Karl Reichelt

• MD,PhD
• University of Oslo

Background: Autoimmune phenotypes are prevalent in major psychiatric disorders. Disequilibria of cellular processes occurring in the gastrointestinal (GI) tract likely contribute to immune dysfunction in psychiatric disorders. As the venue of a complex community of resident microbes, the gut in a homeostatic state equates with a functional digesti...

Problem: There is a need to collect the many and varied data on AD/HD (Attention deficit hyper-activity disorder) into a meaningful overview. Method: Based on peer reviewed and published data as well as own research we try to make sense of the physiological mechanisms resulting in the relevant symptoms. Conclusion: AD/HD clearly has a genetic dispo...

Although mutations in the MECP2 gene are associated with many cases of Rett syndrome (RS), the phenotype remains unexplained. At least in the early stages, RS and autism have common features; urinary analysis of autistic children has shown an abnormal profile of excretion of sulphur-containing anions, with high levels of sulphite, sulphate and thio...

Double blind tests of drugs and procedures depend on obtaining two equal and randomly assigned groups to be compared. With a diagnosis based only on symptoms, but with different etiologies, this is not very likely. We here show the probability of obtaining two equal groups with one diagnosis but three etiologies. The mathematical name for such a pr...

Aims: To document the evidence for a gut uptake to brain axis. The many hormones, many of them peptides and shared by the intestines and the brain, will not be included in this survey. Methods: Systematic looking through journal publications by means of Pub med and collected information and authors research since 1978. Results: Food-protein antibod...

Problem: The nature of the peptides found increased in urine from autism needs verification of their structure, especially those that show opioid activity. Methods: The peptides were separated on reverse phase C-18 HPLC in Trifluoroacetic acidÁacetonitril gradients. Peaks eluting where synthetic opioids appear, and peaks that are common to most aut...

Unlabelled: We found that malignant cells and tumors contain very little low molecular weight (MW) peptides and amino acids compared to normal cells and tissues. However, the low molecular weight (MW) peptides that inhibit mitosis, cell growth and cause differentiation were recovered from cell growth medium or ascites. We therefore hypothesize tha...

Exorphins from casein and gluten have been found by HPLC and mass spectroscopy with fragmentation pattern in quickly frozen urine. Removing the proteins that contain these peptides, by dietary intervention has been tried with behavioral effects. We wanted to know how fast such changes take place. Method: Parents and caregivers filled out ATEC score...

Dietary intervention as a tool for maintaining and improving physical health and wellbeing is a widely researched and discussed topic. Speculation that diet may similarly affect mental health and wellbeing particularly in cases of psychiatric and behavioral symptomatology opens up various avenues for potentially improving quality of life. We examin...

The nature of the peptides found increased in urine from autism needs verification of their structure, especially those that show opioid activity. The peptides were separated on reverse phase C-18 HPLC in Trifluoroacetic acid-acetonitril gradients. Peaks eluting where synthetic opioids appear, and peaks that are common to most autistic children wer...

Hyperpeptiduria and opioid excess have been re-ported in schizophrenia. According to Prof. Dr. L. Lindström, Sweden opioids may explain the patho-physiology of this syndrome. Therefore it is critical to elucidate the presence and nature of opioids in schi-zophrenia and diagnostic sub groups. First morning urine from untreated schizoaffective patien...

Biochemical, immunological and epidemiological evidence increasingly support the suggestion that there is a causal relationship between gluten/gliadin and schi-zophrenia as originally proposed by F. C. Dohan. Furthermore the necessary physiological mechanisms exist to explain a mechanism involving bioactive pep-tides from these proteins, and these...

The integrin-β 3 gene (ITGB3), located on human chromosome 17q21.3, was previously identified as a quantitative trait locus (QTL) for 5-HT blood levels and has been implicated as a candidate gene for autism spectrum disorder (ASD). We performed a family-based association study in 281 simplex and 12 multiplex Caucasian families. ITGB3 haplotypes are...

Autism is a complex neurodevelopmental disorder, likely encompassing multiple pathogenetic components. The aim of this study is to begin identifying at least some of these components and to assess their association with biological endophenotypes. To address this issue, we recruited 245 Italian patients with idiopathic autism spectrum disorders and...

There is increasing interest in the use of gluten- and casein-free diets for children with autism spectrum disorders (ASDs). We report results from a two-stage, 24-month, randomised, controlled trial incorporating an adaptive 'catch-up' design and interim analysis. Stage 1 of the trial saw 72 Danish children (aged 4 years to 10 years 11 months) ass...

We have shown that urine peptide increase is found in autism, and that some of these peptides have a dietary origin. To be explanatory for the disease process, a dietary effect on the brain must be shown to be possible and probable. Diagnosis was based on DSM-III and DSM-IV criteria. We ran first morning urine samples equivalent to 250 nm creatinin...

Background: Autism is a complex neurodevelopmental disorder, likely encompassing multiple pathogenetic components. Single genes most likely influence a single component, rather than the entire set of autistic signs and symptoms. We have recently shown in 245 ASD patients that at least four principal components provide major contributions to autism...

The purpose of this paper is to show that a more exact diagnosis and dietary intervention in AD/HD (Attention Deficit/Hyperactivity Di­sor­der) is possible and probable. The clinical symptom based diagnosis we suggest may be supplemented with physiological tests. A ge­netic and environmental inter-action is clearly involved and explainable using ph...

Autism is a severe developmental disorder, whose pathogenetic underpinnings are still largely unknown. Temporocortical gray matter from six matched patient-control pairs was used to perform post-mortem biochemical and genetic studies of the mitochondrial aspartate/glutamate carrier (AGC), which participates in the aspartate/malate reduced nicotinam...

Protein kinase C enzymes play an important role in signal transduction, regulation of gene expression and control of cell division and differentiation. The fsI and betaII isoenzymes result from the alternative splicing of the PKCbeta gene (PRKCB1), previously found to be associated with autism. We performed a family-based association study in 229 s...

Autism is a complex and life-long behavioural disorder of unknown aetiology. Recent reports have indicated the involvement of digestive tract dysfunction and possible complications from inadequate nutrition. In this study, 34 autistic children (12 untreated and 22 receiving therapeutic treatments related to digestive function and nutritional uptake...

Head growth rates are often accelerated in autism. This study is aimed at defining the clinical, morphological, and biochemical correlates of head circumference in autistic patients. Fronto-occipital head circumference was measured in 241 nonsyndromic autistic patients, 3 to 16 years old, diagnosed according to DSM-IV criteria. We assessed 1) clini...

Problem behaviour hampers learning and the normal development of skills and competencies. The children in focus in this article from Norway are six-year-olds with persistent problem behaviour. Early identification of these children is imperative for the implementation of structured educational interventions. Knowledge about their behaviour and skil...

The TPH2 gene encodes the enzyme responsible for serotonin (5-HT) synthesis in the Central Nervous System (CNS). Stereotypic and repetitive behaviors are influenced by 5-HT, and initial studies report an association of TPH2 alleles with childhood-onset obsessive-compulsive disorder (OCD) and with autism. GLO1 encodes glyoxalase I, the enzyme which...

Since a genetic disposition for depression is probable, there ought to be biochemical changes. Increased peptide levels with relevant bioactivities have been found in urine in a previous investigation, which may be such changes. Urine from patients with severe depression according to ICD 10 have been run on reversed phase High Performance Liquid Ch...

Autism is a severe developmental disorder. The condition is probably not homogenous. Elevated urine peptides have been found in individuals affected by autism spectrum disorders. This finding may be explained by characteristics of the samples studied. Autistic children without mental retardation (high-functioning autism) or mild mental retardation...

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 rema...

Organophosphates (OPs) are routinely used as pesticides in agriculture and as insecticides within the household. Our prior work on Reelin and APOE delineated a gene-environment interactive model of autism pathogenesis, whereby genetically vulnerable individuals prenatally exposed to OPs during critical periods in neurodevelopment could undergo alte...

Multiple changes in antibodies against various antigens are found in multiple sclerosis (MS). We wanted to measure immunoglobulin A (IgA) antibodies to some common food antigens in MS and also IgG against gliadin and gluten. The IgA antibodies were measured in serum against gluten, gliadin, lactoglobulin, lactalbumin, casein and ovalbumin in patien...

The term "chalone" was coined about 40 years ago to describe endogenous growth-inhibiting factors with a tissue-specific and reversible effect. A large number of "chalones" were reported in the 1970's and early 80's. The term was, however, used rather indiscriminately and attempts at purification of the active component(s) were without success. As...

We have previously described linkage/association between reelin gene polymorphisms and autistic disorder. APOE also participates in the Reelin signaling pathway, by competitively antagonizing Reelin binding to APOE receptor 2 and to very-low-density lipoprotein receptors. The APOE2 protein variant displays the lowest receptor binding affinity compa...

We have proposed that the mitosis inhibiting peptide, pyroGlu-His-Gly (pEHG), a colon-specific negative feedback regulator of cell proliferation, works through a G protein-coupled receptor (GPCR), as do many other pyroglutamyl-peptides. Non-tumorigenic YAMC (colon mucosa of Immorto mice), IMCE (Immorto-Min mouse hybrid) and human hepatoma (HepG2) c...

The colon mitosis inhibiting peptide pyroglutamyl-histidyl-glycine (pEHG) increases the expression of c-fos, fosB and egr-1 genes in the colon carcinoma cell line HT-29. However, the effect on non-tumorigenic colonic cells has not been investigated. After exposure of the cell lines YAMC (from colon mucosa of Immorto mice) and IMCE (fromn Immorto-Mi...

The HOXA1 gene plays a major role in brainstem and cranial morphogenesis. The G allele of the HOXA1 A218G polymorphism has been previously found associated with autism. We performed case-control and family-based association analyses, contrasting 127 autistic patients with 174 ethnically matched controls, and assessing for allelic transmission diseq...

Autistic syndromes are characterized by impaired social, communicative, and imaginative skills. Urinary peptide abnormalities, in part due to gluten and casein, have been detected in some individuals With autism. These abnormalities reflect processes With opioid effect, Which may explain the behavioral abnormalities seen in autism. The aim of this...

We recently isolated and characterized a tripeptide, acetylGlu-Ser-GlyNH2 (Ac-ESG), which inhibits proliferation of lymphoid cells. In this paper we describe the effects of Ac-ESG on growth-related gene expression and cell cycle progression in two lymphoma cell lines, Ramos and Molt, representing B and T lymphocytes, respectively. RNA was extracted...

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...

The intestinal mitosis-inhibiting peptide pyroglu-His-GlyOH (pEHG), inhibits normal intestinal epithelial cells and the human colon adenocarcinoma cell line HT-29 and increases the expression of c-fos (1). In this study, we investigated the mechanisms of the growth-inhibiting effects of pEHG. cDNA expression array was hybridized with cDNA from HT-2...

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...

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 elevati...

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...

Neuroblastoma, the most frequent malignant tumour in neonates and young children, has an unusual clinical behaviour, age being the most important single factor. This could indicate that some growth-regulating mechanism in lost, or changed, during the first years of life. In search for possible growth-modifying factors, we identified a tetrapeptide,...

The tripeptide pyroGlu-His-GlyOH (pEHG), isolated from intestinal extracts (1), suppresses growth of human colonic epithelial cells and human colorectal adenocarcinoma cells (HT-29) both in vitro and in vivo. The present study represents the first attempt to relate alterations in relevant gene expression to the effect on cell growth. Northern blot...

Autism is a biologically-heterogeneous disease. Distinct subgroups of autistic patients may be marked by intermediate phenotypes, such as elevated serotonin (5-HT) blood levels, potentially associated with different underlying disease mechanisms. This could lead to inconsistent genetic association results, such as those of prior studies on serotoni...

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.

To investigate the relation between psychological functioning of subjects with Down syndrome, and their levels of urine peptide and serum antibodies to food proteins. 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...

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.

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...

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 descri...

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...

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 t...

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 t...

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 ass...

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 t...

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 wa...

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. 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 chil...

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 cy...

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 syst...

Anni-Mari Knivsberg, Karl-L. Reichelt and Magne Nødland outline the problems resulting from comorbidity (the simultaneous occurrence of two or more disorders) in children, the effects of which tend to be more serious than those resulting from a single disorder. Two of the most common developmental disorders are dyslexia and ADHD (attention deficit...

Abnormal urinary peptide patterns and peptide levels are reported in autism. These abnormalities are in part peptides from gluten, gliadin and casein, and some of them are opioids. These opioids cross the blood-brain barrier and effect the central nervous system. A seven year old girl with autistic behaviour who benefited from a diet without gluten...

Seasonal changes in cell physiology are well known. Fluctuations of mood in humans are reflected in the serotonin metabolism in platelets. The mechanisms involved remain unknown. Over four years we have studied the increase in levels of platelet calcium caused by minimal doses of the agonists adenosine 5' diphosphate (ADP) and arginine vasopressin...

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 cy...

In celiac disease, the mucosa in the small intestine is damaged. This study was conducted to determine whether the normal peptide and protein uptake from the gut is increased in patients with celiac disease. The low-molecular-weight peptides were measured in urine from children and adults with untreated celiac disease. A reversed-phase technique wa...

Considering the large number of factors that modulate cell growth and differentiation, it might seem naive to assume that cell renewal is basically regulated according to a negative feedback principle, involving one tissue-specific chemical signal system in each organ/tissue. This concept is, nevertheless, about 60 years old. In 1937, Simms and Sti...

The function and proliferation of melanocyte cell populations are influenced by a wide range of hormones and growth factors. Local cell renewal after sudden melanocyte loss appears to be regulated according to a negative feedback principle, however. In accordance with this assumption, we have examined growth-inhibitory activity in water extracts of...

Urinary samples from children with autistic syndromes, diagnosed according to the DSM III, were collected from seven different countries. The excretion of peptides was analyzed by a new and fast HPLC method, and the increased amount excreted was observed to be statistically the same. A 4-year follow-up of the original cohort of autistic children pl...

1. Dohan has proposed that schizophrenia is a genetic disposition which interacts with an overload of dietary proteins such as casein and gluten or gliadin. 2. A systematic attempt is made to see if this hypothesis is possible faced with aspects of schizophrenia that must be accounted for. 3. The authors conclusion is that it is possible, but more...

Unlabelled: The activation of the laryngeal chemoreflex may be a pathogenic mechanism in apnoea, apparent life threatening events, and SIDS. Infants with apnoea and increased levels of beta-endorphin immunoreactivity in CSF have been successfully treated with naloxone. Beta-endorphin may induce respiratory depression, and naloxone is a beta-endorp...

Six schizophrenic patients had their urinary peptide levels measured before and after 5 weeks of treatment with neuroleptic medications. For two patients, levels were also measured after a reduction in the neuroleptic dose. Because of the heterogeneity of peptide peaks with the same bioactivity, the overall peptide levels were compared to initial l...

Dietary intervention was applied to 15 subjects with autistic syndromes, with pathological urine patterns, and increased levels of peptides found in their twenty‐four‐hour urine samples. The peptides, some of which are probably derived from gluten and casein, are thought to have a negative pharmacological effect on attention, brain maturation, soci...

To determine whether beta-endorphin is involved in the laryngeal chemoreflex, we initially injected 0.01-1 mg of beta-endorphin into the cisterna magna (i.c.m.) and registered the respiratory and cardiovascular patterns in 5-10-d-old piglets. From 0.1 to 1 mg of beta-endorphin i.c.m. induced a decrease in the minute volume, heart rate, and blood pr...

IgA antibody levels in serum were examined in two groups of schizophrenic patients. All were diagnosed according to DSM-III-R criteria. One group of 36 males and 12 females were compared to historical controls. The other group consisted of 13 males off drugs for at least 3 months; these were compared with age- and sex-matched controls. An increase...

In 1984 we identified and characterized a growth-inhibiting pentapeptide, pyroGlu-Glu-Asp-Ser-GlyOH, [EPP] from mouse epidermis. Later, other pyroGlu N-terminal oligopeptides have been isolated and characterized from liver and mouse intestine. The three pyroGlu-terminal mitosis inhibitory peptides are structurally similar and have several biologica...

A single intraperitoneal (i.p.) injection of picomolar doses of the epidermal pentapeptide (EPP), pGlu-Glu-Asp-Ser-GlyOH, is followed by a reversible inhibition of mouse epidermal cell proliferation. An equimolar mixture of zinc and EPP injected i.p. into hairless mice reversed the inhibitory activity, resulting in an immediate stimulation of epide...

An increased level of immunoglobulin A (IgA) antibodies to food antigens has been found in Down syndrome. Biopsy did not show any anomaly of the gut. Increased IgA levels against specific proteins reflect increased transmucosal transport of antigens. The antigens presented may be immunogenic peptides or intact antigens. In this paper, we wished to...

The amount of low molecular weight amino acids and peptides measured in the form amino acids released by hydrolysis was found to be very low in malignant tissues and cell lines compared to normal tissues and cell lines. The ratios of acid soluble proteins to these low molecular weight compounds were statistically different in normal and malignant c...

An increased level of immunoglobulin A (IgA) antibodies to food antigens has been found in Down syndrome. Biopsy did not show any anomaly of the gut. Increased IgA levels against specific proteins reflect increased transmucosal transport of antigens. The antigens presented may be immunogenic peptides or intact antigens. In this paper, we wished to...

Beta-endorphin may induce respiratory depression and bradycardia. Elevated levels of hypoxanthine (HX) in vitreous humour (VH) may possibly indicate hypoxia before death. Furthermore, gliosis in the brain stem may reflect a previous hypoxic/ischaemic injury in the brain. In the present study we relate beta-endorphin immunoreactivity (BENDI) in the...

Beta-endorphin may induce respiratory depression and bradycardia. Infants with apnea and increased level of beta-endorphin immuno-reactivty in CSF have been succesfully treated with naloxone. Therefore, LCR apnea was activated in five groups of 5-10 days old piglets: 1) untreated n=6 (CONTR), 2) 0.1mg beta-endorphin in cist.erna maqna (L.c.m.) n =...

These syndromes show a genetic disposition. Some diagnostic problems are caused by hybrids with other syndromes. Central to the pathology is the demonstration of increased serotonin uptake into platelets caused by a serum and urine peptide. Furthermore, bovine casomorphin immunoreactive peptides have been found in urine and dialysis fluid as part o...

In nucleus tractus solitarius (NTS) beta-endorphin (BEND) induces bradycardia and respiratory depression which have been reported to precede death in sudden infant death (SID). Of SID victims, 50% have elevated levels of beta-endorphin immunoreactivity (BENDI) in the cerebrospinal fluid (CSF), and 50% had undetectable levels. We therefore investiga...

By focusing the consequences of loading platelets with the fluorescent calcium indicator, fura-2, in buffer or plasma the influences of plasma constituents on calcium responses in blood platelets has been worked out. Proteins were removed from the pre-incubation medium before agonist stimulation and measurement of intracellular calcium concentratio...

The mitosis inhibitory pentapeptide, pGlu-Glu-Asp-Ser-GlyOH (EPP), which was isolated from mouse epidermis extracts, belongs to a group of growth inhibitory peptides that all have pyroglutamyl at the N-terminal end. Earlier experiments with crude or partially purified skin extracts have shown that the inhibitory effect could be enhanced by beta-rec...

Pediatric Research (1994) 35, 268–268; doi:10.1203/00006450-199402000-00081

The effect of the physiological epidermal proliferation inhibitory substance (EPP) pGlu-Glu-Asp-Ser-GlyOH on the promotion phase in two-stage carcinogenesis was investigated. EPP could be the active component in what has been called epidermal chalone. Hairless mice were given an initial application of 100 nmol 7,12-dimethylbenz[a]anthracene in 200...

Beta-endorphin (BEND) may induce respiratory depression. Elevated levels of beta-endorphin immunoreactivity (BENDI) in the CSF are found in children with apnoea and in about 50% of sudden infant death (SID) victims. Premortal hypoxia in SID victims has been indicated by elevated hypoxanthine (HX) levels in the vitreous humour (VH). In this study we...

Treatment of posthaemorrhagic ventricular dilatation in neonates is still a matter of debate. In 8 neonates between 26 and 31 weeks with posthemorrhagic hydrocephalus the effect of a decrease in intracranial pressure (ICP) on cerebral oxygenation was evaluated by NIRS. Lumbar puncture (LP) had been performed postnatally between 31 and 38 weeks. All...

The subcellular distribution of γ-glutamylaminotransferase (EC 2.3.2.2) and transglutaminase (EC 2.3.2.1) has been investigated in rat brain tissue fractionated by a centrifugation and sedimentation technique. Neither of these enzymes was enriched in the synaptosomal fraction. Comparing the in vitro grown astrocytes with synaptosomes, we find that...

Repeated i.p. injections of the synthetic peptides pyroglutamylglutamylglycylserylasparagine and pyroglutamylglutamylglycylserylaspartic acid inhibited the long-term growth of MH1C1 rat hepatoma cells by 50-70% in three in vivo models: metastatic colony growth in the lungs of young Buffalo rats; s.c. tumor growth in young Buffalo rats; and s.c. tum...

A test system for growth regulators based on the time course of liver regeneration in male NMRI mice injected intraperitoneally (ip) with 50 nmol CCl4 at 12 is described. Regenerative DNA synthesis (labelling index) peaked at 36 h after CCl4 injury, and the Colcemid-assessed mitotic rate (MR) at 42 h, i.e., 6 h later. This response pattern was used...