Comparison of the in vitro effects of colchicine and its derivative colchiceine on chondrocyte morphology and function

Colchiceine is a colchicine-metabolite which has been reported to inhibit axonal transport although not binding to brain tubulin. In the present study, colchiceine was shown not to depolymerize cytoplasmic microtubules, nor to mimic other effects of colchicine on the ultrastructure of cultured chondrocytes. In addition, the synthesis of proteoglycans was inhibited by colchicine but slightly stimulated by colchiceine. These results support the idea that the disturbances in cultured chondrocytes caused by colchicine are specifically related to a loss of cytoplasmic microtubules.     

Hormone content of mouse pancreatic islets subjected to different in vivo and in vitro functional demands

Summary Mice treated for 4 days with tolbutamide displayed decreased serum glucose values with a concomitant decrease of their islet insulin content. Mouse islets cultured for 1 week at a low (3 mM) or a high (28 mM) glucose concentration contained less insulin than non-cultured islets and islets cultured at a medium (11 mM) glucose concentration. All groups of cultured islets contained more glucagon than non-cultured islets. The somatostatin content of high- and medium-glucose cultured islets was higher than that of freshly isolated islets.The skilled technical assistance of Astrid Nordin, Ewa Forsbeck and Eva Törnelius is gratefully acknowledged. Financial support was received from the Swedish Medical Research Council (12X-109; 12X-2297), the Nordic Insulin Fund and the Swedish Diabetes Association.     

Imparied bone resorption of cultured calvaria from mice with abnormal lysosomal function (the Chediak-Higashi syndrome)

Summary Spontaneous bone resorption is reduced in cultured calvarial bones from mice with the Chediak-Higashi syndrome, as indicated by decreased mobilization of calcium from the bones to the medium. Although bone resorption in calvaria from mice with this disease can be stimulated by PGE₂ and 1 (OH)D₃, the amounts of mineral released after stimulation is also decreased.This investigation was supported by grants from the Swedish Association against Rheumatic Diseases, from the Royal 80 Year Fund of King Gustav V, and from the Swedish Medical Research Council (project No 14X-05426).     

The effect of Apamin® on nonadrenergic,noncholinergic nervous vasodilatations in the cat small intestine

Summary The intestinal vasodilation evoked by mechanical mucosal stimulation or by transmural electrical field stimulation was abolished by close i.a. injection of Apamin, a polypeptide originally isolated from bee venom. Apamin also blocked the vasodilatation induced by close i.a. infusion of vasoactive intestinal polypeptide (VIP). It is suggested that Apamin is a VIP receptor antagonist.This research was sponsored by grants from the Swedish Medical Research Council (14X-2855), from the Swedish Society for Medical Sciences, from Magnus Bergvalls Stiftelse and from the Medical Faculty, University of Göteborg.     

The effect of hexamethonium on the secretion induced by sodium deoxycholate in the rat jejunum

Summary The i.v. administration of hexamethonium reduces or abolishes net water secretion induced by sodium deoxycholate in the denervated rat jejunum. The findings suggest that a local nervous reflex may be involved in bile salt-induced intestinal secretion.This research was sponsored by grants from the Swedish Medical Research Council (14X-2855), from the Swedish Society for Medical Sciences, from Magnus Bergvalls Stiftelse and from the Medical Faculty, University of Göteborg.     

The effect of lidocaine on the secretion induced by cholera toxin in the cat small intestine

Summary The intraluminal administration of lidocaine, a local anaesthetic agent, inhibits the net loss of fluid into the intestinal lumen produced by cholera toxin in the cat. It is suggested that the activation of a nervous reflex is involved in the pathogenesis of cholera.This research was sponsored by grants from the Swedish Medical Research Council (14X-2855), from the Swedish Society for Medical Sciences, from Magnus Bergvalls Stiftelse and from the Medical Faculty, University of Göteborg.     

Is tubulin involved in the electrically-induced mechanical activity of the isolated rat sciatic nerve?

Summary The electrically-induced mechanical activity of isolated segments of rat sciatic nerves remains unaffected following incubation with 10^–4 M colchicine, vinblastine or melatonin. Vinblastine depressed tubulin levels in incubated nerves. These results suggest that microtubules are not involved in nerve mechanical activity in vitro.This work was supported by grant No. 6638 from the CONICET (Argentina). It is dedicated to the memory of C.E. Valenti, decreased November 1979.     

Evidence for the presence of virus in clonal insulin-producing RINm5F cells

Summary The ultrastructural morphology of the clonal insulin-producing cell line, RINm5F, was investigated. Virus-like particles, probably C type viruses, were identified both intra- and extracellularly. Because these particles could not be found in the original transplantable tumor, it is probable that viruses were induced at some later stage in the development of the RINm5F cell line. All investigators using the RINm5F cells should be aware of the fact that these cells may contain one or several types of viruses, and of the possibility that these particles may interfere with a variety of cellular functions.This work was supported by grants from the Lake County Medical Center Developmental Agency (to VH and PWB) and the American Heart Association, Indiana Affiliate (to PWB,^*USA) and by the Swedish Medical Research Council (12X-562), the Swedish Diabetes Association, the Nordic Insulin Foundation and Åke Wibergs Foundation (^**Sweden). Per-Olof Berggren is a recipient of a postdoctoral fellowship from the Swedish Medical Research Council.     

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).     

Coating of centrospheres by reticulum cisternae and formation of spindle residues in segmentation mitosis under the action of an antitubulin substance: nocodazole]

When cleaving eggs are treated by nocodazole the reticulum cisternae coat the centrospheres instead of the chromosomes, as normally occurs at the late anaphase. At the same time the spindle is reduced to a common mass or spindle remnant, constituted of unorientated and fragmented microtubules which embed the kinetochores, i. e. the star configuration of the chromosomes. This action is quite similar to that of chloralhydrate but is different from that of colchicine.     

Intraluminal bile salt increases rate of firing in afferent fibers from the small intestine of the rat

Summary Perfusion of a rat intestinal segment with a solution containing sodium deoxycholate (8 mM) increases the rate of firing in periarterial afferent nerves from the gut. This observation indirectly supports our earlier proposal that bile salt evokes a net fluid secretion in the small intestine via an activation of the enteric nervous system.This study was supported by grants from the Swedish Medical Research Council (2855), The Medical Council of Swedish Life Insurance Companies and the Faculty of Medicine, University of Göteborg.     

Somatostatin content and release of isolated pancreatic islets from obese-hyperglycemic mice

Summary The somatostatin content in pancreatic islets of obese-hyperglycemic mice was much lower than in the islets of normal mice. Also the release of somatostatin was decreased from the islets obtained from the obese-hyperglycemic mice. Tissue culture for 1 week changed neither the content of, nor the amount of somatostatin released from, the pancreatic islets.This work was supported by the Swedish Medical Research Council, Nordic Insulin Foundation, Swedish Diabetes Association, the Bergwalls stiftelse and the Anders Swärds stiftelse.     

Transport and diffusion of Tau protein in neurons

In highly polarized and elongated cells such as neurons, Tau protein must enter and move down the axon to fulfill its biological task of stabilizing axonal microtubules. Therefore, cellular systems for distributing Tau molecules are needed. This review discusses different mechanisms that have been proposed to contribute to the dispersion of Tau molecules in neurons. They include (1) directed transport along microtubules as cargo of tubulin complexes and/or motor proteins, (2) diffusion, either through the cytosolic space or along microtubules, and (3) mRNA-based mechanisms such as transport of Tau mRNA into axons and local translation. Diffusion along the microtubule lattice or through the cytosol appear to be the major mechanisms for axonal distribution of Tau protein in the short-to-intermediate range over distances of up to a millimetre. The high diffusion coefficients ensure that Tau can distribute evenly throughout the axonal volume as well as along microtubules. Motor protein-dependent transport of Tau dominates over longer distances and time scales. At low near-physiological levels, Tau is co-transported along with short microtubules from cell bodies into axons by cytoplasmic dynein and kinesin family members at rates of slow axonal transport.     

Labelling of ribosomal RNA peaks in the liver of rats after administration of tritiated fluorouracil

Zusammenfassung Nach i.p. Injektion von 5-Fluorouracil-³H wurde bei Ratten zu verschiedenen Zeiten die RNS-Neubildung der Leber bestimmt. Die Resultate sprechen dafür, dass Fluorouracil in die ribosomale RNA der Leber eingebaut wird.

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This work was supported by grants from the Swedish Medical Research Council (Project No. K68-12X-623-04), the Swedish Cancer Society (Project No. 95-K68-02X), the Faculty of Medicine, University of Uppsala, Sweden, and the Swedish Society for Medical Research.     

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).     

Action of diphenylhydantoin on chromosomes

The effect of diphenyl hydantoin, (DPH) a nonbarbituate anticonvulsant drug, on chromosomes and fertility was tested in cultured human lymphocytes, mouse fertility, and rat maternal marrow chromosomes and fetal development. Whole human blood from 5 male and 5 female subjects was cultured for 68 hours with phytohemagglutinin, then incubated for 2 hours in isotonic salts with .05-.3 mg per ml DPH, .02 mcg per ml colchicine, or .4 mg per ml sodium diethylbarbiturate. The mean number of metaphases per 1000 stimulated cells was 10.0 in controls, 40.3 with colchicine, 27.9 with diethylbarbiturate, and 30.5 with .25 mg DPH per ml. Both diphenylbarbiturate and DPH produced linear dose effect curves. These results were demonstrated not to be due to urea, since there were no differences in urea content, with a 2 hour urease micromethod. Mouse fertility was totally inhibited in 6 virgin mice given .1mg DPH daily for 10 days compared to 41 pups both of 6 control mice. In 6 pregnant rats given 25 mg DPH per 100 gm/orally 4 times daily for 2 days on gestation Days 7 and 8, there were 5 rats with all fetuses resorbed and 1 rat with 3 living and several resorptions. 6 controls had 6-14 normal fetuses each. 50 metaphase plates from each rat's femoral marrow and each fetus were examined 2 hous after injecting .3 mg colchicine per 100 gm. 30% of the metaphase cells from treated females and fetuses showed strongly contracted chromosomes and reduced number os "pulverized" chromosomes. These phenomena may have been due to inhibition by DPH of folic acid metabolism which is involved in purine synthesis.     

Role of lysosomes, microtubules and microfilaments in the mechanism of the lactogenic action of prolactin in the rabbit mammary gland]

The lysosomotropic agents, ammonium chloride and chloroquine, added to the culture medium of pseudopregnant Rabbit mammary gland, did not inhibit the initiation of casein synthesis by prolactin. By contrast, they considerably reduced the down-regulation of prolacting receptors. Converse-y, colchicine totally blocked the lactogenic action of prolactin without altering the down-regulation of the receptor. Cytochalasin B inhibited only partly the lactogenic action of prolactin while it has no effect on the down-regulation of the receptor. These data suggest that the degradation of the prolactin-receptor complex in lysosome is not a compulsory step in the mechanism of prolactin action. The integrity of microtubules but not of microfilaments is required for prolactin to initiate casein synthesis. These elements of the cytoskeleton are not strictly involved in the down-regulation of the receptor.     

Effect of tranexamic acid on progress of experimental tumours and on DNA-synthesis

Summary The fibrinolytic inhibitor tranexamic acid affects certain experimental tumours; it prolongs survival (Lewis lung adenocarcinoma), decreases tumour weight (C3H breast carcinoma), and inhibits ascitic production (AH 130 rat hepatoma). However, it does not significantly influence DNA-synthesis in cell suspensions prepared from the same tumours.Acknowledgment. This study was supported by grants from Malmö Allmänna Sjukhus and the Swedish Medical Research Council (B79-17X-04523-05B).     

Beta1-adrenoceptor mediated salivary gland enlargement in the rat

Summary In the rat, prolonged activation of ₁-adrenoceptors causes a gain in salivary gland weight, whereas prolonged blockade of these receptors causes a reduction in weight.This work was supported by grants to J.E. from the Medical Faculty in Lund and the Swedish Medical Research Council (05927).     

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.