Biomedical subjects
Publications and source records attributed to M Fujiwara.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
The presence of antibodies to poly(ADP-ribose) was demonstrated in the sera of MRL/Mp-lpr/lpr (MRL/l) mice by an enzyme linked immunosorbent assay (ELISA). Antibody to poly(ADP-ribose) was strongly inhibited by single stranded DNA (ssDNA) and poly(ADP-ribose), and less by double stranded DNA (dsDNA). Affinity purified anti-poly(ADP-ribose) antibodies bound more with immobilized ssDNA than with poly(ADP-ribose), and were significantly inhibited by soluble ssDNA, although poly(ADP-ribose) was the best soluble inhibitor. On the contrary, affinity purified anti-ssDNA antibodies bound best with ssDNA and significantly but less with poly(ADP-ribose); however, they were scarcely inhibited by poly(ADP-ribose). These results suggest that similar antigenic determinants exist in poly(ADP-ribose) and ssDNA. It is conceivable, however, at the present moment that 'naturally occurring antibodies to poly(ADP-ribose)' in MRL/l mice are subpopulations of anti-ssDNA antibodies that react equally well with poly(ADP-ribose) and ssDNA.
Explore the source record for details and available documents.
In order to clarify role of lpr gene of MRL/Mp-lpr/lpr (MRL/l) mice in the development of immunological abnormalities and lupus nephritis, F2 mice were obtained from crosses of (MRL/1 X AKR) F1 mice and examined with regard to lymph node enlargement, numbers of immunoglobulin (IgM and IgG) producing cells (PC) in the spleen, serum levels of anti-trinitrophenyl (TNP) and anti-DNA antibodies, amounts of circulating immune complexes (IC) and histopathological findings of the kidney. Out of total numbers of 234 F2 mice, 54 mice (F2[+]mice) (23.1%) were with lymphoproliferation and 180 mice (F2[-]mice) (76.9%) without it. As parental controls, 39 MRL/1, 27 AKR and 21 F1 mice were also checked. There were significant differences in the all of the parameters tested between F2 (+) and F2 (-) mice. Significant differences were also observed between F2 (+) and MRL/l mice in the weight of mesenteric lymph nodes, numbers of IgGPC, levels of IgG antibodies and amounts of IC, but not in the numbers of IgMPC and levels of IgM antibodies. All of F1 mice tested mimicked AKR mice in the values of various parameters described above. In MRL/l and F2 (+) mice, there were no significant correlations between the weight of mesenteric lymph nodes and other parameters. These data seem to show that the lpr gene behaves as a single recessive trait and there exists gene(s) which suppresses expression of the lpr gene.
A 57-year-old woman was referred to our hospital because of epigastric tumor on Jan. 16, 1980. Two advanced gastric carcinomas were recognized in the antrum and the corpus by X-ray and endoscopic examinations. The biopsy diagnosis was poorly differentiated adenocarcinoma. She was treated with FT-207 suppositories and subcutaneous injection of OK-432 without operation because of a suspicion of ascites and Virchow's metastasis. After five months, the tumor of the corpus disappeared, and, after nine months, that of the antrum changed to a scarlike lesion. On July 30, 1981, total gastrectomy with extended nodal dissection was performed. Histological examination revealed complete absence of carcinoma cells in the stomach and regional lymph nodes.
This report presents the first patient in Japan with primary malignant melanoma of the ovary. The patient was a 62-year-old woman with the complaint of progressive left hemiparesis due to metastatic brain tumor. She died in the course of two months. At autopsy, there was a large tumor containing brownish fluid at the right ovary. The inner lining of the tumor was covered with a black friable mass with hairs. Histologically, the tumor was composed of polygonal, melanotic or amelanotic cells. Metastases were found in the cerebrum, uterine cervix, etc. In conclusion, the tumor was thought to be malignant melanoma arising in a dermoid cyst. This is an extremely rare condition, reported in only 12 cases throughout the world. The histological findings and histogenesis are presented and discussed.
Explore the source record for details and available documents.
For the echocardiographic assessment of intramyocardial blood flow distribution by intravenous contrast echocardiographic technique, we measured the echo intensity of a point (phi 6 mm) in the interventricular septum using a lightmeter in end-diastole before and after the intravenous injection of various dosages of ether or hydrogen peroxide in one open-chest and four closed-chest dogs. Before the injection of contrast media, the echo intensity of the myocardium varied within a range of 6.1 +/- 4.6% After the injection of ether or hydrogen peroxide, the echo intensity of the myocardium increased. After the occlusion of the left anterior descending artery, echo enhancement of the left ventricular wall occurred, except for the left ventricular anterior wall and the interventricular septum. Between dosage (x) and % increase (y), relations of y = 127x - 3, in ether and y = 1.17x + 1.11, in hydrogen peroxide were observed. We found that the intravenous injection of at least 0.2 ml ether or 15 mg hydrogen peroxide was necessary to achieve effective echo enhancement of the myocardium in dogs.
Fundamental and clinical studies on a new cephalosporin antibiotic, cefpiramide (CPM), was carried out under a joint study program, in order to evaluate the usefulness of the drug in treating infection of the female genital organs. The results obtained were as follows: CPM was readily transported to female genital organ tissues, and the concentrations of the drug exceeded 35 micrograms/g in various organ tissues in about 1 hour, following intravenous injection of 1 g. A level of more than 2 micrograms/g was maintained even 14 hours after the injection. The transport of CPM to various tissues was also studied following intravenous drip infusion of 1 g for 1 hour. The concentrations in tissues were slightly low but similar to those following intravenous injection. The peak concentration of the drug in the dead space exudate was 3.1-20.4 micrograms/ml, following intravenous injection and intravenous drip infusion of 1 g. The MIC80 of CPM were 3.13-12.5 micrograms/ml against S. aureus, Klebsiella sp., P. mirabilis and P. aeruginosa. Clinical effects of CPM were analyzed in 158 patients, including 56 cases with intrauterine infection, 37 cases with intrapelvic infection, 22 cases with external genital infection, 31 cases with adnexitis, 6 cases with postoperative wound infection and 6 cases with other infections. Excellent response was seen in 28 cases (17.7%), good response in 120 (75.9%) poor response in 10 (6.3%). The rate of response was calculated as 93.7%. Safety of the drug was analyzed in 258 patients, and side effects occurred in 4 (1.6%). Of these 4 patients, rash was in 1 patient, heat sensation in 1 patient, nausea in 1 patient and rash accompanying edema in 1 patient. Abnormal values in clinical laboratory findings were seen in 7 patients. Elevations of transaminase were seen in 5 patients and decrease of platelet was seen in a patient, and then elevations of transaminase with decrease of platelet was seen in a patient, and no other changes of particular note appeared.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
beta-Adrenergic receptors and the activities of adenylate cyclase, phosphodiesterase and protein kinase were examined in two human glioma cell lines, U 251 and LM, as well as in rat C6 glioma. [3H]Dihydroalprenolol binding to beta-adrenergic receptors was specific, saturable and of high affinity in each cell line. The dissociation constant (Kd) and maximal binding (Bmax) extrapolated from Scatchard curves were Kd = 17.4 +/- 3.2 nM and Bmax = 1110 +/- 197 fmol/mg protein for the U-251 cells; Kd = 14.4 +/- 2.2 nM and Bmax = 655 +/- 105 fmol/mg protein for the LM cells; and Kd = 5.6 +/- 1.1 nM and Bmax = 454 +/- 80 fmol/mg protein for the C6 glioma cells. L-Isoproterenol stimulated cyclic AMP formation in all 3 cell lines. beta-Adrenergic agonists also increased calcium-dependent and calcium non-dependent phosphodiesterase activity in these tumor cells. Cytosolic protein kinase in the 3 cell lines phosphorylated exogenous histone as a substrate. The phosphorylation was enhanced by cyclic AMP. Cytosolic protein kinase also phosphorylated endogenous cytosolic macromolecules. The phosphorylated proteins had molecular weights of 30,000, 51,000 and 90,000 in the two human glioma cell lines. The present results indicate that human glioma cell lines have functional beta-adrenergic receptors linked to adenylate cyclase. These beta-receptors can also regulate phosphodiesterase activity and cyclic AMP in human glioma cells can activate protein kinase and induce the phosphorylation of specific proteins.
Specific [3H]yohimbine binding to the homogenates of bovine cerebral arteries was saturable and of high affinity (KD = 21 nM) with a Bmax of 720 fmol/mg protein. On the other hand, there was no detectable specific [3H]prazosin binding to these tissues. Scatchard and Hill plot analyses of specific [3H]yohimbine binding indicated one class of binding sites. Specific binding of [3H]yohimbine was displaced effectively by alpha 2 adrenergic agents and less effectively by alpha 1 adrenergic agents. IC50 values for adrenergic drugs of [3H]yohimbine binding were as follows: yohimbine, 55 nM; tramazoline, 270 nM; clonidine, 580 nM; methoxamine, 15 microM; prazosin, 47 microM, phenylephrine, 49 microM; norepinephrine, 60 microM; epinephrine, 150 microM. These results suggest that alpha adrenergic receptors in bovine cerebral artery are mostly of the alpha 2 subtype.
The effects of Goniopora toxin (GPT), isolated from the Goniopora species, on the action potential and membrane currents of bullfrog atrial muscle were studied using the double sucrose-gap method. GPT at concentrations above 10 nmol/l prolonged the duration of the action potential and sometimes induced arrhythmias. The prolongation was also induced in the presence of Ca channel blockers (Mn or verapamil). These effects were not reversed by continuous superfusion of GPT-free solution, but were rapidly antagonized by tetrodotoxin (1 mumol/l). The resting potential was not affected by GPT. Voltage clamp experiments revealed that sustained inward current flows following the fast sodium current upon depolarization, in the presence of GPT. The current was elicited by the toxin in Mn-treated fibers and abolished in the presence of TTX. The delayed outward current (Ix) was slightly reduced; the background K current (IK1), inward background current (Ib) and slow inward current (Islow) were not altered by GPT. These results suggest that GPT acts on sodium channels to give rise to a prolonged sodium current which is in turn responsible for the prolongation of the action potential.
Plasma amino acid, plasma pancreatic glucagon and serum insulin levels were simultaneously measured in cirrhotic patients with (drinkers) and without a history of alcohol drinking (non-drinkers), as compared to those in alcoholics without liver disease. Clinical characteristics in drinkers and non-drinkers, such as the extent of liver dysfunction, which may affect plasma amino acid levels, were strictly matched. Plasma pancreatic glucagon levels in the drinker group were much higher than those in the non-drinker group. In the former group, the elevated plasma pancreatic glucagon levels were correlated (p less than 0.05) to total amino acid levels (the sum of 20 kinds of L-amino acid concentrations) and, elevated AAA concentrations leading to a diminished BCAA/AAA ratio. Drinkers with histories of hepatic encephalopathy presented grossly elevated glucagon levels and severely abnormal aminograms similar to those observed in hepatic insufficiency.
Plasma amino acid concentrations and plasma glucagon and serum insulin levels were studied in male patients with compensated alcoholic and nonalcoholic liver cirrhosis. Age, nutritional status, and liver function tests were similar in both groups; none of the patients presented hepatic encephalopathy. Plasma valine and leucine concentrations were lower, and tyrosine, higher in alcoholic than nonalcoholic liver cirrhosis. As a result, the molar ratios of branched-chain amino acids (BCAA) to aromatic amino acids (AAA) were reduced markedly in this group. Although correlation coefficients comparing BCAA/AAA ratios and KICG in alcoholic and nonalcoholic liver cirrhosis were similar, a steeper regression line was observed in alcoholics. Plasma glucagon and proline levels were significantly higher in alcoholic than nonalcoholic liver cirrhosis, the former correlated with AAA concentrations only in alcoholic liver cirrhosis, but not with BCAA levels. These results indicated that alcoholic liver cirrhosis presented a more deranged plasma amino acid pattern than nonalcoholic, and the amino acid imbalances, except for depressed BCAA and elevated proline, were derived, in part, from the hyperglucagonemia.