Biomedical subjects
Publications and source records attributed to M Maeda.
We discussed application of in vitro mutagenesis on H+-ATPase (F0F1) of Escherichia coli. The oligonucleotide-directed site specific mutagenesis and construction of a set of truncated subunits were useful for identifying essential residues of beta subunit and a functional region of epsilon subunit, respectively, of this complicated membrane enzyme.
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Aldehyde dehydrogenase isozymes (ALDH1 or E1 and ALDH2 or E2 according to the classification by Greenfield NJ, Pietruszko R, Biochim Biophys Acta 483:35, 1977) were purified from the human liver to homogeneity by the use of ion exchange chromatography on CM-Sephadex, DEAE-Sephadex, and QAE-Sephadex and affinity chromatography on 5'-AMP Sepharose 4B, and preparative isoelectric focusing agarose electrophoresis. These were injected in rabbits to elicit antibodies against ALDH1 and ALDH2, respectively and their specificities were tested by double immunodiffusion. By gel filtration, the antibodies were separated into F'ab fragments, conjugated with horseradish peroxidase, and served to detect ALDH1 and ALDH2 proteins in normal liver tissue. Immunoelectron microscopy by the preembedding method revealed that the electron-dense materials reacted with anti-ALDH1 antibody were located in the cytoplasm of hepatocytes, mainly around the nuclear membrane, mitochondria, and endoplasmic reticulum; in the mitochondria, however, no staining was demonstrated. In contrast, the reaction with anti-ALDH2 antibody was observed only in the mitochondria. Immunostaining, performed by the enzyme-labeled antibody method demonstrated that in the hepatic lobule, there were no differences of the intensity of ALDH1 antigenicity and that of ALDH2 antigenicity between periportal (zone 1) and pericentral (zone 3) hepatocytes. These results suggest that in the human liver ALDH1 and ALDH2 are distributed equally in the periportal and centrilobular regions.
A 56-year-old man was admitted to Miyazaki Prefectural Hospital with a complaint of pain in the right upper quadrant. The liver was moderately enlarged on palpation with tenderness in the upper abdomen. Ultrasonography and abdominal CT showed gallbladder tumor with multiple space-occupying lesions in the liver. In addition, serum levels of CEA and CA19-9 were markedly elevated. These findings suggested gallbladder cancer with liver metastasis, and he was soon started on tegafur rectally (1,000 mg/day) and PSK orally (3.0 g/day). Two months later, the lesions in the liver almost disappeared, although little change in size of the gallbladder tumor was noted. This condition lasted for 6 months indicating partial response. Subsequently, he died of liver failure 14 months after the start of treatment. Since few antineoplastic agents have been reported to be effective against gallbladder cancer, tegafur and PSK might be a good combination for this disease.
A 46-year-old man with Fabry's disease having aortic regurgitation and complete atrioventricular (AV) block was presented. In spite of severe aortic regurgitation (Seller's grade 3/4), his two-dimensional (2-D) echocardiogram revealed increased thickness of the left ventricular wall with mild dilatation. The myocardial echo showed a fine granular sparkling texture suggesting phospholipid deposition in the myocardial tissue. The membranous portion of the interventricular septum was thickened, and the aortic valve was thickened and had imperfect coaptation. Endomyocardial biopsy of the right side of the interventricular septum revealed intramyocardial vacuolization by light microscopy. Electron microscopy confirmed the presence of myelinoid lamellar inclusion. Electrophysiologic examination revealed an intra-Hissian AV block. A DDD pacemaker was implanted and the patient's symptoms were improved. Valvular replacement was not attempted due to the danger of suture failure. The patient's brother (41-year-old) also had increased thickness of his left ventricular wall on echocardiography, and a complete AV block by ECG, but no valvular abnormalities. His sister (45-year-old) had increased thickness of the left ventricular wall on echocardiography, and negative T waves by ECG, but she had no cardiac symptoms. The possibility of cardiac involvement in this heterozygous woman with Fabry's disease should also be considered. The patient's 38-year-old sister and all the children of all family members had normal left ventricular wall thicknesses and normal ECG. These findings may correspond to the age-related disease severity. The possibility of cardiac abnormalities should be considered in heterozygous women with Fabry's disease.
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A 54-year old man was admitted with a complaint of a pulsating tumor (7 x 6 x 2 cm) above the sternum accompanied by dysphagia. DSA showed the pulsating tumor was an aneurysm arising from the ascending aorta. CT gram of the sternum showed that the sternum was destroyed partially at the level of the 1st rib. We did the Y shaped skin incision. The clavicles, 1st and 2nd ribs were dissected out periosteally and perichondrially. We cut the clavicles and ribs, and dissected the mediastinum median to the internal mammary artery. Under the perfusion, F-F bypass and brain perfusion, the upper half of the sternum was dissected safely from the aneurysm. The aneurysm was false aneurysm and the perforating ostium was 3.5 cm in diameter. The margin of the perforating ostium had a deposit of calcium. Using an occlusion balloon catheter from the ostium, patch closure was done. The postoperative course was uneventful. We believe that this new approach is preferable to the severe erosion of the sternum by the aneurysm.
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A 45-year-old female manifested lower abdominal fullness and symptoms of hypercalcemia with nausea, vomiting, and thirst. Physical examination showed a right ovarian mass and laboratory data demonstrated hypercalcemia (14.6 mg/dl). The radiographic findings confirmed a right ovarian tumor without any evidence of bone metastasis. Tests revealed that her PTH, nephrogenic urinary cyclic AMP, and 1-25 (OH)2 Vitamin D were not high but that her prostaglandin E2 (PGE2) was elevated. After correction of her calcium elevation with infusion and prednisolone, right oophorectomy with tumor excision was performed. A histological examination of the tumor revealed a mucinous cysto-adenocarcinoma. The postoperative course has been uneventful, with normal calcium and PGE2 values. This case illustrates that hypercalcemia associated with an ovarian carcinoma (Malignancy-associated hypercalcemia) can be mediated by the patient's PGE2 in part.
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Lymphocyte subsets of peripheral blood in patients with cancers were analyzed through two color analysis using FCM. Leu-2/Leu-3 and Leu-2+15+/Leu-8-3+ were compared during radiotherapy and periods of follow up in cases with uterine cervical ca. and lung ca. They did not show similar tendencies but just a opposite one in some cases. Both of them, on the other hand, did not appear to be related with the prognosis of patients. However, CTL and NK (potent) did show a relevance with it through the period of follow up. They might be indices which allow to predict the clinical course of Patients with cancers. Further study is now in progress.