Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0019204 (hepatocellular carcinoma)
 71,386 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In Zajdela hepatoma cells (ZHC) the plasma membrane Ca2+ pump displayed no sensitivity to glucagon (19-29) (mini-glucagon), whereas in hepatocyte this metabolite of glucagon evoked a biphasic regulation of the Ca2+ pump system via a cholera toxin-sensitive G protein. Analysis of G protein subunits in ZHC membranes indicated the presence of cholera toxin-sensitive Gs alpha and G beta gamma proteins, whose functionality was manifested by GTP and NaF stimulation of adenylylcyclase activity, and pertussis toxin-catalyzed ADP-ribosylation of Gi alpha, respectively. However, immunoblotting experiments suggested a lower content in beta gamma subunits in ZHC as compared with hepatocyte plasma membranes. Complementation of ZHC or hepatocyte plasma membranes with purified beta gamma subunits from transducin (T beta gamma) caused inhibition of the basal activity of the Ca2+ pump at 10 and 300 ng/ml, respectively, and revealed (in ZHC) or increased (in hepatocytes) sensitivity of the system to mini-glucagon. After cholera toxin treatment of ZHC, T beta gamma no longer reconstituted the response of the Ca2+ pump to mini-glucagon, suggesting that the mechanism of beta gamma action is dependent on an association with the alpha subunit of a cholera toxin-sensitive G protein. It is concluded that G beta gamma subunits control both the basal activity of the plasma membrane Ca2+ pump and its inhibition by mini-glucagon.
 ...
PMID:Role of G protein beta gamma subunits in the regulation of the plasma membrane Ca2+ pump. 131 Mar 15

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

The cellular mechanism by which the angiotensin II (AII) agonist, Sar1-AII, inhibits production and release of angiotensinogen in human hepatoma HepG2 cells was examined. Pretreatment of HepG2 cells with pertussis toxin attenuated the ability of Sar1-AII to block angiotensinogen production. This effect could be correlated with the in situ ADP-ribosylation of a protein(s) of apparent molecular weight 39,000-41,000 on SDS-PAGE, and attenuation of the ability of Sar1-AII to inhibit cAMP accumulation. The role of cAMP in angiotensinogen production was examined. A transient increase in cAMP accumulation above basal could be evoked by forskolin (8-fold) or by glucagon (5-fold) using insulin-deficient media. Although neither forskolin nor glucagon had a significant effect on angiotensinogen production agents producing a sustained increase in intracellular cAMP (8-bromo-cAMP, dibutyryl-cAMP, cholera toxin) were able to increase angiotensinogen production. Although these data indicate that intracellular cAMP is a regulatory factor in angiotensinogen production other evidence suggests that modulation of intracellular cAMP is not entirely responsible for the effects of Sar1-AII.
 ...
PMID:Involvement of a pertussis toxin-sensitive G protein in the regulation of angiotensinogen production by an angiotensin II analog in HepG2 cells. 217 1

Ethiopia is a country of 45 million people in northeast Africa. With a stagnant, agriculture-based economy and a per capita gross national product of $110 in 1984, it is one of the world's poorest nations. 70% of the children are mildly to severely malnourished, and 25.7% of children born alive die before the age of 5. Life expectancy is 41 years. The population is growing at the rate of 2.9%/year, but only 2% of the people use birth control. After the 1974 revolution, the socialist government nationalized land and created 20,000 peasant associations and kebeles (urban dwellers' associations), which are the units of local government. The government has set ambitious goals for development in all sectors, including health, but famine, near famine, forced resettlement programs, and civil war have prevented any real progress from being made. The government's approach to health care is based on an emphasis on primary health care and expansion of rural health services, but the Ministry of Health is allocated only 3.5% of the national budget. Ethiopia has 3 medical schools -- at Addis Ababa, Gondar, and the Jimma Institute of Health Sciences. Physicians are government employees but also engage in private practice. A major problem is that a large proportion of medical graduates emigrate. Ethiopia has 87 hospitals with 11,296 beds, which comes to 1 bed per 3734 people. There are 1949 health stations and 141 health centers, but many have no physician, and attrition among health workers is high due to lack of ministerial support. Health care is often dispensed legally or illegally by pharmacists. Overall, there is 1 physician for 57,876 people, but in the southwest and west central Ethiopia 1 physician serves between 200,000 and 300,000 people. In rural areas, where 90% of the population lives, 85% live at least 3 days by foot from a rural health unit. Immunization of 1-year olds against tuberculosis, diphtheria-pertussis-tetanus, poliomyelitis, and measles is 11, 6, 6, and 12% respectively. Infectious diseases dominate the medical scene in Ethiopia. In 1984, tuberculosis accounted for 11.2% of hospital admissions and 12.2% of deaths. The leading cause of childhood mortality in 1984 was diarrhea (45%). Malaria, trypanosomiasis, schistosomiasis, leishmaniasis, and meningococcal meningitis are endemic. Intestinal parasitism is rampant, and the nationwide prevalence of leprosy is 3/1000. Venereal diseases were the 9th most common cause of hospital outpatient visits in 1984, but AIDS is rare. The leading noninfectious diseases are rheumatic and syphilitic heart disease, hypertension, diabetes mellitus, hepatoma, and elephantiasis. Ethiopia has the highest number of cases of nonfilarial elephantiasis -- an estimated 350,000 cases -- in the world. Aside from a large influx of money, the most necessary changes to improve the health system are lowering the salaries of doctors and nurses, reorienting physician training toward primary health care, increasing the quality of existing health services, more efficient management, and better coordination between the Ministry of Health and the voluntary organizations.
 ...
PMID:Health and medical care in Ethiopia. 271 Jan 85

Hepatic metabolism and gene expression are among the factors controlled by the cellular hydration state, which changes within minutes in response to aniso-osmotic environments, cumulative substrate uptake, oxidative stress and under the influence of hormones such as insulin. The signalling events coupling cell-volume changes to altered cell function were studied in H4IIE rat hepatoma cells. Hypo-osmotic cell swelling resulted within 1 min in a tyrosine kinase-mediated activation of the extracellular signal-regulated protein kinases Erk-1 and Erk-2, which was independent of protein kinase C and cytosolic calcium. Activation of mitogen-activated protein kinases was followed by an increased phosphorylation of c-Jun, which may explain our recently reported finding of an about 5-fold increase in c-jun mRNA level in response to cell swelling. Pretreatment of cells with pertussis or cholera toxin abolished the swelling-induced activation of Erk-1 and Erk-2, suggesting the involvement of G-proteins. Thus, a signal-transduction pathway resembling growth factor signalling is activated already by osmotic water shifts across the plasma membrane, thereby providing a new perspective for adaption of cell function to alterations of the environment.
 ...
PMID:Activation of extracellular signal-regulated kinases Erk-1 and Erk-2 by cell swelling in H4IIE hepatoma cells. 761 47

UNICEF decided to achieve the 1977 World Health Organization objective Health For All By The Year 2000 through primary health care, utilizing growth monitoring, oral rehydration therapy, breast-feeding, immunization, family planning, and education of women. Since the 1960s BCG (bacillus Calmette-Guerin) vaccination, DPT (diphtheria, pertussis, tetanus) and OPV (oral polio vaccine) have been available in Sri Lanka. The expanded program of immunization has almost eliminated diphtheria, pertussis, neonatal tetanus, and poliomyelitis. Tuberculous meningitis, bone and joint tuberculosis, measles, and miliary tuberculosis have become very rare. Among other vaccine-preventable diseases, mumps is the commonest cause of aseptic meningitis and viral encephalitis in children. Maternal rubella in the first trimester causes abortion or gross teratogenic effects including congenital heart disease. Safe vaccines may be used to prevent mumps and rubella. In recent years there has been a resurgence of measles in North America among school children, and presently a 2nd dose of vaccine is recommended for children. Japanese B encephalitis has a mortality rate of over 30% and half the survivors have residual brain damage. The Ministry of Health has immunized susceptible children in some of the prevalent areas. This vaccine also gives partial protection against dengue hemorrhagic fever. In Hong Kong, Singapore, and Taiwan hepatitis B vaccine is part of the national immunization schedule because of the common occurrence of primary hepatoma of the liver. At present this vaccine is recommended for health workers in Sri Lanka. Meningococcal meningitis occurs in some Middle East countries such as Saudi Arabia, thus Haj pilgrims are advised to be vaccinated against it before the pilgrimage. In Sri Lanka beta-thalassemia major is prevalent, and as most of these patients are subjected to splenectomy, pneumococcal vaccine should be given to them. Currently research work is being carried out for development of vaccines against rotavirus, streptococcal, and hepatitis A infection.
 ...
PMID:Improving child survival through immunisation. 814 30

Quinones are widely distributed substances of often potential toxicological significance. On the other hand, cyclic AMP is known to promote a cell-survival response and to retard apoptosis [Berridge, Tan and Hilton (1993) Exp. Hematol. 21, 269-276]. Therefore the effects of quinones on adenylate cyclase were tested. Adenylate cyclase is rapidly inhibited by quinones, with IC50 values of 40-45 microM for p-benzoquinone (BQ) or 200 microM for dichlorophenol-indophenol (DCIP), with 2-substituted quinones being inactive. Membrane solubilization decreases the IC50 values for BQ and DCIP to 18 microM and 40 microM respectively. The inhibition is not affected by GTP, GDP or analogues, or by cholera and pertussis toxins; therefore it is not mediated by a G-protein or the activation of a defined receptor. Further, the inhibition stoichiometrically competes with forskolin activation of adenylate cyclase, equimolar concentrations of quinone and forskolin restoring the enzyme activity to its basal value. Reduction of BQ with sodium dithionite stoichiometrically prevents the inhibition of adenylate cyclase; in turn, oxidation of hydroquinone with ferricyanide fully restores it, indicating that the oxidized state of the quinone is required for inhibition. In addition, BQ is cytotoxic in vivo on HepG2, a human hepatocellular carcinoma cell line, but the effect can be prevented with forskolin. In plasma membranes, BQ tightly binds only one major and two minor proteins; these BQ-binding proteins were purified by means of labelling with [14C]BQ followed by PAGE under native conditions. Together these observations indicate that the action of quinone can be traced to targeting a limited number of proteins at the plasma membrane in a highly selective way and to affecting key enzymes such as adenylate cyclase.
 ...
PMID:Selective inhibition of adenylate cyclase in bovine cortex by quinones: a novel cellular substrate for quinone cytotoxicity. 819 59

A lipopolysaccharide (BP-LPS) isolated from killed Bordetella pertussis (Tohama strain) was determined to have low toxicity based on the mortality and decrease in body weight of BP-LPS-injected mice. BP-LPS, administered intradermally or intraperitoneally, clearly inhibited the growth of an MM46 murine mammary carcinoma. When compared with a toxic Escherichia coli-derived LPS, BP-LPS displayed excellent anti-tumour activity against MH134 hepatoma and Meth A fibrosarcoma. As part of a combined chemotherapy/immunotherapy regimen, BP-LPS also seemed to prolong the lifespan of mice inoculated with Lewis lung carcinoma. BP-LPS thus appears to have valuable characteristics as an anti-tumour agent.
 ...
PMID:Anti-tumour activity of low-toxicity lipopolysaccharide of Bordetella pertussis. 819 67

The effect of anisoosmolarity on the abundance of various mRNA species was examined in perfused rat liver and H4IIE rat hepatoma cells. Hyperosmotic exposure (385 mosmol/l) of isolated rat livers increased mRNA levels for tyrosine aminotransferase (TAT) by 246% and those for phosphoenolpyruvate carboxykinase (PEPCK) by 186%, whereas hypoosmotic exposure (225 mosmol/l) decreased their levels to 43% and 42%, respectively. mRNA levels for fructose-1,6-bisphosphatase (FBP), argininosuccinate lyase (ASL), argininosuccinate synthetase (ASS), glutamine synthetase (GS), glutaminase (GA) and glucokinase (GK) were largely unaffected. In H4IIE cells the modulation of TAT and PEPCK mRNA levels by anisoosmotic exposure was similar to that found in perfused rat liver. ASL and glutaminase mRNA levels were influenced in an opposite manner. The effects of anisoosmolarity on PEPCK mRNA levels in H4IIE cells were largely abolished in the presence of the protein kinase inhibitors H-7, H-89 and HA-1004. Other protein kinase inhibitors such as Go-6850, KN-62, Rp-8-CPT-cAMPS, rapamycin, wortmannin, genistein or herbimycin did not prevent the osmosensitivity of PEPCK mRNA levels. Also pertussis and cholera toxin, vanadate and colchicine did not affect the osmosensitivity of PEPCK mRNA levels. The data suggest that anisoosmotic exposure acts on the levels of some but not all mRNA species and that this action may involve changes in protein phosphorylation. They further indicate that the recently identified osmosensitive signal transduction pathway which involves a G-protein and tyrosine kinase dependent activation of mitogen-activated protein kinases is apparently not involved in the osmoregulation of PEPCK mRNA levels.
 ...
PMID:Anisoosmotic regulation of hepatic gene expression. 892 14

The influence of aniso-osmolarity on the activity of the MAP kinases Erk-1 and Erk-2 was studied in C6 glioma cells. Hypo-osmotic treatment (205 mosmol/l) led to an increased activity of Erk-1 and Erk-2 within 3 min, which became maximal at 10 min and returned to basal level within 120 min. In contrast, Erk activity was reduced under hyper-osmotic conditions (405 mosmol/l), compared to the normo-osmotic control (305 mosmol/l). Erk activation was accompanied by a mobility shift of Raf-1. Hypo-osmotic exposure increased the cytosolic Ca2+ concentration ([Ca2+]i). Absence of extracellular Ca2+ largely abolished the [Ca2+]i response to hypo-osmolarity, whereas Erk activation following hypo-osmotic stimulation remained unaffected, suggesting a Ca2+ independence of the osmosignalling pathway to the MAP kinases. Both the Ca2+ response as well as the Erk activation following hypo-osmotic exposure were maintained in the presence of the phospholipase C inhibitor U73122. Application of 8-CPT cAMP, forskolin/isobutylmethylxanthine or isoproterenol blocked Erk activation following hypo-osmotic treatment of the cells, suggesting a role of the Ras/Raf pathway upstream from Erk-1 and Erk-2. Protein kinase C (PKC) is unlikely to play a role in the hypo-osmolarity- induced signalling towards MAP kinases, as revealed by inhibition of PKC with Go6850. Inhibition of pertussis- or cholera toxin-sensitive G-proteins as well as inhibition of tyrosine kinases with genistein and of PI3 kinase by wortmannin had no effect on the Erk response to hypo-osmolarity. It is concluded that osmosignalling in C6 glioma cells differs upstream of the MAP kinases from that observed in primary rat astrocytes, H4IIE rat hepatoma cells and isolated rat hepatocytes.
 ...
PMID:Osmosignalling in C6 glioma cells. 900 90


1 2 3 4 Next >>