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Biomedical subjects

H Matsuo

Publications and source records attributed to H Matsuo.

At least 253 records · Page 14Linked to original sources

Inhibition of vinblastine efflux mediated by P-glycoprotein by grapefruit juice components in caco-2 cells.

We investigated the effect of components in grapefruit juice (GFJ) on the transport of vinblastine, a substrate of P-glycoprotein (P-gp), across Caco-2 cells. The apical to basolateral flux of [3H]vinblastine was increased in the presence of GFJ extracts. The steady-state uptake of [3H]vinblastine from the apical side was significantly increased in the presence of GFJ in a dose-dependent manner within the range of 2.5 to 50% (v/v) of GFJ. Although naringin and naringenin reduced apical efflux of [3H]vinblastine at the concentration present in GFJ and increased steady-state uptake from the apical side to 124 and 240%, respectively, the observed effect of naringin was not enough to account for the effect of GFJ and naringenin is not naturally present in GFJ. To investigate the effective components in GFJ, we examined the inhibitory effect of several organic solvent extracts of GFJ on the transport of [3H]vinblastine in Caco-2 cells. Organic solvent extracts of GFJ enhanced the apical to basolateral transcellular transport and inhibited the apical efflux. The permeability coefficient of apical to basolateral transport of [3H]vinblastine increased in the order of the ethyl acetate>diethyl ether>methylene chloride extracts of GFJ. Since the extracted amount of naringenin by ethyl acetate was less than that with the other organic solvents, the primary inhibitor in GFJ is suggested to be different from this flavonoid. The present study demonstrated the existence of inhibitory components in GFJ for the P-gp function in Caco-2 cells, which are distinct from known components such as naringin or naringenin.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

Responses of natriuretic peptides to acute and chronic salt loading in normotensive and hypertensive subjects.

Responses of endocrine systems to acute and chronic salt loading were examined in normotensive and hypertensive subjects. In the acute salt load study, isotonic saline (20 ml/kg for 1 h) was intravenously infused in 10 normotensive subjects and 12 patients with essential hypertension. Plasma noradrenaline was suppressed by saline infusion in the normotensive subjects (-19%, p < 0.05), but was not suppressed in the hypertensive patients (-5%, NS). Plasma brain natriuretic peptide concentration was significantly increased in the hypertensive patients (+15%, p<0.05), while it was unchanged in the normotensive subjects. In the chronic salt load study, 9 normotensive subjects and 30 patients with essential hypertension underwent two 7-d periods of 30 and 260 mmol/d sodium intake. On the basis of the blood pressure change, 17 hypertensive patients were classified as salt-resistant and 13 as salt-sensitive. The salt-sensitive hypertensive patients had suppressed plasma renin activity even during low-salt intake. During high salt intake, the plasma noradrenaline concentration failed to decrease in the salt-sensitive hypertensive patients (-6%, NS), whereas it fell significantly in the normotensive subjects (-27%, p < 0.05) and the salt-resistant hypertensive patients (-33%, p < 0.01). The high-salt intake also increased plasma concentrations of brain natriuretic peptide as well as atrial natriuretic peptide in all groups. In the salt-sensitive hypertensive patients, there was a positive correlation between the increase in blood pressure and that in atrial natriuretic peptide (r= 0.84, p< 0.01). These data indicate that brain natriuretic peptide is involved in chronic changes in body fluid volume. In patients with essential hypertension, acute volume expansion also evokes the response of brain natriuretic peptide. Salt-sensitive hypertension seems to be characterized by blunted response of the sympathetic nervous system. In addition, an increase in atrial natriuretic peptide is likely to play an important role in mechanisms counteracting salt-induced elevation of blood pressure.

Adult↗

Serum deprivation-induced apoptosis in cultured porcine granulosa cells is characterized by increased expression of p53 protein, Fas antigen and Fas ligand and by decreased expression of PCNA.

Although serum deprivation induces apoptosis in several cell lines, biochemical characterization of the apoptosis in primary granulosa cells (GCs) induced by serum deprivation has rarely been reported. In the present study, GCs from small follicles of porcine ovaries were precultured under a serum-containing condition for seven days, then stepped down to a serum-free condition and cultured for the subsequent two days. GCs were subjected to DNA fragmentation and immunoblot analyses. Data indicated that serum deprivation induced GC apoptosis characterized by DNA laddering, which was associated with decreased expression of proliferating cell nuclear antigen (PCNA) and increased expression of p53 protein, Fas antigen and Fas ligand. Serum deprivation also resulted in an increase in a 115 kDa protein expression despite no detectable expression of a 66 kDa c-myc protein. This suggests that serum removal from primary GCs may activate multiple apoptotic pathways such as a p53-associated pathway and a Fas-Fas ligand pathway.

Animals↗

An object-modeling method for hospital information systems.

Our goal is to increase the software productivity of hospital information systems (HISs) by applying object-oriented technologies. We propose a new object-modeling method for HISs that combines three general methods--an object modeling technique (OMT), class responsibilities collaboration (CRC) cards, and a use-case approach--to extract objects effectively. Our method also takes HIS functionality characteristics such as history and patient-staff linking into consideration to increase the reusability of objects. To test this method, we applied it to several HISs such as a drug-history system, a nursing-support system and an electronic patient record (EPR). We found that the software productivity of the drug-history system was more than doubled by using the combined method. Also, more than 40% of the logic classes could be reused in the nursing-support system and EPR. These findings confirmed that the proposed method can significantly increase the software productivity of HISs.

Clinical Pharmacy Information Systems↗

Mobile PCIS: point-of-care information systems with portable terminals.

We have developed a Point-of-Care Information System (PCIS) that uses portable terminals and supports the entire loop of daily nursing work for the first time. Nursing work includes a great deal of indirect nursing work, such as documenting patient information, conferring with other health-care providers, and so on, as well as direct patient care. The time needed for this indirect work often exceeds the time actually spent directly caring for patients and needs to be reduced. Our system was developed with the goal of doing this to make nursing work more efficient. The system consists of personal digital assistants (PDAs) that nurses carry in the hospital wards and a server computer located in the nursing station. The system has three main functions: 1) Data Browsing provides patient information such as a brief history, vital-sign charts, and handwritten notes; 2) Schedule Planning helps nurses organize doctors' instructions and make To-do lists for the day; and 3) Care Management reminds nurses when they should execute the doctors' orders and provides tools for data entry. These three functions cover the entire loop of daily nursing work. The PDAs and the server computer can share up-to-date information by data transmission through telephone lines (low-power cellular phones can be used), infrared devices, or RS-232C cables. Results from a preliminary hospital evaluation showed that use of the system can reduce the time needed for nursing documentation by 60% (a 10% saving of a nurse's total working time), and that more than 80% of the nurses who used the system felt it would make nursing work more efficient.

Attitude to Computers↗

Quantitative prediction of the interaction of midazolam and histamine H2 receptor antagonists in rats.

To quantitatively evaluate drug-drug interactions involving metabolic processes in the liver, we attempted to predict the increasing ratio of the plasma concentration of midazolam (MDZ) in the presence of cimetidine (CIM) or nizatidine (NZD) in rats. Under steady-state conditions for the plasma concentration of CIM or NZD, MDZ was administered through the portal vein. The AUC of MDZ in the presence of CIM was 2.5-fold higher than that in the absence of CIM. There was no effect of NZD on the AUC of MDZ. The liver/plasma concentration ratios for CIM and NZD were 4.0 and 2.7, respectively. The estimated liver unbound concentration (CH,f)/plasma unbound concentration (Cp,f) ratios for CIM and NZD were 1.9 and 2.4, respectively, suggesting concentrative hepatic accumulation of both drugs. The oxidative metabolism of MDZ in rat liver microsomes was competitively inhibited by CIM or NZD, and the Ki values of CIM and NZD were 110 and 2600 microM, respectively. Based on these data obtained in vivo and in vitro, the increasing ratios for MDZ in the presence of CIM or NZD were predicted using the equations Rp = 1 + Cp,f/Ki and RH = 1 + CH,f/Ki. The observed increasing ratios in the presence of CIM were very close to RH, compared with Rp. However, Cp, f and CH,f were much less than Ki and there was no difference between Rp and RH in the presence of NZD. Consequently, Cp,f and CH, f were greater than or equal to Ki and Cp,f was not equal to CH,f, as in the presence of CIM, and it was indicated that CH,f was more suitable for quantitatively predicting the drug-drug interactions than was Cp,f.

Animals↗

[Precipitating factors in patients with repetitive exacerbation of chronic left heart failure].

The precipitating factors of repetitive exacerbation were investigated in 110 consecutive patients with chronic left heart failure admitted due to acute exacerbation more than twice to the medical emergency ward of National Cardiovascular Center from January, 1992 to December, 1996. The controls were 189 consecutive patients with chronic left heart failure admitted to the ward due to acute exacerbation only once during the same period. Excessive intake of water or sodium, overwork and infection were common precipitating factors in the first decompensation of left heart failure, but the former two factors became less common with repeated admission. Patient mistakes such as excessive intake of water or sodium, overwork and noncompliance with medications, and new onset arrhythmias were common precipitating factors in patients (n = 13) admitted to the ward more than four times. Infection was a common precipitating factor (63%) in patients with a time interval between readmission and the last discharge of longer than 2 years. Despite repeated admission, infection was a common precipitating factor in patients with valvular heart disease (n = 31), patient mistakes were common in heart disease with left ventricular hypertrophy (n = 20), and infection and new onset arrhythmias were common in dilated cardiomyopathy (n = 28) and old myocardial infarction (n = 31). Patient mistakes and new onset arrhythmias were the common factors that led to repetitive exacerbation of left heart failure, and precipitating factors were characterized by the etiology of left heart failure.

Aged↗

[Mitral valve tissue characterization using acoustic microscopy].

Mitral valve hardness in the rough and clear zones was evaluated by measuring the propagation velocity (m/sec) of ultrasound through the valve, based on the hypothesis that harder tissues will have larger ultrasonic velocity values passing through the tissue. Mitral valve specimens were obtained from 16 normal subjects (age, 15-72 years) at autopsy. An acoustic microscope, operating at 450 MHz, was used to measure the ultrasonic velocity through the three layers of the valve: the atrialis; the spongiosa; and the fibrosa. Furthermore, the mean ultrasonic velocity through the three layers was measured. These measurements were conducted in the rough and clear zones of the valve. In the rough zone, the ultrasonic velocities were 1,634 +/- 71 in the atrialis, 1,574 +/- 37 in the spongiosa, and 1,726 +/- 97 m/sec in the fibrosa. In the clear zone, the ultrasonic velocities were 1,691 +/- 117 in the atrialis, 1,575 +/- 44 in the spongiosa, and 1,909 +/- 131 m/sec in the fibrosa. There were significant differences between velocities in the three layers in both the rough and clear zones. Furthermore, the mean ultrasonic velocity in the three layers in the clear zone (1,887 +/- 138 m/sec) was higher than that in the rough zone (1,642 +/- 53 m/sec; p < 0.001). These findings show that fibrosa, which is rich in collagen fibers, is harder than atrialis, which is rich in elastic fibers, and the spongiosa, which is poor in connective tissues, is the softest. The higher mean ultrasonic velocity in the clear zone than in the rough zone indicates that the clear zone is harder than the rough zone, although the clear zone is thinner than the rough zone.

Adolescent↗

Two cases of glufosinate poisoning with late onset convulsions.

Glufosinate ammonium (GLA), the active ingredient in the non-selective herbicide BASTA (18.5% GLA), is a phosphinic acid analogue of glutamic acid. We report 2 cases of GLA poisoning with late onset convulsions and increased serum CK in spite of low blood concentrations of GLA after hemodialysis. A 69-y-old female was admitted to the emergency department after taking 500 ml of BASTA. On arrival she was conscious, and gut decontamination, hemodialysis and hemoperfusion were performed. However, 8 1/2 hours after ingestion, general convulsions occurred. Her serum OK increased to a peak of 24,900 IU/L on the third day of admission. An 87-y-old male was admitted to the emergency department 3 1/2 hours after taking 200 ml of BASTA and receiving gastric lavage at a local emergency room. On arrival he was conscious, and serial activated charcoal and hemodialysis was performed. Blood concentration of GLA after hemodialysis decreased from 1.56 micrograms/ml to 0.68 micrograms/ml. Thirty hours after admission he had general convulsions. GLA was not detected in the cerebrospinal fluid 6 h after the convulsions. His serum CK increased to a peak of 17,870 IU/L on the fifth day of admission.

Aged↗

Possible mechanisms of vascular relaxation induced by pulsed-UV laser.

This study was designed to examine the mechanism of vasorelaxation induced by pulsed-UV laser. Luminal diameters of rat femoral arteries were measured prior to and following krypton-fluoride excimer laser irradiation of 248 nm in wavelength. The diameter was enlarged to 1.3 times the preirradiated size at 1 or 10 Hz irradiation when the fluence was over 2.0 mJ/pulse/mm2, while the diameter reached 1.8 times at 100 Hz with a fluence of 0.8 mJ/pulse/mm2. Vasorelaxation by the 100 Hz irradiation was inhibited when the artery was pretreated with methylene blue but was enhanced with superoxide dismutase. Pathological analysis revealed an ablation crater and vacuole formation in the vessel at 1 or 10 Hz irradiation, but these changes were not remarkable in the 100 Hz-exposed sample. These findings suggest that vasorelaxation induced by the pulsed UV irradiation at 1 or 10 Hz results from structural alteration of vascular smooth muscle by the ablation crater or vacuolization. On the other hand, a possible mechanism of vasorelaxation at the 100 Hz irradiation is partially related to nitric oxide.

Animals↗

[Guanylin family: new intestinal peptides regulating salt and water homeostasis].

Guanylin and uroguanylin are novel peptides that are first isolated from rat jejunum and opossum urine, respectively. They bind to and activate guanylyl cyclase-C (GC-C) to regulate intestinal and renal fluid and electrolyte transport through the second messenger, cyclic GMP. Heat-stable enterotoxins produced by pathogenic bacteria have close structural similarities to guanylin and uroguanylin, and they use this mimicry to act on GC-C, causing life-threatening secretory diarrhea. Guanylin primarily is restricted to the intestine, whereas uroguanylin is present in the stomach kidney, lung and pancreas in addition to intestine. Guanylin and uroguanylin in the intestine are secreted into the lumen and blood in response to sodium chloride administration. These peptides will function in salt and water transport in the intestine and kidney by luminocrine and/or endocrine actions. Guanylin peptide family links the intestine with the kidney and could play the physiological roles in the control of water and electrolyte balance.

Amino Acid Sequence↗

[Pharmacological and exercise stress echocardiography].

Stress echocardiography (SE) is a recently developed technique to detect coronary artery disease and myocardial ischemia, and in increasing importance because several advantages are offered over nuclear perfusion imaging. Particularly, it is well established in acute coronary syndrome, that impaired left ventricular function is not always an irreversible process, and the information obtained using SE is useful for evaluating myocardial viability. Additionally, a progress in computer technology permits us to quantitatively assess the regional myocardial function during ischemia induced. Then, we introduced the feasibility of the pharmacological and exercise stress echocardiography for detecting myocardial ischemia and viability in this report.

Acute Disease↗

Prediction of catalepsies induced by amiodarone, aprindine and procaine: similarity in conformation of diethylaminoethyl side chain.

Recently, clinical cases of parkinsonism due to antiarrhythmics drugs amiodarone and aprindine and a local anesthetic drug procaine have been reported. We performed both in vivo and in vitro experiments to quantitatively predict the intensity of catalepsy by these drugs and haloperidol in mice. Haloperidol showed the most potent relative intensity of catalepsy, followed by aprindine, metoclopramide, tiapride, amiodarone and procaine, in that order. In vivo dopamine D1 and D2 receptor occupancies of the six drugs to the striatum were observed. In vitro binding affinity (Ki) of these drugs to the D1 and D2 receptors in the striatum synaptic membrane was within the range of 60 nM to 706 microM, 0.5 nM to 75 microM and 860 nM to 115 microM, respectively. A good correlation between the relative intensity of drug-induced catalepsy and the Ki values for the dopamine D1 and D2 receptors was obtained (r =.911 and r =.896, respectively; P <.05). The partial tertiary structure of the tested drugs was well superimposed on that of haloperidol. In conclusion, these drug-induced catalepsies were due to the blockade of the D1 and D2 receptors, which was related to the analogous tertiary structures (diethylaminoethyl side chain).

Amiodarone↗

Biology of human trophoblast.

In order to elucidate the regulation of placental growth, we have characterized the expression of proliferating cell nuclear antigen (PCNA), apoptotic DNA fragmentation and bcl-2 protein in human placenta during pregnancy. PCNA and bcl-2 protein expression were examined by immunohistochemical techniques, while the occurrence of apoptotic DNA fragmentation was assessed by in situ analysis of DNA 3'-end labeling method. Both PCNA expression and apoptotic DNA fragmentation were found in cytotrophoblasts (C-cells), being most abundant in early placenta, less abundant in midterm placenta and least abundant in term placenta. In contrast, bcl-2 protein expression was found in syncytiotrophoblasts (S-cells), being least abundant in early placenta, less abundant in midterm placenta and most abundant in term placenta. These data indicate that early placenta is characterized by the highly proliferative activity of C-cells associated with the increased occurrence of apoptosis, whereas term placenta is characterized by the abundant expression of bcl-2 protein in S-cells. Furthermore, effects of EGF on the proliferative activity and differentiated function of trophoblasts were investigated using an organ culture system. Explants of trophoblastic tissues were cultured with or without EGF, in the presence or absence of 10(-8)M triiodo-L-thyronine (T3) in a serum-free condition. In 4-5 week placentas, EGF and EGF receptor were almost exclusively localized in C-cells, and EGF augmented the proliferative activity of C-cells without affecting the ability to secrete hCG and hPL. By contrast, in 6-12 week placentas, EGF and EGF receptor were predominantly localized in S-cells, and EGF stimulated hCG and hPL secretion without affecting the proliferative activity of C-cess. The addition of T3 (10(-8)M) resulted in an increased secretion of immunoreactive EGF by cultured placental explants. These findings suggest that EGF acts as a local factor in regulating early placental growth and function in synergy with thyroid hormone. On the other hand, progesterone selectively inhibited pleise hCG (alpha, beta) mRNAs expression and decreased hCG secretion in normal placental tissues, whereas choriocarcinoma did not respond to progesterone. This suggests that inhibitory regulation of hCG synthesis in choriocarcinoma is different from normal placenta. It was also found that in molar trophoblasts and choriocarcinoma cells PCNA expression was high, but both bcl-2 protein and apoptotic signal expression were low. Characterization of choriocarcinoma hCG revealed that there are striking differences in carbohydrate structures between normal hCG and choriocarcinoma hCG. Sialic acid content in choriocarcinoma hCG was extremely lower compared to that in normal hCG. The detection of the alteration in hCG sugar chains is useful for biochemical diagnosis of choriocarcinoma.

Cell Differentiation↗

[Benign pulmonary nodule: morphological features and contrast enhancement evaluated with contiguous thin-section CT].

The morphological changes in 54 benign lung nodules, including 8 histologically proven nodules of tuberculoma, 10 of focal organizing pneumonia (FOP), 1 of lung abscess and 35 other benign nodules, were evaluated with contiguous thin-section (3mm) CT. In addition, incremental dynamic studies were carried out in 25 of these nodules. The three-dimensional shapes of the nodules were found to be quite varied and were classified into four types: (A) round mass (n = 18), (B) polygonal mass with concave or straight margins (n = 20), (C) oval or band-like mass extending along the bronchovascular bundle (n = 7), (D) oval mass attached to the pleura with broad contact (n = 9). Forty-two (78%) of the 54 nodules were located along the bronchovascular bundle. The maximum increments in CT values over 20HU were observed after contrast enhancement in 18 (72%) of the 25 benign nodules, among which all tuberculomas showed little or no contrast enhancement. The number of small vessels quantified microscopically in teh center of the nodules were minimal in tuberculomas with little enhancement and plentiful in lesions of FOP and abscess which showed marked enhancement. Our results suggest that the differentiation between benign and malignant pulmonary nodules is not possible simply on the basis of the degree of contrast enhancement. Therefore, morphological features and the anatomical relation to the bronchovascular bundles should also be taken into consideration in the diagnosis of pulmonary nodules.

Adult↗

Genomic structure and chromosomal localization of human uroguanylin.

Uroguanylin, a member of the guanylin peptide family, is a novel peptide regulator in intestinal salt and water transport. We isolated the gene for uroguanylin from a human genomic library and determined its structure. This gene consists of three exons and two introns within an overall length of 2.5 kb. The 5' flanking region has TATA and CAAT boxes. The gene also has multiple binding sites for promoter-specific transcription factor, activator protein-1, and activator protein-2, and a cAMP-regulated enhancer element. Fluorescence in situ hybridization showed the uroguanylin gene at human chromosome 1p33-p34. RNA blot analysis showed that human uroguanylin mRNA is expressed in the gastric fundus and pylorus as well as in the intestine.

Amino Acid Sequence↗

Production of bleomycin N-acetyltransferase in Escherichia coli and Streptomyces verticillus.

Bleomycin-producing Streptomyces verticillus ATCC 15003 has two bleomycin resistance genes, designated blmA and blmB. Bleomycin N-acetyltransferase, encoded by blmB, was overproduced in Escherichia coli as a protein fused to the maltose-binding protein. The protein (fBAT), purified to homogeneity after digestion of the fusion product with blood coagulation factor Xa protease, had an additional 6 N-terminal amino acid residues, but retained its bleomycin-acetylating activity, as did the entire fusion protein. The K(m) and Vmax values of purified fBAT for the substrate bleomycin were 13.0 microM and 3.4 nmol [corrected] min-1 ml-1, respectively. The optimal pH for the acetylating activity was 6.0 in 10 mM phosphate buffer. The molecular mass and pI value of fBAT were estimated by polyacrylamide gel electrophoresis to be about 34500 and 6.13, respectively. An anti-fBAT monoclonal antibody was generated and used to show that bleomycin N-acetyltransferase is expressed simultaneously with bleomycin production in S. verticillus.

Acetyltransferases↗