Karl Reichelt - Academia.edu (original) (raw)

Papers by Karl Reichelt

Research paper thumbnail of Gut Uptake, Brain and Behaviour

To document the evidence for a gut uptake to brain axis. The many hormones, many of them peptides... more 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 antibodies, food-protein derived peptides and direct physiological evidence point to considerable effect of the digestive system on behavior and mood. Removal of specific proteins from diet ameliorates the clinical condition. Conclusion: Uptake from the gut of various substances has effect on behaviour.

Research paper thumbnail of Altered amino acid excretion in children with autism

Nutritional Neuroscience, 2008

Autism is a complex and life-long behavioural disorder of unknown aetiology. Recent reports have ... more 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) and 29 control subjects (all 5-15 years of age) were investigated to determine whether there were any anomalies in the urinary excretion of amino acids, glucose, sucrose, arabinose and tartaric acid using GC/FID and GC/MS analysis techniques. Significantly lower relative urinary levels of essential amino acids were revealed for both the untreated (mean ± SEM, 32.53 ± 3.09%) and treated (31.98 ± 2.87%) autistic children compared with the controls (37.87 ± 1.50%). There were no significant differences in measured excretions of sugars or tartaric acid. It was concluded that the untreated autistic children had evidence of altered metabolic homeostasis.

Research paper thumbnail of Transmitter-dependent peptide synthesis in the central nervous system

Advances in biochemical psychopharmacology

Research paper thumbnail of Peptides' role in autism with emphasis on exorphins

Problem: The nature of the peptides found increased in urine from autism needs verification of th... more 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 autistic children were analyzed by mass spectrometry and fragmentation pattern on a quadropole mass-spectrometer. Results: We could demonstrate exorphins in the urine from autistic children, and their length varied from one patient to the next. Conclusion: Exorphins are found in urine of autistic children and may account for their symptoms.

Research paper thumbnail of Urinary peptides in schizophrenia and depression

Stress Medicine, 1985

Page 1. STRESS MEDICINE, VOL. 1: 169-181 (1985) URINARY PEPTIDES IN SCHIZOPHRENIA AND DEPRESSION ... more Page 1. STRESS MEDICINE, VOL. 1: 169-181 (1985) URINARY PEPTIDES IN SCHIZOPHRENIA AND DEPRESSION KARL L. REICHELT, MD, PhD, PAUL D. EDMINSON, PhD AND KIM G. TOFT, PhD Pediatric Research Institute ...

Research paper thumbnail of Autistic Syndromes and Diet: a follow‐up study

Scandinavian Journal of Educational Research, 1995

Problem: Some researchers have not found the opioids in urine of autistic children. We have there... more Problem: Some researchers have not found the opioids in urine of autistic children. We have therefore looked at this problem again. Method: Mass spectrometry and fragmentation mass spectrometry (MS/MS) have been carried out on peaks from the HPLC that show co-chromatography with synthetic standards and peaks that are shared by different autistic children. Results: In quickly frozen urine we find the presence of exorphins, and can also demonstrate a rather fast break down at room temperature of these peptides in urine. Conclusion: Exorphins are present in urine in autistic children, but must be protected against break down and aggregation by fast freezing or acetic acid and adjusting declustering potential and collision potential during mass-spectroscopy. Specific antibody increases and the effect of removing precursor proteins from the diet reinforce this view.

Research paper thumbnail of Mouse epidermal cell renewal after topical treatment with different concentrations of the epidermal peptide pyroGlu-Glu-Asp-Ser-GlyOH

Virchows Archiv. B, Cell pathology including molecular pathology, 1990

Earlier work has shown that epidermal cells contain a peptide, pyroGlu-Glu-Asp-Ser-GlyOH, that in... more Earlier work has shown that epidermal cells contain a peptide, pyroGlu-Glu-Asp-Ser-GlyOH, that induces a moderate but long-lasting inhibition of epidermal cell proliferation when given at low (picomol) doses ip in vivo and in vitro. In the present study, the epidermal pentapeptide was applied topically to the back skin of hairless mice at different concentrations and in a water-miscible cream. A single topical application of either high (0.25% wt/wt) or low (0.004% or 0.02% wt/wt) doses of the pentapeptide was followed by oscillations in epidermal DNA synthesis and G2-M cell flux (mitotic rate). In general, epidermal cell proliferation was inhibited during the first 10-day period after treatment with the two lower doses, while the highest concentration of pentapeptide (0.25%) stimulated epidermal cell proliferation. In spite of the effects on epidermal cell proliferation the size of the epidermal cell population in the treated area (number of nucleated cells and epidermal thickness)...

Research paper thumbnail of Inhibitory epidermal pentapeptide modulates proliferation and differentiation of transformed mouse epidermal cells in vitro

Virchows Archiv. B, Cell pathology including molecular pathology, 1991

A transformed mouse epidermal cell line ("308 cells") and nontransformed rat tongue squ... more A transformed mouse epidermal cell line ("308 cells") and nontransformed rat tongue squamous epithelial cells ("RT10 cells") were treated 3 times weekly for a period of two weeks with relatively large doses (150 micrograms/ml) of a synthetic inhibitory epidermal pentapeptide; pyroGlu-Glu-Asp-Ser-GlyOH. The peptide was recently isolated from mouse skin extracts and inhibits normal epidermal cells in vivo and in vitro at a restricted and low dose level. Repeated treatments with the large dose was followed by a 30-40% reduction in the number of 308 cells per well, starting as early as day 1. The number of RT10 cells was reduced about 20% only at termination of the experiment on day 14. In contrast to this, the number of unattached cornified envelopes on day 10 in the RT10 cells was increased by 85%, while the number of cornified, unattached 308 cells was similar to that in the controls. The effects of the pentapeptide thus seem to affect differentiation stronger tha...

Research paper thumbnail of Mouse liver regeneration after carbon tetrachloride injury as test system for hepatic growth regulators

Virchows Archiv B Cell Pathology Including Molecular Pathology, 1992

A test system for growth regulators based on the time course of liver regeneration in male NMRI m... more A test system for growth regulators based on the time course of liver regeneration in male NMRI mice injected intraperitonelly (ip) with 50 nmol CC14 at 12 is described. Regenerative DNA synthesis (labelling index) peaked at 36 h after CC14 injury, and the Colcemid-assessed mitotic rate (MR) at 42 h, i.e., 6 h later. This response pattern was used to assess the effects of factors in liver extracts that regulate or modulate hepatocyte proliferation. The effect of one, two, four or eight ip injections of an aqueous mouse liver extract on MR was tested at 48 h. A 30-70% inhibition was seen only after single injections at 12 h, 29 h or 44 h after CC14 treatment. A 30-80% stimulation was observed after a single injection of the liver extract at 0, 5 or 24 h, and after two or four injections. The assay system could thus detect the presence of growth modulators in the extract. The experiments also showed that the timing was crucial. We recently isolated and characterized a growth inhibitory pentapeptide from mouse liver extracts. Using a synthetic pentapeptide with the same structure we reassessed the timing for growth inhibition seen with the liver extract. The following test system for growth inhibitors seemed most expedient: inhibitor administration at 29 h to affect G1-S transition, measured as reduced DNA synthesis at 36 h, or inhibitor administration at 44 h to affect G2-M transition, measured as reduced MR at 48 h.

Research paper thumbnail of Purification and characterization of a growth inhibitory hepatic peptide

Virchows Archiv B Cell Pathology Including Molecular Pathology, 1987

A pentapeptide isolated from normal mouse liver seems to inhibit DNA synthesis (3Hthymidine incor... more A pentapeptide isolated from normal mouse liver seems to inhibit DNA synthesis (3Hthymidine incorporation into liver DNA and labelling indices) and the mitotic rate (G2-M cell flux)

Research paper thumbnail of An endogenous colon mitosis inhibitor reduces proliferation of colon carcinoma cells (HT 29) in serum-restricted medium

Virchows Archiv B Cell Pathology Including Molecular Pathology, 1988

Extracts of mouse intestine contain a colonic epithelial mitosis inhibitor that has recently been... more Extracts of mouse intestine contain a colonic epithelial mitosis inhibitor that has recently been purified and identified as a tripeptide (pGlu-His-GlyOH). In order to elucidate further the biological characteristics of this peptide, the effect of the tripeptide on cell proliferation in a human colon carcinoma cell line (HT 29) was examined. The incorporation of tritiated thymidine was significantly reduced at 20-30 h after addition of the tripeptide. The dose-response relationship was bellshaped with loss of inhibitory effect at high or low doses. The number of cells were significantly reduced at a peptide concentration of l0 -8 M at 24 h, but not at 48 or 72 h after addition of the peptide. The inhibition was reversible, and was only observed when the cells were grown in a serum-restricted medium (1%). The inhibitory effect was abolished by increasing the serum content to 10% or adding insulin to the medium.

Research paper thumbnail of Influence of human plasma or serum albumin on ADP- or vasopressin-induced calcium increases in human platelets

Scandinavian Journal of Clinical & Laboratory Investigation, 1994

By focusing the consequences of loading platelets with the fluorescent calcium indicator, fura-2,... more 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 concentration [Ca2+]i. We found that moderate amounts (1-33%, v/v) of plasma added to the buffer during pre-incubation stimulated the mobilization of cytoplasmic calcium, delta[Ca2+]i, and reduced the time from agonist stimulation to peak level of [Ca2+]i in platelets stimulated with ADP or arginine vasopressin A8VP. With the buffer used, calcium response was restored by addition of 33% (v/v) plasma to the same level as found for unwashed platelets in the platelet rich plasma (cf. methods). The presence of human serum albumin during the pre-incubation also influenced the calcium response, but not to the same extent as plasma. From a resting level of 73 +/- 10 nmol l-1, addition of 0.4 mumol l-1 ADP increased the [Ca2+]i by 24 +/- 13 nmol l-1 (n = 20), 65 +/- 30 nmol l-1 (n = 5), and 144 +/- 44 nmol l-1 (n = 22) in platelets pre-incubated with buffer, 5 gl-1 albumin, and 33% (v/v) plasma, respectively. The corresponding values after stimulation with 0.05 mumol l-1 A8VP were 49 +/- 34 nmol l-1, 105 +/- 27 nmol l-1, and 170 +/- 39 nmol l-1, (n = 7). In platelets incubated in buffer only, the delta t from stimulation with 0.4 mumol l-1 ADP was 18.9s.(ABSTRACT TRUNCATED AT 250 WORDS)

Research paper thumbnail of Variation in cytoplasmic calcium increase in platelets as a normal response in healthy persons

Scandinavian Journal of Clinical & Laboratory Investigation, 1998

Seasonal changes in cell physiology are well known. Fluctuations of mood in humans are reflected ... more 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 (A8VP) using the calcium-selective fluorescent probe fura-2. We found that in blood platelets from healthy people the basal level of calcium, the amount of calcium mobilized to the cytoplasm and, for vasopressin, the rate of calcium rise, varied periodically and sufficiently to be statistically significant.

Research paper thumbnail of Decreased urinary peptide excretion in schizophrenic patients after neuroleptic treatment

Psychiatry Research, 1995

Six schizophrenic patients had their urinary peptide levels measured before and after 5 weeks of ... more 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 levels. A neuroleptic effect on peptide levels was demonstrated. Several research groups have reported enzyme induction caused by neuroleptics in vivo.

Research paper thumbnail of ?-Glutamylaminotransferase and Transglutaminase in Subcellular Fractions of Rat Cortex and in Cultured Astrocytes

Journal of Neurochemistry, 1992

ABSTRACT

Research paper thumbnail of Purified Epidermal Pentapeptide Inhibits Proliferation and Enhances Terminal Differentiation in Cultured Mouse Epidermal Cells

Journal of Investigative Dermatology, 1986

Research paper thumbnail of Attention Deficit Disorders

Journal of Developmental & Behavioral Pediatrics, 1988

ABSTRACT

Research paper thumbnail of Antiproliferative Effect of the Tripeptide PyroGlu-Phe-GlyNH2on Murine Melanocytes: Transitory Delay of Cell Growthin Vitroand the Cell Cycle Specificity

Experimental Cell Research, 1998

Cell growth and differentiation in melanocyte cell populations are regulated by a wide range of b... more 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.

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

Down Syndrome Research and Practice, 2001

Aims: To investigate the relation between psychological functioning of subjects with Down syndrom... more 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 signifi cantly increased total urine peptide levels. There were no signifi cant correlations between peptide levels and psychological functioning. Signifi cantly increased levels of IgG activity to gliadin and gluten, and IgA activity to gliadin, gluten and casein were found. There were signifi cant negative correlations (Spearman r=-0.13 to -0.51) between psychological functioning, and IgG and IgA activity to gliadin and gluten. Conclusions: A signifi cant relation between antibodies to gluten and psychological functioning was documented. The mechanism and potential causal link are still unknown.

Research paper thumbnail of Moderate enhancement of the promotion phase of skin tumorigenesis in hairless mice by topical pretreatment with a mitosis-inhibiting epidermal pentapeptide

Carcinogenesis, 1993

The effect of the physiological epidermal proliferation inhibitory substance (EPP) pGlu-Glu-Asp-S... more 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 microliters acetone. One week later promotion was started with topical applications of 17 nmol 12-O-tetradecanoylphorbol-13-acetate (TPA) twice a week. Ninety minutes before each TPA application the control group received a topical application of 200 microliters reagent grade acetone and the two experimental groups were given either 0.005% or 0.01% EPP in 200 microliters acetone. The mice were observed for time of occurrence and time of regression of papillomas. The number of tumors produced by the group given the inhibitory substances before TPA increased, and so did the percentage of tumor-bearing animals. There was also a tendency towards a higher degree of papilloma regression in the animals treated with EPP before TPA. We have previously shown that EPP enhances methylnitrosourea (MNU) carcinogenesis. Since we regard TPA as a skin-irritating promoter with weak carcinogenic potency, very different from MNU, the fact that EPP has the same enhancing effect on promotion as it has on complete MNU carcinogenesis raises some very interesting questions, and may indicate a similarity between the mechanisms in promotion and complete carcinogenesis. Some possible explanations of the results are discussed, e.g. whether the transit zone late G1/S of the cell cycle is the most sensitive one for carcinogenic or tumorigenic effects.

Research paper thumbnail of Gut Uptake, Brain and Behaviour

To document the evidence for a gut uptake to brain axis. The many hormones, many of them peptides... more 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 antibodies, food-protein derived peptides and direct physiological evidence point to considerable effect of the digestive system on behavior and mood. Removal of specific proteins from diet ameliorates the clinical condition. Conclusion: Uptake from the gut of various substances has effect on behaviour.

Research paper thumbnail of Altered amino acid excretion in children with autism

Nutritional Neuroscience, 2008

Autism is a complex and life-long behavioural disorder of unknown aetiology. Recent reports have ... more 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) and 29 control subjects (all 5-15 years of age) were investigated to determine whether there were any anomalies in the urinary excretion of amino acids, glucose, sucrose, arabinose and tartaric acid using GC/FID and GC/MS analysis techniques. Significantly lower relative urinary levels of essential amino acids were revealed for both the untreated (mean ± SEM, 32.53 ± 3.09%) and treated (31.98 ± 2.87%) autistic children compared with the controls (37.87 ± 1.50%). There were no significant differences in measured excretions of sugars or tartaric acid. It was concluded that the untreated autistic children had evidence of altered metabolic homeostasis.

Research paper thumbnail of Transmitter-dependent peptide synthesis in the central nervous system

Advances in biochemical psychopharmacology

Research paper thumbnail of Peptides' role in autism with emphasis on exorphins

Problem: The nature of the peptides found increased in urine from autism needs verification of th... more 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 autistic children were analyzed by mass spectrometry and fragmentation pattern on a quadropole mass-spectrometer. Results: We could demonstrate exorphins in the urine from autistic children, and their length varied from one patient to the next. Conclusion: Exorphins are found in urine of autistic children and may account for their symptoms.

Research paper thumbnail of Urinary peptides in schizophrenia and depression

Stress Medicine, 1985

Page 1. STRESS MEDICINE, VOL. 1: 169-181 (1985) URINARY PEPTIDES IN SCHIZOPHRENIA AND DEPRESSION ... more Page 1. STRESS MEDICINE, VOL. 1: 169-181 (1985) URINARY PEPTIDES IN SCHIZOPHRENIA AND DEPRESSION KARL L. REICHELT, MD, PhD, PAUL D. EDMINSON, PhD AND KIM G. TOFT, PhD Pediatric Research Institute ...

Research paper thumbnail of Autistic Syndromes and Diet: a follow‐up study

Scandinavian Journal of Educational Research, 1995

Problem: Some researchers have not found the opioids in urine of autistic children. We have there... more Problem: Some researchers have not found the opioids in urine of autistic children. We have therefore looked at this problem again. Method: Mass spectrometry and fragmentation mass spectrometry (MS/MS) have been carried out on peaks from the HPLC that show co-chromatography with synthetic standards and peaks that are shared by different autistic children. Results: In quickly frozen urine we find the presence of exorphins, and can also demonstrate a rather fast break down at room temperature of these peptides in urine. Conclusion: Exorphins are present in urine in autistic children, but must be protected against break down and aggregation by fast freezing or acetic acid and adjusting declustering potential and collision potential during mass-spectroscopy. Specific antibody increases and the effect of removing precursor proteins from the diet reinforce this view.

Research paper thumbnail of Mouse epidermal cell renewal after topical treatment with different concentrations of the epidermal peptide pyroGlu-Glu-Asp-Ser-GlyOH

Virchows Archiv. B, Cell pathology including molecular pathology, 1990

Earlier work has shown that epidermal cells contain a peptide, pyroGlu-Glu-Asp-Ser-GlyOH, that in... more Earlier work has shown that epidermal cells contain a peptide, pyroGlu-Glu-Asp-Ser-GlyOH, that induces a moderate but long-lasting inhibition of epidermal cell proliferation when given at low (picomol) doses ip in vivo and in vitro. In the present study, the epidermal pentapeptide was applied topically to the back skin of hairless mice at different concentrations and in a water-miscible cream. A single topical application of either high (0.25% wt/wt) or low (0.004% or 0.02% wt/wt) doses of the pentapeptide was followed by oscillations in epidermal DNA synthesis and G2-M cell flux (mitotic rate). In general, epidermal cell proliferation was inhibited during the first 10-day period after treatment with the two lower doses, while the highest concentration of pentapeptide (0.25%) stimulated epidermal cell proliferation. In spite of the effects on epidermal cell proliferation the size of the epidermal cell population in the treated area (number of nucleated cells and epidermal thickness)...

Research paper thumbnail of Inhibitory epidermal pentapeptide modulates proliferation and differentiation of transformed mouse epidermal cells in vitro

Virchows Archiv. B, Cell pathology including molecular pathology, 1991

A transformed mouse epidermal cell line ("308 cells") and nontransformed rat tongue squ... more A transformed mouse epidermal cell line ("308 cells") and nontransformed rat tongue squamous epithelial cells ("RT10 cells") were treated 3 times weekly for a period of two weeks with relatively large doses (150 micrograms/ml) of a synthetic inhibitory epidermal pentapeptide; pyroGlu-Glu-Asp-Ser-GlyOH. The peptide was recently isolated from mouse skin extracts and inhibits normal epidermal cells in vivo and in vitro at a restricted and low dose level. Repeated treatments with the large dose was followed by a 30-40% reduction in the number of 308 cells per well, starting as early as day 1. The number of RT10 cells was reduced about 20% only at termination of the experiment on day 14. In contrast to this, the number of unattached cornified envelopes on day 10 in the RT10 cells was increased by 85%, while the number of cornified, unattached 308 cells was similar to that in the controls. The effects of the pentapeptide thus seem to affect differentiation stronger tha...

Research paper thumbnail of Mouse liver regeneration after carbon tetrachloride injury as test system for hepatic growth regulators

Virchows Archiv B Cell Pathology Including Molecular Pathology, 1992

A test system for growth regulators based on the time course of liver regeneration in male NMRI m... more A test system for growth regulators based on the time course of liver regeneration in male NMRI mice injected intraperitonelly (ip) with 50 nmol CC14 at 12 is described. Regenerative DNA synthesis (labelling index) peaked at 36 h after CC14 injury, and the Colcemid-assessed mitotic rate (MR) at 42 h, i.e., 6 h later. This response pattern was used to assess the effects of factors in liver extracts that regulate or modulate hepatocyte proliferation. The effect of one, two, four or eight ip injections of an aqueous mouse liver extract on MR was tested at 48 h. A 30-70% inhibition was seen only after single injections at 12 h, 29 h or 44 h after CC14 treatment. A 30-80% stimulation was observed after a single injection of the liver extract at 0, 5 or 24 h, and after two or four injections. The assay system could thus detect the presence of growth modulators in the extract. The experiments also showed that the timing was crucial. We recently isolated and characterized a growth inhibitory pentapeptide from mouse liver extracts. Using a synthetic pentapeptide with the same structure we reassessed the timing for growth inhibition seen with the liver extract. The following test system for growth inhibitors seemed most expedient: inhibitor administration at 29 h to affect G1-S transition, measured as reduced DNA synthesis at 36 h, or inhibitor administration at 44 h to affect G2-M transition, measured as reduced MR at 48 h.

Research paper thumbnail of Purification and characterization of a growth inhibitory hepatic peptide

Virchows Archiv B Cell Pathology Including Molecular Pathology, 1987

A pentapeptide isolated from normal mouse liver seems to inhibit DNA synthesis (3Hthymidine incor... more A pentapeptide isolated from normal mouse liver seems to inhibit DNA synthesis (3Hthymidine incorporation into liver DNA and labelling indices) and the mitotic rate (G2-M cell flux)

Research paper thumbnail of An endogenous colon mitosis inhibitor reduces proliferation of colon carcinoma cells (HT 29) in serum-restricted medium

Virchows Archiv B Cell Pathology Including Molecular Pathology, 1988

Extracts of mouse intestine contain a colonic epithelial mitosis inhibitor that has recently been... more Extracts of mouse intestine contain a colonic epithelial mitosis inhibitor that has recently been purified and identified as a tripeptide (pGlu-His-GlyOH). In order to elucidate further the biological characteristics of this peptide, the effect of the tripeptide on cell proliferation in a human colon carcinoma cell line (HT 29) was examined. The incorporation of tritiated thymidine was significantly reduced at 20-30 h after addition of the tripeptide. The dose-response relationship was bellshaped with loss of inhibitory effect at high or low doses. The number of cells were significantly reduced at a peptide concentration of l0 -8 M at 24 h, but not at 48 or 72 h after addition of the peptide. The inhibition was reversible, and was only observed when the cells were grown in a serum-restricted medium (1%). The inhibitory effect was abolished by increasing the serum content to 10% or adding insulin to the medium.

Research paper thumbnail of Influence of human plasma or serum albumin on ADP- or vasopressin-induced calcium increases in human platelets

Scandinavian Journal of Clinical & Laboratory Investigation, 1994

By focusing the consequences of loading platelets with the fluorescent calcium indicator, fura-2,... more 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 concentration [Ca2+]i. We found that moderate amounts (1-33%, v/v) of plasma added to the buffer during pre-incubation stimulated the mobilization of cytoplasmic calcium, delta[Ca2+]i, and reduced the time from agonist stimulation to peak level of [Ca2+]i in platelets stimulated with ADP or arginine vasopressin A8VP. With the buffer used, calcium response was restored by addition of 33% (v/v) plasma to the same level as found for unwashed platelets in the platelet rich plasma (cf. methods). The presence of human serum albumin during the pre-incubation also influenced the calcium response, but not to the same extent as plasma. From a resting level of 73 +/- 10 nmol l-1, addition of 0.4 mumol l-1 ADP increased the [Ca2+]i by 24 +/- 13 nmol l-1 (n = 20), 65 +/- 30 nmol l-1 (n = 5), and 144 +/- 44 nmol l-1 (n = 22) in platelets pre-incubated with buffer, 5 gl-1 albumin, and 33% (v/v) plasma, respectively. The corresponding values after stimulation with 0.05 mumol l-1 A8VP were 49 +/- 34 nmol l-1, 105 +/- 27 nmol l-1, and 170 +/- 39 nmol l-1, (n = 7). In platelets incubated in buffer only, the delta t from stimulation with 0.4 mumol l-1 ADP was 18.9s.(ABSTRACT TRUNCATED AT 250 WORDS)

Research paper thumbnail of Variation in cytoplasmic calcium increase in platelets as a normal response in healthy persons

Scandinavian Journal of Clinical & Laboratory Investigation, 1998

Seasonal changes in cell physiology are well known. Fluctuations of mood in humans are reflected ... more 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 (A8VP) using the calcium-selective fluorescent probe fura-2. We found that in blood platelets from healthy people the basal level of calcium, the amount of calcium mobilized to the cytoplasm and, for vasopressin, the rate of calcium rise, varied periodically and sufficiently to be statistically significant.

Research paper thumbnail of Decreased urinary peptide excretion in schizophrenic patients after neuroleptic treatment

Psychiatry Research, 1995

Six schizophrenic patients had their urinary peptide levels measured before and after 5 weeks of ... more 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 levels. A neuroleptic effect on peptide levels was demonstrated. Several research groups have reported enzyme induction caused by neuroleptics in vivo.

Research paper thumbnail of ?-Glutamylaminotransferase and Transglutaminase in Subcellular Fractions of Rat Cortex and in Cultured Astrocytes

Journal of Neurochemistry, 1992

ABSTRACT

Research paper thumbnail of Purified Epidermal Pentapeptide Inhibits Proliferation and Enhances Terminal Differentiation in Cultured Mouse Epidermal Cells

Journal of Investigative Dermatology, 1986

Research paper thumbnail of Attention Deficit Disorders

Journal of Developmental & Behavioral Pediatrics, 1988

ABSTRACT

Research paper thumbnail of Antiproliferative Effect of the Tripeptide PyroGlu-Phe-GlyNH2on Murine Melanocytes: Transitory Delay of Cell Growthin Vitroand the Cell Cycle Specificity

Experimental Cell Research, 1998

Cell growth and differentiation in melanocyte cell populations are regulated by a wide range of b... more 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.

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

Down Syndrome Research and Practice, 2001

Aims: To investigate the relation between psychological functioning of subjects with Down syndrom... more 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 signifi cantly increased total urine peptide levels. There were no signifi cant correlations between peptide levels and psychological functioning. Signifi cantly increased levels of IgG activity to gliadin and gluten, and IgA activity to gliadin, gluten and casein were found. There were signifi cant negative correlations (Spearman r=-0.13 to -0.51) between psychological functioning, and IgG and IgA activity to gliadin and gluten. Conclusions: A signifi cant relation between antibodies to gluten and psychological functioning was documented. The mechanism and potential causal link are still unknown.

Research paper thumbnail of Moderate enhancement of the promotion phase of skin tumorigenesis in hairless mice by topical pretreatment with a mitosis-inhibiting epidermal pentapeptide

Carcinogenesis, 1993

The effect of the physiological epidermal proliferation inhibitory substance (EPP) pGlu-Glu-Asp-S... more 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 microliters acetone. One week later promotion was started with topical applications of 17 nmol 12-O-tetradecanoylphorbol-13-acetate (TPA) twice a week. Ninety minutes before each TPA application the control group received a topical application of 200 microliters reagent grade acetone and the two experimental groups were given either 0.005% or 0.01% EPP in 200 microliters acetone. The mice were observed for time of occurrence and time of regression of papillomas. The number of tumors produced by the group given the inhibitory substances before TPA increased, and so did the percentage of tumor-bearing animals. There was also a tendency towards a higher degree of papilloma regression in the animals treated with EPP before TPA. We have previously shown that EPP enhances methylnitrosourea (MNU) carcinogenesis. Since we regard TPA as a skin-irritating promoter with weak carcinogenic potency, very different from MNU, the fact that EPP has the same enhancing effect on promotion as it has on complete MNU carcinogenesis raises some very interesting questions, and may indicate a similarity between the mechanisms in promotion and complete carcinogenesis. Some possible explanations of the results are discussed, e.g. whether the transit zone late G1/S of the cell cycle is the most sensitive one for carcinogenic or tumorigenic effects.