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Biomedical subjects

K Takeuchi

Publications and source records attributed to K Takeuchi.

At least 577 records · Page 32Linked to original sources

[A comparative study on the efficacies of ritipenem acoxil and cefotiam hexetil in bacterial pneumonia 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 bacterial pneumonia, we conducted a multi-center double-blind comparative study using cefotiam hexetil (CTM-HE) as the control drug. Both RIPM-AC and CTM-HE were orally administered at 200 mg t.i.d. for 14 days, in principle. The results were as follows: The total number of patients enrolled in this trial was 208, of which 152 cases (RIPM-AC group: 73, CTM-HE group: 79) were evaluable for clinical efficacy. 1. The clinical efficacy rates (excellent + good) were 91.8% (67/73) in the RIPM-AC group and 94.9% (75/79) in the CMT-HE group. There was no significant difference between the two groups, and 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 84.6% (22/26) in the RIPM-AC group and 91.7% (22/24) in the CTM-HE group, with no significant difference between the two groups. 3. Side effects were noted in 9 cases (9.6%) of the RIPM-AC group and 5 cases (4.9%) of the CTM-HE group. Abnormal laboratory test findings were observed in 23 cases (26.7%) of the RIPM-AC group and 15 cases (15.6%) of the CTM-HE group. There was no significant differences between the two groups in the incidence of side effects nor of abnormal laboratory test findings. In the safety evaluation, RIPM-AC was judged to be safe in 64 cases (68.1%) and CTM-HE in 82 cases (80.4%), with no significant difference. 4. The usefulness rates (markedly useful+useful) were 86.5% (64/74) in the RIPM-AC group and 92.5% (74/80) 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 bacterial pneumonia.

Adolescent↗

[Cardiac disfunction and myocardial energy metabolism caused by interleukin-2 (IL-2)].

There is accumulating evidence that inflammatory cytokines are involved in the pathophysiology of cardiac dysfunction found in sepsis, myocardial infarction and acute rejection after heart transplantation. Although there are some previous reports on cytokines and myocardial depression, myocardial energy metabolism caused by cytokines have not been established yet. The purpose of the present study is to determine if the IL-2 effect on contractile function is related to impaired energy production. In isolated perfused rabbit hearts (n = 6), we measured developed pressure, ATP and phosphocreatine by 31P-NMR spectroscopy during and after a 5 minute infusion of IL-2 (200 U/ml/min). Although there was slightly increased inorganic phosphate which might be affect on myocardial contractility reduced, high energy phosphate and intracellular pH did not change by IL-2 infusion, suggesting another mechanism for myocardial depression caused by inflammatory cytokine, IL-2.

Animals↗

Increased expression of histamine H1 receptor mRNA in allergic rhinitis.

BACKGROUND: Histamine plays an important role in producing nasal symptoms via histamine H1 receptor (H1R) in allergic rhinitis. It is reported that the minimum histamine concentration that induces sneezing is lower in allergic patients than in normal control subjects. Previous studies by binding assay on H1R gave divided results on whether the number of H1Rs is increased in allergic rhinitis or not. OBJECTIVE: The objective of this study was to examine if H1R mRNA expression is increased in patients with allergic rhinitis compared with normal healthy volunteers. METHODS: We extracted RNA from scrapings of inferior turbinate mucosa of 10 patients suffering from allergic rhinitis and 10 control subjects. As the H1R gene lacks introns, we treated RNA pellets by DNase to distinguish RNA from contaminating genomic DNA. Since amplification of H1R and beta-actin mRNA remained in an exponential phase at 35 cycles, H1R and beta-actin mRNAs were amplified for 35 cycles by reverse transcription-polymerase chain reaction (RT-PCR). The PCR products were hybridized with internal probes and band intensities were quantitated by a densitometer. RESULTS: The mean +/- SD of H1R/beta-actin ratio was 0.88 +/- 0.62 for the patients with allergic rhinitis and 0.29 +/- 0.17 for the normal subjects; the difference was statistically significant (P < 0.01). CONCLUSIONS: These data suggest that expression of H1R mRNA is increased in the nasal mucosa of the patients with allergic rhinitis.

Actins↗

Functional analysis and chromosomal gene assignment of rat kidney prostaglandin EP3 receptor.

We have reported two isoformes of rat prostaglandin EP3 receptor with their different carboxyl-terminal tails (rEP3A and rEP3B receptors), which are derived by alternative RNA splicing, and both receptors have been shown to be localized to renal distal tubules. In the present study, we characterized the signal transduction system of rat kidney EP3 receptors either in a renal cell line mimicking renal distal tubule cells, TKC2, or in COS-7 cells by functional expression of these receptors. We also examined the chromosomal localization of the EP3 receptor gene by fluorescence in situ hybridization (FISH). In TKC2 cells, vasopressin (AVP, 10(-7) M), prostaglandin (PG) E2 (10(-7) M), or forskolin (10(-8) M) markedly stimulated cyclic AMP formation. Overexpression of the rEP3A receptor significantly attenuated the AVP-, PGE2- or forskolin-induced cyclic AMP formation, whereas there was no change with rEP3B receptor expression. On the other hand, in COS-7 cells transfected with rEP3A receptor cDNA, PGE2 (10(-7) M) did not affect cytosolic free calcium concentration ([Ca2+]i), whereas transfection of rEP3B receptor cDNA evoked PGE2-induced increases in [Ca2+]i. Moreover, we have revealed that the rEP3 receptor gene is localized to rat chromosome 2q44-45. In conclusion, rEP3A or rEP3B receptor is suggested as a mediator of the natriuretic/diuretic action of PGE2 in renal distal tubules via a decrease in cyclic AMP formation or an increase in [Ca2+]i, respectively. Information of the gene assignment of rat EP3 receptor to rat chromosome 2q44-45 is useful for further analysis of the role of EP3 receptor in genetically hypertensive rat models.

Alprostadil↗

[Lymphangiomyomatosis with chylous ascites treatment successfully by peritoneo-venous shunting].

A 49-year-old woman was admitted to our hospital because of coughing and dyspnea. A chest roentogenogram showed emphysematous changes and a diffuse reticular shadow. A high-resolution CT scan of the chest showed many small cysts throughout the lungs. Lymphangiomyomatosis was diagnosed after examination of a specimen obtained by transbronchial biopsy. Abdominal distention due to chylous ascites developed during the hospital stay despite anti-estrogen therapy. Because the ascites was resistant to conservative therapy, we decided to begin peritoneo-venous shunting with a Denver Shunt system. After the operation, the abdominal distention was controlled for 1 year and 11 months, at which time the patient died of respiratory and heart failure with pneumonia. At autopsy, the shunt was patent and functional although about 900 ml of serous ascites fluid was present. An adenocarcinoma was found in the upper lobe of the right lung, but it may not have been related to the lymphangiomyomatosis. Peritoneovenous shunting with a Denver Shunt can be used to treat chylous ascites due to lymphangiomyomatosis when conservative therapy is insufficient.

Adenocarcinoma↗

[The pollen count of Cryptomeria japonica and nasal symptom of Cryptomeria japonica pollinosis patients in recent three years in Mie Prefecture].

Airborne scattering of Cryptomeria japonica pollen depends on climate. Total pollen count and scattering pattern varies from one year to another. We counted Cryptomeria japonica pollen in February and March from 1993 to 1995 at several points in Mie Prefecture. One-third to two-thirds of all the patients who visited our clinic for the first time in the pollen period were occupied by allergic patients. The pollen count in 1995 amounted to 17943/cm2 at Tsu and 99512/cm2 in the whole prefecture, which is the largest in the past 12 years. The number of days in which patients severely suffered was correlated to the pollen count for the past three years. It was shown that nasal symptoms developed after certain amount of pollen had scattered, but the severity of symptoms thereafter largely depended on the total pollen count. At Tsu in 1995, we scarcely had pollen scattering in February but had tremendous amount of pollen count in March. Percentage of development of nasal symptoms among thirty patients was well correlated to the logarithm of accumulated pollen count. When accumulated pollen count reached to 100/cm2, half the patients developed symptoms. Most of the patients developed symptoms when it reached to 1000/cm2. Since there is a great interindivisual difference in when and how much patients have nasal symptoms, the choice of therapy should be based not only on the pollen count but also on the symptom and condition of each patient.

Adult↗

[Inappropriate preservation of myocardium by topical cooling with iced slush].

Topical cooling with iced slush has been applied as a conventional myocardial preservation in open heart surgery. However, there might be several disadvantages due to topical cooling with iced slush which melted to be liquid, because of membrane integrity decreased during ischemia. To understand more detailed mechanism of deterioration for myocardium by immersion in some liquid during ischemia, we subjected isolated crystalloid perfused rabbit hearts to a 30 minute of ischemia with immersion in Krebs-Henseleit (K-H) solution (I), K-H+hexamethlyamiloride which was Na+/H+ channel blocker (II) and histidine containing cardioplegia (HBS) designed to accelerate anaerobic glycolysis by a proton buffering (III), followed by a 30 minute of reperfusion. These groups were compared to the hearts hanging in air during ischemia (control). Phosphocreatine (PCr), ATP and intracellular pH were measured by 31 PNMR in group I, II, III. Developed pressure (Dev P) and diastolic pressure (EDP) with a intracavitary balloon were also evaluated with monitoring of 2 mmHg diastolic contracture during ischemia. Dev P declined to 46%, 54% of preischemic value in group I and group II, respectively, although % recovery of control heart was 74% after ischemia-reperfusion process. Diastolic function was severely deteriorated in group I and II, as compared to control heart. ATP and intracellular pH showed a similar decline as PCr in group I and II which was not seen in group III during ischemia. HBS prevented the deterioration of PCr, ATP and intracellular pH during ischemia along with excellent recovery of myocardial function. We therefore conclude that 1) significant deterioration of myocardium occurs with ischemia if the heart preserved in Krebs-Heseleit solution and the mechanism of injury by immersion in liquid on the heart appears to be due to proton accumulation caused by intracellular acidification and loss of high energy phosphate.

Animals↗

[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↗

[A case of an old woman with Sjögren's syndrome associated with insulin-dependent diabetes mellitus].

Insulin-dependent diabetes mellitus (IDDM) is thought to result from the autoimmune destruction of the insulin-dependent beta cells of the pancreas. Sjögren's syndrome is also an autoimmune disease characterized by the destruction of the lacrimal and salivary glands that leads to keratoconjunctivitis sicca and xerostomia. But it is a very rare case that a patient with Sjögren's syndrome developed IDDM. We present a case of a 65-year old woman with Sjögren's syndrome who developed diabetic ketoacidosis due to IDDM. Recent studies have revealed that there was molecular mimicry between glutamic acid decarboxylase (GAD) and coxsackievirus. Furthermore, some reports have shown that sialadenitis was represented in IDDM model mice. This case shows the possibility that a causal relationship between IDDM and Sjögren's syndrome may exist.

Aged↗

Proton magnetic resonance spectroscopy of the left medial temporal and frontal lobes in chronic schizophrenia: preliminary report.

Proton magnetic resonance spectroscopy (MRS) was performed in 30 medicated schizophrenic patients and 30 normal subjects. Two groups, each containing 15 schizophrenic patients and 15 age-and sex-matched normal subjects, received MRS examinations for different volumes of interest, either the frontal lobe or the medial temporal lobe. Schizophrenic patients showed a decrease in the ratios of N-acetylaspartate (NAA)/choline-containing compounds (Cho) and NAA/creatine-phosphocreatine (Cr). The patients also showed an increase in the ratio of Cho/Cr in the left medial temporal lobe but not in the left frontal lobe. The age at onset of illness correlated positively with the ratios of NAA/Cho and NAA/Cr in the medial temporal lobe. No significant correlation was observed between the ratios of NAA/Cho, NAA/Cr, or Cho/Cr in the left medial temporal and frontal lobes and clinical symptomatology as assessed by the Scale for the Assessment of Negative Symptoms and the Positive and Negative Syndrome Scale.

Adult↗

Inhibition of metastasis of Lewis lung carcinoma by urinary trypsin inhibitor in experimental and spontaneous metastasis models.

A purified human urinary trypsin inhibitor (UTI) and its related synthetic peptides were examined to determine whether they could inhibit production of experimental and spontaneous lung metastases by murine Lewis lung carcinoma (3LL) cells. Three peptides, peptide I, peptide 2 and peptide 3, representing the amino acid sequences within the UTI molecule, were synthesized. UTI and peptide 2 inhibited human leukocyte elastase (HLE). UTI and peptide 3 specifically inhibited human and murine plasmin activity. Peptide I had essentially no inhibitory activity. In an in vivo spontaneous metastasis model, multiple s.c. injections of UTI or peptide 3 for 7 days immediately after s.c. tumor cell inoculation significantly inhibited the formation of lung metastasis in C57BL/6 mice in a dose-dependent manner. UTI reduced lung tumor colonization more effectively than peptide 3. Peptides 1 and 2, however, did not affect the formation of lung metastasis. Inhibition of lung metastasis was not due to direct anti-tumor effects of UTI and peptide 3. In an in vivo experimental metastasis assay, multiple s.c. injections of UTI for 7 days after i.v. tumor cell inoculation inhibited metastatic lung tumor colonization, while peptide 3 did not affect metastasis. Peptides 1 and 2 did not affect the formation of lung metastasis. When examined with an in vitro assay system using a modified Boyden chamber, UTI and peptide 3 suppressed the invasion of tumor cells through Matrigel. UTI and peptide 3 inhibited neither cell proliferation nor the binding of tumor cells to Matrigel and showed no significant suppression of chemotactic migration of tumor cells to fibronectin. Our results suggest that UTI efficiently regulates the mechanism involved in not only the entry into vascular circulation of tumor cells (intravasation, though, at least in part, inhibition of the proteolytic enzyme plasmin) but also the extravasation step of the metastatic process.

Amino Acid Sequence↗

Improved protection of the hypertrophied left ventricle by histidine-containing cardioplegia.

BACKGROUND: Myocardial hypertrophy has been shown to lead to increased susceptibility to ischemia with accelerated loss of high-energy nucleotides, greater accumulation of H+ and lactate, and earlier onset of contracture. METHODS AND RESULTS: To determine whether promoting anaerobic glycolysis during ischemia by buffering H+ results in improved preservation of the hypertrophied heart, we studied the effect of a histidine-containing solution (HBS) on recovery of contractile function and energetic state. Hypertrophied rabbit hearts (aortic banding at 10 days) were subjected to 40 minutes of 37 degrees C ischemia and reperfusion in an isolated Langendorff model. This group was compared with groups receiving St Thomas solution and high-potassium Krebs buffer solution (KCl). Although both phosphocreatine (PCr) and ATP were lower in hypertrophied hearts by end-ischemia compared with nonhypertrophied age-matched controls, there was significantly higher PCr, ATP, and intracellular pH in the HBS group compared with the St Thomas and KCl groups. Recovery of left ventricular developed pressure was best in the HBS group (91% of preischemic values) as was end-diastolic pressure after 30 minutes of reperfusion. Lactate production was also significantly greater in the HBS group, suggesting augmentation of anaerobic glycolysis. CONCLUSIONS: We concluded that administration of histidine-containing cardioplegia promotes anaerobic glycolysis and improves recovery of high-energy phosphates and contractile function in hypertrophied myocardium.

Animals↗

1 alpha,25-dihydroxyvitamin D3 analogs featuring aromatic and heteroaromatic rings: design, synthesis, and preliminary biological testing.

Aromatic compounds 2a-c, analogs of 1 alpha, 25-dihydroxyvitamin (calcitriol, 1), and heteroaromatic compounds 4a-c and 5a-c, analogs of 19-nor-1 alpha, 25-dihydroxyvitamin D3 (3), were designed to simulate the topology of their biologically potent parent compounds while avoiding previtamin D equilibrium. Convergent and facile total syntheses of the analogs (+)-2b, (+)-2c, (-)-4b, and (-)-5b were achieved via carbonyl addition of regiospecifically formed organolithium nucleophiles to the enantiomerically pure C,D-ring ketone (+)-17, characteristic of natural calcitriol (1). Likewise, hybrid analogs 20a-c were prepared to determine whether incorporation of a known potentiating side chain would lead to increased biological activity. Preliminary in vitro biological testing showed that aromatic analogs (+)-2b, (+)-2c, and 20a-c as well as heteroaromatic analogs (-)-4b and (-)-5b have very low affinities for the calf thymus vitamin D receptor but considerable antiproliferative activities in murine keratinocytes at micromolar concentration. No biological advantage was observed in this keratinocyte assay for the doubly modified hybrid analogs 20a-c over the singly modified parent (+)-2b. Analog (+)-2b, but surprisingly not the corresponding analog 20b differing from (+)-2b only in the side chain, showed considerable activity in nongenomic opening of calcium channels in rat osteosarcoma cells.

Animals↗

Analysis of the autoantibody response to fibrillarin in human disease and murine models of autoimmunity.

Fibrillarin, a component of the U3 RNP particle, is a target for the spontaneously arising autoantibodies in human scleroderma and a monoclonal autoantibody (72B9) derived from the autoimmune mouse strain (NZB x NZW) F1. Autoantibodies against fibrillarin can also be induced in H-2s mice by treatment with mercuric chloride (HgCl2). The objective of this study was to compare the spontaneously occurring anti-fibrillarin autoantibody response with the autoantibody response induced by HgCl2 treatment. Immunofluorescence microscopy on human HEp2, mouse 3T3, and Xenopus XIK-2 cells, immunoblotting with use of nuclear extract from human MOLT-4, mouse 3T3, and Xenopus XIK-2 cells, and immunoprecipitation with use of in vitro translation products of RNA transcripts from yeast fibrillarin cDNA were used in this analysis. Both spontaneous and induced autoantibodies displayed common reactivity in that, irrespective of the antigenic source, they gave the same nucleolar immunofluorescence pattern and a restricted immunoblotting reactivity targeting predominantly the 34-kDa protein fibrillarin. Immunoprecipitation of N- and C-terminal truncated fibrillarin constructs also demonstrated a common pattern of reactivity. All Abs precipitated a fragment comprising amino acids 1-312 but not a smaller fragment containing amino acids 1-257. The majority of sera could not precipitate an N-terminal truncated molecule consisting of amino acids 157-327. These immunoprecipitation experiments support recognition of a common epitope requiring both N- and C-regions, which may be exemplified by the reactivity of murine monoclonal anti-fibrillarin autoantibody 72B9. Our results indicate that spontaneous human and toxin-induced murine autoantibodies to fibrillarin share common reactivity against this highly conserved nucleolar protein.

Amino Acid Sequence↗

cDNA cloning of mouse VLA-3 alpha subunit.

cDNA clones for mouse VLA (very late antigen)-3 alpha subunit (alpha 3 integrin) were isolated and sequenced. The encoded mouse alpha 3 integrin subunit was composed of 1,053 amino acid residues. The results of sequence analysis revealed similar structural characteristics of other VLA alpha subunits. For example, the presence of a large extracellular domain including three putative metal binding sequences, a transmembrane domain, and a short cytoplasmic domain. A higher level of its message was detected in thymus than in kidney, stomach, spleen, liver, brain, or lung by Northern blotting analysis.

3T3 Cells↗

Direct detrimental effects of L-arginine upon ischemia--reperfusion injury to myocardium.

The effects of L-arginine on recovery of myocardial contractile function and oxidative metabolism were investigated in a model of reversible global normothermic, ischemic injury using an isolated, buffer-perfused rabbit heart preparation. One mM L-arginine was infused into hearts for 2 min at the onset (group 1) of a 35 min period of ischemia or at the onset of reperfusion (group 2). In non-ischemic hearts, L-arginine caused a slight increase in developed pressure but had no effects on diastolic pressure, oxygen consumption (MVO2), coronary flow, or lactate production. When administered either before or after ischemia-reperfusion. L-arginine caused a significant increase in the diastolic pressure-volume relationship (PVR) and decline in systolic function when compared to untreated control hearts receiving the same ischemic injury. Recovery of MVO2 and high energy phosphates (phosphocreatine and ATP), measured by 31P-NMR spectroscopy, were significantly impaired in L-arginine-treated hearts compared to reperfused control hearts. Lactate release on reperfusion was also higher in both arginine-treated groups. Nitric oxide release into the coronary circulation (measured in separate experiments by the conversion of [15N]L-arginine to [15N]nitrate/nitrite using gas chromatography/mass spectroscopy) was not increased by L-arginine administration. Thus, we conclude that L-arginine acts synergistically with ischemia reperfusion to augment myocardial injury, which includes inhibition of oxidative metabolism and mitochondrial function.

Animals↗