Biomedical subjects
Publications and source records attributed to M Okamoto.
VLCD was useful and effective not only for body weight reduction but also for improvement of glucose intolerance in the treatment of obese non-insulin dependent diabetes mellitus (NIDDM).
The high incidence of hepatitis following cardiopulmonary bypass has stimulated attempts to develop a technique of perfusion without homologous blood. Between October, 1987 and March, 1988, 36 patients underwent open heart surgery without homologous blood transfusion were investigated. Patients with infective endocarditis and urgent surgical cases were excluded from this study. Out of 36 patients using hemoconcentrator, autologous blood and the Variable Prime Cobe Membrane Lung (VPCML), 28 patients (78%) could avoid homologous blood transfusion during the operation and 24 patients (67%) received no homologous blood throughout their hospital stay. Thus, the application of lower volume extracorporeal oxygenator system, reinfusion of residual pump volume using hemoconcentrator and predonated autologous blood could achieved cardiac surgery without homologous blood transfusions in the majority of patients. Moreover, the VPCML had sufficient gas transfer in adult patients with body weight ranging from 37 kg to 70 kg. In renal function, serum creatinine levels in patients without homologous blood were within normal limits throughout 1 month after surgery. However, creatinine level was significantly elevated at the third postoperative day in the homologous blood transfusion group. Thus, these results suggest that application of VPCML and hemoconcentrator combined with predonated autologous blood is useful to achieve open heart surgery without donor blood.
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An equi-toxic dose of CDDP and its analogues (254-S, NK-121, CBDCA and DWA-2114 R) was administered to rabbits and S.180 bearing mice, and the pharmacokinetics were studied. Blood levels: Plasma total platinum (Pt) curves of 5 drugs decreased, showing a biphasic function. The shortest t 1/2 alpha and the longest t 1/2 beta were observed in CDDP group, which correlated with the rate of protein binding (CDDP greater than DWA-2114R greater than NK-121 greater than CBDCA greater than 254-S). Tissue distribution: The tissue levels of Pt decreased slowly, and showed a similar pattern among 5 drugs. The highest level was observed in the kidney, liver and skin, with a moderate high level in the tumor, lung, spleen and thymus, followed by the heart, pancreas, stomach, intestine, muscle and testis in that order. The lowest level was in the brain in S.180 bearing mice.
Intrapulmonary or bronchial neurilemmoma are rare neoplasms and there have been only 29 cases reported in the foreign and domestic literature. We experienced a case of neurilemmoma of the right upper lobe in a 41-year-old male. The patient had no complaint but, a small coin lesion (1.2 x 1.4 cm) was pointed out by chest X-ray examination. The tumor was diagnosed as neurilemmoma by transbronchial lung biopsy and a right upper lobectomy was performed. He has remained asymptomatic in the 18 months after operation.
It has been reported that malignant ovarian tumor is complicated in a ratio of one to 25,000 pregnancies. In the present study, a 22-year-old, nulliparous woman was presented, who had had her right ovary extirpated for serous cystadenoma (low potential for malignancy) and had undergone chemotherapy previously. Seven years later, she was subjected to celiotomy in the fourth month of gestational age because of left ovarian tumor. Intraoperative work-up disclosed a mucinous cystadenoma (low potential for malignancy) of stage Ia (FIGO). Left salpingo-oophorectomy and omentectomy were undertaken, and fetus-bearing uterus was preserved for the sake of the patient. Serum CA 19-9, with a preoperative level of 106.7 U/ml, fell exponentially into the normal range one month after the operation, and she successfully gave birth to a baby at term. After that, combination chemotherapy was instituted against an elevated level of CA 19-9, and she has been in remission while caring for her child.
A 51-year-old woman with an abnormal shadow in the right upper mediastinum and systolic heart murmur was diagnosed as mediastinal cyst and atrial septal defect (ASD). Before the operation, the cyst was suspected as bronchogenic cyst or cystic thymoma based on the findings by CT and NMR. Both cystectomy and closure of ASD was successfully performed and the cyst was diagnosed as pericardial cyst by pathological examination. A brief of literature on the pericardial cyst is given.
The anticonvulsant affects of bifemelane hydrochloride, a novel therapeutic drug for cerebrovascular dementia, were investigated in the kindling model of epilepsy in rats. The results obtained were as follows. (i) Both the seizure stage and afterdischarge duration of kindled seizures from the amygdala and hippocampus were significantly suppressed following systemic injection of bifemelane hydrochloride (5-30 mg/kg) in a dose-dependent manner. (ii) The efficacy of anticonvulsant action on kindled seizures from the hippocampus was more potent than from the amygdala. (iii) The maximum anticonvulsant effects were observed between 1 and 4 h after injection, and this time course was very similar to that of the previously reported increasing effects of bifemelane hydrochloride on noradrenaline levels in the rat brain. Thus, it is suggested that these anticonvulsant effects in kindling may be mediated by central noradrenergic systems. These results indicate that bifemelane hydrochloride has a potent anticonvulsant action on kindled seizures and may be useful for dementia patients with epilepsy or other seizure disorders.
Anticonvulsant action of MK-801, a novel non-competitive antagonist of N-methyl-D-aspartate (NMDA) receptors, was investigated in the kindling model of epilepsy in rats. The results obtained were as follows. (1) Both the seizure stage and afterdischarge duration of previously kindled seizures from the amygdala were significantly suppressed following systemic injection of MK-801 (0.25-4 mg/kg) in a dose-dependent manner. The maximum effects were observed between 2 and 4 after the injection. (2) The MK-801 also showed significant anticonvulsant effects on kindled seizures from the frontal cortex and the ventral and dorsal hippocampus. The efficacy, however, significantly differed between these kindled sites. (3) Daily treatment of MK-801 (0.25 and 1 mg/kg) prior to each electrical stimulation of the amygdala significantly retarded kindling seizure development and increased the total amount of afterdischarge (accumulated AD) required to reach the first stage 5 seizure. During drug sessions of 1 mg/kg MK-801 for 19 days, all rats showed only partial seizures and the growth of afterdischarge was strongly prevented. (4) Pretreatment with reserpine did not antagonize the anticonvulsant effects of MK-801 on previously kindled seizures from the amygdala, suggesting that the effects may not be mediated by catecholaminergic systems. These results indicate that MK-801 has potent anticonvulsant actions on kindled seizures from both limbic and cortical foci, the NMDA system may play a critical role in the seizure-triggering mechanism of kindling. The possible application of NMDA antagonists in clinical epilepsy is suggested.
Among 11 patients with oral cancer that disappeared after combined treatment with bleomycin and radiotherapy without surgery, one had an early recurrence and three had recurrences after 2 years or more. These late occurring recurrences were microcancers on mucous membranes that were thought to have been cured. Two of the three patients whose tumors recurred and another patient were found to have epithelial dysplasia at 1 year and 2 months, 4 years and 2 months, and 1 year and 3 months later, respectively. Among 59 patients who underwent surgery after the combined treatment, no viable cancer cells were found in the resected specimens of 20 patients, but moderate or severe epithelial dysplasia was noted in ten of the 20 patients. The present findings imply that patients in whom an apparent cure has been brought about by conservative treatment may harbor latent malignancy.
Rat spleen supernatant contained two forms of calcium-dependent cellular phospholipase A2 which could be separated from each other by TEAE-cellulose chromatography. The phospholipase A2, named PLA2 S-1, present in the major flow-through fraction was purified to homogeneity. The structural and catalytic properties of splenic PLA2 S-1 were systematically compared with those of rat pancreatic phospholipase A2. Structural evidence, including the sequence of the N-terminal 32 residues, peptide maps obtained on Achromobacter protease I digestion and cyanogen bromide cleavage, and the amino acid composition, showed the close similarity of the two enzymes. Their catalytic and immunochemical properties were also similar. These results demonstrated the existence of a pancreatic type phospholipase A2 in a non-pancreatic organ as a member of the cellular phospholipases A2 and suggest the potential functional involvement of pancreatic type phospholipase A2 in cellular phospholipid metabolism.
A membrane-associated phospholipase A2 was purified from rat spleen. The phospholipase A2 was solubilized from the 108,000 x g pellet fraction with 0.3% lithium dodecyl sulfate and then purified to homogeneity by successive DEAE-Cellulofine AM, octyl-Sepharose, Cellulofine GCL 300-m, S-Sepharose, and Bio-Gel P-30 chromatographies in the presence of 0.5% 3-[(3-cholamidopropyl)dimethylammonio]-1-propane-sulfonate. The apparent Mr of the enzyme, estimated on sodium dodecyl sulfate polyacrylamide gel electrophoresis, was about 13,600. The purified enzyme had a pH optimum in the range of pH 8.0-9.5 and required the presence of Ca2+ (4 mM) for its maximal activity. The enzyme preferentially hydrolyzed the 2-acyl ester bonds of phosphatidylglycerol in the presence and absence of sodium cholate or sodium deoxycholate. Unlike the phospholipase A2 of rat spleen supernatant, no immunocross-reactivity was observed between the purified enzyme and anti-rat pancreatic phospholipase A2 antibody. The N-terminal amino acid sequence of the enzyme was determined and found to be homologous to that of viperid and crotalid venom phospholipases A2. The results in this and the preceding report (Tojo, H., Ono, T., Kuramitsu, S., Kagamiyama, H., and Okamoto, M. (1988) J. Biol. Chem. 263, 5724-5731) demonstrate that rat spleen contains two genetically distinct phospholipase A2 isoenzymes.
Platelet activating factor induced slow, but sustained contraction of isolated rat colon in a dose-dependent manner. The contraction persisted even when the strips were washed several times with Tyrode solution. However, the addition of high concentrations of bovine serum albumin to the washing solution led to the rapid relaxation of the strips to the basal level, possibly by removing platelet activating factor tightly bound to rat colon. These strips then responded normally to a second addition of platelet activating factor. Neither the cholinergic nervous system nor release of histamine, serotonin, prostaglandins or leukotriene D4 were significantly involved in the contraction induced by platelet activating factor. FR-900452 and CV-3988, recently found to be antagonists of platelet activating factor, selectively blocked the contraction of rat colon induced by the active phospholipid, indicating that it induced contraction by a direct stimulatory effect on the smooth muscle of rat colon in a receptor-mediated manner.
A phospholipase A2, which is immuno-crossreactive with the anti-rat pancreatic phospholipase A2 antibody, is present in rat gastric mucosa. The content of the enzyme in the gastric mucosa was comparable to that in the pancreas, but the specific activity in the gastric mucosa homogenate (60.7 +/- 19.5 nmol/min/mg) was higher than that in the pancreas homogenate (3.16 +/- 0.77 nmol/min/mg). A greater proportion of the enzyme was found in the particulate fraction. The gastric enzyme and its proenzyme were purified from the supernatant. The amino acid sequence of the N-terminal 15 residues of the gastric enzyme was determined and found to be identical with that of rat pancreatic phospholipase A2. Like the pancreatic proenzyme, the gastric proenzyme was activated on trypsin treatment.
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The effect of column temperature on the reversed-phase retention of polycyclic aromatic hydrocarbons has been investigated using various chemically bonded phases. Four solutes, coronene, tetrabenzo[a,cd,j,lm]perylene, tetrabenzo[a,cd,f,lm]perylene and benzo[lm]phenanthro[4,5,6-abcd]perylene, were used as the test probes. The temperature dependences of the retention are almost linear (the logarithm of capacity factor is proportional to the reciprocal of the column absolute temperature) with monomeric C18, monomeric C18 with endcapping and diphenyl bonded phases, while non-linear behaviour was observed with polymeric C18 phases. These differences in behaviour of the stationary phases are interpreted in terms of their structural differences.
Recent studies have suggested a critical role of specific gene loss in several embryonic tumours and certain adult cancers. In retinoblastoma, hemizygosity or homozygosity of a recessive mutant allele results in the loss of normal gene product, and this seems to cause the manifestation of the disorder. Familial polyposis coli (FPC) is a human autosomal dominant trait characterized by numerous adenomatous polyps of the colon and rectum, and a high incidence of colon carcinoma. Karyotype analyses have failed to detect specific deletion or translocation. We report the use of polymorphic DNA markers to look for the somatic loss of heterozygosity at specific loci. Investigation of 38 tumours from 25 FPC patients, and 20 sporadic colon carcinomas from 19 patients, revealed frequent occurrence of allele loss on chromosome 22, with some additional losses on chromosomes 5, 6, 12q and 15. The FPC gene-linked DNA probe C11p11 also detected frequent allele loss in both familial and sporadic colon carcinomas but not in benign adenomas. These results suggest the possible involvement of more than one chromosomal locus in the development of familial and sporadic colon carcinomas.
Pyrogen-free cartilage fragments from patients with fracture, osteoarthritis, or rheumatoid arthritis were found to stimulate the production of interleukin-1 alpha-like and interleukin-1 beta-like factor by peripheral blood mononuclear cells from healthy individuals and rheumatoid arthritis patients. The stimulatory cartilaginous component was type II collagen, and the major stimulatory determinant on type II collagen was found to be cyanogen bromide 11 peptide. These results suggest a possible pathogenic role of the intact cartilaginous component in interleukin-1-mediated joint destruction.