the PHO5 promoter in Saccharomyces cerevisiae upon PHO5 activation.

The PHO5 promoter from Saccharomyces cerevisiae can exist in two chromatin configurations depending on its state of activity. In the repressed promoter a short hypersensitive site containing a binding site for the transcription factor PHO4 is flanked by specifically positioned nucleosomes. After induction two nucleosomes upstream and two downstream of the hypersensitive site are disrupted, and the entire promoter becomes accessible. We have investigated mechanisms responsible for setting up the structure of the repressed state and for the transition. Episomal centromeric plasmids bearing the PHO5 promoter show the same chromatin structure as the endogenous chromosomal copy arguing that the chromosomal context is not essential and that the nucleosomal organization is not set up from a distance. Deleting most of the hypersensitive region including the PHO4 binding site also leaves the positioning of the adjacent nucleosomes in the repressed promoter unchanged indicating that histone-DNA interactions play an important role in setting up nucleosome positions. However, when half of the DNA of a nucleosome is deleted a new nucleosome forms at the same location with respect to the neighboring nucleosome indicating that boundary effects also contribute to nucleosome positioning in the native promoter. Disruption of the nucleosomes under activating conditions is shown to require interaction of PHO4 with its binding site located within the hypersensitive region. This disruption takes place also in two independent constructs in which the TATA box had been deleted and as a result the gene was not transcribed. This result shows for the first time that the generation of active chromatin at a regulated promoter is not the result of gene expression but occurs prior to transcription.

Base Sequence↗