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Biomedical subjects

N Ishizuka

Publications and source records attributed to N Ishizuka.

At least 19 recordsLinked to original sources
PubMed2000

Performance of a monolithic silica column in a capillary under pressure-driven and electrodriven conditions

A continuous macroporous silica gel network was prepared in a fused-silica capillary and evaluated in reversed-phase liquid chromatography. Under pressure-driven conditions, the monolithic silica column derivatized to C18 phase (100 microns in diameter, 25 cm in length, silica skeleton size of approximately 2.2 microns) produced plate heights of about 23 and 81 microns at 0.5 mm/s with a pressure drop of 0.4 kg/cm2, and at 4.0 mm/s with 3.6 kg/cm2, respectively, in 90% acetonitrile for hexylbenzene with a k value of 0.7. The separation impedance, E, calculated for the present monolithic silica column was much smaller at a low flow rate than those for particle-packed columns, although higher E values were obtained at a higher flow rate. Considerable dependence of column efficiency on the linear velocity of the mobile phase was observed despite the small size of the silica skeletons. A major source of band broadening in the HPLC mode was found in the A term of the van Deemter equation. The performance of the continuous silica capillary column in the electrodriven mode was much better than that in the pressure-driven mode. Plate heights of 7-8 microns were obtained for alkylbenzenes at 0.7-1.3 mm/s, although the electroosmotic flow was slow. In HPLC and CEC mode, the dependency of plate height on k values of the solutes was observed as seen in open tube chromatography presumably due to the contribution of the large through-pores. Since monolithic silica capillary columns can provide high permeability, the pressure-driven operation at a very low pressure can afford a separation speed similar to CEC at a high electric field.

Journal Article↗
PubMed2000

The influence of different insufflation pressures during carbon dioxide pneumoperitoneum on the development of pulmonary metastasis in a mouse model.

BACKGROUND: The effects of different insufflation pressures on the development of pulmonary metastasis was investigated in a mouse laparoscopy model. METHODS: BALB/C mice intravenously inoculated with colon 26 cells were randomized to one of five treatment groups (10 mice per group): pneumoperitoneum at different pressures of 5, 10 or 15 mmHg; full laparotomy for 60 min; or anesthesia control. Cancer nodules on the lung surface 19 days postoperatively were compared between groups. RESULTS: (a) As compared with the control group, pneumoperitoneum at 10 and 15 mmHg and laparotomy enhanced the growth of pulmonary metastases (p < 0.01). (b) The growth of metastases also was greater in laparotomy group mice than in mice undergoing pneumoperitoneum at 5 and 10 mmHg (p < 0.05). CONCLUSIONS: These results suggest that the effects of different insufflation pressures on the growth of pulmonary metastases are not identical, and that pneumoperitoneum with high pressure may promote pulmonary metastases similar to those with laparotomy.

Analysis of Variance↗
PubMed1999

A noninvasive method of measuring wave intensity, a new hemodynamic index: application to the carotid artery in patients with mitral regurgitation before and after surgery.

Wave intensity (WI) is a new hemodynamic index, which is defined as (dP/dt)(dU/dt) at any site of the circulation, where dP/dt and dU/dt are the time derivatives of blood pressure and velocity, respectively. Arterial WI in normal subjects has two positive sharp peaks. The first peak occurs during early systole when a forward-traveling compression wave is generated by the left ventricle. The magnitude of this peak increases markedly with an increase in cardiac contractility. The second peak, which occurs towards the end of systole, is caused by generation of a forward-traveling expansion wave by the ability of the left ventricle to actively stop aortic blood flow. The interval between the R wave of the ECG and the first peak of WI (R-1st peak interval) and the interval between the first and second peaks (1st-2nd interval) are approximately equal to the preejection period and left ventricular ejection time, respectively. Using a combined Doppler and echo-tracking system, we obtained carotid arterial WI noninvasively. We examined the characteristics of WI in 11 patients with mitral regurgitation (MR) before and after surgery, and 24 normal volunteers. In the MR group before surgery, the second peak was decreased and the (1st-2nd interval)/(R-R interval) ratio was reduced, compared with the normal group (140 +/- 130 vs 750 +/- 290mmHg m/s3. P < 0.0083; 20.7% +/- 3.4% vs 26.7% +/- 2.8%, P < 0.083). There were no significant differences in the first peak between the normal group and the MR group before and after surgery. The second peak in the MR group was increased significantly (P < 0.016 vs before surgery) to 1,150 +/- 830mmHg m/s3 in the early period after surgery (stage I), and to 1,090 +/- 580mmHgm/s3 in the late period after surgery (stage II). These values did not differ significantly from that of the normal group. At stage I, the (R-1st peak interval)/ (R-R interval) ratio was increased from 13.4% +/- 2.7% to 20.6% +/- 5.6% (P < 0.016 vs before surgery). At stage II, this ratio decreased to 16.2% +/- 2.8% (P < 0.016 vs stage I). but was still significantly higher than that before surgery. The (1st-2nd interval)/(R-R interval) ratio increased significantly after surgery (P < 0.016 vs before surgery) to values (27.0% +/- 4.5% at stage I and 28.9% +/- 2.6% at stage II) which did not differ significantly from that of the normal group. The recovery of the second peak after surgery suggests that the left ventricle had recovered the ability to actively stop aortic blood flow. Wave intensity is useful for analyzing changes in the working condition of the heart.

Adult↗
PubMed1999

Tumor necrosis factor alpha signaling pathway and apoptosis in pancreatic beta cells.

Cytokines induce apoptosis in pancreatic beta cells, but the exact mechanisms and sequence of events are not clear. Here, we investigate a role for tumor necrosis factor alpha (TNF-alpha) in the apoptosis of beta cells. Using the ribonuclease (RNase) protection assay and the reverse transcriptase-polymerase chain reaction (RT-PCR) method, we confirmed that TNF receptor 1 (TNFR1), TNFR1-associated death domain protein (TRADD), Fas receptor-associated intracellular protein with death domain (FADD), and FADD-like interleukin-1beta-converting enzyme (FLICE) were expressed in the pancreatic beta cell line, MIN6 cells. Fluorescent microscopic examination using Hoechst 33342 dye (Sigma, St Louis, MO) demonstrated that TNF-alpha induced time- and dose-dependent apoptotic nuclear changes in these beta cells. In situ end-labeling (ISEL) DNA analysis revealed that 10 nmol/L TNF-alpha generated new 3'-OH DNA strand breaks. Moreover, qualitative assessment of the induced DNA damage on agarose gels showed that 10 nmol/L TNF-alpha produced characteristic apoptotic patterns of DNA fragments formed by internucleosomal hydrolysis of static chromatin. In addition, C2-ceramides and natural ceramides dispersed in a solvent mixture of ethanol and dodecane induced characteristic features of apoptosis in MIN6 cells, mimicking TNF-induced DNA damage. We also determined endosomal ceramide production after TNF-alpha (10 nmol/L) treatment in MIN6 cells using the diacylglycerol kinase assay. These results suggest that TNF-alpha can cause apoptosis in pancreatic beta cells through TNFR1-linked apoptotic factors, TRADD, FADD, and FLICE, and TNF-induced ceramide production may be involved in the pathways.

Adaptor Proteins, Signal Transducing↗
PubMed1999

Synthesis and structure-activity relationship of a new series of potent angiotensin II receptor antagonists: pyrazolo[1,5-a]pyrimidine derivatives.

We have already reported 7-oxo-4,7-dihydropyrazolo[1,5-a]pyrimidine-3-carboxylic acid derivatives, which are potent in vitro angiotensin II (AII) antagonists, but have no oral antihypertensive activity. Removal of the carboxylic acid and replacement of the heteroaromatic system afforded potent in vitro antagonists. Removal of the carbonyl oxygen and changing the position of the biphenyltetrazole substituent were critical to the display of oral activity. To improve the in vitro and oral activities, modifications were made of the substituents at the 3- and 5-positions of the pyrazolo[1,5-a]pyrimidine. Structure-activity studies showed the methyl substituent at the 3-position to be essential for potent in vivo activity. We present the design, syntheses, and biological data of a series of pyrazolo[1,5-a]pyrimidine derivatives, which are orally active AII receptor antagonists.

Angiotensin II↗
PubMed1999

[Mitral valve replacement under cardiopulmonary bypass which complicated by multiple sclerosis: a case report].

The 60-year-old women who complicated by multiple sclerosis was referred to our hospital under diagnosis of mitral valve stenosis and tricuspid valve regurgitation. The mitral valve replacement and the tricuspid valve annuloplasty were performed under cardiopulmonary bypass. In the state of multiple sclerosis, even an operation by general anesthesia could become a cause of abrupt change, but by appropriate management during and after surgery, the post operative course was uneventful without any complications, and the patient discharged on the 35th post operative day.

Cardiopulmonary Bypass↗
PubMed1999

[A successful surgical case of billowing mitral leaflet syndrome (Barlow syndrome) combined with severe mitral regurgitation].

We report a successful surgical case of billowing mitral leaflet syndrome combined with severe mitral regurgitation. A 45-year-old man suffered from congestive heart failure and admitted our institution for precise examination. A heart murmur was pointed out by a medical examination at his high school, and mitral valve prolapse was detected by echocardiography at 23 year of age. No medication was applied because he showed no symptom. From 44 year of age, he noted palpitation on exercise. Holter monitor showed blocked PAC and Wenckebach A-V block, and transesophageal echocardiography indicated severe mitral regurgitation due to the billowing of voluminous both leaflets. At his operation, we recognized the billowing of both leaflets with torn chordae, and size of the mitral valve orifice was 8.5 x 5 cm. The huge mitral valve was replaced with a CarboMedics 31M prosthetic valve by plicating mattress stitches of native mitral annulus. Histopathologic findings showed accumulation of acid mucopolysaccharide. Postoperative echocardiography showed reduction of the left ventricular volume and preservation of the left ventricular function. Relatively slow progression of the billowing mitral leaflet syndrome did not cause apparent symptoms of heart failure in this patient. Therefore, proper selection of the procedure and timing of surgical treatments might be important for successful long-term results after operation of the billowing mitral leaflet syndrome.

Cardiac Surgical Procedures↗
PubMed1999

[CBDCA, etoposide and epirubicin high-dose combination chemotherapy supported by peripheral blood stem cell transplantation (PBSCT) in metastatic breast cancer].

Six metastatic breast cancer patients, including one brain metastasis, one lung metastasis, three local recurrences and one bone metastasis, underwent multidrug chemotherapy with CBDCA, Etoposide (ETP) and Epirubicin (EPI). Each patient received two courses of PBSC mobilization chemotherapies and subsequently received high-dose chemotherapies for at least two courses. CBDCA AUC 4, ETP 300 mg/m2 and EPI 40 mg/m2 were administered intravenously as a PBSC mobilization chemotherapy, and high-dose chemotherapies were performed under the regimen of CBDCA AUC 8, ETP 900 mg/m2 and EPI 60 mg/m2. Severe bone marrow suppression due to high-dose chemotherapies was off sct by autologous peripheral blood stem cell transplantation (PBSCT). The PBSC mobilization chemotherapies resulted in one CR, three PR, one NC and one PD in the six patients. The PD patient died before high-dose chemotherapy. Consequently, the remaining five patients received the high-dose chemotherapies, which achieved three CR, one PR and one PD in the five patients. The response rate of high-dose chemotherapy was 80% (4/5 cases). In overall outcome, three patients have continued 16, 12 and 10 months tumor-free survival, and three patients died of cancer progression. High-dose chemotherapy with CBDCA, ETP and EPI has led to increased CR rates in metastatic breast cancer, and such therapy has desirable effect on the patient's prognosis.

Adult↗
PubMed1998

Adrenomedullin synergistically interacts with endogenous vasodilators in rats: a possible role of K(ATP) channels.

To examine synergistic interactions among naturally occurring vasodilators, we investigated the effects of i.v. infusion of adrenomedullin (ADM) alone and in combination with low-dose vasoactive intestinal polypeptide (VIP) or calcitonin gene-related peptide (CGRP) on adenosine-induced vasodepression in rats. I.v. infusion of the combination of low-dose ADM (0.1 ng kg(-1) min(-1)) and VIP (3 ng kg(-1) min(-1)), as well as that of ADM (1 ng kg(-1) min(-1)) alone, significantly enhanced the vasodepressor responses to bolus i.v. doses of adenosine (3-100 microg kg(-1)), but not those to acetylcholine (0.1 microg kg(-1)). The observed potentiation did not occur in the presence of glibenclamide (20 mg kg(-1) i.v.), an antagonist of K(ATP) channels. Simultaneous i.v. infusion of low-dose ADM and CGRP (0.1 ng kg(-1) min(-1)) failed to enhance the effects of adenosine as well as acetylcholine. In the whole-cell voltage clamp experiments using single cells of the rat mesenteric artery, ADM (10(-11)-10(-7) M) as well as CGRP (10(-11)-10(-7) M) produced increases of inward current in a concentration-dependent manner. The ADM-induced current was not affected by iberiotoxin, a specific blocker of large conductance Ca2+-activated K+ channels, but suppressed markedly by glibenclamide and CGRP(8-37), a selective antagonist of CGRP1 receptors. From the results, we conclude that several naturally occurring vasodilators involving ADM synergistically interact, probably in link with K(ATP) channels, and furthermore that ADM may act, in part through CGRP1 receptor activation.

Adenosine↗
PubMed1998

Flavor deterioration in yogurt.

Volatile components of flavored yogurt preserved at 5 degrees C in the dark for 0 day, 3 days and 10 days were recovered by simultaneous distillation extraction (SDE) and headspace (HS) procedures. Gas chromatography (GC) and GC-mass spectrometry (GC-MS) analyses of those samples showed remarkable changes in some compounds. Aldehydes which contribute to expressing citrusy notes were reduced to alcohols during fermentation process and storage. As a result, the strength of flavors which expressed well-balanced citrusy notes in yogurt were weakened, and fatty or oily notes mainly caused from alcohols were strengthened reversely. Hydrocarbons were also digested by bacteria during a fermentation process. A small amount of other compounds, such as esters and terpene alcohols changed. Fewer effects of sorption into a package material and chemical reactions, such as hydrolysis esters, hydration or oxidation of hydrocarbons, were observed.

Adsorption↗
PubMed1998

Hypotensive mechanism of [Leu13]motilin in dogs in vivo and in vitro.

The effects of [Leu13]motilin were examined in vivo after its intravenous administration into anesthetized dogs and in vitro with isolated preparations of canine mesenteric artery. [Leu13]Motilin (0.1-10 nmol x kg(-1), i.v.) induced both strong and clustered phasic contractions in the gastric antrum and duodenum. At doses of over 1 nmol x kg(-1), [Leu13]motilin also produced transient decreases in arterial blood pressure, left ventricular pressure, maximum rate of rise of left ventricular pressure, and total peripheral resistance, and an increase in aortic blood flow and heart rate. A selective motilin antagonist, GM-109 (Phe-cyclo[Lys-Tyr(3-tBu)-betaAla] trifluoroacetate), completely abolished the gastric antrum and duodenal motor responses induced by [Leu13]motilin. In contrast, hypotension induced by [Leu13]motilin (1 nmol x kg(-1)) was unchanged in the presence of GM-109. In isolated mesenteric artery preparations precontracted with U-46619 (10(-7) M), [Leu13]motilin (10(-8)-10(-5) M) induced an endothelium-dependent relaxation, and this was inhibited by a pretreatment with N(omega)-nitro-L-arginine, a competitive inhibitor of NO synthase (10(-4) M). A high dose (10(-4) M) of GM-109 slightly decreased [Leu13]motilin-induced relaxation, and shifted the concentration-response curve of [Leu13]motilin to the right. However, the pA2 value (4.09) of GM-109 for [Leu13]motilin in the present study was conspicuously lower than that previously demonstrated in the rabbit duodenum (7.37). These results suggest that [Leu13]motilin induces hypotension via the endothelial NO-dependent relaxation mechanism and not through the receptor type that causes upper gastrointestinal contractions.

15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5↗
PubMed1998

[A case report of neoadjuvant intra-arterial injection chemotherapy combined with peripheral blood stem cell reinfusion in an advanced breast cancer patient].

A seventy-one year-old woman suffered from Stage IIIb advanced breast cancer complicated with direct thoracic invasion and skin eruption. An indwelling intra-arterial catheter was inserted into the subclavian artery for the administration of anti tumor agents. After three courses of neoadjuvant chemotherapy combined with G-CSF and/or PBSCT reinfusion, the breast cancer revealed a remarkable size reduction and was absent from direct thoracic and pectoral muscle, invasion within the physical status and visual analysis by CT scan. Thereafter, the patient underwent a radical mastectomy. In the pathological findings of the operation specimen, despite a remarkable tumor collapse, the microscopic invasion remained in the shallow layer of the pectoral muscle. Thus, the patient should be given additional postoperative irradiation. The patients has had six months of stable tumor-free survival since the mastectomy.

Aged↗
PubMed1998

[Treatment of cardiovascular Behçet's disease: a problem with valve replacement].

The treatment of aortic regurgitation (AR) caused by cardiovascular Behçet's disease was retrospectively analyzed in five patients with Behçet's disease complicated by moderate or severe AR (four men and one woman, with a mean age of 47 +/- 5.8 years; complete 1, incomplete 2, and suspected 2). The preoperative left ventricular end-diastolic diameter was larger than 60 mm (mean: 74 mm) in all patients, and the left ventricular fractional shortening was less than 0.28 in three patients. Aortic valve replacement (AVR) was performed in four patients, but perivalvular regurgitation developed in all patients after a mean of 5.4 +/- 1.2 months (range: 0.6-10 months) following surgery, causing the death of three patients. One patient (grade III) who did not undergo operation showed gradually increasing end-diastolic diameter, but he is still being followed up medically due to the poor outcome of surgery. Because of inflammation-induced tissue fragility, AVR was associated with postoperative perivalvular regurgitation and suture breakdown, resulting in an extremely poor outcome. Thus, AVR was considered best avoided even if Behçet's disease was complicated with moderate or severe AR.

Adult↗
PubMed1997

Effect of skeleton size on the performance of octadecylsilylated continuous porous silica columns in reversed-phase liquid chromatography.

We prepared continuous porous silica rods that had silica skeletons with sizes of 1.0-1.7 microns and through-pores of 1.5-1.8 microns, and evaluated their performance as a column in reversed-phase liquid chromatography. The mesoporous silica monoliths (mesopore size: 14 or 24 nm) were derivatized to C18 phase by on-column reaction with octadecyldimethyl-N,N-diethylaminosilane. The C18 silica rods gave minimum plate heights of 10-15 microns for aromatic hydrocarbons in 80% methanol and of 20-30 microns for insulin in acetonitrile-water mixtures in the presence of trifluoroacetic acid. The performance of the silica rods at a high flow-rate was much better than that of conventional columns packed with 5 microns C18 silica particles with pores of 12 or 30 nm, especially for high-molecular-mass species. Silica rods with the smaller sized silica skeletons resulted in Van Deemter plots showing a minimum plate height linear velocity of the mobile phase and a smaller dependence of plate height on the linear velocity. Separation impedance of less than 1000 was achieved with the continuous silica columns. The higher performance and lower pressure drop of silica rods at high flow-rates compared with particle-packed columns is provided by the small silica skeletons and large through-pores.

Animals↗
PubMed1997

[Transesophageal echocardiographic findings in patients after heart transplantation].

The diagnostic value of transesophageal echocardiography was investigated in heart transplant recipients, i.e., four patients who received orthotopic heart transplantation and one patient who received total heart transplantation. Donor-recipient atrial anastomosis was identified in the four patients with orthotopic heart transplantation, but not in the patient with total heart transplantation. Transthoracic and transesophageal echocardiography detected no thrombus or spontaneous echo contrast in any of the patients. Color Doppler transesophageal echocardiography showed trivial mitral regurgitation in all patients. Total heart transplantation resulted in no protruding suture line and normal atrial cavity size. The patient with total heart transplantation showed some difference in the peak flow velocity of the right and left pulmonary veins (left superior pulmonary vein: 48 cm/sec; right superior pulmonary vein: 86 cm/sec), possibly due to stenosis at the suture line between the left atrium and right superior pulmonary vein, or compression of the right superior pulmonary vein by the anastomosis between the superior vena cava and right atrium. Transesophageal echocardiography was helpful for detecting thrombus in the left atrium and left atrial appendage after heart transplantation, and allowed evaluation of the flow pattern in the pulmonary veins and left atrial appendage as well as abnormal flow in the atrium. In conclusion, transesophageal echocardiography is useful in the follow-up of heart transplant recipients.

Adult↗
PubMed1997

[Right atrial thrombus recognized 18 years after tricuspid valve replacement: a case report].

A 53-year-old man, who had undergone tricuspid valve replacement with Hancock valve and direct closure of a ventricular septal defect when aged 34 years, was admitted with signs of right heart failure. Two-dimensional echocardiography showed bioprosthetic tricuspid valve malfunction with right atrial thrombus. He was treated by tricuspid valve replacement using a Hancock II valve and removal of the right atrial thrombus with remarkable improvement. Transesophageal echocardiography was the most useful method for recognizing the presence of right atrial thrombus and assessing its actual or potential hemodynamic effects.

Echocardiography↗
PubMed1996

Na pump current can be separated into ouabain-sensitive and -insensitive components in single rat ventricular myocytes.

The present study was undertaken to identify functional isoforms of the Na,K-ATPase in single rat cardiac myocytes. Na,K-ATPase activity was measured as ouabain-sensitive, extracellular K-activated outward current (Na pump current) in ventricular myocytes voltage-clamped with single low-resistance (0.5- 1 M omega) patch electrodes at 36 degrees C. Solutions to block contaminating currents allowed Na pump current to be measured without significant contamination in 140 mM Na-containing superfusion solutions. The current-voltage relationship had a positive slope at potentials from -125 to 0 mV but became almost voltage-independent at positive potentials. The apparent Km for activation of this current at -40 mV by extracellular K was 2.7 +/- 0.3 mM (mean +/- SEM, n = 3) and increasing electrode Na increased the amplitude of the current to a maximum density of 4.11 +/- 0.17 pA/pF (n = 34). Intracellular vanadate (100 microM) produced an extracellular K-dependent inhibition of Na pump current that was rapidly reversed in K-free superfusion solution. Dose-dependent inhibition of Na pump current by ouabain was best described as the sum of two Michaelis-Menten binding sites: one with higher affinity (K1/2 = 1.0 +/- 0.7 microM) comprising 33 +/- 9% (n = 5-6) of the total current and the second with a K1/2 of 43 +/- 14 microM. Changing electrode [Na] from 15 to 100 mM had no effect on the dose-dependent inhibition of the current by ouabain. Thus, the properties of high and low affinity components of Na pump current are consistent with the presence of different Na,K-ATPases isoforms that have a similar ion dependence for transport activity.

Animals↗