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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↗
PubMed1975

Demecolcin and vinblastine sulphate as stathmokinetic agents for different tissues of the hairless mouse.

The dose/response relationship of the kinetostatic effect of demecolcin (ColcemidR) and vinblastine sulphate (VelbeR) was estimated in the epidermis, the forestomach, the jejunum and the colon of the hairless mouse (hr/hr) at 3 hours after intraperitoneal (i.p.) injection. A dose of 0.15 mg Colcemid per animal was found to be the lowest effective dose in all the organs tested. The value did not differ much from the corresponding effective dose of Velbe. This dose of Colcemid was then used to study the accumulation of arrested mitoses during the first 4 hours after i.p. injection. An almost linear increase in the mitotic count was found up to 4 hours in the epidermis, 3.5 hours in the forestomach and 3 hours in the jejunum and the colon. A dose of 0.15 mg Colcemid per animal i.p. with an observation time of 3 hours is thus a reliable method for estimation of the mitotic rate in many organs. It is also concluded that both Colcemid and Velbe can be used as reliable stathmokinetic drugs for both epidermis, forestomach and jejunum and colon mucosa provided that correct doses and short enough accumulation time (3 hours) is used.

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↗
PubMed1992

The cytoskeleton and the cellular traffic of the progesterone receptor.

Previous studies on glucocorticoid receptors have suggested the existence of interactions between the receptor and microtubule or actin networks. It was hypothesized that such interactions may contribute to the guidance of steroid hormone receptors towards the nucleus. We used a permanent L cell line expressing the delta 638-642 progesterone receptor. This mutant has all the characteristics of the wild type receptor except that the deletion of five amino acids inactivates the constitutive karyophilic signal. Consequently, the receptor is cytoplasmic in the absence of hormone but is shifted into the nucleus when administration of hormone activates the second karyophilic signal. Optical microscopy and confocal laser microscopy were used in intact cells or in cells depleted of soluble elements by permeabilization with detergents. By immunofluorescence, the receptor was found to be mainly concentrated in the perinuclear area. A small fraction of progesterone receptor (PR) persisted in this region after Triton X100 treatment. These observations suggested that the receptor could interact with some insoluble constituent(s) of the cytoplasm. However, careful colocalization studies showed that this heterogenous distribution was not due to interactions with microtubule, microfilament, or intermediate filament networks. Functional involvement of these networks in the translocation of the receptor into the nucleus was studied after cell treatment with cytoskeletal drugs such as nocodazole, demecolcine and cytochalasin. None of these compounds prevented or even delayed the hormone-dependent transfer of delta 638-642 PR into the nucleus. Similar conclusions were reached with the wild type receptor expressed by transfection in Cos-7 cells. PR was shifted from the nucleus into the cytoplasm by administration of energy-depleting drugs. After disruption of the various cytoskeletal networks normal nuclear reaccumulation of the receptor was observed when these drugs were removed. The results thus suggest that the progesterone receptor is not colocalized with the main cytoskeletal components. Disruption of the cytoskeletal networks does not prevent its nuclear translocation. Thus, karyophilic signals and interactions with the nuclear pore seem to be the primary determinants of the cellular traffic of the progesterone receptor.

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↗
PubMed1992

Cytogenetic mechanisms in the selective toxicity of cyclophosphamide analogs and metabolites towards avian embryonic B lymphocytes in vivo.

Cyclophosphamide (CP) is selectively toxic to avian and mammalian B lymphocytes, but the mechanisms of action are incompletely understood. We used a structure-activity approach to determine the cytogenetic mechanisms underlying the selective lymphoid toxicity in chicken embryos at 18-19 days of incubation. Two doses of 5-bromo-2'-deoxyuridine (BrdU; 3 mg/200 microliters x 2) were pipetted onto the inner shell membrane to label lymphocyte DNA over 20 h. A single dose of the CP analogs or metabolites was given 1 h after the initial BrdU application. After a terminal 3-h exposure to demecolcine to block cells in metaphase, the embryos were sacrificed at hour 20, and their bursae and thymi were removed for cytogenetic processing. Microscope slide preparations of metaphases were stained by the fluorescence-plus-Giemsa technique to differentiate the sister chromatids for an assessment of sister-chromatid exchange (SCE) induction and cell cycle progression based on replication cycle-specific staining patterns. Isophosphamide (1.25-40 mg/kg), phosphoramide mustard (0.7-45.7 mg/kg), and 4-methylcyclophosphamide (1.3-42.1 mg/kg) selectively damaged B cells as shown by dose-related reductions in the mitotic activity, inhibition of cell cycle kinetics, and approximately 9-15-fold increases in the SCE frequency above control. B cells were up to 392 times more susceptible to the toxicity of these three bifunctional alkylating agents compared to T cells based on reductions in the mitotic activity. At most of the drug doses tested, the T-cell mitotic index was not depressed significantly and was usually higher than the control value by as much as 50-60%. Importantly, monochloroethylcyclophosphamide (70-245 mg/kg; monofunctional alkylation) did not induce differential lymphoid toxicity, although a 9-fold increase in the SCE frequency of B cells was observed at the highest dose. Didechlorocyclophosphamide (181-422 mg/kg; acrolein generation only) was a weak SCE inducer (approximately 1.8-fold increase) and was not selectively toxic to B cells. Our data show that selective toxicity to B lymphocytes is strongly associated with bifunctional alkylation via the chloroethyl groups rather than with monofunctional alkylation and acrolein-mediated damage. In addition, the results with phosphoramide mustard and 4-methylcyclophosphamide emphasize that aldehyde dehydrogenase activity is not the primary determinant in the relative sparing of T lymphocytes in vivo.

Animals↗
PubMed1992

Effect of B-ring substituents on absorption and circular dichroic spectra of colchicine analogues.

Near-ultraviolet absorption and circular dichroic spectra of several B-ring derivatives of colchicine have been obtained in a variety of solvents. The spectra of the molecules in solvent were analyzed and compared with spectra of the molecules bound to tubulin. Absorption spectra of deacetamidocolchicine, deacetylcolchicine, demecolcine, and N-methyldemecolcine [B-ring substituents = H, NH2, NHCH3, and N(CH3)2, respectively] were analyzed by multiple differentiation of the spectrum. It was found that an amine substituent at the C-7 position on the B-ring of the colchicinoid affected the higher energy transition of the near-ultraviolet spectra of the colchicinoid in the absence of tubulin in a manner consistent with a hyperconjugative alteration of this transition. The fourth derivatives of the absorption spectra of all four molecules bound to tubulin were similar to each other and to colchicine. As was true in the case of colchicine, the negative near-ultraviolet circular dichroic band of the aminoclochicinoids was relatively unaffected by solvent, but the molar ellipticity of the band was greatly reduced with tubulin binding. It is concluded that the binding site environments of the B-ring analogues of colchicine, as probed by absorption and circular dichroic spectroscopy, are equivalent.

Animals↗
PubMed1992

Cytogenetic evidence of the multistep origin of head and neck squamous cell carcinomas.

BACKGROUND: Head and neck squamous cell carcinomas are associated with tobacco and alcohol use; therefore, the incidence of this type of tumor is expected to rise in the future as a result of the increasing numbers of female and adolescent smokers. Previous reports of cytogenetic analysis of this type of tumor have implicated a number of chromosomal regions in recurring changes, but no clear pattern of characteristic changes has emerged. PURPOSE: We have undertaken cytogenetic analysis of 10 cell lines which were established from squamous cell carcinomas of the head and neck, to determine the possible sites of additional tumor suppressor genes and oncogenes that may contribute to malignant transformation. METHODS: Metaphases were harvested from cultures of cells in the exponential growth phase, following exposure to Colcemid (demecolcine) at a final concentration of 30 ng/mL for 5 hours. Air-dried slides were G-banded using trypsin and Giemsa. Fifteen metaphases were photographed and fully karyotyped. RESULTS: We observed that several chromosomal regions were lost at high frequency, including 18q (10 of 10 lines), 10p (eight of 10 lines), 3p (six of 10 lines), 8p (seven of 10 lines), and the short arms of the acrocentric chromosomes (seven of 10 lines). Nine of 10 lines had additional copies of 7p. We also noted clustering of breakpoints in a number of chromosome bands, including 1p22, 10q11.2, 11q13, and the short arms of the acrocentric chromosomes. CONCLUSION: The observation of loss of multiple chromosomal regions in a significant number of lines analyzed is consistent with the theory that tumorigenesis occurs as the result of the accumulation of a number of genetic alterations, as proposed for colorectal carcinoma. The high frequency with which these changes are seen suggests that genes located in these regions have a role in the etiology of this type of tumor.

Carcinoma, Squamous Cell↗
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↗