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Biomedical subjects

K L Reichelt

Publications and source records attributed to K L Reichelt.

At least 73 records · Page 4Linked to original sources

Increased calcium response to ADP in blood platelets from women during ovulation compared with menstruation: cytoplasmic calcium measured with the fura-2 technique.

Blood platelets from women showed increased sensitivity to adenosine diphosphate (ADP) during ovulation compared with menstruation. The increased sensitivity was registered as an increase in cytoplasmic calcium response measured with the fluorescent indicator fura-2. Agonist dose-response studies revealed an increased maximal response, but the dose that gave half maximal response was unchanged. This indicates an increased mobility of calcium, without changed affinity to receptor(s).

Adenosine Diphosphate↗

An endogenous colon mitosis inhibitor and dietary calcium inhibit the increased colonic cell proliferation induced by cholic acid.

We have previously reported that a single intraperitoneal injection of the tripeptide pGlu-His-GlyOH (colon mitosis inhibitor (CMI] is followed by a transient reduction of cell proliferation in the colonic epithelium in mice. The effect of the tripeptide on accelerated cell proliferation in the colonic epithelium was tested during the acute response of the epithelial cells to a diet supplemented with cholic acid. The kinetics of this response was first examined with different amounts of calcium in the feed. We found an increased labeling index (LI) and mitotic rate 2 days after changing the diet, and this response was stronger in animals with a low-calcium cholic acid diet than in animals with cholic acid diet with a standard amount of calcium or a high-calcium cholic acid diet. After 2 weeks of treatment cell proliferation remained significantly elevated only in the animals with low-calcium cholic acid diet. The effect of CMI was tested 7 days after the change to a low-calcium cholic acid diet. Under these conditions a single dose of CMI (10(-12) mol per animal) was still followed by a transient reduction in the proliferative indices in the colonic epithelium. However, the decreases in LI was observed earlier after CMI treatment (at 2 h) in the animals fed a low-calcium cholic acid than in animals with a standard diet.

Animals↗

Attention deficit disorders: a study of peptide-containing urinary complexes.

In several behavioral disorders, we have observed that abnormal amounts of peptides and protein-associated peptide complexes are excreted in the urine. The gel filtration patterns of these excreted substances have some specificity for the different disorders. The urinary excretion of peptide-containing complexes was studied in 91 boys and 13 girls (mean age 9.4 years, range 1-23) with the clinical diagnosis of attention deficit disorder (ADD), with or without hyperactivity. The gel filtration of urine precipitate showed patterns in all patients that were different from those seen in 36 normal controls. Sixty-four patients had increased benzoic acid-glycoprotein-peptide complexes in the late peaks. The symptoms of all these patients fit the criteria for diagnosis of attention deficit disorder with hyperactivity (ADDH). Thirty-five patients showed reduced amounts of uric acid complexes in the late peaks. Clinically, this group, with the exception of three patients, fit the criteria for diagnosis of attention deficit disorder without hyperactivity. Five patients showed reduced amounts of all urinary complexes; four of these were hyperactive. Moderate exercise in control children did not change the urinary pattern. One urinary peptide fraction from hyperactive patients, purified to homogeneity, increased the uptake of 14C[5-HT] in platelets. Strict clinical, neuropsychological, and psychophysiological selection of the patients reduced the heterogeneity of the patterns. Although more studies are needed, the findings seem promising for the possibility of developing biochemical tests that may be helpful diagnostically.

Adolescent↗

Isolation and structure of an epidermal mitosis inhibiting pentapeptide.

A mitosis inhibiting peptide pyroGlu-Glu-Asp-Ser-GlyOH has been isolated from mouse skin extracts. Both the biological and a synthetic peptide with the same structure reversibly inhibit epidermal mitoses in a curvilinear fashion after intraperitoneal injection. The two compounds are chromatographically identical.

Animals↗

Purification and characterization of a growth inhibitory hepatic peptide. A preliminary note.

A pentapeptide isolated from normal mouse liver seems to inhibit DNA synthesis (3H-thymidine incorporation into liver DNA and labeling indices) and the mitotic rate (G2-M cell flux) in regenerating mouse liver. The inhibitor is somewhat similar to the growth inhibitory pentapeptides previously reported for granulocytes and epidermis. It is active at very low dose levels, showing a bell-shaped dose-response curve.

Animals↗

Childhood autism: a complex disorder.

Twenty-four-hour urine samples from psychotic and autistic children were precipitated with benzoic acid at pH 4.3. Fractionation of the aromatic complexes thus formed with benzoic acid-protein and peptides and uric acid, proteins and peptides on G-25 columns-yielded filtration patterns that may be of diagnostic value. Peptide material could be extracted from the formed complexes and refractionated on P2 gels. Increased levels of peptide material, especially of N-substituted peptides, could be demonstrated. Several bioactive factors (Reichelt et al. 1981) are under study. Possible etiological factors are discussed, and a working hypothesis is presented.

Adolescent↗

Purified epidermal pentapeptide inhibits proliferation and enhances terminal differentiation in cultured mouse epidermal cells.

Skin extracts contain an epidermal mitosis inhibitor that recently has been purified and identified as a pentapeptide. To develop an in vitro assay system for further biologic characterization, primary mouse epidermal cells and an established mouse epidermal cell line (line 308) were used for testing of the purified pentapeptide. In primary cell cultures the mitotic activity, as estimated by means of vinblastine, was reversibly inhibited by 44% at a peptide concentration of 10(-8) M in high-calcium (1.2 mM Ca++), and by 27-38% at peptide concentrations of 10(-10) and 10(-8) M in low-calcium (0.02 mM Ca++) medium. The 308 cells were inhibited by 46% at a peptide concentration of 10(-6) M but only after the cells had reached near-confluence and had a moderate rate of proliferation. A low concentration of adrenaline (0.18 micrograms/ml) in the medium rendered the primary cultures more sensitive to the peptide. After repeated peptide treatments over 24 h, the number of cornified envelopes (a marker of terminal differentiation) was increased both in primary cultures and in the 308 cells. The epidermal pentapeptide thus seems to influence both proliferation and terminal differentiation in cultured mouse epidermal cells.

Animals↗

Peptide-containing fractions in depression.

A mixture of peptides and glycoproteins has been found in benzoic acid-precipitable material from urines of psychomotorically agitated and retarded endogenous depressive patients. This complex mixture of compounds is fractionated on a Sephadex G-25 gel, from which the different peaks are further separated on Biogel P2. The G-25 elution profiles ultraviolet absorbance, 280 nm) from depressive patients deviated from the normal pattern. The increase in hydrolyzable ninhydrin-colorable material of the P2 fractionation step encountered in psychotic depression was several-fold that of the normal population. Neurochemically active peptide-containing fractions were found. As explanation of these findings, it is probable that a genetically determined peptidase insufficiency is present, causing a peptide overflow when the secretion outstrips the breakdown. This model could easily combine more psychodynamic models with the genetic-biological models. The variability of the peptide patterns could possibly reflect the considerable clinical variability of the syndrome. Furthermore, the presence of a group of active compounds with different neuropharmacological activities might reflect the composite nature of the depressive syndrome.

Adult↗

Different acute in vivo effects of bacterial derived and pituitary growth hormone preparations on plasma levels of glucagon, insulin and free fatty acids in rabbits.

Intravenous injection of high doses of bacterial derived growth hormone (1 and 2 mg Somatonorm) did not affect the plasma levels of glucagon, insulin and free fatty acids in fasted and fed rabbits. On the other hand, 1 and 2 mg human extracted growth hormone (Crescormon) had stimulatory effects on plasma levels of glucagon, insulin and free fatty acids. These results indicate that the observed stimulatory effects in the rabbits were not due to the growth hormone molecule itself. It was shown by gel filtration and SDS electrophoresis that Crescormon contained constituents that were not present in Somatonorm. The differences in the observed metabolic effects of bacterial derived and pituitary growth hormone preparations in the rabbits could possibly be attributed to a human pituitary lipid-mobilizing factor LMF.

Animals↗

Biologically active peptide-containing fractions in schizophrenia and childhood autism.

It is well documented that peptides have a major role in the effective functioning of higher animals at all levels from enzyme stabilization to homeostatic mechanisms governing essential functions such as eating, sexual behavior, and temperature regulation. The effects of exogenously administered peptides on neurotransmitter release, uptake, metabolism and behavioral consequences are also well established. We have attempted to extend these findings by postulating peptidergic neurons as transducers of multisignal inputs, and that development of pathological states may be due to genetically-determined reduced levels of activity of key peptidases, leading to excretion of regulatory peptides into the circulation. We have been able to demonstrate that, in schizophrenia and autism (in well defined clinical cases), the patterns of peptides and associated proteins from urinary samples differ considerably from each other and from normal controls. In addition to this, further purification of the material obtained has led to the discovery of a number of factors capable of modulating the function of major neurotransmitters. Some of these are in the final stages of characterization as peptides, while the remainder are also probably peptides, as purification has been followed by both biological testing and chemical analysis for peptidic material. We have outlined a number of parameters which we consider relevant in any attempt to put psychiatric disorders on a biological foundation. Any new advances in the neurochemical understanding of such disorders must take into consideration the observations of several different disciplines including genetics and psychology. However, at this stage of research it is far too early to speculate on the relevance of the various biological activities to the etiology and symptomatology of schizophrenia and childhood autism.

Autistic Disorder↗

Patterns of peptides and protein-associated-peptide complexes in psychiatric disorders.

Peptidic neurones may be considered as multisignal intergrators and transducers. When formation or release of peptide outstrips genetically determined breakdown capacity, overflow of peptides to the body fluids and urine may be expected. In this paper, pathological urinary chromatographic patterns of peptides are shown for genetic, functional and mixed disorders. Part symptoms of the disorders may be induced with the biologically isolated and purified peptides as well as with chemically synthesized peptides.

Adolescent↗