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Biomedical subjects

K Takeuchi

Publications and source records attributed to K Takeuchi.

At least 523 records · Page 29Linked to original sources

[beta-blocker in hypertension].

The beta-blockers are either nonselective and affect both beta 1- and beta 2-receptors, are relatively selective for the alpha 1 subclass, or are able to have activity against alpha-receptors. The ability to reduce blood pressure is very common among all beta-blockers, and beta-blockers are recommended for one of the first-line drugs in hypertension treatment by JNCV. beta-blockers should be used considering their pharmacological properties and potential side effects, according to the pathophysiological conditions involved. The superiority of beta-blocker to other types of antihypertensive drug has not yet been evidenced by larger scale clinical trials which have been carried out so far. To verify more precisely the usefulness of beta-blocker in hypertension treatment, more large scale clinical trials are required to be carried out. The fixed-dose combination of beta-blockers and calcium blockers appears to be more effective rather than that of beta-blockers and diuretics.

Adrenergic beta-Antagonists↗

[Palliative intubation of esophageal prosthesis in two patients with lung cancer].

Case one: A 61-year-old man was admitted to the hospital because of coughing. Adenocarcinoma of the lung was diagnosed. The patient was treated with bronchial artery infusion of cisplatin and mitomycin C, followed by irradiation; and there was a partial response. Eighteen months later he was admitted to the hospital because of dysphagia. An esophageal prosthesis was inserted because of esophageal stenosis surrounded by local recurrent tumor. After intubation, the patient was able to eat and was discharged. Although the patient died 5 months later, the tube was patent and functional until that time. Case two: A 63-year-old man was admitted to the hospital because of coughing. Adenocarcinoma of the lung was diagnosed. The patient was treated with 3 cycles of chemotherapy consisting of cisplatin, vindesine, and mifomycin C, which were followed by irradiation; and there was a partial response. Six months later he was admitted to the hospital because of dysphagia. An esophageal prosthesis was inserted because of esophageal stenosis surrounded by mediastinal lymph nodes. Although the patient was able to eat, bilateral pleuritis and mediastinitis developed and he died ten days after intubation. At autopsy the esophagus was found to have been perforated. Palliative intubation of an esophageal prosthesis can be effective in patients with esophageal stenosis due to lung cancer, but care must be taken to prevent fatal complications.

Adenocarcinoma↗

Gastric hyperemic response during vagally mediated acid secretion by TRH analog in rats.

The mechanisms of gastric hyperemic response during vagally mediated acid secretion induced by YM-14673, an analog of thyrotropin-releasing hormone, were investigated in urethane-anesthetized rats. The stomach was mounted on an ex vivo chamber and perfused with saline, and gastric mucosal blood flow (GMBF) was measured using a laser Doppler flowmeter, simultaneously with acid secretion. The i.v. injection of YM-14673 (0.1 approximately 1 mg/kg) increased both GMBF and acid secretion in a dose-dependent manner, and these responses persisted during a 90-min test period. The increases in GMBF and acid secretion induced by YM-14673 (0.3 mg/kg) were totally abolished by either bilateral vagotomy or atropine. Sensory ablation by capsaicin also significantly attenuated GMBF response without affecting acid secretion. On the other hand, N(G)-nitro-L-arginine methyl ester (L-NAME), but not D-NAME, significantly attenuated the increase in GMBF in an L-arginine-sensitive manner, although acid secretion was slightly augmented; in particular, gastric hyperemic response during the first 30 min (early period) was almost totally abolished. In contrast, omeprazole significantly attenuated GMBF response only in the late period, although it completely inhibited acid secretion in response to YM-14673. Combined treatment of omeprazole and L-NAME totally abolished hyperemic responses induced by YM-14673 during the test period. YM-14673 significantly elevated the release of nitrite and nitrate into the gastric lumen, and this response was inhibited by either atropine or L-NAME. These results suggest that YM-14673 increases GMBF as well as acid secretion, mediated by vagal-cholinergic pathways, and that gastric hyperemia is further regulated by two distinct mechanisms. The response in the early period is independent of acid secretion and mediated mainly by nitric oxide, whereas that in the later period occurs in association with acid secretion and may be mediated by nitric oxide and sensory neurons.

Animals↗

[A clinical application of histidine buffered cardioplegia].

Blood cardioplegia has been widely accepted due to better oxygen delivery, pH buffering and free radical scavenge. We have found that a crystalloid cardioplegia solution formulated to accelerate anaerobic glycolysis with high buffering capacity. To conserve blood cardioplegia, we formulated a crystalloid cardiopletia containing 100 mM histidine for buffering. This cardioplegia (HBS) was compared to cold blood cardioplegia in patients requiring open heart surgery. Eighty patients including HBS (n = 28), and CBC (n = 40) were involved in this study. Left ventricular end-systolic elastance (Emax; mmHg/cm3) was evaluated pre- and postoperatively. Cardiac index and inotropic requirement were also monitored at 1, 3, and 12 hours after cardiopulmonary bypass. There was no death in either group. All hearts returned to previous rhythm in HBS group, whereas total 12 DC cardioversions were requested in 6 patients. Emax was significantly higher in HBS group (5.2 +/- 0.6 mmHg/cm3) than in CBC group (3.4 +/- 0.4 mmHg/cm3). Cardiac index was also significantly higher in HBS group postoperatively than in CBC group with lower inotropic requirements. We conclude that histidine containing crystalloid cardioplegia provides excellent recovery of cardiac performance with lower inotropic requirements in open heart surgery. The ease of use, and lack of blood are other important advantages of this crystalloid cardioplegia.

Cardiac Surgical Procedures↗

Function of angiotensin II type 2 receptor in the postglomerular efferent arteriole.

The balance of vasucular tone between afferent (Af-Art) and efferent arterioles (Ef-Art) is a critical determinant of the glomerular hemodynamics. We recently reported that selective activation of angiotensin II type 2 receptor (AT-2R) causes dilation in the Af-Art. However, the functional role of AT-2R in the Ef-Art has not been defined. In the present study, we microperfused rabbit Ef-Art in vitro, and examined the effect of angiotensin II (Ang II; 10(-11) to 10(-8) M) on the luminal diameter in the presence or absence of an AT-2R antagonist PD123319 (PD; 10(-7) M). Angiotensin II caused dose-dependent constriction in Ef-Arts, with a significant constriction occurring at 10(-11) M; at 10(-10) M the diameter decreased by 28 +/- 4% (N = 6). Pretreatment with PD significantly (P < 0.0125) augmented vasoconstrictor action of Ang II; at 10(-10) M the diameter decreased by 44 +/- 4% (N = 6). We then examined whether blockade of Ang II type 1 receptor (AT-1R) uncovers vasodilator action of Ang II mediated by AT-2R. Efferent arterioles were preconstricted by about 40% with norepinephrine and AT-1R was blocked with its selective antagonist CV11974 (CV; 10(-8) M). Angiotensin II added to preconstricted and CV-pretreated Ef-Arts caused a dose-dependent dilation; at 10(-8) M diameter increased by 28 +/- 3% (N = 5). The dilation was completely abolished by simultaneous pretreatment with PD (N = 4). Our results demonstrate that in the Ef-Art selective activation of AT-2R causes vasodilation, which opposes the vasoconstrictor action of Ang II.

Angiotensin II↗

[An autopsy case of Goodpasture syndrome preceded with membranous glomerulonephritis].

Goodpasture syndrome (GS) is an autoimmune disorder characterized by the association of pulmonary hemorrhage and rapidly progressive glomerulonephritis. The pathogenesis of GS is still unknown, but was shown to be the result that antibodies directed against glomerular basement membrane (GBM) antigens could injure both glomerular and pulmonary alveolar basement membrane. And membranous glomerulonephritis (MGN) is a glomerular disease characterized by epimembranous immune deposits and basement membrane thickening. MGN typically presents with the onset of nephrotic syndrome, but it often presents with only asymptomatic proteinuria. We reported an autopsy case of GS preceded with MGN. A 70-year-old man was admitted to our hospital with acute renal failure in May 2, 1996. Percutaneous renal biopsy demonstrated a crescentic glomerulonephritis associated with MGN and linear immunofluorescent staining of the basement membrane with antibodies to IgG. Two weeks later on admission he began to develop slight hemoptysis and chest X-ray showed pulmonary hemorrhage, Furthermore, his serum anti-GBM antibodies titer was very high. He was diagnosed as GS associated with MGN and treated with plasma exchange, glucocorticoid, and cyclophosphamide. Though his symptom was improved for intensive support, he suddenly died on June 22. Autopsied lungs showed focal pulmonary hemorrhage, but were not considered to be life-threatening. The cause of the death remained unclear.

Aged↗

24R,25-(OH)2 vitamin D3 inhibits 1alpha,25-(OH)2 vitamin D3 and testosterone potentiation of calcium channels in osteosarcoma cells.

Calcium influx via L-type calcium channels in osteoblast cells causes a rapid (in seconds) elevation in intracellular calcium initiated by plasma membrane receptors for 1alpha, 25-dihydroxyvitamin D3 (1alpha,25-D3). 24R,25-Dihydroxyvitamin D3 (24,25-D3) alone, in concentrations up to 200 nM, does not cause potentiation of calcium currents in osteoblasts, but it does inhibit the current potentiation by 1alpha,25-D3. To determine how various steroids interact in their potentiation of calcium channels, the action of vitamin D3 analogues and testosterone with calcium channels in the rat osteoblast-like cell line ROS 17/2.8 was investigated. Bath additions of both 1alpha,25-D3 and testosterone at doses below K1/2 (the dose causing 50% left shift in the current-voltage relationship) are additive in their ability to potentiate calcium channels. When 1alpha,25-D3 and testosterone are added together at concentrations that would cause a maximal shift in the current-voltage relationship by each agent alone (Vmax), the effect of these steroids is not additive. Taken together these data suggest one population of calcium channels is activated by 1alpha, 25-D3 or testosterone. The shift in the current-voltage relationship caused by 1alpha,25-D3 is reduced by 1beta,25-dihydroxyvitamin D3 (1beta,25-D3), an agent which is thought to act specifically on the plasma membrane receptor for 1alpha,25-D3, but the potentiation caused by testosterone is not blocked by 1beta,25-D3. However, 24, 25-D3 inhibits the left shift in the peak current-voltage relationship mediated by either 1alpha,25-D3 and testosterone. This result implies that 1) 1beta,25-D3 directly displaces 1alpha,25-D3 but not testosterone from its plasma membrane receptor, and 2) the rapid (in seconds) stimulatory effects of 1alpha,25-D3 and testosterone on calcium channels are mediated by separate plasma membrane receptors for testosterone and 1alpha,25-D3, which are blocked by another receptor for 24,25-D3. The interaction of these three receptors with L-type calcium channels is pertussis toxin-sensitive.

24,25-Dihydroxyvitamin D 3↗

Effect of zeta potential of cationic liposomes containing cationic cholesterol derivatives on gene transfection.

Cationic liposomes are known to be useful tools for gene transfection. However, the relation between transfection efficiency and physicochemical properties of liposomes has not been well understood. Here, we synthesized eight cationic derivatives of cholesterol which contain a tertiary amino head group with a different spacer arm. Transfection of plasmid pSV2CAT DNA into cells was done by cationic liposomes made of a mixture of dioleoylphosphatidylethanolamine (DOPE) and each cationic cholesterol derivative. At the same time we measured zeta potential of cationic liposomes by laser Doppler spectroscopy. The present results indicated that zeta potentials of cationic liposomes were well related to transfection activity of pSV2CAT DNA. This suggested that zeta potential of cationic liposomes is one of important factors which control gene transfection.

3T3 Cells↗

Identification of genes differentially expressed in association with metastatic potential of K-1735 murine melanoma by messenger RNA differential display.

To identify genes differentially expressed in association with the metastatic potential of K-1735 mouse melanoma cells, the mRNA differential display method was applied to compare mRNAs from high- and low-metastatic K-1735-derived cells. Three of the high- and three of the low-metastatic clones were used to reduce the false positives in the initial screening, and Southern blot screening against reverse transcription-PCR products was used to confirm that cDNA fragments detect differential expression between high- and low-metastatic cells. By using 256 different combinations of modified long arbitrary primers which provide broad screening of expressed genes, approximately 12,000 cDNA fragments were amplified from mRNA of each cell line. Among them, eight genes were identified as being expressed in either high- or low-metastatic cells using Northern blot analysis. Integrin alpha6 and two unknown genes were expressed in high-metastatic cells, whereas beta-tropomyosin, macrophage colony-stimulating factor, inhibin/activin betaB subunit, and two unknown genes were expressed in low-metastatic cells. These results indicate that the acquisition of metastatic potential in tumor cells was regulated by activation and/or inactivation of several specific genes, such as those for cell adhesion molecule, cytoskeletal protein, and growth factors.

Animals↗

The mumps virus SH protein is a membrane protein and not essential for virus growth.

By immunoprecipitation analysis using antisera against oligo peptides synthesized based on the deduced N-terminal and C-terminal amino acid sequences of the SH proteins of the mumps virus, the SH protein was detected in mumps virus-infected cells. The SH protein expressed from cDNA by the vaccinia-T7 expression system was recovered in the membrane fraction. Association of the SH protein with the membrane was resistant to high salt, EDTA, and alkaline treatment but sensitive to detergents. Indirect immunofluorescence experiments showed that the SH protein is involved in the exocytotic pathway. These data indicate that the SH protein is a membrane protein. Treatment of microsomes with TPCK-trypsin suggested that the SH protein is oriented in the membrane with its C-terminal facing the cytoplasm. Furthermore the SH protein was not detected in a particular strain (Enders strain) of mumps virus, indicating that the mumps virus SH protein is not essential for virus replication.

Amino Acid Sequence↗

Inhibition by antipsychotic drugs of L-type Ca2+ channel current in PC12 cells.

Inhibition by antipsychotic drugs of voltage-gated L-type Ca2+ channels was characterized in rat neuronal cell line pheochromocytoma PC12 cells. Under whole-cell voltage-clamp, haloperidol and chlorpromazine (1-100 microM) inhibited Ba2+ current permeating through Ca2+ channels. Fluspirilene and pimozide the Ba2+ current at lower concentrations (fluspirilene, 0.1 pM to 1 nM; pimozide 10 pM to 1 microM). Effects of dopamine receptor antagonists and calmodulin antagonists were tested because antipsychotic drugs are known to exhibit these pharmacological activities. Sulpiride (1 and 10 microM), an antagonist to dopamine D2 receptors, and SCH-23390 (R(+)-7-chloro-8-hydroxy-3-methyl-l-phenyl-2,3,4,5-tetrahydro-1H-3- benzazepine; 1 and 10 microM), an antagonist to dopamine D1 receptors, also inhibited the Ba2+ current. As for calmodulin antagonists, W-7 (N-(6-aminohexyl)-5-chloro-1-naphthalenesulfonamide; 10 and 100 microM) as well as calmidazolium (10 nM to 1 microM) reduced the Ba2+ current. The inhibition by haloperidol or fluspirilene of the Ba2+ current was not affected when GTP in intracellular solution was replaced with GDP beta S. These properties of the Ca2+ channel inhibition are discussed by comparing with those of the K+ channel inhibition and in relation to therapeutic relevance.

Animals↗

Proton magnetic resonance spectroscopy of basal ganglia in chronic schizophrenia.

Proton spectra in the regions of the right and left basal ganglia were studied in 14 medicated patients with chronic schizophrenia using proton magnetic resonance spectroscopy (1H MRS). Ratios of N-acetyl-aspartate (NAA) to choline-containing compounds (Cho) were significantly reduced in the bilateral basal ganglia regions compared to normal subjects. The relative level of Cho was increased in the left basal ganglia region in comparison to normal subjects. This finding suggests the presence of disturbances in phospholipid metabolism in the basal ganglia. The level of NAA was decreased in the bilateral basal ganglia regions, which may indicate neuronal dysfunction. The 1H MRS study demonstrated dysfunctions in the basal ganglia regions in medicated patients with chronic schizophrenia.

Adult↗

Transcriptional regulation of the lysozyme gene in airway gland serous cells.

Lysozyme is expressed in serous, but not mucous, cells of the tracheobronchial glands and thereby constitutes a marker of the serous cell lineage in these glands. To identify DNA regulatory elements and transcription factors mediating the commitment of progenitor cells to the serous cell lineage, we have characterized the regulatory activity and DNA-protein interactions of the 5'-flanking region of the bovine lysozyme gene lys 5a. Results obtained from these studies indicate that although approximately 94 bp of 5'flanking DNA are necessary for high level expression in transient transfection assays, an evolutionarily conserved promoter within 66 bp of the transcription start site is sufficient to confer serous cell-specific expression. Farther upstream, within 6.1 kb of the 5' flanking region, are 4 silencers. Analysis of the serous cell-specific lysozyme promoter by electrophoretic mobility shift assay (EMSA) revealed the presence of binding sites for 3 serous cell nuclear proteins, designated LSF1, LSF2 and LSF3. Binding of LSF2 and LSF3 was localized to a 20-mer subdomain (-50/-30) of the cell-specific promoter using binding competition assays. More accurate identification of the protein binding site(s) was achieved through the use of mutagenesis, which implicated the motif 5' AAGGAAT 3' (-46/-40) in both protein binding and serous cell-specific transcriptional activity. This motif has previously been identified as a binding site for ets protein transcription factors, suggesting that serous cell-specific regulation of lys 5a transcription is partly controlled by the binding of ets-like protein(s) to the motif 5'AGGAAGT3'.

Amino Acid Sequence↗

Reduction in hippocampal formation volume is caused mainly by its shortening in chronic schizophrenia: assessment by MRI.

We performed contiguous, 1 mm thick, magnetic resonance imaging scans in 18 men with chronic schizophrenia and in 18 age-matched healthy subjects to test in living patients the findings of a previous postmortem study. The schizophrenic patients showed bilaterally shortening (left, -6%; right, -9%) and volume reduction (left, -9%; right, -11%) of the hippocampal formation (HF). Volumes of HF correlated positively with HF length in the schizophrenic patients. The reduction in bilateral HF volumes was small after controlling for HF lengths (left, -3%; right, -3%). In schizophrenic patients, significant negative correlations were found bilaterally between the length of HFs and the scores for attention, bizarre behavior, and positive formal thought disorder. The results suggest that the volume reduction seen in the HFs of schizophrenic patients was caused mainly by a shortening of the HF and that these clinical symptoms may be associated with shorter HF length.

Adolescent↗