FK506 reduces oxidative hepatic injury following cold ischemic preservation and transplantation.
Explore the source record for details and available documents.
Biomedical subjects
Publications and source records attributed to S Kitano.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
In chronic idiopathic thrombocytopenic purpura (ITP), the two main therapeutic choices are steroid treatment or splenectomy. The adult form of ITP is described as a disease found primarily in young adults, with a female predominance. Treatment with steroids effects a complete response in less than 30% of patients, whereas splenectomy is successful in more than 60% of patients who undergo it. The minimal access afforded by laparoscopic splenectomy is considered highly desirable for these patients. The purpose of this study was to compare the clinical benefits of a laparoscopic splenectomy with those of conventional open surgery for patients with ITP. From 1968 to 1993, splenectomy was performed on 51 patients: 10 operations done laparoscopically and 41 performed conventionally. Complications, postoperative pain, recovery, and hospital charges were then compared. Laparoscopic splenectomy involved minimal incisions, and a significantly lower frequency of analgesia was required for postoperative abdominal pain (1.3 vs. 3.3); hospital stay was shorter (8.2 vs. 20.1 days) (p < 0.005). Operative time was significantly longer for the laparoscopic surgery (249.2 vs. 99.8 min) (p < 0.0001), but blood loss was less (176.0 vs. 511.7 g) (p < 0.01). No intraoperative or postoperative major complications occurred with the laparoscopic procedures, compared with 46.3% with conventional surgery. Finally, the total hospital costs were lower with laparoscopic splenectomy, especially for postoperative care (p < 0.05). A laparoscopic splenectomy may well be considered the surgical treatment of choice for patients requiring a splenectomy in view of both quality of life and economy.
We report a case of rheumatoid pachymeningitis involving the posterior fossa. A 71-year-old woman presented with headache, vertigo and dizziness. MRI demonstrated hypertrophic masses in the meninges of the left cerebellar tentorium, cerebellopontine angle and the fourth ventricle. Six months of treatment with betamethasone, prednisolone and azathioprine improved the patient's neurological status. Because an inappropriate immune process and systemic immune disease may cause idiopathic pachymeningitis, the performance of immunological studies for idiopathic cases is mandatory.
OBJECTIVE: To assess the preventive effect of simple in situ cooling on ischaemic injury in human livers. DESIGN: Randomised study. SETTING: University department of surgery, Japan. SUBJECTS: 20 patients who were to undergo liver resection (right lobectomy, n = 6, left lobectomy, n = 3, and posterior segmentectomy, n = 1, in each group); all but 2 who had normal remnant livers and were randomised to undergo either warm ischaemia or in situ cooling (n = 10 in each group). INTERVENTIONS: Hypothermia was induced by rapid infusion of roughly 450 ml of cold Ringer's lactate into the portal vein during occlusion of the portal triad before resection. MAIN OUTCOME MEASURES: Occlusion time, ATP concentrations, biochemical indicators of liver damage, and coagulation profile. RESULTS: The mean (SD) occlusion time was 55 (6) minutes for the warm ischaemia group and 53 (3) for the in situ cooling group. After in situ cooling the state of the liver as indicated by serum alanine aminotransferase activity (ALT) and prothrombin time had improved substantially. Mean (SD) ALT activity was 516 (168) U/I in the warm ischaemia group compared with 305 (154) in the in situ cooling group (p < 0.02) on the first postoperative day. The respective figures for prothrombin time (%) were 56 (23) compared with 77 (14), (p < 0.05). CONCLUSION: In situ cooling lessened the amount of ischaemic damage done to the liver during hepatectomy compared with treatment with warm ischaemia.
Laparoscopic splenectomy was carried out for the treatment of patients with splenic disorders; 20 idiopathic thrombocytopenic purpura, 1 hamartoma and 3 hereditary spherocytosis. With the patients in the right lateral position, four trocars were used. Under CO2 pneumoperitoneum with a pressure of 10 mmHg, the surrounding ligaments were divided with electrocautery. At the splenic hilum, the splenic artery and vein were exposed using ultrasonic dissector. After double ligation of these vessels, the spleen was dissected with an autostapler. The resected spleen contained in a nylon bag was fragmented with finger-fracture method and extracted through a port site extended up 2 or 3 cm in length. All the patients tolerated the procedure and no blood transfusion was required. Laparoscopic splenectomy is the preferred choice to resect the spleen because of the short hospital stay, less pain and good cosmesis.
PURPOSE: Knowledge of the mechanisms by which retinal ganglion cells are damaged may provide information required to develop novel treatments for diseases that cause retinal ganglion cell death. The authors investigated whether the expression of the 72-kDa heat shock protein in cultured rat retinal ganglion cells increases tolerance to hypoxic and excitotoxic injury. METHODS: Hyperthermia (42 degrees C for 1 hour) and sublethal hypoxia (9% O2 for 6 hours) were used to induce synthesis of the 72-kDa heat shock protein in cultured rat retinal ganglion cells and cultured retinal Müller cells. Induction of the 72-kDa heat shock protein was detected with immunocytochemical and immunoblot techniques. Survival of cultured retinal ganglion cells after exposure to anoxia (< 1% O2 for 6 hours) and glutamate (200 microns for 6 hours) was measured and compared to control cultures stressed previously by hyperthermia or sublethal hypoxia. The effect of quercetin, a blocker of heat shock protein synthesis, was evaluated in parallel experiments. RESULTS: Heat shock protein immunoreactivity was expressed in cultured retinal ganglion cells and Müller cells after hyperthermia and sublethal hypoxia. The mean (+/- standard deviation) retinal ganglion cell survival rates after exposure to anoxia (expressed as a percentage of untreated control cultures) in cells pretreated with sublethal hypoxia (83% +/- 17%) and hyperthermia (82% +/- 19%) were significantly greater than for cells that had no pretreatment (50% +/- 18%, P < 0.001). The mean (+/-standard deviation) retinal ganglion cell survival rate after exposure to glutamate in cells pretreated with sublethal hypoxia (82% +/- 19%) and hyperthermia (86% +/- 17%) were significantly greater than for cells that had no pretreatment (56% +/- 17%, P < 0.001). Inhibition of heat shock protein synthesis with quercetin abolished the protective effects of sublethal hypoxia and hyperthermia on cell survival after anoxia and glutamate exposure. CONCLUSIONS: The neuroprotective effect of hyperthermia and sublethal hypoxia suggests that heat shock proteins confer protection against ischemic and excitotoxic retinal ganglion cell death.
In this work, we demonstrate the signal-transducing mechanism of TGF-beta 1 for gene expression of monocyte chemoattractant JE/monocyte chemoattractant protein 1 (MCP-1) in clonal osteoblastic MC3T3-E1 cells. TGF-beta 1-induced JE/MCP-1 gene expression in the cells was inhibited markedly by H-7 (1-(5-isoguinolinesulfonyl)-2-O-methylpiperazine-dihydrochloride) and staurosporine, potent inhibitors of protein kinase. TGF-beta 1-induced expression of both early proto-oncogenes c-fos and c-jun in the cells was also inhibited by H-7 and staurosporine. Antisense oligonucleotides to c-fos and c-jun genes inhibited significantly the cytokine-induced JE/MCP-1 gene expression. Curcumin, a specific inhibitor of c-jun/AP-1, inhibited the cytokine-induced c-jun gene expression in a dose-dependent manner, though the c-fos gene expression was not affected. TGF-beta 1 stimulated transcriptionally the JE/MCP-1 gene expression, and this stimulation was inhibited significantly by curcumin. Curcumin-induced inhibition of the JE/MCP-1 gene product was also evidenced by both an assay involving immunoprecipitation with antiserum specific for JE/MCP-1 and an assay for monocyte chemotaxis. Curcumin markedly inhibited AP-1 binding activity to 12-tetradecanoyl phorbol-13-acetate-responsive element (TRE) in the cytokine-treated cells. Furthermore, H-7 and staurosporine also inhibited the binding activity to TRE in the cells treated by the cytokine. These results demonstrate that TGF-beta 1 induces expression of monocyte chemoattractant JE/MCP-1 via the transcriptional factor AP-1 induced by protein kinase in the osteoblastic cells.
The effects of lysophosphatidylcholine (LPC), a vasoactive phospholipid, on intracellular free calcium concentration ([Ca2+]i), DNA synthesis and cytotoxicity of vascular smooth muscle cells (VSMC) were studied. LPC from 10(-7) to 10(-5) mol/l dose-dependently induced a sustained increase in [Ca2+]i. In contrast to the response of [Ca2+]i induced by angiotensin II, that induced by LPC was totally abolished when extracellular Ca2+ was removed, was not affected by pretreatment of the cells with islet-activating protein, and was not desensitized by repeated addition. 8-(N,N-Diethylamino)octyl 3,4,5-trimethoxybenzoic acid (TMB-8), an inhibitor of Ca2+ release from intracellular Ca2+ stores, 1-(5-isoquinolinesulfonyl)-2-methylpiperadine dihydrochloride (H-7), an inhibitor of protein kinase C, KT5823, an inhibitor of protein kinase G, and Ca2+ channel blockers failed to suppress the LPC-induced increase in [Ca2+]i. LPC at 10(-5) mol/l caused significant stimulation of [3H]thymidine incorporation into VSMC, and at concentrations of 10(-5) mol/l and higher dose-dependently stimulated release of lactate dehydrogenase in cell culture supernatants. Moreover, digitonin mimicked the effects of LPC on [Ca2+]i, and also caused similar effects to those of LPC on DNA synthesis and cytotoxicity in VSMC. These observations suggest that LPC causes both cell growth and cell injury of VSMC, at least partly, through its detergent action, causing membrane leakiness and resultant [Ca2+]i overload in vitro, thus indicating the possible participation of LPC in atherosclerosis and/or injury of the vascular wall.
Between 1983 and 1994, we treated 51 patients with esophageal varices and portal trunk and main branch invasion of hepatocellular carcinoma, using endoscopic injection sclerotherapy. Variceal bleeding was controlled in 28 of 29 patients (96.6%), esophageal varices were completely eradicated in 28 (54.9%), and only 2 of 28 (7.1%) bled from small, dilated, venous vessels after eradication. The cumulative nonbleeding rate at 3 years was 87.5%. Death caused by hepatocellular carcinoma accounted for 89.4% of the patients, whereas the rate of bleeding from esophageal varices was 4.3%. Variables significantly associated with the duration of survival were Okuda's clinical stage, alpha-fetoprotein, eradication of esophageal varices by sclerotherapy, and treatment of hepatocellular carcinoma, as determined in a univariate analysis. Multivariate analysis showed that eradication of esophageal varices by sclerotherapy, Okuda's clinical stage, and age were independent factors which significantly influenced survival time. We propose that complete eradication of esophageal varices and close follow-up using endoscopy may lead to a reduction in bleeding from esophageal varices, and hence may reduce mortality rates related to this bleeding.
The effects of pneumoperitoneum with carbon dioxide and helium on systemic hemodynamics and arterial blood gases were investigated in pigs in an attempt to clarify the mechanisms by which pneumoperitoneum may induce organ dysfunction. A total of 16 anesthetized female pigs underwent pneumoperitoneum with carbon dioxide or helium (n = 8 each) in a stepwise fashion to intraabdominal pressures of 8, 10, 12, 16, and 20 mmHg. Changes in cardiac output; renal and hepatic blood flow; mean arterial, mean pulmonary arterial, mean pulmonary arterial wedge, inferior vena caval, and portal venous pressures; and total peripheral resistance were measured. Arterial blood samples were obtained at the same time the above parameters were determined. Urine volume was measured as an indicator of renal function. Pneumoperitoneum with either carbon dioxide or helium significantly increased venous pressures and simultaneously decreased cardiac output. These changes were associated with decreases in organ blood flow due to increased peripheral resistance. Urinary output was reduced to a similar degree in the two groups. Blood gas analysis revealed pneumoperitoneum-induced metabolic acidosis in both groups, although hypercapnia was observed only in the carbon dioxide group. These findings suggest that pneumoperitoneum-related organ dysfunction may be due to increased intraperitoneal pressure rather than to hypercapnia.
A 40-year-old woman with Peutz-Jeghers syndrome and an appendiceal intussusception is reported. In this patient, the lead point was a large sessile, appendiceal polyp. The invaginated and inverted portion of the appendix resembled the long stalk of a pedunculated polyp on roentgenography and endoscopic examination. Histologically, the appendiceal polyp was a villous adenoma with mild to severe atypia and focal carcinoma in situ. In patients with Peutz-Jeghers syndrome, hamartomatous polyps and colorectal adenomatous polyps with highly malignant potential can coexist and must be managed appropriately. Therefore, when evaluating a polypoid or a pedunculated lesion in the cecal lumen, the possibility of an appendiceal intussusception should also be investigated.
The role of glucagon as a mediator of gastric hyperdynamic circulation, induced by carbon tetrachloride (CCl4), was assessed in cirrhotic rats. A selective elimination of pancreatic glucagon from the circulation was achieved by the intravenous infusion of a glucagon antiserum. Gastric blood flow was measured by laser-Doppler flowmetry. The glucagon antiserum had no effect on the blood flow in the stomach in control rats, while in cirrhotic portal hypertensive rats, the glucagon antiserum significantly reduced gastric blood flow (30%). The glucagon antiserum did not completely exclude the gastric hyperdynamic state in the cirrhotic rats. It would thus appear that glucagon contributes to a portion of the gastric hyperdynamic circulation associated with cirrhotic portal hypertension.
Our previous study (Y. Kawata, S. Hanazawa, S. Amano, Y. Murakami, T. Matsumoto, K. Nishida, and S. Kitano, Infect. Immun. 62:3012-3016, 1994) showed that Porphyromonas gingivalis fimbriae stimulate bone resorption in vitro. Since it has recently been demonstrated that tyrosine kinase encoded by the c-src gene plays an important role in osteoclastic bone resorption, in the present study we examined the effect of a tyrosine kinase inhibitor on the fimbria-stimulated bone resorption. Genistein, a potent inhibitor of tyrosine kinase, markedly inhibited bone resorption stimulated by the fimbriae. Genistein also inhibited induction of several tyrosine-phosphorylated proteins in the fimbria-treated calvarial bone cells from mouse embryos.
To define the pathophysiological role of nitric oxide (NO) released from vascular smooth muscle cells (VSMC), we examined whether NO released from VSMC induces cytotoxicity in VSMC themselves and adjacent endothelial cells (EC) using a coculture system. Prolonged incubation with interleukin-1 (IL-1) induced large amounts of NO release and cytotoxicity in VSMC. NG-Monomethyl-L-arginine, an inhibitor of NO synthesis, inhibited both NO release and cytotoxicity induced by IL-1. In contrast, DNA synthesis in cocultured EC was not inhibited but rather stimulated by prolonged incubation with IL-1 or sodium nitroprusside (SNP), a NO donor. However, IL-1 and SNP did not stimulate but inhibited DNA synthesis in EC alone. On the other hand, conditioned medium from VSMC incubated for a long period with IL-1 or SNP stimulated DNA synthesis in EC alone. Furthermore, the concentration of basic fibroblast growth factor in the conditioned medium was increased and correlated with the degree of cytotoxicity in VSMC. These results indicate that NO released from VSMC induces VSMC death, which results in release of basic fibroblast growth factor, which then stimulates adjacent EC proliferation. Thus, NO released from VSMC may participate in the mechanism of neovascularization in atherosclerotic plaques.
Seventy-five surgically treated patients with hepatocellular carcinoma (HCC) of Stage III or IV-A were divided into two groups: group I, control without postoperative adjuvant infusion (PAI); group II, patients treated with PAI. In the PAI group, 29 patients (mean diameter of tumors = 71 mm) prophylactically underwent PAI after hepatic resection. Chemotherapeutic agents, (5-FU, ADM, MMC, CDDP and Lipiodol) were administered 4 times a year via the hepatic artery through Infuse A port. The remaining 46 patients (mean diameter of tumors = 70 mm) served as the historical control without PAI. The 4-year cumulative survival rate was higher in the PAI group (45.6%) than in the control (25.4%, p = 0.0424). The 4-year disease-free survival rate was also improved in the PAI group (37.0%) compared with that in the control (14.4%, p = 0.0096). Intrahepatic multiple recurrence was recognized in 8 out of 29 patients in the PAI group (28%) and in 24 out of 46 in the control (53%, p = 0.036) within 1 year after surgery. Extrahepatic recurrence without diseases in the remnant liver tended to occur with higher frequency in the PAI group than in the control. Based on our data, we suggest that PAI is effective in alleviating intrahepatic multiple recurrence within 1 year after hepatic resection for advanced HCC and that systemic chemotherapy may be necessary for preventing extrahepatic recurrence.
We report here the operative findings, the incidence of successful laparoscopic treatment, and the perioperative complications in patients with nonvisualized gallbladder on drip infusion cholangiography (DIC). Eighty-five patients with a nonvisualized gallbladder on DIC were entered into the study. None of the patients had a minimal adhesive gallbladder; 51 to 85 patients (60.0%) had moderate adhesive gallbladders, and 34 (40.0%) had severely adhesive ones. The rate of successful laparoscopic treatment, including laparoscopy-assisted abdominal surgery, was 97.6% (83 of 85 patients). Perioperative complications occurred in only three patients (3.5%), and there were no deaths related to the operation. Thus, when patients with a nonvisualized gallbladder on DIC undergo laparoscopic cholecystectomy, meticulous procedures must be carried out; however, as the rate of successful laparoscopic treatment is high, cholecystectomy under laparoscopy is feasible for experienced surgeons.
In eight Japanese patients, three different laparoscopic procedures were used to excise an early gastric carcinoma; partial resection in four, intragastric resection of the gastric mucosa in two, and laparoscopic-assisted distal partial gastrectomy with the abdominal wall-elevating method in two patients. Histological examinations revealed that the lesions were completely resected, and there was no evidence of lymphatic metastasis. The operation time ranged from 2 to 4 h. These forms of laparoscopic gastric surgery for patients with early gastric carcinomas may be useful from the standpoint of minimal access, rapid recovery, less pain, and good cosmesis.