Human immunodeficiency virus infection presenting with lymphoepithelial cysts in a six-year-old child.
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Biomedical subjects
Publications and source records attributed to M Mayer.
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BACKGROUND: Gliadin amino acid sequence(s) responsible for toxicity in susceptible individuals have not been fully elucidated. Previous in vitro studies have suggested the presence of active sequences in the NH(2)-terminal part of the A-gliadin molecule. In this paper the in vitro activity of A-gliadin synthetic peptides 31-55, 31-43, and 44-55 has been investigated. METHODS: Organ culture of jejunal mucosa from untreated and treated coeliac patients was used. In the first system enterocyte height was used as a measure of peptide toxicity; in the second system evidence of activated mucosal cell-mediated immune response was sought. RESULTS: Peptides 31-55 and 31-43 were active on untreated coeliac mucosa at a concentration of 0.5 mg/ml and peptide 44-55 only at a concentration of 3 mg/ml. In in vitro-cultured treated coeliac mucosa peptides 31-55 and 31-43 at 1 mg/ml and peptide 44-55 at 3 mg/ml were able to induce enhanced epithelial expression of HLA-DR and 4F2 molecules and the appearance of CD25 positive cells. CONCLUSIONS: Our results suggest that 31-43 and 44-55 A-gliadin peptides are both active, even if to different extents. In vitro systems remain essential tools to screen material to be subsequently tested in vivo.
Laboratory cost management deals with the economical use of laboratory resources such as capital, equipment and manpower. Cost analysis is a tool for cost management, by means of which the laboratory manager can properly set priorities, choose appropriate test procedures, set personnel policies and make better investments of his resources. This article sets out some important aspects of cost analysis, such as the construction of cost curves, the factors that enter into cost analysis, the context in which cost analysis is used, and the limitations of this type of analysis.
OBJECTIVE: To assess the potential involvement of cytokines and nitrites in the hyperpermeability characterizing the ovarian hyperstimulation syndrome (OHSS). DESIGN: A controlled clinical study comparing peritoneal fluid (PF) from patients with severe OHSS and from non-OHSS controls. SETTING: Women hospitalized with severe OHSS in three tertiary medical centers. PATIENTS: Twelve patients with severe OHSS necessitating paracentesis and 20 non-OHSS controls. INTERVENTIONS: The criteria for ultrasound-guided paracentesis were tense ascites, hydrothorax, hemoconcentration, or oliguria. MAIN OUTCOME MEASURES: Interleukin (IL) 1 beta IL-1 receptor agonist, IL-2, IL-6, IL-8, and tumor necrosis factor alpha (TNF alpha) levels in PF were assayed by ELISA; nitrites were measured by the "Griess" reaction. Estradiol and P were determined by RIA. RESULTS: Ovarian hyperstimulation syndrome patients had significantly higher PF IL-6 (3,523 versus 30 pg/mL), TNF alpha (14 versus 4.2 pg/mL), and IL-8 (1,695 versus 900 pg/mL). In the serum, only IL-6 levels were significantly higher (375 versus 11 pg/mL). Conversely, nitrite levels were significantly lower in PF of OHSS patients (0.5 versus 34 nmol/mL). Interleukin 1 levels were higher and IL-1 receptor antagonist levels were lower in OHSS patients, suggesting potentially increased biologic potency of IL-1. CONCLUSION: These findings suggest that these substances could be involved in mediating the capillary hyperpermeability characterizing this syndrome.
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During the anticipation of a stimulus that induces a predetermined pattern of behavior, a slowly increasing negative electric potential can be recorded from the human scalp at central and parietal electrodes and has been named contingent negative variation (CNV). We used a simple and a choice reaction time paradigm to investigate premovement potentials in patients with Parkinson's disease (PD) and in normal controls. There was a clear CNV in young subjects whereas it was negligible in the elderly control subjects and absent in the patients. In addition, we found a slowly increasing positive frontal potential. In normals the steepness of this potential decreased with the complexity of the task (simple vs. choice) and with age. This difference was abolished in the patients: If a slowly increasing positivity was observed at all, it was, on average, larger in the choice task. Reaction times of the patients were disproportionally prolonged in the simple compared to the complex task. These findings support the hypothesis that storing or initiating a simple preprogrammed motor response is more impaired in PD than selecting and initiating a motor response of a more complex task. The electrophysiological recordings suggest that impaired activation of the frontal lobes may be responsible for this deficit.
Mirror movements (MMs) are involuntary movements executed on one side of the body during voluntary movements of the contralateral homologous body parts which may abnormally persist into adulthood. In 6 subjects affected by persistent MM with autosomal dominant inheritance, movement-related cortical potentials (MRCPs) during self-paced, voluntary extensions of either the left or right middle finger were recorded from 30 EEG electrodes simultaneously with the electromyogram (EMG) of both extensor digitorum communis muscles. The negative potentials before and during EMG onset were evaluated statistically for the two electrodes next to the cortical hand areas. A comparison with 7 normal subjects revealed no marked differences for the Bereitschaftspotential (BP) and the negative slope (NS'). Only in the periods around EMG onset (from -50 to +50 msec) a significant difference between both groups was found. The MM subjects showed fairly symmetric potentials over the right and left hemispheres, whereas the potentials of the control subjects were lateralized to the hemisphere contralateral to the intended movement. No difference was found for the amplitude of the maximum negative peak of MRCP following EMG onset. Our data showed no evidence for a different type of movement preparation in MM subjects as compared to normals. We propose that the additional ipsilateral cortical activation around movement onset may be the cortical mechanism, which compensates for abnormal ipsilateral corticospinal pathways in subjects with persistent MM.
Adolescents with celiac disease often fail to adhere to a strict gluten-free diet. The value of endomysial antibodies in assessing the dietary compliance of such adolescents has been assessed in 23 patients divided into four groups according to their daily gluten intake. Serum endomysial antibodies were absent in all subjects on a gluten-free diet and consistently present in those ingesting > 2 g/day of gluten. Only one of six and three of six teenagers with celiac disease with an intake of < 0.5 and 0.5-2 g/day, respectively, had endomysial antibodies in their serum, despite the presence in three of six and five of six of significant changes in the mucosal architecture, as shown by computerized morphometry of jejunal biopsies. In conclusion, endomysial antibodies cannot be considered a valid marker for slight dietary transgressions.
Amino acid methyl dithioesters may be coupled in the presence of DMAP and salts to a growing peptide chain on a polymeric resin with high coupling yields and low racemization.
The aim of this study was to compare a non-invasive test of small bowel permeability with a more invasive approach involving endoscopy, mucosal biopsy, and oesophageal pH monitoring for rapidly differentiating gastro-oesophageal reflux (GOR) and cows' milk intolerance in 25 infants with persistent vomiting. Each subject underwent a cellobiose/mannitol permeability study, upper gastrointestinal endoscopy with oesophageal and small bowel biopsies, and a 24 hour pH study. Reflux disease and/or cows' milk intolerance was responsible for vomiting in 24 (96%) of the subjects. Sixteen (64%) of the infants had GOR alone, four (16%) had GOR and cows' milk intolerance, and four (16%) had cows' milk intolerance alone. Morphometric analysis of small bowel biopsies was abnormal in 19% of the patients with GOR alone and in 67% with cows' milk intolerance with or without GOR. The permeability test was abnormal in only 6% of the patients with GOR but in 100% with GOR and cows' milk intolerance and in 100% with cows' milk intolerance alone. The non-invasive permeability study aimed at rapid determination of cows' milk intolerance should pre-empt a more invasive approach in the evaluation of infants with persistent vomiting.
In continuation of earlier observations on the involvement of interleukin-1 (IL-1) in ovarian function, we examined the ability of IL-1 to modulate plasminogen activator (PA) activity and prostaglandin (PG) synthesis in human granulosa lutein cells (GLCs). Toward this goal, GLCs were obtained from women undergoing in vitro fertilization, preincubated with 10% fetal calf serum for 48 h, and subsequently cultured for 48 h in serum-free media in the absence or presence of IL-1 beta (10 ng/mL). Cellular PA activity was measured by plasminogen-dependent cleavage of the chromogenic substrate H-D-valyl-L-leucyl-L-lysine-p-nitroanilide (S-2251). Prostaglandin E (PGE) levels were assayed by conventional RIA. Exposure of GLCs to IL-1 resulted in a 50% increase in PGE production, a 33% suppression of PA activity, and a 75% increase in the ability of the corresponding conditioned media to inhibit exogenous urokinase activity. The inhibitory capacity was attributable to an IL-1-mediated increase in PA inhibitor type-1 (PAI-1) production, inasmuch as urokinase inhibition could be abolished by the administration of a polyclonal antihuman PAI-1 immunoglobulin G. IL-1 treatment had no effect on plasmin or trypsin inhibition. Exposure of GLCs to IL-1 receptor antagonist abolished the ability of IL-1 to enhance PA inhibitory activity and PGE production, thereby establishing specific IL-1 receptor-mediated effects. The ability of IL-1 to suppress PA activity and to produce PAI-1 persisted in the presence of indomethacin, a potent inhibitor of PG synthesis. Likewise, transforming growth factor-beta 1 suppressed the ability of IL-1 to stimulate PGE production without affecting the IL-1-induced effects on the PA system. The present findings suggest a pluripotent response of GLCs to IL-1, characterized by the induction of PAI-1 and the suppression of PA occurring concurrent with, but independent of, PG production. These observations support the potential involvement of IL-1 in the regulation of human ovulatory processes.
Prostaglandins (PGs) play a major role during implantation and labor, and their level is regulated by various cytokines. Interleukin-1 (IL-1) is a known mediator of prostaglandin E (PGE) production in various cell types, including endothelial, amniotic, and endometrial cells; however, its role in the regulation of PGE production in the trophoblast cells is yet unknown. As IL-1 and PGE are both known to be synthesized in the human trophoblast cells, we examined the possibility that IL-1 regulates PG production in human trophoblast cells. To this end, use was made of first and third trimester trophoblast cells, obtained from first trimester terminations of pregnancies and elective cesarean sections. The trophoblast cells were separated by trypsin degradation and fractionation on Percoll gradients, and cultured for 18 h under serum-free conditions in the absence or presence of IL-1 (10 ng/mL). IL-1 induced a 5-fold increase in PGE production, a response that was cell density, time, and dose dependent. IL-1-induced PGE biosynthesis was prevented in the presence of either IL-1 receptor antagonist or the soluble IL-1 receptor, suggesting a receptor-mediated response. Significantly, de novo production of PGE by trophoblast cells in the absence of IL-1 was also markedly (50%) reduced by either the IL-1 receptor antagonist or the soluble IL-1 receptor, further supporting the notion that IL-1 is involved in PGE synthesis even under basal conditions. Transforming growth factor-beta 1, a putative modulator of the effects of IL-1, significantly attenuated IL-1-stimulated PGE production, supporting the possibility that transforming growth factor-beta 1 may serve as a regulator of the effects of IL-1 in trophoblast cells. These observations suggest a pivotal role of IL-1 in the regulation of PGE economy by trophoblast cells. As trophoblast cells are in intimate contact with maternal cells, understanding the regulation of PGE levels may explain crucial processes at the feto-maternal interface, including implantation of the developing blastocyst, immunosurveilance, and the initiation of labor.
Clinical records of all patients treated from 1983 to 1991 in a university clinic for lang-term-use of benzodiazepines were examined. Daily intake of benzodiazepines began in 80% immediately after the first prescription. At the time of admission, 34% reported intake of more than 3 DDD, i.e. more than 30 mg of diazepam. In patients 70%, additional abuse of alcohol and/or other psychotropic substances was established. Benzodiazepines were the first substances abused in 49%. The diagnosis of abuse or dependency was made in 65% before admission. Symptoms of organic brain syndrome were described in 30% of all records. Symptom leading to first benzodiazepine intake were somatic complaints (40%), depressed mood (39%), insomnia (37% and anxiety (24%). Between first intake and admission, there was a significant increase in patients with somatic complaints, depressed mood and anxiety. After detocification, symptoms leading to admission improved in 80% of all patients.
We describe two members of a German family with cerebral autosomal dominant arteriopathy (CADASIL), which is characterized by recurrent subcortical ischemic strokes, mild dementia and leukoencephalopathy. The clinical features of the disease are suggestive of Binswanger's subcortical arteriosclerotic encephalopathy. However, it differs by the lack of hypertension and familial aggregation with autosomal dominant inheritance. Magnetic resonance imaging (MRI) of the brain shows subcortical ischemic infarcts affecting the periventricular white matter, the basal ganglia and the brain stem. On T2-weighted imaging, areas of hyperintensity were found in the white matter of both cerebral hemispheres with preponderance of frontal and anterotemporal regions. We assume that the underlying disease in this family is CADASIL with subcortical infarcts and leukoencephalopathy. The recently assigned disease locus on chromosome 19 was confirmed in this family. A treatment trial with acetylsalicylate was started in the affected members of the family.
The ability of the sugar permeability test to detect minor degrees of mucosal damage is uncertain, particularly in children. This paper reviews experience with the cellobiose/mannitol test at a referral centre of paediatric gastroenterology, relating the results of intestinal permeability to the jejunal morphometry. Two hundred patients underwent the cellobiose/mannitol test at the same time as jejunal biopsy; morphometric analysis of the biopsy specimens was performed by a computerized image analysis system. Increased sugar permeability was revealed in 89%, 80%, 67% and 18% of subjects with subtotal villous atrophy, severe partial villous atrophy, mild partial villous atrophy and normal histological picture, respectively. Nevertheless, once the patients with the most severe changes in their mucosal architecture had been excluded, there was no statistically significant correlation between cellobiose/mannitol ratio and villous and crypt length, villous/crypt ratio and intraepithelial lymphocytes density. The cellobiose/mannitol test is a good indicator of severe mucosal damage; it does not discriminate subjects with minor degrees of mucosal abnormalities, but may give useful indications on the functional state of the jejunal mucosa.
The polymerized beta-lactam antibiotic ampicillin inhibits the proteolytic activity of human plasmin upon 125I-labeled fibrin clots. The inhibition is dose-dependent, with half-maximal inhibition occurring at 1.25 mM of the polymerized antibiotic. Polymerized ampicillin also inhibits binding of plasmin to fibrin, and 38% inhibition of binding occurs at 10 mM of the antibiotic. Furthermore, polymerized ampicillin inhibits the activation of plasminogen by either urokinase-like plasminogen activator (uPA) or tissue type-plasminogen activator (tPA). At 7.5 mM of polymerized ampicillin, the uPA-mediated plasminogen activation is suppressed by 94%, and half-maximal inhibition is obtained at 0.66 mM. The direct activity of uPA on the chromogenic substrate L-pyroglutamyl-glycyl-L-arginine p-nitroanilide hydrochloride (S-2444) is unaffected by polymerized ampicillin levels of up to 10 mM. The inhibitory effects of the polymerized antibiotic on the activation of plasminogen by both uPA and tPA is totally abolished in presence of fibrin. These interactions may serve as a novel model for ligands that enhance the clot-specificity of thrombolytic agents.
We have discovered that N-acetyl-L-cysteine (NAC) protects cells against death induced by exposure to noxious stimuli and against programmed cell death (apoptosis) associated with exposure to inadequate amounts of trophic factors. NAC prevented glutamate-induced death of oligodendrocytes and tumor necrosis factor alpha (TNF-alpha)-induced death of oligodendrocytes and L929 fibroblasts. Moreover, suboptimal doses of NAC plus ciliary neurotrophic factor (which also protects oligodendrocytes against TNF-alpha-mediated killing) acted synergistically to protect oligodendrocytes against TNF-alpha-induced death. Protection against death by growth factor deprivation was provided by the combination of (i) NAC, vitamin C, or Trolox (a water-soluble analogue of vitamin E) with suboptimal concentrations of protein trophic factors, (ii) NAC, vitamin C, or Trolox with progesterone, and (iii) NAC with either vitamin C or Trolox; these latter experiments suggest that the addition of tyrosine kinase stimulators is not required to promote cell survival. In all paradigms, NAC was either equally or more effective than the other compounds examined. In light of the long history of therapeutic application of NAC, we suggest that use of this compound may be of interest in conditions where certain toxin-mediated forms of cell death and/or apoptosis contribute significantly to disease.