Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0043167 (pertussis)
 19,595 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Intracellular calcium [Ca2+]i acts as an important intracellular messenger system for secretion and synthesis, cell growth and differentiation. In order to demonstrate definitively that a change in [Ca2+]i is responsible for a physiological event, one has to measure [Ca2+]i directly within intact cells and correlate the time course of any [Ca2+]i changes with the biological response. Measurement of [Ca2+]i was done in a single cell preloaded with fluorescent Ca indicator fura2 using a fluorescent unit (lonoquant) consisting of an inverted microscope (Zeiss IM 35) equipped with a mercury lamp and a rotating filter wheel containing filters at wavelengths of 340 and 380 nm. Cells were alternately excited and emission signals of fura 2-loaded cells were collected by a photomultiplier and recorded on-line on a computer screen. As a model system, the rat C-cell carcinoma cell line rMTC 6-23 secreting calcitonin was used. An acute elevation of extracellular calcium resulted in an increase in [Ca2+]i within 5 sec and rapid release of preformed calcitonin. This tight linkage between extracellular calcium and [Ca2+]i is mediated via Ca influx through voltage-dependent Ca channels. These channels are modulated by intracellular cAMP, yielding a rhythmic oscillation of [Ca2+]i, as well as by extracellular somatostatin blocking the Ca channel and the increase of [Ca2+]i via a pertussis toxin sensitive Gi protein. The change in [Ca2+]i is associated with changes in calcitonin secretion, confirming the stimulus secretion coupling via voltage-dependent Ca channels in C-cells.
 ...
PMID:Measurement of free cytosolic calcium in single cells: method and application. 135 76

The mechanisms by which somatostatin inhibits hormone release are complex and involve, among other things, reduction of both intracellular cAMP and intracellular calcium. We studied the influence of the long-acting somatostatin analogue octreotide on norepinephrine (NE)-induced changes in intracellular calcium ([Ca2+]i) in fura-2 loaded single cells of a rat medullary carcinoma cell line, rMTC 6-23. Increases in the extracellular calcium concentration ([Ca2+]e) induced a sudden rise in [Ca2+]i which could be blocked by EGTA or the calcium channel blocker verapamil. NE evoked a similar increase in [Ca2+]i, which also could be blocked by the addition of EGTA or verapamil. Octreotide prevented or reversed the NE-induced increase in [Ca2+]i. Pretreatment of the cells with pertussis toxin abolished the inhibitory effect of octreotide. Thus we conclude that the NE-induced rise in [Ca2+]i is due to an influx of [Ca2+]e, most probably through voltage-dependent calcium channels. Octreotide inhibits the NE-stimulated rise in [Ca2+]i by a pertussis toxin-sensitive G-protein, most probably through a direct effect on NE-activated calcium channels.
 ...
PMID:Somatostatin inhibits the norepinephrine-activated calcium channels in rMTC 6-23 cells: possible involvement of a pertussis toxin-sensitive G-protein. 136 Jan 85

A low-toxic lipopolysaccharide (BP-LPS) was isolated from killed Bordetella pertussis (Tohama strain). LD50 of BP-LPS was about 0.8 mg/mouse which was about 10-fold higher than the LD50 of E. coli-LPS(80 micrograms/mouse). Toxicity measured by decrease in body weight of BP-LPS-injected mice was similarly low. BP-LPS had strong antitumor activities against various murine syngeneic tumors, and its systemic administration caused clear regression of such as MM46 mammary carcinoma and Meth A fibrosarcoma. It is noteworthy that a tolerable dosage of BP-LPS (375 micrograms/mouse) showed clear antitumor activity against MH134 hepatoma, which is known to be insusceptible to usual types of BRM including bacterial LPS. These findings suggest that BP-LPS is a promising candidate as an antitumor agent for clinical use. Biological activities of BP-LPS were examined and compared with those of toxic LPS extracted from Escherichia coli and other enterobacteria. Activation or stimulation of macrophages and lymphocytes by these LPS, including TNF induction, was found to be similar. However, activation of human or murine neutrophils, as estimated by neutrophil-adherence assay in vitro, though induced by all other toxic LPS tested, was not induced by BP-LPS. This inability of BP-LPS to activate neutrophils is assumed to be related to its low toxicity.
 ...
PMID:BRM activities of low-toxic Bordetella pertussis lipopolysaccharides. 141 7

Interleukin-1 beta (Il-1 beta) and interleukin-1 alpha (Il-1 alpha) were shown to act as motility factors for the human breast carcinoma cell lines SK-BR-3 and ZR-75-1 in vitro. Both cytokines induced transition from the stationary to the motile phenotype (spreading). Il-1 beta stimulated translocation, shape change and random migration (chemokinesis) of SK-BR-3 cells as demonstrated by time-lapse video recordings and by a modified Boyden chamber assay. Interleukin-6 (Il-6) stimulated spreading of the SK-BR-3 cells; an additive effect with Il-1 beta on spreading and fast plasma membrane movements was evidenced. In the SK-BR-3 cell line, the signal transduction of Il-1 beta and Il-6 differed, since only the effect of Il-6 on spreading was sensitive to pertussis toxin. Both Il-1 beta and Il-6 required protein synthesis to stimulate spreading, since cycloheximide inhibited the effect of the cytokines. Induction of an autocrine loop of Il-6 in the SK-BR-3 cells by Il-1 beta was unlikely, since after stimulation with Il-1 beta, no induction of Il-6 activity was measured, nor was inhibition of stimulated spreading seen in the presence of an antiserum against Il-6. Addition of Il-8 or of an antiserum against Il-8 did not affect spreading. We concluded that Il-1 and Il-6 could act as motility factors for human breast carcinoma cells, in both an independent and an additive way.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Interleukin-1 is a motility factor for human breast carcinoma cells in vitro: additive effect with interleukin-6. 149 10

In past studies we observed that the chloride channel blocker, diphenylamine-2-carboxylate (DPC) and chemically related drugs (Hoechst compounds 131, 143, 144) inhibited cAMP formation in mouse pituitary tumor cells. The object of this study was to determine whether these drugs inhibited chloride transport in human T-84 colonic carcinoma cells through an effect on cAMP metabolism. Chloride secretion (measured as 125I efflux from isotope-preloaded cells) was stimulated in a concentration-dependent manner by vasoactive intestinal polypeptide (VIP) (EC50 = 1.5 x 10(-10) M) which similarly increased cAMP synthesis (EC50 = 1.6 x 10(-8) M). The cAMP response to VIP was inhibited 17, 52, 55, and 78% maximally by DPC and compounds 144, 143, and 131, respectively. In untreated T-84 cells, 125I secretion fell by 66% after 3 min; VIP (10(-7) M) increased secretion about fivefold over the same period. Both basal and VIP-stimulated 125I secretion were inhibited up to 60% by compound 131. Pretreatment of cells with pertussis toxin did not attenuate the inhibitory effect of channel blockers on either VIP-stimulated cAMP synthesis or 125I secretion. The cationophore, A-23187, which had no effect on cAMP formation, and 8-Br-cAMP both stimulated 125I secretion from T-84 cells. These secretory responses were inhibited by compound 131. The mechanism by which phenylanthranilic acids antagonize cAMP synthesis and its significance is not known; however, the data suggest that this family of drugs may inhibit chloride transport by both cAMP-dependent and independent mechanisms.
 ...
PMID:Antagonists of epithelial chloride channels inhibit cAMP synthesis. 164 53

Tumor metastasis requires highly motile cells that can respond to appropriate stimuli. A2058 human melanoma cells were shown previously to secrete a highly potent autocrine motility factor (AMF) that stimulates chemokinetic movement. We have shown that the insulin polypeptides (IPs; insulin-like growth factors I and II [IGF-I, -II] and insulin) stimulated A2058 cell chemotaxis and chemokinesis. We now report that the IPs and AMF stimulate locomotion in other human malignant cell lines. Insulin (100 nM) induced motility of up to 50% of the magnitude of the AMF response in human carcinoma lines MDA-231 (breast), T24 (bladder), and OVCAR3 (ovarian). The tumorigenic and metastatic 5R Haras-transfected rat embryo fibroblast cell line responded to insulin with both chemotaxis and chemokinesis and was 100% of that seen for AMF. The ED50 for IGF-I in the carcinoma cell lines was in the order of I nM, but the magnitude of the responses at this concentration was 40% of the AMF-stimulated response, with the exception of the A2058 cells, which were maximally stimulated at I nM. IGF-II induced maximal motility of 75 to 130% of the AMF-stimulated response in the carcinoma lines with ED50 of less than or equal to 10 nM. IGF-II-stimulated motility in the carcinoma lines was predominantly chemotactic by modified checkerboard analysis. Cell pretreatment with pertussis toxin inhibited 90-100% of AMF-induced motility, whereas migration to the IPs was not pertussis toxinsusceptible. In growth studies, IGF-I induced mitogenesis up to 140% of basal media control growth. In general, maximal growth stimulation was seen at 100 nM IGF-I, and optimal migration was seen at 10 nM IGF-I. The IGFs are secreted by normal stroma in a number of organs that are common sites for primary and metastatic disease. Therefore, we suggest that IPs may be important homing and mitogenic signals for tumor cells in the process of invasion and metastasis and that the differential motility stimulation and respective mechanisms of action by these physiologically important agents may underlie the diversity of the metastatic process.
 ...
PMID:Heterogeneity of the motility responses in malignant tumor cells: a biological basis for the diversity and homing of metastatic cells. 211 98

Intratumoral induction of tumour necrosis factor (TNF) by administration of Bordetella pertussis vaccine (BPV) as compared with that by the agent OK-432 was investigated in mice. Two hours after such administration tumour tissues tested were resected from the mice, homogenised, and the TNF activities in the homogenate were assayed using a L-929 fibroblast assay. Intravenous injection of BPV into mice bearing the MM46 carcinoma resulted in a greater concentration of TNF in the tumour homogenate than in the serum. With OK-432, however, there was a greater concentration of TNF in the serum than in the tumour homogenates. A high level of intratumoral TNF induction by BPV was also observed in mice bearing Meth A fibrosarcoma or Lewis lung carcinoma. The therapeutic effect against the Meth A fibrosarcoma was in parallel with the intratumoral TNF activity. Intratumoral TNF activity is therefore believed to be a good index of therapeutic effect.
 ...
PMID:Intratumoral induction of tumour necrosis factor by systemic administration of Bordetella pertussis vaccine. 220 45

The rabbit ovarian carcinoma model was prepared by injecting VX-2 carcinoma into the ovary and the effects of endogenous Tumor Necrosis Factor (TNF)-induction therapy in combination with chemotherapy were studied. In this model, carcinoma metastasizes easily to the abdominal cavity, lung and liver, and resists treatment. Endogenous TNF was induced by a series of injections of OK-432 0.3KE and OK-432 3KE at 3 hour intervals (OK-OK group), or 1 x 10(10) cells of Bordetella pertussis vaccine (BPV group). Another group were sequential given a series of injections of CDDP (2mg/kg) intraperitoneally and OK-432 intravenously (an OK-OK and CDDP group). Higher activity of endogenous TNF was induced by BPV in comparison with OK-OK plus OK-OK and CDDP. Obvious hemorrhagic necrosis was observed in the implanted ovary in the BPV group. Compared with the control group, pulmonary metastasis was seen in the OK-OK and OK-OK plus CDDP groups (partial remission). These results show that the endogenous TNF induction therapy could be expected to be an effective antitumor therapy for advanced ovarian cancer.
 ...
PMID:[The effect of endogenous tumor necrosis factor (TNF)-induction therapy in the model of VX-2 ovarian carcinoma in the rabbit]. 227 1

Several drugs known to induce differentiation in tumor cells were analyzed for their effects on the beta-adrenergic receptor-coupled adenylate cyclase system in two human carcinoma cell lines, HeLa and A431. Each of the drugs was tested alone or in combination with sodium butyrate (NaBu), a known inducer of this signal transduction system. Puromycine amino nucleoside (PMAN) caused the largest increase in beta-adrenergic receptors in HeLa cells followed by hexamethylenebisacetamide (HMBA) whereas 5'-azacytidine (5AZC) was ineffective. In addition, PMAN but not the others acted together with NaBu to elevate receptor levels 12-fold over control values. In contrast, HMBA and 5AZC were much more effective on A431 cells, PMAN caused only a slight increase in beta receptors and none of the drugs acted in concert with NaBu. The increase in beta receptors was usually accompanied by a corresponding increase in isoproterenol-stimulated adenylate cyclase activity. These effects of the drugs appeared to require protein synthesis as they were blocked by cycloheximide. In addition, some of the drugs caused a substantial decrease in basal adenylate cyclase activity. This effect on basal activity was abolished in cells treated with pertussis toxin, which ADP-ribosylates the inhibitory GTP-binding protein, Gi. Both HeLa and A431 cells contained a 41 kDalton substrate for the toxin which corresponds to the alpha subunit of Gi. The Gi subunit was ADP-ribosylated by the toxin to a similar extent in membranes from control and drug-treated cells. Thus, the drugs appear to induce quantitative changes in beta-adrenergic receptors and qualitative changes in Gi which results in a highly responsive beta-adrenergic-stimulated adenylate cyclase.
 ...
PMID:Modulation of the beta-adrenergic receptor-coupled adenylate cyclase by chemical inducers of differentiation: effects on beta receptors and the inhibitory regulatory protein Gi. 245 8

In human adipocyte plasma membranes, pertussis toxin catalysed the ADP-ribosylation of an apparently single 40 kDa protein. The same protein was also observed in Western blots by using an antibody which identifies the C-terminal decapeptide of Gi alpha (alpha subunit of Gi). In analogous experiments, cholera toxin and an antibody raised against the C-terminal decapeptide of Gs alpha (alpha subunit of Gs) were used to identify two proteins of 42 and 45 kDa, the former of which was more prominent. A method was developed to estimate the relative amounts of Gi and Gs in crude adipocyte plasma membranes in a single immunoblot by using the two antisera. In animal models, changes in the amounts of G-proteins have been suggested to explain alterations in hormone-responsiveness in hypothyroidism and obesity. However, the amounts of Gi and Gs were unaltered in thyroidectomized papillary-carcinoma patients who had been without hormone substitution for 4 weeks. In adipocyte plasma membranes prepared from markedly obese subjects, the amounts of both Gi alpha and Gs alpha as calculated per mg of protein were decreased, but the Gi/Gs ratio remained unaltered in comparison with control subjects.
 ...
PMID:Guanine-nucleotide-binding proteins Gi and Gs in fat-cells from normal, hypothyroid and obese human subjects. 250 51


1 2 3 4 5 6 Next >>