Lennart Wetterberg

Genetic control of plasma dopamine- β -hydroxylase

Abstract Plasma dopamine- β -hydroxylase activity was studied in a twin pair material. Monozygotic twins showed higher concordance for DBH activity than dizygotic twins. Dizygotic twins had a high correlation coefficient, significantly different from a random distribution. The data indicate that plasma DBH in human is partially genetically controlled.

Increase of harderian gland porphyrin content in castrated male hamsters dependent on light and visual function

Abstract The porphyrin content in the Harderian gland of normal male golden hamsters is less than 1% of the porphyrin content of the female. Removal of the testes was followed by an increase in Harderian gland porphyrin content of hamsters kept under diurnal lighting condition (12L : 12D) or in constant light for 72 days but not in animals kept in constant darkness for the same length of time. The porphyrin content in the Harderian gland of blinded castrated male hamsters kept in constant light was as low as in castrated male hamsters kept in total darkness, which indicates that in addition to light exposure, the visual function of the eye is necessary for the increase in porphyrin content in the Harderian gland of castrated male hamsters.

Catechol-O-methyltransferase, histamine-N-methyltransferase and methanol forming enzyme in the rat pineal gland

Abstract Catechol- O -methyltransferase (COMT) enzyme (EC 2.11.6) activity in the Sprague-Dawley male rat pineal gland is between 30 and 40 picomoles per gland per hour and shows a 24-hour rhythm with the highest levels during the light period and the lowest during darkness. The rhythmic variation of COMT is abolished when animals are kept in continuous light. The methanol forming enzyme activity is low and histamine- N -methyltransferase (EC 2.11.8) activity was not measurable at anyone of three time points over a 24-hour period.

Enzyme regulation of melatonin synthesis in the pineal gland of Japanese quail

Abstract The enzymes N-acetyltransferase and hydroxyindole-O-methyltransferase (HIOMT) which are responsible for the conversion of serotonin to melatonin were assayed in pineal glands from both sexes of the Japanese quail in the middle of the dark and the light period of a 12:12 hour light-darkness cycle. The measured N-acetyltransferase activities were twice as high during the dark period as compared to the light period in both sexes. HIOMT activity was not significantly different between quails sacrificed at noon and at midnight. Thus, N-acetyltransferase activity might be responsible for the diurnal variation in melatonin content in the Japanese quail.

GENETICS AND BIOCHEMISTRY OF SCHIZOPHRENIA IN A DEFINED POPULATION

ABSTRACT Over 200 schizophrenic patients belonging to three major and interrelated complexes have been investigated. A major dominant gene is operating in these pedigrees. Hypotheses that schizophrenia might be caused by gene controlled deficiencies in the catecholamine metabolism were tested in a few selected families. Schizophrenia was significantly associated with decreased activities of dopamine-hydroxylase (DBH) in plasma and monoamine oxidase (MAO) in platelets and with the genetic marker Gc 2 (Group specific antigen). There was no significant difference in the catechol-0-methyltransferase (COMT) activity in the red blood cells between schizophrenics and their non-schizophrenic relatives.

Mutations in acute intermittent porphyria detected by ELISA measurement of porphobilinogen deaminase

To study the existence of different mutations in acute intermittent porphyria, erythrocyte porphobilinogen deaminase activity and enzyme protein concentration were investigated in 125 porphyria gene carriers from 31 families, and in 121 apparently healthy controls. Porphobilinogen deaminase concentration (micrograms/gHb) was quantified using a recently developed double-sandwich ELISA. The ratio of enzyme catalytic activity to the concentration of enzyme protein was expressed as the porphobilinogen specific activity (nkat/g). The controls had a mean porphobilinogen deaminase concentration of 160 +/- 35 micrograms/gHb and a specific activity of 762 +/- 127 nkat/g. Two different types of mutation causing acute intermittent porphyria were detected. The majority (91%) of gene carriers, from 25 families, had a diminished porphobilinogen deaminase concentration of 102 +/- 18 micrograms/gHb, with a slightly lowered specific activity of 634 +/- 105 nkat/g. In 9% of the gene carriers, representing six different families, an increase in porphobilinogen deaminase concentration to 269 +/- 46 micrograms/gHb, and a highly significant reduction in specific activity to 234 +/- 48 nkat/g, were found, which indicates the presence of a different mutation.

Dopamlne metabolism in red blood cells in schizophrena

A method was developed for the separation by thin‐layer chromatography of 14C‐labelled 3‐methoxy, 4‐hydroxyphenethylamine, 3‐hydroxy, 4‐methoxyphenethylamine and 3,4‐dimethoxyphenethylamine (DMPEA) after incubation of dopamine with catechol‐O‐methyltransferese (COMT) in lysates of human red blood cells (RBC). 14C‐methyl‐S‐adenosyl‐menthionine was used as the methyl donor. Total COMT activity with noradrenaline or dopamine as substrates, respectively, and the pattern of 14C‐methylated metabolites of dopamine were measured in RBC of 47 schizophrenic patients and in 34 control subjects. There were no differences between patients and controls. DMPEA was not formed by RBC in schizophrenic patients (or in controls), a finding which argues against the “pnk spot”/DMPEA hypothesis of schizophrenia. The methods used seem suitable for studies of other human disorders where COMT might be involved.

THYROTOXIC MYOPATHY AND VITAMIN B 6 METABOLISM

The symptoms of thyrotoxic periodic paralysis are inseparable from those found in familial periodic paralysis. The syndrome consists of periodic attacks of muscle weakness. The paresis is often symmetrical and affects especially the proximal muscles, leaving the distal intact, and only rarely are the cranial muscles involved. The attacks usually appear in the early morning and after large meals, and have a duration from a few hours to two or three days. Remissions are spontaneous. Between the attacks the neurological findings are normal. The sensorium and the sphincter control are unaffected. The disease can be distinguished from familial periodic paralysis by its disappearance on adequate antithyroid therapy. The following classification of periodic paralysis has been suggested.