Screening for cystic fibrosis among newborns in Norway by measurement of serum/plasma trypsin-like immunoreactivity. Results of a 2 1/2-year pilot project.

A pilot project for neonatal screening for cystic fibrosis (CF) by measuring trypsin-like immunoreactivity (TLI) in liquid serum or plasma samples was carried out in Norway from May 1982 to December 1984. A total of 72,320 newborns was screened. Twelve infants were recalled for sweat testing; 11 were confirmed to have CF. One infant had normal sweat sodium and chloride levels and no clinical symptoms. The incidence of CF in this study was 1:6574, and the recall rate for second blood samples was 0.6%. No false-negative cases have yet been reported. The level of TLI was affected by the use of heparin in plasma preparation, being reduced by about 20% as compared to serum levels.

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.

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.

The isolation and characterization of an insulin-releasing tetrapeptide from urines of patients with lipoatrophic diabetes.

The tetrapeptide pyroGlu-Glu-Asp-GlyOH and its gamma-amide have been isolated from the urines of lipodystrophic patients with insulin-resistant diabetes. Both peptides induce insulin release only at high blood glucose levels.

First visualization of glutamate and GABA in neurones by immunocytochemistry.

Immunocytochemical methods for peptides and serotonin have greatly advanced the study of neurones in which these substances are likely to be transmitters. Such direct techniques have not so far been available for the amino acid transmitter candidates. We report here the selective immunocytochemical visualization of the putative transmitters glutamate (Glu) and gamma-aminobutyrate (GABA) by the use of antibodies raised against the amino acids coupled to bovine serum albumin (BSA) with glutaraldehyde (GA). The tissue localizations of Glu-like and GABA-like immunoreactivities (Glu-LI and GABA-LI) matched those of specific uptake sites for Glu and GABA, and, in the case of GABA-LI, also that of the specific marker enzyme glutamic acid decarboxylase (GAD). Thus, GABA-LI was located in what are believed to be GABAergic inhibitory neurones, whereas Glu-LI was concentrated in excitatory, possibly glutamatergic neurones. Preliminary electron microscopic observations suggest that the transmitter amino acids are significantly concentrated in synaptic vesicles.

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.

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.