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Biomedical subjects

H Takagi

Publications and source records attributed to H Takagi.

At least 829 records · Page 46Linked to original sources
PubMed1991

Establishment of drug resistance in human gastric and colon carcinoma xenograft lines.

We established multidrug-resistant human gastric and colon xenograft lines by means of intratumoral injections of four agents, doxorubicin (DXR), cisplatin (CDDP), 5-fluorouracil (5-FU) and mitomycin C (MMC), into subcutaneous SC1NU and SW480 tumors once a week or less. Such intermittent drug exposure is commonly used in clinical chemotherapeutic protocols. All xenograft lines acquired resistance to the injected drugs as evaluated by in vivo drug-resistance tests. Many of the drug-resistant lines showed various patterns of cross resistance to other drugs. In order to analyze the mechanism of resistance in vivo, we investigated the expression of drug resistance gene, which has been extensively studied in vitro. We used four complementary DNAs (cDNAs) for multidrug resistance (MDR1), glutathione S-transferase-pi (GST-pi), thymidylate synthase (TS) and dehydrofolate reductase (DHFR), as probes. We observed GST-pi, DHFR and TS mRNA expression at various levels, but MDR1 mRNA expression was found only in SW480/DXR by the method of poly (A+) RNA selection. Four resistant SW480 lines had higher TS mRNA expressions. Six resistant lines had stronger GST-pi mRNA expression. Five resistant lines had higher DHFR mRNA expression. Drug resistance genes related to the treated drug were also expressed in this in vivo model; MDR1 in SW480/DXR, GST-pi in SW480/CDDP and in SC1NU/CDDP and TS in SW480/5-FU. In contrast to in vitro resistant lines which have been reported as models of drug resistance, the expression of drug resistance genes in vivo was not always correlated to the acquisition of cross resistance. These resistant xenograft lines and the methods developed to induce drug resistance in vivo should be useful for studies on the mechanism of drug resistance in the clinical setting.

Animals↗
PubMed1991

Effects of thromboxane A2 synthetase inhibitor on postischemic liver injury in rats.

This study was designed to clarify the mechanism of a reversal of the ischemia-induced decrease in adenosine triphosphate (ATP) in relation to the changes in liver blood flow. All vessels to the left and median lobes were occluded for 15 or 30 min and then reperfused for 15 or 30 min, respectively. Ischemia led to a significant decrease in the ATP level. ATP levels recovered fully after 30 min of reperfusion following 15 min of occlusion. However, a significantly low ATP level was observed even after 30 min of reperfusion following 30 min of occlusion. Premedication with CV-4151 (5 mg/kg, i.v.), a thromboxane A2 (TXA2) synthetase inhibitor, significantly improved the recovery of ATP levels after 30 min of reperfusion following 30 min of occlusion. Liver blood flow was restored fully immediately after reperfusion following 15 min of occlusion. In contrast a significantly low liver blood flow was observed after 30 min of reperfusion following 30 min of occlusion. Premedication with CV-4151 accelerated the recovery of liver blood flow after reperfusion. Morphological studies revealed that microthrombi were formed during ischemia, and CV-4151 mitigated the formation of microthrombi. These results indicate that the formation of microthrombi, which might be associated with TXA2 synthesis during ischemia, inhibited the restoration of liver blood flow, which might be responsible for the obstruction of the recovery of ATP.

Adenosine Triphosphate↗
PubMed1991

Effects of long-acting superoxide dismutase on liver metabolism after major hepatic resection in rats with cirrhosis.

The aim of this study is to clarify the liver metabolic changes after major hepatic resection. The survival rate after 70% hepatectomy of rats with cirrhosis was significantly depressed compared with that of the control group. Mitochondrial function in the cirrhotic liver was disturbed compared with the control group. Tissue levels of hypoxanthine and xanthine increased both in the cirrhotic group and the control group. The increase in xanthine levels was remarkable and was prolonged in the cirrhotic group compared with the control group. Decreases in adenine nucleotides were observed after resection both in normal and cirrhotic livers. These were remarkable and were prolonged in rats with cirrhosis. Administration of polyoxyethylene-modified superoxide dismutase improved the survival rate and lessened decreases in adenine nucleotide levels. Moreover, it accelerated the recoveries of serum glutamic oxaloacetic and pyruvic transaminase levels after resection in rats with cirrhosis. These results indicate that disturbances in energy metabolism and increases in oxygen free radical formation are more remarkable in the cirrhotic liver than in the normal liver, which contributes to a low survival rate in rats with cirrhosis.

Adenine Nucleotides↗
PubMed1991

Dexamethasone-nonsuppressible cortisol in two cases with aldosterone-producing adenoma.

Forty-one patients with aldosterone-producing adenoma (APA) were subjected to a dexamethasone suppression test (DST) before surgery. Serum cortisol and urinary excretion of 17-hydroxycorticosteroids were suppressed by dexamethasone in 39 patients [DST(+)]. In two patients (cases A and B), they were not suppressed [DST(-)]. Clinical manifestations of the two DST(-) patients were similar to those of DST(+) patients. Hypertension, hypokalemia, high serum aldosterone levels, and suppressed PRA were found in all of the patients. The cut surfaces of the adenomas from all of the patients, including cases A and B, were golden yellow, which is typical of APA. However, atrophies of the adjacent normal tissues were evident exclusively in the two DST(-) patients. After removal of the affected adrenals, the serum cortisol level was suppressed by dexamethasone in one of the DST(-) patients (case B). These findings suggested autonomous cortisol production by APA. To evaluate whether cortisol could be produced from the adenoma tissue, the presence of several steroidogenic enzymes was studied by immunohistochemistry and mRNA analysis in the adenomas and the adjacent nonneoplastic adrenals from the 2 DST(-) and 5 DST(+) patients. Immunohistochemical analysis demonstrated that steroidogenic enzymes were expressed in APA tumor tissues from both DST(-) and DST(+) patients. In both groups, mRNAs coding steroidogenic enzymes were present not only in the nonneoplastic but also in the tumor tissues. Quantitative analysis of the mRNA levels revealed that in the adrenals from DST(+) patients, the mRNAs were more abundant in nonneoplastic tissue than in tumor tissue. However, in those from DST(-) cases, the mRNAs were much more abundant in the tumor tissues than in the nonneoplastic tissues. These results indicate that tumor cells of the two DST(-) patients autonomously synthesized not only aldosterone but also cortisol. The diameters of the tumors from the two DST(-) patients exceeded 3 cm, while those from other DST(+) patients were smaller. In patients with large APA, adrenal insufficiency should be anticipated upon removal of the tumor.

Adenoma↗
PubMed1991

Immunohistochemical localization of laminin in the periodontal Ruffini endings of rat incisors: a possible function of terminal Schwann cells.

Ruffini endings in the periodontal ligament of rodents are ensheathed by a special type of terminal Schwann cell with a particularly developed rough endoplasmic reticulum and Golgi apparatus, and further enveloped by a characteristic multi-layered structure. In order to reveal the functional significance of the structures, localization of a laminin molecule in the periodontal Ruffini endings of rats was immunohistochemically investigated at the levels of light and electron microscopy. Immunostaining using an anti-laminin serum clearly demonstrated the profiles of the Ruffini endings as well as those of the blood vessels. Ultrastructurally, reaction products for laminin were deposited in the entire thickness of the multi-layered structure, supporting the idea that this structure is derived from the basal lamina. The basal lamina, immunoreacting with laminin antiserum, was penetrated by periodontal collagen fibers, possibly serving as an adhesive device between the Ruffini endings and surrounding collagen fibers. The laminin immunoreactive materials were also recognized in the vesicles and caveolae of the terminal Schwann cells which tended to gather at the interstitial surface of the cells. The terminal Schwann cells are therefore believed to be directly involved in the formation of the multilayered basal lamina through the active production of its materials.

Animals↗
PubMed1991

Fenestration of the intracranial internal carotid artery--case report.

A rare case of fenestration of the intracranial internal carotid artery (ICA) was identified by angiography in a 51-year-old female with suspected subarachnoid hemorrhage. Only two similar cases have been reported previously. Fenestration tends to develop on the right side and near the bifurcation of the ophthalmic artery. Congenital factors at the 4 mm embryonic stage may be involved in the fenestration of the intracranial ICA.

Carotid Artery, Internal↗
PubMed1991

Effects of prostaglandin E1 on the recovery of ischemia-induced liver mitochondrial dysfunction in rats with cirrhosis.

Interruption of hepatic blood supply for 60 min deteriorated liver mitochondrial respiratory functional indices--that is, respiratory control index (RCI) and the rate of oxygen consumption in state-III respiration (ST III O2). Recovery of ischemia-induced decreases in these functional indices in a saline-administered cirrhotic liver group was retarded compared with that in a normal liver group, and significantly low RCI and ST III O2 persisted 15 min after reperfusion. Prostaglandin E1 (PGE1) did not improve ischemia-induced decreases in RCI and ST III O2 but accelerated the recovery of mitochondrial respiratory function after reperfusion. Adenosine triphosphate (ATP) levels were markedly decreased during ischemia, and retardation of ATP recovery was also observed in rats with cirrhosis. PGE1 improved the recovery of ATP level in rats with cirrhosis. Liver blood flow in the cirrhotic liver was significantly lower than that of the normal liver. PGE1 enhanced liver blood flow. These results indicate that retardation of the recovery of RCI and ST III O2 in the cirrhotic liver might be based on the decrease in tissue blood flow and that agents increasing tissue blood flow might contribute to the acceleration of the recovery of mitochondrial respiratory function.

Adenine Nucleotides↗
PubMed1991

Effects of manipulating dietary cation-anion balance on macromineral balance in sheep.

Effect on macromineral balance in sheep of dietary excess of inorganic anions (Cl and S) or inorganic cations (Na and K) was studied. Dietary cation-anion balance was calculated as milliequivalents [(Na + K) - (Cl + S)] kg-1 of DM. Eight crossbred wethers were fed two levels of Ca, designated high Ca (.82%) or normal Ca (.48%), with four treatment each, three of which differed in dietary cation-anion balance. Control and two treatments had +284, +61, and -27 meq kg-1 of DM for high Ca and +343, +218, and +63 meq kg-1 of DM for normal Ca, respectively. A fourth treatment was control plus injection of vitamin D3 (16,670 IU kg-1 of BW). Reducing dietary cation-anion balance reduced Ca retention by increasing excretion of urinary Ca. Apparent absorption of Ca was similar across cation-anion balances. There was no correlation observed between dietary cation-anion balance and concentration of plasma Ca. No difference was observed in apparent absorption of Ca between high and normal Ca. This result may be related to an oversupply of dietary Ca. Magnesium retention as a proportion of that absorbed for lowest cation-anion balance was smaller than that for the intermediate balance and control plus vitamin D3, although not different from control. Results showed that reduced dietary cation-anion balance resulted in a reduction of Ca retention.

Analysis of Variance↗
PubMed1991

Effects of various dietary cation-anion balances on response to experimentally induced hypocalcemia in sheep.

We examined the effect of dietary cation-anion balance on bone Ca mobilization, measured by challenging wethers with a 5.6% EDTA infusion at a rate of 1.4 ml kg of BW-1. Dietary cation-anion balance was calculated as milliequivalents [(Na + K) - (Cl + S)]. Six crossbred wethers (average BW, 67.8 kg) were fed rations with high Ca (.74% dry basis) or normal Ca (.45%) and three different dietary cation-anion treatments, which differed in their mineral supplementation. Dietary cation-anion balances were 354, 125, and 32 meq kg of DM-1 for control and two treatments. A 6 x 4 incomplete Latin square design (six treatments, four periods) was used with five 15-d periods of 14 d of adaptation followed by 1 d of EDTA infusion. Concentrations of total and EDTA titratable plasma Ca were not affected by the level of dietary Ca or treatments. The decrease in plasma EDTA titratable Ca at conclusion of EDTA infusion (120 min) was least in wethers fed the lowest cation-anion balance within high Ca, and recovery of plasma EDTA titratable Ca during the 240-min postinfusion period was faster for sheep fed this diet than for the control. The amount of Ca mobilized and its rate of mobilization during the EDTA infusion period tended to be higher for diets with reduced cation-anion balances than for the control. Thus, reducing cation-anion balance increased the sheep's ability to mobilize Ca during hypocalcemia.

Acute Disease↗
PubMed1991

Effects of reducing dietary cation-anion balance on calcium kinetics in sheep.

A Ca kinetic study with a four-compartment model being fitted to radioisotope and balance data using the CONSAM (conversational, simulation, analysis, and modeling) computer program was conducted to examine the effects of dietary cation-anion balance, calculated as milliequivalents [(Na + K] - (Cl + S)]. Twelve crossbred wethers were used as eucalcemic control (period 1); then Ca loss during lactation was simulated by continuous infusion of ethylene glycol tetraacetate (period 2). Dietary cation-anion balance was manipulated by supplementation of various mineral salts and was +339, +35, and -127 meq of kg DM-1 during period 1 and +429, +68, and -147 meq of kg DM-1 during period 2 for control and two treatments, respectively. Animals responded to the simulated lactational Ca loss (period 2) by increasing true intestinal absorption of Ca and bone resorption and by reducing Ca accretion by bone. No difference was observed in concentration of total Ca in plasma, but treatments produced increased concentration of plasma ionized Ca during both periods. Both treatments produced hypercalciuria during both periods, and the lowest cation-anion balance increased true intestinal absorption of Ca and reduced bone accretion during period 2. The size of total exchangeable Ca pool did not differ between treatments or periods, but amount of Ca movement between the pools increased with the intermediate cation-anion balance during period 1 and with both treatments during period 2 compared with control. These results indicated that feeding reduced cation-anion balance diets increased Ca flux through the exchangeable Ca pool with no changes in the size of the pool, particularly when Ca demand was increased.

Animal Feed↗
PubMed1991

[Sequential structure of behavior and its modification in inbred strains of mice in a passive avoidance situation].

Behavior in a shuttle-box of four inbred strains of mice (BALB, C3H, C57BL and DBA) was observed by time-sampling method with 11 behavioral items in order to determine how their dyadic sequential structure of the items would be modified under a passive avoidance procedure. Mice in the safe-compartment could enter freely into the shock-compartment, the grid of which was electrified during Days 1-5. A common structure mainly composed of six items was found in every strain on Day 0 when the grid floor was not electrified. The structure was modified on Days 1-5. Entries into the shock-compartment were greatly reduced in all strains as the shock-experience increased, indicating the establishment of passive-avoidance. However, the way they avoided shocks was quite different between BALB and the other strains. In the latter the transitions between 'locomotion' and 'peeping' and between 'sniffing' and 'peeping' did not extinguish, while in BALB these transitions extinguished after Day 1, which means they avoided even 'peeping' into the shock-compartment. It was concluded that the passive avoidance strategy may be different among inbred strains.

Animals↗
PubMed1991

[The significance of extent of resection in the treatment of hepatoma].

The relationship between the types of hepatectomy in each stage of hepatoma and the outcome was examined in 222 patients with hepatoma, according to the rules established by Liver Cancer Study Group of Japan. In Stage 1, the survival rate after absolute curative resection was better than that after relative curative resection. In Stage II, the survival after segmentectomy or lobectomy was significantly better than that after subsegmentectomy or less. Tumor recurrence rates in the remaining liver after segmentectomy or lobectomy were significantly lower than that after smaller resections. In Stages III and IV, there was no difference in survival among the various extents of hepatectomy. Incidence and cause of death after hepatectomy were not influenced by the extent of hepatectomy, as far as it was not beyond the preoperatively estimated safety limits. These results indicate the following: 1) In Stage I, absolute curative resection must be carried out. (2) In Stage II, segmentectomy or lobectomy should be applied when feasible. (3) The patients treated with subsegmentectomy or less for Stage II tumor, and the patients with Stage III or Stage IV tumor are at high risk of recurrence, and those patients need adjuvant therapy after hepatectomy.

Adult↗
PubMed1991

[Expression and clinical significance of type-1 blood group antigens (Lea, Leb, CA19-9) in colorectal cancer--comparison with CEA].

The immunohistochemical analysis using the monoclonal antibodies to the blood group associated antigens Lea, Leb, CA19-9, and CEA, were performed on the tissues of the colorectal cancers, adenomas, normal mucosae and distant metastatic lesions, to determine whether the given degree of expression have some relation to the prognosis of patients or the potential of metastasis. We also analysed the serum levels of CA19-9 and CEA by RIA and compared them with the results of immunopathology. The more pronounced expression of CEA, Lea, Leb, and CA19-9 was observed in proportion to the progress of the cancer. In those cases of immunohistochemically Lea negative results in tissues, CA19-9 was not detected either in the serum level nor in tissue sections, therefore all cases of Lea negative results were eliminated in the evaluation of the clinical significance of CA19-9. Positive expression of CA19-9 in tissue of cancer indicated a poor prognosis of the patient and high risk of distant metastasis. Higher intensity of staining was observed in hepatic metastasis, in comparison with the primary lesion. These studies demonstrated that immunohistochemical analysis of CA19-9 and blood group antigens in useful tool for evaluation of prognosis and risk of metastasis in colorectal cancer.

Adult↗
PubMed1991

Clinical evaluation of plasma abnormal prothrombin (des-gamma-carboxy prothrombin) in hepatobiliary malignancies and other diseases.

Des-gamma-carboxy prothrombin (DCP), a protein induced by vitamin K absence or antagonist-II (PIVKA-II) was measured in the plasma of patients with primary hepatocellular carcinoma and those with various other hepatobiliary and pancreatic diseases. DCP levels were determined by enzyme immunoassay (E-1023), using an anti-DCP monoclonal antibody. Forty-two of the 91 patients (46.2%) with hepatocellular carcinoma had abnormally elevated levels of DCP, whereas only one of the 24 patients with hepatic cirrhosis showed a slight increase. An increase was also observed in some patients with obstructive jaundice. There was no correlation between plasma levels of DCP and those of serum alpha-fetoprotein (AFP). In most patients with hepatocellular carcinoma, plasma DCP levels normalized after curative surgical resection. Plasma DCP levels were not related to the plasma concentration of vitamin K in the patients with hepatocellular carcinoma. Plasma DCP determination may be useful in the diagnosis and postoperative monitoring of the response of hepatocellular carcinoma.

Biliary Tract Diseases↗
PubMed1991

Coexpression of the stem cell factor and the c-kit genes in small-cell lung cancer.

Stem cell factor (SCF) is a pluripotent growth factor which is suggested to play an important role in proliferation and differentiation in various types of fetal and adult tissues as the ligand of the c-kit proto-oncogene product. However, very little is known about expression of the SCF gene in human malignancies. We analysed DNA and RNA extracted from 28 cell lines and 16 fresh tumor specimens of lung cancer as well as 24 cancer cell lines of various origin for SCF expression. Now we report that the SCF gene is expressed in a wide variety of human cancers including lung cancer, in marked contrast to c-kit, which is expressed in very few types of cancers. As a consequence, coexpression of both the ligand and the receptor is seen only in small-cell lung cancer, suggesting possible involvement of autocrine stimulation via this ligand-receptor system in the pathogenesis of this aggressive cancer. In addition, this study revealed that the human SCF gene is transcribed into two major forms of alternatively spliced mRNAs with different molar ratio in fetal, adult and malignant tissues.

Base Sequence↗
PubMed1991

Experimental study on the hemodynamic effects of veno-arterial extracorporeal membrane oxygenation with an automatically driven blood pump on puppies.

Hemodynamics, mainly the pressure of the heart, was studied while performing veno-arterial extra-corporeal membrane oxygenation (VA-ECMO) on 16 puppies between the right atrium and the right carotid artery with a unique ECMO circuit using an automatically driven blood pump. The resulting decrease in the mean pulmonary arterial pressure indicated a definite support of VA-ECMO on the volume work of the right heart. The right and left ventricular end-diastolic pressures decreased during the low flow bypass, but increased significantly with flow over 50 ml/min/kg. The results indicated biventricular pressure strain due to the increase in afterload. The left ventricular systolic pressure gradually increased despite the steady decrease in the systemic arterial systolic pressure when bypass flow exceeded 60 ml/min/kg. The findings were similar to those in peripheral circulatory insufficiency. The authors concluded that VA-ECMO flow should be kept as low as possible, in view of undesirable hemodynamic effects on both ventricles.

Animals↗