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Biomedical subjects

Y Kamiyama

Publications and source records attributed to Y Kamiyama.

At least 73 records · Page 4Linked to original sources
PubMed1999

Immunosuppressant FK506 inhibits inducible nitric oxide synthase gene expression at a step of NF-kappaB activation in rat hepatocytes.

BACKGROUND/AIMS: Recent evidence indicates that an increase in nitric oxide production after liver transplantation is associated with acute allograft rejection. Nitric oxide mediates cellular injury under various pathological conditions in the liver. Studies were performed to determine whether the immunosuppressants FK506 and cyclosporin A directly influence gene expression of inducible nitric oxide synthase by interleukin 1beta in hepatocytes. METHODS: Primary cultures of rat hepatocytes were treated with interleukin 1beta in the presence and absence of FK506 or cyclosporin A. Release of nitrite (nitric oxide metabolite) into culture medium, levels of inducible nitric oxide synthase protein and mRNA, and activation of nuclear factor-kappaB were compared with the two drugs. RESULTS: Interleukin 1beta increased levels of inducible nitric oxide synthase protein and inducible nitric oxide synthase mRNA, as well as nitric oxide production, in the cultured hepatocytes. Nuclear factor-kappaB, an important transcription factor in inducible nitric oxide synthase gene expression in response to inflammation, also appeared in the nuclear fraction of hepatocytes after addition of interleukin 1beta. FK506 markedly inhibited the nitric oxide formation, inducible nitric oxide synthase protein synthesis and inducible nitric oxide synthase mRNA expression induced by interleukin 1beta, but cyclosporin A had no effects. Furthermore, FK506 inhibited nuclear factor-kappaB activation and decreased mRNA levels of the p50/p65 subunits of nuclear factor-kappaB. CONCLUSIONS: These results demonstrate that FK506, but not cyclosporin A, inhibits the induction of inducible nitric oxide synthase expression during nuclear factor-kappaB activation. FK506 may influence liver function during diseases by modulating the nitric oxide pathway, in addition to its immunosuppressive effect.

Animals↗
PubMed1999

Different responses to surgical stress between extra domain A+ and plasma fibronectins.

1. Fibronectins (FN) are believed to have a role in haemorheological perturbation associated with tissue damage. Fibronectins exist in two antigenically related forms, plasma (p) and cellular fibronectin, which has the extra domain sequences A (EDA) or B (EDB). The present study was designed to determine changes in plasma p-FN and EDA + FN under different types of surgical stress. 2. Sixty-two patients were divided into three groups: (i) group A, 33 patients undergoing hepato-pancreato-biliary surgery; (ii) group B, 19 patients undergoing laparoscopic cholecystectomy; and (iii) group C, 10 patients with postoperative complications. Plasma FN and EDA + FN levels were measured in these patients undergoing different types of surgical operation and either with or without liver cirrhosis using an enzyme-linked immunosorbent assay. 3. After surgery, a significant decrease in p-FN levels and a significant increase in EDA + FN levels was observed in all patient group compared with pre-operative levels. The duration of increased EDA + FN levels, but not p-FN levels, in group A patients was significantly longer than in group B patients. Although changes in p-FN levels between patients with and without liver cirrhosis were significantly different, there were no significant differences in the EDA + FN levels between these two patient groups. 4. In conclusions, EDA + FN and p-FN levels were found to exhibit opposite responses to surgical stress. Furthermore, with greater surgical stress, greater increases in EDA + FN levels were seen. The presence of liver cirrhosis had no significant effect on EDA + FN levels during the perioperative period; however, p-FN levels were significantly affected. 5. Thus, it is suggested that plasma EDA + FN levels reflect the magnitude of surgical stress more closely than do p-FN levels.

Adult↗
PubMed1999

Ureteropyeloscopy in the diagnosis of patients with upper tract hematuria: an initial clinical study.

BACKGROUND: To study the usefulness and safety of ureteropyeloscopy in the diagnosis of upper tract hematuria of unknown etiology by standard diagnostic methods. METHODS: Fifteen patients with upper tract hematuria of unknown etiology were the subjects of the present study. Prior to ureteropyeloscopy, they underwent standard diagnostic methods, including cystourethroscopy, excretory urography and computed tomography scan. The upper tract (ureter, renal pelvis and calyces) was inspected systematically with a flexible ureteropyeloscope under epidural anesthesia. A biopsy specimen was obtained when neoplasm of a suspicious lesion was seen. Bleeding and hemangiomatous lesions were fulgurated at the time of ureteropyeloscopy. RESULTS: Unilateral gross hematuria was seen in 12 patients. Imaging studies revealed a filling defect in four patients, ureteral stenosis in one patient and nutcracker phenomenon in one patient. Urine cytology was positive in three patients and suspicious in four patients. Results of ureteropyeloscopy were papillary tumor in three patients, whitish encrustation in one patient, redness of the renal pelvis in one patient, bleeding from the renal calyx in two patients, hemangiomatous lesion in one patient, ureteral stenosis in two patients and no abnormalities in five patients. Biopsies were performed in five patients. The pathology results were transitional cell carcinoma in four patients and no abnormality in one patient. Although a ureteral stent catheter was placed in one patient, no serious complications were encountered during or after the procedures. CONCLUSIONS: Ureteropyeloscopy was useful and relatively safe. This endoscopic examination can differentiate insignificant lesions from significant lesions by visual inspection of the lesions, in addition, pathological diagnosis by biopsy specimen can also be performed if deemed necessary. Ureteropyeloscopy is recommended in the diagnosis of upper tract hematuria of unknown etiology.

Adult↗
PubMed1999

Ex vivo liver perfusion with arterial blood from a pig with ischemic liver failure.

To simplify liver support using an ex vivo perfused liver, an isolated pig liver was perfused with arterial blood from the recipient pig while monitoring the metabolic capacity of the ex vivo perfused liver. It was possible to perfuse the isolated liver for more than 24 h using arterial blood from a pig with ischemic liver failure. The viability of the isolated liver during support from the liver failure pig was well maintained as evidenced by the high adenylate energy charge (0.815) and a constant ketone body ratio (KBR) of over 1.0 sampled from the hepatic vein. Oxygen consumption (mean, 29.0 microl/min/g of liver) and bile production (mean, 24.2 microl/h/g of liver) were significantly higher in the isolated liver connected to the liver failure pig than in the organ connected to the pig without liver failure (15.5 microl/min/g and 7.3 microl/h/g, respectively). These findings suggest that this liver support system has sufficient metabolic capacity to support a failed liver. Further studies may provide the experimental basis necessary for the clinical application of this device in treatment of patients with acute liver failure.

Animals↗
PubMed1999

Acceptance of skin allografts in pigs by portal venous injection of donor bone marrow cells.

OBJECTIVE: To confirm in pigs whether a new method for organ allografts, originally established in mice by the authors, might be applicable to humans. SUMMARY BACKGROUND DATA: The authors recently established a new method for organ allografts in mice that includes the injection of donor bone marrow cells (BMCs) using the portal vein (PV), followed by the administration of cyclosporin A (CsA) on days 2 and 5, and the intravenous injection of BMCs on day 5. In the present study, they modify this method (a single-day protocol) and apply it to pigs. METHODS: Allogeneic BMCs of donor pigs were injected using the PV (a superior mesenteric vein). The skin grafting was carried out on the day of the PV injection. The recipient pigs received donor grafts, autologous grafts, and third-party grafts at the same time. In addition, an open wound was made as the epithelized control. Full-thickness skin grafts were harvested from the dorsal wall of the donors. CsA (10 mg/kg) was injected intramuscularly into recipient pigs on days 2 and 5 after the PV injection. RESULTS: One hundred percent of skin grafts survived for >300 days when donor BMCs were injected using the PV (n = 6). However, the skin grafts of the three pigs that had received BMCs using the intravenous route were rejected within 3 to 4 weeks after transplantation. The third-party skin grafts showed necrotic changes on day 21 after transplantation. CONCLUSIONS: One hundred percent of skin allografts can be obtained, even in pigs, by injecting donor BMCs using the PV, carrying out skin allografts, and administering CsA on days 2 and 5. This single-day protocol would be of great advantage for human organ transplantation.

Animals↗
PubMed1999

Selective ablation of porcine and rabbit liver tissue using radiofrequency: preclinical study.

Temperature changes and their distribution induced by 13.56-MHz radiofrequency (RF) heating of agar phantom and porcine and rabbit liver were investigated. It was possible to produce selective local heating of approximately 50 degrees C in the RF field of 2 x 2 x 2 cm(3) of the pig or rabbit liver. Coagulation necrosis after heating became pronounced and the margin between the coagulated lesion and normal tissue became clearer with time. Within 1 week after RF heating at 50 degrees C for 20 min, the coagulated area was replaced selectively and totally by necrotic tissue.

Animals↗
PubMed1999

Bilateral emphysematous pyelonephritis with autosomal-dominant polycystic kidney disease successfully treated by conservative method.

Emphysematous pyelonephritis (EPN) is an uncommon and potentially life-threatening necrotizing inflammation of the renal parenchyma. EPN associated with autosomal dominant polycystic kidney disease (ADPCK) is extremely rare. We report such a case of bilateral EPN with ADPCK that was successfully treated with conservative methods. To our knowledge, our case is only the second to document bilateral EPN occurring with ADPCK and the first one to be treated successfully with conservative methods.

Anti-Bacterial Agents↗
PubMed1998

A strategy for organ allografts without using immunosuppressants or irradiation.

A strategy to achieve regular and long lasting organ and tissue allografts without using immunosuppressants and/or irradiation has been established for mice. One hundred percent of skin allografts can be induced to survive >350 days after transplantation if spleen cells from the same donors are first injected into the portal vein of the recipients. The mechanisms underlying this long-term tolerance induction can be described as follows: (i) donor T cells from the spleen of the donor facilitate the acceptance of the allogeneic engraftment, (ii) donor-specific anergy is induced in the cytotoxic T-lymphocytes of the recipients, (iii) T helper type 2 cells become the dominant T cells in the recipients that are accepting the skin transplants, and (iv) a lasting chimerism (microchimerism) is established in these recipients. This strategy, perhaps with minor modifications, might permit one also to overcome major barriers to organ allografting in humans. If this were the case, it could represent production of long lasting immunologic tolerance without need for irradiation or cytotoxic chemo-preparative regimen and as such could greatly facilitate allotransplantation free of episodes of chronic or acute rejection or toxic and damaging preparatory regimens.

Adoptive Transfer↗
PubMed1998

Therapeutic significance of palliative operations for gastric cancer for survival and quality of life.

BACKGROUND AND OBJECTIVES: There have been few reports on the objective assessment of quality of life (QOL) in patients with gastric cancer following palliative operations. The benefit of a palliative operation for survival and QOL of patients with gastric cancer is not clear. METHODS: Survival and hospital-free survival (HFS), which is considered to be one objective indicator of QOL, were studied in 95 patients undergoing palliative operations for gastric cancer. Univariate and multivariate analyses were used to determine the clinicopathologic factors potentially related to survival of patients. RESULTS: In univariate analysis, palliative gastrectomy and absence of peritoneal dissemination were significantly correlated with better survival. The significance of palliative gastrectomy for survival was, therefore, evaluated for various degrees of peritoneal dissemination: P0 no dissemination; P1, metastasis to the adjacent peritoneum; P2, a few scattered metastases to the distant peritoneum; and P3, numerous metastases. Survival and achievement of HFS for 3 months or longer were higher following palliative gastrectomy than gastrojejunostomy. Among gastrectomies, however, total gastrectomy performed in patients with P2 or P3 showed a poorer outcome for survival and HFS than total gastrectomy performed with P0 or P1 and distal gastrectomy. CONCLUSIONS: As a palliative measure, gastrojejunostomy and total gastrectomy performed with P2 or P3 peritoneal dissemination had no beneficial effect on the prolongation of survival or improvement of QOL of patients with gastric cancer.

Adult↗
PubMed1998

Interleukin 1beta and interleukin 6, but not tumor necrosis factor alpha, inhibit insulin-stimulated glycogen synthesis in rat hepatocytes.

Recent evidence indicates that inflammatory cytokines are involved in changes of blood glucose concentrations and hepatic glucose metabolism in infectious diseases, including sepsis. However, little is known regarding how cytokines interact with glucoregulatory hormones such as insulin. The objective of the present study is to investigate if and how cytokines influence insulin-stimulated glycogen metabolism in the liver. Interleukin 1beta (IL-1beta) and interleukin 6 (IL-6) markedly inhibited the increase of glycogen deposition stimulated by insulin in primary rat hepatocyte cultures; however, tumor necrosis factor alpha had no effect. Labeling experiments revealed that both cytokines counteracted insulin action by decreasing [14C]-glucose incorporation into glycogen and by increasing [14C]-glycogen degradation. Furthermore, it was discovered that IL-1beta and IL-6 inhibited glycogen synthase activity and, in contrast, accelerated glycogen phosphorylase activity. In experiments with kinase inhibitors, serine/threonine kinase inhibitor K252a blocked IL-1beta- and IL-6-induced inhibitions of glycogen deposition, as well as glycogen synthase activity, whereas another kinase inhibitor staurosporine blocked only IL-6-induced inhibition. Tyrosine kinase inhibitor herbimycin A blocked only IL-1beta-induced inhibition. These results indicate that IL-1beta and IL-6 regulate insulin-stimulated glycogen synthesis through different pathways involving protein phosphorylation in hepatocytes. They may mediate the change of hepatic glucose metabolism under pathological and even physiological conditions by modifying insulin action in vivo.

Animals↗
PubMed1998

Hepatocyte growth factor stimulates synthesis of lipids and secretion of lipoproteins in rat hepatocytes.

We have reported that infusion of recombinant human hepatocyte growth factor (rhHGF) stimulates liver regeneration after hepatectomy in cirrhotic rats and increases the level of serum lipids and secretion of very-low density lipoprotein (VLDL). Studies were now performed to determine whether rhHGF directly influences lipid synthesis and its secretion in cultured rat hepatocytes. Isolated cells were cultured in the presence or absence of rhHGF (20 ng/mL) for 2 days. During the first 12 hours, rhHGF transiently inhibited the release of lipids (triacylglycerol, total cholesterol, and phospholipids), but stimulated their releases with maximal levels achieved at 36 hours. [3H]-glycerol experiment with the transcriptional and translational inhibitors revealed that rhHGF stimulated de novo synthesis of lipids by affecting activities of lipid metabolic gene. [35S]-Methionine experiment also revealed de novo synthesis of apolipoprotein B by rhHGF. Furthermore, lipid analysis of lipoprotein fractions in the conditioned medium showed that rhHGF enhanced levels of triacylglycerol, total cholesterol, and phospholipids by 50% to 200% in both VLDL and low-density lipoproteins (LDL)/high-density lipoprotein (HDL). Genistein, a tyrosine kinase inhibitor, blocked the secretion of VLDL, as well as synthesis of lipids and apolipoprotein B stimulated by rhHGF. These results indicate that HGF likely stimulates lipid biosynthesis and lipoprotein secretion in hepatocytes through its tyrosine kinase-associated receptor, c-met, and accelerates the progress of cell maturation in liver regeneration.

Androstadienes↗
PubMed1998

Palliative operation for cancer of the head of the pancreas: significance of pancreaticoduodenectomy and intraoperative radiation therapy for survival and quality of life.

The benefits of a palliative operation and intraoperative radiation therapy (IORT) for survival and quality of life (QOL) of patients with cancer of the head of the pancreas are not clear. Survival and hospital-free survival (HFS), which are considered to be objective indicators of QOL, were studied in 13 patients who underwent palliative pancreaticoduodenectomy (PD) and 32 patients who underwent surgical bypass. Although there was no significant difference in the survival of patients who underwent PD or bypass (median survivals of 9 months and 7 months, respectively), HFS for 3 months or longer was achieved in 84.6% of the patients who underwent PD, which was significantly higher than that of the 53.1% in patients who underwent surgical bypass (p < 0.05). Among TNM stage III patients, a significant difference in survival was observed between surgical bypass associated with IORT and bypass alone (p < 0.05); the median survival time of the IORT group was 10 months, whereas that of the control group was 5 months. In addition, HFS of 3 months or longer was achieved in 83.3% of patients who underwent bypass with IORT but in only 25.0% of the patients who underwent surgery alone (p < 0.01). The addition of IORT to palliative PD neither prolonged survival nor improved HFS. These results show the beneficial effect of palliative PD on QOL, and the efficacy of IORT for survival and QOL was proved in cases with stage III pancreatic cancer who underwent surgical bypass. For patients subjected to palliative PD, however, IORT is not thought to be beneficial for either survival or QOL.

Adult↗
PubMed1998

Managing bile duct injury during and after laparoscopic cholecystectomy.

Laparoscopic cholecystectomy is now the treatment of choice for gallstones, but there has been concern that bile leakage after a laparoscopic cholecystectomy is more frequent than after an open cholecystectomy. We have experienced 16 patients with bile duct injury after a laparoscopic cholecystectomy. Five patients had a circumferential injury to the major bile duct, and we employed a converted open technique for biliary reconstruction. The other 11 patients had partial injury to the major bile duct, and we performed laparoscopic restoration; all 11 of these patients received endoscopic retrograde cholangiography (ERC) on the day after the operation and stenting for biliary decompression and drainage. No complications were identified and the duration of hospitalization in these patients was significantly shorter than in those who had the converted procedure. If intraoperative cholangiography is performed routinely, the presence and form of bile duct injury can be clearly identified, and the decision to restore the site of injury or to convert to the open technique for biliary reconstruction can be made immediately.

Adult↗
PubMed1998

Seroma with fibrous capsule formation requiring a surgical resection after a modified radical mastectomy: report of a case.

Seroma formation is the most common complication of a modified radical mastectomy for breast cancer. Although various management or risk factors for seroma formation have been previously reported, little has been published concerning seromas with fibrous capsule formation which ultimately require a surgical resection. We herein present a case who developed a seroma with a fibrous capsule after a modified radical mastectomy for breast cancer, in spite of an uneventful intraoperative and postoperative course. The seroma was refractory to all conventional treatments, and thus finally required a surgical resection.

Axilla↗
PubMed1998

A simplified model of hypoxic injury in primary cultured rat hepatocytes.

The Anaeropack system for cell culture, which was originally designed for the growth of anaerobic bacteria, was used to produce a hypoxic atmosphere for cultured hepatocytes. We measured changes in the oxygen and carbon dioxide concentrations and the atmospheric temperature in an airtight jar. We also measured changes in the pH of the medium during hypoxia to assess the accuracy of this system. Moreover, we used three durations (2, 3, and 4 h) of hypoxia and 8 h of reoxygenation in cultured rat hepatocytes, and then measured the lactate dehydrogenase (LDH), ketone body concentration (acetoacetate + beta-hydroxybutyrate), and the ketone body ratio (KBR: acetoacetate/beta-hydroxybutyrate) in the medium in order to assess the suitability of this system as a model for reperfusion following liver ischemia. The oxygen concentration dropped to 1% or less within 1 h. The concentration of carbon dioxide rose to about 5% at 30 min after the induction of the hypoxic conditions, and was maintained at this level for 5 h. No effect of the reaction heat produced by the oxygen absorbent in the jar was recognized. The extent of cell injury produced by changing the hypoxic parameters was satisfactorily reflected by the KBR, the ketone body concentration, and the LDH activity released into the medium. Because this model can duplicate the conditions of the hepatocytes during revascularization following ischemic liver, and the Anaeropack system for cell culture is easy to manipulate, it seems suitable for the experimental study of hypoxic injury and revascularization in vitro.

Animals↗
PubMed1998

Prolonged decreases in plasma nitrate levels at early postoperative phase after hepato-pancreato-biliary surgery.

Nitric oxide (.NO) is known to influence circulatory, neural, immunologic, and metabolic alterations. To evaluate the clinical significance of .NO production under surgical stress, serial measurements of plasma nitrite plus nitrate levels were performed in 45 surgical patients. Group A included 19 patients who underwent major surgery with uneventful postoperative courses. Group B included 18 patients who underwent laparoscopic cholecystectomy. Group C included 8 patients whose surgery was complicated by intra-abdominal abscesses. Eight healthy volunteers served as controls. Plasma nitrate levels were determined with a redox chemiluminescence .NO analyzer and coincided with measurements made by high-performance liquid chromatography (r = 0.868, p < 0.0001, 58 samples). During laparotomy, arterial nitrate levels correlated well with peripheral, portal, and hepatic venous nitrate levels (r = 0.966, 0.938, and 0.949, respectively; p < 0.0001). A significant decrease in nitrate from preoperative levels in groups A (postoperative day (POD) 1 and 3; p < 0.0005) and B (POD 1, p < 0.0001) was observed; nitrate levels in group C did not decrease for 14 days after surgery. Plasma nitrate levels in groups A and B were significantly different (POD 1 through 6, p < 0.05) and at POD 3 were significantly lower in group A (p < 0.005). Plasma nitrate levels measured before and after fasting or food intake were not significantly different. These results suggest that surgical stress leads to a decrease in the end product of .NO in the whole body, and that the greater the surgical stress the longer the duration of decreased .NO production.

Adult↗
PubMed1998

Stimulation of nitric oxide release from rat spinal cord by prostaglandin E2.

1. We recently demonstrated that intrathecal administration of prostaglandin E2 (PGE2) and PGF2alpha induced allodynia through a pathway that includes the glutamate receptor and nitric oxide (NO)-generating systems from pharmacological studies. In order to clarify the involvement of NO in prostaglandin-induced allodynia, we measured NO released from rat spinal cord slices by a chemiluminescence method. 2. PGE2 stimulated NO release from both dorsal and ventral regions all along the spinal cord. PGE2 stimulated the release within 10 min and increased it in a time-dependent manner. 3. The PGE2-induced NO release was observed at 100 nM-10 microM. PGF2alpha stimulated the release at concentrations higher than 1 microM, but PGD2 (up to 10 microM) did not enhance it. 4. 17-Phenyl-omega-trinor PGE2 (EP1 > EP3) and sulprostone (EP1 < EP3) were as potent as PGE2, but PGE1 was less potent, in stimulating NO release. While M&B 28767 (EP3) did not enhance the release, butaprost (EP2) stimulated it at 1 microM. The PGE2-evoked release was blocked by ONO-NT-012, a bifunctional EP1 antagonist/EP3 agonist. 5. The PGE2-evoked release was Ca2+-dependent and blocked by MK-801 (NMDA receptor antagonist) and L-NAME (NO synthase inhibitor). The release was also inhibited by PGD2 and dibutyryl-cyclic AMP. 6. The present study demonstrated that PGE2 stimulates NO release in the rat spinal cord by activation of NMDA receptors through the EP1 receptor, and supports our previous findings that the NO-generating system is involved in the PGE2-induced allodynia.

Animals↗