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Biomedical subjects

K L Reichelt

Publications and source records attributed to K L Reichelt.

At least 19 recordsLinked to original sources

IgA antibodies in Rett syndrome.

The level of IgA antibodies to gluten and gliadin proteins found in grains and to casein found in milk, as well as the level of IgG to gluten and gliadin, have been examined in 23 girls with Rett syndrome and 53 controls. Highly statistically significant increases were found for the Rett population compared to the controls. The reason for this remains unknown, but because IgA antibodies reflect the uptake of proteins and/or epitopes of proteins from the gut, this may be indicative of increased protein uptake.

Adolescent↗

Urinary peptide levels in women with eating disorders. A pilot study.

The aim of this study was to evaluate whether the urinary excretion of low molecular weight peptides is increased in women with a history of anorexia nervosa/self starvation. The study group consisted of 12 women aged 20-38 years who were treated in a specialised day care unit for eating disorders in Stockholm between January and December 1998; the controls were eight women with primary bulimia treated in the same unit (A) and ten healthy women without any eating disorder (B). The chromatographically measured urinary peptide levels in the study group were significantly higher than those in control group A (and B when one highly influential individual with very low peptide excretion in the study group was excluded from the analyses). These findings offer some support to the speculative hypothesis that eating disorder symptoms may be linked to increased levels of neuroactive peptides, although it is necessary to define the peptides further before any definite conclusion can be drawn. Furthermore, the study group was characterised by many interpersonal differences in eating behaviour that could explain the increased urinary peptide levels.

Adult↗

Can the pathophysiology of autism be explained by the nature of the discovered urine peptides?

Opioid peptides derived from food proteins (exorphins) have been found in urine of autistic patients. Based on the work of several groups, we try to show that exorphins and serotonin uptake stimulating factors may explain many of the signs and symptoms seen in autistic disorders. The individual symptoms ought to be explainable by the properties and behavioural effects of the found peptides. The data presented form the basis of an autism model, where we suggest that exorphins and serotonin uptake modulators are key mediators for the development of autism. This may be due to a genetically based peptidase deficiency in at least two or more peptidases and, or of peptidase regulating proteins made manifest by a dietary overload of exorphin precursors such as by increased gut uptake.

Aging↗

A randomised, controlled study of dietary intervention in autistic syndromes.

Impaired social interaction, communication and imaginative skills characterize autistic syndromes. In these syndromes urinary peptide abnormalities, derived from gluten, gliadin, and casein, are reported. They reflect processes with opioid effect. The aim of this single blind study was to evaluate effect of gluten and casein-free diet for children with autistic syndromes and urinary peptide abnormalities. A randomly selected diet and control group with 10 children in each group participated. Observations and tests were done before and after a period of 1 year. The development for the group of children on diet was significantly better than for the controls.

Autistic Disorder↗

Urinary peptides in Rett syndrome.

Rett syndrome is a neuro-developmental disorder related to autistic behavior. Persons with autism have previously been found to have hyperpeptiduria. We here report a significantly higher level of peptides in the first fasting morning urine from 53 girls with Rett syndrome (both classical and congenital) compared with 53 healthy girls. This elevation in urinary peptides was similar to that in 35 girls with infantile autism. As in persons with autism, the individual levels of urinary peptides in the Rett syndrome group varied, and about a fifth were within the normal range. Levels of peptides were lower in girls with classic Rett syndrome than in girls with congenital Rett syndrome. This may be due to different etiological causes or to active and stagnant phases of the disease. Urine from girls with Rett syndrome was found to have higher frequency and higher levels of some urinary peptides that may cause inhibition of brain maturation and epilepsy

Adolescent↗

Reelin gene alleles and haplotypes as a factor predisposing to autistic disorder.

Autistic disorder (MIM 209850) is currently viewed as a neurodevelopmental disease. Reelin plays a pivotal role in the development of laminar structures including the cerebral cortex, hippocampus, cerebellum and of several brainstem nuclei. Neuroanatomical evidence is consistent with Reelin involvement in autistic disorder. In this study, we describe several polymorphisms identified using RNA-SSCP and DNA sequencing. Association and linkage were assessed comparing 95 Italian patients to 186 ethnically-matched controls, and using the transmission/disequilibrium test and haplotype-based haplotype relative risk in 172 complete trios from 165 families collected in Italy and in the USA. Both case-control and family-based analyses yield a significant association between autistic disorder and a polymorphic GGC repeat located immediately 5' of the reelin gene (RELN) ATG initiator codon, as well as with specific haplotypes formed by this polymorphism with two single-base substitutions located in a splice junction in exon 6 and within exon 50. Triplet repeats located in 5' untranslated regions (5'UTRs) are indicative of strong transcriptional regulation. Our findings suggest that longer triplet repeats in the 5'UTR of the RELN gene confer vulnerability to autistic disorder.

Adult↗

Reports on dietary intervention in autistic disorders.

Autism is a developmental disorder for which no cure currently exists. Gluten and/or casein free diet has been implemented to reduce autistic behaviour, in addition to special education, since early in the eighties. Over the last twelve years various studies on this dietary intervention have been published in addition to anecdotal, parental reports. The scientific studies include both groups of participants as well as single cases, and beneficial results are reported in all, but one study. While some studies are based on urinary peptide abnormalities, others are not. The reported results are, however, more or less identical; reduction of autistic behaviour, increased social and communicative skills, and reappearance of autistic traits after the diet has been broken.

Adult↗

No association between the 4g/5G polymorphism of the plasminogen activator inhibitor-1 gene promoter and autistic disorder.

Plasmin, a serine protease, is involved in many physiologically relevant processes, including haemostasis, cellular recruitment during immune response, tumour growth, and also neuronal migration and synaptic remodelling. Both tissue-type and urokinase-type plasminogen activators can be efficiently inhibited by plasminogen activator inhibitor-1 (PAI-1), a protease inhibitor of the serpin family. The human PAI-1 gene is located on chromosome 7q, within or close to a region that has been linked to autism in several linkage studies. Autism seems to be characterized by altered neuronal cytoarchitecture, synaptogenesis and possibly also cellular immune responses. We began addressing the potential involvement of the PAI-1 gene in autistic disorder with this linkage/association study, assessing transmission patterns of the 4G/5G polymorphism in the PAI-1 gene promoter that was previously shown to significantly affect PAI-1 plasma levels. No linkage/association was found in 167 trios with autistic probands, recruited in Italy and in the USA. We thus found no evidence that this polymorphism, or putative functionally relevant gene variants in linkage disequilibrium with it, confer vulnerability to autistic disorder.

Adolescent↗

The relation between the psychological functioning of children with Down syndrome and their urine peptide levels and levels of serum antibodies to food proteins.

AIMS: To investigate the relation between psychological functioning of subjects with Down syndrome, and their levels of urine peptide and serum antibodies to food proteins. METHODS: 55 children with Down syndrome in a cross-sectional study. Psychological functioning was measured by the Stanford-Binet Intelligence Scale: Fourth Edition, McCarthy Scales of Children's Abilities and Fagan's computer based test of novelty preference. RESULTS: The participants, and their siblings, were found to have significantly increased total urine peptide levels. There were no significant correlations between peptide levels and psychological functioning. Significantly increased levels of IgG activity to gliadin and gluten, and IgA activity to gliadin, gluten and casein were found. There were significant negative correlations (Spearman r = -0.13 to -0.51) between psychological functioning, and IgG and IgA activity to gliadin and gluten. CONCLUSIONS: A significant relation between antibodies to gluten and psychological functioning was documented. The mechanism and potential causal link are still unknown.

Child↗

A serotonin uptake-stimulating tetra-peptide found in urines from ADHD children.

A tetra-peptide has been isolated from the urines of children with Attention Deficit Hyperactivity Disorder (ADHD) that we could not find in control urines. The tetra-peptide (G-S-E-N) stimulates the uptake of serotonin into platelets. The peptide may explain why serotonin is increased in platelets of ADHD children.

Adolescent↗

Adenosine deaminase alleles and autistic disorder: case-control and family-based association studies.

Adenosine deaminase (ADA) plays a relevant role in purine metabolism, immune responses, and peptidase activity, which may be altered in some autistic patients. Codominant ADA1 and ADA2 alleles code for ADA1 and ADA2 allozymes, the most frequent protein isoforms in the general population. Individuals carrying one copy of the ADA2 allele display 15 to 20% lower catalytic activity compared to ADA1 homozygotes. Recent preliminary data suggest that ADA2 alleles may be more frequent among autistic patients than healthy controls. The present study was undertaken to replicate these findings in a new case-control study, to test for linkage/association using a family-based design, and to characterize ADA2-carrying patients by serotonin blood levels, peptiduria, and head circumference. ADA2 alleles were significantly more frequent in 91 Caucasian autistic patients of Italian descent than in 152 unaffected controls (17.6% vs. 7.9%, P = 0.018), as well as among their fathers. Family-based tests involving these 91 singleton families, as well as 44 additional Caucasian-American trios, did not support significant linkage/association. However, the observed preferential maternal transmission of ADA2 alleles, if replicated, may point toward linkage disequilibrium between the ADA2 polymorphism and an imprinted gene variant located in its vicinity. Racial and ethnic differences in ADA allelic distributions, together with the low frequency of the ADA2 allele, may pose methodological problems to future linkage/association studies. Direct assessments of ADA catalytic activity in autistic individuals and unaffected siblings carrying ADA1/ADA1 vs ADA1/ADA2 genotypes may provide stronger evidence of ADA2 contributions to autistic disorder. Am. J. Med. Genet. (Neuropsychiatr. Genet.) 96:784-790, 2000.

Adenosine Deaminase↗

Novel lymphocyte growth-inhibiting tripeptide: N-acetyl-glu-ser-GlyNH(2).

The limited and predetermined number of cells that constitutes an organ or specialized cell population is to all appearances regulated according to a negative feedback principle involving growth inhibitors with sufficient tissue specificity. To find growth-inhibiting factors in lymphoid cells, we followed established purification procedures and assays. We found a single-peak fraction in water extracts of dog spleen homogenates that inhibited proliferation of Molt (T cell) lymphoma cells at low concentrations in vitro, with no significant effect on a B cell lymphoma cell line (Ramos). C-terminal amino acid sequencing and MS analysis showed the factor to be a tripeptide: N-acetyl-Glu-Ser-GlyNH(2). Treatment with a synthetic tripeptide with the structure N-acetyl-Glu-Ser-GlyNH(2) decreased the number of cell doublings of Molt cells. The peptide also delayed cell flux at the G(2)-M transition of the cell cycle, while incorporation of tritiated thymidine was not altered at the examined time points in this cell line. However, DNA synthesis in PPD-stimulated normal human lymphocytes was significantly inhibited and with a bell-shaped dose-response curve.

Animals↗

An endogenous melanocyte-inhibiting tripeptide pyroGlu-Phe-GlyNH2 delays in vivo growth of monoclonal experimental melanoma.

The melanocyte-inhibiting tripeptide (MTP) pyroGlu-Phe-GlyNH2 is present in tissue cultures of non-transformed melanocytes and melanoma cells and influences melanocyte growth in vitro. The objective of the present study was to investigate a possible effect of MTP on the in vivo growth of B16A2, a monoclonal experimental melanoma. The B16A2 clone was established by the limited dilution technique. It has a reduced DNA content and displays slower growth both in vivo and in vitro compared to the parent cell line (B16). B16A2 cells were injected subcutaneously into hairless mice at four sites (300 000 cells in 0.25 ml buffer/site). MTP was given by i.p. injection 3 times a week at two concentrations (1 pmol and 1 nmol/animal). The control animals received the equal volume of solvent. The animals were sacrificed 1 and 2 weeks after tumour transplantation, and all tumours were weighed. One week after transplantation, the animals who received 1 pmol MTP had fewer tumours and a reduced tumour load. Two weeks after the transplantation, the differences between control and treated animals were no longer observed. The results indicate that MTP temporarily delays in vivo tumour growth.

Animals↗

Serotonin uptake stimulating peptide found in plasma of normal individuals and in some autistic urines.

We have isolated a tripeptide from normal plasma and autistic urines which stimulates the uptake of serotonin (5-HT) into platelets. This peptide was purified by high-performance liquid chromatography (HPLC) and characterized by sequenation and mass-spectrometry. Synthetic peptide showed co-chromatography with the biological sample in the HPLC systems used. Close to 60% of the autistic children diagnosed using the Diagnostic Statistical Manual III-R had an increased HPLC peak eluting like this peptide in their urines compared with controls.

Amino Acid Sequence↗

The effect of arginine vasopressin, lysine vasopressin or oxytocin on ADP or arginine vasopressin-induced Ca2+ increase in human platelets.

Oxytocin (OT), lysine vasopressin (L8VP), arginine vasopressin (A8VP) or arginine vasotocin (A8VT) are found in plasma from several species and stimulate various cell types by activation of the polyphosphoinositide metabolism and mobilization of intracellular calcium. We therefore studied the effects of the nonapeptides OT, A8VT, L8VP or A8VP on cytoplasmic calcium (Ca2+) and the effect of the nonapeptides on A8VP-induced Ca2+ mobilization. The preincubation of platelets with 'physiological' concentrations of A8VP (2-4 pmol l-1) did not enhance the intracellular calcium increase caused by the agonists used. However, the ADP-induced calcium increase was enhanced by prior addition of subthreshold concentrations of A8VP (less than 1 nmol l-1) to the platelet suspension (by 10%, P = 0.027, n = 12). Neither OT nor A8VT in concentrations from 10(-5) mumol l-1 to 1 mumol l-1 increased the cytoplasmic calcium concentration. We found that both OT and A8VT blocked the effect of subsequent exposure to A8VP. ADP (0.4 mumol l-1) did not block the effect of A8VP.

Adenosine Diphosphate↗

Gluten-free diet decreases urinary peptide levels in children with celiac disease.

BACKGROUND: Increased urine secretion of peptides has been found in celiac disease, probably resulting from increased intestinal uptake of peptides caused by damage to the small gut mucosa. METHODS: High-performance liquid chromatography of low-molecular-weight peptides in the urine was performed over 6 months, before and after a gluten-free diet was instituted in children who clinically improved while consuming the diet. RESULTS: A significant decrease of peptide levels was observed in children consuming the gluten-free diet. Certain peptide peaks thought to be gluten related decreased the most after the patients began the diet. CONCLUSIONS: Because the peptides decrease in patients consuming a gluten-free diet, it is reasonable to conclude that such peptides have a mostly dietary origin.

Adolescent↗

Antiproliferative effect of the tripeptide pyroGlu-Phe-GlyNH2 on murine melanocytes: transitory delay of cell growth in vitro and the cell cycle specificity.

Cell growth and differentiation in melanocyte cell populations are regulated by a wide range of bioactive substances. Recently, the tripeptide pyroGlu-Phe-GlyNH2 which inhibits melanocyte growth in vitro was identified in both murine nontransformed melanocytes and malignant melanoma cells. The present study was undertaken to investigate the cell cycle specificity as well as the growth inhibitory profile of the tripeptide after a single or repeated administration to melanocyte cultures. Dose-related effects of the peptide were studied using three different bioassay systems: estimation of cell number, DNA synthesis, and cell flux into mitosis. Growth of melanocyte cultures as well as melanocyte mitotic activity were found to be reduced significantly by the tripeptide at two separate dose levels (10(-11) and 10(-14)-10(-15) M). Growth inhibition of melanocyte population did not last long: less than 36 h after the first and less than 24 h after the second peptide addition to the cultures. The level of DNA synthesis in melanocytes remained unchanged after a single peptide administration. The findings indicate that the tripeptide pyroGlu-Phe-GlyNH2 causes transitory delay of cell growth in cultured melanocyte population resulting from a reversible inhibition of melanocyte transition from the G2-phase of the cell cycle into mitosis.

Animals↗