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Biomedical subjects

T Manabe

Publications and source records attributed to T Manabe.

At least 181 records · Page 10Linked to original sources

Acute terminal pancreatitis occurring in jejunal heterotopic pancreas.

CONCLUSION: We report a unique case of acute terminal pancreatitis occurring in the jejunal heterotopic pancreas. Unlike previously reported cases, acute pancreatitis was not found histologically in the ordinary pancreas. BACKGROUND: Heterotopic pancreas may show the same inflammatory or neoplastic changes, such as acute pancreatitis and adenocarcinoma, as those that occur in the ordinary pancreas. However, histologically proven acute pancreatitis occurring in heterotopic pancreas is very rare and only three reports have been described. METHODS: A 53-yr-old Japanese man died of hepatic failure, and autopsy was performed. RESULTS: Autopsy incidentally revealed heterotopic pancreas of the jejunum. Microscopically, focal acute pancreatitis was observed in the jejunal heterotopic pancreas, whereas the pancreas of the normal location showed no abnormality. In addition, no clinical evidence of pancreatic disease was noted before death. Therefore, we diagnosed this case as acute terminal pancreatitis occurring in the jejunal heterotopic pancreas.

Acute Disease↗

[A case of gastric cancer with decreased dihydropyrimidine dehydrogenase activity].

We analyzed the pyrimidine metabolite in the urine of a patient with severe mucositis and hand and foot syndrome, who was administered 5-fluorouracil for recurrence of gastric cancer. From our analysis, it was suggested that the patient had decreased dihydropyrimidine dehydrogenase activity. Dihydropyrimidine dehydrogenase activity is usually measured in peripheral blood mononuclear cells, but this time it was estimated from the analysis of uracil, dihydrouracil, thymine, and dihydrothymine in the urine. We concluded that urinary analysis of the pyrimidine metabolism is effective as screening for the prediction and prevention of 5-fluorouracil toxicity.

Adenocarcinoma↗

Epilepsy and exacerbation of brain injury in mice lacking the glutamate transporter GLT-1.

Extracellular levels of the excitatory neurotransmitter glutamate in the nervous system are maintained by transporters that actively remove glutamate from the extracellular space. Homozygous mice deficient in GLT-1, a widely distributed astrocytic glutamate transporter, show lethal spontaneous seizures and increased susceptibility to acute cortical injury. These effects can be attributed to elevated levels of residual glutamate in the brains of these mice.

ATP-Binding Cassette Transporters↗

Effects of catholytes on the mobilization of proteins after capillary isoelectric focusing.

Purified proteins and human plasma proteins were separated by capillary isoelectric focusing and detected by cathodic mobilization, e.g. by replacing the cathodic sodium hydroxide solution by solutions containing another anion. The effect of catholyte anions on the resolution of mobilized proteins was examined. Compared with the chloride or phosphate anion, organic anions having small dissociation constants improved protein resolution, especially in the range of acidic proteins. Among the catholytes examined, acetic acid gave the best resolution for purified proteins and human plasma proteins. Measurement of the changes of electric current during the mobilization process indicated that organic anions with low mobility move slowly towards the anode and retard changes of pH gradient in the capillary. Isoelectric focusing, cathodic mobilization, and direct pH measurement in polyacrylamide gel columns (1.3 mm internal diameter and 38 mm long) also revealed these effects of low mobility anions. In order to visualize the behavior of human plasma proteins in the mobilization step, micro two-dimensional polyacrylamide gel electrophoresis was employed. The results indicated that the proteins migrate towards the cathode, preserving their relative positions attained during the isoelectric focusing step.

Acetic Acid↗

Separation of human plasma/serum proteins by capillary isoelectric focusing in the absence of denaturing agents.

Human plasma/serum proteins were separated by capillary isoelectric focusing in the absence of denaturing agents. Proteins focused in a fused silica capillary were mobilized by replacing the catholyte sodium hydroxide to acetic acid. The performance of the separation of human plasma proteins has been examined by changing the duration of the step of isoelectric focusing, carrier ampholyte concentration, and plasma protein concentration. The separation patterns of plasma proteins were compared with those obtained by micro two-dimensional polyacrylamide gel electrophoresis (2-D PAGE) run in the absence of denaturants in order to locate the major plasma proteins on the capillary electropherograms. Using the established electrophoretic conditions and the results of peak identification, proteins in the sera of IgG myeloma patients were analyzed by capillary isoelectric focusing. The advantages of capillary isoelectric focusing in plasma protein analysis compared with 2-D PAGE are discussed.

Acetic Acid↗

Effects of partial pancreatectomy on liver regeneration in rats.

Pancreatoduodenectomy with major hepatectomy has recently been employed for patients with advanced biliary malignancies as potential curative surgery. However, postoperative liver decompensation is a major unfavorable complication with this procedure; the main cause of the sequelae is disturbance growth. In our present study, hepatic regeneration and nutritional status following simultaneous resection of the liver and the pancreas were evaluated in an experimental animal model. Eighty SD rats were divided into four groups: control group (sham laparotomy, n = 20), 50% partial pancreatectomy group (Px, n = 20), 68% hepatectomy group (Hx, n = 20), and Px plus Hx group (n = 20). Five rats in each group were sacrificed for blood and liver collection on the first, second, third, and seventh postoperative days, respectively. One hour before sacrifice, 5-bromo-2-deoxyuridine (20 mg/kg/body weight) was injected intraperitoneally and BrdU-labeled nuclei in the liver were demonstrated immunohistochemically to allow examination of the mitotic response. Body weight increase rate (BWR), the liver wet weight (LWW), the ratio of the LWW to body weight, and the liver regeneration rate were calculated. Serum activity of alanine aminotransferase and levels of serum bilirubin and albumen were also measured. The LWW was relatively decreased after simple Px with no change in the BrdU labeling index or mitotic index. The highest peak of DNA synthesis of hepatocytes in the remaining lobes was markedly reduced on the first day after Hx + Px, with a delay in the hepatic regeneration response extending to the seventh postoperative day. Decrease in BWR in both the Px group and the Hx + Px group was observed on the first 3 postoperative days, with gain of BWR in the former case being slower. Removal of a portion of the pancreas can decrease hepatic weight under both normal and regenerative conditions. Simultaneous major resection of the liver and a portion of pancreas results in reduction and delay in the highest peak of DNA synthesis of hepatocytes in the remnant liver. We speculate that the pancreatic exocrine glands may play a distinct role in supporting the liver and in triggering hepatocyte proliferation.

Alanine Transaminase↗

Primary sclerosing cholangitis in Japan--analysis of 192 cases.

Primary sclerosing cholangitis is very rare in Japan. The aim of the present study was to identify the characteristics of such patients in Japan. A questionnaire was sent to the members of the Japanese Society of Gastroenterology and responses for 192 cases were analyzed. There was male predominancy (61%), and two peaks in the age distribution at diagnosis (20-30 years and 50-70 years). Bile duct damage was mainly intra + extrahepatic (69%) versus intrahepatic (17%) or extrahepatic (14%). The incidences of eosinophilia and positivity for anti-nuclear antibody were 27% and 30%, respectively. The incidence of associated inflammatory bowel disease was 21% (38 ulcerative colitis and 2 Crohn's disease). Chronic pancreatitis, gallstones, and biliary cancers occurred in 15%, 12%, and 4%, respectively, of the 192 patients. Patients less than 40 years of age had a higher incidence than the patients 40 years old or more of damage intra + extrahepatic bile ducts (89% vs 56%) and of associated ulcerative colitis (36% vs 9%), whereas the incidence of chronic pancreatitis was lower in patients aged less than 40 years (4%). The characteristics of patients with primary sclerosing cholangitis in Japan differ from those in other countries in regard to age distribution and the incidence of complications, and at least two different groups of patients seem to exist in terms of the degree of bile duct damage and the incidence of complications.

Adult↗

Pulmonary blood flow regulates plasma tissue plasminogen activator concentrations in patients with congenital heart defects.

OBJECTIVE: The wall shear stress generated by blood flow regulates the expression of fibrinolytic proteins by endothelial cells in vitro. In the present study, the effects of pulmonary blood flow on fibrinolytic activity were studied in patients with congenital heart defects and pulmonary hypertension. METHODS: Twenty-seven patients who underwent cardiac operation because of congenital heart defects were divided into four groups according to the severity of pulmonary hypertension. Group I consisted of seven patients with normal pulmonary artery pressure, group II consisted of nine patients with pulmonary hypertension caused by increased pulmonary blood flow, group III consisted of six patients with pulmonary hypertension caused by increased pulmonary vascular resistance, and group IV consisted of five patients with tetralogy of Fallot. Plasma concentrations of tissue plasminogen activator, plasmin, and thrombin were assayed as the inhibitor-bound forms. RESULTS: The preoperative concentration of tissue plasminogen activator was higher in group II than in all other groups (p = 0.0003). However, the postoperative concentration decreased only in patients in group II when compared with the preoperative value (p = 0.01). By Pearson's correlation analysis, pulmonary blood flow was found to correlate with the preoperative concentration of tissue plasminogen activator (95% confidence interval = 3.99 to 10.58, p = 0.0001). No definite conclusion was found for the relationship between tissue plasminogen activator and plasmin concentration. Further, the preoperative thrombin concentration was similar in all groups. CONCLUSIONS: These findings suggest that pulmonary blood flow may regulate the plasma concentration of tissue plasminogen activator in patients with congenital heart defects.

Child, Preschool↗

Blood cyst of the pulmonary valve in an adult: report of a case and review of the literature.

We report a case of a blood cyst originating from the pulmonary valve cusp of a 43-year-old Japanese woman with pulmonary stenosis. Cineangiography revealed a pedunculated tumor on the arterial surface of the pulmonary valve. It was successfully removed by a transpulmonary artery approach. The cyst contained old blood and calcified thrombi, and its wall consisted of collagenous fibrous tissue. Immunohistochemically, a monolayer of flat cells lining the cyst was confirmed as endothelium using antibodies to von Willebrand factor and CD34, as well as UEA-I lectin. To the best of our knowledge, blood cysts of the pulmonary valve are rare and only 10 such cases have been reported, including six pediatric cases. This case is the oldest and fifth adult patient with a blood cyst found on the pulmonary valve. A possible histogenesis is discussed.

Adult↗

Functional coupling of the nociceptin/orphanin FQ receptor with the G-protein-activated K+ (GIRK) channel.

Nociceptin/orphanin FQ is a heptadecapeptide which was recently isolated from brains. It induces hyperalgesia, in contrast to the analgesic effects of opioid ligands, although it and its receptor structurally resemble opioid peptides and opioid receptors, respectively. To investigate the molecular mechanism underlying nociceptin/orphanin FQ actions, we performed Xenopus oocyte expression assays, in situ hybridization histochemistry and electrophysiological analyses of neurons. We found that the nociceptin/orphanin FQ receptor is functionally coupled with the G-protein-activated K+ (GIRK) channel in Xenopus oocytes, and that the receptor mRNA and GIRK1 mRNA co-exist in various neurons, including hippocampal pyramidal cells. Furthermore, we found that nociceptin/orphanin FQ induces hyperpolarizing currents via inward-rectifier K+ channels in hippocampal pyramidal cells, suggesting that the nociceptin/orphanin FQ receptor couples with the GIRK channel in this region. We conclude that the nociceptin/orphanin FQ receptor couples with the GIRK channel in various neurons, including hippocampal pyramidal cells, thereby modulating neuronal excitability.

Animals↗

Calcium- and calmodulin-dependent phosphorylation of AMPA type glutamate receptor subunits by endogenous protein kinases in the post-synaptic density.

We have detected immunoreactivities of AMPA receptor subunits GluR1-4 in post-synaptic density (PSD) fraction and tested whether they can be phosphorylated by endogenous kinases. Incubation of PSD with Ca2+ and calmodulin increased phosphorylation of GluR1 and GluR2/3. The phosphorylation of GluR1 was largely blocked by a Ca2+/calmodulin-dependent protein kinase type II inhibitor. Thus Ca2+/calmodulin-dependent phosphorylation of glutamate receptor may be a mechanism underlying enhanced post-synaptic receptor responsiveness in LTP.

Animals↗

A modification of hepatic portoenterostomy (Kasai operation) for biliary atresia.

BACKGROUND: Although the proportion of patients with biliary atresia remaining jaundice-free after hepatic portoenterostomy (i.e., Kasai operation) has recently been increasing, in many cases repeated reoperation is required to achieve this result. Also, with assessment of jaundice using 2.0 mg/dL of serum total bilirubin as the cutoff, progressive liver fibrosis has occurred in longterm survivors, making liver transplantation necessary. Reoperations result in difficulty in removing the liver for this purpose and cause an increase in the probability of sequelae. STUDY DESIGN: We have performed a new modification of the Kasai operation on a series of patients using the Cavitron ultrasonic suction aspirator (CUSA) for obtaining persistent biliary drainage. We assessed the results using <1.5 mg/dL of serum total bilirubin as the criterion for jaundice-free patients. RESULTS: Since 1988, 39 patients were available for review of their clinical results to evaluate our new modification. Thirty patients (77%) were completely and continuously free of jaundice, without living-related liver transplantation or reoperation, and the maximum level of total bilirubin was <1.1 mg/dL. CONCLUSIONS: Our new approach to Kasai operations using CUSA as an integral aid to freeing the biliary remnants and facilitating enteric anastomosis is effective for persistent and complete disappearance of jaundice, without complicated reconstruction or reoperation, and decreases the need for liver transplantation.

Anastomosis, Roux-en-Y↗

A phase I/II study of a hypoxic cell radiosensitizer KU-2285 in combination with intraoperative radiotherapy.

A fluorinated 2-nitroimidazole radiosensitizer KU-2285 was given before intraoperative radiotherapy (IORT) to 30 patients with unresectable, unresected or macroscopic residual tumours. Twenty-three patients had pancreatic cancer and five had osteosarcoma. The IORT dose was 30 Gy for unresectable pancreatic cancer and 60 Gy for osteosarcoma. The dose of KU-2285 administered ranged from 1 to 9 g m-2. Four patients received a dose of 9 g m-2, and ten received 6.8-7 g m-2. All patients tolerated KU-2285 well, and no drug-related toxicity was observed. The average tumour concentration of KU-2285 immediately after IORT was 166 microg g-1 at dose of 6.8-7 g m-2 and 333 microg g-1 at 9 g m-2. The average tumour-plasma ratio was > or = 0.82. Eleven patients with unresectable but localized pancreatic cancer treated with KU-2285 plus IORT and external beam radiotherapy had a median survival time of 11 months and 1-year local control rate of 50%, which compares favourably with those of 8 months (P = 0.26) and 28% (P = 0.10) for 22 matched historical control patients. The five patients with osteosarcoma attained local control. The results of this first study on KU-2285 and IORT appear encouraging, and further studies of this compound seem to be warranted.

Adolescent↗