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Biomedical subjects

B Falck

Publications and source records attributed to B Falck.

At least 127 records · Page 7Linked to original sources

Glutathionedopa in malignant melanoma.

A human melanoma metastasis was found to contain a substance identical with synthetic glutathionedopa when examined by means of an automatic amino acid analyser, chromatography on a Dowex-50 column, thin-layer electrophoresis, and by fluorimetry. The presence of glutathionedopa in melanoma tissue and of enzymes capable of hydrolysing the glutathione moiety of the molecule, together with the absence of glutathionedopa in the urine, suggest that glutathionedopa is an intermediate substance in the formation of 5-S-cysteinyldopa.

Cysteinyldopa↗

Possibilities for a cholinergic action on smooth musculature and on sympathetic axons in brain vessels mediated by muscarinic and nicotinic receptors.

A pharmacological identification and characterization of cholinergic receptors was carried out in pial arteries of cats. In one series of experiments, the middle cerebral artery was suspended in an organ bath for recording fo circular motor activity. Parasympathomimetic compounds produced either a relaxation or a contraction. The relaxation occurred at low doses (up to 10(-6) M), and the response was inhibited in a competitive manner by atropine. The mean KB value (determined with acetylcholine as agonist) was 3.85 X 10(-11) M, and the corresponding pA2 value 10.43. At higher doses, the parasympathomimetics produced a contraction. This effect, too, was inhibited in a competitive manner with atropine. The calculated mean KB value with acetylcholine as agonist was 1.12 X 10(-11) M, and pA2 was 10.07. The motor responses did not require an intact perivascular sympathetic innervation, which shows that the effects were mediated by muscarinic type of cholinergic receptors present in the smooth musculature. In another series of experiments, pial arteries were preincubated in the presence of 3H-norepinephrine, and the amount of tritium efflux was measured in a superfusion system before or during electrical field stimulation (12 V, 1 msec pulse duration, 10 Hz). The efflux was minimized by sympathetic denervation, and the effect of transmural stimulation abolished by bretylium and guanethidine, which shows that the bulk of tritium overflow during stimulation originated from the perivascular sympathetic nerves. The marked elevation of tritium efflux during stimulation was enhanced by hexamethonium, and it was inhibited by nicotine and acetylcholine, whose effects were counteracted by hexamethonium (but not by atropine). This finding indicates the presence of nicotinic type of cholinergic receptors on the perivascular adrenergic nerves, allowing inhibition of norepinephrine by acetylcholine that may be liberated from the adjacent cholinergic terminals in the autonomic nerve plexus.

Acetylcholine↗

[An improved histofluorescence procedure for freeze-dried paraffin-embedded tissue based on combined formaldehyde-glyoxylic acid perfusion with high magnesium content and acid pH].

A technique is described for highly sensitive and precise visualization of central catecholamine systems in paraffin sections of freeze-dried tissue. The procedure is based on perfusion of the animal with a solution containing formaldehyde and/or glyoxylic acid, in the presence of a very high magnesium content (40 g MgSO4/150 ml solution) and acid pH. The perfused tissue is rapidly frozen, freeze-dried, treated with formaldehyde vapours (at +80 degrees C for 1 h), embedded in parffin in vacuo, and finally sectioned. The present technique has a sensitivity for the dopamine- and noradrenaline-containing systems that is comparable with that of the glyoxylic acid-Vibratome technique, which utilizes fresh, glyoxylic acid-perfused tissue. Thus, the preterminal axon pathways become fluorescent throughout their full extent and the several new terminal systems, discovered with the glyoxylic acid-Vibratome method, are well demonstrable. The method is also highly useful for the study of the cell bodies and their dendritic processes. The catacholamine fibre systems are visualized without any signs of diffusion and with a richness in detail. In animals pretreated with L-tryptophan and MAO-inhibitor the technique is also useful for studies on central indolamine-containing systems.

Animals↗

Diagnostic possibilities for the nuchal evoked potential.

As a response to stimulation of the arm nerves an evoked potential can be recorded in the posterior neck region in man. This nuchal evoked potential (NEP) was recorded in three selected patients with A) cervical rib, B) syringomyelia, and C) prolapse of cervical intervertebral disc. Patients A and C had low-amplitudic NEPs with increased latencies when the affected side was stimulated and "normal" NEPs when the unaffected side was stimulated. Patient B had grossly abnormal, polyphasic NEPs (regardless of the side stimulated) but the simultaneously recorded somatosensory evoked potential was "normal". No systematic differences in the parameters of the NEP due to different recording locations on the neck could be observed.

Adult↗

On the occurrence of cysteinyldopa and dopa in melanocytes and benign nevi cells.

Previous studies have demonstrated a specific cytoplasmic fluorescence in human melanocytes, as well as in pigmented nevi and in malignant melanomas, when the formaldehyde histofluorescence method for visualization of certain catechol and indole derivatives was used. In malignant melanoma two fluorogenic substances, dopa and cysteinyldopa, were found previously. In human melanocytes and benign nevi cells the fluorogenic catechols have so far not been characterized, since chemical analyses are difficult to perform on skin, due to the small amounts of catechols present. However, using split thickness skin quantitative determinations are possible by sensitive fluorometric methods. The chemical analyses of cysteinyldopa showed that in human adult skin most or all was located in the superficial layers. The only specific fluorescence in the thin skin was found in dendritic melanocytes. The findings leave little doubt that cysteinyldopa is stored in melanocytes although the possibility of a concomitant occurrence of other thioethers is not excluded. Nevi and giant nevi were also similarly studied and we found considerable amounts of cysteinyldopa in the nevi. It seems as if the cysteinyldopa is stored in the fluorescent nevi cells. There was no consistent difference in the content of the catechol derivatives between intradermal and compound nevi.

Adolescent↗

Demonstration of 3-methoxytyrosine in the urine of melanoma patients.

With the aid of gas chromatography and mass spectrometry a metabolite of dopa, 3-methoxytyrosine, has been demonstrated in the urine of 2 patients with melanoma metastases, the amounts excreted being 4.0 mg and 8.5 mg/24 hours, respectively. 3-Methoxytyrosine could not with certainty be identified in the urines of two normal subjects.

Chromatography, Gas↗

Measurement of endometrial blood flow in guinea-pig uterus by clearance of intraluminally applied 133xenon: effects of oophorectomy, estrogen treatment and pregnancy.

Endometrial blood flow (EBF) was studied atraumatically in guinea-pigs by the 133xenon clearance technique. With the aid of an otoscope, a xdnon-saline solution was deposited via the vagina through a cannula into the uterine lumen. Radioactivity curves were obtained by a small external scintillation detector. Oophorectomy lowered total flow wheras this was markedly increased (also per unit weight) by estrogen treatment, alone or in combination with oophorectomy. During early pregnancy there was a tendency to increase in the flow, while the values (for the parietal decidua) were markedly reduced at later stages of pregnancy. In the fetus-placenta unit (133xenon solution injected intra-amniotically) the flow was three times higher than in the parietal decidua at this advanced stage of pregnancy.

Animals↗

Reduced level of uterine norepinephrine transmitter during hCG-induced pseudopregnancy in the rabbit.

The bulk of rabbit uterine norepinephrine is present in short adrenergic neurons which have unique functional properties. Pseudopregnancy was induced in adult nulliparous rabbits by a single injection of 1,500 IU of human chorionic gonadotrophin (hCG). By the 6th day of pseudopregnancy, the total uterine content of norepinephrine was reduced to a level only 40% of that found in untreated controls. At 12 days after the injection the amine level was greater than at 6 days but still significantly less than in controls. By 18 days, when the progestational proliferation of the endometrium had subsided, the levels in uteri of control and injected animals were similar. The findings support previous findings indicating the presence of a peripheral neuro-endocrine mechanism influencing uterine motor function.

Animals↗

Formation of cysteinyldopa from glutathionedopa in melanoma.

Glutathionedopa injected intravenously into mice is metabolized and excreted in the urine as a compound with the fluorescence characteristics of cysteinyldopa. Glutathionedopa incubated with a guinea-pig kidney homogenate is metabolized to a compound with the fluorescence characteristics of cysteinyldopa. Boiling of the kidney homogenate prevents the metabolism of glutathionedopa. Incubation of glutathionedopa with a homogenate of a melanoma metastasis led to the formation of a compound with the fluorescence characteristics of cysteinyldopa. Boiling of the melanoma homogenate prevented the metabolism of glutathionedopa. Large amounts of glutathione added to the incubate inhibited the reaction. Lung tissue and blood plasma had no detectable ability to metabolize glutathionedopa. The results show that human melanoma contains one or several enzymes capable of metabolizing glutathionedopa to a smaller dopathioether, probably cysteinyldopa. Such enzymes seem to be normally present in mice and guinea-pigs and have been demonstrated in the guinea-pig kidney.

Animals↗

Excretion of 5-S-cysteinyldopa in the urine of healthy subjects.

Seventy-six Caucasians, 30 men and 46 women, were investigated for the 24-hour excretion of 5-S-cysteinyl dopa in the urine during the months of September to November, 1973. No subject had had strong sun exposure for at least 4 weeks prior. A preliminary finding of a variation of 5-S-cysteinyldopa with season necessitated this precaution. The excretion varied between 9.0 and 242 mug/24 hours. The mean value in men was 100 mug/24 hours and in women 77.8 mug/24 hours. Subjects with white hair had lower values than those with pigmented hair, but there was no other difference between the excreted amounts in subjects with differing hair colour. There was no variation with age when the subjects with white hair were excluded. No variation with weight or body surface was found. Excretion of dopa and dopamine determined together did not correlate with the excretion of 5-S-cysteinyldopa.

Adolescent↗

Urinary excretion of 5-S-cysteinyldopa in patients with primary melanoma or melanoma metastasis.

Urinary excretion of 5-S-cysteinyldopa was studied in 9 patients with primary melanoma. All had 5-S-cysteinyldopa excretion in the normal range. In 8 of the patients excretion values decreased after removal of the tumour. Twenty-four patients with clinical signs of melanoma metastasis were examined for 5-S-cysteinyldopa and dopa+dopamine in the urine. 16 of the 24 had pathologically increased excretion of 5-S-cysteinyldopa and 7 of the 24 had pathological excretion of dopa+dopamine. Six of the latter belonged to the group with increased 5-S-cysteinyldopa excretion and one patient had a borderline value of 5-S-cysteinyldopa. Determination of 5-S-cysteinyldopa seems to be of value in the follow-up of patients operated on for primary melanoma.

Adult↗