Occurrence of trichochromes in the urine of a melanoma patient

Summary The presence of two phaeomelanic pigments, trichochrome B and C, was demonstrated in the urine of a patient with malignant melanoma metastases.Supported by grants from the Swedish Cancer Society (No. 626-B75-04XA), 869-B75-01P, the Swedish Medical Research Council (No. B76-04X-00056-12), and the Walter, Ellen and Lennart Hesselman Foundation for Scientific Research. ProfessorProta was a visiting scientist of the Swedish Cancer Society (No. 626-B75-04U).     

The mutator phenotype theory of carcinogenesis and the complex histopathology of tumours: support for the theory from the independent occurrence of nuclear abnormality,loss of specialisation and invasiveness among occasional neoplastic lesions

The mutator phenotype theory of carcinogenesis suggests that genetic instability is an early and essential part of tumour development. This instability provides for substantially random cell-to-cell genomic variation (genomic heterogeneity) to arise among cells of individual tumours. Genetically unstable cells then produce 'successful' clones of cells with the necessary mutations for malignant behaviour. In a previous paper (Bignold L. P., Cell. Mol. Life Sci. 2002; 59: 950-958), it was pointed out that a population of cells which is heterogeneous for behaviour-related genes may well also be heterogeneous for morphology-related genes. This would result in cellular pleomorphism among cells of individual tumours, and so explain this almost universal characteristic of solid malignancies. paragraph sign If the concept of random genomic variability applies fully to the histopathology of tumours, then most tumours should show a mixture of neoplastic features, especially nuclear atypia, loss of specialised function (such as loss of production of mucus by glandular cells) and invasiveness. However, occasional lesions might be expected to occur which show these characteristics independently. That is, lesions should exist which exhibit one or two of the three characteristics of neoplasms without the other(s). paragraph sign This paper identifies, among human tumours, lesions which show independence of these characteristics. Two of the examples discussed are a Bowenoid solar keratosis that shows severe nuclear atypia, but no apparent loss of specialisation and no invasiveness. On the other hand, anaplastic small cell carcinoma of the lung often exhibits marked loss of differentiation, very aggressive invasion and metastasis, but little nuclear pleomorphism. paragraph sign These examples are considered to provide further support for the importance of the mutator phenotype to the pathogenesis of neoplasia.     

Isolation of 2-S-cysteinyldopa and 2,5-S,S-dicysteinyldopa from the urine of patients with melanoma

Summary Urine from patients with melanoma metastases is shown to contain, in addition to the previously described 5-S-cysteinyldopa (I), 2 closely related metabolites which have been isolated and identified as 2-S-cysteinyldopa (II) and 2, 5-S, S-dicysteinyldopa (III).Supported by grants from the Swedish Cancer Society (No. 626-B76-05XB and 869-B75-01P), the Swedish Medical Research Council (No. B76-04X-00056-12), and the Walter, Ellen and Lennart Hesselman Foundation for Scientific Research. Professor Prota was a visiting scientist of the Swedish Cancer Society (No. 626-B75-04V). The authors are indebted to Dr Soshuke Ito for samples of 2-S-cysteinyldopa and 2,5-S,S-dicysteinyldopa.     

Sympathetic influence on cerebral blood volume: Time-dependent effect of decentralization of the superior cervical ganglia in mice

Zusammenfassung Neue Befunde über die Neuronale Regulation der Hirndurchblutung. Durchschneidung der präganglionären Fasern des Hals-Sy. verursachen eine starke Initiale und eine etwas weniger ausgeprägte dauerzunahme der Durchblutung, was durch Unterbechung der innervation und Sensitivierung der Rezeptoren erklärt wird.

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This work was supported by grant No. B71-14X-732-05 from the Swedish Medial Research Council, and was carried out within a research organization sponsored by the Swedish Medical Research Council (Projects No. B71-14X-712-06A and B71-14X-56-07A).     

Seasonal changes in the uptake capacity of the suprachiasmatic nucleus for3H-serotonin

Summary The suprachiasmatic nucleus, a hypothalamic center important in mediation of circadian and estrous cycles, is shown in adult rats to have seasonal changes in its uptake capacity in vitro for³H-serotonin.Supported in part by grants from the National Institute of Mental Health (MH-25091), the National Institute of Health (HD-10263, HD-03352, 5-T01-HD00104-10), USPHS, and the Ford Foundation (grant No. 630-0505 B, C).     

Tumeurs mammaires et leucémies dans une nouvelle souche de souris (PS): Etude au microscope électronique

Summary In the recently isolated Mouriquand strain of mice, virus-like particles of the A and B type are abundant in mammary tumours, and fewer particles of the C type are present in leukaemic and non-leukaemic organs. In one animal all three kinds of particles have been shown. Striking cytological features of the mammary tumours are described.     

Characterization and relative abundance of maxi-chloride channels in Epstein-Barr virus (EBV) producer: B95-8 cells

Several Epstein-Barr virus (EBV)-transformed cell lines were used to investigate the pathogenesis of lymphoproliferative diseases and nasopharyngeal carcinoma. The studies focus on the events occurring inside the membrane. On only one occasion, the cell membrane of EBV-transformed B lymphocytes from a cystic fibrosis patient was found to express defective Cl channels (CFTR; Cystic Fibrosis Transmembrane conductance Regulator), as in the airway epithelial cell. No other type of channel in EBV-transformed cells has so far been investigated. In this study, the cell membrane of the B95-8 cell was examined by the patch-clamp technique and compared to the non-EBV-infected BJAB cell. The high conductance (300 pS) maxi-chloride (Cl) channel activity was the most frequently observed event in inside-out configurations. Under similar experimental conditions, we have found a significantly higher probability of detecting maxi-Cl channel activity on the cell membrane of B95-8 cells (69%) than on BJAB cells (27%), or as previously reported on resting murine B lymphocytes (38%) or intact human T lymphocytes (37%). The relative abundance of the maxi-Cl channel on B95-8 cells may be linked to EBV infection and/or secretory ability.     

Phaeomelanic pigments from a human melanoma

Summary The pigments in melanomas from 2 patients were studied with regard to solubility and chemical composition. Melanoma pigment from a patient with red-blonde hair was alkali-soluble and contained 9 or 10% sulfur and was thus of phaeomelanic type. Melanoma pigment from a patient with red-brown hair was insoluble in 0.2N NaOH. Its sulfur content was 6%. This pigment was eumelanic with regard to solubility characteristics but the sulfur content was higher than previously observed for eumelanin.Supported by grants from the Swedish Cancer Society (No. 626-B75-04XA), the Swedish Medical Research Council (No. B76-04X-00056-12), and the Walter, Ellen, and Lennart Hesselman Foundation for Scientific Research. ProfessorProta was a visiting scientist of the Swedish Cancer Society (No. 626-B75-04U).     

Release of plasminogen activator from normal and neoplastic endometrium

Summary In the medium of endometrial carcinoma cultures, anti-urokinase-reacting plasminogen activator was released in contrast to cultures of normal or hyperplastic endometrium.This investigation was supported by grants from Malmö General Hospital, the Council for Tobacco Research, USA and the Swedish Medical Research Council (B79-17X-04523-05B).     

Organization of reflex responses elicited in man by muscle stretch applied to uni- and bi-functional muscles]

The organization of human forearm reflexes following the application of extension torque perturbations has been studied in three flexors of the elbow: brachioradialis (BR), biceps (B), and pronator teres (PT). Two of these flexors are also involved in wrist supination: (B) and pronation (PT). During the perturbation, the wrist was fixed at various angles: from full supination to full pronation. The results show that the amplitude of the reflex responses of B and PT is highly dependent on wrist position. By eliminating biceps length changes as a source of observed reflex variation, it has been shown that the normalized reflex amplitude of B increases by 300% when the wrist position is varied from full pronation to full supination. In contrast, the BR muscle has a reflex response which is independent of wrist position. These results are discussed in relation to the role of reciprocal innervation and the possible action of receptors encoding wrist angle.     

Reserpine-induced depletion of gastric vitamin B12-binding proteins in the rat

Zusammenfassung Reserpin mobilisiert Histamin und den «Intrinsic factor» aus dem Rattenmagen. Eine trunkuläre Vagotomie hebt diese Wirkung von Reserpin auf. Reserpin hat keinen Effekt auf den «Intrinsic factor» des Magens von Maus, Hamster, Meerschweinchen und Kaninchen.

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Supported by grants from the Swedish Medical Research Council (No. B71-14X-1007-05C and No. B71-19X-766-05C), the Medical Faculty of Lund, and Albert Pahlson's Foundation.     

Distribution of free and conjugated ecdysteroids between follicle cell sheath and ooplasm in oocytes of the cockroachNauphoeta cinerea

Summary It is shown that both follicle cell sheath and ooplasm contain only small quantities ofHelix-hydrolyzable ecdysteroid conjugates and that 20-hydroxy-ecdysone is the predominant free ecdysteroid. Its concentration is very high in the follicle cell sheath immediately before chorion formation (6825 ng/g) and much lower after chorion formation (150 ng/g), while it is 234 ng/g and 95 ng/g in the ooplasm at the same stages respectively.Thanks are due to Dr J.D. O'Connor (Los Angeles) for the ecdysone antiserum, to Dr J. Koolman (Marburg) for 23,24-[³H]-ecdysone and to Mrs A. Tschan for technical assistance. A fellowship to X. Zhu from the Chinese Ministry of Education and financial support from the Swiss National Science Foundation (grant no. 3.714-0.80 to B. Lanzrein) are gratefully acknowledged.     

Circadian variation in urinary melatonin in clinically healthy women in Japan and the United States of America

Summary Urinary melatonin excretion is lower in East-Asian (Japanese) than in North-American (whites of mixed ethnic origin) women. Moreover, a statistically significant circadian rhythm is demonstrated by population-mean cosinor in the data pool from both groups of women. Furthermore, statistical significance characterizes interactions of effects from geographic differences (between ethnic groups) with temporal factors. Such spatio-temporal interactions await further scrutiny with a view inter alia of carcinogenesis as it is influenced by a spectrum of intermodulating rhythms.Supported by U.S. Public Health Service (5-K6-GM-13981-17), National Cancer Institute (1R01-CA-14445-05 and N01-CP-5-5702), National Institute of Occupational Safety and Health (OH-00631-01), National Institute of Aging (AG-00158), Environmental Protection Agency (R804513-01-0), Swedish Medical Research Council grant 3371 and the St Paul Ramsey Medical Research and Education Foundation. R.B. Sothern and Jung-Keun Lee, Scientists, Chronobiology Laboratories, University of Minnesota provided valuable help.     

Tyrosine hydroxylase activity in a transplantable islet cell tumour of golden hamster

Zusammenfassung In einem transplantierbaren Insel-zelltumor des Goldhamsters ist eine Tyrosinhydroxylase-Aktivität gefunden. Die hohe Aktivität der Enzyme zusammen mit einer starken Konzentration von Tyrosin deutet auf eine schnelle Synthese von Dopa in den Tumorzellen. Die Anwesenheit der Dopametaboliten DOPAC und HVA im Tumor wurde gezeigt.

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This work was supported by grants from the Swedish Cancer Society (No. 67-111) and was carried out within a research organization sponsored by the Swedish Medical Research Council (Projects No. B70-14X-712-05 and No. B70-14X-56-06).     

Micro-diver studies on isolated intestinal cells

Zusammenfassung Der Sauerstoffverbrauch in isolierten Epithelzellen aus dem Dünndarm von Ratten wurde mit dem Kartesischen Taucher untersucht. Die Zellen aus den Villusbasen zeigten einen höheren Sauerstoffverbrauch als Zellen von den Villusspitzen.

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This study was supported by grants from the Swedish Medical Research Council No. B70-14X-2873-01 and No. B70-14X-2855-01 and from US Public Health Service No. HE-05675-09.     

Depletion and repletion of noradrenaline in adrenergic nerves of the rat after decaborane treatment

Zusammenfassung Mit Hilfe der Fluoreszenz-Technik werden die Veränderungen in sympathischen Fasern der Ratteniris nach Noradrenalin-Depletion durch Boron-Hydrid Decarboran (Dopa-Dekarboxylase-Hemmer) analysiert.

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This work has been supported by grants from the Swedish Medical Research Council under project No. B70-14x-97-06B, B70-14x-711-05B and Knut and Alice Wallenberg Foundation.     

Endorcine cells producing regulatory peptides

Summary Recent data on the immunologication of regulatory peptides and related propeptide sequences in endocrine cells and tumours of the gastrointestinal tract pancreas, lung, thyroid, pituitary (ACTH and opioids), adrenals and paraganglia have been revised and discussed. Gastrin, xenopsin, cholecystokinin (CCK), somatostatin, motilin, secretin, GIP (gastric inhibitory beenrevised and discussed. Gastrin, xenopsin, cholecystokinin (CCK), somatostatin, motilin, secretin, GIP (gastric inhibitory polypeptide), neurotensin, glicentin/glucagon-37 and PYY (peptide tyrosine tyrosine) are the main products of gastrointestinal endocrine cells; glucagon, CRF (corticotropin releasing factor), somatostatin, PP (pancreatic polypeptide) and GRF (growth hormone releasing factor), in addition to insulin, are produced in pancreatic islet cells; bombesin-related peptidesare the main markers of pulmonary endocrine cells; calcitonin and CGRP (calcitonin gene-related peptide) occur in thyroid and extrathyroid C cells; ACTH and endorphins in anterior and intermediate lobe pituitary cells, -MSH and CLIP (corticotropoin-like intermediate lobe peptide) in intermediate lobe cells; met- and leu-enkephalins and related peptides in adrenal medullary and paraganglionic cells as well as in some gut (enterochromaffin) cells; NPY (neuropeptide Y) in adrenalin-type adrenal medullary cells, etc.. Both tissue-appropriate and tissue-inappropriate regulatory peptides are produced by endocrine tumours, with inappropriate peptides mostly produced by malignant tumours.     

Protective effect of N-(2-propynyl)-2-(5-benzyloxy-indolyl) methylamine (PF9601N) on mitochondrial permeability transition

PF9601N, N-(2-propynyl)-2-(5-benzyloxy-indolyl) methylamine, an monoamine oxidase (MAO) B inhibitor, has shown neuroprotective properties against dopaminergic toxins. To elucidate the mechanisms involved in this protection, the effect of PF9601N on mitochondria was assessed. PF9601N prevents mitochondrial swelling, drop in the electrical potential and oxidation of sulfhydryl groups, glutathione and pyridine nucleotides induced by Ca²⁺. These observations demonstrate the protective effect of PF9601N on the induction of mitochondrial permeability transition. This protection is due to the interaction of the secondary protonated amino group in the molecule with pore-forming structures and to its antioxidant property, rather than to inhibition of MAO B activity. PF9601N also prevents the release of cytochrome c from mitochondria, suggesting its potential inhibitory effect on mitochondria-mediated apoptosis. The low IC⁵⁰ value for this inhibition, in comparison with deprenyl, make it a more efficient compound than propargylamines and other amines in protecting the bioenergetic functions of mitochondria. Received 9 March 2006; received after revision 10 April 2006; accepted 21 April 2006     

Dopa-decarboxylase and monoamine oxidase activities in a transplantable islet cell tumour of the golden hamster

Zusammenfassung In einem transplantierbaren Inselzelltumor des Goldhamsters, der neben 5-Hydroxytryptamin, Dopa und Dopamin eine bisher unidentifizierte, vermutlich monoaminähnliche Substanz enthält, wurde eine hohe Dopadecarboxylase- und Monoaminooxydaseaktivität gefunden. Nach Dopa-decarboxylasehemmung wurde eine starke Anhäufung von Dopa im Tumorgewebe beobachtet; dieser Befund weist auf eine schnelle Monoaminsynthese und einen schnellen Monoaminumsatz im Tumorgewebe hin.

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This work was supported by grants from the Swedish Cancer Society (67–111) and was carried out within a research organization sponsored by the Swedish Medical Research Council (Projects No. B69-14X-56-05C and B69-14X-712-04C).     

Semisynthesis and biological properties of the [B24-leucine]-, [B25-leucine]- and [B24-leucine,B25-leucine]-analogues of human insulin

Summary Trypsin-catalyzed coupling of porcine desoctapeptide-insulin with synthetic octapeptides produced the [Leu^B24]-(I), [Leu^B25]- (II) and [Leu^B24, Leu^B25]- (III)analogues of human insulin. I, II and III displayed respectively 20–30%, 1–2% and 0.5% of the receptor binding activity of the normal hormone. Biological activities of these analogues seemed to be proportional to their binding potencies when assayed in vitro, while in an in vivo assay analogue I was fully active and II exhibited 10–20% of normal activity. III was less active than II in all assays tested.