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Biomedical subjects

S Miyamoto

Publications and source records attributed to S Miyamoto.

At least 163 records · Page 9Linked to original sources

Increased rate of formation of small-sized platelet aggregates in patients with acute coronary syndromes.

Coronary thrombosis has been implicated in the pathogenesis of acute coronary syndromes, and platelet activation plays a pivotal role in the pathogenesis of coronary thrombus. A new platelet aggregometer using a laserlight scattering beam was trialled for assessment of platelet aggregation. Platelet aggregability, especially small-sized platelet aggregates, was investigated on admission using the laser-light scattering method and again after treatment in 23 patients with acute coronary syndromes. The platelet aggregability in 14 patients with stable exertional angina and in 14 control subjects was also examined. On admission, the number of small- and medium-sized platelet aggregates in the acute coronary syndromes group was significantly greater than in the stable exertional angina group or control group. However, the number of large-sized platelet aggregates on admission was not increased in the acute coronary syndromes group. Furthermore, the number of small- and medium-sized platelet aggregates decreased significantly after treatment in the acute coronary syndromes group. The increased number of small-sized platelet aggregates may sensitively reflect attacks of thrombosis in patients suffering acute coronary syndromes.

Acute Disease↗

Epithelial cells release proinflammatory cytokines and undergo c-Myc-induced apoptosis on exposure to filarial parasitic sheath protein-Bcl2 mediates rescue by activating c-H-Ras.

Circulating filarial proteins elicit strong immunologic reactions in humans leading to the chronic manifestations in human lymphatic filariasis such as lymphatic occlusion, fibrosis, edema, and in some cases, tropical pulmonary eosinophilia. Our earlier studies, in vitro, conclusively prove that filarial parasitic sheath proteins induce apoptosis in HEp2 cells, an epithelial cell line, by a pathway inhibitable by bcl2. The present findings provide evidence that c-myc activation triggers apoptosis in HEp2 cells and that it is also responsible for the burst of abortive proliferation at 6 d of treatment of HEp2 bcl2 cells that overexpress bcl2, with filarial parasitic sheath protein, demonstrating the interplay between the two genes c-myc and bcl2, wherein bcl2 acts by restoring the prosurvival signal to c-myc and keeping its apoptotic tendency in check. This study also indicates that bcl2 upregulates c-H-ras, engaging ras to bring about the suppression of apoptosis through protein tyrosine kinase elevation, thus promoting the survival of the HEp2 bcl2 cells. In addition to the activation of these "signal switches," we also observe that these cells release cytokines like IL-6 and IL-8 through the upregulation of c-fos, when exposed to filarial parasitic sheath protein, reflecting on the immunomodulatory capacity of the epithelium to elicit a host immune response by setting up a chemotactic gradient, attracting inflammatory cells to the site of infection.

Animals↗

Bone regeneration at rabbit skull defects treated with transforming growth factor-beta1 incorporated into hydrogels with different levels of biodegradability.

OBJECT: Skull bone regeneration induced by transforming growth factor-beta1 (TGFbeta1)-containing gelatin hydrogels (TGFbeta1-hydrogels) was investigated using a rabbit skull defect model. Different strengths of TGFbeta1 were examined and compared: different TGFbeta1 doses in gelatin hydrogels with a fixed water content, different water contents in gelatin hydrogels with a fixed TGFbeta1 dose, and TGFbeta1 in solution form. In addition, regenerated skull bone was observed over long time periods after treatment. METHODS: Soft x-ray, dual energy x-ray absorptometry, and histological studies were performed to assess the time course of bone regeneration at a 6-mm-diameter skull defect in rabbits after treatment with TGFbeta1-hydrogels or other agents. The influence of TGFbeta1 dose and hydrogel water content on skull bone regeneration by TGFbeta1-hydrogels was evaluated. Gelatin hydrogels with a water content of 95 wt% that incorporated at least 0.1 microg of TGFbeta1 induced significant bone regeneration at the rabbit skull defect site 6 weeks after treatment, whereas TGFbeta1 in solution form was ineffective, regardless of dose. The in vivo degradability of the hydrogels, which varied according to water content, played an important role in skull bone regeneration induced by TGFbeta1 -hydrogels. In our hydrogel system, TGFbeta1 is released from hydrogels as a result of hydrogel degradation. When the hydrogel degrades too quickly, it does not retain TGFbeta1 or prevent ingrowth of soft tissues at the skull defect site and does not induce bone regeneration at the skull defect. It is likely that hydrogel that degrades too slowly physically impedes formation of new bone at the skull defect. Following treatment with 0.1-microg TGFbeta1-hydrogel (95 wt%), newly formed bone remained at the defect site without being resorbed 6 and 12 months later. The histological structure of the newly formed bone was similar to that of normal skull bone. Overgrowth of regenerated bone and tissue reaction were not observed after treatment with TGFbeta1 -hydrogels. CONCLUSIONS: A TGFbeta1-hydrogel with appropriate biodegradability will function not only as a release matrix for the TGFbeta1, but also as a space provider for bone regeneration. The TGFbeta1-hydrogel is a promising surgical tool for skull defect repair and skull base reconstruction.

Absorptiometry, Photon↗

Clinical implications of immunoreactivity of thymidylate synthase and dihydropyrimidine dehydrogenase in gastric cancer treated with oral fluoropyrimidine (S-1). Study Group of S-1 for Gastric Cancer.

Many reports have demonstrated that thymidylate synthase (TS) and dihydropyrimidine dehydrogenase (DPD) are biomarkers for the response and prognosis of patients treated with 5-fluorouracil (5-FU)-based chemotherapy. A newly developed orally administered drug, fluoropyrimidine (S-1), has been developed with clinical efficacy when combined with an inhibitor of DPD. In this study, the relationship between immunoreactivity to TS and DPD in biopsy specimens and the effects of chemotherapy was investigated in 41 patients treated with S-1 therapy for advanced gastric cancer. Response rates were 54% (13/24) in TS(+) and 53% (9/17) in TS(-) patients (p=0.938), and those of DPD(+) and (-) patients were 61% (11/18) and 48% (11/23) (p=0.397), respectively. The median survival time of all the subjects was 253 days. There was no significant difference in median survival time between TS(+) patients (284 days) and (-) patients (189 days: p=0.670). The 18 DPD(+) patients had median survival times slightly longer (338 days) than the 23 patients with DPD(-) (207 days: p=0.206). This study indicates that S-1 may be effective in the treatment of gastric cancer patients, regardless of intratumoral TS and DPD immunoreactivity status. Further studies are needed to confirm these results with larger numbers of patients.

Adult↗

[Autologous blood transfusion in surgery of urologic malignant tumor].

BACKGROUND: Autologous blood transfusion has been widely endorsed, because of the adverse effects attributed to homologous blood transfusion. So we employed autologous blood transfusion to avoid homologous blood transfusion in operation of urological malignant patients. We reviewed our experience with autologous blood transfusion in 48 patients. METHODS: A total of 48 patients underwent operation with 400 to 1,200 ml preoperative autologous blood donation, in 41 patients with administration of erythropoietin and 7 patients without erythropoietin. The details of operations are radical nephrectomy in 18 cases (2 cases were bilateral), radical nephro-ureterectomy in 2 cases, retroperitoneal lymph node dissection (RPLND) in 2 cases, radical prostatectomy in 12 cases and radical cystectomy in 14 cases. RESULTS: The volume of surgical blood loss were 381 +/- 522 ml in nephrectomy (1,158 +/- 202 ml in bilateral case), 517 +/- 5 ml in radical nephro-ureterectomy 636 +/- 574 ml in RPLND, 665 +/- 291 ml in radical prostatectomy and 1,123 +/- 417 ml in radical cystectomy. Only three cases needed homologous blood transfusion. CONCLUSION: We can avoid homologous blood transfusion in 94% of patients. Autologous blood transfusion is recommended as safe and convenient.

Adult↗

Purification and characterization of factor VII inhibitor found in a patient with life threatening bleeding.

We recently observed a patient with acquired inhibitor-induced F.VII deficiency whose plasma level of F.VII was < 1.0%. However, the biochemical nature of the inhibitor has not yet been clarified. In the present study, we purified the F.VII inhibitor from the patient's plasma by using activated F.VII (F.VIIa)-conjugated gel and characterized the inhibitor. The results showed that the inhibitor comprised two kinds of antibodies: one was eluted with EDTA (antibody 1) and the other with glycine-HCl buffer (pH 2.3) (antibody 2) from the F.VIIa affinity gel. SDS-polyacrylamide gel electrophoresis (SDS-PAGE) and immunoblotting analysis of these inhibitors demonstrated that both antibodies had features of immunoglobulin G1 (IgG1) with kappa and lambda-light chains. Antibody 1 bound to the immobilized F.VIIa with a high affinity in the presence of calcium ion, while antibody 2 bound to the F.VIIa very weakly and the binding was independent of calcium ion. Immunoblotting analysis demonstrated that antibody 1 bound to the light chain of F.VIIa after reduction with 2-mercaptoethanol, while it did not react with either the gamma-carboxyglutamic acid (Gla)-domainless light chain of F.VIIa or the heavy chain with the protease domain. Antibody 1 markedly inhibited the activity of tissue factor-F.VIIa complex. Based on these observations, it is suggested that F.VIIa autoantibody (antibody 1) recognizes the calcium-dependent conformation within or near the Gla domain and inhibits F.VIIa activity by interacting with the light chain.

Antibodies↗

[Surgical treatment for spontaneous hemopneumothorax complicated by delayed re-bleeding: a case report].

A 34-year-old man was admitted to the hospital due to spontaneous hemopneumothorax. A chest tube drainage was performed, and hemorrhagic plueral effusion of 1,600 ml was drained. Because of this, the patient was transferred to the emergency center of our hospital. Following a blood transfusion, we continued to treat conservatively for nine days, because no more bleeding was recognized. On day ten, the patient suddenly started bleeding again, thus, an emergency operation was performed. At the operation under a thoracoscope, a bleeding point was ligated with surgical clip, however, it was difficult to remove blood clots that were attached with the lung surface, it was impossible to continue the thoracoscopic surgery. If re-bleeding occurs after the acute phase, problems may arise from conservative treatment. So, early surgical treatment should be considered.

Adult↗

Comparison of the effects of clozapine, risperidone, and olanzapine on ketamine-induced alterations in regional brain metabolism.

The ability of subanesthetic doses of N-methyl-D-aspartate (NMDA) antagonists to induce positive, negative, and cognitive schizophrenia-like symptoms suggests that reduced NMDA receptor function may contribute to the pathophysiology of schizophrenia. An increasing body of evidence indicates that antipsychotic drugs, especially those with "atypical" properties, can antagonize the effects of NMDA antagonists in a variety of experimental paradigms. We demonstrated previously that clozapine, the prototype of atypical antipsychotics, but not haloperidol, the typical antipsychotic, blocked ketamine-induced alterations in brain metabolism. In this study, effects of clozapine were compared with two of the newer atypical antipsychotic drugs, risperidone and olanzapine, on ketamine-induced alterations in regional [(14)C]2-deoxyglucose (2-DG) uptake. A subanesthetic dose of ketamine (25 mg/kg) induced robust increases in 2-DG uptake in limbic cortical regions, hippocampal formation, nucleus accumbens, and basolateral amygdala. Pretreatment of rats with risperidone (0.3 mg/kg) before ketamine administration did not alter the effects of ketamine. These data suggest that novel pharmacological properties may contribute to the effects of clozapine in this model, in addition to the well characterized actions at D(2) and 5HT(2A) receptors. In contrast to the results with risperidone, olanzapine blocked ketamine-induced increases in 2-DG uptake. However, a higher dose of olanzapine (10 mg/kg) was required to completely block the effects of ketamine than would be expected if D(2) and 5HT(2) receptor blocking properties of the drug were solely responsible for its action. The results suggest that the ketamine challenge 2-DG paradigm may be a useful model to identify antipsychotic drugs with atypical characteristics and to explore mechanisms of atypical antipsychotic action.

Animals↗

Rapid change of platelet aggregability in acute hyperglycemia. Detection by a novel laser-light scattering method.

We examined the alteration of platelet aggregability in acute hyperglycemia during 75-gram oral glucose tolerance tests (OGTT). Twenty subjects underwent 75-gram OGTT and venous blood samples were obtained before (0 min), 60, 120 and 180 min postload. Platelet aggregability shown as the number of small platelet aggregates was measured with a novel laser-light scattering (LS) method. Platelet aggregability increased in parallel with both glucose and immunoreactive insulin (IRI) levels. The number of mean small aggregates at 60 min (12.30 +/- 1.10 X 10(4)) was significantly higher than the one at 0 min (8.32 +/- 0.88 x 10(4), p <0.001), 120 min (10.63 +/- 0.98 x 10(4), p <0.05) and 180 min (8.28 +/- 0.84 x 104, p <0.001) (mean +/- SEM). Small aggregates correlated positively with plasma glucose levels at 60 min postload (r = 0.67, p = 0.001) while not with IRI. It might be important to suppress transient hyperglycemia for preventing the onset of acute coronary syndromes that could be closely related to platelet hyperaggregability.

Acute Disease↗

[The influence of corneal thickness and curvature on the difference between intraocular pressure measurements obtained with a non-contact tonometer and those with a Goldmann applanation tonometer].

PURPOSE: The influence of corneal thickness and curvature on the difference between intraocular pressure (IOP) measurements obtained with a non-contact tonometer (NCT) and those with a Goldmann applanation tonometer (GAT) was studied. METHODS: The corneal thickness and curvature were obtained in 230 eyes of 115 subjects. The correlation between them and ratios of measurement with NCT to that with GAT ([NCT/GAT]) were examined. RESULTS: [NCT/GAT] and corneal thickness showed a significant positive correlation (r = 0.556, p < 0.01), but, the correlation between [NCT/GAT] and the radius of corneal curvature was not statistically significant (r = -0.035, p = 0.30). CONCLUSION: The thick cornea has more influence on the measurement with NCT than GAT, because IOP is measured with NCT over a wider applanation area. The corneas with steeper curvature also cause higher corneal rigidity and produce more overestimation of NCT measurement, while they have stronger capillary attraction of the precorneal tear film for the GAT tip and also produce overestimation of GAT measurement. As a result, [NCT/GAT] was believed to be not influenced by the corneal curvature.

Cornea↗

Interleukin-16 in synovial fluids from cases of various types of arthritis.

OBJECTIVES: To examine the characteristic relationship between interleukin-16 (IL-16) and clinical data in various types of arthritis. METHODS: We measured IL-16 levels of the synovial fluids (SF) of patients with various types of arthritis, which included rheumatoid arthritis, traumatic arthritis, pseudogouty arthritis, gouty arthritis, and osteoarthritis, by an enzyme immunosorbent assay, and examined their correlations with clinical parameters. RESULTS AND CONCLUSIONS: Higher levels of IL-16 in synovial fluid from patients with rheumatoid arthritis, traumatic arthritis, and pseudogouty arthritis, compared to those with osteoarthritis, and gouty arthritis were indicated. Also, synovial IL-16 levels in patients with rheumatoid arthritis correlated significantly, especially with synovial matrix metalloproteinase-3 levels. But the IL-16 levels of both synovial fluid and peripheral blood did not correlate with conventional inflammatory parameters such as C-reactive protein, erythrocyte sedimentation rate, or rheumatoid factor. Although the function of IL-16 in inflammatory arthritis has not yet been defined, these data indicated some essential features of IL-16.

Adult↗

[Risk factors and physical activity levels at the onset of acute myocardial infarction in young men].

OBJECTIVES: The pathogenesis and triggering factors of acute myocardial infarction in young men remain unknown. To clarify the pathogenesis of acute myocardial infarction in young Japanese men, we compared the clinical features of patients with acute myocardial infarction in 2 age groups in Japan. METHODS: There were 37 male patients aged < 40 years (Young group; mean age 36 +/- 4 years, range 23-39 years) among 2,879 patients with acute myocardial infarction admitted to the coronary care unit of the National Cardiovascular Center, Japan, from 1977 through 1996. The clinical features of this group were compared with those of 110 consecutive male patients with acute myocardial infarction aged > or = 65 years (Old group; mean age 72 +/- 6 years, range 65-96 years) admitted in 1993-1994. Demographic features, physical activity levels at or within 2 hours before the onset of acute myocardial infarction, and coronary angiographic findings were analyzed. RESULTS: Compared with the Old group, the Young group had lower incidences of hypertension (p < 0.01) and diabetes mellitus (p < 0.01), a higher incidence of smoking (p < 0.01), higher levels of total cholesterol (p < 0.05) and body mass index (p < 0.05), and a lower level of high-density lipopotein (HDL)-cholesterol (p < 0.01). Also, the Young group had a higher prevalence of 0-1 vessel disease than the Old group (72% vs 35%, p < 0.01). The physical activity level was significantly higher in the Young group than in the Old group (2.6 +/- 2.2 vs 1.8 +/- 1.1 METs, p < 0.01). Furthermore, patients with multivessel disease in the Young group had a higher incidence of hypertension, a higher level of total cholesterol and a lower level of HDL-cholesterol (all p < 0.05), whereas those with 0-1 vessel disease had a higher incidence of heavy smoking (73% vs 50%, p = 0.1) and a tendency to higher physical activity level at the onset (2.7 +/- 2.2 vs 2.4 +/- 2.3, NS). CONCLUSIONS: Young male patients with acute myocardial infarction may be characterized by 2 distinctive patterns: one associated with smoking and a higher physical activity level at the onset of acute myocardial infarction with 0-1 vessel disease and the other with hypertension and hypercholesterolemia with multivessel disease.

Adult↗

Conformational analysis of 2-[2-(3-methoxyphenyl) ethyl]phenoxyalkylamines with high 5-HT2 receptor binding affinity.

A conformational analysis of three groups of 2-[2-(3-methoxyphenyl)ethyl]phenoxyalkylamines with high 5-HT2 receptor binding affinity has been performed using the systematic search. Two groups of compounds with different lengths of alkyl chains connecting the amine nitrogen and the central oxygen showed a one order difference in their 5-HT2 receptor binding affinity. The computational analysis of these compounds confirmed the differences in the N--O distances between the two groups, quantitatively. A probable active conformation was proposed based on a superimposition of the stable conformations over a rigid molecule, mianserin. Two hydroxy derivatives in the third group showed a significant difference in their binding affinity depending on the stereochemistry of the hydroxy group. The difference in the energetically favorable order of the stable conformations reasonably explained the relationship between the stereochemistry and the binding activity. A molecular dynamics-based conformational search was also carried out to compare it with the systematic search.

Alkanes↗

[Penetrating lung and diaphragmatic injuries with no abnormal finding of chest X-ray: a case report].

A case of penetrating lung and diaphragmatic injuries with no abnormal findings of chest X-ray is reported. A 76-year-old man was admitted to our hospital due to penetrating chest trauma. A simple X-ray film of the chest on admission revealed no abnormal finding. An emergency operation was performed. On exploring the back open wound, we found a laceration of 7 cm in diameter in the right diaphragm and lung laceration. Then we repaired primarily with absorbable material. The postoperative course was uneventful, and the patient was discharged 12 days later. Penetrating truncal traumas can result in diaphragmatic injury. Sometimes the clinical and roentgenographic findings are unreliable. If the diagnosis is missed, a diaphragmatic injury may occur delayed diaphragmatic hernias within hours to years. Accordingly, initial wound exploration are important for the diagnosis of diaphragmatic injury in avoiding serious complications.

Aged↗

Ascending aortic infected pseudoaneurysm with aortic insufficiency following cardiac operation for infective endocarditis.

An infected pseudoaneurysm of the ascending aorta after heart surgery is a fatal disease due to its rapid progress, worsening of the systemic condition and a tendency of recurrence. We report a 53-year-old man with this condition who presented with fever and an aortic regurgitation due to compression of the ascending aortic root 2 months after mitral valve replacement for infective endocarditis. We performed an aneurysmectomy with a cardiopulmonary bypass using groin cannulation and moderate systemic hypothermia. A pseudoaneurysm developed 5 mm proximally of the previous aortotomy. There was no dehiscence of the former aortic suture line. After debridement of the ascending aorta involving the previous aortotomy and pseudoaneurysm, we elected to directly close the aortic defect using Teflon felt strips to avoid a prosthetic graft. The aortic valve had no infective endocarditis and other abnormality. Postoperatively, there was no aortic regurgitation, and the cause of the previous aortic regurgitation was believed to be due to a compression of the aortic root from outside. The postoperative course has been good.

Aneurysm, False↗

Immunosuppressants FK506 and rapamycin have different effects on the biosynthesis of cytoplasmic actin during the early period of T cell activation.

FK506 and rapamycin are immunosuppressants that interfere with T cell activation. FK506 inhibits early events of T cell activation such as the induction of cytokine transcription, whereas rapamycin inhibits later interleukin 2 signalling events. However, both reagents either directly or indirectly reduce protein synthesis. Therefore a kinetic study was conducted in human primary T lymphocytes examining increased synthesis of proteins stimulated by either ionomycin+phorbol myristate acetate (PMA) or PMA alone. Three patterns of protein expression were observed. Synthesis of one group of proteins had enhanced synthesis with FK506, but reduced synthesis with rapamycin. A second group had reduced synthesis with rapamycin and either no change or a slight reduction with FK506 and a third group had reduction with both FK506 and rapamycin. One major protein of the first group, p42, had a rapid increase in synthesis that decreased by 8 h. Its synthesis was strongly enhanced by FK506, but reduced by rapamycin after ionomycin+PMA stimulation. In contrast, this protein was strongly induced by PMA alone in these cells and not affected by FK506 treatment, but still reduced by rapamycin. p42 was identified as cytoplasmic actin. mRNA levels of both gamma- and beta-actin were found to be enhanced with FK506 treatment suggesting that regulation of actin was at a transcriptional or post-transcriptional level. Results with actinomycin D indicated that FK506 is regulating actin biosynthesis at the post-transcriptional level. Rapamycin, however, appeared to be operating at the level of translation.

Actins↗