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Biomedical subjects

M Yoshida

Publications and source records attributed to M Yoshida.

At least 1,207 records · Page 67Linked to original sources

[Comparative study on the efficacy of ritipenem acoxil and cefotiam hexetil in chronic lower respiratory tract infections by the double-blind method].

To objectively evaluate the efficacy, safety and usefulness of the newly developed penem oral antibiotic, ritipenem acoxil (RIPM-AC), against chronic lower respiratory tract infections, we conducted a multi-center double-blind comparative study using cefotiam hexetil (CTM-HE) as a control drug. RIPM-AC was orally administered at 200 mg, and CTM-HE at 400 mg, t.i.d. for 14 days, in principle. The results were as follows: The total number of patients enrolled in this trial was 202, of which 151 cases (RIPM-AC group: 75, CTM-HE group: 76) were evaluable for clinical efficacy. 1. The clinical efficacy rates (excellent+good) were 85.3% (64/75) in the RIPM-AC group and 80.3% (61/76) in the CTM-HE group. There was no significant difference between the two groups, hence the clinical equivalency of RIPM-AC to CTM-HE was demonstrated. 2. In the patients enrolled in the evaluation of clinical efficacy, the eradication rates of the causative organisms were 50.0% (13/26) in the RIPM-AC group and 75.0% (18/24) in the CTM-HE group, with no significant difference between the two groups. 3. Side effects were noted in 10 cases (11.0%) of the RIPM-AC group and 10 cases (10.9%) of the CTM-HE group. Abnormal laboratory test findings were observed in 8 cases(9.5%) of the RIPM-AC group and in 14 cases (16.7%) of the CTM-HE group. There were no significant differences between the two groups in the incidence of side effects and abnormal laboratory test findings. In the safety evaluation, RIPM-AC was judged to be safe in 73 cases (80.2%) and CTM-HE in 71 cases (77.2%), with no significant difference. 4. The usefulness rates (markedly useful+useful) were 79.5% (62/78) in the RIPM-AC group and 76.9% (60/78) in the CTM-HE group. There was no significant difference between the two groups. Since RIPM-AC showed clinical efficacy similar to those of CTM-HE and posed no particular safety problems, it is expected to be a useful antibiotic for the treatment of chronic lower respiratory tract infections.

Adult↗

[Microcirculatory disturbances after surgical insults--important role of inflammatory cytokines].

Microcirculatory disturbances in the gastric mucosa was investigated in rats after thermal injury using intravital video microscopy. Mucosal blood flow decreased significantly 5 hrs after thermal injury and increased neutrophil-endothelial cell interaction was observed at the same time. Zymosan stimulated-free radical production from peripheral blood was also increased and acute gastric mucosal lesion (AGML) appeared 5 hrs after thermal injury. These data suggest that neutrophil-endothelial cell interaction and increased free radical production induce AGML formation and that microcirculatory disturbance is one of the main reasons for organ failure after surgical insults. The role of inflammatory cytokines in hepatic microcirculatory disturbance was also studied in endotoxin-injected rats using IL-1 receptor antagonist (IL-1Ra) or TNF binding protein (TNFbp). Pretreatment with IL-1Ra or TNFbp significantly improved hepatic microcirculatory disturbance and reduced both the number of leukocytes adhered to the sinusoidal wall and the number of injured cells as well. These data suggest that inflammatory cytokines play a crucial role in microcirculatory disturbance after surgical insults by promoting neutrophil-endothelial cell interaction and systemic excessive inflammation.

Animals↗

[Early esophageal cancer--concept, diagnosis and treatment].

In spite of the conventional definition of early esophageal cancer which includes mucosal and submucosal cancers without lymph node metastasis, esophageal mucosal cancers are now considered as the early cancer in clinical field. The esophageal mucosal cancers are subclassified into m1 (intraepithelial cancer), m2(lamina propria mucosae) and m3(muscularis mucosae) in clinical view points. M1 and m2 esophageal cancers which had no lymph node metastasis could be treated completely by endoscopic mucosal resection. On the other hand, the patients with m3 cancer which showed lymph node metastasis in 10% of the cases should be treated by esophagectomy with lymph node dissection. For the diagnosis of the depth of carcinoma invasion, now, endoscopy with dye iodine stain and toluisine blue stain were most useful. Fundamentally, macroscopic appearance of lesions classified by Japanese Society for Esophageal Diseases are well related to the depth of invasion. Almost all mucosal cancers showed the superficial and flat type (0-IIc type). Subclassification of m1, m2 and m3 were easily differentiated by endoscopic observation of their characteristic appearances. In the evaluation of the methods of treatment for mucosal cancer, endoscopic mucosal resection and esopagostomy showed a complete resectability. While, the former was superior in the quality of life after treatment.

Esophageal Neoplasms↗

Ocular hypotensive mechanism of intravitreally injected brain natriuretic peptide in rabbit.

PURPOSE: To determine whether brain natriuretic peptide (BNP) affects intraocular pressure (IOP), aqueous humor dynamics, and cyclic guanosine monophosphate (cGMP) concentration in the aqueous humor of the rabbit eye. METHODS: Twenty microliters of 10(-4) M and 10(-5) M (2 nmol, 0.2 nmol) BNP or atrial natriuretic peptide (ANP) were injected intravitreally into rabbit eyes, after which the IOP was measured using a pneumatonometer. Aqueous humor dynamics were studied at approximately 6 hours after the intravitreal injection of 2 nmol BNP. Aqueous humor flow was measured by fluorophotometry, and outflow facility was measured by the two-level constant pressure perfusion method, whereas uveoscleral outflow was measured by the fluorescein isothiocyanate-dextran perfusion method. The concentration of cGMP in the aqueous humor at 6 hours after injection of 2 or 0.2 nmol BNP also was measured by enzyme immunoassay. RESULTS: Intravitreal administration of BNP or of ANP caused a decrease in IOP, with a maximum effect at approximately 6 hours after the injection. Total outflow facility in eyes treated with 2 nmol BNP increased by 29%, although the aqueous humor flow and uveoscleral outflow did not show significant changes. The concentration of cGMP in the aqueous humor increased significantly in BNP-treated eyes. CONCLUSIONS: Intravitreal injection of BNP into rabbit eyes reduced IOP because of an increase in the outflow facility. Brain natriuretic peptide also increased the concentration of cGMP in the aqueous humor. It is probable that BNP-activated guanylate cyclase induced an upregulation of cGMP in the aqueous humor.

Animals↗

[Erythropoietin improved anemia in a case of multicentric Castleman's disease].

Severe anemia A 37 year-old male with therapy resistant multicentric Castleman's disease (MCD) anemia was treated by subcutaneous injection of erythropoietin. Although immunoglobulin and CRP concentration increased, anemia obviously improved with hemoglobin levels increasing from 4.8 g/dl to 8.5 g/dl without any side effects. Colony assay revealed that the bone marrow mononuclear cells responded to erythropoietin in a dose dependent manner. The mechanism of anemia of MCD is not clearly understood, and treatment is sometimes very difficult. There is no other previous report concerning erythropoietin as a treatment for anemia in MCD.

Adult↗

A simple technique for the prevention of lower limb ischemia during femoral veno-arterial cardiopulmonary support.

OBJECTIVE: We describe a simple technique to prevent the lower limb ischemia during femoral veno-arterial cardiopulmonary support (CPS). PATIENTS: Between July 1994 and September 1995, five patients underwent the insertion of femoral veno-arterial CPS with distal limb perfusion for the treatment of circulatory collapse after cardiac surgery. METHODS: After CPS is established, the ipsilateral superficial femoral artery (SFA) is punctured downward with a 14-gauge Teflon catheter and connected to the side port of the membrane oxygenator. RESULTS: None of the patients were complicated by lower limb ischemia for up to 77 hrs on CPS with distal limb perfusion. CONCLUSIONS: Active perfusion through a 14-gauge Teflon catheter downstream to the ipsilateral SFA is effective in preventing lower limb ischemia during prolonged femoral veno-arterial CPS after cardiac surgery.

Adult↗

A new simplified method for laser sinus node modification without electrophysiological technique.

As the treatment of inappropriate sinus tachycardia, beta-adrenoreceptor blockade therapy is the most common method for pharmacological heart rate control, but it is occasionally limited by side effects of the drugs, especially in patients with cardiac dysfunction. On the other hand, cryoablation or surgical exclusion of the sinus node have not been accepted generally for their necessity of permanent pacemaker implantation. Modification of the sinus node function is a new method of nonpharmacological treatments, although the skillfull and troublesome technique is required. In this study, the efficacy and safety of laser sinus node modification without electrophysiological technique were investigated as a new simplified method. In six mongrel dogs, the laser-tissue interactions by epicardial Nd-YAG laser irradiation were investigated by measuring the diameter and the depth of the irradiated lesions. Laser irradiations were performed from the head to the tail on the sinus node areas directed only by terminal groove for the visual landmark without electrophysiological technique until about 25% decrease in heart rate occurred in other six open-chest dogs.

Animals↗

[Indications and techniques for surgical treatment of pulmonary emphysema].

We compared two surgical treatments for pulmonary emphysema: unilateral thoracoscopic surgery and bilateral volume reduction (pneumectomy). There were no significant complications with either technique. Symptoms were relieved and pulmonary function improved with both. Post-operative pain was more severe and postoperative blood loss was greater after pneumectomy, but the improvement in pulmonary function was also greater. Possible advantages of bilateral thoracoscopic surgery over pneumectomy should be studied.

Endoscopy↗

[Effects of in vivo instillation of genes coding for cytokines on pulmonary fibrosis].

Interstitial pneumonia is characterized by alveolitis that results in interstitial fibrosis. To study the role of humoral factors in the pathogenesis of interstitial fibrosis, we introduced expression vectors into Wistar rats via the trachea, to cause local overexpression of these humoral factors in the lung. Genes for human interleukin (IL)-6 and for the IL-6 receptor caused lymphocytic alveolitis without marked proliferation of fibroblasts. In contrast, overexpression of the genes for human transforming growth factor (TGF)-beta 1 and for human platelet-derived growth factor (PDGF)-B caused only mild cellular infiltration in the alveoli. However, both caused marked proliferation of fibroblasts and deposition of collagen fibrils. Introducing an expression vector that coded for a mutant form of the PDGF beta receptor that lacks its cytoplasmic domain markedly alleviated the pathohistologic changes caused by bleomycin in murine lungs. These findings show that TGF- and PDGF-B may be closely related to fibrosis in the lung, and that artificial regulation of them may be effective for treatment of lung fibrosis.

Animals↗

Decay-accelerating factor (DAF, CD55)-negative T lymphocytes in the peripheral blood of Sjögren's syndrome patients.

OBJECTIVE: To clarify possible associations of decay-accelerating factor (DAF, CD55), expressed on circulating lymphocyte subsets and other hematologic cells, with corresponding cytopenias observed in primary Sjögren's syndrome (SS). METHODS: DAF expression on peripheral blood (PB) cells was determined in 21 patients with SS and 11 healthy controls by single or 2 color flow cytometry. RESULTS: In the PB from SS patients, anemia, monocytopenia, neutropenia, and lymphocytopenia were observed. Compared to the controls, the percentages of DAF-negative cells were higher in CD4+ and CD8+ T cell subsets from SS patients, but the expression of DAF was similar in the other PB cells, including CD19+ B cells, CD56+ NK cells, monocytes, granulocytes, and erythrocytes. The percentages of DAF-negative cells among the CD4+ and CD8+ cells were positively correlated in SS patients, but the numbers of cells in both subsets were decreased in those patients being treated with prednisolone. However, these proportional changes are thought to reflect a decrease in the numbers of DAF-positive CD4+ and CD8+ cells, because the absolute numbers of circulating DAF-positive CD4+ and CD8+ cells, but not DAF-negative cells, were significantly decreased in SS patients. In addition, DAF-negative cells were detectable in both CD45RA+ (naive) and CD45RO+ (memory) T cells from healthy individuals, and the expression of DAF was remarkably increased in both subsets after in-vitro activation with concanavalin-A. CONCLUSION: DAF-negative cells are proportionally increased among circulating CD4+ and CD8+ T cells in SS patients, although such changes are due to decreased numbers of DAF-positive cells within each subset. When considering previous observations, the DAF-negative CD4+ and CD8+ cells probably belong to activated T cell subsets in both SS patients and controls. However, the patterns of DAF expression seemed to be different between activated T cells recognized in the PB, and those induced by in vitro-stimulation.

Adult↗

Concentrations of vascular endothelial growth factor in the sera of normal controls and cancer patients.

Vascular endothelial growth factor (VEGF) is known to play crucial roles in tumor angiogenesis. We have investigated the circulating level of VEGF in sera from cancer patients as well as from healthy normal controls using a sensitive enzymatic immunoassay. Immunoreactive VEGF proteins were detectable in normal sera, and the cutoff level was determined to be 180 pg/ml. In examined patients with all types of cancer, including breast, gastrointestinal, hepatobiliary, and lung cancer, an aberrant increase in the circulating level of VEGF was detected. For example, in 137 primary breast cancer patients, 12 (8.8%) showed an aberrant increase in VEGF levels. This aberrant expression of VEGF in sera was significantly associated with the progression of the disease, and with VEGF protein expression in tumor tissues. In addition, a Western blot analysis confirmed the presence of the VEGF165 form in sera from a patient with recurrent breast cancer. It was concluded that VEGF was detectable in normal sera, and its level was increased in some populations of cancer patients. A positive angiogenesis regulator, VEGF might function as an endocrine growth factor, particularly for solid tumors.

Adult↗

The alpha 3 beta 3 gamma complex of the F1-ATPase from thermophilic Bacillus PS3 containing the alpha D261N substitution fails to dissociate inhibitory MgADP from a catalytic site when ATP binds to noncatalytic sites.

ATP hydrolyses by the wild-type alpha 3 beta 3 gamma and mutant (alpha D261N)3 beta 3 gamma subcomplexes of the F1-ATPase from the thermophilic Bacillus PS3 have been compared. The wild-type complex hydrolyzes 50 microM ATP in three kinetic phases: a burst decelerates to an intermediate phase, which then gradually accelerates to a final rate. In contrast, the mutant complex hydrolyzes 50 microM or 2 mM ATP in two kinetic phases. The mutation abolishes acceleration from the intermediate phase to a faster final rate. Both the wild-type and mutant complexes hydrolyze ATP with a lag after loading a catalytic site with MgADP. The rate of the MgADP-loaded wild-type complex rapidly accelerates and approaches that observed for the wild-type apo-complex. The MgADP-loaded mutant complex hydrolyzes ATP with a more pronounced lag, and the gradually accelerating rate approaches the slow, final rate observed with the mutant apo-complex. Lauryl dimethylamide oxide (LDAO) stimulates hydrolysis of 2 mM ATP catalyzed by wild-type and mutant complexes 4- and 7.5-fold, respectively. The rate of release of [3H]ADP from the Mg[3H]ADP-loaded mutant complex during hydrolysis of 40 microM ATP is slower than observed with the wild-type complex. LDAO increases the rate of release of [3H]ADP from the preloaded wild-type and mutant complexes during hydrolysis of 40 microM ATP. Again, release is slower with the mutant complex. When the wild-type and mutant complexes are irradiated in the presence of 2-N3-[3H]ADP plus Mg2+ or 2-N3-[3H]ATP plus Mg2+ and azide, the same extent of labeling of noncatalytic sites is observed. Whereas ADP and ATP protect noncatalytic sites of the wild-type and mutant complexes about equally from labeling by 2-N3-[3H]ADP or 2-N3-[3H[ATP, respectively, AMP-PNP provides little protection of noncatalytic sites of the mutant complex. The results suggest that the substitution does not prevent binding of ADP or ATP to noncatalytic sites, but rather that it affects cross-talk between liganded noncatalytic sites and catalytic sites which is necessary to promote dissociation of inhibitory MgADP.

Adenosine Diphosphate↗

Conformational dynamics monitored by His-179 and His-200 of isolated thermophilic F1-ATPase beta subunit which reside at the entrance of the 'conical tunnel' in holoenzyme.

When monitored by 1H NMR at various pH values, most of the C-2 proton signals from 12 His residues of the isolated beta subunit of thermophilic F1-ATPase (TF1) could be separately observed. Two of them were assigned to His-179 and His-200 which reside at the entrance of a 'conical tunnel' to reach catalytic site in the crystal structure of F1-ATPase. His-200 gave doublet, suggesting that this region is not a rigid alpha-helix in the isolated beta subunit. The binding of Mg.AMP-PNP changed the chemical shifts of His-179 and His-200 significantly. Although His-119 located at the opposite side of the conical tunnel was not affected by the nucleotide-binding, it contributed to the stability of beta subunit and the efficiency of the catalysis of the holoenzyme.

Bacillus↗