Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0011570 (depression)
 172,036 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The hemodynamics during hemodilution occurred after hepatectomy for hepatocellular carcinoma with liver cirrhosis and its influences on the liver functions were studied. The hematocrit value gradually decreased about 10% until the 4th postoperative day owing to hemodilution after hepatectomy. While anemia progressed, cardiac index inversely increased. Under such a condition, oxygen consumption was maintained so that acidosis did not develop. Arterial blood ketone body ratio was also kept within a normal range except for a case whose hematocrit value decreased to 17.1%. Although the escaped hepatic enzymes such as GOT and GPT increased in the serum after hepatectomy, hemodilution was not responsible for their increase. While total bilirubin increased in the severe hemodiluted group, the increase was not due to hemodilution but caused by blood transfusion. The protein synthesis of the liver measured by rapid turnover protein levels in plasma was depressed after surgery, and this depression prolonged to the 14th postoperative day in the group whose hematocrit value decreased below 20%. These results suggest that it is better to keep hemodynamics without blood transfusion unless the hematocrit value decrease below 20%, and also better to maintain the hematocrit above 20% for liver regeneration after hepatectomy.
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PMID:[The hemodynamics during hemodilution and its influence on the liver functions after hepatectomy for hepatocellular carcinoma with liver cirrhosis]. 165 85

Sixteen children, aged 16 days to 13 years with hepatoblastoma (HB) (13 patients) or hepatocellular carcinoma (HCC) (3 patients), were given a total of 89 courses of cisplatin and doxorubicin (PLADO) as IV continuous infusion. All tumors were confined to the liver except for 1 hepatoblastoma patient with pulmonary metastases at presentation. Tumor response to PLADO was evaluable in 10 children (8 HB, 2 HCC) treated with preoperative chemotherapy and in another 2 HB patients treated when they developed pulmonary metastases after initial treatment with surgery alone. There were 2 complete responses (2 HB with pulmonary recurrences), 7 very good partial responses (6 HB and 1 HCC), 2 partial responses (1 HB, 1 HCC), and 1 stable disease (HB). The last patient underwent orthotopic liver transplantation whereas all the other patients had their tumor completely excised at delayed surgery. Documented toxicity was BM depression (16 patients), infection (11), vomiting (11), mucositis (3), hearing loss (1), and cardiotoxicity (1). These data indicate that PLADO in continuous infusion is effective in the treatment of malignant epithelial liver tumors with acceptable toxicity.
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PMID:Effectiveness and toxicity of cisplatin and doxorubicin (PLADO) in childhood hepatoblastoma and hepatocellular carcinoma: a SIOP pilot study. 185 Aug 17

An overview was presented of our approach of inhibition of de novo and salvage pathways in pyrimidine and purine metabolism. 1. Combination of acivicin, an inhibitor of de novo biosynthesis, and dipyridamole, a transport inhibitor, provided synergistic cytotoxicity in hepatoma and colon carcinoma cells. 2. AZT, a competitive inhibitor of the salvage enzyme, thymidine kinase, and 5-FU or MTX provided synergistic cytotoxicity in hepatoma 3924A. In human colon carcinoma HT-29 cells AZT and methotrexate yielded synergistic cytotoxicity and thymidine and hypoxanthine together provided protection from the action of these drugs. 3. These observations are significant because in rat hepatoma 3924A and in human cell lines HT-29, HL-60 and K562 thymidine kinase activity was 16- to 67-fold higher than that of dTMP synthase. Therefore, inhibition of dTMP synthase activity alone may provide poor responses because the salvage pathways can circumvent this block. 4. In leukemic patients treated with tiazofurin, an inhibitor of IMP dehydrogenase, the rate-limiting enzyme of GTP biosynthesis, and with allopurinol, which inhibits GPRT activity through raising plasma hypoxanthine levels, synergistic therapeutic results were obtained. The responses in sensitive patients entailed a decrease in IMP dehydrogenase activity and GTP concentration in leukemic cells and down-regulation of the ras and myc oncogenes. The down-regulation of the ras oncogene by tiazofurin through the decrease of GTP concentration has now been shown in K562, HL-60 and hepatoma cells and in patients with chronic granulocytic leukemia in blast crisis. Tiazofurin may be useful in studies on selective depression of the expression of the ras oncogene. 5. In 27 consecutive patients 50% responded positively to tiazofurin treatment. From this group, 10 out of 12 patients (83%) with chronic granulocytic leukemia in blast crisis responded to tiazofurin treatment.
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PMID:Regulation of de novo and salvage pathways in chemotherapy. 187 99

We have studied the effect of intraarteric infusion chemotherapy with missile chemotherapy, induced hypertensive chemotherapy and/or two-route infusion chemotherapy in 14 liver tumors (7 cases with liver metastasis from gastric cancer, 3 cases with liver metastasis from colonic cancer, 4 cases with hepatoma). Results indicated that PR in 6 (46.1%) out the 13 evaluated cases. The toxicity was not evident except for slight bone marrow depression with 5 cases and a low grade fever with 2 cases. These results indicate that intraarterial infusion chemotherapy with drug delivery system can be considered one of the treatment therapies available for a nonresectable tumor.
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PMID:[Study of intraarteric infusion chemotherapy with drug delivery system]. 211 2

To evaluate the significance of natural killer (NK) cell activity in the clinical assessment of patients with hepatocellular carcinoma (HCC), 32 patients combined with liver cirrhosis (LC) and HCC, and 29 LC patients were studied. The NK cell activity was markedly decreased in HCC patients and the LC group as compared with the control group, but there was no statistical difference between the NK cell activity of the HCC group and the LC group. The depression of NK cell activity in HCC patients was inversely correlated with the patient's age, and the HCC patients with venous invasion or with both lobes involved had lower NK cell activity. These results suggest that the decreased NK cell activity in HCC patients might be related to the coexistent liver disease, and marked decrease in NK cell activity might be one of the causes for the early development and invasion of HCC.
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PMID:Natural killer cell activity in patients with hepatocellular carcinoma relative to early development and tumor invasion. 215 37

A transient depression of HBV serologic markers has been reported for some chronically infected patients treated with human interferons. To determine a molecular basis for these observations, a human, HBV-carrying, hepatocellular carcinoma cell line (PLC/PRF/5) was treated with human alpha, beta, or gamma interferons. Administration of these interferons resulted in a marked depression of HBV surface antigen (HG-sAg) levels in the culture medium. This inhibition was transient, with media levels of HBsAg rising substantially within 48 hours following the termination of interferon treatment. Cell growth rates were not affected by alpha interferon treatment, indicating that overall cell protein synthesis was not substantially altered. Although all three classes of interferons were effective in lowering HBsAg levels in the culture medium, intracellular levels of HBsAg-specific RNA were unaffected. These results suggest that the transient depression of HBV serologic markers in interferon-treated patients may be a consequence of the failure to disrupt the intracellular pools of HBV RNA in the liver.
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PMID:Direct modulation of HBV surface antigen in a human, HBsAg-producing hepatocellular carcinoma cell line by alpha, beta, or gamma interferons. 217 72

A complementary DNA (cDNA) clone (B4) encoding the catalytic subunit of a cAMP-dependent protein kinase (PKAc) was isolated from a lambda gt10 rat brain cDNA library, using a synthetic oligonucleotide probe whose sequence was based on the known amino acid sequence of a bovine cardiac PKAc. Sequence analysis of this clone revealed a region of 1002 nucleotides which encodes a protein that is 92% homologous to amino acids 17-350 of the bovine cardiac PKAc protein. This clone lacks coding sequences for amino acids 1-16 of the latter protein. Nevertheless, it provided a useful probe to analyze expression of the related gene in a variety of systems. Northern blot analyses using a 32P-labeled probe prepared from a 0.6-kilobase PstI fragment of clone B4 revealed an abundant 4.6-kilobase band in rat brain RNA and lesser amounts of this 4.6-kilobase RNA in rat heart and liver. A 4.6-kilobase RNA was also detected in RNA samples obtained from mouse fibroblasts. This probe also detected homologous RNA in a variety of nonrodent species. In subsequent experiments, this cDNA was used as a probe to elucidate the role of PKAc in post-surgical hepatic regeneration and diethylnitrosamine-induced hepatomas in the rat. These experiments revealed that, following partial hepatectomy, PKAc mRNA is decreased 3-fold by 12 h, returning to normal by 72 h; hepatomas showed no consistent pattern of change in PKAc mRNA levels as compared to controls. Our results indicate that this cDNA encodes an isoform of PKAc which is distinct from PKAc-alpha isolated by Uhler et al. (Proc. Natl. Acad. Sci. USA, 83: 1300-1304, 1986) but highly homologous to PKAc-beta isolated by Showers and Maurer (J. Biol. Chem., 261: 16288-16291, 1986), that depression of cAMP-dependent protein phosphorylation may be an important mechanism in the regeneration of mature rat liver but is not a consistent alteration in chemically induced hepatoma, and that this cDNA is useful as a probe for the study of the role of PKAc gene expression in growth control, particularly in rodent species.
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PMID:Isolation of a complementary DNA encoding the catalytic subunit of protein kinase A and studies on the expression of this sequence in rat hepatomas and regenerating liver. 230 20

We defined the acute phase behaviour of a number of rabbit plasma proteins in studies (in vivo) and studied the effects of monokine preparations on their synthesis by rabbit primary hepatocyte cultures. Following turpentine injection, increased serum levels of C-reactive protein, serum amyloid A protein, haptoglobin, ceruloplasmin, and decreased concentrations of albumin were observed. In contrast to what is observed in man, concentrations of alpha 2-macroglobulin and transferrin were increased. Co-culture of primary hepatocyte cultures with lipopolysaccharide-activated human peripheral blood monocytes or incubation with conditioned medium prepared from lipopolysaccharide-activated human or rabbit monocytes resulted in dose-dependent induction of serum amyloid A, haptoglobin, ceruloplasmin and transferrin and depression of albumin synthesis, while C-reactive protein synthesis and mRNA levels remained unchanged. A variety of interleukin-1 preparations induced dose-dependent increases in the synthesis and secretion of serum amyloid A, haptoglobin, ceruloplasmin and transferrin and decreased albumin synthesis. Human recombinant tumour necrosis factor (cachectin) induced a dose-dependent increase in synthesis of haptoglobin and ceruloplasmin. In general, human interleukin-1 was more potent than mouse interleukin-1 and tumour necrosis factor. None of the monokines we studied had an effect on C-reactive protein synthesis or mRNA levels. These data confirm that C-reactive protein, serum amyloid A, haptoglobin and ceruloplasmin display acute phase behaviour in the rabbit, and demonstrate that, in contrast to their behaviour in man, alpha 2M and transferrin are positive acute phase proteins in this species. While both interleukin-1 and tumour necrosis factor regulate biosynthesis of a number of these acute phase proteins in rabbit primary hepatocyte cultures, neither of these monokines induced C-reactive protein synthesis. Comparison of these findings with those in human hepatoma cell lines, in which interleukin-1 does not induce serum amyloid A synthesis, suggests that the effect of interleukin-1 on serum amyloid A synthesis may be indirect.
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PMID:Regulation of rabbit acute phase protein biosynthesis by monokines. 246 85

To evaluate the clinical value of splenectomy for hepatic resection, a total of 20 patients with hepatocellular carcinoma and hypersplenism were examined focusing on a change of total serum bilirubin values after surgery. Both hepatectomy and splenectomy were simultaneously performed in 12 patients, and in 8 patients as a staged operation. Postoperatively, a significant depression of bilirubin values was observed in a group with the preoperative values between 1.0mg/dl and 2.0mg/ml. Three factors (bilirubin, albumin and prothrombin time) in clinical stage were improved just after splenectomy with a statistical significance (p less than 0.05) in a group received staged operation. In 7 out of 8 patients, clinical stages were getting better as one or two stages prior to the hepatectomies. Therefore, we recommend the addition of splenectomy to hepatectomy in the patients whose hyperbilirubinemia are assumed to be correlated with coexisting hypersplenism.
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PMID:[The role of splenectomy in patients with hepatocellular carcinoma and hypersplenism as an aid to hepatectomy]. 255 82

Substrate regulation of System A transport activity in rat H4 hepatoma cells is described. The uptake of several amino acids was tested in the presence of system-specific inhibitors. System A activity was increased in a RNA- and protein synthesis-dependent manner by amino acid deprivation of the cells (adaptive regulation), whereas transport by Systems ASC, N, y+, and L was unaffected. Unlike human fibroblasts, the H4 cells did not require serum to exhibit the depression of System A. At cell densities between 88 X 10(3) and 180 X 10(3) cells/cm2, the degree of adaptive regulation was inversely related to cell density. Both transport of AIB and adaptive regulation of System A were nearly abolished if either K+ or Li+ was substituted for Na+ in the medium. The presence of cycloheximide or tunicamycin blocked further increases in starvation-induced activity within 1 hr of addition, suggesting the involvement of a plasma membrane glycoprotein. In contrast, if the medium was supplemented with actinomycin after the stimulation of System A had begun, the activity continued to increase for an additional 2 hr before being slowed by the inhibitor. The contributions of trans-inhibition and repression to the amino acid-induced decay of System A activity were estimated for several representative amino acids. In general, the System A activity in normal rat hepatocytes was much less sensitive to trans-inhibition than the corresponding activity in H4 hepatoma cells. The half-life values for the amino acid-dependent decay of System A ranged from 0.5 to 2.0 hr.
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PMID:Adaptive regulation of neutral amino acid transport System A in rat H4 hepatoma cells. 257 76


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