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Biomedical subjects

T Tsukahara

Publications and source records attributed to T Tsukahara.

At least 19 recordsLinked to original sources

The additive effect of alpha-difluoromethylornithine (DFMO) and radiation therapy on a rat glioma model.

The effects of alpha-difluoromethylornithine (DFMO), radiation and the therapy of their combination were investigated in rats bearing G-XII glioma. DFMO treatment as well as radiation therapy prolonged the survival period when compared to the results in non-treated control rats. The combination therapy showed a greater effect on the survival rate than the single therapies, the effect being additive. The concentration of putrescine, spermidine, and N1-acetylspermidine in tumor tissue was lowered by DFMO, while that of spermine was slightly elevated. Radiation decreased the concentration of all the polyamines, putrescine, spermidine, spermine and N1-acetylspermidine. The concomitant treatment with DFMO and radiation further decreased the concentrations of putrescine and N1-acetylspermidine in tumor tissues. The survival period of glioma-bearing rats is inversely correlated with the tissue levels of putrescine plus N1-acetylspermidine.

Animals

Cerebrovascular effects of substance P after experimental subarachnoid haemorrhage.

The vasoactive effects of substance P (SP), as well as the content of cyclic guanine monophosphate (cGMP), were determined in the rabbit basilar artery after subarachnoid haemorrhage (SAH). Out of 47 rabbits, 24 were subjected to a SAH, induced by injecting 5 ml of autologous arterial blood into the cisterna magna; 23 were used as controls. In 20 animals (10 SAH and 10 controls), isometric tension recording of isolated rings of the basilar artery--dissected 2 days after SAH--was employed to assess the dose-dependent vasodilatation to SP (10(-10) to 10(-6) M) after precontraction with serotonin (10(-8) to 10(-5) M). In 15 animals (8 SAH and 7 controls), the basal cGMP content was measured in the basilar artery 2 days after SAH. In the other 12 animals (6 SAH and 6 controls), the increase in cGMP content was measured in the basilar artery after a 10-minute incubation with SP (10(-6) M). SP caused significantly less dilatation in animals subjected to SAH than in controls, especially for concentrations between 10(-9) and 10(-6) M (p < 0.001). The cGMP content in the arteries 2 days after SAH was significantly lower than in control arteries (31.5 +/- 7.3 against 57.3 +/- 4.3 pmoles/g tissue). In the preparations incubated with SP, the increase of cGMP was 440 +/- 115% in the control arteries, and only 97 +/- 30% in the arteries after SAH. It is concluded that the vasodilator activity of SP is significantly impaired after SAH.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals

Significance of monocytosis in varicella and herpes zoster.

Percent ratios and absolute numbers of peripheral blood monocytes in patients with varicella and herpes zoster were determined and compared with those in patients with herpes simplex virus infection, measles and rubella. Monocytosis during the acute stage (p less than 0.01) was statistically significant in varicella and generalized and localized herpes zoster, compared with the levels in herpes simplex virus infection, measles and rubella. Absolute monocyte counts in varicella and HZ were significantly increased (p less than 0.02) beyond those of measles and rubella. The high % ratios of monocytes in varicella and herpes zoster during the acute stage decreased to normal ranges with cure.

Acute Disease

A case of cytophagic histiocytic panniculitis with sicca symptoms and lupus nephritis.

A 48-year-old Japanese woman presented with many subcutaneous nodules. The skin was purplish in color and tender; the nodules were scattered over the entire surface. Histological findings of biopsy specimens from the nodules indicated septal panniculitis comprised of histiocyte and/or macrophage infiltrates, often with erythro- and/or leukophagocytosis. Phagocytic cells were OKM1 (CD11b), MT1 (CD43), LeuM3 (CD14), and histiocyte antigen positive, indicating the presence of histiocytes and/or macrophages. The patient had sicca symptoms, positive homogenous, speckled pattern ANA (x320), and diffuse proliferative lupus nephritis.

Female

Effect of nicardipine on basilar artery vasoactive responses after subarachnoid hemorrhage.

The effect of the dihydropyridine calcium antagonist, nicardipine, on the vasoactive responses of the basilar artery was investigated after subarachnoid hemorrhage (SAH). Forty-five rabbits were separated into one control group and four groups receiving SAH (nine animals each). The SAH was induced by injecting 5 ml of autologous arterial blood into the cisterna magna. SAH animals were subjected to one of the following: 1) no treatment; 2) intravenous (i.v.) saline infusion (vehicle); 3) i.v. infusion of low-dose nicardipine (0.01 mg/kg/hr), or 4) i.v. infusion of high-dose nicardipine (0.15 mg/kg/hr). The i.v. infusions were started immediately after SAH and continued for 48 hours. Serotonin (5-HT) (10(-8) to 10(-5) mol/L) was used to evoke dose-dependent vasoconstriction of isolated rings of the basilar artery 2 days after SAH. Acetylcholine (ACh) (10(-8) to 10(-4)) and adenosine-triphosphate (ATP) (10(-8) to 10(-4) mol/L) were applied after maximal contraction with 5-HT, evoke a dose-dependent vasodilatation. Compared with controls, in animals subjected to SAH serotonin caused similar or slightly larger contractions; nicardipine infusion did not decrease the amount of contraction observed after SAH. ACh and ATP caused significantly less dilatation in animals submitted to SAH than in controls. After high-dose nicardipine, ACh- and ATP-induced dilatations were significantly more pronounced (57% and 68% of initial contractile tone) than in the other animals receiving SAH (36%-39% and 45%-55%, respectively).(ABSTRACT TRUNCATED AT 250 WORDS)

Acetylcholine

[Study of yearly changes in intractable disease patients receiving financial aid for treatment].

Yearly changes of intractable disease patients receiving financial aid for treatment were observed for 24 intractable disease patients from 1983 to 1987. The results obtained were as follows. 1. The number of intractable disease patients receiving financial aid for treatment increased from 1983 to 1987 for 23 of the diseases. Only the number of SMON patients did not increase. 2. Medical care expenditures for these patients also increased since 1983. Greater increases for in-patients than for out-patients were seen for Huntington's chorea and Behcet's disease, while larger increases were seen for out-patients with Parkinson's disease, Scleroderma.dermatomyositis.primary multiple myositis, Buerger's disease, and others. 3. The proportion of national health insurance holders among intractable disease patients was 42.1% as compared with 34.7% among total national patients. The proportion was especially higher for Huntington's chorea (64.6%), Parkinson's disease (64.1%) and SMON (59.4%) patients.

Behcet Syndrome

High cervical intradural lipoma--case report.

A rare high cervical intradural subpial lipoma unassociated with spinal dysraphism manifested by a slowly progressive myelopathy simulating Brown-Sequard syndrome in a 37-year-old male. The diagnosis was based on neuroradiological imaging. Intraoperative recording of somatosensory evoked potentials showed recovery of the prolonged N20 latency, indicating adequate decompression was achieved.

Adult

[Non-Hodgkin's lymphoma in an elderly patient complicated by cyclophosphamide-induced allergic hepatic dysfunction].

A 77-year-old male presented at our Department of Urology in August 1990 with a gradually enlarging swelling in the right scrotum. On August 21, right high orchietomy was performed. This was diagnosed histologically as non-Hodgkin's lymphoma (diffuse large cell type), and the patient was transferred to our department on September 11 for further examination and treatment. As enlargement of the lymph nodes around the abdominal aorta was evident, it was diagnosed as stage IIA according to the Ann Arbor Classification. Beginning on September 21, three courses of COP-BLAM therapy (CPM, VCR, PDN, BLM, ADR, PCZ) were administered (the third course started on November 8) to achieve complete remission. Hepatic dysfunction appeared, however, from November 16, and by November 19, GOT and GPT increased to 6700 and 2120, respectively, with aggravation of jaundice. PDN therapy was instituted, and GOT and GPT improved gradually, but jaundice did not improve. On December 22, laparoscopy was performed, and liver biopsy produced histologic findings of drug-induced hepatitis. Further, lymphoblastic response was positive for CPM. Hepatic failure occurred on December 29, and plasma exchange was performed, but it failed to improve the condition, and the patient died on January 15. We described a case of non-Hodgkin's lymphoma complicated by hepatic dysfunction, probably induced by CPM, in an elderly patient who died to hepatic failure.

Aged

[Elderly non-Hodgkin's lymphoma presenting with pulmonary squamous cell carcinoma as a complication of chemotherapy for malignant lymphoma].

The authors report a case of pulmonary squamous cell carcinoma which occurred after chemotherapy of non-Hodgkin's lymphoma (NHL). A 76-year-old man, who was admitted to our department because of swelling of cervical lymph nodes, was diagnosed as having NHL (follicular mixed cell lymphoma). He was treated with 11 courses of CHOP therapy. Thereafter, chemotherapy including ifosfamide was carried out for approximately three years. In June, 1991, he was readmitted to our department because of swelling and pain in his left thigh and an abnormal shadow on chest X-ray. Chest CT demonstrated a cavitated shadow (about 5 cm in diameter) with an irregular margin in right S1, which was suggested to be lung cancer or pulmonary infiltration of malignant lymphoma. Bronchoscopy, which was carried out on July 12, showed bloody sputa from the right B1 ramus and markedly reddened mucosa at the orifice of the right upper bronchus. Sputum cytology revealed no malignancy. ACVP-16 chemotherapy including ara-C, CBDCA and VP-16 was initiated on July 14 because of enlarged superficial lymph nodes. On July 18, he fell out of bed and fractured his left femur. He also suffered from respiratory failure. He died of pulmonary haemorrhage on July 26. Autopsy revealed pulmonary squamous cell carcinoma. The occurrence of pulmonary squamous cell carcinoma is rare after the chemotherapy of malignant lymphoma.

Aged

Superselective intra-arterial infusion of papaverine for the treatment of cerebral vasospasm after subarachnoid hemorrhage.

This report describes the successful treatment of cerebral vasospasm after subarachnoid hemorrhage with superselective intra-arterial infusion of papaverine hydrochloride. Thirty-seven vascular territories in 10 patients with symptomatic vasospasm were treated according to the following protocol. Percutaneous transluminal angioplasty was performed in two steps. First, a silicone balloon was used for dilation of the internal carotid artery and the proximal portions of the middle cerebral artery. A silicone leak balloon or Tracker-18 catheter was then introduced into or just proximal to the site of vasospasm not accessible to the angioplasty balloon catheter for superselective infusion of 0.2% papaverine. Thirty-four of 37 vascular territories were successfully dilated, and eight of 10 patients showed improvement in neurological function after the procedure. There were no serious side effects due to infusion of papaverine. It is essential to infuse the papaverine just proximal to the spastic vessels in order to deliver sufficient concentration of drug, and infusion should be carried out as early as possible before the artery loses its ability to return to a normal luminal size. Superselective intraarterial infusion of papaverine is an alternative method of treatment for symptomatic vasospasm.

Adult

Changes of lysosomal proteinase activities and their expression in rat cultured keratinocytes during differentiation.

The cathepsins B, H and L, lysosomal cysteine proteinases, play a major role in intracellular protein degradation. These proteinase activities and expressions were examined in a Ca2+ regulated epidermal culture system which consists of two morphological cell types: undifferentiated cells grown in low Ca2+ (0.1 mM concentration) and differentiated cells grown in high Ca2+ (1.8 mM concentration), respectively. Cathepsin B and L activities of the differentiated cells showed a several-fold increase compared to that of the undifferentiated cells. In addition, by using CM-cellulose column chromatography, cathepsin B and L were separated and the level of cathepsin L activity increased significantly. Cathepsin B, L and H were also detected by using an immunoblotting procedure in which their bands were expressed after differentiation was induced by the increasing calcium concentration. Cathepsin L activity and immunostaining intensity reached a maximum at 1 or 2 days of differentiation. In contrast, cystatin alpha (an endogenous inhibitor of cysteine-dependent cathepsins) appeared in the final stage of differentiation. These results indicate that the expression of epidermal cathepsins and their endogenous inhibitor are involved in part of the program of cell differentiation and the terminal differentiation process in cultured rat keratinocytes.

Animals

26S multicatalytic proteinase complexes decrease during the differentiation of murine erythroleukemia cells.

Changes in multicatalytic proteinase activity during differentiation were investigated using Me2SO-induced differentiation of murine erythroleukemia cells as a model. The apparent ATP-dependent multicatalytic proteinase activity decreased in the Me2SO-treated cells with ATP-dependent incorporation of [3H]diisopropyl fluorophosphate decreasing notably after Me2SO-treatment. This decrease in activity does not seem to arise from a cessation of cell-proliferation, because no significant changes in proteinase activity were observed under different culture conditions. Hydroxyapatite column chromatography was employed to analyze the form of multicatalytic proteinase. It was clearly demonstrated that the 26S form of the proteinase decrease in the differentiated cells relative to normal cells. Multicatalytic proteinase-associated proteins that bind to the proteinase in an ATP-dependent manner were purified on an anti-multicatalytic proteinase IgG conjugated column. Only a small amount of protein was recovered from the differentiated cells. These results suggest that the decrease in multicatalytic proteinase-associated proteins that occurs upon cell-differentiation abolishes the ATP-dependent activity of the proteinase.

Animals

Effects of chlorpromazine on phosphatidylinositol turnover following thrombin stimulation of human platelets.

Thrombin stimulation of human platelets is known to result in phosphatidylinositol turnover (PI response), the activation of protein kinase C (C-kinase), and the release of arachidonic acid (AA). The authors studied the effects of chlorpromazine (CPZ) on these responses. At a concentration of 100 microM, CPZ inhibited the phosphorylation of 40,000-dalton protein through C-kinase activation. CPZ failed to inhibit initial transient synthesis of 1,2-diacylglycerol (1,2-DAG) through the PI response, although it slowed the concurrent decreasing process. CPZ inhibited promotion of compensatory synthesis of phosphatidylinositol 4,5-bisphosphate (PIP2), and also inhibited the synthesis of phosphatidic acid (PA). These results suggest that phosphatidylinositol 4-monophosphate kinase and diacylglycerol kinase (DAG-kinase) may be inhibited by CPZ. CPZ also intensified the accumulation of inositol phosphates caused by the PI response, indicating possible inhibition of the phosphatases that metabolize these phosphates. Thus, CPZ partially inhibited the PI response. However, it appears likely that the inhibition of C-kinase activity by CPZ was not due to inhibition of 1,2-DAG production nor to direct inhibition of phospholipase C. CPZ also inhibited AA release. This action might be partially a result of the inhibitory effect of CPZ on PA production.

Adult

[Effect of nizofenone on the symptomatic vasospasm after aneurysmal subarachnoid hemorrhage and its relationship to the levels of serum complements (CH50, C3 and C4)].

Serum complements (CH50, C3 and C4) after aneurysmal subarachnoid hemorrhage were measured in 42 patients over 2 to 3-week period. Nizofenone, an anti-vasospasmotic agent, was administered to 11 patients. In the nizofenone-treated group, 8 patients showed decreased serum C4 levels 5 days after the onset of subarachnoid hemorrhage, but among them, only 2 patients showed symptomatic vasospasm. Considering our previous data (majority of patients who showed decreased serum C4 levels presented with symptomatic vasospasm), these results suggest a favorable effect of nizofenone on the symptomatic vasospasm after aneurysmal subarachnoid hemorrhage.

Adult

Aminopeptidase A in human placenta and pregnant serum.

The activities of serum aminopeptidases (APs) derived from the placenta rise during pregnancy. To confirm the localization of AP-A, which liberates N-terminal acidic amino acids, in placental tissue and to identify it in the serum of pregnant women, chromatographic separation was performed. When a placental extract was subjected to DEAE cellulose column chromatography, the Glu-MCA degradative activity, or AP-A, was separated into two entities. Inhibition testing revealed that the enzyme eluted in Fraction No. 20 from the DEAE-cellulose column consisted of typical AP-A with a molecular weight of approximately 500,000. When the Glu-MCA degradative activity was observed by filtering pregnant serum through HPLC TSK G3000 gel, the activity was found to be due to serum CAP rather than AP-A. What had been thought to be a biochemicophysiological action inherent in blood AP-A raised additional questions.

Aminopeptidases

Identification of an elastase-like activity, that decreased during the differentiation of MEL cells, as a prolyl endopeptidase.

1. A Suc-APA-MCA hydrolytic activity was significantly decreased in murine erythroleukemia cells during DMSO-induced differentiation, but not in DMSO-resistant cells. 2. The Suc-APA-MCA hydrolytic enzyme was purified by ion exchange, adsorption, gel filtration and affinity chromotographies. The results of the chromatographies showed that only one enzyme hydrolyzed Suc-APA-MCA in MEL cells. 3. This enzyme is more sensitive to hydrolysis by Suc-GPLGP-MCA than Suc-APA-MCA at slightly acidic pH, and its activity is stimulated by 2-mercaptoethanol. 4. A cysteine proteinase inhibitor did not affect the activity, but a specific inhibitor of prolyl endopeptidase, Z-thioprothiazolidine, completely inhibited it. These results suggest that the Suc-APA-MCA hydrolytic enzyme is identical to a prolyl endopeptidase.

Amino Acid Sequence

Preservation of the C-terminus of dystrophin molecule in the skeletal muscle from Becker muscular dystrophy.

Duchenne muscular dystrophy (DMD) is a fatal X-linked recessive disorder of muscle in children. The DMD gene product, "dystrophin", is absent from DMD, while the allelic disease, Becker muscular dystrophy (BMD), exhibits dystrophin of abnormal size and/or quantity. But we are still uncertain about the scenario that internally deleted (or duplicated) dystrophin in BMD possesses its carboxy (C)-terminal region, and severely truncated dystrophin in DMD does not. Here we use a new monoclonal antibody directed against an peptide in the C-terminal end of the dystrophin molecule to show that the C-terminus is preserved in 30 BMD and 24 control skeletal muscles but not in 21 DMD specimens. This result, taken together with data on deletions of the dystrophin gene, emphasizes both the diagnostic and biological importance of the C-terminal domain which is required for proper function and stability of dystrophin, and substantiates the validity of the reading frame hypothesis for DMD versus BMD deletions on a biochemical level.

Amino Acid Sequence

A study of the effectiveness of the iron-chelating agent deferoxamine as vasospasm prophylaxis in a rabbit model of subarachnoid hemorrhage.

The pathogenesis of cerebral vasospasm occurring after subarachnoid hemorrhage (SAH) is unknown. Several lines of experimentation have suggested a free radical mechanism in the etiology of vasospasm. Iron is an important catalyst in the generation of free radicals and lipid peroxides in response to tissue injury. We hypothesize that the elaboration of iron from the subarachnoid clot might result in enhanced generation of free radicals and lipid peroxidation. If so, then treatment with deferoxamine, an iron-chelating compound, might reduce the formation of free radicals and thereby ameliorate vasospasm. This hypothesis was examined in a rabbit model of experimental cerebral vasospasm. New Zealand White rabbits were divided into the following experimental groups: control (normal) animals (n = 7), control animals treated with deferoxamine (n = 3), animals subjected to SAH and killed on Day 2 (n = 7), animals subjected to SAH on Day 2 and treated with deferoxamine (n = 9), animals subjected to SAH killed on Day 3 (n = 7), and animals subjected to SAH on Day 3 and treated with deferoxamine (n = 7). Deferoxamine treatment (50 mg/kg/8 hours) was begun 16 hours before the induction of SAH and continued until the animals were killed by perfusion fixation. The basilar artery caliber was assessed using morphometric techniques. The diameter of the basilar arteries in the control animals was 0.64 +/- 0.02 mm. Deferoxamine treatment alone did not alter the artery diameter.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals