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Biomedical subjects

M Yamazaki

Publications and source records attributed to M Yamazaki.

At least 577 records · Page 32Linked to original sources

[A case of spinal cord glioblastoma multiforme].

A 35-year-old woman was admitted to our hospital with a 3 month history of progressive paraparesis and impairment of bowel and bladder function. MRI suggested a malignant glioma at the level of T9 to L1. Laminectomy and subtotal removal of the tumor was performed. The surgical specimen was a glioblastoma multiforme. An aggressive adjuvant therapy was scheduled to prevent rapid local regrowth and leptomeningeal dissemination. Radiotherapy with a total dose of 65Gy was delivered with chemotherapy including ACNU (2mg/kg) and vincristine (0.2mg/kg). Lymphokine-activated killer (LAK) cells were given intrathecally with a total dose of 1.6 x 10(9) LAK cells with 3 x 10(4) units of IL-2. MRI taken 6 months after surgery revealed no residual tumor, and no malignant cell was detected in the patient's CSF. After physiotherapy, she became able to walk with a stick and was discharged. Chemotherapy (ACNU 2mg/kg/8 weeks) had been further continued for 2 years. She did well until 14 months after surgery, when paraparesis recurred and rapidly progressed to completism. MRI revealed a spinal cord swelling with marked edema, suggesting delayed radiation necrosis. Two years after surgery, MRI showed a marked atrophy of the spinal cord, and no residual tumor. But 3 years after surgery, a round tumor at the level of T11 and T12 was revealed on MRI, and she was admitted to our hospital again. A spinal cord amputation was performed, and the tumor was totally removed without worsening her neurological symptoms. Surgical specimen of the tumor was glioblastoma multiforme again.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

[Acute relapsing sensory neuropathy following upper respiratory infections--a case report].

A 44-year-old man developed numbness in his hands and feet and an unsteady gait following an upper respiratory symptoms. The symptoms progressed rapidly and reached maximum in a few days, followed by a gradual improvement over a few weeks, but his gait remained unsteady. His symptoms progressively increased over 14 years, with 11 relapses of similar episodes. Neurologic examination showed normal limb strength. Deep tendon reflexes were absent. Touch, cold, and pinprick sensation were impaired in his hands and feet. There was a profound loss of position and vibration sense in all extremities. He demonstrated an unsteady and broad-based gait. Electrophysiologic and histologic examination on the peripheral nerves revealed evidences of axonal degeneration without demyelination involving the sensory nerves.

Acute Disease↗

Amelioration of dermal lesions in streptozotocin-induced diabetic rats by aminoguanidine.

As aminoguanidine (AG) is known to prevent non-enzymatic glycosylation in various tissues, we have histologically and biochemically evaluated AG effects on the skin in control, SZ-diabetic and AG-treated (25 mg/kgbw/day, 10w) diabetic rats. HbA1c and plasma glucose levels in diabetic and AG-treated diabetic rats were maintained about two times higher than those in control rats during the 10 weeks of the experiment. Histological findings revealed that the dermis in diabetic rats was thin and edematous, associated with swelling and degeneration of collagen fibers. Necrobiotic changes were seen in the lower dermis. These changes were greatly improved in AG-treated diabetic rats. Skin glucose contents in diabetic and AG-treated diabetic rats were about 10 times higher than those in the controls, whereas there was no difference in the sorbitol contents between three groups. Dry weight of the skin and collagen content was well correlated (r = 0.9044) and collagen represented 78.0 +/- 2.3% of the dry weight. By SDS-PAGE analysis of cyanogen bromide digests it was shown that high molecular weight peptides were increased in diabetic rats, but were decreased in AG-treated diabetic rats. The mean of glycosaminoglycan (GAG) contents of diabetic skin was 54% of that in the controls (1.58 +/- 0.09 vs. 2.94 +/- 0.39 micrograms/mg dry weight, P < 0.0025), which increased significantly in AG-treated diabetic rats (1.75 +/- 0.07 microgram/mg dry weight, P < 0.01 vs. diabetic).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

The role of insulin-sensitive phosphodiesterase in insulin action.

The physiological role of the insulin-sensitive phosphodiesterase in mediating the antilipolytic actions of insulin was investigated in rat fat cells with two phosphodiesterase inhibitors, namely, 3-isobutyl-1-methylxanthine (IBMX) and griseolic acid. Insulin activates the phosphodiesterase when incubated with intact fat cells and blocks isoproterenol-induced cellular cAMP production and lipolysis, in a time- and dose-dependent manner. High concentrations of IBMX (1 mM), but not lower concentrations (0.1 mM), increased fat cell cAMP levels and lipolytic responses and overcame the antilipolytic effects of insulin; however, this treatment does not inhibit insulin-stimulated phosphodiesterase activity at earlier times (less than 30 min of incubation). These results may suggest that the level of cAMP under these conditions may be sufficient to stimulate lipolysis maximally, even though increases in cellular cAMP accumulation associated with the higher concentration of IBMX (1 mM) are partially suppressed by insulin. Cellular cAMP accumulation and the phosphodiesterase activation induced by IBMX are suppressed by the nonhydrolyzable adenosine analogue N6-phenylisopropyladenosine (PIA). These results suggest the involvement of adenosine receptors in mediating these responses. A novel phosphodiesterase inhibitor, griseolic acid, suppresses basal phosphodiesterase activity (approximately 50%), increases cellular cAMP content, and stimulates lipolysis in intact fat cells. It also partially suppresses insulin-stimulated phosphodiesterase activity (approximately 50%) and reduces the ability of insulin to decrease cellular cAMP concentration (approximately 40%) and lipolysis (approximately 65%). Because, unlike IBMX and other drugs, griseolic acid demonstrates only inhibition of phosphodiesterase activity, it may be a useful tool for studying the mechanism of insulin action in intact cells. The present work supports the concept that insulin's antilipolytic action is mediated by an activation of fat cell phosphodiesterase.

1-Methyl-3-isobutylxanthine↗

Prothrombin fragment F1 + 2 and thrombin-antithrombin III complex are useful markers of the hypercoagulable state in atrial fibrillation.

It is well known that atrial fibrillation (AF) is one of the most important diseases that predispose patients to thrombosis. We have attempted to identify patients with AF in the hypercoagulable state by measuring molecular markers such as thrombin-antithrombin III complex (TAT) and prothrombin fragment 1 + 2 (PTF) and determining the effect of antithrombotic therapy on these markers; 83 patients with AF were studied. Increased levels of plasma TAT and PTF were more frequently observed in patients with AF and associated mitral stenosis than in patients with AF alone. In cases of AF without mitral stenosis, plasma levels of TAT and PTF were significantly lower in those patients receiving antithrombotic agents (aspirin or warfarin) than in those receiving no antithrombotic agents. Furthermore, plasma levels of PTF were significantly lower in patients given warfarin than in those receiving aspirin. These results suggest that (1) patients with AF and mitral stenosis who are not given warfarin are in an extremely hypercoagulable state and (2) some patients with AF without mitral stenosis who are not given antithrombotic agents are also moderately hypercoagulable. In vivo activation of blood coagulation was more effectively controlled in patients receiving warfarin than in those taking aspirin.

Aged↗

Effect of FR121196, a novel cognitive enhancer, on the memory impairment of rats in passive avoidance and radial arm maze tasks.

Passive avoidance performance was impaired in young rats by scopolamine (1.0 mg/kg) or by nucleus basalis magnocellularis lesions and in aged rats (24-26 months old). FR121196[N-(4-acetyl-1-piperazinyl)-4-fluorobenzenesulfonamide+ ++], a newly introduced cognitive enhancer, ameliorated the failure in memory retention with bell-shaped dose-response curves in doses ranging from 0.1 to 10 mg/kg. Similar dose-response curves also were obtained with methamphetamine (0.1-10 mg/kg), whereas physostigmine (0.01-1.0 mg/kg) attenuated the amnesia in scopolamine-treated rats, but hardly affected that in nucleus basalis magnocellularis-lesioned or aged rats. In radial arm maze tasks, behavioral indices of spatial memory, such as first correct choices and number of errors, were impaired by an injection of scopolamine (0.5 mg/kg) or by lesions of the medial septum or fimbria-fornix. FR121196 ameliorated the scopolamine-induced memory deficit with a bell-shaped dose-response curve, whereas methamphetamine had the opposite effect. These two drugs had little effect on memory deficits brought about by medial septum or fimbria-fornix lesioning, whereas physostigmine ameliorated these deficits in scopolamine-treated and medial septum-lesioned rats, but not in fimbria-fornix-lesioned rats. Behavioral studies using Animex demonstrated that FR121196, in contrast with methamphetamine, does not increase locomotor activities in rats up to a dose of 10 mg/kg. These results are discussed in relation to the cholinergic and dopaminergic mechanisms of memory.

Aging↗

Formation of multicellular spheroids composed of rat hepatocytes.

A novel method for the preparation of spheroids containing two types of cells (hetero-spheroid) has been successfully developed by using a collagen-conjugated thermo-responsive polymer, poly-N-isopropyl acrylamide, as a cell substratum. The hetero-spheroid was prepared by detaching the confluent monolayer composed of parenchymal and non-parenchymal rat liver cells at a temperature below lower critical solution temperature and culturing it on the non-adhesive substratum. The hetero-spheroid had activity in albumin secretion and PNPA hydrolase activity over a period of 60 days in dishes. These findings suggest that this spheroid formation system is a useful model of an alternative to animal tests of hepatotoxicity.

Acrylic Resins↗

Possible involvement of hyperinsulinemia and adrenergic activation in the pathogenesis of indomethacin-induced antral ulcers in nonfasted hamsters and refed rats.

Subcutaneous doses of indomethacin (IND) produced mainly antral ulcers in refed rats, almost exclusively corpus erosions in fasted rats, but no antral or corpus mucosal insult in nonfasted rats. In contrast, IND-treatment in nonfasted hamsters caused antral ulcers but minimal corpus erosions. Mild and severe hyperinsulinemia were observed in refed rats and nonfasted hamsters, respectively. The hyperinsulinemia and antral ulcers in the animals were significantly attenuated by a pretreatment (80 mg/kg, i.v., in rats, 60 mg/kg, i.p., in hamsters) of streptozotocin. Furthermore, the antral ulcers were dose-dependently attenuated by prazosin, an adrenergic alpha-1 antagonist, and yohimbine, an adrenergic alpha-2 antagonist, but not by propranolol, an adrenergic beta antagonist. The large doses of atropine (3.2-10 mg/kg, p.o.) also attenuated the ulcers. The histamine H2 receptor antagonist, famotidine (1-10 mg/kg, p.o.), significantly attenuated the antral ulcers in nonfasted hamsters, but not in refed rats. The latter two drugs exhibited greater inhibition of the corpus erosions in fasted rats compared with the antral ulcers in refed rats and nonfasted hamsters. The corpus erosions were more extensive after streptozotocin treatment (80 mg/kg, i.v.) and were aggravated significantly by yohimbine, whereas they were hardly affected by prazosin or propranolol. It is thus concluded that hyperinsulinemia and adrenergic activation are commonly involved in the etiology of the IND-induced antral ulcers in refed rats and nonfasted hamsters. Vagal activity, which plays a crucial role in the etiology of the corpus erosions in fasted rats, may play a part in the antral ulcer formation in nonfasted hamsters, but not in refed rats.

Animals↗

[Bacteriological, pharmacokinetic and clinical studies of 5% and 10% granules of cefdinir in the pediatric field].

Bacteriological, pharmacokinetic and clinical studies on cefdinir (CFDN, FK482), a new oral cephalosporin, 5% and 10% granules, were performed in the field of pediatrics. The results are summarized below. 1. Antibacterial activities Antibacterial activities of CFDN against Staphylococcus aureus, Streptococcus pyogenes, Streptococcus pneumoniae, Haemophilus influenzae, Branhamella catarrhalis, Escherichia coli and Klebsiella pneumoniae were studied in comparison with those of cefaclor (CCL), cefixime (CFIX) and amoxicillin (AMPC). MIC80's of CFDN against S. aureus, S. pneumoniae, S. pyogenes, H. influenzae, B. catarrhalis, K. pneumoniae and E. coli were 0.78, 0.20, less than or equal to 0.025, 0.39, 0.10, 0.20 and 0.10 micrograms/ml, respectively. These results show that CFDN has high antibacterial activities against these organisms. MIC80's of CFDN against Gram-positive bacteria were similar to those of AMPC, and was lower than those of CCL and CFIX. As for antibacterial activities against Gram-negative bacteria (GNB), the MIC80 of CFIX against H. influenzae was 0.05 micrograms/ml, which was slightly lower than that of CFDN. THe MIC80's of CFDN against other GNB were similar to those of CFIX. 2. Absorption and excretion Blood concentrations and urinary excretion rates of CFDN 5% and 10% granules and 100 mg capsule were determined. The data on CFDN 10% granules were similar to those on CFDN 5% granules. At a dose of 3 mg/kg, peak blood concentrations (Cmax's) of CFDN ranged from 0.20 to 2.12 micrograms/ml with 5% granules and from 0.50 to 1.15 micrograms/ml with 10% granules at 2 to 3 hours after dosing. At a dose of 6 mg/kg, peak concentrations were 0.66-2.06 micrograms/ml and 0.70-1.52 micrograms/ml with 5% granules and with 10% granules, respectively. At 8 hours after dosing, blood concentrations were 0.04-0.54 micrograms/ml at 3 mg/kg and 0.06-0.27 micrograms/ml at 6 mg/kg. Blood half-lives were 1.33-4.36 hours at 3 mg/kg and 1.14-3.27 hours at 6 mg/kg. AUC's were 1.7-11.0 micrograms.hr/ml with 3 mg/kg and 2.4-8.7 micrograms.hr/ml with 6 mg/kg. With administration of single 100 mg capsule, Cmax's, blood concentrations after 8 hours, T1/2's and AUC's were 0.79-1.88 micrograms/ml, 0.20 micrograms/ml, 1.54-2.72 hours, and 5.2 micrograms.hr/ml, respectively. Urinary recovery rates in the first 8 hours ranged from 6.85 to 39.2% with 3 mg/kg and 6.08-25.5% with 6 mg/kg.(ABSTRACT TRUNCATED AT 400 WORDS)

Adolescent↗

[Rapid detection of motile Salmonella in chicken meat by the 1-2 Test].

The 1-2 Test (BioControl) is an enrichment culture/immuno-diffusion assay for detecting Salmonella in foods by use of poly-H-antibodies. The performance of the 1-2 Test was compared with that of the traditional culture method on 85 chicken meat samples. The results were as follows: The detection frequency of Salmonella by the 1-2 Test 24-hour assay (28/85, 32.9%) was greater than that by the 8-hour assay (16/85, 18.8%) and almost equal to that by the traditional method (26/85, 30.6%). The 8-hour assay gave a 46.2% sensitivity and 93.2% specificity. The 24-hour assay gave an 84.6% sensitivity and 89.8% specificity. Detection appeared to show some influence from the number of Salmonella, number of viable cells (SPC) and coliform groups. Differences in serotypes of Salmonella detected by the 1-2 Test and the traditional methods were also observed. Although there were some differing results between the 1-2 Test and the traditional method, this system appears to be useful for detecting Salmonella in foods, since results can be obtained at least 24 hours earlier than by the conventional procedures.

Animals↗

[Antiplatelet effect of clopidogrel].

Clopidogrel is a new thieno-pyridine derivative and has a more potent inhibitory effect on platelet aggregation, dependent on ADP rather than ticlopidine. In a phase I study performed in Japan, significant inhibition of ADP-induced platelet aggregation and prolongation of bleeding time was observed in the dose range of 25, 50 and 75 mg. These effects were comparable to 200 or 300 mg of ticlopidine. Antithrombotic effects have also been shown in experimental animal models. Clopidogrel is expected to reduce the incidence of neutropenia since smaller doses are sufficient to suppress platelet aggregation compared to ticlopidine. Clopidogrel has been proven to be a potent and well-tolerated antiplatelet agent for atherosclerosis patients at risk of thrombosis, in Europe.

Adenosine Diphosphate↗

[A case of paraneoplastic cerebellar degeneration--success in early detection of cancer by anti-Purkinje cell antibody].

A 70-year-old woman was admitted to our hospital because of rapidly progressive cerebellar ataxia. Neurological examinations showed saccadic eye movement, downbeat nystagmus, scanning speech, proximal dominant muscle weakness and severe truncal and limb ataxia. Based on these clinical features, she was suspected to have paraneoplastic cerebellar degeneration (PCD), although the malignant tumor was not detected through clinical intensive surveys. Her serum and CSF revealed to have anti-Purkinje cell antibodies immunohistochemically, and western blot analysis showed that they reacted with 58 kd band. In view of previous reports of PCD, she was strongly suspected to have gynecological cancers. The trial laparotomy found early stage fallopian tubal cancer, which had not been detected by CT scan, ultrasonogram and MRI. It is important to detect and characterize these autoantibodies found in the PCD patients for early diagnosis and treatment of underlying cancer.

Aged↗

Effect of lard, palm and rapeseed oils life conservation in aged mice.

Effects of lard, palm and rapeseed oil diets on the survival and fatty acid composition of liver and brain lipids were studied in male and female mice for 15 months. Over 80% of mice fed on lard and rapeseed oil (n-3 PUFA sufficient) diets survived to the end of feeding trial, however, 60% of male mice fed on palm oil (n-3 PUFA deficient) diet died before the end. Although a survival curve in female mice fed on palm oil diet was similar to that in male, it was not as dramatic as that of the male. The fatty acid analyses revealed that severe n-3 PUFA deficiency occurred in the mice fed on a palm oil diet. Moreover, the fatty acid was more deficient in the male than in the female. These results suggest that short life in mice may be caused by n-3 PUFA deficiency and, therefore, the fatty acid may be essential in enjoying a long life.

Aging↗

Anemia and mast cell depletion in mutant rats that are homozygous at "white spotting (Ws)" locus.

Mice possessing two mutant alleles at the W or Sl locus are anemic and deficient in mast cells. These mouse mutants have black eyes and white hair. Because homozygous mutant rats at the newly found white spotting (Ws) locus were also black-eyed whites, the numbers of erythrocytes and mast cells were examined. Suckling Ws/Ws rats showed a severe macrocytic anemia and were deficient in mast cells. When bone marrow cells of normal (+/+) control or Ws/Ws rats were injected into C3H/He mice that had received cyclophosphamide injection and whole-body irradiation, remarkable erythropoiesis occurred in the spleen of +/+ marrow recipients but not in the spleen of Ws/Ws marrow recipients. When skin pieces of Ws/Ws embryos were grafted under the kidney capsule of nude athymic rats, mast cells did develop in the grafted skin tissues. Therefore, the anemia and mast cell deficiency of Ws/Ws rats were attributed to a defect of precursors of erythrocytes and mast cells. Because the magnitude of the anemia decreased and that of the mast cell deficiency increased in adult Ws/Ws rats, this mutant is potentially useful for investigations about differentiation and function of mast cells.

Anemia↗

Characterization of Ws mutant allele of rats: a 12-base deletion in tyrosine kinase domain of c-kit gene.

Homozygous mutant rats at the newly found white spotting (Ws) locus were anemic and deficient in mast cells and melanocytes. Because the phenotype of Ws/Ws rats resembled the phenotype of mice possessing a double-gene dose of mutant alleles at the W locus and because the c-kit gene was mapped at the W locus of mice, we characterized the c-kit gene of Ws/Ws rats. The authentic sequence of the rat c-kit cDNA was determined by using a cDNA library prepared from the hippocampus of Sprague-Dawley rats. The c-kit cDNA of Ws/Ws and normal (+/+) control rats was obtained by reverse transcriptase modification of the polymerase chain reaction. When compared with the authentic sequence, a deletion of 12 bases was found in the c-kit cDNA of Ws/Ws rats. This change was shown to be a result of the deletion of the genomic DNA. Four amino acids encoded by the deleted 12 bases (ie, Val-Lys-Gly-Asn) were located at two amino acids downstream from the tyrosine autophosphorylation site in the c-kit kinase and were conserved not only in mouse and human c-kit kinases but also in mouse and human c-fms kinases (ie, receptors of colony-stimulating factor-1). Taken together, the Ws/Ws rat is the first characterized mutant of the c-kit gene in an animal species other than the mouse.

Alleles↗

Comparison of responses to angiotensin II of dog mesenteric arteries and veins.

Responses to angiotensin II (AII), arachidonic acid (AA) and prostaglandin (PG) I2 were compared in helical strips of dog mesenteric arteries and veins. Arterial strips contracted in response to AII, whereas venous strips responded with a transient, slight contraction followed by a moderate relaxation. The peptide-induced responses were abolished by treatment with saralasin, but were not influenced by ONO3708, an inhibitor of vasoconstrictor PG actions, or by endothelium denudation. Treatment with indomethacin potentiated the contractile response of the arteries and reversed the relaxant response of veins to a contraction. The concentration of exogenous PGI2 methylester needed to produce a tension development similar to that induced by PGI2 released by AII was greater in the mesenteric arteries than in the veins. The amount of 6-keto PGF1 alpha in the bathing media measured by radioimmunoassay was increased in the arteries and veins stimulated by AII. Exogenously applied PGI2 elicited relaxations of similar magnitude in the arteries and veins. AA-induced relaxations were greater in the veins; indomethacin suppressed the arterial and venous relaxations. The magnitude of the endothelium-dependent relaxation induced by A23187 was similar in the arteries and veins. It appears that the heterogenous responses to AII of dog mesenteric arteries and veins are due mainly to the difference in the AII receptors responsible for smooth muscle contraction and also to the difference in the ability to produce and liberate PGI2. The synthesis and the action of EDRF (endothelium-derived relaxing factor) does not seem to differ in the arteries and veins.

6-Ketoprostaglandin F1 alpha↗

High-performance liquid chromatographic determination of alpha-acetyldigoxin in Digitalis lanata leaves.

An analytical method for the determination of alpha-acetyldigoxin in Digitalis lanata leaves by HPLC has been developed. The procedure consists of extraction of dry leaf powder with 50% methanol and cleanup by a Sep-Pak C18 cartridge prior to HPLC analysis. The quantitation is carried out by the incorporation of beta-methyldigoxin as an internal standard. HPLC is performed on an octylsilyl bonded silica column with acetonitrile/methanol/water (100/11/188, v/v). The effluent is monitored by uv absorption at 220 nm. The amount of alpha-acetyldigoxin per 100 mg of dry leaf powder is estimated at 5.55 +/- 0.21 micrograms (mean +/- SD). The average recovery of alpha-acetyldigoxin from added samples is 97.2%. The present method is sensitive, reliable, and relatively simple. Application of this HPLC method to the analysis of samples obtained by fermentation of the leaf powder is also demonstrated.

Acetyldigoxins↗