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Biomedical subjects

K Ouchi

Publications and source records attributed to K Ouchi.

At least 19 recordsLinked to original sources

Portal venous pressure following splenectomy in patients with portal hypertension of differing etiology.

To clarify the effect of splenomegaly on portal hemodynamics in patients with portal hypertension and esophageal varices, manometric studies were carried out before and after splenectomy during an operation for esophageal varices. The 118 patients evaluated retrospectively had underlying liver cirrhosis (LC) (62), idiopathic portal hypertension (IPH) (42), and extrahepatic portal occlusion (EHO) (14). The weight of the spleen did not differ significantly among the three diagnostic groups: 640 +/- 473.5 g for LC, 780 +/- 414.6 g for IPH, and 683 +/- 457.2 g for EHO. Before splenectomy, portal pressure was significantly elevated in the patients with EHO (410 +/- 85.2 mm H2O) as compared to either the LC or IPH groups (348 +/- 64.1 and 348 +/- 73.5 mm H2O). Following splenectomy the reduction of portal pressure was significantly greater in the EHO group (29 +/- 15.5%) than in either the LC (18 +/- 17.4%) or IPH (19 +/- 17.0%) groups. Each group was subdivided according to severity of splenomegaly: marked (spleen weight > or = 500 g) or slight (spleen weight < 500 g). Patients with LC and marked splenomegaly showed a reduction in liver function parameters as shown by the prolongation of indocyanine retention rate at 15 min as compared to those with slight splenomegaly. Though it is not statistically significant, the average portal pressure tended to be higher among those with marked splenomegaly.(ABSTRACT TRUNCATED AT 250 WORDS)

Esophageal and Gastric Varices

Isolation and genetic study of p-fluoro-DL-phenylalanine-resistant mutants overproducing beta-phenethyl-alcohol in Saccharomyces cerevisiae.

p-Fluoro-DL-phenylalanine (PFP)-resistant mutants which produce a large amount of beta-phenethyl-alcohol, a rose-like flavor component, were isolated from the isogenic strains X2180-1A and X2180-1B of Saccharomyces cerevisiae. Cells of these mutants accumulated phenylalanine and tryptophan more than 3-fold times that of wild-type cells, while they accumulated less than half the tyrosine. The activity of prephenate dehydrogenase (PDG) (EC 1.3.1.12) was markedly decreased while that of 3-deoxy-D-arabino-heptulosonate-7-phosphate synthase (EC 4.1.2.15) was increased. Genetic analysis revealed that the mutation occurred at the TYR1 locus, encoding PDG, and that the mutated TYR1 gene, try1-pfp, caused both PFP resistance and beta-phenethyl-alcohol overproduction. This was supported by molecular genetic studies with cloned tyr1-pfp DNA.

Alleles

A mutated ARO4 gene for feedback-resistant DAHP synthase which causes both o-fluoro-DL-phenylalanine resistance and beta-phenethyl-alcohol overproduction in Saccharomyces cerevisiae.

o-Fluoro-DL-phenylalanine (OFP)-resistant mutants which overproduce beta-phenethyl-alcohol were isolated from a laboratory strain of Saccharomyces cerevisiae. Cells of one of the mutants accumulated tyrosine and phenylalanine 1.5-3 fold more than did wild-type cells. Its 3-deoxy-D-arabino-hepturosonate-7-phosphate (DAHP) synthase (EC 4.1.2.15), encoded by ARO4, was free from feedback inhibition by tyrosine. Genetic analysis revealed that the mutation was controlled by a single dominant gene, ARO4-OFP, encoding feedback-resistant DAHP synthase by tyrosine, and that this gene caused both the OFP resistance and beta-phenethyl-alcohol overproduction. This was supported by molecular genetic studies using cloned ARO4 both from the wild-type and its mutant strain.

3-Deoxy-7-Phosphoheptulonate Synthase

Energy metabolism changes and oxidative attack after hepatic arterial embolization and chemoembolization in thioacetamide-induced cirrhotic livers.

Hepatic energy metabolism and oxidative attack were studied after transcatheter arterial embolization (TAE) and chemoembolization (TAC) of the left and median lobes of the liver using thioacetamide (TAA)-induced cirrhotic rats. TAE was carried out using gelatin sponge (1.5 mg/cm3) dissolved in saline solution (SS). TAC was performed by adding mitomycin C (MMC) (1.6 mg/kg body weight) to the previous embolic solution. The energy charge (EC) of embolized lobes decreased from 0.86 to 0.78 and 0.74 1 h after TAE and TAC, respectively, but was restored 3 h later. Adenosine 5'-triphosphate (ATP) and total adenine nucleotide content (TAN) of embolized and non-embolized lobes was also temporarily decreased. Total hepatic blood flow (THBF) of embolized and chemoembolized lobes was reduced in almost 50%, and it took 1 week to become normalized. After TAC (3 and 6 h, respectively), total glutathione (TGSH) content was reduced from 7.02 mumol/g of liver to around 4.5 mumol/g, and malondialdehyde (MDA) content increased from 196.94 nmol/g of liver to values above 300 nmol/g. TAE in cirrhotic livers did not induce any changes in these parameters. In conclusion, after TAE and TAC the hepatic energy metabolism is temporarily altered by ischemia. TAC-induced oxidative attack, in addition to ischemia and MMC, could be one of the mechanisms explaining the effectiveness of this therapy.

Adenine Nucleotides

Glucose overload and hepatic energy metabolism after resection of the cirrhotic liver in rats.

The effect of glucose hyperalimentation on energy metabolism in the cirrhotic rat liver after 70% hepatectomy was studied. After resection, rats received either 30 kcal/kg per day (group I) or 200 kcal/kg per day (group II) of glucose for 48 h. In both groups, hepatic mitochondrial ATP synthesis was accelerated when palmitic acid was used as substrate and suppressed when pyruvate was used. This suggests that the energy substrate of the remnant liver was principally fatty acids rather than glucose. Hepatic energy charge was within normal limits in group I, but decreased significantly in group II after hepatectomy. An abundance of glucose in the early postoperative period, therefore, caused a hepatic energy derangement by suppressing fatty acids utilization; this suppression was corroborated by the findings of lower immunoreactive glucagon and non-esterified fatty-acid concentrations in group II. To determine optimal glucose administration, the predicted value of glucose disposal rate (GDR) was calculated after an intravenous glucose tolerance test. GDR decreased significantly after hepatectomy and did not increase appreciably even with a large dose of insulin administration. These results suggest that glucose administration should be tailored to the GDR values after resection of the cirrhotic liver.

Adenosine Triphosphate

Construction of a sucrose-fermenting bakers' yeast incapable of hydrolysing fructooligosaccharides.

Fructooligosaccharides stimulate the growth of intestinal bifidobacteria which are related to the favorable health and nutrition of humans and other animals. Since the efficient amount of fructooligosaccharide for an adult human is relatively large (about 5 g per day), its addition to daily foods like bakery goods might be beneficial. However, commercial Bakers' yeast hydrolyses fructooligosaccharides by the action of invertase encoded in SUC genes and ferments the resulting monosaccharides. According to the findings that strains carrying the MAL-constitutive gene and lacking the SUC gene fermented sucrose and not fructooligosaccharide, we constructed a sucrose-fermenting strain, YOY920, incapable of hydrolysing fructooligosaccharide, by cross-breeding a baking strain and a laboratory strain. In a molasses medium, the cell yield of YOY920 was comparable to that of a baking strain FSC6001, and much higher than that of the non-sucrose-fermenting strains. Although fructooligosaccharide inhibited the dough leavening ability of YOY920, white bread containing fructooligosaccharide could be produced in the defined dough formula using the new strain.

Animals

Ultrastructure of neurofibrillary tangles in Alzheimer's disease by means of tilt-stage electron microscopy.

Neurofibrillary tangles (NFT) in the brains of patients with Alzheimer's disease were examined by means of tilt-stage electron microscopy. Observing a longitudinal direction, constricted parts of the NFT did not move in an axial direction. In a transverse section, a fibril of the NFT consisted of globular subunits having a hollow structure in the center and did not appear as paired filaments. From these findings, it was considered that a fibril of NFT consists of twisted protofilaments made up of globular subunits and does not consist of paired helical filaments.

Aged

[Prevalence of antibodies to Chlamydia pneumoniae (strain TWAR) and other Chlamydia in Japan].

Chlamydia pneumoniae (Strain TWAR), the new third species of genus Chlamydia, is emerging as an important human respiratory pathogen in Western countries. However, little is known about it in Japan. In this study, 1330 serum samples were tested for seroprevalence of three species of genus Chlamydia including C. pneumoniae in Hiroshima. Microimmunofluorescence test was used to measure serum IgG antibody, and formalin fixed elementary bodies of C. trachomatis, C. psittaci, and C. pneumoniae were used as antigen. Serum titer of 1:32 or greater was considered positive. Seropositive rate of C. pneumoniae began to increase around the 6 month to 3 year old age group and reached 44% in the 8 to 11 year olds. A peak of seroprevalence according to age was around 20 year old, and about half of the adults were seropositive. Outpatients and healthy persons held almost the same seropositive rate. The positive rate in childhood was higher and the peak appeared earlier than some former studies in Western countries. The seropositive rate of C. trachomatis was noted 1-2% in the 6 month-7 year old age group, but no seropositive child was found in the 8-15 year olds. The rate was increased after adolescence and reached 10% in adults. The seroprevalence of C. psittaci was 1%. These data suggest C. pneumoniae is the most prevalent Chlamydia in Japan and as prevalent as in the Western countries.

Adolescent

Prevalence of antibody to Chlamydia pneumoniae TWAR in japan.

Chlamydia pneumoniae TWAR is a newly recognized Chlamydia species that is a pathogen of respiratory tract infection. To clarify the endemic status of C. pneumoniae in Japan, we evaluated the incidence of C. pneumoniae antibody in 1,330 serum samples (660 from outpatients, 600 from normal individuals, and 70 from cord blood). The antibody titer was determined by a microimmunofluorescence test by using the elementary body of C. pneumoniae TW-183 as the antigen. Immunoglobulin G antibody titers of 1:32 or higher were regarded as evidence of past infection. The detection rate of C. pneumoniae antibody rapidly increased in subjects between the ages of 4 and 7 years, reached 44% in subjects between the ages of 8 and 11 years, and was about 50% in older subjects. The rate did not differ between healthy subjects and outpatients. These results suggest that C. pneumoniae infection is highly endemic in Japan as it is in Western countries. However, the antibody prevalence was high in the low age groups in Japan compared with that in Western countries.

Adolescent

Some correlations between local anesthetic-induced convulsions and gamma-aminobutyric acid in rat spinal cord.

The effects of local anesthetics (procaine and lidocaine) on the gamma-aminobutyric acid (GABA) and L-glutamic acid (Glu) levels in rat spinal cord were studied during the convulsive process. The present study also investigated the influence of central GABA manipulations on the local anesthetic-induced convulsions. An increase in spinal GABA levels was observed at the preconvulsive and convulsive states after administration of procaine (170 mg/kg, i.p.) or lidocaine (120 mg/kg, i.p.), which induced clonic convulsions; in the depressive state, GABA levels returned to normal; in all states, Glu levels were unchanged. Semicarbazide (25-100 mg/kg, i.p.), a glutamic acid decarboxylase inhibitor, produced a decrease in spinal GABA content and strongly enhanced both local anesthetic-induced convulsions as shown by a shortening of the latency and an increase in the mortality. Aminooxyacetic acid (AOAA; 10-40 mg-kg, i.p.), a GABA transaminase inhibitor, dose-dependently increased spinal GABA content and markedly suppressed procaine-induced convulsions. However, lidocaine-induced convulsions were enhanced by AOAA. These results suggest that the spinal GABA neuron may respond to the convulsions induced by local anesthetics. Furthermore, there is a clear relationship between spinal GABA content and procaine-induced, but not lidocaine-induced, convulsions.

Aminooxyacetic Acid

Efficacy of patient-controlled analgesia for management of pain after abdominal operations.

In order to control pain during the early post-operative period, patient-controlled analgesia (PCA) with buprenorphine as an analgesic drug was applied in 23 patients undergoing abdominal operations. With this "on demand" system, the patient was allowed to self-administer narcotic analgesic medication using a programmable infusion pump. Overdose could be minimized with a mandatory lock-out interval between allowable injections. Average total requirement of buprenorphine was 0.355 mg at 48 hr after operation. Nineteen of the 23 (82.6%) patients characterized their pain control as "excellent" or "good". In these patients there existed high correlation between the total number of patient attempts and the number of successful injections. The PCA system was thought to provide improved pain relief at smaller total drug dosages. In addition, earlier and greater spontaneous physical activity was maintained with PCA therapy. The potential for overdose could be minimized, and thereby PCA appears to be an efficacious and safe method of providing for postoperative pain relief.

Abdomen

[Hepatic resection under the Pringle maneuver induces endotoxemia and lipoperoxidative attack in the jaundiced rat liver].

Sixty percent hepatectomy under two times of the Pringle maneuver (temporal occlusion of the hepatic inflow of the hepatic artery and portal vein) for 25 min was carried out on rats with obstructive jaundice. Hepatic energy charge which was markedly decreased during the Pringle maneuver did not recover 3 hrs after release of the maneuver. In addition, systemic endotoxemia associated with increased level of malondialdehyde and decreased levels of total glutathione and alpha-tocopherol in the liver was demonstrated. These changes were more dominant in rats with obstructive jaundice for 3 weeks than those for 1 week. It can be said that deteriorated hepatic energy charge after release of the Pringle maneuver may partly be caused by the production of oxygen free radicals which may be enhanced by endotoxemia in resection of the jaundiced liver. In contrast, after release of the Pringle maneuver, deterioration of hepatic energy charge due to oxidative attack was not found in jaundiced rats without hepatic resection.

Animals

Undifferentiated sarcoma of the liver in a 21-year-old woman: case report.

A successful surgical case of malignant undifferentiated (embryonal) sarcoma of the liver (USL), a rare tumor normally found in children, is reported. The patient was a 21-year-old woman, complaining of epigastric pain and abdominal fullness. Chemical analyses of the blood and urine and complete blood counts revealed no significant changes, and serum alpha-fetoprotein levels were within normal limits. A physical examination demonstrated a film, slightly tender lesion at the liver's edge palpable 10 cm below the xiphoid process. CT scan and ultrasonography showed an oval mass, confined to the left lobe of the liver, which proved to be hypovascular on angiography. At laparotomy, a large, 18 x 15 x 13 cm tumor, found in the left hepatic lobe was resected. The lesion was dark red in color, encapsulated, smooth surfaced and of an elastic firm consistency. No metastasis was apparent. Histological examination resulted in a diagnosis of undifferentiated sarcoma of the liver. Three courses of adjuvant chemotherapy, including adriamycin, cis-diaminodichloroplatinum, vincristine and dacarbazine were administered following the surgery with no serious adverse effects. The patient remains well with no evidence of recurrence 12 months after her operation.

Adult

[Effects of mitochondrial lipoperoxidation on liver regeneration after partial hepatectomy of the cirrhotic rat liver].

Lipoperoxide levels in mitochondrial fraction and mitochondrial respiratory activity during hepatic regeneration were studied serially in normal (N) and cirrhotic (C) rats following one-third (I) or two-third (II) partial hepatectomy. Recovery of liver weight after 14 days was about 90% in each group except C-II group, in which it was 71.3%. ATP synthetic activity (ATP-S) was always higher in N-II group than N-I which reached maximum on the first postoperative day (POD) and returned to the preoperative levels on the 14th POD. Lipoperoxide peak value of N-II group was obtained sooner than that of N-I group, in addition the peak value of N-II group was higher than that of the N-I group. ATP-S of C-II group reached maximum levels on the third POD and thereafter decreased progressively. In contrast, ATP-S of C-I group returned to preoperative level on the 14th POD. Peak lipoperoxide levels were obtained on the first POD in both groups, but that of C-II group was 1.6 times higher than that of C-I. Moreover, it was observed that inhibition of lipoperoxidation by alpha-tocopherol administration improved respiratory activity significantly. From these results it can be said that hepatectomy-induced lipoperoxidation in massive resection of the cirrhotic liver may inhibit activation of mitochondrial respiration and hepatic regeneration.

Adenosine Triphosphate

Transcatheter arterial embolization and chemoembolization induce the production of free radicals in the normal rat liver.

Superselective transcatheter arterial embolization (TAE) of the left and median lobes of the normal rat liver was performed using gelatin sponge (1.5 mg/ml). Superselective transcatheter arterial chemoembolization (TAC) of the same lobes was done adding mitomycin (MMC) at a dose of 1.6 mg/ml to the embolic solution. In another group of rats MMC alone was injected intraarterially into those lobes. It was found that both embolic procedures and the arterial injection of MMC decrease the hepatic total glutathione content. Glutathione peroxidase activity and alpha-tocopherol content remained unchanged. Lipoperoxides were detected 3 and 6 h after TAC in chemoembolized and non-chemoembolized lobes. Similar findings in both injected and noninjected lobes were found after MMC injection. The TAE lobes only showed elevated lipoperoxide content 6 h after embolization, this parameter remained unchanged in the non-TAE lobes. These findings suggest that free radicals are formed after TAE, and that the addition of MMC to the embolic solution increases the oxidative attack and/or that the oxidative reactions after TAC are mainly mediated by lipid peroxidation due to the presence of MMC.

Animals

Continuous removal of middle molecules by hemofiltration in patients with acute liver failure.

In patients with acute liver failure and hepatic coma, an increase in the abnormal "middle molecules" seen on the chromatograms of the sera is suspected of playing an etiologic role in the coma. A pilot study of continuous hemofiltration using a high-performance membrane was conducted in 16 such patients in an attempt to decrease the serum levels of the middle molecules. The procedure was used alternately with plasma exchange. High-performance liquid chromatography showed a notable removal of the substances in the filtrates and a sequential removal from the serum by hemofiltration. Eight (50%) of the 16 patients had amelioration in level of consciousness and were weaned successfully from hemofiltration. Although only three of the 16 patients survived the acute illness, 13 others lived an average of 15 days and five patients survived greater than 3 wk. While the continuous removal of middle molecules from the serum may not reverse liver failure, this procedure used in conjunction with plasma exchange may provide a means of life support, e.g., for patients awaiting a liver transplant.

Blood Flow Velocity

[Plasma and tumor gastrin in patients with primary hyperparathyroidism].

It is well known that primary hyperparathyroidism is often associated with peptic ulcer. The purpose of this study is to confirm the relationship between the gastrin-levels before and after parathyroidectomy in fourteen patients with primary hyperparathyroidism, and to determine the localization of gastrin in the surgically resected parathyroid tumor. The results obtained were as follows: 1) Three patients had peptic ulcer (gastric ulcer and duodenal ulcer), the incidence being 21%. 2) The basal serum gastrin levels were 123.0% +/- 68.1 pg/ml before operation and decreased to 90.2 +/- 44.5 pg/ml after operation. In the 3 patients with slightly elevated gastrin levels, the mean level before operation was 209.1 +/- 61.2 pg/ml. The gastrin level decreased to 116.4 +/- 62.0 pg/ml after operation. 3) Gastrin immunoreactivity was detected in 10 out of 14 tumors and its localization was at the periphery of tumor cells. From these results, we conclude that extragastric gastrin secretion from parathyroid tumors may be one of the cause of peptic ulcer in patients with primary hyperparathyroidism.

Calcium

The development and extension of hepatohilar bile duct carcinoma. A three-dimensional tumor mapping in the intrahepatic biliary tree visualized with the aid of a graphics computer system.

Computer-assisted three-dimensional (3D) reconstruction of the biliary tree including extrahepatic and intrahepatic parts was performed from surgical or autopsy materials from 12 patients with hepatohilar bile duct carcinoma in an effort to visualize three-dimensionally the distribution of carcinoma and dysplasia. In each case, material including a hepatic lobe was reduced to serial slices 1 mm thick using a ham slicer, then the tumors, ducts with carcinoma in situ, and those with dysplasia were submitted to reconstruction. In a 3D map of biliary tree reproduced on a display, a dysplastic zone was shown in most cases surrounding a focus of carcinoma, justifying the assumption of a dysplasia-carcinoma sequence. The carcinoma itself proved to form multiple foci along bile ducts in as many as 42% of the patients, in some of whom the foci were independent without any intervening dysplasia. These results suggest that as extensive a surgical measure as possible should be taken in designing a strategy against this tumor.

Adenoma, Bile Duct