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Biomedical subjects

M Stern

Publications and source records attributed to M Stern.

At least 19 recordsLinked to original sources
PubMed1996

The IgA subclass distributions of endomysium and gliadin antibodies in human sera are different.

Subclass distributions of total IgA, IgA gliadin antibodies and IgA endomysium antibodies were investigated in 26 sera of patients with coeliac disease or dermatitis herpetiformis by means of enzyme immunoassay and fluorescence microscopy. Eight-point-three percent of total IgA belonged to the IgA2 subclass. The fraction of IgA2 gliadin antibodies amounted to 30.6% of IgA gliadin antibodies and was significantly different from the proportion of total IgA2. The relative percentage of IgA2 endomysium antibodies was very close to that of total IgA2 in serum (6.2%) and significantly lower than that of IgA2 gliadin antibodies. The results suggest an intestinal origin of gliadin antibodies. Different subclass distribution of IgA endomysium antibodies may be due to extraintestinal production or to the different nature of the endomysium antigen eliciting a more prominent IgA1 response than gliadin.

Antibodies↗
PubMed1996

A neurotransmitter transporter encoded by the Drosophila inebriated gene.

Behavioral and electrophysiological studies on mutants defective in the Drosophila inebriated (ine) gene demonstrated increased excitability of the motor neuron. In this paper, we describe the cloning and sequence analysis of ine. Mutations in ine were localized on cloned DNA by restriction mapping and restriction fragment length polymorphism (RFLP) mapping of ine mutants. DNA from the ine region was then used to isolate an ine cDNA. In situ hybridization of ine transcripts to developing embryos revealed expression of this gene in several cell types, including the posterior hindgut, Malpighian tubules, anal plate, garland cells, and a subset of cells in the central nervous system. The ine cDNA contains an open reading frame of 658 amino acids with a high degree of sequence similarity to members of the Na+/Cl(-)-dependent neurotransmitter transporter family. Members of this family catalyze the rapid reuptake of neurotransmitters released into the synapse and thereby play key roles in controlling neuronal function. We conclude that ine mutations cause increased excitability of the Drosophila motor neuron by causing the defective reuptake of the substrate neurotransmitter of the ine transporter and thus overstimulation of the motor neuron by this neurotransmitter. From this observation comes a unique opportunity to perform a genetic dissection of the regulation of excitability of the Drosophila motor neuron.

Amino Acid Sequence↗
PubMed1996

Peptic-tryptic digests of gliadin: contaminating trypsin but not pepsin interferes with gastrointestinal protein binding characteristics.

For many years, peptic-tryptic digests of gliadin, known as Frazer's fraction III, have been used in investigations of gliadin effects. Potential contamination by the proteases pepsin and trypsin, however, was not considered. To investigate the influence of contaminating proteases on binding of gliadin peptides to rat small intestinal brush border membranes we compared binding characteristics of different gliadin digests. Binding of biotinylated probes was studied in dot blots and Western blots with an enhanced chemiluminescence system. In gliadin peptide preparations only contaminating trypsin, but not pepsin, was detectable by specific antisera. Digestion with insoluble proteases attached to cross-linked beaded agarose yielded gliadin peptides free of contaminating pepsin and trypsin. These peptides bound 30% less to brush border membranes. Using these peptides, there was no trypsin-typical binding pattern to low molecular mass membrane proteins in contrast to peptide preparations which contained contaminating trypsin. In conclusion contaminating trypsin might alter gliadin peptide binding characteristics by direct binding to brush border membranes and by interfering with interactions between gliadin peptides and brush border membranes.

Animals↗
PubMed1996

Prospects for gene therapy in Parkinson's disease.

Numerous advances in in vivo and ex vivo gene-therapy approaches to Parkinson's disease offer promise for direct clinical trials in patients in the next several years. These systems are predicated on introducing gene that encode enzymes responsible for dopamine biosynthesis or neurotrophic factors that may delay nigrostriatal degeneration or facilitate regeneration. We review the current status of experimental approaches to gene therapy for Parkinson's disease. Comparative advantages and disadvantages of each system are enumerated, and preclinical trials of some of the systems are evaluated. Although the specific in vivo or ex vivo methods used for gene transfer into the brain are likely to be supplanted by newer technology over the next decade, the principles and approaches developed in current studies likely will remain the same.

Adenoviridae↗
PubMed1996

Once daily mometasone furoate aqueous nasal spray is as effective as twice daily beclomethasone dipropionate for treating perennial allergic rhinitis patients.

BACKGROUND: Perennial allergic rhinitis is chronic and persistent, may lead to a constellation of secondary complaints including sinusitis, mouth-breathing, and some symptoms resembling a permanent cold, and often requires constant medical intervention. Well-tolerated nasal corticosteroids, alone or in combination with antihistamines, have been found to be very effective in treating this condition. OBJECTIVE: To compare the effectiveness and tolerability of mometasone furoate aqueous suspension, a new once daily nasal spray, to placebo vehicle and to beclomethasone dipropionate, administered twice daily, in patients with perennial allergic rhinitis. METHODS: This was a randomized, double-blind, placebo-controlled, double-dummy, parallel group study, in 427 patients age 12 years and older at 24 centers in Canada and Europe. Patients allergic to at least one perennial allergen, confirmed by medical history, skin testing, and adequate symptomatology were eligible to receive one of the following regimens for 3 months: mometasone furoate, 200 micrograms only daily; beclomethasone dipropionate, 200 micrograms twice daily (400 micrograms total dose); or placebo vehicle control. The primary efficacy variable was the change from baseline in total AM plus PM diary nasal symptom score over the first 15 days of treatment. RESULTS: Three hundred eighty-seven patients were valid for efficacy. For the primary efficacy variable, mometasone furoate was significantly (P < or = .01) more effective than placebo and was indistinguishable from beclomethasone dipropionate. Similar trends were seen among individual symptoms, physician symptom evaluations, and therapeutic response. There was no evidence of tachyphylaxis. All treatments were well tolerated. CONCLUSIONS: Mometasone furoate nasal spray adequately controls symptoms of perennial allergic rhinitis, offers the advantage of once daily treatment, and is well tolerated.

Administration, Intranasal↗
PubMed1996

Mutation of the axonal transport motor kinesin enhances paralytic and suppresses Shaker in Drosophila.

To investigate the possibility that kinesin transports vesicles bearing proteins essential for ion channel activity, the effects of kinesin (Khc) and ion channel mutations were compared in Drosophila using established tests. Our results show that Khc mutations produce defects and genetic interactions characteristic of paralytic (para) and maleless (mle) mutations that cause reduced expression or function of the alpha-subunit of voltage-gated sodium channels. Like para and mle mutations, Khc mutations cause temperature-sensitive (TS) paralysis. When combined with para or mle mutations, Khe mutations cause synthetic lethality and a synergistic enhancement of TS-paralysis. Furthermore, Khc: mutations suppress Shaker and ether-a-go-go mutations that disrupt potassium channel activity. In light of previous physiological tests that show that Khc mutations inhibit compound action potential propagation in segmental nerves, these data indicate that kinesin activity is required for normal inward sodium currents during neuronal action potentials. Tests for phenotypic similarities and genetic interactions between kinesin and sodium/potassium ATPse mutations suggest that impaired kinesin function does not affect the driving force on sodium ions. We hypothesize that a loss of kinesin function inhibits the anterograde axonal transport of vesicles bearing sodium channels.

Animals↗
PubMed1996

Mutations in the Drosophila pushover gene confer increased neuronal excitability and spontaneous synaptic vesicle fusion.

We describe the identification of a gene called pushover (push), which affects both behavior and synaptic transmission at the neuromuscular junction. Adults carrying either of two mutations in push exhibit sluggishness, uncoordination, a defective escape response, and male sterility. Larvae defective in push exhibit increased release of transmitter at the neuromuscular junction. In particular, the frequency of spontaneous transmitter release and the amount of transmitter release evoked by nerve stimulation are each increased two- to threefold in push mutants at the lowest external [Ca2+] tested (0.15 mM). Furthermore, these mutants are more sensitive than wild type to application of the potassium channel-blocking drug quinidine: following quinidine application, push mutants, but not wild-type, display repetitive firing of the motor axon, leading to repetitive muscle postsynaptic potentials. The push gene thus might affect both neuronal excitability and the transmitter release process. Complementation tests and recombinational mapping suggest that the push mutations are allelic to a previously identified P-element-induced mutation, which also causes behavioral abnormalities and male sterility.

Animals↗
PubMed1996

Indirect parameters of pancreatic function in cystic fibrosis (CF) during a controlled double-blind trial of pancreatic supplementation.

During two treatment periods (4 weeks each), serum immunoreactive trypsin (IRT), immunoreactive human lipase in stool (IRL), and chymotrypsin (CT) activity in stool were determined in 16 cystic fibrosis patients and compared with fecal fat excretion (72-h sampling). Fecal fat estimation revealed mild to severe steatorrhea in all 16 patients (X = 13.7 +/- 9.0 g/24 h) in at least one study period. Stool fat excretion was highest in underweight adolescents and adults. Comparison of IRT and IRL with stool fat values showed no significant statistical correlation. IRT values revealed an inverse exponential correlation with age, with a steep decline at the age of 5 years. CT levels were very high in 14 of our 16 patients during supplementation therapy, whereas 2 patients showed subnormal CT values. We conclude that since indirect parameters of pancreatic function do not correlate with stool fat excretion, stool fat remains the best indirect parameter for the assessment of pancreatic insufficiency in cystic fibrosis. Leaving pancreatic enzyme supplementation in cystic fibrosis patients on the basis of normal serum trypsin or fecal lipase values does not appear to be adequate.

Adolescent↗
PubMed1996

Serological screening for coeliac disease: methodological standards and quality control.

To establish methodological standards for serological investigation and screening of coeliac disease, a joint venture has been launched by the European Medical Research Council and the European Society for Paediatric Gastroenterology and Nutrition. Before general screening can be recommended, robust methods and technical standards ought to be introduced. Joint test protocols were defined: an enzyme-linked immunosorbent assay for IgG and IgA gliadin antibodies and an immunofluorescent test for IgA endomysium antibodies. Protocols have now been tested prospectively by one laboratory. Eighty-eight Tuebingen patients were studied (47 coeliac disease on normal diet, 22 coeliac disease on a gluten-free, and 19 disease controls). Single tests did not produce acceptable levels, but combinations of IgA gliadin antibodies and IgA endomysium antibodies showed 98% sensitivity, 100% specificity and 98% predictive efficiency. Only standardized and refereed methods established by ring testing can serve as a reliable basis for serological coeliac screening.

Case-Control Studies↗
PubMed1996

Defective 'gut processing' of gliadin in mice with graft-versus-host enteropathy.

The gut mucosa plays an important role in the induction of oral tolerance. Extending previous observations, we have here shown that serum containing gut-absorbed gliadin induces suppression of the specific systemic immune response in recipient mice parenterally immunized with gliadin. Graft-versus-host reaction (GvHR) has profound effects on the gut mucosa, representing a model of immune-mediated enteropathy. The aim of our work was to investigate the gut handling and processing of gliadin in mice with GvHR. Binding to enterocytes, passage through the epithelium, and ability of the epithelium to convert this antigen into a tolerogenic form were assessed in BDF1 mice weaned on gluten-free diet, 2 weeks after the induction of a semiallogeneic GvHR. Binding of gliadin peptide B3144 to enterocytes was similar in controls and GvHR mice. After feed, serum levels of gliadin were comparable in the two groups of mice, but when serum collected from GvHR mice and containing gut-absorbed gliadin was transferred intraperitoneally into naive recipient mice, this did not induce suppression of the specific immune response. These experiments indicate that during GvHR enteropathy the ability of the intestine to convert gliadin into a tolerogenic form is lost. Defective antigen gut processing may contribute to the observed failure in oral tolerance induction.

Animals↗
PubMed1996

In vitro hydrolysis of gliadin and casein peptides: secondary defect in coeliac disease shown by organ culture.

BACKGROUND: Small-intestinal organ culture was used as an in vitro model of coeliac disease, studying biopsy specimens from patients with coeliac disease, cow's milk allergy, and controls. METHODS: Organ culture incubations were done using the pure gliadin peptide B3144 (amino acid sequences 3-56 of alpha-type gliadins) and a control peptide from casein (amino acid sequences 152-193 of alpha s1-casein). The importance of using negative controls was stressed by non-specific tissue damage. By reversed-phase high-performance liquid chromatography of organ culture supernatants, 27 specimens were further investigated. RESULTS: There was good retrieval of peptide calibration peaks after culture. Qualitative and quantitative evaluation of chromatography runs showed degradation of at least 29% of B3144 and 37% of Cas-P. Normal mucosa (controls and coeliac patients on a gluten-free diet) was able to hydrolyse peptide fractions completely, whereas incubation with damaged mucosa (coeliac disease, cow's milk allergy) left initial peptides. CONCLUSION: It is concluded, using a pure single gliadin peptide, that deficient peptide hydrolysis in coeliac disease was a secondary event.

Adolescent↗
PubMed1996

[Bronchial anastomotic complications after pulmonary transplantation. X-ray computed tomographic evaluation].

PURPOSE: To determine the sensitivity and specificity of CT in depicting bronchial anastomotic complications after lung transplantation. MATERIALS AND METHODS: A retrospective, blinded review of 105 CT scans obtained after single (n = 17) or double (n = 10) lung transplantation in 27 patients was done by two radiologists in consensus. CT images, were analyzed with respect to the status of bronchial anastomoses, with three possible answers given to the readers: normal, dehiscence, or stenosis. CT features were correlated to bronchoscopic and follow-up findings, which were considered as standard of reference. RESULTS: CT had a 60% sensitivity and 98% specificity for the diagnosis of bronchial dehiscence, and 40% and 99% for the diagnosis of anastomotic stenosis. One case of bronchial disruption was diagnosed on CT scan only and subsequently confirmed by repeated bronchoscopy. CONCLUSION: In our study, CT has a low sensitivity but a high specificity in the detection of bronchial anastomotic complications after lung transplantation. However, CT remains useful in some cases, as it can show complications not seen bronchoscopically.

Adult↗
PubMed1996

Human monocyte-derived macrophage phagocytosis of senescent eosinophils undergoing apoptosis. Mediation by alpha v beta 3/CD36/thrombospondin recognition mechanism and lack of phlogistic response.

Eosinophils may mediate tissue injury in a number of allergic diseases. Previously, we reported that eosinophils constitutively undergo apoptosis (programmed cell death) in culture. As this led to phagocytosis of the intact senescent cell by macrophages, we proposed that apoptosis represented an injury-limiting eosinophil disposal mechanism. Ingestion of apoptotic neutrophils by human monocyte-derived macrophages (M phi s) was found to be mediated by adhesive interactions between thrombospondin and the M phi alpha v beta 3 vitronectin receptor integrin and M phi CD36. As this failed to elicit a pro-inflammatory response from M phi s, we sought evidence that this specific, nonphlogistic clearance mechanism may operate in eosinophil disposal. In this study, we found that M phi ingestion of apoptotic eosinophils was specifically inhibited by monoclonal antibodies to M phi alpha v beta 3, CD36, and thrombospondin and by other inhibitors of this recognition mechanism including RGD peptide and amino sugars. Furthermore, not only did M phi ingestion of intact apoptotic eosinophils fail to stimulate release of the phlogistic eicosanoid thromboxane, but there was also a lack of increased release of the pro-inflammatory cytokine granulocyte/macrophage colony-stimulating factor. However, increased release of these mediators was observed when M phi s took up senescent post-apoptotic eosinophils that had been cultured long enough to lose plasma membrane integrity. The data indicate that the nonphlogistic alpha v beta 3/CD36/thrombospondin macrophage recognition mechanism is available for clearance of intact senescent eosinophils undergoing apoptosis. Furthermore, our findings suggest that, by contrast, phagocytosis of post-apoptotic eosinophils may elicit undesirable pro-inflammatory responses.

Amino Sugars↗
PubMed1995

Changes of brain anatomy in patients with posttraumatic stress disorder: a pilot magnetic resonance imaging study.

No abnormalities in magnetic resonance images were recorded in patients with posttraumatic stress disorder other than an increased incidence (50%) of a small cleft in the callosal-septal interface, a cavum of the septum pellucidum. A similar grade of cavum was obtained in 14% of normal volunteers matched for age, socioeconomic background, and military experience. The cavum is believed to have antedated the disorder and is conceived to be a neurodevelopmental aberration. The possibility that the cavum is a marker of vulnerability to stress in psychopathology is discussed.

Adult↗