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Biomedical subjects

M Asano

Publications and source records attributed to M Asano.

At least 235 records · Page 13Linked to original sources

Sequential involvement of NK cells and CD8+ T cells in granuloma formation of Rhodococcus aurantiacus-infected mice.

We investigated the effect of in vivo administration of antibodies against T-cell subsets and natural killer (NK) cells on endogenous gamma interferon (IFN-gamma) production and granuloma formation in Rhodococcus aurantiacus-infected mice. High titers of endogenous IFN-gamma were detected in the extracts of the livers and spleens during 24 hr of the infection, reaching the peak at 8 hr, and the IFN-gamma production was reduced by in vivo administration of anti-NK 1.1 monoclonal antibody (MAb) or antibody against asialo GM1+ cells. Endogenous IFN-gamma declined until 2 days of the infection, then reappeared from 1 week and peaked at 3 weeks. Endogenous IFN-gamma at 1 and 3 weeks was reduced by in vivo administration of anti-CD8 MAb, but not by anti-CD4 MAb or anti-NK 1.1 MAb. Granulomatous lesions in the livers and spleens began to appear from 1 week of the infection and developed in 3 weeks. In vivo administration of rat anti-IFN-gamma MAb reduced the development of granulomas. In addition, granuloma formation was reduced by depletion of NK cells prior to the infection or depletion of CD8+ T cells at 1 week of the infection. Based on these findings, it is presumed that the biphasic production of IFN-gamma is attributable to NK cells in the early phase of the infection and CD8+ T cells in the phase of granuloma formation, and that granuloma formation is regulated by NK cells and CD8+ T cells through the secretion of endogenous IFN-gamma.

Actinomycetales Infections↗

The accuracy of references in Anaesthesia.

We reviewed all the references quoted in Volume 45 (1990) (n = 3967) and half the references quoted in Volume 49 (1994) (n = 2183) of Anaesthesia. The references were numbered sequentially and 100 references from each year were randomly selected. Citations of non-journal articles were omitted leaving 197 citations for careful scrutiny. The authors' names, article title, journal title, volume number, page numbers, and year were examined in each selected reference. A reference was deemed correct if each element of the citation was identical to its source. Of the references examined, 32% and 41% contained one or more errors in 1990 and 1994, respectively. The elements most likely to be inaccurate were, in descending order of frequency, article title, author, and page number. There was no significant difference in the error rate between the 2 years. It is the responsibility of contributors to ensure that all references are carefully checked.

Anesthesia↗

The accuracy of reference lists in Acta Anaesthesiologica Scandinavica.

To determine the accuracy of bibliographic citation in Acta Anaesthesiologica Scandinavica, we reviewed all 1990 volumes and part of 1994 volumes of the journal and sequentially numbered all references appearing in those years (n = 2701 and 2158 in 1990 (No. 1-No. 8) and 1994 (No. 1-No.5), respectively). We randomly selected 100 references from each year. After citations of nonjournal articles were excluded, the remaining 195 citations were carefully scrutinized. Authors' names, article title, journal title, volume number, page numbers, and year were examined in each selected reference. A reference was deemed correct if each element of the citation was identical to its source. Of the examined references, 40% and 45% contained one or more errors in 1990 and 1994, respectively. The elements most likely to be inaccurate were, in descending order of frequency, article title, author, and page number. No significant differences existed in the error rate between the two years. We have found many citation errors in the reference lists of Acta Anaesthesiologica Scandinavica and no improvement in these latest four years. All contributors to Acta Anaesthesiologica Scandinavica should thoroughly check the accuracy of reference lists.

Anesthesiology↗

Increased Ca2+ influx in the resting state maintains the myogenic tone and activates charybdotoxin-sensitive K+ channels in femoral arteries from young SHR.

1. To determine the possible role of voltage-dependent Ca2+ channels (VDCC) and Ca2+-activated K+ (KCa) channels in the regulation of resting tone of arteries from young spontaneously hypertensive rats (SHR), mechanical responses to the agents which interact with these channels were examined in endothelium-denuded strips of femoral arteries from 4 week old SHR and age-matched normotensive Wistar-Kyoto (WKY) rats. Systolic blood pressures at this age were not significantly different between SHR and WKY. 2. The strips from SHR, but not from WKY, maintained a myogenic tone; that is, the resting tone decreased when nifedipine was added. 3. Studies using 1 or 5 min pulse labelling of the strips with 45Ca showed that the basal Ca2+ influx was increased in SHR when compared with WKY, and this increase in SHR was abolished by nifedipine. Similar results were obtained when the cytoplasmic Ca2+ concentration ([Ca2+]i) in the resting state of the strips was measured by fura-PE3. 4. The addition of charybdotoxin (ChTX, a blocker of large conductance KCa channels) to the resting state caused a concentration-dependent contraction, which was much greater in SHR than in WKY. The ChTX-induced contraction in SHR was abolished by nifedipine. 5. In strips preloaded with 86Rb, the basal 86Rb efflux rate constant was significantly greater in SHR than in WKY. The increase in 86Rb efflux in SHR was abolished by nifedipine. 6. The results suggest that the Ca2+ influx via L-type VDCC was increased in the resting state of the femoral artery from 4 week old SHR, and therefore the myogenic tone was maintained and ChTX-sensitive K+ channels were highly activated.

Animals↗

Effect of barnidipine on blood flow to major organs and renal function in anaesthetized dogs and spontaneously hypertensive rats.

1. The effects of barnidipine on blood flow to major organs and on renal function were investigated in anaesthetized dogs and conscious spontaneously hypertensive rats (SHR), and the results were compared with those for nicardipine, nitrendipine, nisoldipine, manidipine and amlodipine. 2. In anaesthetized dogs, barnidipine (0.3-3 mu g/kg i.v.) dose-dependently decreased blood pressure and increased or preserved blood flow in the vertebral, coronary, femoral and renal arteries. The effect of barnidipine on blood flow was the most potent of the compounds tested. In conscious SHR, barnidipine (0.3-3 mg/kg p.o.) produced a dose-dependent antihypertensive effect and decreased renal vascular resistance. Barnidipine also dose-dependently increased urinary volume. The antihypertensive and diuretic effects of barnidipine were the most potent of the drugs tested. 3. In summary, barnidipine was shown to preserve or increase blood flow to major organs and to produce diuretic activity with a decrease in blood pressure. These findings suggest that barnidipine maintains or promotes renal function at antihypertensive doses.

Anesthesia↗

A monoclonal antibody against T-cell receptor alpha beta induces endogenous cytokines and prevents mice from a lethal infection with Listeria monocytogenes.

In vivo induction of cytokines by a monoclonal antibody (mAb) against T-cell receptor (TCR) alpha beta and the protective effect induced by the mAb on a lethal infection with Listeria monocytogenes were studied. Injection of anti-TCR alpha beta mAb induced rapid production of endogenous tumour necrosis factor in the spleens, and gamma interferon and interleukin-6 in the blood streams and spleens of mice. Administration of anti-CD4 mAb, anti-CD8 mAb, or anti-Thy1.2 mAb resulted in suppression of anti-TCR alpha beta mAb-induced endogenous cytokine production. Mice were protected against lethal L. monocytogenes infection when treated with anti-TCR alpha beta mAb. The protective effect was not demonstrated in CD4+ cell- or CD8+ cell-depleted mice. These results suggest that anti-TCR alpha beta mAb shows a protective effect on a lethal infection with L. monocytogenes in mice and that the mAb-induced endogenous cytokines might be involved in the effect of anti-TCR alpha beta mAb.

Animals↗

DNA gyrase mutations in quinolone-resistant clinical isolates of Neisseria gonorrhoeae.

Eight quinolone-resistant clinical isolates of Neisseria gonorrhoeae were shown to carry mutations in their GyrA proteins. Six isolates had a single amino acid change of serine to phenylalanine at the position corresponding to Ser-83 in Escherichia coli. In addition to the change of serine to phenylalanine, two isolates had another change of aspartic acid to asparagine at the position corresponding to Asp-87 in E. coli.

Amino Acid Sequence↗

Endogenous gamma interferon, tumor necrosis factor, and interleukin-6 in Staphylococcus aureus infection in mice.

The production and roles of endogenous gamma interferon (IFN-gamma), tumor necrosis factor (TNF), and interleukin-6 (IL-6) in both lethal and nonlethal infections of Staphylococcus aureus were investigated in mice. In the case of nonlethal infection, although no bacteria were detected in the bloodstreams, bacteria that colonized and proliferated persistently for 3 weeks were found in the kidneys. All mice given lethal injections died within 7 days, and large numbers of bacteria were detected in the bloodstreams, spleens, and kidneys. The first peaks of IFN-gamma, TNF, and IL-6 were observed in the bloodstreams and spleens of the mice with nonlethal and lethal infections within 24 h. Thereafter, in the nonlethal cases, IFN-gamma, TNF, and IL-6 peaked again in the spleens and kidneys during the period of maximum growth of bacteria in the kidneys, although only IL-6 was detected in the sera. In contrast, in the case of lethal infection, the titers of IFN-gamma and IL-6 in the sera and TNF in the kidneys peaked before death. Effects of in vivo administration of monoclonal antibodies (MAbs) against IFN-gamma and TNF on the fates of S. aureus-infected mice were studied. In the nonlethal infections, anti-TNF alpha (anti-TNF-alpha) MAb-treated mice, but not anti-IFN-gamma MAb-treated mice, died as a result of worsening infection, suggesting that endogenous TNF plays a protective role in host resistance to S. aureus infection. In the mice that received lethal doses, injection of anti-TNF-alpha MAb accelerated death. However, although injection of anti-IFN-gamma MAb inhibited host resistance of the infected mice early in infection, most of the animals survived the lethal infection by injection of anti-IFN-gamma MAb, suggesting that endogenous IFN-gamma plays a detrimental role in S. aureus infection. Thus, this study demonstrated that IFN-gamma and TNF play different roles in S. aureus infection.

Animals↗

Efficacy of Ibudilast on lower limb circulation of diabetic patients with minimally impaired baseline flow: a study using color Doppler ultrasonography and laser Doppler flowmetry.

Ibudilast is a prostacyclin-mediated vasodilator and antiplatelet agent. The hemodynamic effects of ibudilast were evaluated in 41 patients with non-insulin-dependent diabetes mellitus by means of two-dimensional Doppler ultrasonography and laser Doppler blood flowmetry. Before and one hour after oral administration of ibudilast (10 mg), or elastase (1800 U) as a control, the cross-sectional area (CSA) of the dorsal pedis artery, its blood flow index (BFI), and dermal microcirculatory blood volume (MBV) were measured. In the ibudilast group, all of the parameters (CSA, BFI, and MBV) significantly increased as compared with the elastase group. These data suggest that ibudilast is effective in ameliorating diabetic macroangiopathy and microangiopathy of the lower limbs.

Administration, Oral↗

[Discovery and development of tamsulosin hydrochloride, a new alpha 1-adrenoceptor antagonist].

Benign prostatic hyperplasia (BPH) is an age-related disorder characterized by urinary outlet obstruction. This obstruction is due to both mechanical compression of the urethra by the hypertrophied prostate and to functional contraction of the prostate and urethra by sympathetic stimulation. We invented a novel compound tamsulosin hydrochloride, a sulphamoylphenethylamine derivative which possesses potent and selective alpha a-antagonism, and showed that this compound selectively reduced the intra-urethral pressure in the prostatic segment of the urethra in vivo. We also found that the alpha 1-adrenoceptor plays an important functional role in the prostate and urethra. For clinical use, a control release formulation was developed. This formulation did not induce orthostatic hypotension and could be administered at a fixed dose. A placebo-controlled double-blind dose finding study resulted in 0.2 mg/d as the optimal dose. This formulation significantly improved urinary outlet obstruction without affecting blood pressure as compared with placebo in P-III study, and was approved in 1993 for use in the treatment of bladder outlet obstruction associated with BPH. Tamsulosin hydrochloride is the first alpha 1-antagonist which improves bladder outlet obstruction associated with BPH without affecting blood pressure, and the treatment can be initiated and maintained at a fixed dose. Recently, the alpha 1-adrenoceptor subtypes alpha 1A, alpha 1B and alpha 1C were identified. The alpha 1C subtype is predominant and plays an important role in the human prostate. Tamsulosin hydrochloride shows high selectivity for this subtype, further supporting the clinical findings that tamsulosin hydrochloride improves bladder outlet obstruction associated with BPH with no effect on the cardiovascular system.

Adrenergic alpha-Antagonists↗

Production and characterization of keratinase of a feather-degrading Bacillus licheniformis PWD-1.

The keratinase produced by Bacillus licheniformis PWD-1 was induced by feather powder. Maximal enzyme production could be achieved by culturing in a medium containing 1% hammer-milled feather powder (100 mesh) at 45 degrees C for 30 h. Maximal growth of PWD-1 was achieved at 50 degrees C, and maximal enzyme induction was at 45 degrees C. The molecular mass and isoelectric point of this enzyme were 31.4 kDa and 8.5, respectively. This enzyme was stable from pH 5 to 12. The optimal reaction pHs for feather powder and casein were 8.5 and 10.5 to 11.5, respectively. The optimal reaction temperature was 50 degrees C to 55 degrees C. The relative activity of this enzyme toward casein, feather powder, keratin, elastin, and collagen was 100:52:41:18:7, and 100:56:32:3 for Suc-AAPL-pNA, Suc-AAPF-pNA, Suc-AAPM-pNA, and Suc-AAVA-pNA (Suc, succinyl; pNA, p-nitrophenylanilide).

Amino Acid Sequence↗

Increased function of voltage-dependent Ca++ channels and Ca(++)-activated K+ channels in resting state of femoral arteries from spontaneously hypertensive rats at prehypertensive stage.

The present study examined the possible role of voltage-dependent Ca++ channels (VDCs) and Ca(++)-activated K+ (KCa) channels in the regulation of resting tone of arteries from spontaneously hypertensive rats (SHR) at a prehypertensive stage. Differences in the effects of agents that interact with these channels were assessed in endothelium-denuded strips of femoral arteries isolated from 4-week-old SHR and age-matched normotensive Wistar-Kyoto rats (WKY). Systolic blood pressures at this age were not significantly different between SHR and WKY. The arterial strips from SHR maintained a myogenic tone in the resting state; that is the resting tone in the SHR artery was abolished when either the bathing solution was replaced with a Ca(++)-free solution or 10(-7) M nifedipine was added. Studies using 1- or 5-min pulse labeling of the arteries with 45Ca showed that the resting Ca++ influx was significantly increased in SHR when compared with WKY, and this increase in SHR was abolished by 10(-7) M nifedipine. In strips preloaded with fura-PE3, the addition of 3 x 10(-6) M verapamil to resting muscles decreased the resting cytosolic Ca++ level and caused a relaxation. These effects of verapamil were more evident in SHR than in WKY. The addition to the strips of charybdotoxin and iberiotoxin, blockers of large conductance KCa channels, caused a concentration-dependent contraction, which was significantly greater in SHR than in WKY.(ABSTRACT TRUNCATED AT 250 WORDS)

3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethy↗

[An operative case of the dumbbell type retromediastinal schwannoma].

Neurogenic tumors of the mediastinum with an intraspinal component connected by a narrowed segment in the intervertebral one are generally described as dumbbell or hour-glass tumors, which need cautious and precise diagnoses and remedies, compared with other neurological tumors. A 62-year-old male was admitted to our hospital for abnormal tumor shadow in the chest X-ray film. We diagnosed this case as dumbbell type neurogenic tumor by MRI and CT. An operation was performed by modified Grillo's method: One-stage operation. With patient in prone position, L-shaped skin incision was made. Through total laminectomy of T-5 and T-6 and resection of the 6th rib, paravertebral portion of the tumor was removed, and thoracotomy in the same position under the same view enabled us to remove the residual tumor. Histopathological diagnosis was schwannoma. After the operation, no neurological complications were detected.

Humans↗

[A case report of prostate cancer resistant to endocrine therapy successfully treated with intra-arterial chemotherapy].

A 73-year-old male with low abdominal pain on urination and frequent urination was diagnosed as poorly differentiated adenocarcinoma of prostate. He received endocrine therapy with DESD and bilateral orchiectomy. This treatment was not effective, so he was given intra-arterial infusion chemotherapy with MTX, ADM and CDDP using the reservoir system. After 2 courses of this chemotherapy the regression rate was 75%, and the pathological examination after the chemotherapy revealed no cancer cells. There is no established chemotherapy for prostate cancer at present. Thus this case is very suggestive for the treatment of prostate cancer.

Adenocarcinoma↗

Mitochondrial gene mutations that affect the binding of the termination factor and their prevalence among Japanese diabetes mellitus.

An A-to-G mutation at np3243 in tRNA(Leu) (UUR) gene of the mitochondrial DNA has been described to associate with diabetes mellitus. This exists within the sequence that is important for binding termination factor, which ends the transcription of one of the two major transcripts. We investigated the prevalence of this mutation in randomly selected 276 NIDDM+ 24 IGT, 94 IDDM, and 115 non-diabetic control subjects. The mutation was also reported to exist frequently in slowly progressive IDDM. We recruited 116 juvenile onset autoimmune Type 1 diabetes and 154 autoimmune thyroid diseases to see if this mutation is involved in autoimmunity. We identified this mutation in 3 of 300 NIDDM+IGT (1%). None from IDDM or control group, nor from autoimmune disease group had this mutation. The patients with this mutation did not have cerebro-muscular symptoms as were observed in MELAS. One patient had only slight glucose intolerance indicating diabetes with this mutation may have various phenotypes. Genetic area around tRNA(Leu) (UUR) is a hot spot for pathological mutations. We directly sequenced this area of mtDNA from diabetes and identified a new polymorphism in ND-1 gene, which is situated downstream of tRNALeu (UUR) gene. We screened 154 IDDM and 254 NIDDM+ IGT patients, and identified it in 3 NIDDM and 2 IGT subjects. Both of the NIDDM patients had bilateral hearing impairment. None from 207 non-diabetic control subjects and IDDM were positive for this mutation. Its prevalence was a little more than that of an A-G mutation at np3243.

Case-Control Studies↗

IL-2 can support growth of CD8+ T cells but not CD4+ T cells of human IL-2 receptor beta-chain transgenic mice.

We have generated transgenic mice expressing the human (h) IL-2R beta-chain on lymphoid cells under the control of the mouse H-2Kd promoter. Spleen cells and thymocytes of the transgenic mice were cultured in the presence of 5 nM hIL-2. After a 10-day culture, the expanded populations were analyzed by flow cytometry and shown to be composed of CD8+ T cells and gamma delta T cells. Surprisingly, CD4+ T cells of the transgenic mice did not proliferate in response to hIL-2, although the CD4+ T cells expressed the transgenic hIL-2R beta-chain as well as the endogenous gamma-chain on their surface and bound 125I-labeled IL-2. When CD4+ T cells of the transgenic mice were stimulated with anti-CD3 mAb, the CD4+ T cells proliferated in response to hIL-2. These findings suggest that CD4+ T cells may require another triggering signal to respond to IL-2 even when IL-2Rs are expressed. By contrast, CD8+ T cells and gamma delta T cells respond to IL-2 as long as IL-2Rs are expressed.

Animals↗

Effects of 15-deoxyspergualin in vitro and in vivo on cytokine gene expression.

Reverse transcriptase-polymerase chain reaction showed that interleukin 3, IL-4, IL-5, IL-6, interferon-gamma and stem cell factor mRNA expression were higher in 15-deoxyspergualin-treated spleen cells than in control spleen cells. Increased IL-2 and IFN-gamma mRNA expression were observed in 15-deoxyspergualin-treated bone marrow cells. On the other hand, increased platelet counts in BALB/c-->C3H/He bone marrow chimeras were observed from days 20 to 33 in our previous work, when they were treated with 15-deoxyspergualin from days 14 to 25. In contrast, marked leukocytopenia and anemia were simultaneously observed, although a marked leukocytosis and a rapid recovery of anemia were observed on day 33 and thereafter. To analyze effects of 15-deoxyspergualin on hematopoiesis and the immune system, we examined mRNA expression in bone marrow and spleen cells from BALB/c-->C3H/He bone marrow chimeras treated with 15-deoxyspergualin from days 14 to 25. Reverse transcriptase-polymerase chain reaction showed that IL-3, IL-4, IL-6, stem cell factor, granulocyte colony-stimulating factor, and granulocyte/macrophage colony-stimulating factor mRNA expression were higher in 15-deoxyspergualin-treated chimeras than in control chimeras, indicating that these cytokines are responsible for an enhancement of hematopoiesis. It was conceivable that IL-6 supported thrombopoiesis in concert with other cytokines. On the contrary, increased IFN-gamma, IL-2, IL-3, IL-4, and IL-10 mRNA expression may play an immunosuppressive role in vivo.

Actins↗