Plasma levels of transforming growth factor beta 1 in chronic liver disease.
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Hepatitis C↗
Biomedical subjects
Y Kanda
Publications and source records attributed to Y Kanda.
Etoposide with/without G-CSF with busulfan and cyclophosphamide as conditioning for bone marrow transplantation. The BMT Team.
To increase the efficacy of bone marrow transplantation (BMT), we have tried to add etoposide (VP-16) to busulfan/cyclophosphamide (BU/CY). Twelve patients received 16 mg/kg of BU and 120 mg/kg of CY with 15-30 mg/kg of VP-16. Another two patients received 5 micrograms/kg of G-CSF with 30 mg/kg of VP-16. Patients tolerated escalating doses of VP-16 without any significant hepatotoxicity. Their maximal level of bilirubin was 37.6 micromol/L (2.2 mg/dl), and there was no significant skin toxicity or mucositis. By contrast, two patients who received G-CSF with 30 mg/kg of VP-16 developed hyperbilirubinemia and veno-occlusive disease, which terminated this phase I study. VP-16 can be safely combined with BU/CY < or = 30 mg/kg in three divided doses, and its effect on survival should be evaluated. G-CSF added to this regimen, however, should be used with great caution.
Adolescent↗
Prognostic value of monolayer culture patterning in primary cell culture of oesophageal cancer.
The growth of primary cell cultures of oesophageal cancer was compared with the clinical outcome of patients from whom the cancers were taken. Ninety-three patients underwent curative resection, with no operative deaths, and were divided into three groups according to the monolayer culture pattern of the primary cell culture: culture from 43 patients (46 per cent) grew no malignant cells (group 1), 21 (23 per cent) produced monolayer epithelial growth (group 2) and the rest (from 29 patients) established cell lines (group 3). The 5-year survival rate of patients in group 2 (29 per cent) and group 3 (23 per cent) was significantly lower (P < 0.005) than that of those in group 1 (51 per cent). Monolayer epithelial growth potential is a significant prognostic factor in patients with oesophageal cancer.
Adult↗
Change of plasma leukotriene C4 during myocardial ischemia in humans.
Changes in leukotriene C4 levels during different degrees of myocardial ischemia in humans were examined by comparing radioimmunoassay measures of leukotriene C4 plasma levels obtained during transient and prolonged myocardial ischemia. Leukotriene C4 levels in systemic arterial and coronary sinus blood were determined in patients with chronic stable angina before and after myocardial ischemia induced either by exercise (supine bicycle ergometer exercise stress testing; n = 14; age, 52 +/- 8 years) or by coronary occlusion during angioplasty (n = 14; age 53 +/- 7 years). Temporal changes of leukotriene C4 were also followed in arterial and pulmonary artery blood within 24 h after the onset of chest pain (acute phase), and 1 day, 1 week, and 1 month later in 22 patients with acute myocardial infarction (AMI) (12 patients with thrombolytic therapy, age 61 +/- 10 years; 10 patients without thrombolytic therapy, age 60 +/- 11 years). Clinical characteristics, including coronary risk factors and the severity of coronary artery disease, were not significantly different among the groups. Exercise-induced myocardial ischemia and coronary occlusion did not induce any significant leukotriene C4 changes in the chronic stable angina patients, whereas AMI patients had significantly higher plasma leukotriene C4 levels in both arterial and pulmonary artery blood in the acute phase compared with those of chronic stable angina patients (arterial blood, 471 +/- 164 pg/ml and 477 +/- 235 pg/ml vs. 275 +/- 254 pg/ml or 240 +/- 66 pg/ml, p < 0.05; pulmonary artery blood in AMI, 543 +/- 162 pg/ml vs. 234 +/- 125 pg/ml or 225 +/- 64 pg/ml, coronary sinus blood in chronic stable angina, p < 0.05). These results suggest that leukotriene C4 is involved more in prolonged myocardial ischemia than in transient myocardial ischemia, and that leukocyte function might play a significant role in the pathogenesis of patients with AMI.
Adult↗
Elevated platelet count features the variant type of BCR/ABL junction in chronic myelogenous leukaemia.
A variant form of BCR/ABL junction was identified in a patient with chronic myelogenous leukaemia (CML). The BCR/ABL fusion mRNA of this patient showed in-frame junction between BCR exon c3 and ABL exon 2. Although the diagnosis of CML was made, the patient showed clinical features of essential thrombocythaemia (ET) rather than that of typical CML. Treatment with interferon-alpha showed no cytogenetic response. The c3-a2 type of BCR/ABL junction seems to be associated with elevated platelet count and thus could form a novel clinical entity different from typical CML.
Adolescent↗
Elevated plasma levels of matrix metalloproteinase-9 (92-kd type IV collagenase/gelatinase B) in hepatocellular carcinoma.
BACKGROUND: Matrix metalloproteinase 9 (MMP-9), a 92-kd gelatinase/type IV collagenase, has been implicated as playing an important role in cancer invasion and metastasis. A previous study showed that serum type IV collagenase activity correlated with metastasis by hepatocellular carcinoma (HCC). The aims of this study were to determine the plasma levels of immunoreactive MMP-9 in patients with HCC and to compare the levels with the clinical features including vascular invasion. PATIENTS AND METHODS: This study included 100 patients with HCC, 21 patients with chronic hepatitis (CH), 24 patients with liver cirrhosis (LC), and 138 healthy control subjects. Plasma MMP-9 levels were measured with a specific one-step sandwich enzyme immunoassay. RESULTS: Plasma MMP-9 levels in HCC (62 [33 to 130 ng/mL] median [25%, 75%], 13 to 660 ng/mL, minimum, maximum) were significantly elevated compared with those in normal controls (36 [25 to 45], range, 2.8-70 ng/mL), in CH (28 [18 to 30], 13 to 66 ng/mL) and in LC (35 [26 to 58], 16 to 86 ng/mL) (P < .0000001; P = .0000003; and P = .00205, respectively). When the cut-off level was defined as 60 ng/mL from a receiver operating characteristic curve, plasma MMP-9 concentrations had a sensitivity of 53% and a specificity of 89% for the detection of HCC from CH and LC. The levels were significantly higher in HCC patients with macroscopic portal venous invasion (79 [36 to 160], 15-660 ng/mL) than those without the invasion (44 [27 to 80], 13 to 210 ng/mL) (P = .00726). Plasma MMP-9 levels in patients with HCC were not correlated with tumor number, size, volume, or serum alpha-fetoprotein levels. CONCLUSIONS: The present data suggest that plasma MMP-9 levels can be a candidate for a novel marker for HCC. The levels appear to reflect its potential and ongoing activity of vascular invasion. A long-term follow-up of the patients will be necessary to determine whether increased plasma MMP-9 levels are predictive of more invasive and metastatic HCC.
Adult↗
Arachidonic acid metabolites in acute myocardial infarction.
Abnormalities of arachidonic acid metabolism are implicated in spasm and thrombosis in coronary arteries. Therefore, arachidonic acid metabolites were examined in patients with acute myocardial infarction (AMI). Plasma levels of thromboxane B2 (TXB2), 6-keto-prostaglandin F1 alpha (6KPGF1 alpha), leukotriene B4 (LTB4), and slow reacting substance of anaphylaxis (SRS-A) composed of leukotriene C4 (LTC4), leukotriene D4 (LTD4) and leukotriene E4 (LTE4), were measured in 19 AMI patients. Plasma levels of TXB2, LTB4, and SRS-A in systemic artery blood were significantly elevated during the acute stage (within twenty-four hours after the onset of chest pain) of AMI (TXB2, 0.36 ng/mL; LTB4, 0.75 ng/mL; and SRS-A [LTC4+LTD4+LTE4], 0.96 ng/mL compared with those of normal controls (TXB2, 0.18 ng/mL; LTB4, 0.44 ng/mL; and SRS-A (LTC4+LTD4+LTE4], 0.31 ng/mL). These values decreased to near-normal control levels by one month after the AMI attack. The findings in this study suggest that abnormalities of arachidonic acid metabolism accompany, and may play a role in the pathogenesis of, AMI.
6-Ketoprostaglandin F1 alpha↗
Synthesis and antitumor activity of duocarmycin derivatives: modification of segment A of duocarmycin B2.
Several A-ring pyrrole derivatives of duocarmycin B2 were synthesized effectively from the 3-hydroxy compounds by utilizing an interesting acid-catalyzed rearrangement, their anticellular activity was preliminarily evaluated by assays of growth inhibition of HeLa S3 cells (in vitro) and antitumor activity against murine sarcoma 180 (in vivo). The 8-O-N,N-dialkylcarbamoyl derivatives of the A-ring pyrrole compound showed remarkably potent in vivo antitumor activity, superior to that of duocarmycin B2. these derivatives were subjected to further biological evaluation. They exhibited potent antitumor activity toward murine solid tumors including M5076 sarcoma, B-16 melanoma and Colon 26 adenocarcinoma. Their most noteworthy feature was their efficacy against various human xenografts including LC-6 (lung), St-4 (stomach), and Co-3 (colon).
Animals↗
[Histological and immunohistochemical study of nasal polyps].
Nasal polyps, in general, have been histologically classified as edematous, adenocystic and fibrous types. It has recently been pointed out that eosinophilic infiltration in nasal polyps has increased along with an increase in nasal allergy. The purpose of this study was to classify the nasal polyps histologically and to examine the mode of infiltration and activation of eosinophils by means of immunohistochemistry. The subjects were 101 patients who underwent surgery for nasal polyps. There were 66 males and 35 females ranging in age from 12 to 76 years. Resected polyps were fixed in formalin, embedded in paraffin, and sliced at a thickness of 4 microns. Hematoxylin-eosin staining and streptavidin- biotinyl peroxidase complex staining were used to detect eosinophils. The results were as follows: 1) The nasal polyps were, histologically, edematous in 88.1%, adenocystic in 47.5%, and fibrous in 19.8%. 2) The number and distribution of EG1-positive cells and EG2-positive cells were almost the same in the superficial layer of the lamina propria. This study suggests that eosinophilic infiltration into nasal polyps occurs mainly in edematous polyps and that the majority of the infiltrating eosinophils are activated.
Adolescent↗
[Pharmacokinetics of norfloxacin and lomefloxacin in aqueous humour analysed by microdialysis].
The pharmacokinetics of norfloxacin (NFLX) and lomefloxacin (LFLX) in rabbit aqueous humour after instillation of 0.3% solution (20 microliters) and oral administration (20 mg/kg) were investigated by microdialysis. We also measured plasma concentration of fluoroquinolones after oral administration. After instillation, the maximum concentration (Cmax) of NFLX and LFLX in the aqueous humour was 0.80 and 1.20 micrograms/ml, and elimination half time (t1/2) was 130 and 96 min, respectively. After oral administration, the Cmax in plasma of NFLX and LFLX was 2.06 and 1.89 micrograms/ml, and the Cmax in aqueous humour was 0.16 and 0.62 microgram/ml, respectively. t1/2 of NFLX in aqueous humour and plasma was 225 and 295 min, and t1/2 of LFLX was 188 and 175 min, respectively. The ratio of aqueous humour/serum concentration of NFLX and LFLX was 7.8 and 35.3% 4 hrs after oral administration. These results suggest that, after instillation, LFLX penetrated better into the aqueous humour, and was eliminated faster, than NFLX, and that after oral administration, NFLX could not panetrate well into the aqueous humor from the blood.
Animals↗
Prostaglandin E1 ameliorates decreased tracheal blood flow after esophagectomy and aggressive upper mediastinal lymphadenectomy for esophageal carcinoma.
BACKGROUND: Aggressive upper mediastinal lymphadenectomy contributes to a better survival rate after esophageal resection to treat esophageal carcinoma, but it also increases postoperative respiratory complications. Devascularization of the airways because of mediastinal dissection is considered to be a cause of respiratory dysfunction. The present study attempts to clarify whether or not tracheal blood flow (TBF) deteriorates after esophagectomy and, if so, whether or not intravenous prostaglandin E1 (PGE1) attenuates the deterioration. STUDY DESIGN: Patients undergoing esophagectomy and aggressive upper mediastinal lymphadenectomy for the treatment of esophageal carcinoma (EC group, n = 12) or abdominal surgery (control group, n = 6) were enrolled in this study. Measurement of TBF was performed using a laser Doppler flowmeter. Changes in TBF induced by surgery and postoperative intravenous PGE1 were studied in both groups. RESULTS: The TBF deteriorated significantly in the EC group (21.78 +/- 9.60 to 11.24 +/- 4.45 mL/minute/10(-1) kg, p = 0.002) but did not change in the control group (26.13 +/- 6.84 to 26.61 +/- 4.69 mL/minute/10(-1) kg, p = 0.7371). Postoperative intravenous PGE1 partially, but significantly, reversed the deterioration in TBF in the EC group (11.53 +/- 4.58 to 14.87 +/- 6.30 mL/minute/10(-1) kg, p = 0.0207) but did not effect the control group (29.41 +/- 7.89 to 29.41 +/- 8.79 mL/minute/10(-1) kg, p = 0.9989). CONCLUSIONS: Esophagectomy and aggressive upper mediastinal lymphadenectomy cause a deterioration in TBF that is partially attenuated by PGE1.
Alprostadil↗
[A case of gastric cancer developed in the gastric tube 11 years after subtotal esophagectomy for esophageal cancer].
A case of adenocarcinoma developed in the reconstructed gastric tube after esophagectomy was reported. The patient was 66 years old man and he had received subtotal esophagectomy for the carcinoma of the esophagus 11 years previously. The follow-up examination of upper GI series revealed an ulcerative lesion in the lower part of the gastric tube and endoscopic biopsy showed adenocarcinoma. The partial resection of the lower gastric tube with mediansternotomy was performed because of limiting the invasion of the carcinoma. Pathological examination showed that poorly differentiated adenocarcinoma with signet ring cells had invaded muscularis propria. The postoperative course was uneventful and he is well without any recurrence 6 months after the operation. A double carcinoma, such as esophageal cancer concomitant gastric cancer is not rare, but a carcinoma of the gastric tube which was substituted for the esophagus is rare. Recently, the incidence of carcinoma of the gastric tube is increasing due to the increasingly long-term survival rate of patients who had esophageal carcinoma. In order to ensure the early detection of a second carcinoma which can minimalize damage from curative resections, follow up examinations should be conducted with the utmost diligence.
Adenocarcinoma↗
Cloning of several species of MLL/MEN chimeric cDNAs in myeloid leukemia with t(11;19)(q23;p13.1) translocation.
The t(11;19)(q23;p13.1) translocation is thought to play an important role in pathogenesis of myeloid leukemias in older patients. The MLL gene involved in other 11q23 abnormalities was also rearranged by this translocation. Screening of cDNA libraries of the t(11;19)(q23;p13.1)-carrying leukemic cells resulted in the isolation of several species of fusion cDNAs between the MLL gene and an unknown gene on 19p13.1, named MEN (myeloid eleven-nineteen translocation), which is ubiquitously expressed. Although the MLL gene was alternatively spliced, the fusion protein should contain an N-terminal half of the MLL, including AT hook motifs, that is fused to the MEN protein with a lysine-rich sequence, suggesting that the MLL/MEN fusion protein could be a chimeric transcription factor. The MLL/MEN fusion transcripts of 8.0 kb were detected in leukemic cells of two cases with the translocation. The MLL/MEN fusion was consistent in all three cases of the t(11;19)(q23;p13.1)-carrying leukemia examined by RNA-based polymerase chain reaction. These findings strongly suggest that the t(11;19)(q23;p13.1) results in the fusion formation encoding a new class of potential chimeric transcription factor that contributes to leukemogenesis of myeloid lineage.
Acute Disease↗
Interleukin-6 stimulates cell proliferation of rat pituitary clonal cell lines in vitro.
We investigated the effect of recombinant human IL-6 (rhIL-6) on cell proliferation using the MtT/E rat pituitary tumor cell line, which was recently established by Inoue et al. This cell line expresses the homeodomain protein Pit-1/GHF 1 and does not produce any significant amount of pituitary hormones, but retains its tumorigenicity by back-transplantation into rats, resulting in production of prolactin. MtT/E cells were seeded into Falcon 24-well plates at a density of 2 x 10(4) cells/well in a cultured medium, containing 10% horse serum and 2.5% fetal bovine, with test drug. After four-days (12 days for the time-course study) incubations, the cells were counted using a hemocytometer. Incubation for 4 days with rhIL-6 caused concentration-dependent stimulation of MtT/E cell growth and [3H]-thymidine incorporation into MtT/E cells. Addition of 20 ng/ml rhIL-6 to the culture medium stimulated MtT/E cell growth in a time-dependent manner, withdrawal of rhIL-6 from the culture medium reduced MtT/E cell growth, and re-addition of rhIL-6 to the culture medium again stimulated MtT/E cell growth. Among the cytokines tested, granulocyte colony-stimulating factor (rh G-CSF) also showed a slight but significant mitogenic activity on the MtT/E cells. Analysis of 125I-rhIL-6 binding to the MtT/E cells indicated a dissociation constant of 0.953 x 10(-9) mmol/l and the presence of 968 binding sites per cell.(ABSTRACT TRUNCATED AT 250 WORDS)
Animals↗
Correlation between serum prolactin levels and hepatocellular tumorigenesis induced by 3'-methyl-4-dimethylaminoazobenzene in mice.
Ovariectomy at 1 month of age promotes development of hepatocellular adenomatous nodules in female C57BL/6 x DS-F1 mice treated neonatally with 3'-methyl-4-dimethylaminoazobenzene (3'-Me-DAB). Implantation of oestradiol-17 beta (E2) pellets at 1 month of age suppresses nodule development. Since E2 increases serum levels of prolactin, high serum levels of prolactin in mice that have received implants of E2 pellets may play a role in the suppression of hepatocellular tumorigenesis. Therefore, to investigate the role of prolactin in hepatocellular tumorigenesis, we examined development of adenomatous nodules in female mice that had been treated neonatally with 3'-Me-DAB and had undergone ovariectomy at 1 month of age, under various serum levels of prolactin. Treatment of these mice with perphenazine (dopamine antagonist) from 6 months of age or transplantation of pituitary glands under the renal capsule at 6 months of age markedly increased serum levels of prolactin and significantly suppressed the incidence of adenomatous nodules at 12 months of age. Implantation of E2 pellets at 1 month of age increased serum levels of prolactin to a greater extent and further decreased the incidence of adenomatous nodules. Treatment of mice that had received implants of E2 pellets at 1 month of age with bromocriptine (dopamine agonist) from 6 months of age decreased serum levels of prolactin, and was accompanied by an increase in the incidence of nodules. The present results showed that an increase in serum levels of prolactin was accompanied by a decrease in incidence of liver tumours induced by 3'-Me-DAB in mice, suggesting a suppressive effect of prolactin on liver tumorigenesis in mice. Thus, it is possible that the suppressive effect of oestrogen on liver tumorigenesis in mice is mediated, at least in part, by prolactin.
Adenoma↗
Mutation of the nm23 gene, loss of heterozygosity at the nm23 locus and K-ras mutation in ovarian carcinoma: correlation with tumour progression and nm23 gene expression.
Alteration of expression levels of the nm23 genes has previously been correlated with metastatic status of ovarian epithelial carcinoma. To elucidate the relevance of the qualitative changes of the nm23 genes to progression of ovarian carcinoma and/or to nm23 expression levels of the tumour, 41 samples of epithelial ovarian tumours [three benign, three low malignant potential (LMP), and 35 frankly malignant tumours] were studied for mutation of the nm23-H1 and the nm23-H2 genes using single-strand conformational polymorphism (SSCP) analysis. In addition, loss of heterozygosity (LOH) at the nm23 locus on chromosome 17q was studied by CA repeat polymorphism analysis. Mutation of the K-ras gene was also analysed in the same specimens. A novel mutation of the nm23 gene was found in one case of stage III serous carcinoma without lymph model metastases. Sequencing of the subcloned mutant cDNA revealed a missense mutation from TGG to CGG at codon 133 of the nm23-H2 gene, resulting in a change from Trp to Arg. LOH at the nm23 locus was detected in 5 of 23 (21.7%) informative cases of ovarian carcinoma. Mutation of the K-ras gene was detected in 2 of 35 (5.7%) carcinomas at codons 12 and 13 respectively. There was no correlation between clinical stage or metastatic status of ovarian carcinoma and nm23 mutation, LOH at the nm23 locus or K-ras mutation. The expression levels of both the nm23-H1 and the nm23-H2 genes were lower in the tumour with nm23-H2 mutation and higher in those with K-ras mutation. This suggests that mutation of the nm23 genes and the K-ras gene affects carcinogenesis or progression of ovarian carcinoma by modulating expression of the nm23 genes.
Adult↗
A sporadic case of Ehlers-Danlos syndrome type IV: diagnosed by a morphometric study of collagen content.
A sporadic case of a young woman with Ehlers-Danlos syndrome (EDS) type IV is described. Multiple aneurysms of medium-sized arteries were noted. Histological study revealed deposition of acid mucopolysaccharides in the media of major arteries and in the intima of smaller arteries with intimal thickening. Systemic changes related to stenosis were observed in arteries more than 100 microns in diameter. Histologic study revealed hyperplasia of adipocytes in the submucosal layer of the intestines and the trachea, and fibrosis of Langerhans' islets of the pancreas. Typical signs for EDS such as skin hyperelasticity and joint hypermobility, and positive family history were not present. However, type III collagen was not detected on frozen sections from either the skin or the anterior cerebral artery by immunohistochemical quantification. Thus, it was concluded that the present case is a variant of EDS.
Adolescent↗
Oxytocin stimulates mitogen-activated protein kinase activity in cultured human puerperal uterine myometrial cells.
The regulation of mitogen-activated protein (MAP) kinase by oxytocin in cultured human uterine myometrial cells was investigated. Oxytocin caused the rapid stimulation of MAP kinase activity detected in 32P incorporation of MAP-2. Oxytocin also stimulated the phosphorylation of MAP kinase detected in incorporation of [32P]orthophosphate into MAP kinase. Furthermore, oxytocin induced the tyrosine phosphorylation of MAP kinase. The oxytocin-dependent increase in the tyrosine phosphorylation of MAP kinase displayed a transient time course and was dependent on the concentration of oxytocin applied to the cells. Furthermore, we examined the mechanism by which oxytocin induced MAP kinase phosphorylation. Islet-activating protein (100 ng/ml), which inactivates Gi/Go proteins, blocked the oxytocin-induced phosphorylation of MAP kinase. Moreover, 1 microM ritodrine, which is known to relax uterine muscle contraction, attenuated oxytocin-induced MAP kinase activity and phosphorylation. These results provide evidence that oxytocin acutely activates MAP kinase through an islet-activating protein-sensitive G-protein in human uterine myometrial cells, suggesting that this new pathway may play an important role in the biological action of oxytocin on these cells.
Calcium-Calmodulin-Dependent Protein Kinases↗