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At least 19 recordsLinked to original sources
PubMed1977

The formation of free axonal sprouts from a dorsal root ganglion-nerve preparation maintained in organotypic culture, and the effects of demecolcine.

Nerve-ganglion preparations from rat dorsal spinal nerve roots were maintained in organotypic culture for 20 h. Free axonal sprouts formed at the cut tips. Clear and dense-core vesicles, mitochondria and smooth endoplasmic reticulum accumulated in the axons for a distance of 500 micronm behind the cut, as has previously been described in dorsal roots sectioned in vivo. Sprouting did not occur in dorsal roots maintained in culture without their ganglia attached. Sprouting was also prevented by demecolcine (3 x 10(7) M) which reduced the number of microtubules in non-myelinated, small myelinated and large myelinated axons to respectively 45, 30 and 20% of control values. The sprouts contained several types of vesicle including small clear vesicles, large and small dense-core vesicles and flattened vesicles. The possible relevance of the vesicles to transmitter mechanisms in these neurones is discussed.

Animals↗
PubMed1976

Effect of colchicine and demecolcine on the serum ceruloplasmin level in rats.

Six hours after the administration of demecolcine (0.3 mg/100 g b.w.), a decrease in the ceruloplasmin level was recorded in rat serum. The time course of the decrease in the rat serum ceruloplasmin concentration after the same dose of colchicine was then studied. After two to three hours, the serum ceruloplasmin concentration fell significantly in both male and female rats. Eight hours after the administration of colchicine, the serum ceruloplasmin level began to rise again in female rats, but not in male rats. Mortality among females was lower than among males.

Animals↗
PubMed1977

Localization of bovine brain filament antibody on intermediate (100 A) filaments in guinea pig vascular endothelial cells and chick cardiac muscle cells.

Guinea pig vascular endothelial cells contain naturally occurring rings of intermediate filaments that completely encircle the nucleus. Indirect immunofluorescence staining showed that these perinuclear rings bound antibody prepared against protein from bovine brain 9-nm filaments. In endothelial cells grown in the presence of 1 muM demecolcine (Colcemid) the perinuclear ring "coils" into a juxtanuclear "cap". Throughout this process we could demonstrate staining of the intermediate filaments. Chick cardiac muscle cells in culture stained diffusely with the antibody. After treatment for 24 hr with 1 muM demecolcine the cardiac cells accumulated large bands of intermediate filaments. These bands stained intensely with the antibody. Our findings suggest that intermediate filaments in guinea pig endothelial cells and those induced in chick cardiac muscle cells are antigenically similar to bovine brain filaments. The staining of these filaments is not affected by treatment with demecolcine.

Animals↗
PubMed1977

The effects of colchicine and its derivates on the collagen biosynthesis in vitro.

Recent evidence shows that colchicine decreases collagen production and favourably influences some fibroproductive processes in experimental animal and clinical practice. In our study we investigated the influence of two colchicine derivates--demecolcine and desacetylcolchiceine--on the synthesis of collagen and non-collagen proteins in new born rat skin after the incubation of tissues slices with 14C-proline for 2 h. Collagen was separated in fractions soluble in either 0.45 M NaCl or 2% semi-carbazide that in an insoluble residue. Demecolcine (10(-3)--5.10(-5) M), desacetylcolchiceine (10(-2)--5.10(-4) M), as well as colchicine (10(-4)-10(-6)), inhibited the synthesis of soluble collagen, depending on the drug concentration in the incubation media. Higher concentrations of tested agents also decreased the formation of insoluble collagen. Significant inhibition of non-collagen protein synthesis was ascertained only in the presence of desacetylcolchiceine.

Animals↗
PubMed1979

The binding of colchicine and its derivatives to bovine and human serum albumin and human plasma.

The protein binding of colchicine and its derivatives demecolcine and desacetylcolchiceine was studied by equilibrium dialysis at 22 degrees C and pH 7.38 in bovine and human serum albumin and human plasma. Colchicine and demecolcine (2 X 10(-4) -5 X 10(-4) mol/l) is not bound to proteins. The binding of desacetylcholchiceine was 60--80% in the range 10(-4)-5 X 10(-4) mol/l. The association constant for a single binding site was 8.03 X 10(3) 1/mol for human serum albumin and 13.20 X 10(3) 1/mol for human plasma. The binding profiles for desacetylcholchiceine were quite similar in human serum albumin (4% conc.) and human plasma (3.8% conc. of albumin fraction). We suggest that desacetylcolchiceine was likely to be bound predominantly to albumin. Salicylic acid in vitro, at clinical concentrations (1.8--14.5 X 10(-4) mol/l), significantly decreases the binding of desacetylcolchiceine to human serum albumin.

Animals↗
PubMed1977

Localization of amyloid-related serum protein SAA-like material to intermediate (10 nm) filaments of cultured human embryonal fibroblasts.

Further studies are presented on the intracellular localization of the amyloid-related serum protein SAA previously shown to be produced by embryonal fibroblasts. In cultured embryonal fibroblasts, the fine fibrillar cytoplasmic immunofluorescence obtained by anti-SAA was distinguished from that of microfilaments and microtubules. By using electron microscopy and cells treated with drugs known to specifically alter intracellular fibrils, SAA was localized to 10-nm intermediate size filaments. These filaments form characteristic perinuclear bundles upon treatment with drugs such as demecolcine or vinblastine which disrupt micotubules. The results indicate that SAA is a constituent of the intracellular cytoskeleton.

Amyloid↗
PubMed1977

Size distribution of in-vitro-induced antigen-specific helper and suppressor cells.

Specific helper and suppressor cells were induced in vitro with low and high doses, respectively, of protein antigen in Marbrook cultures. On different days of culture the cells from helper and suppressor cultures were size-fractionated by 1-g velocity sedimentation and the different fractions tested for specific activity in secondary co-operative cultures after challenge with protein-hapten conjugate. We observed a change in the size distribution of both helper and suppressor cells during their in vitro differentiation; the first helper and suppressor cell to be detected is a large (blast) cell, whereas later both help and suppression is mediated by medium- and small-sized lymphocytes. A difference between helper and suppressor cells with regard to their relative dependence on DNA synthesis and proliferation during their induction was also seen. Although both DNA synthesis and divisions are needed for the optimal generation of both types of cells, some suppressor activity was still induced in cultures treated with mitosis-arresting concentrations of demecolcine (Colcemid). Treatment of helper cell cultures with Colcemid or with 5-bromodeoxyuridine plus light completely abolished the help.

Animals↗
PubMed1978

Mononuclear leucocyte chemotaxis in Boyden chambers: inhibition by subantimitotic concentrations of antitubulins.

The chemotaxis of Lymphoprep -isolated human mononuclear leucocytes (L-MNs) from peripheral blood was inhibited by subantimitotic concentrations of the antitubulins demecolcine, podophyllic acid ethylhydrazide, vinblastine and griseofulvin. It is suggest that L-MN chemotaxis, like polymorphonuclear leucocyte (PMN) chemotaxis, is composed of a direct antitubulin-insensitive chemotaxis and a leukocyte-induced antitubulin-sensitive chemotaxis.

Antineoplastic Agents↗
PubMed1978

Effect of microtubule inhibitors on malignant invasion in vitro.

The malignant C3H/3T3 mouse cells MO4 invaded embryonic chick heart fragments in an organotypic coculture system on semisolid medium, which mimicked malignant invasion. In this system, at a dose of 1 microgram/ml, the microtubule inhibitors colchicine, demecolcine, vincristine sulfate, vinblastine sulfate, or methyl[5-(2-thienylcarbonyl)-1H-benzimidazol-1-yl]-carbamate (Nocodazole) totally inhibited malignant invasion. At the same dose the drugs were also mitostatic, which was apparent from C-mitoses and from the absence of postmetaphase figures. At a mitostatic dose of 10 microgram/ml, 5-fluorouracil (FUra), cytosine arabinoside, or bleomycin did not interfere with malignant invasion. Combined treatment of the cocultures with the antimetabolite FUra (10 microgram/ml) plus the microtubule inhibitor Nocodazole (1 microgram/ml) completely inhibited invasion. These cocultures also showed the effective inhibition of mitosis by FUra, because Nocodazole-induced C-mitoses were absent. The reversibility of the anti-invasive effect of 4-day treatment with Nocodazole (1 microgram/ml) was demonstrated in shaker cocultures with the use of fluid medium. Our in vitro experiments indicated that cytoplasmic microtubules were involved in malignant invasion and that cell division and invasion constituted separate characteristics of malignant cells.

Benzimidazoles↗
PubMed1978

Variably occlusive tape systems and the mitotic activity of stripped human epidermis. Effects with and without hydrocortisone.

This study elaborates on the effect of occlusive, partially occlusive, and nonocclusive tape systems containing hydrocoritsone on human epidermal mitotic activity that has been increased by tape stripping. The experimental variables included tape delivery systems affording total, partial (50%), or no occlusion to normal human skin. The test corticosteroid was hydrocortisone at a dose range of 1, 4, and 20 microgram/sq cm. Utilizing demecolcine cream, biopsy specimens, were taken and mitotic figures determined. Results suggest that potent antimitotic effects occur equally with semiocclusive and nonocclusive tapes containing hydrocortisone as with total occlusive tapes. Verification of the practicality of this in clinical use will depend on appropriate clinical trials in diseased states.

Cellulose↗
PubMed1978

Effects of occlusive tape systems on the mitotic activity of epidermis. With and without corticosteroids.

This study was designed to elaborate on the effects of occlusion and corticosteroids on human epidermal mitotic activity. The experimental variables included tape delivery systems that afforded total, partial (50%), or no occlusion to normal human skin. In some experiments, hydrocortisone, flurandrenolide, betamethasone, betamethasone valerate, and fluorometholone were added to these tape systems. Using demecolcine cream, biopsies were taken, and mitotic figures were determined. Results suggest that potent antimitotic effects occur with semiocclusive and nonocclusive tapes that contain corticosteroids, and that total occlusion is not necessary for this physiological effect. This suggests the possibility that the presumably better tolerated nonocclussive and partially occlusive systems might be used as dermatological drug delivery systems.

Administration, Topical↗
PubMed1977

Stimulation of cell division in ectopic kidney grafts following unilateral removal of the lung.

Small fragments of kidney tissue were grafted into the right lung (Xenopus laevis) and the left lung was subsequently removed. This stimulated compensatory hyperplasia (increased mitotic rate) in alveolar tissue of the right lung and in the kidney graft. This suggests that the stimulus to compensatory hyperplasia is location-specific rather than tissue- or organ-specific. After implantation into the lung the kidney grafts are revascularized by the surrounding pulmonary supply. Damage or functional impairment of an organ usually produces a localized increase in the rate of blood flow and we therefore propose that this may lead to an increased rate of cell division in one of two ways: by permitting an increased functional capacity in the tissue concerned, or by causing a more rapid local clearance of mitotic control factors.

Animals↗
PubMed1979

The effect of colcemid on the structure and secretory activity of ameloblasts in the rat incisor as shown by radioautography after injection of 3H-proline.

Enamel secretion by ameloblasts was investigated in the incisors of 100 gm normal and colcemid-injected male rats. Morphological studies were done on rats given a single intraperitoneal injection of 0.1 mg (1.25 mM) of colcemid and sacrified 1 to 4 hours after injection. Protein synthesis and secretion were investigated with radioautography in normal and colcemid-treated rats injected with 3H-proline and sacrificed at intervals between 0.5 and 3.5 hours after injection. Colcemid was injected 0.5 hours prior to 3H-proline in each experimental rat. Electron microscopic examination revealed several morphological alterations between 1 and 4 hours after injection of colcemid. These changes included fragmentation of the normally elongated rough endoplasmic reticulum into shorter profiles; a disorganization of the normally tubular configuration of the Golgi apparatus into a number of seples and profiles of smooth endoplasmic reticulum from Tomes' processes; and the accumulation of secretion granules at the mature face of the Golgi stacks, as well as in the infranuclear cytoplasm where thye are normally not found. Radioautography revealed that protein synthesis by the rough endoplasmic reticulum had continued in colcemid-altered ameloblasts. Labeled secretion granules were found at the mature surface of the Golgi stacks and in the infranuclear cytoplasm, however they did not migrate into Tomes' processes. Consequently, labeled enamel matrix did not appear extracellularly at the same time as in normal controls. Quantitative radioautography in the light microscope revealed that the effect of colcemid, although reversed within 4 hours, had temporarily inhibited normal migration, and exocytosis of secretion granules.

Ameloblasts↗
PubMed1975

Colcemid-induced polyploidy and aneuploidy in normal and tumour cells in vitro.

The frequency of colcemid-induced genome mutations (aneuploidy and polyploidy) in normal and SV40-transformed cultures of Djungarian hamster embryonic cells was studied. Genome mutations were easily induced by the drug in transformed but not in normal cultures. Elevation of colcemid concentration and prolongation of the incubation period did not substantially increase the frequency of genome mutations in normal cells. An attempt was made to study the causes of the differences in sensitivity to colcemid-mutagenicity of normal and transformed cells. Transformed cells did not include more 3H-colchicine than normal cells, and binding of the drug to cell homogenates was similar in both kinds of cultures. According to these data the higher sensitivity of transformed cells to colcemid is not connected either with increased permeability of the cell to the drug or with changes in its binding to tubulin.

Aneuploidy↗