Biomedical subjects

H Sakaguchi

Publications and source records attributed to H Sakaguchi.

At least 19 recordsLinked to original sources

PubMed1995

Effect of warm ischemia and cryopreservation on cell viability of human allograft valves.

Fibroblast viability of the allograft valve leaflet has been suggested to affect clinical durability. Warm ischemic time is thought to be one of the critical determinants of cell viability. We assessed cell viability of allograft valves by flow cytometry, using a fluorescein diacetate-propidium iodide stain to characterize the effects of warm ischemia and cryopreservation on viability. Twelve human pulmonary valves with harvest-related warm ischemic times (range, 70 to 520 minutes; mean +/- standard deviation, 225 +/- 157 minutes) were studied by flow cytometry. We assessed cell viability of the allograft valve leaflets before and 30 days after storage. A significant negative correlation was found between warm ischemic time (x minutes) and cell viability (y%) before (y = -0.024x + 96.7; r2 = 0.62; p = 0.002) and after 30 days of storage (y = -0.036x + 94.0; r2 = 0.86; p = 0.001). Cell viability of the cryopreserved allograft valves was well preserved (> 70%) with a warm ischemic time less than 520 minutes (8.7 hours).

Adult↗

PubMed1995

Expression of the retinoblastoma gene product in human hepatocellular carcinoma.

Using the mouse anti-human retinoblastoma gene product (pRB) monoclonal antibody, PMG3-245, pRB was detected immunohistocytochemically in human hepatocellular carcinoma (HCC) tissues and a human HCC cell line, designated OCUH-16, recently established in our laboratory. This antibody reacted with human pRB and yielded a single band of approximately 110 kd from cultured OCUH-16 cells. The granules that stained for pRB were found mostly in the HCC cell nuclei, with a few granules observed in the rough endoplasmic reticulum by electron microscopy. Most of the stained granules were located in the euchromatin-rich areas. The percentage of OCUH-16 cells that expressed pRB or DNA polymerase alpha (DNA-PA) decreased over time as the number of OCUH-16 cells increased. The number of HCC cells that stained for pRB in the biopsy specimens from 11 patients varied and pRB expression was well maintained in early and advanced HCC. The level of pRB expression did not correlate with the differentiation of HCC cells or the clinical prognosis. The expression of pRB statistically correlated with that of DNA-PA (P < .01; r = .92). Some sinusoidal cells also stained for pRB. These findings imply that large deletions in the pRB gene are rare in the initiation or promotion of HCC. The correlation between pRB and DNA-PA may suggest that stained pRB participates in the proliferation of both HCC and non-HCC cells.

Adult↗

PubMed1995

Correlation between metastatic site, histological type, and serum tumor markers of gastric carcinoma.

Gastric carcinoma is classified into intestinal type carcinoma (IC) and diffuse type carcinoma (DC). Intestinal type carcinoma usually tends to metastasize to the liver and DC to the peritoneal cavity. However, discrepant cases are sometimes seen: IC with peritoneal metastasis or DC with liver metastatic site with special reference to these discrepant cases. We also studied the serum tumor markers (carcinoembryonic antigen [CEA] and carbohydrate antigen [CA] 19-9). We studied 124 autopsied specimens of patients who died of gastric carcinoma. The primary tumors were classified as IC or DC. The discrepant cases included 19 DCs with liver metastasis and 19 ICs with peritoneal dissemination. Most discrepant cases focally had histological features in the primary tumor consistent with our main supposition. On the other hand, discrepant foci were seen only very rarely in the primary tumor of cases with the corresponding usual metastatic site. The serum CEA levels of specimens from cases with liver metastases were higher than those without liver metastases. The serum CA 19-9 levels showed no significant correlation with the metastatic site of the carcinoma. In conclusion, in gastric carcinoma (1) the metastatic site was correlated with histological type (2) even in cases showing a discrepant metastatic site, focal areas of the histological type consistent with our main findings could be found in the primary tumor, and (3) serum CEA levels correlated with liver metastasis.

CA-19-9 Antigen↗

PubMed1995

Pancreaticoduodenal artery aneurysm: a case report and review of the literature.

A case of true pancreaticoduodenal artery (PDA) aneurysm is reported. A calcified lesion was initially detected by plain x-ray films, and an essential diagnosis was made before operation by intravenous digital subtraction angiography (IVDSA). Surgical resection of the aneurysm was performed successfully. Additionally, we reviewed a total of 82 cases with PDA aneurysm out of the 88 cases that had been reported in the English-language literature up to 1993. Fifty-three cases were accompanied by aneurysmal rupture (rupture group), and 29, including our case, were without rupture (nonrupture group). Because of the high mortality rate (49.1%) in the rupture group, a precise diagnosis and adequate treatment of PDA aneurysm before rupture is important. In the nonrupture group, a calcification on radiography appeared in 61.6% of the cases in which aneurysms were not found incidentally; this seems to be a significant indication for angiography. Moreover, intravenous digital subtraction angiography is quite useful for the screening of PDA aneurysm because it is an easy and noninvasive examination.

Aged↗

PubMed1995

Size-reduced cryopreserved pulmonary valve allograft for an RV-PA conduit: technical modification and functional evaluation.

Cryopreserved pulmonary allografts harvested from adults at the time of kidney donation were size reduced and used in two children with pulmonary atresia and ventricular septal defect. A technical modification for the creation of size-reduced pulmonary allograft conduits is described. Postoperative ultrasonic and cineangiographic assessments revealed excellent function of the pulmonary bicuspid valved conduit with a minimal pressure gradient and essentially no regurgitation. Although the long-term fate of cryopreserved bicuspid pulmonary valve and conduit is unknown, this conduit provides excellent handling characteristics that render allograft conduits preferable to synthetic conduits. In addition, the remodeled bicuspid pulmonary allograft conduits have exhibited excellent hemodynamic characteristics and are a reasonable alternative to other types of conduits when an appropriate size allograft is not available.

Adult↗

PubMed1995

Perichondrial localization of ETA receptor in rat tracheal and xiphoid cartilage and in fetal rat epiphysis.

Autoradiographic studies using 125I-labeled endothelin-1 (ET-1) on sections of rat cartilage tissues, including the trachea, xiphisternum, and fetal rat epiphysis, revealed dense localization of endothelin receptors in the perichondrium. In contrast, the binding of ET-1 was not detected in the chondrocytes, cartilage matrix, and other connective tissues of the cartilage tissues tested. The perichondrial binding of 125I-ET-1 was completely abolished with BQ-123 [an endothelin receptor subtype A (ETA) antagonist] but not with BQ-3020 (an ETB agonist), and we demonstrated the perichondrial localization of ETA receptors. [3H]thymidine incorporation in vitro was significantly increased in rat xiphoid cartilage tissues exposed to ET-1. These findings suggest that the ET-1/ETA receptor system plays an important role in regulating cartilage metabolism and endochondral bone formation.

Animals↗

PubMed1995

Mechanisms of the enhanced contractile response to a low concentration of phorbol 12,13-dibutyrate in thoracic aorta isolated from rats with dietary magnesium deficiency.

The mechanisms underlying the enhanced contractile response to phorbol 12,13-dibutyrate (PDBu) were examined in de-endothelialized thoracic aortas isolated from rats with dietary magnesium (Mg) deficiency. PDBu (1.0 nM)-induced contractions were significantly larger in Mg-deficient rats than in the controls. The contraction was completely inhibited by nifedipine, removal of external Ca2+ or by l-(5-isoquinolinesulfonyl)-2-methylpiperazine (H7). PDBu (1.0 nM) and phorbol 12-myristate 13-acetate (1.0 microM) significantly decreased the KD value and increased the Bmax for the binding of [3H]PN200-110 to the aortas. The degree of the decrease in the KD value was significantly greater in Mg-deficient rats than in the controls. The PDBu-induced decrease in the KD value was abolished by H7. These results suggest that activation of protein kinase C by phorbol esters may participate in the activation of L-type Ca2+ channels, which increases both the affinity of [3H]PN200-110 binding and the magnitude of the external Ca(2+)-dependent contraction. Dietary Mg-deficiency may enhance these processes.

Animals↗

PubMed1995

[Bupivacaine-fentanyl continuous infusion is superior to morphine bolus injection in postoperative epidural analgesia].

We compared bolus injection of morphine 51 +/- 9 micrograms.kg-1 (M-S group) with 48 h-continuous infusion of bupivacaine and fentanyl mixture (BF-C group) for postoperative epidural analgesia in 100 patients who had undergone upper abdominal laparotomy. The epidural analgesia was started about 60 min before completion of surgery. The mixed solution, consisting of bupivacaine 48 ml (240 mg), fentanyl 24 ml (1.2 mg) and 0.9% saline (24 ml), was administered at a rate of 2 ml.h-1 by using a 100 ml balloon infuser. Analgesic effects (determined by visual analogue scale, verbal pain scores at rest and with movement, additional requests of other analgesics), comfort and side effects of the epidural analgesia were examined. The evaluation based on postoperative analgesia and comfortable feeling rated higher in the BF-C group compared with the M-S group (P < 0.01 to of 0.05). There were fewer requests for other postoperative analgesics in the BF-C group (P < 0.01 to 0.05). There was no significant difference in side effects between the two groups. The plasma fentanyl concentration in the BF-C group (n = 5) was maintained almost constant for the period from 24 to 49 hours after the start of infusion and was approximately 1.6 ng.ml-1. We conclude that continuous infusion of bupivacaine (2.5 mg.ml-1) and fentanyl (12.5 micrograms.ml-1) at a rate of 2 ml.h-1 is superior to bolus injection of morphine for postoperative analgesia.

Adolescent↗

PubMed1994

Autocrine regulation of rat chondrocyte proliferation by natriuretic peptide C and its receptor, natriuretic peptide receptor-B.

Natriuretic peptide receptor-B (NPR-B) was identified in rat chondrocytes, and its physiological functions were investigated. Rat tissues, including the xiphoid cartilage, brain, lung, liver, adrenal gland, and kidney, were screened for NPR-B activity, which we assayed by receptor guanylate cyclase activity specifically stimulated by C-type natriuretic peptide (CNP), a known selective activator of NPR-B. Cartilage showed distinctly higher NPR-B activity. Furthermore, exposure of cultured rat chondrocytes to CNP (10(-6) M) resulted in a large increase in intracellular cGMP production (376 +/- 38 pmol/well), with threshold responses occurring between 10(-10) and 10(-9) M CNP. Atrial natriuretic peptide and brain natriuretic peptide also stimulated cGMP production in rat chondrocytes but with a potency that was at least 10 times less than that of CNP. Polymerase chain reaction analysis also demonstrated NPR-B gene expression in adult rat xiphisternum and cultured chondrocytes. These findings indicate that NPR-B is present in rat chondrocytes. In rat chondrocytes exposed to CNP, [3H]thymidine incorporation was inhibited in a dose-dependent manner (half-maximal response, 10(-11)M). However, much higher concentrations of atrial natriuretic peptide were required to induce the inhibition of thymidine incorporation. Interestingly, CNP-like immunoreactivity was detected in the conditioned medium from chondrocyte cultures. In addition, TGF-beta 1, a multifunctional cytokine, induced a marked increase in CNP secretion and CNP mRNA levels in chondrocytes. These results indicate that autocrine CNP inhibits mitogenesis in chondrocytes via NPR-B under the control of TGF-beta 1.

Animals↗

PubMed1994

Segmental transarterial chemoembolization with Lipiodol mixed with anticancer drugs for nonresectable hepatocellular carcinoma: follow-up CT and therapeutic results.

We developed segmental Lp-TAE, which is transcatheter hepatic sub-subsegmental, subsegmental, or segmental chemoembolization using Lipiodol introduced into the tumor-bearing hepatic sub-subsegment, subsegment, or segment as the target area. A total of 98 patients with nonresectable hepatocellular carcinoma (HCC) undergoing segmental Lp-TAE (Seg-Lp-TAE) were studied, and the relationship between the CT pattern observed after Seg-Lp-TAE (Seg-Lp-CT) and the therapeutic results obtained in those patients was evaluated. Seg-Lp-CT was classified into four types (type I, homogeneous; type II, defective; type III, inhomogeneous; and type IV, only slight accumulation, if any) according to the Lipiodol accumulation pattern observed after Seg-Lp-TAE. The cumulative nonrecurrence rates of type I were higher than those of types II-IV. The cumulative survival rates of type Ia, in which Lp accumulation is also seen around the main tumor, were the highest (93.8% at 1 year, 85.9% at 2 years, 85.9% at 3 years, and 57.3% at 4 years). The cumulative survival rates achieved with Seg-Lp-TAE were 89.2% at 1 year, 69.4% at 2 years, 58.9% at 3 years, 44.0% at 4 years, and 30.2% at 5 years, which were higher than those achieved with conventional Lp-TAE. Seg-Lp-TAE is very useful in the treatment of HCC limited to one sub-subsegment, subsegment, or segment, and it is important to choose sub-subsegmental, subsegmental, or segmental Lp-TAE on the basis of the size and site of the tumor as well as the type and the number of feeding arteries.

Adult↗

PubMed1994

Superficial spreading type extrahepatic bile duct cancer with lymphatic micrometastasis: report of a case.

We report herein the case of a 69-year-old woman with extrahepatic bile duct cancer which had developed superficially along the ductal mucosa without penetrating the fibromuscularis. She underwent a pancreatoduodenectomy; however, micrometastases were found histologically in the regional lymph nodes and she died with involved para-aortic lymph nodes and bone metastases 14 months after the operation.

Adenocarcinoma, Papillary↗

PubMed1994

Effect of interferon-gamma on nitric oxide hemoglobin production in endotoxin-treated rats and its synergism with interleukin 1 or tumor necrosis factor.

We studied the in vivo effect of interferon-gamma (IFN-gamma) on nitric oxide (NO) generation. ESR spectra of nitric oxide hemoglobin (HbNO) appeared after a lag time of 2h in the blood of rats treated with Escherichia coli lipopolysaccharide (LPS). IFN-gamma enhanced LPS-induced HbNO formation in rats without modifying the time lag, although IFN-gamma alone did not induce HbNO formation. The plasma nitrate concentration was approximately one order of magnitude higher than the HbNO concentration. On treatment with LPS alone, the amount of tumor necrosis factor (TNF) released decreased after 2 h. Simultaneous addition of IFN-gamma and LPS increased TNF release for at least 8 h. Interleukin 1 (IL-1) release was detected only at 2 h in both groups. We also investigated the in vivo interactions of these cytokines. TNF plus IL-1 induced the greatest HbNO generation, followed by TNF plus IFN-gamma, and then IL-1 plus IFN-gamma. These results suggest that increase of TNF release by IFN-gamma plays a key role in NO generation in LPS-treated rats.

Animals↗

PubMed1994

Subtype switching of natriuretic peptide receptors in rat chondrocytes during in vitro culture.

Subtype switching of natriuretic peptide receptor (NPR) during in vitro culture of rat chondrocytes was demonstrated by polymerase chain reaction (PCR) analysis, receptor binding assay, and the cGMP formation method. NPR-B was the predominant form in the receptor guanylate cyclase family (i.e. NPR-A and NPR-B) in both rat xiphoid cartilage and in its cultured cells. However, the chondrocytes began to express NPR-C at high levels when cultured in vitro and NPR-C became the major form (maximal binding capacity: 450 fmol/mg of protein) of NPR in the cultured cells. The abundantly expressed NPR-C had no effect on adenylate cyclase activity or proliferation of chondrocytes.

Animals↗

PubMed1994

Immunohistochemical analysis of retinoblastoma gene product (pRB) expression in malignant and non-malignant liver diseases.

The retinoblastoma gene product is a nuclear phosphoprotein that undergoes cell cycle-dependent changes in its phosphorylation status. To analyze the expression of retinoblastoma gene product in the process of liver regeneration and the initiation of hepatocellular carcinoma, we studied immunohistochemically the expression of retinoblastoma gene product and DNA polymerase alpha (DPA) in 33 patients with various liver diseases. Only a few hepatocytes positive for retinoblastoma gene product were found in undamaged, nonregenerating liver tissues, whereas many hepatocytes positive for retinoblastoma gene product were detected in specimens of regenerating liver obtained from patients with acute or chronic liver diseases. Similarities were found between distribution patterns of hepatocytes positive for retinoblastoma gene product and those of hepatocytes positive for DPA, and a highly significant positive correlation was found between the number of hepatocyte nuclei stained for retinoblastoma gene product per 1000 nuclei examined (R-LI) and the number of hepatocyte nuclei stained for DPA per 1000 nuclei examined (D-LI) in tissues obtained from patients with nonmalignant liver disease. Hepatocellular carcinoma cells positive for DPA were detected in the 14 hepatocellular carcinoma specimens tested. In ten of these specimens, hepatocellular carcinoma cells positive for retinoblastoma gene product were found but not in the other four. For all hepatocellular carcinoma specimens, R-LI was proportional to D-LI. Thus in both nonmalignant and malignant liver, retinoblastoma gene product increased in proportion to proliferation of hepatocytes or hepatocellular carcinoma cells.

Adult↗

PubMed1994

ESR spectral transition by arteriovenous cycle in nitric oxide hemoglobin of cytokine-treated rats.

Nitric oxide (NO) generation was induced in rats by Escherichia coli lipopolysaccharide (LPS) as detected by electron spin resonance (ESR) signals of NO hemoglobin (HbNO). However, there were inconsistencies in ESR spectral shape among them. We have therefore carried out a systematic study to clarify the in vivo spectral changes. First, the spectra of the alpha-NO heme species had the distinct three-line hyperfine structure in venous blood but not in arterial blood in all rats treated with tumor necrosis factor, interleukin-1, and/or LPS, and methemoglobin was not detected at the g = 6 (high-spin methemoglobin) region. Second, when the treated rats died, the three-line hyperfine structure was very distinct even in arterial blood. Third, even if HbNO was formed by injection of nitrite to rats, the three-line hyperfine structure of HbNO in venous blood was more marked than that in arterial blood, independent of the appearance of the methemoglobin signal. Fourth, an ex vivo study using whole blood demonstrated that the three-line hyperfine structure intensified lineally when O2 saturation of hemoglobin decreased but disappeared on reoxygenation of hemoglobin. These results directly demonstrate in vivo quaternary structural transition of the hemoglobin tetramer from the high-affinity state in the arterial cycle to the low-affinity state in the venous cycle. The transition makes the diverse ESR spectra of HbNO in vivo.

Animals↗

PubMed1994

Treatment strategies for hepatic metastases from pancreatic cancer in patients previously treated with radical resection combined with intraoperative radiation therapy.

Since 1984, we have performed extended radical resection combined with extended intraoperative radiation therapy (IORT) for pancreatic cancer. This approach has provided a dramatic improvement in long-term survival and control of local recurrence. Hepatic metastases, however, remain an unsolved problem. Among patients with this combined therapy, we found hepatic metastases in 8 of 22 patients postoperatively. Four of these 8 were considered candidates for further therapy and underwent treatment for their hepatic metastases, the other 4 had too extensive disease. Two patients with multiple hepatic metastases underwent percutaneous ethanol injection therapy and chemotherapy, but they died within a year. Two patients with a solitary hepatic metastases underwent hepatic resection. One patient died two years and six months after the first operation because of multiple metastases in the liver and both lungs, while the other patient is still alive over six years after the first operation with an excellent performance status. When a patient has no local recurrence and a solitary metastasis in the liver, surgical resection of the liver metastasis should be performed.

Adenocarcinoma↗

PubMed1994

Mechanisms of the enhanced contractile response to phenylephrine in thoracic aorta isolated from rats with dietary magnesium deficiency.

The mechanisms underlying the enhanced contractile response to phenylephrine (PE) and increased susceptibility to nifedipine of de-endothelialized thoracic aorta isolated from rats with dietary magnesium deficiency (Mg-deficient rats) were examined by functional and radioligand binding studies. Enhanced PE-induced contractions and increased susceptibility to nifedipine in Mg-deficient rats were not observed in the presence of 10 microM H7. PE significantly decreased the KD value without changing Bmax in the binding of [3H]PN200-110 to de-endothelialized aortic strips. The KD value obtained in the Mg-deficient rats was significantly smaller than that in the controls. Nifedipine displaced the binding of [3H]PN200-110 concentration-dependently, and the pKi value in Mg-deficient rats was significantly larger than that in the controls. A combination of PE and H7 abolished this difference. These results indicate that the modulation of L-type Ca2+ channels via the stimulation of alpha 1-adrenoceptors may be involved in the enhancement of vasoconstriction and increased susceptibility to nifedipine in aortas isolated from Mg-deficient rats. The H7-sensitive mechanisms may play an important role in these phenomena.

1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine↗

PubMed1994

Enhanced contractile response to phenylephrine and increased density of [3H]PN200-110 binding sites in thoracic aorta isolated from dietary magnesium-deficient rats.

The present study was undertaken to examine whether the enhanced contractile response to phenylephrine observed in thoracic aorta isolated from dietary magnesium-deficient rats depends on an increased density of alpha 1-adrenoceptor or calcium channels. Adult male Wistar rats were fed with a magnesium-deficient diet (0.001 per cent magnesium) for 30 days with control groups (0.07 per cent magnesium). The contractile response to phenylephrine was significantly inhibited by nifedipine in both aortas without endothelium, and the degree of the inhibition was significantly greater in magnesium-deficient rats than in controls. Membranes were isolated from both thoracic aortas without endothelium, and the binding of [3H]PN200-110 or [3H]prazosin to the membranes was studied. A single binding site for [3H]PN200-110 or [3H]prazosin was evident for both membranes with high affinity. Dietary magnesium-deficiency increased significantly the maximal number (Bmax) of [3H]PN200-110 binding sites, but not Bmax of [3H]prazosin, and did not alter the binding affinity of both ligands. These results suggest that increased density of calcium channels participates in the enhanced contractile response to phenylephrine in thoracic aortas isolated from dietary magnesium-deficient rats.

Animals↗