Search PubMed⌕ Search

Biomedical subjects

J Schmitz

Publications and source records attributed to J Schmitz.

At least 109 records · Page 6Linked to original sources
PubMed1996

Absence of primary association between DM gene polymorphism and insulin-dependent diabetes mellitus or celiac disease.

The DMA and DMB genes encode class II-like heterodimetric molecules located in a specialized endocytic compartment, where they facilitate efficient loading of antigenic peptides on HLA class II molecules. Both genes are located within the MHC class II region and present a limited allelic polymorphism. Here we report the distribution of DM alleles in a group of 75 IDDM patients, 72 CD patients, and 162 random controls. We found a pronounced decreased frequency of DMA*0102 in both patient groups relative to controls. This difference was, however, mainly secondary to a strong negative linkage disequilibrium (LD) between this allele and the IDDM and CD-associated DRB1*03 allele. The DMB phenotype frequencies were similar in CD patients and controls. By contrast, we observed a decreased frequency of DMB*0101 and an increased frequency of DMB*0102 and DMB*0104 in IDDM patients. These differences disappeared when matching individuals for DRB1*03 or DRB1*04 alleles, which was in accordance with strong negative LD between DMB*0101 and DRB1*04 or DQB1*0302 alleles, and positive LD between DMB*0104 and DQB1*0201. Our data suggest that the apparent associations of IDDM or CD with given DM alleles are mostly secondary to primary associations with alleles at the DRB and DQB loci.

Celiac Disease↗
PubMed1996

[Dermatitis herpetiformis occuring in patients with celiac disease in childhood].

BACKGROUND: Dermatitis herpetiformis (DH) is a chronic papulovesicular immune-mediated disorder associated with gluten-sensitive enteropathy. We report eight cases in which DH appeared many years after celiac disease (CD) in child. PATIENTS AND METHODS: The diagnosis of CD was based on histological features of total or subtotal villous atrophy, full remission after withdrawal of gluten from the diet, and eventually circulating antibodies (IgA gliadin, antireticulin and antiendomysium) at the time of diagnosis and their disappearance under gluten-free diet. The diagnosis of DH was made from clinical findings, histological examination of the involved skin and direct immunofluorescence microscopy of normal or perilesional skin. HLA class II typing was performed in five patients. DRB1, DQA1, DQB1 and DBP1 alleles were studied. RESULTS: DH appeared between 3 and 22 years after the initial diagnosis of CD. Five patients did not show at that time any digestive symptoms. In three cases, a break in the gluten-free diet or a recent revival of the normal diet preceded the rash. In only one case, DH appeared while the patient was under gluten-free diet. In three patients, the rash appeared many years after the gluten-free diet had been stopped. Phenotype DR3 and/or DR7 of the celiac disease could be found in four of the five patients studied; three of them were found to bear DQW2. The DR2 allele was not found in any of the five tested patients. DISCUSSION: These eight cases illustrate the absence of precise nosological barrier between gluten-sensitive enteropathy of the DH and that observed in CD. The presence of the DR7 allele, and especially the absence of the DR2 allele, could explain the particularly severe and symptomatic course of the enteropathy in these patients. The delay in the appearance of DH, after a very variable period of normal diet, could correspond to the necessary time for progressive accumulation of IgA (or immune complex IgA-gluten) in the skin after a digestive sensitization to gluten. The preventive role of gluten-free diet is thus probable. CONCLUSION: CD and DH likely correspond to two different stages of the same disease, thus requiring a prolonged follow-up of both digestive and skin tissues. Long-term eviction of gluten to prevent eventual DH must be balanced with the demand and the cost of such a diet.

Celiac Disease↗
PubMed1996

[Sleeping position, prevention of sudden death syndrome and gastroesophageal reflux].

Based on results of epidemiological studies, dorsal or lateral sleeping positions are now recommanded in the prevention of sudden infant death syndrome (SIDS). This raises an ethical question about the attitude towards the ventral positioning therapy for gastroesophageal reflux (GOR). The consensus conference considers that the ventral position should only be recommanded in GOR when the benefit appears to outweigh the risk of SIDS that it induces. The conference proposes that for infants with simple uncomplicated reflux, sleeping in the prone position should not be introduced in the first line treatment. Prone positioning should be restricted to complicated cases resistant to dietary and medical measures.

Gastroesophageal Reflux↗
PubMed1996

North American Multicenter Study on flow cytometric enumeration of CD34+ hematopoietic stem cells.

Transplant centers often rely on CD34+ cell quantitation by flow cytometry to ensure adequacy of hematopoietic progenitor cell collection. Because of variation in interpretation, a lack of interlaboratory proficiency studies, and no generally accepted methodology, comparison of CD34 data from site to site is difficult. Twenty-one samples from marrow and peripheral blood stem cell collections were shipped to 10 participating North American laboratories for analysis. Duplicate samples were included to assess reproducibility. Participants were surveyed for methodology. Three centers had previously attempted to standardize their methodology among themselves. The variability observed in the CD34 values ranged from a max/min. reported value per sample of 2.9 to 749 (median 76). Exclusion of two outlying sites reduced the variability of results to 1.2 to 27 (median 3.1). Variation among the three standardized sites ranged from 1.2 to 4.4 (median 1.6). Overall reproducibility (excluding the outlying sites B and G) ranged from a minimum of 0-16.5 (percent mean difference) for site C to a maximum of 4.1-133 for site H. Strategies for gating were found to largely influence results. We observed an alarming variation among the CD34 cell counts reported from different laboratories. Standardization substantially reduced observed variation. The need for standardized methodology, reporting, quality control, and proficiency testing is underscored by these findings.

Antigens, CD34↗
PubMed1996

Magnetic resonance imaging for diagnosis of Shwachman's syndrome.

Shwachman's syndrome is a rare disease characterized by the association of chronic diarrhea due to exocrine pancreatic insufficiency, metaphyseal dysostosis, and neutropenia. The diagnosis requires demonstration of lipomatosis, or fatty replacement of the pancreas, which is the typical pathological feature of the disease. Magnetic resonance imaging (MRI) was performed in 13 patients with exocrine pancreatic insufficiency, 7 with Shwachman's syndrome, 2 with Pearson's syndrome, 1 with normal sweat test later diagnosed as cystic fibrosis, and 3 without identified syndrome, and in 7 control children. Ultrasonography in the patients did not differentiate between atrophy and lipomatosis and could not be performed in 3. MRI visualized the pancreas in all. The same image was noted in all patients with Shwachman's syndrome with a normal-sized or enlarged pancreas, a hyperintense signal on T1- and T2-weighted image, and a null signal on short time inversion recovery (STIR)-weighted image, characteristic of fat. In all other patients, the findings were very different: The pancreas was a small structure surrounded with fat. In 1 patient without identified syndrome, the pancreas appeared to be partially replaced with fat. MRI is an excellent imaging technique to correlate the nature of a tissue and its radiological representation, especially fat, which gives a very typical signal. In our brief series of patients with Shwachman's syndrome, MRI had 100% positive predictive value in demonstrating lipomatosis. In atypical cases of pancreatic insufficiency in which some of the clinical features of Shwachman's syndrome are absent. MRI is an invaluable aid in the diagnostic procedure.

Adolescent↗
PubMed1996

Vitamin D regulation of metalloproteinase activity in matrix vesicles.

Matrix vesicles (MVs) are enriched in matrix metalloproteinases (MMPs) capable of degrading proteoglycans. The aim of the present study was to identify which MMPs are present in MVs and determine whether these MMPs are regulated by 1,25-(OH)2D3 [1,25] and 24,25-(OH)2D3 [24,25]. To do this, growth zone (GC) and resting zone (RC) chondrocytes were isolated from rate costochondral cartilage and placed into culture. At confluence, GCs were treated with 1,25 and RCs with 24,25 for 24 hours. MVs, plasma membranes (PMs), and conditioned media were then collected from the cultures. RTPCR demonstrated the presence of mRNA for stromelysin-1 and 72 kDa gelatinase in both RCs and GCs, Casein zymography revealed activity at M(r) 48 and 28 kDa in MV, but not PM or conditioned media; Western analysis confirmed that this activity was stromelysin-1. Gelatinolytic activity, at low levels, was also found in MVs, but not PMs or conditioned media. When enzyme activity was measured using a proteoglycan bead assay, it was found that both GCs and RCs produced MVs and PMs containing neutral metalloproteinase. Both cells also produced MVs and PMs containing plasminogen activator. The addition of 1,25 to GCs caused a significant 4- to 5-fold increase in metalloproteinase activity in MVs, but not PMs. In contrast, MVs from cultures of RCs treated with 24,25 contained decreased metalloproteinase activity; enzyme activity in PMs was unaffected by 24,25. Plasminogen activator in MVs from RC was increased by treatment with 24,25, while MV enzyme activity was decreased after treatment of GC cultures with 1,25. This study shows that both RCs and GCs produce stromelysin-1 and 72 kDa gelatinase and that these enzymes are preferentially localized in MVs. Further, MMP and plasminogen activator activities in MVs and PMs are regulated by vitamin D metabolites.

24,25-Dihydroxyvitamin D 3↗
PubMed1996

Is celiac disease a lifelong disorder?

That celiac disease is a lifelong disorder was suggested by clinical case records and was considered to have been demonstrated through the widespread use of intestinal biopsies by the end of the 1950s. It was clear that the mucosal lesions observed in children and adults were identical and responded similarly to gluten withdrawal. In fact, in 1970 the European Society for Paediatric Gastroenterology and Nutrition instituted the practice of a challenge after diagnosis. A relapse of clinical symptoms and of the intestinal lesions after gluten was reintroduced into the diet demonstrated the "permanent" nature of sensitivity to gluten in children with celiac disease. Twenty-five years later, the permanence of the sensitivity of the intestinal mucosa to gluten is again a matter of debate. Several lines of evidence, gathered during recent years, show that celiac disease is not always a lifelong condition. First, the long-term follow-up of children with proven celiac disease shows that 10% to 20% of them become "tolerant" (defined on clinical, biological and histologic grounds) to gluten during adolescence. Second, it has also been shown, in individual cases, that the mucosal lesions typical of the disease may appear during adulthood. Our increasing knowledge of the long-term evolution of the disease suggests that celiac disease develops and, in some cases, fades in a predisposed group of people with intestinal sensitivity to gluten, which is probably a common condition. The factors leading to the appearance or disappearance of the disease, however, are still unknown.

Adolescent↗
PubMed1995

Investigations on autologous T-cells for adoptive immunotherapy of AIDS.

We report on the preclinical results of an immunotherapeutic approach of AIDS mediated by ex vivo propagated CD4+ and CD8+ T-cells. A mean yield of 6.23 x 10(9) lymphocytes, containing 1.82 x 10(9) CD4+, 3.23 x 10(9) CD8+ T-lymphocytes and 8.39 x 10(6) CD34+ peripheral blood progenitor cells (PBPC) were be obtained by continuous flow cytapheresis (CFC) in 15 asymptomatic HIV infected patients (CD4-count > 350/mm3). The CD4/CD8 ratio (mean: 0.53, SD: +/- 0.15) in the cell concentrates reflected the distribution of the circulating lymphocyte subsets in vivo. Absolute lymphocyte counts decreased at a mean of 404/microliter (25%) immediately after CFC but were replaced from the extravascular pool within one hour. Neither the CD4/CD8 ratio nor p24-antigen and neopterin levels did change significantly after cell separation. No alteration of the number of proviral DNA copies (1/10(3)-1/10(6)) could be detected in peripheral T-helper cells by semiquantitative PCR after lymphapheresis. Cells were cryopreserved in liquid nitrogen without substantial loss of viability or function. Ex vivo propagation of T-cells in a strictly autologous manner in the presence of PHA + IL-2 for 14d resulted in a 50-fold expansion rate (140-fold in healthy controls, p < 0.001). Viral replication could be controlled but not completely eliminated by cocultivation with autologous CD8+ T-lymphocytes as measured by limiting dilution nested PCR (NPCR). The expanded cells showed the typical phenotype of highly activated memory type T-lymphocytes (CD3+ CD45RO+ CD25+ HLA-DR+). The distribution of CD4+ and CD8+ T-cells did not reveal significant changes before and after culture indicating that both subsets were equally expanded. Functionally important membrane or intracellular epitopes which were found to be decreased in HIV infected subjects (CD7, CD55, CD59) before culture were reconstituted after ex vivo propagation of T-cells. The functional importance of the up-regulation of complement regulating epitopes (CD55, CD59) after culture could be proven by a significant inhibition of cytolysis of T-cells in the presence of autologous complement. The majority (75%) of expanded CD8+ T-cells stained positive with mAb TIA-1 which is directed to intracellular granules within cytotoxic T-cells. Furthermore, programmed cell death of expanded T-cells could be prevented by cocultivation with fibroblasts which are believed to secrete a cytokine pattern preventing activated T-cells from apoptosis after withdrawal of IL-2 and other stimuli.(ABSTRACT TRUNCATED AT 400 WORDS)

AIDS-Related Opportunistic Infections↗
PubMed1995

Fluoxetine is ineffective for treatment of cocaine dependence or concurrent opiate and cocaine dependence: two placebo-controlled double-blind trials.

Cocaine dependence has proved difficult to treat, whether occurring alone or in combination with opiate dependence. No medication has been demonstrated to be uniquely effective. Fluoxetine was examined as a candidate in two randomized, double-blind, placebo-controlled trials, one with cocaine-dependent patients (study 1) and the other with patients both cocaine and opiate dependent (study 2). It was selected for known specific action, antidepressant effects, minimum side effects, and data showing reduced cocaine effect and self-administration. Clinic visit frequency requirement, a variable with implications for treatment and cost, was also examined in study 1. A total of 228 patients in study 1 and 21 patients in study 2 completed consent and intake procedures. Patients with serious medical or DSM-III-R diagnoses other than cocaine dependence (study 1) or opiate and cocaine dependence (study 2) were excluded. Study 1 patients were assigned to one of two visit frequency schedules (2 or 5 days/week) and one of three medication doses (0, 20, or 40 mg of fluoxetine/day). Study 2 patients received placebo or 20 mg of fluoxetine and 65 to 80 mg of methadone and attended the clinic 5 days/week. All patients participated in individual therapy sessions. Urine screens were conducted twice weekly. A fluoxetine dose response relationship emerged in study 1 for retention with groups from best to worst being placebo, 20 mg, and 40 mg. Dose effect order was the same for both visit conditions. Cocaine use persisted in all groups. The two visits/week condition was correlated with better retention than the five visits/week condition. A significant interaction emerged between intake urine and visit frequency; patients with benzoylecognine screens at intake used cocaine significantly less in the 5 days/week condition, while exhibiting no reduction in the 2 days/week condition. Patients cocaine positive at intake were better retained with infrequent visits. In study 2, a transient reduction in benzoylecognine-positive drug screens emerged for the fluoxetine group. These complementary studies demonstrate that fluoxetine is ineffective in reducing cocaine use or craving. Study 1 also points to setting conditions modulating treatment outcome.

Adult↗
PubMed1995

Antibody-dependent complement-mediated cytotoxicity in sera from patients with HIV-1 infection is controlled by CD55 and CD59.

Various immune mechanisms have been reported to contribute to the progressive destruction of Th cells in HIV-1-infected patients. Among these, complement mediated lysis of infected cells has been suggested. An increased sensitivity of lymphocytes from HIV-1-infected patients to lysis by monoclonal antibodies directed to MHC class I antigen and complement has been directly correlated with a decreased expression of the decay accelerating factor (CD55). It also has been reported that the expression of the membrane inhibitor of reactive lysis (CD59) is decreased during HIV-1 infection. We examined the effect of antibodies in the serum of HIV-1-positive individuals and normal human serum (NHS) as source of complement on several HIV-1-infected cell lines differing in their expression of CD55 and CD59. When HIV-1-infected target cells without membrane expression of CD55 and CD59 were used, a highly significant cytotoxic effect was observed in the presence of heat inactivated anti-HIV-1-positive sera and NHS, while heat-inactivated anti-HIV-1-negative sera and NHS were unable to induce cytolysis. Similar results were obtained using purified IgG isolated from HIV-1-positive sera and either NHS or guinea pig serum as source of complement. Lysis of HIV-1-infected cells correlated with expression of viral antigens on the cell surface. HIV-1-infected CD55 and CD59 positive target cells showed specific lysis, when the function of these molecules was abrogated by blocking antibodies to CD55 and CD59. The finding of anti-HIV-1-specific cytotoxic antibodies in sera from HIV-1-infected patients should be considered in the pathogenesis of the HIV-1-infection.

Acquired Immunodeficiency Syndrome↗
PubMed1995

Rhythmic patterns in the thoracic nerve cord of the stick insect induced by pilocarpine

Bath application of the muscarinic agonist pilocarpine onto the deafferented stick insect thoracic nerve cord induced long-lasting rhythmic activity in leg motoneurones. Rhythmicity was induced at concentrations as low as 1x10(-4) mol l-1 pilocarpine. The most stable rhythms were reliably elicited at concentrations from 2x10(-3) mol l-1 to 5x10(-3) mol l-1. Rhythmicity could be completely abolished by application of atropine. The rhythm in antagonistic motoneurone pools of the three proximal leg joints, the subcoxal, the coxo-trochanteral (CT) and the femoro-tibial (FT), was strictly alternating. In the subcoxal motoneurones, the rhythm was characterised by the retractor burst duration being correlated with cycle period, whereas the protractor burst duration was almost independent of it. The cycle periods of the rhythms in the subcoxal and CT motoneurone pools were in a similar range for a given preparation. In contrast, the rhythm exhibited by motoneurones supplying the FT joint often had about half the duration. The pilocarpine-induced rhythm was generated independently in each hemiganglion. There was no strict intersegmental coupling, although the protractor motoneurone pools of the three thoracic ganglia tended to be active in phase. There was no stereotyped cycle-to-cycle coupling in the activities of the motoneurone pools of the subcoxal joint, the CT joint and the FT joint in an isolated mesothoracic ganglion. However, three distinct 'spontaneous, recurrent patterns' (SRPs) of motoneuronal activity were reliably generated. Within each pattern, there was strong coupling of the activity of the motoneurone pools. The SRPs resembled the motor output during step-phase transitions in walking: for example, the most often generated SRP (SRP1) was exclusively exhibited coincident with a burst of the fast depressor trochanteris motoneurone. During this burst, there was a switch from subcoxal protractor to retractor activity after a constant latency. The activity of the FT joint extensor motoneurones was strongly decreased during SRP1. SRP1 thus qualitatively resembled the motoneuronal activity during the transition from swing to stance of the middle legs in forward walking. Hence, we refer to SRPs as 'fictive step-phase transitions'. In intact, restrained animals, application of pilocarpine also induced alternating activity in antagonistic motoneurone pools supplying the proximal leg joints. However, there were marked differences from the deafferented preparation. For example, SRP1 was not generated in the latter situation. However, if the ipsilateral main leg nerve was cut, SRP1s reliably occurred. Our results on the rhythmicity in leg motoneurone pools of deafferented preparations demonstrate central coupling in the activity of the leg motoneurones that might be incorporated into the generation of locomotion in vivo.

Journal Article↗
PubMed1995

Histamine-induced itch and alloknesis (itchy skin) in atopic eczema patients and controls.

Alloknesis ("itchy skin") after histamine iontophoresis was studied together with itch sensations and skin reactions in 19 atopic eczema patients and 20 controls at the forearm and at the scapular area. Compared to controls, atopic eczema patients showed significantly reduced alloknesis or total lack of it in the area around a skin site to which histamine had been iontophoretically applied, although histamine elicited itching in most patients. As previously demonstrated, patients with atopic eczema also developed significantly smaller flares. However, covariance analysis revealed that the smaller alloknesis areas in atopic patients were not statistically related to the smaller flares. Our results suggest that in atopic eczema a diminished responsiveness of primary afferent nerves to histamine is not compensated by a higher central nervous sensitivity reflected in more vivid alloknesis responses to histamine. Therefore, we conclude that histamine is probably not the key factor of the spontaneous itch experienced by patients with atopic eczema.

Administration, Cutaneous↗
PubMed1994

A nucleosome precludes binding of the transcription factor Pho4 in vivo to a critical target site in the PHO5 promoter.

Activation of the Saccharomyces cerevisiae PHO5 gene by phosphate starvation is accompanied by the disappearance of two pairs of positioned nucleosomes that flank a short hypersensitive region in the promoter. The transcription factor Pho4 is the key regulator of this transition. By in vitro footprinting it was previously shown that there is a low affinity site (UASp1) which is contained in the short hypersensitive region in the inactive promoter, and a high affinity site (UASp2) which is located in the adjacent nucleosome. To investigate the interplay between nucleosomes and Pho4, we have performed in vivo footprinting experiments with dimethylsulfate. Pho4 was found to bind to both sites in the active promoter. In contrast, it binds to neither site in the repressed promoter. Lack of binding under repressing conditions is largely due to the low affinity of Pho4 for its binding sites under these conditions. Despite the increased affinity of Pho4 for its target sites under activating conditions, binding to UASp2 is prevented by the presence of the nucleosome and can only occur after prior disruption of this nucleosome in a process that requires UASp1. Protection of the PHO5 UASp2 by the nucleosome is not absolute, however, since overexpression of Pho4 can disrupt this nucleosome even when UASp1 is deleted. Also under these conditions, with only UASp2 present, all four nucleosomes at the PHO5 promoter are disrupted, whereas no chromatin change at all is observed when both UAS elements are destroyed.

Allosteric Regulation↗
PubMed1994

The transactivation domain of Pho4 is required for nucleosome disruption at the PHO5 promoter.

The chromatin structure of the PHO5 promoter is disrupted when the promoter is derepressed by phosphate starvation. The transactivator, Pho4, is primarily responsible for this change. We have used deletion mutations of Pho4 in order to determine which protein domains are involved in nucleosome dissolution. Our results show that the DNA binding domain by itself is not sufficient to trigger chromatin disruption, even when overexpressed. In vivo footprinting reveals that Pho4 derivatives lacking the N-terminal activation domain can bind to UASp1, which resides in a constitutively nucleosome-free region, but not to UASp2, which lies within a nucleosome in the repressed PHO5 promoter. The acidic activation domain of Pho4 appears to be involved in nucleosome disruption. Substitution of the native transactivation domain of Pho4 with that from VP16 results in substantial chromatin disruption. In every case, the ability of the Pho4 mutants to activate transcription correlates with their ability to disrupt nucleosome structure in the PHO5 promoter. Therefore, we conclude that the Pho4 activation domain has at least two roles: (i) to trigger disruption of nucleosome structure over the promoter, thereby facilitating the binding of transcription factors, and (ii) to interact with the transcriptional apparatus at the proximal promoter.

Amino Acid Sequence↗