Growth-inhibiting N-substituted endogenous peptides.
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Animals↗
Biomedical subjects
K L Reichelt
Publications and source records attributed to K L Reichelt.
Variation in cytoplasmic calcium increase in platelets as a normal response in healthy persons.
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.
Adenosine Diphosphate↗
Peptide excretion in celiac disease.
BACKGROUND: 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. METHODS: The low-molecular-weight peptides were measured in urine from children and adults with untreated celiac disease. A reversed-phase technique was used. RESULTS: The excretion of peptides increased compared with that in an age- and sex-matched reference group. CONCLUSIONS: Celiac patients have hyperpeptiduria. It is possible that some of these peptides are bioactive and may mediate varying systemic effects also found in untreated celiac disease.
Adolescent↗
Identification of a melanocyte growth-inhibiting tripeptide and determination of its structure.
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 cultured non-transformed melanocytes and melanoma cells (B16 cells). The extracts were fractionated by gel filtration on Sephadex G-25 and Fractogel MG 2000, by ion-exchange chromatography on DEAE-cellulose and Dowex 50 and by reverse-phase high-performance liquid chromatography on Bondesil and Partisil columns. Two peptides were isolated with the structures pyroGlu-Phe-GlyNH2 and pyroGlu-Cys-GlyNH2 as revealed by mass spectrometry, peptide sequencing and amino acid analysis. The two peptides were synthesized and tested for the ability to inhibit the growth of melanocyte cultures. Only pyroGlu-Phe-GlyNH2 was inhibitory. The dose-response curve was bell-shaped with maximum inhibition around 10(-15) M. The melanocyte tripeptide thus appears to be a new member of a group of N-substituted growth-regulating oligopeptides found in other tissues.
Animals↗
Dialysis in schizophrenia: successful only in a subtype?
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Female↗
Could schizophrenia be reasonably explained by Dohan's hypothesis on genetic interaction with a dietary peptide overload?
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 serious work in this field is urgently needed.
Dietary Proteins↗
Beta-endorphin immunoreactivity levels in CSF after laryngeal chemoreflex activation correlate with apnoea duration in piglets.
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-endorphin antagonist. We therefore wanted to measure beta-endorphin levels in CSF before and after the chemoreflex induced apnoea. This study includes 13 piglets, 5-10 days of age, treated with and without naloxone. Respiration, blood pressure, and heart rate were monitored. CSF was sampled before and after the laryngeal chemoreflex induced apnoea. We found a shorter duration of apnoea in the piglets which had received naloxone than in those which did not (p = 0.02). The beta-endorphin immunoreactivity levels in CSF increased after apnoea, and the increased levels correlated positively with the duration of the apnoea in the piglets which had not received naloxone (r = 0.94, p = 0.02), but not in those pretreated with naloxone (r = 0.1, p = 0.8). The median amount of beta-endorphin immunoreactivity in CSF after apnoea in the naloxone-treated piglets was not significantly different from that in the non-treated piglets: 615 +/- 589 (n = 7) fmol/ml CSF and 984 +/- 851 (n = 6) fmol/ml CSF, respectively. The beta-endorphin immunoreactivity levels measured before the apnoea were less than 4.3 fmol/ml CSF. CONCLUSION: The laryngeal chemoreflex induced apnoea may possible be partly mediated by beta-endorphin.
Animals↗
Decreased urinary peptide excretion in schizophrenic patients after neuroleptic treatment.
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.
Adolescent↗
Specific IgA antibody increases in schizophrenia.
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 specific IgA antibodies was found. More schizophrenics than controls showed IgA antibody levels above the upper normal limit to gliadin, beta-lactoglobulin, and casein.
Adolescent↗
Zinc and the mitosis-inhibitory epidermal pentapeptide (EPP) form a stimulatory chelated dimer.
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 epidermal G2-M cell flux. The stimulatory effect was strongest at the lowest dose (5 pmol). This effect was probably caused by a dizinc-dipentapeptide dimer, as shown by gel filtration and atomic emission spectrometry. When zinc was added in excess (EPP:Zn 1:9) no such dimer could be identified, and the mixture had no stimulatory effect. The results are discussed in terms of epidermal cell kinetics, and in relation to the use of zinc in dermatology.
Animals↗
An enzyme/brain-barrier theory of psychiatric pathogenesis: unifying observations on phenylketonuria, autism, schizophrenia and postpartum psychosis.
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Autistic Disorder↗
Beta-endorphin may be a mediator of apnea induced by the laryngeal chemoreflex in piglets.
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 pressure within 15 min. Within the next 30 min respiratory pauses accompanied by blood pressure increases and reductions in heart rate developed, similar to the respiratory and cardiovascular pattern of the induced laryngeal chemoreflex. Based on these initial data, we decided to induce a laryngeal chemoreflex in piglets pretreated with 0.1 mg of beta-endorphin i.c.m (n = 6), 0.2 mg of beta-endorphin i.c.m. (n = 6), 0.1 mg of beta-endorphin i.c.m. and 100 micrograms/kg naloxone i.v. (n = 6), 100 micrograms/kg naloxone i.v. (n = 6), or water i.c.m. (n = 6). Because elevated levels of hypoxanthine in the vitreous humor may indicate hypoxia before death, we therefore measured the postmortem hypoxanthine levels in the vitreous humor. The laryngeal chemoreflex-induced apnea was shortened in the piglet group pretreated with water i.c.m and naloxone i.v. (p < 0.01) and in the piglet group pretreated with 0.1 mg of beta-endorphin i.c.m and naloxone i.v. (p < 0.05), but not significantly prolonged in the piglet groups pretreated with 0.1 or 0.2 mg of beta-endorphin i.c.m. when compared with the piglets pretreated with water i.c.m.(ABSTRACT TRUNCATED AT 250 WORDS)
Aging↗
Biologically active pyroglutamyl N-terminal oligopeptides: parts of larger molecules?
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 biological properties in common. A number of questions remain, however, to be answered, e.g., a) Are the peptides part of larger molecules; b) Do they bind to specific receptors on the target cells; c) How are they related to other growth-modulating factors, and c) Are they coded for by genes that are related to known growth regulating proto-oncogenes, especially to growth suppressing genes. To search for soluble parts of possible receptors, or carrier molecules, in water extracts of mouse epidermis we have used affinity columns coated with EPP with either the N-terminal end or the carboxy-end free. Both types of column bind a 70 kD protein. The protein bound to the column with a free N-terminal end splits into two small components under reducing conditions. To look for larger molecules of which EPP could be a fragment, we have used western blotting techniques and a polyclonal rabbit antiserum against EPP. Preliminary experiments have indicated that two different molecules bind to the antiserum.
Amino Acid Sequence↗
[Biochemistry and psychophysiology of autistic syndromes].
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 of a general peptiduria. Peptiduria is usually caused by defects in peptide metabolizing enzymes such as peptidases. Because of considerable heterogeneity of peptides we suspect that different sets of peptidases may be defective in different families. Increased galvanic skin conductance and poor habituation in the pure syndromes reconcile with increased metabolism in attention related brain areas. The trophic effects of exorphins may explain the varied morphological defects and the increasing frequency of epilepsy with age.
Autistic Disorder↗
Inverse relationship between beta-endorphin immunoreactivity in cerebrospinal fluid and nucleus tractus solitarius in sudden infant death.
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 investigated the relationship of BENDI in the CSF to BENDI levels in the NTS area. This study included SID victims (CSF from n = 47, brain stem from n = 16), borderline SID victims (CSF and brain stem from n = 2), sudden death in childhood (CSF and brain stem from n = 1), and controls (CSF from n = 32, brain stem from n = 11). BEND in CSF and NTS area, after extraction, was measured by radioimmunoassay. High performance liquid chromatography was used for closer identification of BENDI. We found that the SID victims divided into two subpopulations, one having a relatively high BENDI level in CSF and one having no detectable level (P < 0.01). Furthermore, an inverse relationship was found between BENDI level in CSF and BENDI level in NTS area in the SID victims (P < 0.05). We conclude that increased BENDI level in CSF is associated with low BENDI level in the NTS area in 50% of SID victims. The low BENDI level in the NTS area may be due to increased release of BEND.
Chromatography, High Pressure Liquid↗
Beta-endorphin immunoreactivity in spinal fluid and hypoxanthine in vitreous humour related to brain stem gliosis in sudden infant death victims.
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 CSF to the presence or absence of reactive astrocytosis in the nucleus olivae inferior (NOI). The relationship between the HX concentration in VH and the number of reactive astrocytes in sudden infant death (SID) cases (n = 17) and controls (n = 23) was also studied. The number of reactive astrocytes was examined in the NOI by immunohistochemical demonstration of glial fibrillary acidic protein (GFAP). The BENDI in CSF and the number of reactive astrocytes in the NOI divided the SID victims into two subpopulations (P < 0.01). One had a median of < 4 fmol/ml BENDI in CSF (range < 4) and 2 reactive astrocytes (range 0-15), and was similar to the controls that died from infections. The other subpopulation had a median of 260 fmol/ml BENDI in CSF (range 160-400) and 13 reactive astrocytes (range 7-33), similar to the control infants with previous hypoxia. In this latter SID subpopulation the number of reactive astrocytes correlated positively with BENDI in CSF (r = 0.7, P < 0.05). All the SID victims had elevated levels of HX in VH. In the SID subpopulation with high level of BENDI in CSF and increased number of activated astrocytes, the correlation factor between HX in VH and activated astrocytes was r = 0.7 (P < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)
Astrocytes↗
Increased levels of antibodies to food proteins in Down syndrome.
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 exclude an institutional cause such as infections and also age differences.
Adolescent↗
Influence of human plasma or serum albumin on ADP- or vasopressin-induced calcium increases in human platelets.
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)
Adenosine Diphosphate↗