Biomedical subjects

K Takizawa

Publications and source records attributed to K Takizawa.

At least 19 recordsLinked to original sources

PubMed1997

Renal effect of YM435, a new dopamine D1 receptor agonist, in anesthetized dogs.

The renal effects of YM435 ((-)-(S)-4-(3,4-dihydroxyphenyl)-7,8-dihydroxy -1,2,3,4-tetrahydroisoquinoline hydrochloride hydrate), a dopamine D1 receptor agonist, were investigated in anesthetized dogs. Intravenous infusion of YM435 (0.1-3 micrograms/kg per min) increased renal blood flow and decreased mean blood pressure in a dose-dependent manner with little effect on heart rate. Glomerular filtration rate, urine flow and urinary sodium excretion were concomitantly increased. The renal effect of YM435 by intravenous infusion at 0.3 microgram/kg per min was completely blocked by treatment with the selective dopamine D1 receptor antagonist SCH 23390 (7-chloro-8-hydroxy-3-methyl-1-phenyl-2,3,4,5-tetrahydro-(1H)-3-benzazep ine hydrochloride). Furthermore, intravenous infusion of YM435 (0.3 microgram/kg per min) reversed the angiotensin II-induced decreases in renal blood flow, glomerular filtration rate, urine flow and urinary sodium excretion, and prevented the decrease in renal blood flow, glomerular filtration rate and urine flow induced by renal nerve stimulation and platelet-activating factor (PAF). These results suggest that intravenous administration of YM435 produces renal vasodilating and diuretic/natriuretic effects by stimulation of dopamine D1 receptors, and demonstrate that YM435 can inhibit angiotensin II-, renal nerve stimulation- and PAF-induced renal dysfunction.

Anesthesia↗

PubMed1997

Hemodynamic characterization of YM435, a novel dopamine DA1 receptor agonist, in anesthetized dogs.

The cardiovascular effects of YM435, a dopamine DA1 receptor agonist, were compared with those of dopamine in open-chest anesthetized dogs. Intravenous infusion of YM435 (0.1-3 microg/kg/min) increased renal blood flow and cardiac output and reduced renal vascular resistance and total peripheral vascular resistance, with a decrease in mean blood pressure, in a dose-dependent manner, with little change in heart rate. At 1 microg/kg/min i.v., renal blood flow increased by 20 +/- 7%, cardiac output increased by 14 +/- 6%, renal vascular resistance decreased by 22 +/- 4%, total peripheral vascular resistance decreased by 18 +/- 4%, and mean blood pressure decreased by 7 +/- 1%. The striking difference between the cardiovascular effects of YM435 and those of dopamine was that YM435 caused no vasoconstriction or increase in heart rate, even at high doses. The cardiovascular effects of YM435 (1 microg/kg/min i.v.) were almost completely inhibited by treatment with SCH 23390, a selective dopamine DA1 receptor antagonist. Furthermore, intravenous infusion of YM435 (0.1-3 microg/kg/min) dose-dependently reversed the increase in blood pressure and renal vascular resistance induced by angiotensin II or norepinephrine in closed-chest anesthetized dogs. Our results demonstrate that intravenous infusion of YM435 produces dose-dependent renal vasodilating and hypotensive effects by stimulation of dopamine DA1 receptors and suggest that YM435 may be useful for the parenteral treatment of acute elevation of blood pressure.

Angiotensin II↗

PubMed1997

Polymorphism of TAP1 and TAP2 in Japanese patients with rheumatoid arthritis.

Contribution of polymorphism of transporter associated with antigen processing 1 and 2 (TAP1 and 2) alleles to pathogenesis of Japanese rheumatoid arthritis (RA) was studied in 92 RA patients by PCR-RFLP. The allele frequency of TAP2A was slightly low (38.0%) and the frequencies of TAP2B and TAP2C were slightly high (39.7% and 17.9%) in RA, but these differences were not significant. These increases and decrease were due to the positive or negative associations with HLA-DRB1*0405. It was very likely that slight differences in TAP2A, TAP2B and TA2C in RA were secondary phenomenon reflecting an increase in HLA-DRB1*0405. The prevalence of TAP2E allele was low (3.3%, P < 0.01, Pc = not significant) and not correlated with HLA-DRB1*0405.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

PubMed1997

Cardiovascular effects of YM430, a 1,4-dihydropyridine derivative with beta-adrenoceptor blocking activity, in dogs and rats.

We evaluated the cardiovascular effects of YM430, a novel 1,4-dihydropyridine derivative with beta-adrenoceptor blocking activity, in dogs and rats. In anesthetized dogs, YM430 (0.01-0.3 mg/kg, i.v.) dose-dependently decreased mean blood pressure, total peripheral resistance and double product without increasing the heart rate. YM430 (0.01-0.3 mg/kg, i.v.) increased coronary artery as well as vertebral artery blood flow, whereas its effects on carotid, mesenteric, femoral and renal blood flow were small. At the same dose range as that which induced vasodilation effects, YM430 had little effect on the max. dp/dt or PQ-interval. In conscious dogs, YM430 (0.1-1 mg/kg, i.v.) produced dose-dependent hypotension with tachycardia. In conscious rats, oral dosing of YM430 (100 mg/kg p.o.) produced a long-lasting hypotensive effect with slight tachycardia. YM430 also inhibited isoproterenol (0.1 micrograms/kg i.v.)-induced tachycardia. These two effects of YM430 may be attributable to its calcium entry blocking and beta(1)-adrenoceptor blocking activity, respectively. The time course of the hypotensive (calcium entry blocking) effect of YM430 after oral dosing was very similar to that of its inhibition of isoproterenol-induced tachycardia (beta(1)-adrenoceptor blocking effect). These results indicate that the ratio of the two activities (calcium entry blocking and beta(1)-adrenoceptor blocking) of YM430 is constant after oral administration. In conclusion, YM430 could be both an antianginal and antihypertensive agent, because of its dual activities.

Adrenergic beta-Antagonists↗

PubMed1997

Hypotensive effects of YM430, a 1,4-dihydropyridine derivative, in spontaneously hypertensive rats and renal hypertensive dogs.

The hypotensive effects of YM430 (4(((S)-2-hydroxy-3-phenoxypropyl)amino)butyl methyl 2,6-dimethyl-((S)-4-(m-nitrophenyl))-1,4-dihydropyridine-3,5-dicarboxyla te) were evaluated in hypertensive animals. In conscious spontaneously hypertensive rats (SHR), single oral administration of YM430 (10-100 mg/kg) produced a dose-dependent decrease in mean blood pressure (MBP) with slight reflex tachycardia. The hypotensive effect of YM430 reached its maximum about 2 hr after dosing and lasted for over 10 hr. Importantly, the beta 1-adrenoceptor blocking activity of YM430 had a similar time course to that of its calcium entry blocking activity. In conscious normotensive dogs (NTD: 1-10 mg/kg, p.o.), YM430 decreased MBP without reflex tachycardia, and inhibited isoproterenol (ISO)-induced tachycardia in a dose-dependent manner. In conscious renal hypertensive dogs (RHD: 0.3-3 mg/kg, p.o.), YM430 also produced a sustained hypotensive effect. Furthermore, on repeated oral administration to conscious SHR and NTD, YM430 caused a long-lasting hypotensive effect. This hypotensive activity and inhibition of ISO-induced tachycardia showed neither tolerance, augmentation nor rebound. In conclusion, YM430 has a long-lasting hypotensive effect and behaves as a hybrid compound, combining calcium entry blocking and beta 1-adrenoceptor blocking activities in vivo. In addition, the degree of the blocking activities of YM430 remains nearly constant in the long-term after oral administration.

Administration, Oral↗

PubMed1997

[Examination of scanning technique for lung cancer screening with helical CT].

As a new application of helical CT scanning we evaluated the parameters for lung cancer screening with an extremely low doses and large helical pitch. On the phantom studies, the image quality obtained with the low dose parameter was not inferior to that of the usual screening technique but artifacts were increased with the large helical pitch. A scanning technique using 120 kv, 40-60mA, 10mmth, 20mm/ sec, and a reconstruction pitch of 2 was used for lung cancer screening (screening parameters) (50 cases), and comparison was made between the detectability of the screening parameters and the routine parameters (120 kv, 200mA, 10mmth, 10-13mm/sec, and a reconstruction pitch of 1-1.3). Detectability with the screening parameters was as follows: nodular lesions (< 5mm in size: 76%. 5-10mm: 90-93% 10mm < 100%), linear lesions: 94-95%, infiltrations: 93-100%. There were no false negative lesions, when the reconstruction pitch of the screening parameters was changed from 1 to 0.25. In conclusion, reconstruction pitch had the most influence on lesion detectability.

Adult↗

PubMed1997

[Significant findings on CT performed before presence of post-surgical bowel obstruction].

We evaluated whether CT performed before the presence of bowel obstruction (pre-CT) is useful in predicting the presence of post-surgical bowel obstruction. Thirty-three patients with post-surgical bowel obstructions who had pre-CT were reviewed. The pre-CT findings were compared with the findings of CT performed after the presence of bowel obstruction (post-CT) in 16 patients, and with the intraoperative findings in 18 patients. Pre-CT demonstrated many interesting findings, such as a discrepancy in the caliber of the bowel, the presence of two adjacent collapsed loops, a beak-like appearance of the bowel, focal distention and/or wall thickness of bowel loops, and twisted mesentery. Twenty-three (70%) of 33 patients had one or more of these findings on pre-CT. All patients with a surgically proved closed loop obstruction had two adjacent collapsed loops on both pre- and post-CT. In six (86%) of seven patients who had focal dilated bowel loops and twelve (71%) of seventeen patients who had twisted mesentery on pre-CT, conservative management was proved ineffective. Pre-CT showed many significant findings. Attention should be paid to these findings, because they can predict the presence of post-surgical bowel obstruction. In particular, we stress that two adjacent collapsed loops on pre-CT is a sign of the presence of post-surgical closed loop obstruction.

Adult↗

PubMed1997

[Hippocampal hemosiderin deposit due to large pituitary adenoma presenting temporal lobe epilepsy--a case report].

There have been reports of epilepsy associated with pituitary adenoma, but the epileptogenic zone and its histopathology have never been sufficiently described. We report a case of pituitary adenoma complicated by temporal lobe epilepsy, in which the epileptogenic focus was identified, resected, and examined histopathologically. The patient was a 38-year-old man on bromocriptine therapy for a huge pituitary adenoma (prolactin-producing) since 1985. He also had a history of temporal lobe epilepsy since 1989. CT images in 1985 revealed the tumor extending to the supra- and left para-sellar region. MR images in 1995 showed a significant decrease in the size of the tumor and a signal void area that was interpreted as a hemosiderin deposit in the left mesial temporal lobe. Ictal EEG demonstrated that seizure discharges were elicited at the left sphenoidal electrode and propagated to the both temporal lobes. Interictal SPECT revealed a local area of hypoperfusion in the left fronto-parietal lobe. An epileptogenic focus in the left mesial temporal lobe was diagnosed on the basis of the above examinations. The patient was treated by left anterior temporal lobectomy with partial hippocampectomy. Hemosiderin deposition in the hippocampus was suspected during surgery. Histopathological examination showed pyramidal cell loss and gliosis in the left hippocampus and confirmed the presence of hemosiderin in the CA1 region. The hemosiderin deposition in the hippocampus was inferred to have resulted from intratumoral hemorrhage due to bromocriptine therapy, and it may have caused the temporal lobe epilepsy in this patient. The outcome of surgery was freedom from seizures for eight months. Intra-tumoral hemorrhage in mesial temporal structures must be borne in mind as one of the epileptogenic mechanisms in pituitary adenoma, especially in cases in which hemosiderin is detected on MR images.

Adenoma↗

PubMed1996

Bafilomycin A1 induces apoptosis in PC12 cells independently of intracellular pH.

PC12 cells growth-arrested with bafilomycin A1 died showing apoptotic chromatin condensation in the nuclei. The bafilomycin A1-induced chromatin condensation was preceded by neurite outgrowth (NOG), required higher concentrations of bafilomycin A1 than NOG, and was suppressed by cycloheximide and aurintricarboxylic acid. NH4Cl (10 mM), another acidotropic pH perturbing agent, neither induced apoptotic chromatin condensation by itself nor suppressed that induced by bafilomycin A1, suggesting that bafilomycin A1-induced apoptosis occurs independently of intracellular pH in PC12 cells.

Ammonium Chloride↗

PubMed1996

Ubiquinone systems of the genus Cladosporium and morphologically similar taxa.

The ubiquinone (coenzyme Q) systems of 14 species of Cladosporium were determined. The genus was divided into two groups based on the distribution of the major ubiquinones, Q-10 and Q-10(H2). The group containing Q-10 consisted of six species, four of which were human pathogens, whereas the group containing Q-10(H2) consisted of eight plant pathogenic and/or saprophytic species. The results presented here agree with phylogenetic and physiological studies which have shown that the human-pathogenic species of Cladosporium represent a homogeneous, cohesive group.

Cladosporium↗

PubMed1996

[Brain CT and MRI findings in fat embolism syndrome].

To elucidate brain CT and MRI findings in fat embolism syndrome (FES), we retrospectively analyzed images from 5 patients with FES during the acute and subacute stages. Brain CT examinations demonstrated brain edema in 2 patients and transient spotty low density lesions in 2 patients. Three patients showed no abnormalities. Brain MRI, however, showed brain abnormalities in all patients during the acute stages. These were revealed as spotty high signal intensity lesions on T2WI, and some showed low intensity on T1WI. These spotty lesions were considered to reflect edematous fluid occurring as a result of the unique pathophysiological condition of FES. While the spotty high signal intensity lesions on T2WI were distributed in the cerebrum, cerebellum, brain stem, thalamus, basal ganglia, internal capsule and corpus callosum, cerebral and cerebellar spotty lesions were characteristically located along the boundary zones of the major vascular territories. This characteristic location might be induced by a hypoxic brain condition in FES because the numerous fat globules present in this condition can block entire brain capillaries. This characteristic signal location on T2WI is a useful indicator for differentiating FES from the primary intra-axial brain injury in patients with multifocal trauma.

Adolescent↗

PubMed1996

[Fast two-compartment model analysis with 99mTc-GSA liver scintigraphy].

The use of numerical integration method (N. INT) was evaluated in determining parameters by two-compartment model analysis from liver scintigraphy. Among the 15 subjects, 14 had liver cirrhosis or chronic hepatitis, and one was normal. When using N.INT, the sum of two exponential functions on heart regression curve following intravenous injection of 99mTc-galactosyl human serum albumin (99mTc-GSA) was promptly calculated. The parameters obtained from N.INT, including transfer rate of 99mTc-GSA from extrahepatic blood to liver (k1), dissociation rate from liver to extrahepatic blood (k2), and excretion rate from liver to gallblader (k3), were significantly correlated with those obtained by the nonlinear least square method (NLS). k1/k2 was related with the maximum removal rate of 99mTc-GSA obtained from nonlinear five compartment model analysis (r2 = 0.705, n = 15) and also with the severity score of liver disease as classified by the First Department of Surgery, Mie University Medical School (r2 = 0.686, n = 13). In terms of the time required to obtain these parameters, including the blood retention rate of 99mTc-GSA at 15 min after injection (%ID15), N.INT was faster than the traditional method (NLS).

Aged↗

PubMed1996

[Report of nationwide questionnaire: intraperitoneal chemotherapy for advanced ovarian cancer based on clinical results--reports of 5th "Gynecologic Intraperitoneal Chemotherapy Study Group" meeting].

We established the "Gynecologic Intraperitoneal Chemotherapy Study Group" in October, 1990. To date 5 annual meetings have been held during the Japanese Cancer Therapy Meeting. The members decided to establish a standard protocol of intraperitoneal chemotherapy (IP-CTX) for advanced ovarian cancer based on the clinical results obtained at each institution. Thus we first collected the clinical data from the affiliated institutes. Questionnaires concerning the indication of IP-CTX and the resulting data were sent to physicians working at 267 facilities in January, 1994. As a result, the reply rate was 28.8% (77/267). According to the results from 40 institutions, the consensus was that patients with residuum less than 0.5 cm in diameter after primary debulking surgery were suitable for IP-CTX. However, the remaining 37 institutions reported that patients with a macroscopic residuum less than 2 cm in diameter or those with bulky residuum greater than 2 cm in diameter demonstrated good responses to IP-CTX. Thus, further analyses are required to elucidate the appropriate indication and establish the standard protocol of IP-CTX for ovarian cancer in a clinical setting.

Antineoplastic Agents↗

PubMed1996

[Quantitative analysis of 99mTc-GSA liver scintigraphy with graphical plot method].

99mTc-galactosyl human serum albumin (99mTc-GSA) is a newly developed receptor-binding agent, specific for the asialoglycoprotein receptor, which resides exclusively on the plasma membrane of mammalian hepatocytes. Liver scintigraphy using 99mTc-GSA was performed on 65 patients with liver diseases. Dynamic data were obtained by gamma camera during 20 minutes after the intravenous injection of 3 mg (185 MBq) of 99mTc-GSA. The maximum removal rate of 99mTc-GSA (denoted as P(2)) was measured by two methods: nonlinear five-compartment model analysis adopting the Michaelis-Menten constant for the transfer of 99mTc-GSA from hepatic blood to receptor, and a graphical plot using compartmental dose curves. The graphical plot could estimate easily the maximum removal rate in terms of two data points of 0 and 1 minutes without nonlinear least squares and numerical integration. The results indicated that the maximum removal rate was decided immediately after the intravenous injection of 99mTc-GSA. Although 99mTc-GSA is recognized to accumulate nonlinearly on the liver, the rate constant P(2)*(1/min) of transfer from hepatic blood to the receptor was estimated by graphical plot, assuming a linear five-compartment model. P(2)*Km, which was given by the product of the rate constant P(2)* and the Michaelis constant Km, was well correlated with P(2). Next, for 99mTc-GSA liver scintigraphy, we applied a Patlak plot that was applicable to the linear system, and the rate constant Ku of transfer from extrahepatic blood to the liver was estimated. From the results of graphical plot, it was theoretically shown that Ku represented P(2). This was confirmed by clinical data.

Adult↗

PubMed1995

glial cells missing: a binary switch between neuronal and glial determination in Drosophila.

In the Drosophila CNS, both neurons and glial are derived from neuroblasts. We have identified a gene, glial cells missing (gcm), that encodes a novel nuclear protein expressed transiently in early glial cells. Its mutation causes presumptive glial cells to differentiate into neurons, whereas its ectopic expression forces virtually all CNS cells to become glial cells. Thus, gcm functions as a binary switch that turns on glial fate while inhibiting default neuronal fate of the neuroblasts and their progeny. Similar results are also obtained in the PNS. Analyses of the mutant revealed that "pioneer neurons" can find correct pathways without glial cells and that neurons and glia have a common molecular basis for individual identity.

Amino Acid Sequence↗

PubMed1995

Gastric mucosal protection by YM638, a novel leukotriene D4 receptor antagonist, in rats.

YM638 ([[5-[[3-(4-acetyl-3-hydroxy-2-propylphenoxy)propyl] thio]-1,3,4-thiadiazol-2-yl]thio] acetic acid) is a novel leukotriene D4 receptor antagonist. We investigated the involvement of the leukotriene D4 receptor blocking activity of YM638 in the gastric mucosal protection of this drug in rats. YM638 significantly prevented gastric lesion formation induced by water-immersion restraint stress, indomethacin, absolute ethanol, 0.7 N HCl and the combination of 0.2 N HCl and hemorrhagic shock, with ED50 values of 26.4, 4.1, 4.7, 35.4 and 8.0 mg/kg p.o., respectively. Cetraxate and sofalcone showed inhibitory effects on most of these gastric lesions, but the inhibitory effects of these compounds were much weaker than those of YM638. In contrast, YM638 had no effect on gastric acid secretion and gastric lesion formation in pylorus-ligated rats, or on duodenal lesion formation in cysteamine-administered rats. YM638 competitively antagonized leukotriene D4-induced contraction of the isolated stomach, with a pA2 value of 7.63 +/- 0.18. In anesthetized rats, intravenous YM638 inhibited leukotriene D4-induced aggravation of gastric lesions caused by HCl, and leukotriene D4 and HCl-induced reduction of the potential difference. In addition, oral YM638 significantly increased gastric mucosal blood flow and prevented ethanol-induced increase in gastric vascular permeability. Endogenous prostaglandins, sulfhydryls and nitric oxides were not involved in this inhibitory effect on absolute ethanol-induced gastric lesion. YM638 did not react with the stable free radical 1,1-diphenyl-2-picrylhydrazyl in vitro, indicating that YM638 does not have potential as free radical scavenger. These results suggest that the preventive effect of YM638 on gastric lesions is attributable not only to its leukotriene D4 receptor blocking activity but also to the activation of gastric mucosal defensive mechanisms such as mucosal blood flow and vascular permeability.

Animals↗

PubMed1995

Using Ga-67 scintigraphy in prostatic abscess.

The use of Ga-67 scintigraphy (Ga) in prostate inflammatory diseases may be restricted by the difficulty in distinguishing between the accumulation of Ga-67-citrate (Ga-citrate) in the lesion and feces. The diagnosis of prostatic abscess has been mainly made by other radiologic methods without scintigraphic studies and no finding of Ga has been reported. This patient demonstrated that coordinating the findings of Ga-citrate accumulation can be helpful in making a prompt diagnosis of a possibly fatal prostatic abscess, especially in those patients with poorly defined clinical symptoms and high risk factors.

Abscess↗

PubMed1995

Inhibition of acyl-CoA: cholesterol acyltransferase by isohalobacillin, a complex of novel cyclic acylpeptides produced by Bacillus sp. A1238.

A complex of metabolites consisting of two isomeric cyclic acylpeptides was isolated from a culture of Bacillus sp. A1238 by successive chromatographies on Amberlite XAD-7, silica gel and silica ODS columns. By a combination of spectroscopic and chemical analyses, the two subcomponents were identified as isomers of halobacillin, and the complex was designated isohalobacillin. Each molecule of isohalobacillin subcomponents contains either a 3-hydroxy-1-oxo-13-methyltetradecyl or a 3-hydroxy-1-oxo-12 methyltetradecyl moiety in place of a 3-hydroxy-1-oxopentadecyl moiety that is found in the halobacillin molecule. In a cell-free assay, isohalobacillin inhibited acyl-CoA: cholesterol acyltransferase by 50% at a concentration of 50 microM. When added to a culture of macrophage J774, the agent inhibited oxidized low density lipoprotein-induced synthesis of cholesteryl ester from [14C]oleate without affecting surface binding, internalization and degradation of the lipoprotein in the cells.

Amino Acid Sequence↗