Biomedical subjects

H Takagi

Publications and source records attributed to H Takagi.

At least 505 records · Page 28Linked to original sources

PubMed1995

Intraoperative peritoneal washing cytology with the rapid immunoperoxidase method using microwave irradiation.

The rapid immunocytochemical staining of gastrointestinal cancer-associated antigens, carcinoembryonic antigen (CEA) and carbohydrate antigen 19-9 (CA19-9), for intraoperative peritoneal washing cytology of pancreatic or biliary carcinoma can be completed in only 25 minutes by using microwave irradiation to accelerate incubation of the primary antibody. Only 3-second irradiation at 500 W for fresh smears produced specific antigen staining of malignant cells similar to that obtained with longer incubation, and the sensitivity of intraoperative cytology was greater than by the conventional staining method. The rapid immunocytochemical staining method of peritoneal washings at laparotomy can provide sensitive information for determining more aggressive therapy for intraperitoneal spread of malignant cells before closing the abdominal wall.

Aged↗

PubMed1995

Evidence for tight coupling of gonadotropin-releasing hormone receptors to phosphatidylinositol kinase in plasma membrane from ovarian carcinomas.

Gonadotropin-releasing hormone (Gn-RH) analogs inhibit ovarian cancer cell proliferation in vivo and in vitro. To examine whether Gn-RH receptor (Gn-RHR) mediates direct antiproliferative effects, we attempted to determine inhibitory regulation by Gn-RH of phosphatidylinositol (PtdIns) kinase activity, known to stimulate mitogenic response, in plasma membranes isolated from ovarian carcinoma samples. Ovarian carcinomas surgically removed and cloned cell line SK-OV3 had been screened for Gn-RHR expression prior to plasma membrane isolation. PtdIns kinase activity was measured as phosphorylation of exogenous substrate PtdIns by the purified plasma membranes. Incubation of the plasma membranes isolated from Gn-RHR-positive specimens with [gamma-32P]ATP and PtdIns caused [32P]phosphate incorporation into PtdIns phosphate (PtdInsP) in a time-dependent manner. Concomitant exposure of the membrane preparations to Gn-RH analog buserelin (1 microM) led to a 70% inhibition of the PtdInsP production, when compared to control. After 10 or 15 min of an initial incubation, the addition of analog resulted in similar suppression of PtdIns phosphorylation. This inhibition was dependent on the buserelin dose, and a half-maximal effect occurred at a concentration 0.1 to 1 nM of buserelin. Degradation of the produced PtdInsP in the plasma membranes was not affected by the Gn-RH analog. Similar inhibition of PtdIns kinase activities was observed in membranes prepared from cells that had been pretreated with buserelin (1 microM) for 48 hr prior to assay. These findings demonstrate that PtdIns kinase activity is suppressed by Gn-RH analog in plasma membrane isolated from GnRHR-expressing ovarian carcinomas, suggesting a tight coupling of Gn-RHR to PtdIns. The inhibition of membrane-associated PtdIns kinase by Gn-RHR occupancy may mediate the antimitogenic action of the hormone on human ovarian carcinomas.

1-Phosphatidylinositol 4-Kinase↗

PubMed1995

Duration of liver ischemia and hepatic regeneration after hepatectomy in rats.

Since an occlusion of the vascular inflow to the liver is a useful technique in liver surgery, a relation between ischemia and regeneration in the liver is particularly important. The purpose of this study was to evaluate the effect of ischemic duration on liver regeneration after massive hepatectomy. Animals were subjected to segmental liver ischemia. After 30, 60, or 90 min, nonischemic liver lobes were resected (70% hepatectomy). Hepatectomy without prior liver ischemia was performed in the control group. On the 1st, 3rd, 5th, and 7th days following hepatectomy, a BrdU labeling index was calculated as a marker of liver regeneration. AST, ALT, and liver adeninenucleotides were also measured. Although 30 min of liver ischemia resulted in higher peak AST and ALT levels, liver regeneration and ATP levels were significantly higher than those in control animals. Ninety minutes of liver ischemia resulted in significantly lower liver regeneration and ATP levels compared with the other treatment paradigms. Liver regeneration and ATP levels were almost identical to those in control animals, in rats with 60 min of ischemia preceding hepatectomy. We conclude that livers regenerative capacities can tolerate significant ischemia and that relatively brief periods of ischemia can even accelerate liver regeneration.

Adenosine Triphosphate↗

PubMed1995

Role of endogenous nitric oxide in ischemia-reperfusion injury in rat liver.

Evidence has accumulated that oxygen-derived free radicals contribute to the cellular damage induced by ischemia-reperfusion. It has been suggested that nitric oxide (NO) may act as a protective factor in ischemia-reperfusion injury since NO increases blood flow and may scavenge oxyradicals. Nevertheless, controversy exists as to the role of NO. This study was designed to clarify the role of endogenous NO in ischemia-reperfusion-induced liver injury in rats in vivo. Wistar rats weighing 250-300 g were divided into three groups: (1) untreated group (Control); (2) NG-nitro-L-arginine, a specific inhibitor of NO production (L-NNA); and (3) L-arginine-pretreated L-NNA group (AR+L-NNA). Occlusion of all vessels to the median and left hepatic lobes (60 min) was followed by reperfusion for 1 or 24 hr. L-NNA was administered before ischemia as a 10 mg/kg bolus. L-Arginine was given just before L-NNA administration as a 100 mg/kg bolus. Administration of L-NNA resulted in endothelial cell injury characterized by the elevation of serum hyaluronic acid as well as the reduction of hepatic tissue blood flow, and the recovery of hepatic adenosine triphosphate was depressed compared with the control after both 1 and 24 hr of reperfusion. Furthermore, the leakages of various liver enzymes and lipid peroxide were also increased, associated with histological damage. This effect of L-NNA was completely abolished by pretreatment with L-arginine. These results suggest that endogenous NO provides a protective effect against ischemia-reperfusion injury in rat liver.

Adenine Nucleotides↗

PubMed1995

Clinical and experimental studies of the limulus test after digestive surgery.

A chromogenic limulus test (Toxicolor test) revealed a transiently increased blood endotoxin level in some patients after digestive surgery. However, most showed no clinical signs of endotoxemia. The Endospecy test of these specimens, which reacts specifically with endotoxin, did not show a high value, while the Gluspecy test, which reacts specifically with (1-->3)-beta-D-glucan (glucan), did. These findings thus suggested that the gauze used for surgery contains a large amount of glucan. The intraperitoneal injection of this gauze-saline into rats results in a phenomenon similar to that observed in clinical studies. These findings suggested the involvement of substances other than endotoxin such as glucan in the postoperative positive-Toxicolor phenomenon. In addition, the Toxicolor test also showed a higher value in patients with liver cirrhosis than in those without. In an experimental study in rats, the liver cirrhosis group also showed a significantly high value. These results therefore suggest that the glucan clearance mechanism is impaired in the reticuloendothelial system in liver damage such as cirrhosis.

Adult↗

PubMed1995

Use of the double-stapling technique in esophageal surgery.

This study was conducted to examine the effectiveness of the double-stapling technique (DST) for performing esophageal anastomoses. A total of 17 patients, 10 with esophageal cancer and 7 with gastric cancer, underwent esophageal anastomosis employing this technique. Of the ten patients who underwent esophageal operations, eight received esophageal-gastric tube anastomosis, one esophageal-colon and colon-residual stomach anastomosis, and one pharyngeal-gastric tube anastomosis, while all seven of the patients who underwent operations for gastric cancer received esophagojejunostomy. Thus, a total of 18 anastomoses were performed. No problems were encountered during the anastomoses, and no leakage occurred in any of the patients. Thus, we conclude that DST is a safe and easy technique for performing esophageal anastomosis, especially intrathoracic or intramediastinal anastomoses.

Anastomosis, Surgical↗

PubMed1995

Calcitonin gene-related peptide- and substance P-immunoreactive axons in the nucleus gracilis of the rat with special reference to axonal dystrophy: light and electron microscopic observations.

Calcitonin gene-related peptide (CGRP) and substance P (SP)-immunoreactive (IR) axons in the nucleus gracilis of normal rats (1-15 months of age) were studied by light and electron microscopy. Besides many CGRP-IR and SP-IR varicosities with normal appearance, we found a few swollen (nearly round or oval) varicosities with either CGRP or SP immunoreactivity. Swollen CGRP-IR varicosities were more frequently seen than SP-IR ones, appearing from 3 months of age and increasing in number and size (up to approximately 25 microns in diameter) with advancing age. At the electron microscopic (EM) level, CGRP-IR and SP-IR swollen varicosities showed dystrophic changes, i.e., many membranous dense bodies, and proliferation of microtubules and neurofilaments. CGRP-IR or SP-IR dystrophic axons also contained many mitochondria and sometimes made synaptic contacts with nonreactive dendrites (occasionally with non-IR axons). These findings suggest that the dystrophic CGRP and SP axonal profiles represent a functionally distinct subpopulation of axonal dystrophy in the nucleus gracilis and use CGRP or SP as a neuroactive substance. Using a double-immunostaining method, many of normal CGRP-IR axons were identified to be SP-IR. However, no single dystrophic varicosity was found to contain both CGRP and SP immunoreactivities. These findings suggest that CGRP and SP afferents are independently affected and progress to dystrophic changes.

Animals↗

PubMed1995

Immunosuppressive drugs and their effect on experimental tumor growth.

The effect of cyclosporin (CyA), FK 506, and mycophenolate mofetil (MPM) on tumor growth was investigated using syngeneic mouse colon carcinoma 38. Mice were laparotomized and the tumor cells were injected into the portal vein to establish liver metastasis. The animals were grouped as follows: groups A-1, B-1, and C-1 were given CyA [15 mg/kg body weight (BW)], FK 506 (0.15 mg/kg BW), and MPM (100 mg/kg BW), respectively, 30 min before tumor inoculation and daily for 5 days by gavage; groups A-2, B-2, and C-2 were given CyA (30 mg/kg BW), FK 506 (0.3 mg/kg BW), and MPM (200 mg/kg BW), respectively, with the same dose timing; and groups A-3, B-3, and C-3 received CyA (30 mg/kg BW), FK 506 (0.3 mg/kg BW), and MPM (200 mg/kg BW), respectively, on the 7th post-tumor inoculation day and on the following 5 days. The mean tumor diameter in groups A-1 and A-2 was greater than that in the control group and in groups C-1 and C-2 at 3 weeks (P < 0.05). The mean tumor numbers in groups A-1 and A-2 were greater than those in the control group and in groups C-1 and C-2 at 4 weeks (P < 0.05). With in vitro MTT assay, all three drugs acted cytostatically on tumor cells with a higher concentration (10(-6)-10(-4) mol/l), while no cytostatic effect was noted with CyA at a lower concentration (10(-9)-10(-7) mol/l).(ABSTRACT TRUNCATED AT 250 WORDS)

Adenocarcinoma↗

PubMed1995

Superoxide scavenging activity in experimental liver transplantation.

Superoxide dismutase (SOD) activity was evaluated by measuring superoxide scavenging capability with the aid of an electron spin resonance (ESR) spin trapping method in a swine orthotopic liver transplantation (OLT) model. The animals were divided into two groups, depending on the length of the survival periods: the short survival group (n = 8) survived less than 6 days and the long survival group (n = 15) 6 days or longer. SOD activity was significantly lower in the short survival group than in the long survival group after reperfusion (P < 0.01). During the period of cold preservation, a minimal change in SOD activity was noted, regardless of the length of preservation. Serum aspartate aminotransferase (AST) levels after reperfusion and serum lactate dehydrogenase (LDH) levels 1 h after reperfusion were significantly higher in the short survival group than in the long survival group (P < 0.01 and P < 0.05, respectively). The difference in polymorphonuclear leukocytes (PMN) was significantly greater in the short survival group at 1 h after reperfusion (P < 0.01). The authors conclude that superoxide scavenging activities in the graft reflect the magnitude of reperfusion injury, which can be a reliable parameter for the estimation of graft outcome.

Analysis of Variance↗

PubMed1995

Effect of biotin on ammonia intoxication in rats and mice.

The effects of biotin on ammonia concentration in blood and brain were evaluated in hyperammonemic rats and mice. Rats were injected with 5 mmol/kg BW of ammonium acetate, and mice were injected with 10 mmol/kg BW. Increases in blood ammonia levels in rats 15-30 min after ammonia loading were prevented by treatment with 0.2 ml/100 g BW of biotin or 0.04 ml/100 g BW of arginine-glutamate with statistical significance. Blood ammonia levels after ammonia loading were lower, although not significantly, in the arginine glutamate-treated rats than in the biotin-treated animals. In mice also, increases in blood and brain ammonia levels after ammonia loading were prevented by the administration of biotin. The decrease in brain glutamate and aspartate after ammonia loading was lower and the brain glutamine level was higher in biotin-treated mice than in the controls. These findings indicate the protective effect of biotin against ammonia intoxication.

Acetates↗

PubMed1995

Prevention of experimental hepatic metastasis with thromboxane synthase inhibitor.

To investigate the effectiveness of thromboxane (Tx) synthase inhibitor in the prevention of experimental hepatic metastasis, an in vivo study was designed. Hepatic metastasis was brought about by injection of 1 x 10(5) cells of colon 38 tumor into the portal vein of C57 B1/65 mice. Seven groups (n = 16 in each group) received different treatments: with TxA2 synthase inhibitor (sodium ozagrel), 5, 10 or 15 mg/kg BW before tumor inoculation, and daily for the following 3 days, (groups A, B and C, respectively); with acetyl salicylic acid (aspirin), 1.0, 1.5 or 2.0 mg/kg BW (groups C, D, and E, respectively); a control group, inoculated with vehicle only. Serum TxB2, a stable metabolite of TxA2, and prostaglandin F1 alpha were measured. Labeling index for tumor proliferation by bromodeoxy-uridine radioimmuno-assay was also studied. Incidence of metastasis in groups A (60.5%), B (49.5%), C (43.0%), D (80.5%), E (66.0%) and F (58.4%) was less than that in the control group (100%). Tumor size, number of labeling index did not differ among the groups. Serum TxB2 (pg/ml) levels were significantly lower in all of the groups than in the control. Serum PGF1 alpha levels in the groups with aspirin were lower than those in sodium ozagrel. Tx synthase inhibitor is effective in the prevention of experimental hepatic metastasis when it is given before and immediately after tumor inoculation. As Tx synthase inhibitor leaves metabolic pathway to PGI2 production intact, it is more effective in the prevention of metastasis than aspirin since aspirin inhibits both thromboxane and PGI2.

Animals↗

PubMed1995

Endothelin-1 and in vitro evidence of renal artery vasoconstriction after liver transplantation.

Twelve pigs underwent orthotopic liver transplantation. The mean endothelin-1 (ET-1) levels in the serum samples of the recipient animals 1 h after reperfusion of the graft (6.2 +/- 1.5 pg/ml) was significantly higher (P < 0.05) than in pretransplantation samples (3.2 +/- 0.6 pg/ml). Serum blood urea nitrogen (BUN) 24 h after transplantation was 13.8 +/- 5.9 mg/dl, which was significantly higher than before transplantation (6.4 +/- 2.2 mg/dl). There was a positive correlation between the serum BUN and ET-1 (r = 0.62, P < 0.05). An in vitro isometric tension study was performed for the contractility response rate of the intact renal artery in the bath chamber containing the serum of the corresponding recipient animals. The mean contractility response rates were higher with the serum obtained after reperfusion of the graft (66.9 +/- 32.4%) than with those obtained before transplantation (18.3 +/- 9.2%) when compared to a standard contractility rate of 100% with 40 mM KCI. Moreover, these contractility response rates were significantly reduced (32.8 +/- 21.0%) with the addition of the ET-1 receptor antagonist FR139317. The results of the present study demonstrated that the liver transplantation was associated with elevation of ET-1 in the serum of the recipient animals. It was considered that ET-1 in the serum caused a direct vasoconstriction of the renal artery in vitro. This may help to explain the renal dysfunction that is often seen in the recipients of clinical liver transplantation.

Animals↗

PubMed1995

Regional distribution of messenger RNA encoding the insulin-like growth factor type 2 receptor in the rat lower brainstem.

Distribution of messenger RNA (mRNA) encoding the insulin-like growth factor (IGF) type 2 receptor (IGF2R) is investigated in the rat lower brainstem by in situ hybridization histochemistry. Cells with IGF2R mRNA are distributed widely in a region-specific manner. It is expressed in: (1) motor nuclei such as the oculomotor nucleus, trochlear nucleus, motor trigeminal nucleus, abducens nucleus, facial nucleus, ambiguus nucleus, dorsal motor nucleus of vagus and hypoglossal nucleus; (2) several sensory-related nuclei like the mesencephalic trigeminal nucleus, ventral nucleus of the lateral lemniscus, lateral and spinal vestibular nuclei, ventral and dorsal cochlear nuclei and nucleus of the trapezoid body; and (3) other regions such as the red nucleus, dorsal raphe nucleus, pontine nuclei, three cerebellar nuclei (medial, interposed and lateral), Purkinje cells, cells in the granular layer of the cerebellum, locus coeruleus, several areas of the reticular nucleus and area postrema.

Animals↗

PubMed1995

NG-nitro-L-arginine methyl ester and alpha-methyl-L-ornithine inhibit kyotorphin synthetase from rat brain.

Kyotorphin (KTP), an antinociceptive dipeptide (Tyr-Arg), is formed by KTP synthetase from L-Tyr and L-Arg in the brain. We examined the effects of various L-Arg analogues on immunoreactive KTP (iKTP) formation by KTP synthetase purified partially from rat brain. The NO synthase inhibitor NG-nitro-L-arginine methyl ester (L-NAME), but not NG-nitro-L-arginine and N-iminoethyl-L-ornithine, suppressed iKTP formation by KTP synthetase from 1 mM of L-Arg and L-Tyr, the IC50 value being 2.33 mM. Similarly, alpha-methyl-L-ornithine (alpha-MO) inhibited KTP synthetase, the IC50 value being 2.51 mM. D-Arg at high concentrations also exhibited a weak inhibitory effect. Kinetic experiments indicated that the inhibition by L-NAME and alpha-MO of KTP synthetase is competitive. Thus, these L-Arg analogues appear to act as the competitive inhibitor of KTP synthetase.

Animals↗

PubMed1995

Immunohistochemical evaluation of tenascin in benign eccrine gland tumors: comparison with laminin and fibronectin.

Surgically resected specimens of skin appendage tumors, spiradenoma, poroma of eccrine glands, syringoadenoma, syringoadenoma papilliferum and mixec tumor of skin were evaluated for tenascin, as well as the basement membrane-associated protein laminin, and the extracellular matrix protein fibronectin, using immunohistochemical methods. In normal sweat glands, tenascin was localized as a delicate, thin band in the immediate vicinity of the basement membrane and laminin was limited to the basement membrane. Tenascin in syringoadenoma was also expressed linearly adjacent to the basement membrane. Mixed tumors of skin showed a characteristic distribution of tenascin in the modified myoepithelial cell area adjacent to the tumor epithelia with a heterogeneous pattern, and particularly strong expression in the hyalinous and chondroid areas. In addition, the localization of laminin in the basement membranes of tumors, intracellular immunoreactivity was observed in syringoadenoma, syringocystadenoma papilliferum, and mixed tumor of skin. Fibronectin reactivity was visualized as a diffuse staining in the tumor stroma of eccrine poroma but its expression was restricted in eccrine spiradenoma. The present study suggests a heterogeneity in the distribution of basement membrane and extracellular matrix proteins in skin appendage tumors and elucidation of their functional roles would assist in understanding the changes in the supporting tumor stroma following neoplastic changes.

Cell Adhesion Molecules, Neuronal↗

PubMed1995

Clinical significance of portal invasion by pancreatic head carcinoma.

BACKGROUND: The purpose of the present study was to clarify the indication of aggressive surgery for pancreatic head carcinoma. METHODS: Laparatomy was performed in 153 patients with carcinoma, 101 of whom underwent resection of the carcinoma. With histologic examination the degree of carcinoma invasion into the portal vein was classified into grades 0, I, or II according to the depth of invasion by the carcinoma. Macroscopic carcinoma invasion into portal vein was classified into types A, B, C, or D according to preoperative findings on the portal phase of superior mesenteric angiography or intraoperative portography. RESULTS: Macroscopic findings correlated with the histologic invasion grades. The 1-year survival rate was 39.6% in grade 0, 11.3% in grade I, and 5.5% in grade II cases. The survival rates of patients with type A (p < 0.01), B (p < 0.05), and C invasion (p < 0.01) were higher than those of patients who did not undergo resection; however, no significant difference in the survival rates between patients who did not undergo resection and patients with type D invasion was observed. CONCLUSIONS: For locally advanced carcinoma of the pancreatic head or entire pancreas, patients with type D invasion have no indication of aggressive surgery.

Adult↗

PubMed1995

Role of intravascular ultrasonography in detecting intravascular tumor thrombi: a preliminary report.

BACKGROUND: We evaluated the role of intravascular ultrasonography in the diagnosis of intravascular tumor thrombi. METHODS: During the past 2 years intracaval endovascular ultrasonography was performed in 26 selected patients to diagnose inferior vena cava invasion. Results of positive intracaval endovascular ultrasonogram were correlated with the pathologic findings of resected specimens and autopsy and with other imaging technologies such as computed tomography and angiography. RESULTS: Six patients had positive studies of intracaval tumor thrombus. In all cases detailed horizontal images perpendicular to the inferior vena cava axis were studied. Five of the six patients underwent resection. Intravascular ultrasonography correctly predicted the extent of the tumor thrombus, the degree of tumor adherence to the vessel wall, and the intraluminal movement of the tumor thrombus. Floating thrombi were visualized as an intraluminal to-and-fro movement. Thrombus adhesion to the vessel wall appeared as an absence of space between the tumor and the wall, with no respiratory movement of the thrombus. CONCLUSIONS: Intravascular ultrasonography was useful for the accurate diagnosis of intravascular tumor thrombi and aided in formulating the operative strategy.

Adult↗

PubMed1995

Detection of O2- generation and neutrophil accumulation in rat lungs after acute necrotizing pancreatitis.

BACKGROUND: Polymorphonuclear neutrophils (PMNs) and PMN-derived superoxide anions (O2-) have been found to mediate acute respiratory distress syndrome (ARDS). But the evidence has been obtained only indirectly, (for example, by treatment with free radical scavengers or by measuring lipid peroxides). METHODS: We used chemiluminescence technique to measure O2- generation directly from the surface of rat lungs with necrotizing pancreatitis. Myeloperoxidase activity in the lung tissue was measured by a new chemiluminescence method to quantitate pulmonary neutrophil sequestration. RESULTS: Transient bursts of chemiluminescence that reflected O2- generation were observed at the lung surface 3 to 5 hours after necrotizing pancreatitis was induced. No O2- dependent chemiluminescence was detected at the lung surfaces of the neutropenic rat made by pretreatment with polyclonal antineutrophil antibody. Myeloperoxidase activity was significantly high (mean, 1690 cell numbers/mg wet tissue) in the necrotizing pancreatitis rat lung (p < 0.005). CONCLUSIONS: These data confirmed that activated neutrophils and neutrophil-derived superoxide anions were implicated in lung injury after acute severe pancreatitis.

Acute Disease↗