Biomedical subjects

K Takeda

Publications and source records attributed to K Takeda.

At least 667 records · Page 37Linked to original sources

PubMed1995

Altered cardiovascular responses to purinergic A2 stimulation in the nucleus tractus solitarius of spontaneously hypertensive rats.

OBJECTIVE: To investigate the cardiovascular effects of adenosine A2 receptor stimulation in the nucleus tractus solitarius and whether these effects are altered in hypertension. DESIGN AND METHODS: Ten- or 11-week-old spontaneously hypertensive rats (SHR) or Wistar-Kyoto (WKY) rats were anaesthetized with urethane. Adenosine (100 ng) or adenosine A2 agonist (2-octynyladenosine, 5 ng) were micro-injected (50 nl) into the nucleus tractus solitarius. Blood pressure and heart rate were measured from a femoral artery. Sympathetic nerve activity was recorded from the abdominal splanchnic nerve. RESULTS: Blood pressure, heart rate and sympathetic nerve activity were consistently decreased after the micro-injection of adenosine into normotensive rats. Changes from the baseline in blood pressure, heart rate and sympathetic nerve activity were significantly smaller in SHR than in WKY rats (blood pressure: SHR -5.6 +/- 2.1% versus WKY rats -20.0 +/- 2.1%; heart rate: SHR -5.4 +/- 0.88% versus WKY rats -9.2 +/- 2.3%; sympathetic nerve activity: SHR -5.5 +/- 1.1% versus WKY rats -21 +/- 2.8%). Micro-injection of an A2 agonist into the nucleus tractus solitarius also decreased blood pressure and heart rate, and those responses were not inhibited by pretreatment with an adenosine A1-specific antagonist. The response induced by micro-injection of A2 agonist into the nucleus tractus solitarius was significantly smaller in SHR than in WKY rats, whereas the changes in heart rate did not differ statistically (blood pressure: -23.4 +/- 4.7% versus -10.8 +/- 2.1%; heart rate: -12.1 +/- 1.2% versus -13.6 +/- 2.1%). CONCLUSION: The present results suggest that stimulation of adenosine A2 receptors in the nucleus tractus solitarius decreases both blood pressure and inhibitory sympathetic nerve activity and that those inhibitory responses to adenosine in the nucleus tractus solitarius are deranged in SHR.

Adenosine↗

PubMed1995

Three cases of chemotherapy-induced acral erythema.

Three cases of chemotherapy-induced acral erythema are reported. All the patients had received cyclophosphamide, vincristine, adriamycin, prednisolone, and granulocyte-colony stimulating factor (G-CSF) for the treatment of leukemia or malignant lymphoma. From 35 to 45 days after the start of chemotherapy, painful erythematous lesions developed on their palms, soles, fingers, and toes, resulting in blister formation and desquamation. The recent higher incidence of chemotherapy-induced acral erythema may be correlated with the popularity of G-CSF, which allows the use of higher doses of chemotherapeutic drugs.

Adult↗

PubMed1995

SSCP analysis of pig mitochondrial DNA D-loop region polymorphism.

The sequence polymorphism that occurs in the mitochondrial DNA (mtDNA) displacement (D)-loop region is useful as a cytoplasmic DNA marker. We cloned the mtDNA D-loop regions of five breeds of pig by polymerase chain reaction (PCR) and determined their sequences. The sequence diversities in D-loop regions among five breeds of pig were located in the starting area of heavy-strand replication. From these sequences, we designed primers for PCR-mediated single-strand conformation polymorphism (PCR-SSCP) analysis that amplified the most polymorphic 227 bp fragment of the D-loop region. The results of PCR-SSCP analysis clearly showed that four types of polymorphism (A to D) are found in Landrace (A), Large White (A, B), Duroc (A), Göttingen miniature pig (B) and Meishan (C, D). The same polymorphisms were also detected from each porcine embryo by this method. Our results show that PCR-SSCP analysis is useful in detecting polymorphisms in the D-loop region of pigs and pig embryos.

Animals↗

PubMed1995

Role of nitric oxide in impaired coronary circulation and improvement by angiotensin II receptor antagonist in spontaneously hypertensive rats.

1. To determine whether coronary flow regulation by nitric oxide (NO) is impaired in the hypertensive heart (HTH), coronary perfusion was measured in isolated rat hearts using NO synthesis inhibitor L-NG-monomethyl arginine (L-NMMA) in Wistar-Kyoto (WKY) rat and spontaneously hypertensive rat (SHR) with and without chronic Nomega-nitro-L-arginine-methylester (L-NAME) treatment. Moreover, the effect of angiotensin II receptor antagonist (AT1 receptor antagonist) (TCV-116) on the impaired coronary circulation in HTH was examined. 2. Coronary flow (CF) was decreased in HTH accompanied with cardiac hypertrophy. The decreased response of CF to L-NMMA infusion was diminished in HTH. It is suggested that NO production was reduced in coronary vasculature in HTH. 3. In chronic L-NAME treated SHR, blood pressure and cardiac hypertrophy were accelerated. Although coronary flow resistance (CFR) was increased, the increased response of CFR to L-NMMA infusion was not altered. 4. The AT1 antagonist improved total minimal coronary flow resistance (MCFR) restoring CFR response in SHR, although it did not recover CFR response in chronic L-NAME treated SHR. 5. Taken together the findings suggest that NO production was exhausted in the coronary artery even in the developing stage of hypertension and this exhaustion could contribute to the impairment of coronary circulation of HTH.

Angiotensin II↗

PubMed1995

Effects of gamma-linolenic and eicosapentaenoic acids on blood pressure in SHR.

1. The present study was performed to determine whether chronic treatments with gamma linolenic acid (n-6, GLA) or eicosapentaenoic acid (n-3, EPA) would alter serum and red blood cell (RBC) unsaturated fatty acid composition, and to determine whether these treatments would affect blood pressure (BP), serum lipid metabolism and the development of atherosclerosis in spontaneously hypertensive rats (SHR). 2. To compare the effects on atherosclerosis, some SHR were denuded of aortic endothelium so that the development of atherosclerosis would be accelerated. Olive oil (control), GLA or EPA (low dose: 5 mg/day per rat, high dose: 50 mg/day per kg, respectively) was administered intraperitoneally for 6 weeks in SHR. 3. GLA treatments increased GLA and its metabolite, dihomo-GLA, levels in serum but not in RBC, while EPA treatments increased EPA level both in serum and in RBC. 4. The BP of control SHR was further elevated. EPA significantly reduced this elevation of systolic, mean and diastolic pressure within the first week and thereafter, whereas GLA did not affect BP elevation. Neither heart rate or bodyweight gain was affected by these treatments. 5. Serum total cholesterol (TC), triglyceride (TG), and glucose (G) levels and the development of atherosclerosis were unaffected by either GLA or EPA treatment. 6. In summary, chronic EPA but not GLA treatment slightly reduced BP elevation in SHR. Although chronic GLA or EPA treatment increased the respective serum level, these treatments unaltered serum TC, TG and G levels, and could not prevent the development of aortic atherosclerosis in SHR.

Animals↗

PubMed1995

Hypothalamic and medullary GABAA and GABAB-ergic systems differently regulate sympathetic and cardiovascular systems.

1. To determine whether hypothalamic and medullary GABA (gamma-aminobutyric acid)B stimulation would affect the sympathetic and cardiovascular activities, and to determine whether these effects would be altered in hypertension, baclofen (a GABAB agonist) was injected into a hypothalamic pressor area (ventromedial hypothalamus, VMH), a depressor area (anterior hypothalamus, AH), or a nucleus tractus solitarius (NTS) in normotensive and spontaneously hypertensive rats (SHR). 2. Intracerebroventricular (ICV) injections of a GABAA agonist (muscimol, 1 mu g) decreased blood pressure (BP) and heart rate (HR). ICV injections of baclofen (2 mu g) elicited biphasic depressor and pressor effects, and these effects were abolished by a pretreatment with saclofen (GABAB antagonist, 100 mu g, icv). 3. Muscimol (400 ng) and baclofen (800 ng) injected into VMH decreased sympathetic nerve activity (SNA), BP and HR to almost similar levels, while saclofen injected into VMH increased HR without affecting BP levels. 4. The same dose of baclofen injected into AH increased BP, but muscimol (AH) did not alter BP. 5. Both muscimol and baclofen injected into NTS increased BP, but its magnitude was larger in baclofen injections. 6. Depressor and sympatho-inhibitory effects of baclofen (VMH) in SHR were larger than those in normotensive Wistar-Kyoto (WKY) rats, while pressor responses elicited by baclofen (AH) did not differ between SHR and WKY. 7. In summary, GABA reduces SNA, BP and HR through both GABAA and GABAB receptors in VMH. In addition, the GABAB system acts on AH and NTS to further regulate the cardiovascular activities. In SHR, GABAB-ergic dysfunction in VMH but not in AH might contribute to the development of hypertension.

Animals↗

PubMed1995

Functional alteration of the GABAB receptor in the brain of spontaneously hypertensive rats.

1. We studied the ontogenetic development of GABAB receptors and their coupling to cyclic AMP formation in spontaneously hypertensive (SHR) and normotensive Wistar-Kyoto (WKY) rat brains. GABAB receptor binding to various brain regions was compared in age-matched SHR and WKY rats. 2. The specific [3H]-GABA binding to the posterior hypothalamus (PH) was significantly lower in not only 4 week old (normotensive) but also 11 week old (hypertensive) SHR, when compared with age-matched WKY. 3. Moreover, GABAB receptor agonists (baclofen and DN-2327)-induced suppression of adenylate cyclase activity also showed a decrease in 4 week old and 11 week old SHR PH. 4. We concluded that the number and the functional responsiveness of GABAB receptors in rat brains decrease in SHR, preceding blood pressure elevation. The activity of GABABergic mechanisms may be different in the brains of SHR and WKY rats.

Adenylyl Cyclase Inhibitors↗

PubMed1995

Role of baroreflex and central alpha2-adrenergic receptor systems in the diurnal variation of blood pressure and heart rate in normotensive and hypertensive rats.

1. To elucidate whether baroreflex could contribute to manifest the diurnal blood pressure variations (DBPV) in normotension and hypertension, DBPV were recorded continuously via a femoral artery in awake normotensive (NT) rats and spontaneously hypertensive rats (SHR) with and without sinoaortic denervation (SAD). To determine the role of central alpha2-adrenergic receptor system in DBPV in hypertension, guanabentz (0.5-1.0 mu g/kg per min) was infused in SHR. 2. There were no differences in mean arterial pressure (MAP) variability (SD) of MAP of 24 h (MAP -- SD/MAP) and SD of 24 h heart rate (HR -- SD/HR) between SHR and NT. SAD did not elevate MAP and HR in both SHR and NT. 3. However, in SAD rats, MAP -- SD/MAP was significantly greater than those in sham-operated rats in both SHR and NT, while MAP -- SD/MAP and HR -- SD/HR did not show any difference between the two groups even after SAD. On the other hand, SAD did not augment HR -- SD/HR in either strain. 4. During guanabentz infusion, MAP was significantly lowered in sham-operated and SAD -- SHR. Moreover, MAP -- SD/MAP was significantly reduced in sham-operated, but it was not in SAD -- SHR. 5. These findings suggest that baroreflex could suppress tonically the diurnal change of blood pressure in NT and SHR. The regulation of diurnal blood pressure by baroreflex via a central alpha-adrenergic receptor system may be altered in SHR.

Adrenergic alpha-2 Receptor Antagonists↗

PubMed1995

Antitumour effects and pharmacokinetics of combination of vinblastine with a staurosporine derivative, NA-382, in P388/ADR-bearing mice.

The effects of a staurosporine derivative, N-ethoxycarbonyl-7-oxostaurosporine (NA-382), on the pharmacokinetics of vinblastine were evaluated, compared with those of verapamil, in multidrug-resistant P388/ADR-bearing mice. At first, the in-vitro experiments indicated that NA-382 permeated into the cells better and were more effective in combined cytotoxicity with vinblastine and on accumulation of vinblastine than with verapamil in P388/ADR cells. In combined intraperitoneal injection with vinblastine (200 micrograms kg-1) into P388/ADR-bearing mice, NA-382 in a suspension form (10 mg kg-1) prolonged the life-span of the mice near to that of P388/S-bearing mice treated with vinblastine alone, but verapamil even at the maximum tolerated dosage (30 mg kg-1) barely affected the in-vivo antitumour effect of vinblastine. When simultaneously administered with vinblastine to P388/ADR-bearing mice, NA-382 maintained significantly higher vinblastine levels in the tumour cells for 24 h and gave a larger area under the time-intracellular vinblastine concentration curve (0 to 24 h) than those receiving vinblastine alone, with long retention of the agent in ascitic fluid. Verapamil increased the cellular vinblastine content for only 6 h, accompanying a rapid elimination of the agent from the ascitic fluid. This study indicates that NA-382 is more effective against multidrug-resistance than verapamil, and its suspension is also advantageous for cancer chemotherapy of multidrug-resistant tumours.

Alkaloids↗

PubMed1995

Gastrointestinal motor inhibition by exogenous human, salmon, and eel calcitonin in conscious dogs.

Effects of synthetic eel (E-), salmon (S-), and human (H-) calcitonin (CT) on gastrointestinal motility were studied in conscious beagle dogs, which had been implanted with strain gauge force transducers. Intramuscular administration of E-, S-, or H-CT interrupted gastric migrating motor complexes, digestive pattern, and gastric emptying. The order of potency was E-CT = S-CT > H-CT. Motor inhibition induced by CT occurred independently of plasma immunoreactive motilin levels or hypocalcemia. In addition, E-CT and S-CT induced vomiting without a retrograde giant contraction (RGC) during the postprandial state. Apomorphine or CuSO4 initiated RGC prior to vomiting. RGC induced by apomorphine was inhibited by pretreatment with E-CT as well as hexamethonium, atropine, or surgical vagotomy. E-CT showed no inhibitory effect on nicotine stimulated contraction of isolated guinea-pig ileum. These results suggest that peripherally administered CT inhibits canine gastrointestinal motility at the central nervous system level by lowering vagal activity.

Analgesics↗

PubMed1995

Underestimation of vasodilator effects of nitroglycerin by upper limb blood pressure.

To determine why upper limb blood pressure measurement underestimates the vasodilator effects of nitroglycerin on lowering ascending aortic systolic pressure, we studied 24 patients (58 +/- 11 years, mean +/- SD). Ascending aortic pressure and radial artery pulse calibrated by cuff blood pressure measurement at the brachial artery were recorded simultaneously before and 5 minutes after sublingual administration of 0.3 mg nitroglycerin. Waves were analyzed by a signal processor, and the fourth derivative wave was used to find the early (S1) and late (S2) systolic shoulders (S1 corresponds to the second zero crossing and S2 to the third zero crossing). Before nitroglycerin administration, maximal systolic pressure in the ascending aorta (141 +/- 21 mm Hg) coincided with the late systolic peak in all patients, and in most patients (21 of 24) maximal systolic pressure in the radial artery (140 +/- 19 mm Hg) coincided with the early systolic peak. Maximal systolic pressure decreased more in the ascending aorta than in the radial artery (22 +/- 13 and 11 +/- 11 mm Hg, respectively; P < .001). However, the reduction in the shoulder of late systolic pressure in the radial artery (24 +/- 13 mm Hg) clearly indicated the reduction in maximal systolic pressure (late systolic peak) in the ascending aorta. The augmentation index of the ratio of the height of late systolic pressure to early systolic pressure fell proportionally (r = .74, P < .001) in the radial artery (from 0.88 +/- 0.13 to 0.60 +/- 0.11) and in the ascending aorta (from 1.57 +/- 0.25 to 1.26 +/- 0.24), which indicated the reduction in late systolic pressures.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗

PubMed1995

Transthoracic visualization of pulmonary thrombus that mimicked left atrial thrombus. A case report.

A forty-five-year-old woman with an unusual case of primary pulmonary hypertension is presented. She showed a progressive dilatation of the pulmonary arteries and pulmonary thrombus over twenty-one years. Transthoracic echocardiography showed the presence of pulmonary arterial thrombus that mimicked left atrial thrombus. However, when the transducer was rotated clockwise to obtain the short-axis view, a thrombus was observed in the right pulmonary artery with spontaneous echo contrast. Although the visualization of pulmonary arterial thrombus by echocardiography has been quite limited, it would be worthwhile since patients with primary pulmonary hypertension may have enlarged pulmonary arteries, as observed in the present case.

Diagnosis, Differential↗

PubMed1995

Identification of bone-type alkaline phosphatase mRNA from human periodontal ligament cells.

Tissue-nonspecific-type alkaline phosphatase is found in the bone, liver, kidney, and other tissues, and its gene consists of 12 exons with the coding sequence beginning in the second exon. Recently, an alternative noncoding first exon was identified in the liver message which differed from that of the previously known osteoblast-derived cDNA sequence. Although these two mRNAs produce an identical protein, they have different promoter regions. The periodontal ligament tissue expresses a high level of alkaline phosphatase activity. To identify its mRNA type, we isolated a full-length cDNA for alkaline phosphatase from a cultured human periodontal ligament cell expression library, using bone-derived tissue-nonspecific alkaline phosphatase cDNA as a hybridization probe. The size of this clone was 2.5 kb, and its 5' and 3' untranslated sequences were identical to those of the human tissue-nonspecific type isolated from osteoblastic cells but not to those of the liver type. In addition, the same fragments as in bone-derived tissue-nonspecific-type cDNA were detected by the treatment of the cDNA clone with restriction enzymes Hinc II and Pst I. The results suggest that expression of the same alkaline phosphatase isozyme in human periodontal ligament cells may be regulated by the same transcriptional mechanism as in bone.

Alkaline Phosphatase↗

PubMed1995

Stabilization of the tight junction of the intestinal Caco-2 cell monolayer by milk whey proteins.

The tight junction (TJ) of the human intestinal Caco-2-SF monolayer was shown not to have been stably formed. TJ was stabilized by incubating the cell monolayer with beta-lactoglobulin (beta-Lg) and bovine serum albumin (BSA). Thus, the Caco-2-SF cell-culture system will provide a useful model for studying the factors which stabilize TJ and for investigating the mechanism of TJ regulation.

Animals↗

PubMed1995

Targeting chemotherapy using antibody-combined liposome against human pancreatic cancer cell-line.

Anti-tumor effect of Adriamycin (ADM)-encapsulated and CA19-9 antibody-conjugated artificial lipid membrane follicle liposomes against a human pancreatic cancer cell-line PK-1 was studied in vitro and in vivo. The liposome compound (lipo c ADM = Ab) showed a stronger cell damage than ADM-encapsulated liposome (lipo c ADM) and free ADM, especially when the contact time was short and the concentration was low. The intra-tumor concentration of ADM in the group of i.v. injection of lipo c ADM = Ab showed the highest value, over twice those of lipo c ADM and free ADM after 120 hr. Lipo c ADM = Ab showed a significant inhibitory effect on the tumor growth inhibition test in vivo, and the final tumor weight at the 19th day was 27% in the group of lipo c ADM = Ab and 52% in the group of free ADM as compared with the control. The targeting chemotherapy using liposomes was demonstrated to have a stronger anti-tumor effect than the administration of anti-cancer drug alone owing to enhanced tumor accessibility and good targeting.

Animals↗

PubMed1995

Hypothyroidism preceding hyperthyroidism in a patient with continuously positive thyroid stimulating antibody.

A 62-year-old woman was initially hypothyroid and then developed hyperthyroidism with continuously positive thyroid-stimulating antibody (TSAb). When she visited our hospital with the complaint of the feel of skipping beats, her serum free T4 level was initially low and thyrotropin (TSH) level was slightly elevated. One month after starting the supplement therapy with l-T4, she developed hyperthyroidism with increased 123I-thyroid uptake. TSH-binding inhibitor immunoglobulin (TBII) was slightly elevated only during the hypothyroid stage. Throughout the whole course, TSAb was continuously positive, while thyroid stimulation-blocking antibody (TSBAb) was not detectable. Primary hypothyroidism with TSAb may suggest the possibility of subsequent development of hyperthyroidism.

Female↗

PubMed1995

Molecular cloning and sequence of bovine Msx-1 homeobox-containing gene cDNA from a bovine odontoblast library.

Screening of a bovine odontoblast cDNA library from developing incisor with murine Msx-1 and Msx-2 cDNA probes led to the isolation of three positive clones. All of them encoded for a sequence of a protein containing 297 amino acids. The responsible gene was designated as bovine Msx-1 (bMsx-1) due to the high homology with the human MSX-1 and mouse Msx-1 sequences.

Amino Acid Sequence↗

PubMed1995

Cloning and sequence of bone morphogenetic protein 4 (BMP-4) from a human placental cDNA library.

A cDNA clone encoding bone morphogenetic protein-4 (BMP-4) has been isolated from a human placental cDNA library. Sequence analysis of this clone revealed that the nucleotide sequence of 5' region was different from that of human osteosarcoma BMP-4 and the deduced amino acid sequence indicated deletion of N-terminal 6 amino acids. We confirmed the expression of this type of BMP-4 mRNA in one human osteogenic cell line in addition to the placenta by the polymerase chain reaction (PCR).

Amino Acid Sequence↗