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Biomedical subjects

M Takeuchi

Publications and source records attributed to M Takeuchi.

At least 235 records · Page 13Linked to original sources
PubMed1999

2-(3-Pyridyl)thiazolidine-4-carboxamide derivatives. III.) Synthesis of metabolites and metabolism of 2-(3-pyridyl)thiazolidine-4-carboxamides YM461 and YM264 as platelet-activating factor (PAF) receptor antagonists.

The metabolism of 2-(3-pyridyl)thiazolidine-4-carboxamides YM461 and YM264 was investigated, and their metabolites were compared with separately synthesized materials by measuring 1H-NMR spectra, mass spectra, and HPLC retention times, and evaluated for platelet activating factor (PAF) antagonistic activity. YM461 was metabolized by two different metabolic pathways (cleavage of the thiazolidine ring and oxidation of the benzyl position), whereas YM264 was metabolized by three metabolic pathways. The minor metabolite M7 from YM264 possessed potent PAF antagonistic activity, as strong as YM264 and this existed as an active metabolite. From pharmacokinetics studies, YM264 was almost completely absorbed from the gastrointestinal tract, but readily metabolized in rats. In dogs, pharmacokinetic parameters of YM264 were significantly improved compared to those in rats, and YM264 tended to show better pharmacokinetics than YM461 due to an extension of the half-life period.

Administration, Oral↗
PubMed1999

Beneficial effects of heart rate reduction on cardiac mechanics and energetics in patients with left ventricular dysfunction.

It has been shown recently that the force-frequency relationship is blunted in experimental heart failure models. Furthermore, tachycardia is thought to have adverse effects on the diseased heart for several reasons, one of which is an increase in myocardial oxygen consumption. Inversely, the oxygen-saving effects of bradycardia may be beneficial for the treatment of heart failure. The aim of this study was to elucidate how heart rate (HR) modulates cardiac mechanics and energetics in patients with left ventricular (LV) dysfunction. LV pressure-volume data and myocardial oxygen consumption (MVO2) was assessed using conductance and coronary sinus thermodilution catheters in 14 patients with moderate LV dysfunction (mean ejection fraction 34%) under 3 conditions: (a) basal, (b) HR increased by 20% using atrial pacing, and (c) HR decreased by 16% using a specific bradycardic agent, zatebradine (7.5 mg p.o.). Atrial pacing decreased external work (EW) (from 0.39 to 0.31 J beat(-1) m(-2), p<0.05) at a comparable MVO2 per beat with a marginal increase in LV contractility index (Ees) (from 2.34 to 2.76 mm Hg ml(-1) m(-2), p = 0.08), resulting in a decrease in mechanical efficiency (EW/MVO2) (from 25.9 to 22.1%, p<0.05). In contrast, zatebradine did not decrease Ees (from 2.34 to 2.24 mm Hg ml(-1) m(-2), NS), but increased EW (from 0.39 to 0.42 J beat(-1) m(-2), p<0.05 vs. basal level) without a change in MVO2 per beat, resulting in improved mechanical efficiency (from 25.9 to 29.7%, p<0.05 vs. basal level). These results suggest that mild bradycardia is energetically advantageous and does not decrease myocardial contractility and performance, whereas pacing-induced tachycardia worsens cardiac mechanics and energetics in patients with LV dysfunction. Thus, the oxygen-saving effect of bradycardia may be beneficial for the treatment of heart failure.

Benzazepines↗
PubMed1999

Typing Listeria monocytogenes by random amplified polymorphic DNA (RAPD) fingerprinting.

Twenty epidemiologically unrelated Listeria monocytogenes strains isolated from different animals, locations and on different dates in Japan were classified into 18 types by the random amplified polymorphic DNA (RAPD) fingerprinting technique with four primers. Further, seven epidemiologically related L. monocytogenes strains isolated from raw milk and a bulk tank on a dairy farm represented the same RAPD type suggesting that they were all of the same origin. Therefore, RAPD-polymerase chain reaction (PCR) analysis, which is rapid, simple and inexpensive to perform, can be used in surveys as a convenient epidemiological technique.

Animals↗
PubMed1999

Regional left ventricular motion during early filling phase in patients with right ventricular pressure overload.

Global left ventricular (LV) diastolic function has been reported to be disturbed under conditions of right ventricular pressure overload (RVPO). However, from the standpoint of regional wall motion, only a little information related to the mechanism of LV diastolic dysfunction is available. Eight patients with RVPO and 7 healthy volunteers were investigated using tagged cine magnetic resonance imaging. Regional diastolic fraction (RDF) was determined in 4 segments (anterior, lateral, inferior, and septal) in the mid-ventricular short axis section and in 2 segments (septal and lateral) in the 4-chamber section. A heterogeneity index was obtained from the RDFs of the short axis section. In the RVPO group, in both short axis and 4-chamber sections, the RDF of the septal segment was depressed, and it showed an inverse correlation with the right-to-left ventricular systolic pressure (RV/LV) ratio (r = -0.74, p < 0.05) in the short axis section. In the 4-chamber section, the RDF was lower in the septal segment than in the lateral segment (p < 0.05). The heterogeneity index in the RVPO group was greater than that in the control group (p < 0.01). The index correlated positively with the RV/LV ratio (r = 0.77, p < 0.05). The altered regional diastolic motion results in increased heterogeneity in regional diastolic motion.

Adolescent↗
PubMed1999

Expression of MEF2 genes during human cardiac development.

To better understand the regulatory mechanisms in gene expression of human cardiomyocytes, we studied the expression of MEF2 genes encoding transcription factors during the course of cardiac development. Expression of all four MEF2 transcripts (MEF2A, MEF2B, MEF2C, and MEF2D) were detected in all developmental stage of the human heart, while Mef2b transcripts were down-regulated in mouse heart development. Although none of the MEF2 genes, besides mouse Mef2b, exhibited any remarkable quantitative change in their transcripts, qualitative changes in MEF2 transcripts were found during the course of cardiac development. In particular, MEF2D transcripts showed prominent changes by alternative splicing in the perinatal period. MEF2D transcripts containing the 21-base exon (exon b) were predominantly expressed after birth. At the same time, transcripts of the alpha myosin heavy chain (alphaMHC) gene increased after birth, as the splicing pattern in transcripts of the cardiac troponin T (cTnT) gene changed to decrease the transcripts of cTnT1 after birth. These changes seemed to be correlated with the alternative splicing changes of MEF2 genes, especially MEF2D. The alternative splicing as well as transcriptional regulation in MEF2 genes might be important for regulating the alphaMHC gene and the maturation of cardiomyocytes.

Animals↗
PubMed1999

[Clinical statistics of stage I testicular tumor].

PURPOSE: A survey of stage I testicular tumors in the Chugoku-Shikoku district was taken in order to explore the clinical characteristics. PATIENTS AND METHODS: Three hundred and forty eight cases of stage I testicular tumor treated at 46 facilities in the Chugoku-Shikoku district between 1984 and 1992 were collected. Subjects' background factors, treatment methods and prognosis were studied. RESULTS: Tissue types were 249 (71.6%) seminoma and 99 (28.4%) non-seminoma. Adjuvant therapy for seminoma cases included 138 post-operative radiotherapy (4 recurrences, 3 cancer deaths), 57 chemotherapy (no recurrences, 2 contralateral testis tumor cases) and 48 were under surveillance (no recurrence). Adjuvant therapy for non-seminoma cases included 47 chemotherapy (1 recurrence) and retroperitoneal lymph node dissection was performed on 6 cases. Forty cases were under surveillance (1 recurrence). Of 8 (2.3%) cases with recurrence, 6 showed onset within two years and 2 after two years. Four of the 8 cases with recurrence were seminoma (1.1% of seminoma cases) and the other 4 were non-seminoma (4.0% of non-seminoma cases). All 3 (0.9% of all cases) of the cancer death cases were seminoma that received post-operative radiotherapy, while there were no cancer deaths in non-seminoma cases. CONCLUSION: Prognosis of stage I testicular tumor is good. Although the recurrence rate was higher in non-seminoma cases, cancer deaths were only observed in seminoma cases.

Adolescent↗
PubMed1999

Angiotensin II receptor on BALF macrophages from Japanese patients with active sarcoidosis.

BACKGROUND: Serum angiotensin converting enzyme (ACE) activity and its changes are important markers for disease activity in patients with sarcoidosis. We earlier reported that ACE and its enzymatic product, angiotensin II (A-II), might play a role in maintaining macrophage/T lymphocyte alveolitis by enhancing an accessory function of macrophages in chronic active cases with sarcoidosis. AIM OF THE WORK AND METHODS: We examined whether A-II receptor is present on BALF macrophages by a receptor binding assay using 125I-labeled A-II, and by amplification of A-II receptor gene transcripts using RT-PCR methods and quantification of the amounts of transcripts by HPLC. RESULTS: The receptor binding assay suggested that specific binding of A-II to BALF macrophages was somewhat more prevalent in active sarcoidosis than in controls. A specific band for A-II receptor was detected by RT-PCR. A-II receptor gene expression was standardized as the ratio to beta-actin. An increased ratio was shown in active sarcoidosis (0.70 +/- 0.19; n = 14) compared to inactive cases (0.14 +/- 0.06; n = 5; p = 0.023) and healthy subjects (0.15 +/- 0.09; n = 5, p = 0.029). The ratio correlated positively with the percentage of BALF T lymphocytes (r = 0.60, p = 0.0056), and negatively with BALF macrophages (r = 0.60, p = 0.0055). No difference was detected between nonsmokers and smokers. CONCLUSION: The amounts of A-II receptor gene expression of BALF macrophages correlated with disease activity in patients with pulmonary sarcoidosis.

Adult↗
PubMed1999

[Anesthetic and perioperative management of 1000 cases of congenital heart surgery--massive vasodilator therapy and early extubation].

We report our anesthetic and perioperative management of 1000 cases of congenital heart surgery in Okayama University Medical School over the last six and a half years. Most of these patients were anesthetized by fentanyl and all patients were managed in our ICU postoperatively. Although hospital death rate in all patients was 4.5%, almost half of dead patients were patients with hypoplastic left heart syndrome. Neonatal mortality rate has been still high, 18.9%, which has been our main problem. We tried to extubate patients with complex congenital heart diseases earlier postoperatively for the last three years, using massive dose of vasodilators without nitric oxide.

Adolescent↗
PubMed1999

[A case of interstitial nephritis induced by a super antigen produced by methicillin-resistant Staphylococcus aureus (MRSA) presenting as acute renal failure].

We report the case of a 21-year-old man who had been developing acute renal failure with Methicillin-resistant Staphylococcus aureus (MRSA) colitis and sepsis. He was admitted for consciousness disturbance, nausea, vomiting, and diarrhea. Oliguria was also observed and his serum creatinine level was elevated to 10 mg/dl. Urinary protein was positive and an abundance of hyaline cast were seen in urinary sedimentation. Diarrhea and pyrexia were prolonged and serum C-reactive proteins were elevated, but lymphocyte and leukocyte counts temporarily decreased from the 3rd to the 6th hospital day and remained low until normalizing after the 14th day. His clinical symptoms improved with hemodialysis (HD) and effective antibiotic therapies. An MRSA strain producing toxic shock syndrome toxin-1 (TSST-1), a super antigen which specifically stimulates human V beta 2-positive T cells, was separated from his feces and blood. To ascertain the cause of his renal dysfunction, a renal biopsy was performed on the 8th day. His renal histology revealed acute interstitial nephritis with severe inflammatory cell infiltration around the medullary areas without glomerular changes. Most of the infiltrated cells were small monocytes, and lymphoid cells were rich in the interstitium. With immunohistochemical staining, over 70% of T-cells were V beta 2-positive. TSST-1-producing MRSA was detected in his blood specimen. Furthermore, V beta 2-positive T cells were accumulated in the renal intersititium, and transient lymphocytopenia was observed. These data suggested the following possible pathogenesis for interstitial nephritis: TSST-1 acts as a super antigen in the renal interstitium where major histocompatibility complex (MHC) is class-2-positive, thereby resulting in interstitial nephritis with T cell migration.

Acute Kidney Injury↗
PubMed1999

[Development of cerebellar astrocytoma in a patient with acute myeloid leukemia 8 years after his second bone marrow transplant].

We report a case of cerebellar astrocytoma occurring 8 years after the second bone marrow transplantation (BMT) in 32-year-old man. The patient was admitted to our hospital in December 1997 because of dysarthria and gait disturbance. He had been treated earlier for acute myeloid leukemia (AML M2) with chemotherapy and cranial irradiation followed by allogeneic BMT from a sibling in december 1988. Three months after the first BMT, testicular relapse was observed and followed by systemic relapse. The patient received reinduction therapy and a second successful BMT. He had been well until about 1 month before admission to our hospital. Neurological examination revealed left cerebellar ataxia, and brain magnetic resonance imaging disclosed a left cerebellar tumor. The tumor was surgically resected and a histological diagnosis of cerebellar astrocytoma was made. The patient was further treated by irradiation for residual tumor and discharged without progression of the disease.

Acute Disease↗
PubMed1999

Detection of noncarboxymethyllysine and carboxymethyllysine advanced glycation end products (AGE) in serum of diabetic patients.

BACKGROUND: The advanced stage of the Maillard reaction, which leads to the formation of advanced glycation end products (AGE), plays an important role in the pathogenesis of angiopathy in diabetic patients and in the aging process. N(epsilon)-(carboxymethyl)lysine (CML) is thought to be an important epitope for many of currently available AGE antibodies. However, recent findings have indicated that a major source of CML may be by pathways other than glycation. A distinction between CML and non-CML AGE may increase our understanding of AGE formation in vivo. In the present study, we prepared antibodies directed against CML and non-CML AGE. MATERIALS AND METHODS: AGE-rabbit serum albumin prepared by 4, 8, and 12 weeks of incubation with glucose was used to immunize rabbits, and a high-titer AGE-specific antiserum was obtained without affinity for the carrier protein. To separate CML and non-CML AGE antibodies, the anti-AGE antiserum was subjected to affinity chromatography on a column coupled with AGE-BSA and CML-BSA. Two different antibodies were obtained, one reacting specifically with CML and the other reacting with non-CML AGE. Circulating levels of CML and non-CML AGE were measured in 66 type 2 diabetic patients without uremia by means of the competitive ELISA. Size distribution and clearance by hemodialysis detected by non-CML AGE and CML were assessed in serum from diabetic patients on hemodialysis. RESULTS: The serum non-CML AGE level in type 2 diabetic patients was significantly correlated with the mean fasting blood glucose level over the previous 2 months (r = 0.498, p < 0.0001) or the previous 1 month (r = 0.446, p = 0. 0002) and with HbA(1c) (r = 0.375, p = 0.0019), but the CML AGE level was not correlated with these clinical parameters. The CML and non-CML AGE were detected as four peaks with apparent molecular weights of 200, 65, 1.15, and 0.85 kD. The hemodialysis treatment did not affect the high-molecular-weight protein fractions. Although the low-molecular-weight peptide fractions (absorbance at 280 nm and fluorescence) were decreased by hemodialysis, there was no difference before and after dialysis in the non-CML AGE- and CML-peptide fractions (1.15 and 0.85 kD fractions). CONCLUSIONS: We propose that both CML and non-CML AGE are present in the blood and that non-CML AGE rather than CML AGE should be more closely evaluated when investigating the pathophysiology of AGE-related diseases.

Animals↗
PubMed1999

[Atopic dermatitis on infant physical examination].

The prevalence rate of atopic dermatitis was investigated in 4-month-old infants, who were examined by dermatologists at regular health checks at a health center. Among 739 infants examined, 150 were diagnosed as having atopic dermatitis, giving a prevalence rate of 20.3%. Most of the cases were mild, and no severe cases were observed. The prevalence rate in spring and autumn was significantly higher than that in summer and winter. The eruptions were seen mainly on the head, face, and trunk. A familial history of atopic dermatitis was positively correlated with infant atopic dermatitis in this series, whereas a familial history of bronchial asthma and allergic rhinitis showed no such correlation. It is important to make a correct diagnosis of mild atopic dermatitis by differentiation from other diseases by dermatologists, and it will be of interest to observe the condition of the infants when they attend for their next physical examination at the age of 18 months.

Dermatitis, Atopic↗
PubMed1999

[Estimation of antibacterial activity of various antibiotics against Pseudomonas aeruginosa by score method].

Antibacterial activity of various antibiotics against Pseudomonas aeruginosa isolated from each hospitals depends on the variety or amount of antibiotics used in each hospital. The antibiotic, which is effective to P. aeruginosa in a certain hospital is not always effective to that in other hospital. The excellent antibiotics in antibacterial activity have low MIC and hard to progress in resistance, and such antibiotics may be effective against P. aeruginosa isolated from any hospitals. Therefore we thought that the antibiotic, which was progress to resistance, would show a great difference in MIC among hospitals, and we investigated MIC and difference of MIC of various antibiotics against P. aeruginosa isolated from six hospitals. Furthermore, we converted the data of MICs and difference of MIC among six hospitals into the score, and tried to estimate antibacterial activity of various antibiotics by using those scores. From the results of analysis in this report, we think the antibiotics actually surpass in antibacterial activity may be imipenem, cefozopran, cefsulodin and amikacin. New analytical method proposed in this report will become one of potential methods to estimate antibacterial activity of antibiotics against bacteria isolated from inpatient with bacterial infections.

Anti-Bacterial Agents↗
PubMed1999

[Two cases of spinal epidural lipomatosis].

Two cases of spinal epidural lipomatosis (SEL) were reported. Patient 1 was on oral corticosteroid and patient 2 was obese and had prostate cancer. Patient 1 was a 45-year-old man diagnosed as sarcoid myelopathy at C 5/6 vertebral body levels and had been placed on oral corticosteroid therapy for 14 months. He showed spastic paraplegia, hypesthesia below C 4 level with distal dominancy and dysesthesia below Th 6 level. MRI revealed epidural lipomatosis from Th 3 to Th 9 vertebral bodies, which presented high in T 1 weighted image (WI) and T 2 WI, and non-signal in STIR image. On axial image spinal cord was compressed by this mass. Patient 2 was a 73-year-old man with spastic paraplegia, and superficial and deep sensory disturbances below Th 6. He had been obese (BMI 26.1) upon admission. He was diagnosed as prostate cancer with bone metastasis. On MRI of the thoracic spine revealed epidural mass of high in T 1 WI and T 2 WI, and non-signal in STIR image. SEL is a rare condition known as hyperplasia of normal fat tissue in epidural space which sometimes compresses the spinal cord or spinal nerve roots resulting in neurologic deficit. SEL should be kept in mind as having possible neurologic complications in obese patients or ones on long term steroid therapy.

Aged↗
PubMed1999

[A case of microscopic polyangiitis with severe cardiac and respiratory muscle involvement].

A 66-year-old female was admitted to our hospital in January, 1998, complaining of low grade fever and muscle weakness of her legs. Physical examination revealed muscle weakness of her neck (4/5) and proximal skeletal muscles of her bilateral legs (3/5-4/5). She showed proteinuria and microhematuria. Her serum levels of ureanitrogen, creatinine, aspartate aminotransferase, alanine aminotransferase, creatinekinase, aldolase and myoglobin were all within the normal ranges. Antinuclear antibodies were negative, but her serum levels of pANCA (743 EU) and C reactive protein (18.0 mg/dl) were elevated. Neuroconduction velocity of her left common peroneal nerve was decreased to 40.8 m/sec and electric myograph showed neurogenic changes. Magnetic resonance images (MRI) of her bilateral thigh depicted high signal intensity in quadriceps by T 2 weighed images, but the signals were not enhanced by gadolinium injection. Muscle and renal biopsies revealed necrotizing vasculitis of the small arteries. Crescentic glomerulonephritis was also observed by renal biopsy. These findings supported the diagnosis of microscopic PN. On 16 th admission day, she developed acute cardiac and respiratory failures due to cardiac and respiratory muscle involvements with PN, and was assisted by mechanical ventilation. She was treated with methylprednisolone pulse therapy (500 mg/day, three consecutive days) on 18 th admission day, followed by 40 mg of oral prednisolone daily. However, her symptoms deteriorated, and herserum creatinine levels increased to 2.4 mg/dl. On 24 th admission day, intravenous cyclophosphamide pulse therapy (500 mg/day) was instituted. Her cardiac wall motion on echocardiography and serum creatinine levels gradually improved, but her skeletal and respiratory muscle weakness did not improve. On 38 th admission day, she was complicated with respiratory infection by methicillin resistant Staphylococcus aures. On 62 th admission day, she died of endotoxic shock. This is the first report describing respiratory muscle involvement with PN, and the second report describing MRI findings of muscle involvement by PN. Therefore, our case provides important clinical information for the diagnosis and treatment of the disease.

Aged↗
PubMed1999

[Reliability of disc-diffusion susceptibility testing for arbekacin, vancomycin and teicoplanin against methicillin-resistant Staphylococcus aureus].

We investigated the differences in judgments among four disc-diffusion methods on susceptibility testing of arbekacin (ABK), vancomycin (VCM) and teicoplanin (TEIC) against 37 strains of methicillin-resistant Staphylococcus aureus (MRSA). These results were compared with minimum inhibitory concentrations (MICs) obtained from micro broth-dilution method. A marked difference was noted in the judgment of susceptibility to TEIC in Tri-disc method, that is 2 strains (5.4%) fell into sensitive (+3) 34 strains (91.9%) into moderately sensitive (+2) and 1 strain (2.7%) into moderately resistant (+), while in Sensi-disc method all strains fell into sensitive (S). According to the MICs, no strain of the MRSA tested revealed resistance to ABK, VCM and TEIC. Consequently, these three antimicrobial agents were thought to be effective on MRSA infections. From these results, we concluded that Tri-disc method for glycopeptide against MRSA, especially for TEIC, is not recommendable as a disc-diffusion method in susceptibility testing.

Aminoglycosides↗
PubMed1998

Left ventricular regional systolic motion in patients with right ventricular pressure overload.

Left ventricular regional systolic motion was investigated in patients with right ventricular pressure overload and 10 controls using tagged cine magnetic resonance imaging. The regional shortening fraction was determined in four segments (septal, lateral, inferior, and anterior) on the short-axis image. An asynchrony index, nonhomogeneity of regional shortening, was calculated. Septal shortening in these patients was depressed, and showed an inverse correlation with the right-to-left ventricular peak pressure ratio (r=-0.80, P<0.01). Lateral shortening was greater in the patients than in the controls (P<0.01). The asynchrony index was significantly greater in the patients than in the controls (P<0.01), and correlated with the right-to-left systolic pressure ratio (r=0.64, P=0.02) and the left ventricular end-diastolic pressure (r=0.79, P<0.01). The altered distribution of regional circumferential shortening results in an increased heterogeneity of regional systolic motion. These findings may have important implications for the assessment of ventricular function in patients with right ventricular pressure overload.

Adult↗