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Biomedical subjects

M Asada

Publications and source records attributed to M Asada.

At least 109 records · Page 6Linked to original sources

Effects of single and repeated administration of prostaglandin F2 alpha on secretion of testosterone by male rats.

The effects of single and repeated administration of prostaglandin (PG) F2 alpha on the secretion of testosterone and the effect of PGF2 alpha on the action of human chorionic gonadotropin (hCG) were investigated in adult male rats. The concentrations of plasma and testicular testosterone followed by a single injection of 100 micrograms of PGF2 alpha into each testis were similar to controls given a single injection of 0.05 ml of vehicle into one testis. When 1 or 10 IU of hCG were injected into the jugular vein simultaneously with the intratesticular injection of PGF2 alpha, concentrations of testosterone increased in response to dose; again, the effect was similar in controls. When 100 micrograms of PGF2 alpha was injected into each testis daily for 5 days, plasma testosterone concentration decreased below that in the controls, but the LH concentration was unchanged. When 1 or 10 IU of hCG were injected into the jugular vein the day after the fifth injection of PGF2 alpha, concentrations of plasma and testicular testosterone increased in response to dose; the effect was similar in controls. These results indicate that repeated stimulation by PGF2 alpha directly inhibits testosterone production in the rat testis without mediation by LH, and that PGF2 alpha does not affect the action of an LH-like substance.

Animals↗

[Clinical results of selective cerebral perfusion during reconstruction of the transverse aortic arch].

Selective cerebral perfusion (SPC) has become a reliable method for brain protection during reconstruction of the transverse aortic arch. However, arterial cannulation technique for the branches of the aortic arch varies among groups, and the necessity of perfusion for the left subclavian artery is controversial. To avoid atheroembolism to the brain and malperfusion of the vertebral arterial system, we carefully selected the arterial cannulation technique according to the result of preoperative ultrasonographic and angiographic evaluation of the branches of the aortic arch, and decided the necessity of perfusion for the left subclavian artery according to the dominance of the two vertebral arteries and the result of pressure monitoring of all three branches. In this report, we analyzed our clinical results of selective cerebral perfusion on 22 consecutive patients, which was performed between April 1992 and December 1993. There were 14 atherosclerotic aneurysms and 8 aortic dissections. The flow rate for SCP was controlled by a single blood pump separate from that for systemic perfusion, with the mean value being 13.1 ml/kg/min. Mean of minimum left superficial temporal arterial pressure was 51 mmHg, mean duration of SCP was 134 minutes, and mean of the lowest esophageal temperature was 17.9 degrees C. Blood pH was regulated with alpha-stat strategy. Arterial cannula for SCP was inserted directly into the vessels through a stab wound in most cases. In three of four patients in whom dissection extended to the branches, a balloon catheter was introduced through the lumen of the aortic arch.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

[Myocardial metabolism, oxygen demand and oxygen supply during prostaglandin E1 induced hypotension].

The effects of hypotensive anesthesia induced by PGE1 on myocardial metabolism, oxygen demand and oxygen supply were studied. Nine mongrel dogs were anesthetized with pentobarbital and isoflurane. Mean blood pressure (MBP), cardiac output (CO), blood gases (BG), coronary blood flow (CBF), and myocardial tissue oxygen tension (MPO) were measured. Arterial and coronary venous lactate and pyruvate concentrations were also measured. We calculated myocardial oxygen consumption, L/P ratio, excess lactate, oxygen extraction ratio and lactate extraction ratio to estimate the adequacy of myocardial aerobic metabolism. CO and CBF decreased in accordance with MBP depression. Myocardial oxygen consumption decreased significantly with PGE1 administration. Lactate and pyruvate concentrations, L/P ratio, excess lactate and myocardial tissue oxygen tension were unchanged. These results suggest that PGE1 exerts no significant effect on myocardial metabolism during hypotensive anesthesia.

Alprostadil↗

[The effects of adenosine-induced hypotension on myocardial metabolism].

The effects of hypotension induced by adenosine on myocardial metabolism were studied in ten mongrel dogs anesthetized with 0.5% isoflurane. Adenosine was infused intravenously to reduce mean arterial blood pressure by approximately 30% during a period of 20 min. Although heart rate was unchanged, cardiac output increased and coronary blood flow increased 3-fold of the preinfusion value. Oxygen tension of the myocardium, and oxygen extraction as well as lactate extraction of the myocardium decreased. Myocardial oxygen uptake and myocardial lactate uptake were unchanged, but lactate production was observed in three of ten dogs. In addition, coronary venous lactate/pyruvate ratio and excess lactate increased, and excess lactate became positive in five of ten dogs. The results suggest that adenosine-induced hypotension may inhibit the myocardial aerobic metabolism.

Adenosine↗

Clonal expansion of p53 mutant cells in leukemia progression in vitro.

Using the polymerase chain reaction followed by single-strand conformation polymorphism (PCR-SSCP) analysis and direct nucleotide sequence determination, the p53 gene was analyzed in six fresh leukemia samples from which cell lines with p53 mutations were established. Mutations of the p53 gene which were identical to those in the cell lines were observed in three of the fresh samples. In the other three samples, p53 gene mutations were not detected by the conventional PCR-SSCP method. However, when analyzed using allele-specific gene amplification, less than 10% of the leukemic cell population of the three samples, which were below the detection threshold of PCR-SSCP, were shown to have p53 gene mutations. Two samples taken at the initial presentation of two patients, whose relapse samples were shown to contain p53 mutant clones, were also available for analysis. A small population of clonal cells, comprising less than 1% of the population, was shown to have p53 gene mutations in both of these initial samples. These observations provide a potential biologic basis for the frequent findings of p53 mutations in leukemia cell lines and also suggest a potential role for p53 mutations in the clonal overgrowth of cells responsible for relapse of the disease.

Acute Disease↗

[Effect of 10% carbon dioxide on regional myocardial tissue oxygen tension and myocardial metabolism].

We investigated the effects of arterial carbon dioxide tension on myocardial blood flow, tissue oxygen tension and metabolism in the anesthetized dogs. Eighteen adult mongrel dogs weighing 13.4 +/- 3.6 kg were anesthetized with 0.5% isoflurane, intubated and ventilated mechanically with 50% oxygen to maintain normocapnia. Endtidal CO2 fraction (FECO2) was monitored continuously by capnograph. Regional myocardial tissue PO2 was measured using a monopolar polarographic needle electrode inserted to the myocardium. Electromagnetic blood flow probes were applied on the left anterior descending artery and circumflex artery. For cardiac venous blood sampling, a 23G intravenous catheter was inserted into the cardiac veins (great coronary veins) carefully. After normocapnic ventilation, hypocapnia was induced by increasing the respiratory rate, and hypercapnia was induced by adding 10% carbon dioxide to the inspired gas. The coronary blood flow and myocardial tissue oxygen tension increased during hypercapnia and the myocardial lactate extraction decreased, while excess lactate and cardiac venous L/P ratio increased during hypercapnia. These results indicate that hypercapnia increase coronary flow and myocardial tissue oxygen tension but myocardial aerobic metabolism is impaired during hypercapnia.

Anesthesia, Inhalation↗

Combination of arachidonic acid and guanosine 5'-O-(3-thiotriphosphate) induce translocation of rac p21s to membrane and activation of NADPH oxidase in a cell-free system.

The superoxide-generating NADPH oxidase system in phagocytes consists of membrane-associated cytochrome b558 and three cytosolic components named p67-phox, p47-phox, and rac p21s. In a cell-free system consisting of membrane and cytosol, the oxidase can be activated with guanosine 5'-O-(3-thiotriphosphate) (GTP gamma S) and an unsaturated fatty acid such as arachidonic acid (AA). Incubation of cytosol and membrane with AA alone caused clear translocation of p47-phox and p67-phox to the membrane, but only slight translocation of rac p21s. GTP gamma S alone did not significantly induce the translocation of rac p21s. However, GTP gamma S in combination with AA markedly augmented rac p21s translocation to the membrane. The translocation of rac p21s is not induced by GDP or GDP beta S. These results indicate that the GTP-bound active form of rac p21s is the entity that is translocated to the membrane by the action of AA.

Amino Acid Sequence↗

Effects of pulsed lasers on agar model simulation of the arterial wall.

Coronary laser angioplasty is limited by a high rate of dissection and the occurrence of abrupt closure and perforation. The aim of this study was to visualize the mechanical effects of pulsed lasers on two chamber in vitro models. These models consisted of 1 or 2 agar layers and calcium carbonate inclusions (1-layer model) or lipid (2-layer model) simulating lipid or calcified tissue. The inclusions were irradiated with a holmium-yttrium-aluminum-garnet (Ho-YAG) laser or a xenon chloride excimer laser. The Ho-YAG laser demonstrated dissection-like expansions of the target and perforation-like cracks. The size of dissection was obtained using an the empirical formula of energy (E) and the maximal expansion distance (Dmax) of the targets, Dmax = 0.15E0,87-1,17. The excimer laser showed rare and short perforation-like cracks and little dissection-like expansion of the gaseous products originating from the ablation of material. Ho-YAG laser ablation is likely to induce target tissue dissections and/or perforations. Excimer laser-ablates targets with less traumatic effects than Ho-YAG laser.

Agar↗

Cerebral hyperperfusion during surgical resection of high-flow arteriovenous malformations.

Cerebral hemodynamics were evaluated in 16 patients with arteriovenous malformations (AVMs) using intraoperative thermogradient or laser Doppler flowmeter. The postexcision/preexcision blood flow ratio was determined. Two of seven patients with large AVMs (> or = 4 cm) developed a postoperative hematoma. Their flow ratios were larger than 1.9. In 4 patients with large AVMs, their blood flow ratios were reduced from an initial ratio exceeding 2.0 to less than 1.5 using carotid or special flow regulation clamps. These patients did not develop any hemorrhagic complication. In 9 patients of small AVMs (< 4 cm), the ratio was significantly low and there were no hemorrhagic complications.

Adolescent↗

Effects of Near-Ultraviolet Light on Alkaloid Production in Catharanthus roseus Plants.

Artificial near-ultraviolet light with a peak at 370 nm and the light of natural radiation with wavelengths between 290 and 380 nm stimulated the synthesis of dimeric indole alkaloids in intact plants of CATHARANTHUS ROSEUS. The artificial light also specifically stimulated an IN VITRO FMN-mediated, non-enzymatic coupling of vindoline and catharanthine to synthesize an iminium intermediate, the IN VIVO precursor of dimeric alkaloid synthesis. These results suggest that near-ultraviolet light is necessary for catharanthine oxidation as a trigger reaction of dimer synthesis in the plants.

Journal Article↗

Combination effect of navelbine (vinorelbine ditartrate) with cisplatin against murine P388 leukemia and human lung carcinoma xenografts in mice.

The in vivo combination effect of navelbine (NVB, KW-2307) plus cisplatin was compared with that of vindesine (VDS) plus cisplatin in terms of antitumor activity and side effects. The antitumor activity of NVB or cisplatin against i.p. inoculated P388 leukemia was augmented by their combination on various schedules when the interval of administrations was within 24 h. Against i.v. inoculated P388 leukemia, the most significant combination effect was observed when cisplatin was administered 4 h after NVB injection (ILS(%) > 451) and three long-term survivors were observed. On this schedule, the combination of LD10 of each drug was achieved, indicating the lack of addition of toxicity. This was further proved by examination of body weight change, white blood cell count and platelet count. Interestingly, significant elevation of blood urea nitrogen concentration by cisplatin was prevented by the combination with NVB. The combination of maximum tolerated dose of NVB and cisplatin was also tolerable in nude mice, and their combination effect was observed against human lung large cell carcinoma Lu-65 and adenocarcinoma PC-12. The number of toxic death mice was more in VDS plus cisplatin-treated groups than in NVB plus cisplatin-treated groups, indicating that the combination chemotherapy of NVB plus cisplatin is a better regimen than that of VDS plus cisplatin in experimental tumor systems.

Animals↗

Epstein-Barr virus-infected T lymphocytes in Epstein-Barr virus-associated hemophagocytic syndrome.

The clonal composition of EBV-infected cells was examined in three cases of EBV-associated hemophagocytic syndrome by analysis of the heterogeneity of terminal repetitive sequences in the EBV genome, indicating monoclonal expansion of EBV-infected cells in all cases. Involvement of T lymphoid cells was determined by in situ hybridization using 35S-labeled RNA probes specific for the small EBV-encoded nuclear RNAs, EBER1 and EBER2, in combination with immunostaining for the TCR-beta chain, CD45RO, CD20, CD30 and CD68 antigens in these three cases. The majority of lymphoid cells showing EBER transcripts were stained by antibodies against CD45RO and T cell receptor-beta. In contrast, EBER-specific signals were not detectable on B cells or hemophagocytic cells. These data support the concept that EBV-associated T cell proliferation is a primary feature of EBV-AHS.

Adolescent↗

Solid basal cell epithelioma (BCE) possibly originates from the outer root sheath of the hair follicle.

The presence and distribution of several cytokeratins (CKs) in 20 solid basal cell epitheliomas (BCEs) were investigated and compared with the pattern of CKs in normal epidermis, perilesional skin and in the outer root sheath (ORS) of the human hair follicle. Tissue samples were stained with monoclonal antibodies (MoAbs) against human CKs, using the APAAP technique. Additionally, CK profiles were assessed by gel electrophoresis and immunoblot technique. Cells of BCE and ORS were positively stained with the MoAb KL1, whereas the basal layer of normal epidermis remained negative. Six out of 20 BCEs were partially stained with the MoAb RPN1165, which also stained the lower ORS, but not the epidermal basal layer. Using SDS-PAGE and immunoblot, the CK profiles of BCE and ORS were almost identical, showing the presence of CKs 5, 6, 14, 16 and 17; the CK pattern of normal epidermis, however, showed the presence of CKs 1, 5, 10 and 14. Perilesional skin (< 5 mm) showed keratin changes similar to the BCE pattern; the basal layer was stained with the MoAb KL1 and the suprabasal layer was negative to MoAb CK1, in contrast to normal epidermis. Keratin analysis revealed a CK pattern of perilesional skin different from that of normal epidermis (CKs 1, 5, 6, 10, 14, 16 and 17). Our immunohistochemical and biochemical investigations underline the possible role of the lower ORS as a cellular pool for the generation of BCE.

Antibodies, Monoclonal↗

Analysis of the target cell for Epstein-Barr virus infection in Epstein-Barr virus associated hemophagocytic syndrome (EBV-AHS).

Epstein-Barr virus (EBV) infected cells were examined in three cases of EBV-associated hemophagocytic syndrome (EBV-AHS) by analysis of the heterogeneity of terminal repetitive sequences in the EBV genome, indicating monoclonal expansion of EBV-infected cells in all cases. Involvement of T lymphoid cells was determined by the finding of in situ hybridization using [35S]-labeled RNA probes specific for the small EBV-encoded nuclear RNAs, EBER1 and EBER2, in combination with immunostaining for the TCR-beta chain, CD45RO, CD20, CD30 and CD68 antigens in these three cases. The majority of lymphoid cells showing EBER transcripts were stained by antibodies against CD45RO and TCR-beta. In contrast, EBER-specific signals were not detectable on B cells or hemophagocytic cells. These data support the concept that subclinical EBV-associated T cell proliferation is the primary characteristic of EBV-AHS, rather than proliferations of hemophagocytosing histiocytes.

Adolescent↗

[Risk factors for severe subarachnoid hemorrhage following aneurysmal rupture].

Major reduction in disability and death from severe subarachnoid hemorrhage (SAH) can probably be brought about more effectively by prevention than by better medical or surgical treatment. Identification of the major risk factors for severe SAH should facilitate the preventive efforts. As risk factors for severe SAH, a patient's age, sex, location and size of aneurysms, hypertension, rebleeding including minor leak, and cigarette smoking were selected. The relation between the incidence of severe SAH, a surgical results, and the risk factors was examined in 81 severe SAH cases. Hypertension, rebleeding from aneurysms, large aneurysm exceeding 1.0 cm/sec in size were closely connected to severe SAH. Treatment of hypertension, acute surgery for aneurysms and aggressive surgery for unruptured large aneurysms were the only hope for achieving substantial reduction in the incidence of severe SAH and for improving the surgical results.

Adolescent↗

[Antitumor activity of navelbine (vinorelbine ditartrate), a new vinca alkaloid analog].

The antitumor activity of navelbine (vinorelbine ditartrate, KW-2307) against murine and human transplantable tumors was compared with those of other vinca alkaloids, vindesine (VDS), vincristine (VCR) or vinblastine (VLB). KW-2307 and VDS increased the life span of mice bearing ascitic tumors (P 388 leukemia, L 1210 leukemia, EL-4 lymphoma, Colon 26, FM 3 A mammary carcinoma and M 5076 sarcoma) slightly more than VCR or VLB. A significant difference was not found in the antitumor activities against 6 murine solid tumors (B 16 melanoma, Colon 26, FM 3 A mammary carcinoma, Lewis lung carcinoma, M 5076 sarcoma and Sarcoma 180). However, a remarkable difference was observed in the antitumor activities against 11 human tumors inoculated into nude mice. The activity of KW-2307 was more than those of other 3 drugs against 4 human non-small cell lung carcinomas (Lu-65, Lu-99, LC-6 and L-27) and 2 stomach carcinomas (St-4 and St-40). KW-2307 and VDS were also effective in inhibiting the growth of 2 human breast carcinomas (MX-1 and Br-10).

Animals↗

Molecular diversification of dominant subclones in vivo and in vitro in Ph-positive ALL.

A leukemia line KOPN30bi was established from a patient with acute lymphocytic leukemia (ALL) and Philadelphia (Ph) chromosome. The clonal rearrangement of the immunoglobulin heavy chain (IgH) gene and the expression of the P190 type BCR/ABL chimeric transcript were shown to be identical between KOPN30bi and the predominant clone (S1) in the blast cell population from which KOPN30bi was established, indicating that they are of the same clonal origin. Studies of the T-cell antigen receptor (TCR) gene configuration including the TCR beta, gamma, and delta loci showed that none of them was identical between KOPN30bi and S1. The TCR delta region was rearranged on both of the alleles in KOPN30bi and was deleted on both alleles in S1 indicating that KOPN30bi was not derived from S1. Polymerase chain reaction analysis, using an oligonucleotide probe corresponding to the N region sequence of the V gamma-J gamma juncture of KOPN30bi, indicated that only 0.1% of the blast cells corresponded to KOPN30bi. Thus molecular diversification of dominant subclones in vivo and in vitro was shown in Ph-positive ALL.

Base Sequence↗

Post-translational processing of rac p21s is important both for their interaction with the GDP/GTP exchange proteins and for their activation of NADPH oxidase.

rac1 and rac2 p21s are ras p21-like small GTP-binding proteins which are implicated in the NADPH oxidase-catalyzed superoxide generation in phagocytes. rac1 and rac2 p21s have a Cys-A-A-Leu (A = aliphatic amino acid) structure in their C-terminal region which may undergo post-translational processing including prenylation, proteolysis, and carboxyl methylation. We studied the function of this post-translational processing of rac p21s in their interaction with the stimulatory and inhibitory GDP/GTP exchange proteins for rac p21s, named smg GDS and rho GDI, and in their NADPH oxidase activation. We produced human recombinant rac1 and rac2 p21s in insect cells and purified them from the membrane and soluble fractions as the post-translationally processed and unprocessed forms, respectively. Post-translationally processed rac1 and rac2 p21s were sensitive to both smg GDS and rho GDI, but post-translationally unprocessed rac1 and rac2 p21s were insensitive to them. The GTP gamma S (guanosine 5'-(3-O-thio)triphosphate)-bound form of post-translationally processed rac1 and rac2 p21s stimulated the NADPH oxidase activity, but post-translationally unprocessed rac1 and rac2 p21s were far less effective. These results indicate that both rac1 and rac2 p21s stimulate the NADPH oxidase activity and that their post-translational processing is important not only for their interaction with smg GDS and rho GDI but also for their NADPH oxidase activation.

Amino Acid Sequence↗