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Biomedical subjects

Y Tsuda

Publications and source records attributed to Y Tsuda.

At least 145 records · Page 8Linked to original sources

Laboratory evaluation of a juvenile hormone mimic, pyriproxyfen, against Chironomus fusciceps (diptera: chironomidae).

The efficacy of the insect growth regulator, pyriproxyfen, against Chironomus fusciceps was examined in the laboratory. A series of 6 concentrations (0.1-0.00001 ppm) was used. A positive relationship between mortality and concentration was observed in the pupal stage as well as in the larval stage. Pyriproxyfen caused 50 and 90% emergence inhibition of C. fusciceps at 0.00177 and 0.05369 ppm, respectively.

Animals↗

Design of potent bivalent thrombin inhibitors based on hirudin sequence: incorporation of nonsubstrate-type active site inhibitors.

Hirudin from medicinal leech is the most potent and specific thrombin inhibitor from medicinal leech with a K(i) value of 2.2 x 10(-14) M. It consists of an active site blocking moiety, hirudin1-48, a fibrinogen-recognition exo-site binding moiety, hirudin55-65, and a linker, hirudin49-54, connecting these inhibitor moieties. Synthetic inhibitors were designed based on the C-terminal portion of hirudin. The bulky active site blocking moiety, hirudin1-48, was replaced by small nonsubstrate-type active site inhibitors of thrombin, e.g., dansyl-Arg-(D-pipecolic acid). The linker moiety was replaced by omega-amino acids of (12-aminododecanoic acid)-(4-aminobutyric acid), and hirudin55-65 was used as a fibrinogen-recognition exo-site binding moiety in most of the inhibitors. The crystal structure of the inhibitor in complex with human alpha-thrombin showed that dansyl, Arg, and D-pipecolic acid of the active site blocking moiety occupy S3, S1, and S2 subsites of thrombin, respectively, and were therefore designated as P3, P1, and P2 residues. The use of dansyl-Arg-(D-pipecolic acid) improved the affinity (K(i)) of the inhibitor 10-100-fold (down to 1.70 x 10(-11) M) compared to that of the similar compounds having D-Phe-Pro-Arg as their substrate-type inhibitor moiety (K(i) = 10(-9)-10(-10) M). The linker connected to P2 residue eliminated the scissile peptide bond. The inhibitor was also stable against human plasma proteases. Further inhibitor design revealed that the toxic dansyl group could be replaced by 4-tert-butylbenzenesulfonyl group and 1- or 2-naphthalenesulfonyl group for in vivo studies.(ABSTRACT TRUNCATED AT 250 WORDS)

Amino Acid Sequence↗

Determination of carbenicillin epimers in plasma and urine with high-performance liquid chromatography.

A high-performance liquid chromatographic method was developed for determining the concentrations of carbenicillin (CBPC) epimers in plasma and urine. Samples were prepared for HPLC analysis by solid-phase extraction and the concentrations of CBPC epimers were determined using reversed-phase HPLC with a mixture of 0.05 M ammonium acetate and methanol as a mobile phase. Baseline separation of the two epimers was observed for both plasma and urine samples with a detection limit of ca. 10 micrograms/ml. No peaks interfering with either of the CBPC epimers were observed on the HPLC chromatograms for blank plasma and urine. The presented method was used to determine the protein binding of CBPC epimers in vitro in human and rabbit plasma. The stereoselectivity of the binding of CBPC appeared to be reversed in human and rabbit plasma.

Adult↗

Expression of adhesion molecules on human hematopoietic progenitor cells at different maturational stages.

In this report we examined the expression of several adhesion molecules on human hematopoietic progenitor cells at different maturational stages. Human hematopoietic progenitor cell-enriched fractions were prepared from bone marrow cells by depleting lymphocytes and monocytes (CD2+, CD14+ and CD19+ cells). These cells were separated into adhesion molecule-positive and -negative cell populations by immunomagnetic separation methods and then assessed for their ability to form various colony forming cells (CFC). CD44 and CD49d were expressed on multipotent hematopoietic progenitor cells, or mixed colony forming units (CFU-Mix), erythroid burst forming units (BFU-E), granulocyte-macrophage CFU (CFU-GM) and erythroid CFU (CFU-E). Leu8 was expressed on CFU-Mix, BFU-E and some populations of CFU-GM, but not CFU-E. CD11a was expressed on some populations of CFU-Mix, CFU-GM and BFU-E. CD54 was expressed only on some populations of CFU-GM. These results suggest that Leu8, CD44, CD49d and CD11a appear to play important roles in the differentiation and proliferation of human hematopoietic progenitor cells at different maturational stages in the bone marrow microenvironment.

Antigens, CD↗

Cortical blood flow and cognition after extracranial-intracranial bypass in a patient with severe carotid occlusive lesions. A three-year follow-up study.

The long-term effect of extra-intracranial arterial bypass on cerebral circulation was examined. Cortical blood flow and cognitive ability were evaluated pre- and up to 3 years post-bypass in a 58-years-old man with severe carotid occlusive lesions, who presented with 3 transient cerebral ischaemic attacks which resulted in mental deterioration over 3 years. Regional cerebral blood flow (rCBF) was evaluated pre- and up to 33 months post-bypass by 123Iodine N-isopropyl-p-iodoamphetamine (IMP) single-photon emission CT (SPECT). Mental abilities were evaluated before and up to 33 months after surgery by the Hasegawa's dementia rating scale (HDRS). Pre-operatively, cerebral angiography showed left carotid siphon occlusion and hypoplastic stenosis of left anterior cerebral artery with collaterals from the anterior communicating artery. CT and MRI showed left temporo-parietal borderzone infarction and an enhanced T 1 lesion by gadolinium-DTPA at left periventriculum. rCBF showed extensive hypoperfusion in left anterior-parieto-temporal-cortex. HDRS scores deteriorated apparently on days 3, 5, which recovered gradually on days 8, 10, 75 after onset of mental deterioration. A bypass was performed 4 months after onset. rCBF showed gradual recovery in the left anterior-parietal cortex up to 33 months after bypass. Semiquantitative rCBF showed gradual decreases of regional asymmetry after the bypass. HDRS scores returned to their maximum up to 37 months after onset. Three-year follow-up shows improved cortical rCBF and cognition after the bypass.

Brain Damage, Chronic↗

Synergistic action of cholera toxin B subunit (and Escherichia coli heat-labile toxin B subunit) and a trace amount of cholera whole toxin as an adjuvant for nasal influenza vaccine.

Cholera toxin B subunit (CTB) and Escherichia coli heat-labile toxin (LTB) (2 micrograms), each supplemented with a trace amount of cholera toxin (CT) (0.02-20 ng), were examined for the adjuvant effect on antibody (Ab) response against influenza inactivated HA (haemagglutinin) vaccine in Balb/c mice. Each mouse received a primary intranasal (i.n.) inoculation of the vaccine (1.5 micrograms) and the CT-containing CTB and in 4 weeks a second i.n. inoculation of the vaccine alone. The primary inoculation of the vaccine with CTB alone did not induce either anti-HA IgA or IgG Ab response, or haemagglutination-inhibition Ab responses in the serum. The vaccine with less than 2 ng of CT also failed to induce Ab response. On the other hand, the vaccine with CT-containing CTB induced a high Ab response, which increased depending on the CT dose. Moreover, the second vaccine induced a response more than ten times higher than the primary one and the response increased depending on the CT dose. Similar enhancement was found in the local anti-HA IgA Ab response in the nasal wash. Such synergistic effects were observed also between LTB and CT. The amount of Ab produced by the synergism was considered to be enough to protect against virus infection. These results suggest that CTB (or LTB) containing a trace amount of CT (about 0.1%) can be used practically as a potent adjuvant for nasal vaccination of humans against influenza.

Adjuvants, Immunologic↗

Epidural lidocaine delays arousal from isoflurane anesthesia.

To clarify the effect of epidural lidocaine on arousal from inhaled anesthesia, we investigated the minimum alveolar anesthetic concentration at awakening (MAC-Awake) of isoflurane and the duration between discontinuance of isoflurane inhalation and arousal from anesthesia in 60 female abdominal hysterectomy patients. All patients received epidural catheterization and were randomly assigned to one of five groups. The control group, A, was given normal saline intravenously (IV) and epidurally. Group B was given 1 mg/kg of 2% lidocaine IV as a bolus. Groups C and D were given 0.5 and 1 mg/kg, respectively, of 2% lidocaine IV for 5 min, followed by 30 micrograms.kg-1.min-1. Group E was given 3 mg/kg of 1.5% lidocaine epidurally as a bolus. These doses of lidocaine or control saline were administered 15 min before the end of the surgical procedure. MAC-Awake values in Groups A, B, C, D, and E were 0.30% +/- 0.05%, 0.28% +/- 0.04%, 0.29% +/- 0.04%, 0.31% +/- 0.04%, and 0.18% +/- 0.05% (mean +/- SD), respectively. MAC-Awake in Group E was lower than in the other groups (P < 0.001). The duration until arousal in Group E (21.0 +/- 2.0 min) was longer than in Groups A, B, C, and D (12.6 +/- 1.8 min, 12 +/- 2.3 min, 13.3 +/- 2.5 min, and 14.3 +/- 2.7 min, respectively) (P < 0.001). Plasma lidocaine levels in Groups B, C, D, and E were 0.95 +/- 0.17 microgram/mL, 1.07 +/- 0.16 microgram/mL, 2.09 +/- 0.31 micrograms/mL, and 1.02 +/- 0.16 micrograms/mL, respectively. We conclude that analgesia produced by epidural lidocaine delays arousal from isoflurane anesthesia. Furthermore, lidocaine plasma levels are shown to be too low to cause any sedative effect, thus suggesting that postoperative pain may cause significantly faster arousal from anesthesia.

Adult↗

Effects of hydrocortisone on transmembrane currents in guinea pig ventricular myocytes--possible evidence for positive inotropism.

Steroid hormones are thought to have a positive inotropic action, but the precise electrophysiological effects which underlie this positive inotropism remain unknown. The effects of hydrocortisone on the L-type calcium current (ICa) of the isolated guinea pig ventricular cells were investigated under the whole-cell voltage-clamp recording. Hydrocortisone (10(-6) to 10(-5) M) increased the amplitude of ICa without any changes in the voltage-dependency in ICa. This agent retarded the fast inactivation component of ICa, but not the slow component. On the other hand, hydrocortisone slightly reduced the slope conductance of inward rectifying potassium current (IK1) at potentials less than -50mV. This effect on IK1 is favorable for the activation of ICa. Thus, these results indicate that the positive inotropism of hydrocortisone is mediated, at least in part, by a direct potentiating effect on ICa.

Animals↗

Thrombotic obstruction of the right coronary artery in a postoperative patient with Bland-White-Garland syndrome.

A 53-year-old female presented with symptoms of severe chest and back pain associated with oliguria. The patient had a history of exertional dyspnea since the age of 20, and easy fatigability since the age of 27. At the age of 41, she noted marked exacerbation of these symptoms after suffering from a cold and was ultimately diagnosed as having Bland-White-Garland (BWG) syndrome with mitral valve regurgitation. The patient then underwent re-implantation of an anomalous left coronary artery from the pulmonary artery to the posterolateral wall of the aorta. Eleven years later, she re-presented with symptoms of angina and congestive heart failure. Coronary angiography was subsequently performed and a total occlusion of the right coronary artery with probable thrombus was revealed. The right coronary artery was filled via collaterals from the implanted left coronary artery. Mitral regurgitation was noted during angiography. The patient underwent aorto-coronary artery bypass grafting of the right coronary artery and concomitant mitral valve replacement. Her postoperative condition remained excellent.

Coronary Angiography↗

[The nature of the external ionic modulation of the myocardial electrical propagation: importance of the safety factor].

The mechanisms of conduction change depending on the extracellular K+ and Ca2+ concentrations ([K+]o and [Ca2+]o, respectively) were investigated. Simultaneous measurements of active and passive membrane properties and net membrane excitability were fulfilled by arranging the intra- and extracellular microelectrodes in a superfused and paced guinea pig papillary muscle. Internal longitudinal resistance (ri), as a parameter of passive property, was evaluated by the intra- and extracellular voltage ratio. The maximum upstroke rate (Vmax) was used as an active property. Apparent threshold potential (Vth) was defined by the breakpoint in the action potential upstroke fitted semilogarithmically. Graded rise in [K+]o (from 2.7 to 15.0 mM) evoked a progressive fall in Vmax, and was associated with less negative resting membrane potential and constant ri. Conduction velocity (theta) was the maximum in 9.0 mM [K+]o ("supernormal" conduction) but not in 2.7 mM [K+]o which gave the greatest Vmax ("subnormal" conduction). Safety factor of conduction (S), as an index of net excitability, could most readily account for the [K+]o-dependent change in theta. This was true also in the case of [Ca2+]o elevation (from 0.9 to 5.4 mM). These results indicate that the cation-modulated propagation is governed by the cable theory including S as a matrix of combined active and passive properties.

Action Potentials↗

Blood flow and clinical course in patients with ischemic stroke without cerebrospecific therapy.

To evaluate the course of cerebral tissue perfusion in patients with acute focal cerebral ischemia of the supratentorial compartment regional cerebral blood flow (rCBF) was measured on day 0, 7, 14, 21, and 28 in 132 patients using the 133 Xenon stationary inhalation technique. Ischemic events of the brainstem and hemorrhagic complications were excluded. The clinical status was evaluated using a modified Mathew score. In 34 patients no hemodilution, anti-edema therapy, or Ca(++)-antagonists were used but otherwise best medical therapy was applied. These patients represented the so called "natural course" of cerebral ischemia. In 30/34 patients on day 0 (within 16 hours after onset of symptoms) focal flow abnormalities were found in the involved side. In 9 of these 30 patients and in 1 of the remaining ischemia was observed in the contralateral side. rCBF above normal (relative luxury perfusion) despite pathologic neurologic findings was observed in 8/34 patients on day 3-7. Eight patients presented on day 3-7 with normal flow which later became ischemic again without evidence of another symptomatic episode. Correlation between severity of clinical findings and actual rCBF was low from day 3 to 7 but close on day 0. From day 14-21 hemispheric CBF correlated well with the total neurologic score but focal clinical findings had a lower correlation with focal flow as compared to day 0 and day 28. Contralateral ischemia was never found after day 14. In 5 other cases with "natural course" described above, a transitory decrease of rCBF below the initial ischemia level was found between day 3 and 14.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Changing chemosusceptibility in the second-stage larvae of Toxocara canis by long-term incubation.

Second-stage larvae of Toxocara canis were maintained in vitro for one year. Susceptibility of the larvae to drugs was evaluated by means of minimal larvicidal concentration (MLC) and larval bursting percentage. MLCs of citral and decanoic acid were almost constant throughout all stages of incubation. However, bursting percentage markedly varied within the first 20 weeks of incubation. Therefore, while larvae are available for use in the MLC assay at any stage of incubation, those beyond the first 20 weeks after incubation should be used for the bursting assay to obtain reproducible results.

Acyclic Monoterpenes↗

Stereoselective renal tubular secretion of carbenicillin.

The stereoselective disposition of carbenicillin epimers was studied in healthy human volunteers. There was a difference between the two epimers in the extent of plasma protein binding in vitro, with the unbound fraction of the R epimer being greater than that of the S epimer. Renal clearance (CLR) of each epimer was greater than the glomerular filtration rate, suggesting renal tubular secretion of both epimers. Although the CLR was greater for the R epimer, renal tubular secretion was greater for the S epimer. When probenecid was coadministered, the CLR of each epimer was significantly reduced and was approximately equal to the glomerular filtration rate. The difference in CLR between the two epimers was simply due to differences in plasma protein binding. The observations in the present study suggest that both carbenicillin epimers are secreted by an organic anion transport system in the renal proximal tubule in humans and that the two epimers may be distinguished in the secretion process, resulting in the differences in the secretion rates.

Adult↗

Nematocidal activity of turmeric: synergistic action of curcuminoids.

A new curcuminoid, cyclocurcumin (IV), was isolated from the nematocidally active fraction of turmeric, the rhizome of Curcuma longa, together with three known curcuminoids, curcumin (I), demethoxycurcumin (II) and bisdemethoxycurcumin (III). The structure of IV was elucidated on the basis of spectral data and confirmed by the partial synthesis from curcumin (I). Although the above curcuminoids were ineffective when they were applied independently, the nematocidal activity increased remarkably when they were mixed, suggesting a synergistic action between them.

Animals↗

A patient with congenital plasminogen deficiency manifesting primary pulmonary hypertension.

A 25-year-old Japanese man was diagnosed as having primary pulmonary hypertension, on the basis of the findings of cardiac catheterization and ventilation-perfusion scintiscans. The plasma level of plasminogen in this patient was found to be reduced to 43% by a functional assay and 61 mg/l by an antigenic assay. Based on the family study, the patient was considered to have a heterozygous congenital plasminogen deficiency. Accordingly, it is suggested that the defective fibrinolysis in this patient may have played an important role in the development of primary pulmonary hypertension through microthrombosis.

Adult↗

WS1279, a novel lipopeptide isolated from Streptomyces willmorei. Biological activities.

WS1279, a new lipopeptide isolated from the fermentation broth of Streptomyces willmorei No. 1279, stimulated the proliferation of mouse bone marrow cells in vitro and accelerated the recovery of granulocyte counts in bone marrow from leukopenia induced by mitomycin C (MMC) in mice. The glycerylcysteine moiety of WS1279 is necessary and the lipid peptide structure is required for manifestation of full stimulating activity in vitro. WS1279 was the most effective on the proliferation of bone marrow cells among the tested immunostimulants in vitro. However, the effect of WS1279 on restoration of reduced granulocyte counts in MMC-induced leukopenia in mice was less than that of FK-565, lipopolysaccharide, picibanil or forphenicinol. WS1279 augmented host resistance to infection with Staphylococcus aureus 47 in normal and immunosuppressed mice.

Adjuvants, Immunologic↗

Effect of medication with pravastatin sodium on hemorheological parameters in patients with hyperlipoproteinemia.

Pravastatin sodium, a newly developed potent synthesis inhibitor of HMG-CoA (beta-hydroxy-beta-methylglutaryl-cocarboxylase-A) reductase (Sankyo Co., Ltd., Japan) was medicated, 10 approximately 15 mg/day (mean: 11.1 mg/day) for 10.2 weeks in mean, in 14 patients with primary hyperlipoproteinemia of more than 230 mg/dl of serum cholesterol levels (mean age: 56.9 y.o.). The values of serum cholesterol decreased (from 242 +/- 12 to 207 +/- 22; mg/dl), and of high density lipoprotein (HDL) increased (from 42.3 +/- 8.8 to 45.3 +/- 9.2; mg/dl) significantly (p < 0.05, respectively) 10.2 weeks in mean after medication with pravastatin sodium. The whole blood viscosity, at every shear rate examined, corrected blood viscosity, for the standard hematocrit level of 45%, and plasma fibrinogen decreased significantly (p < 0.05, respectively) at the same time, without showing significant differences any more 10.2 weeks in mean after medication with those in 14 elderly normal subjects (mean age: 56.7 y.o.), which suggested that the hemorheological parameters in patients with primary hyperlipoproteinemia had improved significantly by medication with pravastatin sodium.

Cholesterol↗