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Biomedical subjects

R Kumashiro

Publications and source records attributed to R Kumashiro.

At least 55 records · Page 3Linked to original sources

Roles of the splenic cytokines and arachidonic acid metabolites in severe hepatic injury after lipopolysaccharide injection in chronically alcohol-fed rats.

We examined the early changes after lipopolysaccharide (LPS) injection in chronically alcohol-fed rats with or without splenectomy. Administration of 2 mg/kg body weight LPS caused severe hepatic injury. The plasma aspartate aminotransferase (ASAT) activity was significantly higher in sham-operated rats 8 hr after LPS injection than in splenectomized rats. The plasma tumor necrosis factor (TNF) activity was also significantly higher 1 hr after LPS injection in sham-operated rats than in splenectomized rats. The plasma thromboxane (TX) B2/6-keto-prostaglandin (PG) F1 alpha ratio increased in sham-operated rats after LPS injection. Therefore, the balance of arachidonic acid metabolites was in a hypercoagulated state in sham-operated rats after the LPS injection. Neutrophil infiltration into liver tissue increased in sham-operated rats after the LPS injection. The cytokines and arachidonic acid metabolites released from the spleen after LPS injection in alcohol-fed rats may play important roles in severe hepatic injury.

Animals↗

Clinical and pathological features, and the mechanism of development in severe alcoholic hepatitis, especially in comparison with acute type fulminant hepatitis.

Among the patients with alcoholic hepatitis, the patients with severe alcoholic hepatitis (SAH) were distinguished by clinical course, laboratory data and histological findings. The aim of this study was to clarify the clinicopathological features, pathological condition and pathogenesis of SAH. Twenty-four SAH patients were compared with 55 patients with acute type fulminant hepatitis (FH) and the other types of alcoholic liver disease. SAH showed a very poor prognosis with a survival rate of 25% and was complicated by multiple organ failure earlier than FH. IgA class lipid A antibody, endotoxin (Et) and tumor necrosis factor-alpha (TNF-alpha) levels in the blood well reflected the pathological condition and severity of SAH. The white blood cell count in the peripheral blood was thought to be the simplest indicator for the prediction of the prognosis of SAH. In conclusion, SAH involves hyper-endotoxemia due to dysfunction of the reticuloendothelial system in the liver, and cytokines including TNF-alpha and neutrophils play an important role in the severity of liver injury.

Adult↗

Regulation of inflammation-primed activation of macrophages by two serum factors, vitamin D3-binding protein and albumin.

A very small amount (0.0005 to 0.001%) of an ammonium sulfate [50% saturated (NH4)2SO4]-precipitable protein fraction of alpha 2-globulin efficiently supported inflammation-primed activation of macrophages. This fraction contains vitamin D3-binding protein essential for macrophage activation. Comparative macrophage activation studies with fetal calf serum, alpha 2-globulin fraction, 50% (NH4)2SO4 precipitate, and purified bovine vitamin D3-binding protein revealed that fetal calf serum and alpha 2-globulin fraction appear to contain an inhibitor for macrophage activation while ammonium sulfate precipitate contains no inhibitor. This inhibitor was found to be serum albumin. When bovine serum albumin (25 micrograms/ml) was added to a medium supplemented with 0.0005 to 0.05% (NH4)2SO4 precipitate or 1 to 10 ng of vitamin D3-binding protein per ml, activation of macrophages was inhibited.

Adult↗

Fatal acute hepatitis B virus infection while receiving immunosuppressants after renal transplantation.

A 47-year-old man with acute hepatitis B virus (HBV) infection who had been receiving immunosuppressants after renal transplantation developed progressive liver failure. During the clinical course (approximately 7 months), anti-HBc IgM antibody and HBV-DNA polymerase levels remained high, but the serum alanine aminotransferase (ALT) level was consistently less than 150 K.U. Histopathologic examination of the liver showed submassive hepatic necrosis without significant inflammation accompanied by marked fibrosis. Most hepatocytes showed strong nuclear expression of HBc antigen by immunohistochemical staining and electron microscopy revealed numerous intranuclear core-like particles. Hepatitis B virus infection in immunosuppressed individuals occasionally insidiously progresses, resulting in liver failure. The clinical course of such patients thus merits close scrutiny.

Acute Disease↗

Hydroxyl radical generation and membrane fluidity of erythrocytes treated with lipopolysaccharide.

The effect of lipopolysaccharide (LPS) and/or bile acids on rat erythrocyte membranes was studied in vitro. Addition of LPS isolated from E. coli (J5 mutant) into the erythrocyte resulted in the decrease of membrane fluidity as determined by spin labelling using electron paramagnetic resonance (EPR). This was accompanied by membrane fragility. It was found that hydroxyl radicals were generated from erythrocytes treated with LPS by using DMPO spin trapping. However, pretreatment of erythrocytes with taurine-conjugated bile acids was found to modify the membrane response induced by LPS. Taurocholic acid (TCA) and tauroursodeoxycholic acid (TUDCA) prevented the decrease of membrane fluidity induced by LPS, and, as a result, the membrane integrity was maintained although no significant changes were observed in the amount of hydroxyl radicals produced by LPS addition. However, taurochenodeoxycholic acid (TCDCA) exhibited little beneficial effect on the dynamic properties and the function of the erythrocyte membranes, although the hydroxyl radical declined markedly in the erythrocytes. Therefore, it is suggested that TCA and TUDCA have a protective effect against LPS-induced membrane fragility by modulating membrane fluidity.

Animals↗

A search for the primary abnormality in adult-onset type II citrullinemia.

Deficiency of argininosuccinate synthetase (ASS) causes citrullinemia in human beings. Type II citrullinemia is found in most patients with adult-onset citrullinemia in Japan, and ASS deficiency is found specifically in the liver. Previous studies have shown that the decrease of hepatic ASS activity is caused by a decrease in enzyme protein with normal kinetic properties and that there were no apparent abnormalities in the amount, translational activity, and gross structure of hepatic ASS mRNA. In the present work, we show by sequencing analysis that there was no mutation in the ASS mRNA from two patients with type II citrullinemia. We also report RFLP analysis of a consanguineous family with type II citrullinemia, by using three DNA polymorphisms located within the ASS gene locus. In spite of having consanguineous parents, the patient was not a homozygous haplotype for the ASS gene. The RFLP analysis of 16 affected patients from consanguineous parents showed that 5 of 16 patients had the heterozygous pattern for one of the three DNA probes and that the frequency of the heterozygous haplotype was not different from the control frequency. These results suggest that the primary defect of type II citrullinemia is not within the ASS gene locus.

Adolescent↗

[Evaluation of the lymphatic dissection at the operation of carcinoma of the thoracic esophagus applying the carbon particle (CH 40) for black-staining of the lymph nodes as a guide].

We have injected emulsion of activated carbon particles (CH 40), into the mediastinal lymph nodes at the bifurcation of trachea and examined whether carbon impregnated black lymph node is useful as a guide for more accurate and more appropriate lymphadenectomy at the esophagectomy. The patients subjected to our study were 112 patients with carcinoma of esophagus experienced from 1974 to 1991. Among them, 20 cases underwent 3-field lymph nodes dissection with CH 40 (CH group) and as control groups 41 cases received 2-field lymphadenectomy (2-F group), and 51 patients received 3-field lymphadectomy without CH 40 (3-F group). The average numbers of the lymph nodes dissected in CH group (24.5) was significantly larger in comparison with 2-F group (9.1) and 3-F group (10.5) (p < 0.05). The rate of the number of metastatic lymph nodes per number of lymph nodes dissected in the mediastinum in CH group (55.0%) was higher in those of 2-F group (24.3%) and 3-F group (33.3%). Postoperative pulmonary complications were observed in 20% in the of CH group, but in 41% of 2-F group and 60.0% in 3-F group. Cumulative 3-year survival rate in CH group was better than others. Therefore, it was concluded that the 3-field lymphadenectomy with CH group was useful in the operation of the carcinoma of the esophagus to improve the prognosis and decreasing the postoperative pulmonary complications.

Carcinoma↗

[Clinical significance of flow cytometric DNA analysis in patients with rectal cancer].

DNA content was measured by flow cytometry using paraffin-embedded material from 148 primary rectal cancers and 10 distant metastatic lesions. DNA ploidy pattern was classified into the following three groups in terms of the DNA index: 1.00 was defined as the diploid group (DP), 1.00 < DNA index < 1.60 as the low-aneuploid group (LAP) and > or = 1.60 as the high-aneuploid group (HAP). Primary carcinomas were DP in 26.4%, LAP in 36.5% and HAP in 37.1%. The DNA ploidy pattern of the primary tumor correlated well with clinicopathological findings such as depth of invasion, lymphatic invasion, pathological stage, metastasis to distant organs and curability of the tumor. In patients with HAP tumor after curative operation, the recurrence rate (21.6%) in distant organs was significantly higher than those with DP tumor (2.8%) and LAP tumor (6.4%) [p < 0.05]. Two LAP patients and 8 HAP patients with distant metastatic disease had the same DNA ploidy pattern HAP in the metastatic lesions. These data indicate that tumor DNA ploidy patterns classified into three groups in rectal cancer may play an important role in predicting prognosis, including distant metastasis.

DNA, Neoplasm↗

Radical lymphadenectomy for rectal cancer facilitated by a carbon particle infusion lymphangiography.

For the intraoperative visualization of the para-aortic nodes and those around the iliac vessels, a fine carbon particle solution was infused into the bilateral pedal lymphatic vessels of 12 patients with rectal carcinoma. A low anterior resection with radical lymph node dissection was then performed while preserving pelvic autonomic nerves. Of 444 lymph nodes removed from the iliac arterial region, 430 were stained with carbon black (96.8%), even though the black staining was not perfect in the nodes of the inferior mesenteric arterial region. All of the lateral black stained nodes were clearly visible and hence could be easily excised. The average number of dissected nodes in one patient was 43.8 in this dissection with carbon particle infusion, which was larger than those of conventional lymph node dissection. We then examined the length of time that a postoperative indwelling bladder catheter was needed as an indication for autonomic nerve damage, and it was ascertained that less damage occurred in this operation compared to other types of dissections, such as conventional or extended lymph node dissection.

Carbon↗

Clinical evaluation of tissue plasminogen activator (t-PA) levels in patients with liver diseases.

Tissue plasminogen activator (t-PA) levels in plasma or serum were studied in 416 patients with liver diseases: acute hepatitis (AH, n = 30); fulminant hepatitis (FH, n = 36); chronic inactive hepatitis (CIH, n = 57); chronic active hepatitis (CAH, n = 39); compensated liver cirrhosis (cLC, n = 78); decompensated liver cirrhosis (dLC, n = 84); hepatocellular carcinoma (HCC, n = 64); advanced hepatocellular carcinoma (aHCC, n = 28); and compared with that of a control group (n = 106) of healthy subjects. The t-PA levels showed significant increase in patients with AH, FH, CAH, cLC, dLC and HCC, compared with normal controls. The abnormal rates in t-PA levels (higher than 8.3 ng/ml) for each type of liver diseases were 86.1% in FH, 46.2% in CAH, 50% in cLC, 85.7% in dLC, 67.2% in HCC, and 89.3% in aHCC. t-PA levels tended to be higher in more advanced liver diseases. t-PA levels significantly correlated positively with plasminogen activator inhibitor (PAI-1) in AH, cLC, dLC, HCC and aHCC, and negatively with plasmin alpha 1-plasmin inhibitor complex (PIC), plasminogen (Plg), FDP, AT III and alpha 2-plasmin inhibitor (alpha 2-PI) in dLC, prothrombin time (PT) and fibrinogen (Fbg) in HCC. t-PA levels in patients with FH, CAH and dLC were significantly higher than those in patients with AH, CIH and cLC, respectively. Moreover, the changes of t-PA levels in the clinical courses of various liver diseases revealed that t-PA levels increased sensitively with progression of liver diseases or in advanced liver diseases.(ABSTRACT TRUNCATED AT 250 WORDS)

Biomarkers↗

Thrombolytic therapy of synthetic graft occlusions before vascular reconstructive procedures.

The objective of this study was to evaluate the impact of thrombolysis of synthetic grafts before urgent vascular reconstruction. In 29 patients, 41 thrombosed synthetic grafts that underwent intraarterial thrombolysis were studied. The cases were divided into three groups: group I--complete thrombolysis followed by reconstruction; group II--complete thrombolysis alone; and group III--incomplete lysis requiring reconstruction or sympathectomy. Follow-up ranged from 1 to 556 days (mean: 149 days). Kaplan-Meier analysis was used to determine patency and limb salvage rates. One-year patency and limb salvage rates were 53% and 95%, 34% and 67%, and 38% and 48%, respectively, for groups I, II, and III. Eighteen complications occurred in 16 of the 41 (39%) episodes. One patient died of intracranial hemorrhage. The best results were achieved when complete lysis was followed by appropriate reconstruction. Patency was equally poor in complete thrombolysis alone and reconstructions required by incomplete thrombolysis. Limb salvage was better after complete thrombolysis, regardless of the appropriate reconstruction.

Aged↗

Role of the spleen in endotoxin-induced hepatic injury in chronic alcohol-fed rats.

The present experiments were designed to study the role of the spleen in endotoxin-induced hepatic injury in chronic alcohol-fed rats. Administration of 2 mg/kg body weight of endotoxin caused severe hepatic injury in chronic alcohol-fed rats as compared with controls. This injury was significantly less in those whose spleens had been resected 1 week prior to endotoxin administration. There were no differences in plasma endotoxin levels 16 h after intravenous injection of endotoxin between sham-operated control rats, and chronic alcohol-fed rats with and without splenectomy. The plasma tumor necrosis factor (TNF) level 1 h after intravenous injection of endotoxin was significantly higher in chronic alcohol-fed rats than in controls. However, TNF levels were significantly lower in those with splenectomy. Neutrophil infiltration was seen in the liver sinusoid of sham-operated chronic alcohol-fed rats as early as 1 h after injection of endotoxin, and was observed even 15 h later. These results suggest that endotoxin-induced liver injury is closely related to factors derived from the spleen and induced by plasma endotoxin, especially when Kupffer cell function is reduced by chronic alcohol feeding. In addition, TNF and neutrophils may play an important role in this type of liver injury.

Alanine Transaminase↗

Two fatal cases of hepatitis B virus carriers after corticosteroid therapy for bronchial asthma.

We report two hepatitis B virus (HBV) carriers who had liver failure after withdrawal of corticosteroids (steroids) administered for treatment of serious asthmatic attacks. Liver functions deteriorated 1 to 2 wk after withdrawal of the steroid therapy and liver failure occurred. Steroid readministration and intensive therapy for liver failure did not prevent death. An excessive immune response provoked by steroid withdrawal and decreased reserve capacity due to underlying chronic liver disease were thought to be factors in the liver failure. Caution must be exercised in the administration of steroids to patients with underlying chronic HBV infection to prevent exacerbation of hepatitis. Prompt readministration of steroids is indicated if evidence of liver failure develops.

Aged↗

[Infection of C type hepatitis virus in patients with alcoholism. Studied by serum HCV antibody of C100-3 and 2nd generation].

To investigate the infectious situation and causes of hepatitis C virus (HCV) in patients with alcoholism, C100-3 antibody (C100-3) and HCV antibody of the 2nd generation (HCV-2nd) were examined on admission, and the factors that affected the infection of HCV were studied in 226 alcoholics. The positive rate of anti-HCV was as high as 16.4% by C100-3 and much higher by HCV-2nd as 33.2%. The incidence of cases with the history for blood transfusion, drug addict and/or tattoos in alcoholics was as high as 39.4% (89/226). To clarify the influence of the background such as blood transfusion, drug addict and/or tattoos on HCV infection, the positive rate of anti-HCV was compared between those with the background and without the background. In alcoholics without the backgrounds, the positive rate of C100-3 and HCV-2nd were significantly (p less than 0.001) higher than patients without the backgrounds, namely 27.0% vs 9.5%, 56.2% vs 18.2%, respectively. In alcoholics without the backgrounds, the positive rate of anti-HCV became higher in proportion as the age of the patients grows older from 20 to 60 years. These results suggest that a high incidence of HCV infection in alcoholics may resulted from increased the backgrounds that can provide chances of HCV infection and that in those without the backgrounds, alcohol and aging may lead the tolerance to HCV infection.

Adult↗

Adenocarcinoma in Meckel's diverticulum: report of a case and review of 30 cases in the English and Japanese literature.

A 54-yr-old man who complained of abdominal pain was found to have an adenocarcinoma arising in Meckel's diverticulum, as preoperatively diagnosed with 99mTc-pertechnetate scintigraphy. Angiography of the superior mesenteric artery revealed multiple branched arteries and tumor stain, but the vitelline artery was not clearly identified. Surgery revealed that the tumor had invaded the urinary bladder and the ileum, including the diverticulum, and the bladder had to be partially resected. Histopathological examination of the lesion revealed a diverticulum containing normal small bowel mucosa, ectopic normal gastric tissue, and adenocarcinoma. In a review of 30 cases of adenocarcinoma in Meckel's diverticulum in the English and Japanese literature, our case was the first to be diagnosed preoperatively.

Adenocarcinoma↗

An adapter for stapling of a colorectal anastomosis.

A technique involving the use of an end-to-end anastomosing stapler for low anterior resection has been modified to allow for a low colorectal anastomosis with an anus-pushing rubber adapter. The facility and safety of this procedure, under direct vision, has been confirmed.

Anastomosis, Surgical↗