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Biomedical subjects

M Miyazaki

Publications and source records attributed to M Miyazaki.

At least 1,243 records · Page 69Linked to original sources

Measurement of activities in two different angiotensin II generating systems, chymase and angiotensin-converting enzyme, in the vitreous fluid of vitreoretinal diseases: a possible involvement of chymase in the pathogenesis of macular hole patients.

PURPOSE: To investigate possible involvement of chymase and angiotensin-converting enzyme (ACE) in the pathogenesis of vitreoretinal diseases, both of which are related to the production of angiotensin II. METHODS: We measured chymase and ACE activities in the vitreous in the 54 affected eyes of 54 patients who had undergone vitreous surgery for idiopathic macular holes (MH, n = 14), proliferative diabetic retinopathy (PDR, n = 14), idiopathic epiretinal membranes (ERM, n = 13), and rhegmatogenous retinal detachment (RRD, n = 13). RESULTS: Chymase activities in the vitreous from patients with MH, PDR, ERM, and RRD were 1.87 +/- 0.53, 0.06 +/- 0.04, 0.40 +/- 0.12, and 0.08 +/- 0.03 (mean +/- SE) mU/mg protein, respectively, and ACE activities in the vitreous humor were 0.18 +/- 0.09, 0.30 +/- 0.07, 0.01 +/- 0.01, and 0.03 +/- 0.02 (mean +/- SE) mU/mg protein, respectively. Chymase activity was significantly elevated in MH among these diseases (p < 0.01, Scheffe), and ACE was significantly activated in PDR compared to ERM and RRD (p < 0.05, Scheffe). CONCLUSIONS: Our results suggest that two different angiotensin II generating systems are activated in human vitreous humor; an increased activity of chymase may play a possible role in the formation of macular holes.

Aged↗

Surface roughness of cellulose hollow fiber dialysis membranes and platelet adhesion.

A great deal of research has been conducted focusing on membrane materials with reference to their blood compatibility, but blood compatibility is influenced both by the material used in membranes and their structure, and by the flow conditions at the membrane surface. Accordingly, the relationship between membrane surface roughness and hemocompatibility has been evaluated using five types of membranes of differing surface roughness by evaluating the inner surfaces of the hollow fibers by atomic force microscopy (AFM) and by measuring platelet adhesion ratios using bovine blood. The yield stress, which equates to flow characteristics, was also evaluated using a glycerol suspension of polymethylmethacrylate (PMMA), a Bingham fluid. It was found that membranes having rough surfaces had high platelet adhesion ratios and poor hemocompatibility, whereas those with smoother surfaces had lower platelet adhesion ratios and better hemocompatibility. Measurement of the yield stresses for these membranes revealed higher values for those with rough surfaces, and lower values for those with smoother polyethylene glycol (PEG) grafted surfaces. This suggests that flow conditions at the membrane surface differ according to its surface roughness, and that this difference in flow conditions also influences hemocompatibility.

Cellulose↗

Construction of a differentiated human hepatocyte cell line expressing the herpes simplex virus-thymidine kinase gene.

Transient support using a hybrid artificial liver (HAL) device is a promising treatment for the patients with acute liver failure. Primary human hepatocytes are an ideal source for HAL therapy; however, the number of human livers available for hepatocyte isolation is limited by competition for use in whole organ transplantation. To overcome this problem, we previously established a highly differentiated human fetal hepatocyte cell line OUMS-29. Considering the potential risk when using these genetically engineered cells in humans, additional safeguards should be added to make the cells more clinically useful. In this work, the herpes simplex virus thymidine kinase (HSVtk) gene was retrovirally introduced into OUMS-29 cells. One of the HSVtk-expressed clones, OUMS-29/thymidine kinase (TK), grew in chemically defined serum free medium and expressed the genes of albumin, asialoglycoprotein receptor, glutamine synthetase, glutathione-S-transferase pi, and blood coagulation factor X. In vitro sensitivity of the cells to ganciclovir was evaluated. Intrasplenic transplantation of 50 x 10(6) OUMS-29/TK cells prolonged the survival of 90% hepatectomized rats compared with medium injection alone (control). In the present study, we have established highly differentiated immortalized human hepatocytes with tight regulation. The cells may be clinically useful for HAL treatment.

Albumins↗

Influence of disopyramide, compared with procainamide and quinidine, on isolated dog arteries in response to transmural stimulation and norepinephrine.

In helically cut strips of dog cerebral, coronary, and mesenteric arteries contracted with prostaglandin (PG) F2 alpha, disopyramide phosphate produced moderate contractions that were unaffected by phentolamine, chlorpheniramine, cinanserin, or aspirin. Procainamide and quinidine elicited only a slight contraction. Mesenteric arterial strips contracted with norepinephrine slightly contracted in response to disopyramide but significantly relaxed with procainamide and quinidine. The contractile response of mesenteric arterial strips to transmural electrical stimulation was attenuated by high concentrations (5 x 10(-5) M) of disopyramide or procainamide and by low concentrations of quinidine. Disopyramide-induced attenuation was greater in the response to high-frequency stimulation. Disopyramide at high concentrations potentiated the contractile response of mesenteric arteries to norepinephrine and tyramine, while, in contrast, procainamide and quinidine shifted the dose-response curve for norepinephrine to the right. Treatment with procainamide and quinidine, but not with disopyramide, protected alpha-adrenoceptors from persistent blockade by phenoxybenzamine; quinidine was far more effective than procainamide. It may be concluded that disopyramide possesses a nonspecific vasoconstricting action but not an alpha-adrenoceptor blocking property, whereas quinidine and procainamide show a reversible, competitive alpha-adrenoceptor antagonism. Different hemodynamic actions of these antiarrhythmics in situ appear to be related to such contrasting effects on arterial smooth muscle.

Animals↗

Vasodilatation induced by pinacidil in dogs. Comparison with hydralazine and nifedipine.

In helical strips of dog arteries precontracted with prostaglandin (PG) F2 alpha, pinacidil and nifedipine produced a dose-related relaxation. The potencies of pinacidil were in the order of coronary and renal greater than mesenteric greater than basilar and middle cerebral arteries, whereas those of nifedipine were in the order of basilar and renal greater than mesenteric and coronary arteries. Pinacidil caused a greater relaxation in mesenteric veins than in the arteries. Hydralazine consistently relaxed the arteries only at 10(-3) M. In mesenteric artery strips exposed to Ca2+-free, high K+ media, contractions induced by Ca2+ were reduced by 10(-8) M nifedipine, but they were not influenced by 10(-5) M pinacidil or by 10(-4) M hydralazine. In the arteries exposed to Ca2+-free media and stimulated by PGF2 alpha or norepinephrine, tonic contractions induced by Ca2+ were reduced moderately by 10(-5) M pinacidil but only slightly by 10(-8) M nifedipine. In Ca2+-free media, PGF2 alpha-induced contractions were inhibited only by pinacidil. In isolated mesenteric vasculature, perfusion pressure was lowered by pinacidil and hydralazine. It may be concluded that pinacidil produces vasodilatation due to interference with the transmembrane influx of Ca2+ into smooth muscle evoked by receptor stimulation but not that due to inhibition in the Ca2+ influx associated with K+-induced membrane depolarization. Decreased release of Ca2+ from intracellularly stored sites or increased sequestration to the sites may also be involved. Pinacidil appears to dilate arteries and veins as well as resistance vessels, whereas hydralazine appears to act exclusively on resistance vessels.

Animals↗

Interactions of thromboxane A2 analogs and prostaglandins in isolated dog arteries.

Interactions of ONO3708, a thromboxane (TX) A2 analog, and epithio-methano-TXA2 (sTXA2) or prostaglandins (PGs) were investigated in helical strips of dog cerebral, coronary, renal, and mesenteric arteries. In these arterial strips sTXA2 (10(-10) to 10(-7) M) produced a dose-dependent contraction, whereas ONO3708 up to 10(-6) M failed to contract the arteries but antagonized the contractile response to sTXA2. The inhibition tended to be greater in renal arteries than in the other arteries. Contractions induced by PGF2 alpha, PGE2, and PGD2 were also suppressed by treatment with low concentrations (3 X 10(-9) and 10(-8) M) of ONO3708. The attenuations of the response to sTXA2, PGF2 alpha, PGE2, and PGD2 did not appreciably differ. Norepinephrine-induced contractions were not influenced by ONO3708 up to 2 X 10(-7) M. On the other hand, relaxant responses to PGI2 of cerebral and renal arteries were not reduced by ONO3708. Prostaglandin H2 produced a transient contraction followed by a relaxation in cerebral and renal arteries. The contractile response was abolished by 10(-7) M ONO3708, and the relaxation was potentiated. It may be concluded that ONO3708 selectively antagonizes the vasoconstrictor action of TXA2, its analogs, and PGs but does not alter the action of vasodilator PGs. At least in part, sTXA2, PGF2 alpha, PGE2, and PGD2 appear to share the same receptive site responsible for vascular contraction.

Animals↗

Angiotensin II-generating system in dog and monkey ocular tissues.

1. Angiotensin II (AngII) is generated locally in several tissues, including ocular tissues. Recently, it has been suggested that in addition to angiotensin-converting enzyme (ACE), an alternative AngII-generating enzyme, chymase, is present in the present in the cardiovascular tissues of humans, monkeys and dogs and may be involved in the local production of AngII. The purpose of the present study was to determine whether chymase contributes to AngII generation in dog and monkey ocular tissues and to clarify the intraocular AngII-generating system. 2. Chymase-like and ACE activities were measured in dog and monkey ocular tissues, carotid artery, heart and lung. Their mRNA levels were quantified using the competitive reverse transcriptase-polymerase chain reaction (RT-PCR) method. 3. Chymase-like activity was detected in the anterior uveal tract, choroid and sclera in dog eyes, but not in the cornea, lens or fluid phase (vitreous body and aqueous humor). In monkey eyes, chymase-like activity was detected in the anterior uveal tract and it was higher here than in the heart. Angiotensin-converting enzyme activity was detected in the anterior uveal tract, choroid, retina, sclera and fluid phase in both dog and monkey eyes. Chymase and ACE mRNA were detected in tissues showing enzymatic activity. 4. These findings show for the first time that chymase, in addition to ACE, is expressed locally in dog and monkey ocular tissues and may be involved in local AngII generation in the eye.

Angiotensin II↗

Infantile spasms: localized cerebral lesions on SPECT.

Ten infantile spasms (IS) patients had single photon emission computed tomography (SPECT) with [99mTc]HMPAO, EEG, and magnetic resonance imaging (MRI) studies. SPECT showed localized cerebral hypoperfusion in 7 infants (4 unifocal; 3 multifocal) always involving the temporal regions either unilaterally or bilaterally. EEGs obtained in near time of the SPECT studies showed focal abnormalities in all 7 infants with hypoperfusion on SPECT, with complete correspondence of the abnormalities in 5. MRI showed localized cerebral lesions in only 3 of the 10 infants, all of whom had corresponding areas of hypoperfusion on SPECT. Our study indicates that localized cerebral abnormalities (especially of the temporal lobes) may often be associated with IS and that such patients may have localized cerebral hypoperfusion on SPECT even when the MRI is normal.

Brain↗

Effect of surface coatings on flexural properties of glass ionomers.

The purpose of this study was to investigate the change in flexural strength and fracture toughness of light-cured glass ionomer cements after long-term immersion in water, and to investigate the effect of surface coatings on their properties. 2 resin-modified and 1 conventional glass ionomer cements were employed. For the flexural strength, a 25 x 2 x 2 mm stainless steel mold was used. For the fracture toughness (KtC), single edge notch specimens with dimensions 25 x 2.5 x 5 mm and a 0.5 mm notch (a/W = 0.5) were prepared in a stainless steel mold. Specimens were subjected to the 3 point bending at 0.5 mm/min after storage in 37 degrees C water for the periods of 1 h, 24 h, 1 wk, 1 month, and 6 months. The glass ionomer cements tended to exhibit an increase in mechanical properties over the 24-h period and then to maintain a constant strength. The surface protection of the resin-modified glass ionomer cement has some effect on the mechanical properties during early setting reactions, and it is desirable that the cement should be protected from direct water contact for at least 1 h after cement mixing.

Analysis of Variance↗

Correlation between the neural noise in the thalamus after cerebrovascular disease and computerized tomography. A case report.

The case is presented of a 45-year-old man who suffered from a sudden attack of unconsciousness with right hemiplegia and later developed a spastic hemiparesis accompanied by involuntary movement of the right upper limb. CT scan revealed an old putaminal hemorrhage and almost intact thalamus, but neural noise recordings during the stereotactic thalamotomy of this case showed marked decrease of the neural activity in the thalamus suggesting some functional changes.

Cerebral Hemorrhage↗

Novel features of the functional site and expression of the yeast deoxyhypusine synthase.

A unique amino acid, hypusine, is formed posttranslationally in the precursor of eukaryotic translation initiation factor 5A (eIF-5A). Deoxyhypusine synthase catalyzes the first of two steps in the biosynthesis of hypusine. We reported earlier that the DYS1 gene encoding deoxyhypusine synthase is essential for cell viability and proliferation in yeast. Here, we show by deletion studies that both N- and C-terminal regions, which are not so well conserved, are necessary for the activity of the yeast enzyme. Of the seven cysteine residues present in the yeast enzyme, only one cysteine (position 252; C252) appeared to be essential for its activity. Moderate overexpression of DYS1 showed very little effects on cell growth and no obvious effects on the intracellular level of eIF-5A. However, repression of the expression of DYS1 resulted in near-complete depletion of eIF-5A 24 h after the initiation of repression and was followed by cell growth arrest after another 24 h. This novel finding suggests that the major role of deoxyhypusine synthase in cell proliferation is mediated not only through its modification of the eIF-5A precursor, but also through its regulation of intracellular eIF-5A levels.

Gene Deletion↗

Inverse relationship between P-glycoprotein expression and its proliferative activity in hepatocellular carcinoma.

Hepatocellular carcinomas (HCCs) from 31 patients, cirrhotic livers from 7 patients and normal liver from 8 patients were immunohistochemically assessed in frozen sections using anti-P-glycoprotein (Pgp) monoclonal antibody C219. Immunohistochemical staining with anti-Ki-67 monoclonal antibody MIB-1 was performed for 22 HCCs to assess proliferative activity. Tumor tissues expressed Pgp on the biliary surface and on the luminal surface of cancer cells, which was less extensive than in normal and cirrhotic liver hepatocytes. Expression of Pgp was closely associated with the degree of histological differentiation and the histological type of HCC. Labeling indices (LI) of Pgp expression were 0.68 +/- 0.06 (mean +/- SD) in well, 0.51 +/- 0.14 in moderately and 0.04 +/- 0.06 in poorly differentiated HCC (significant differences among the three groups). LI of Pgp expression in the trabecular (0.55 +/- 0.15) and in the pseudoglandular types (0.44 +/- 0.10) were remarkably higher than in the compact type (0.04 +/- 0.06). The extent of Pgp expression in HCC was significantly inversely related to the extent of Ki-67 expression, in which Pgp expression decreased in highly proliferating tumors. In conclusion, Pgp expression in HCC was clearly related to its proliferative activity.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

Responses of isolated dog cerebral and peripheral arteries to prostaglandins after application of aspirin and polyphloretin phosphate.

In helically cut strips of dog cerebral, coronary, mesenteric and femoral arteries, the contractile response to prostaglandin (PG) F2alpha, and E2, relative to contractions induced by 30 mM K+, did not appreciably differ, whereas relaxations induced by PGE1 relative to those induced by 10(-4) M papaverine were significantly different; the least in cerebral arteries and the greatest in mesenteric arteries. The relaxation of human cerebral arteries in response to PGE1 was similar to that of dog cerebral arteries. Treatment for 60 min with polyphloretin phosphate (3 X 10(-5) and 10(-4) g/ml) suppressed the contractile response to PGF2alpha and E2 but did not alter the response to 25 mM K+. The relaxing effect of PGE1 was not influenced. Aspirin (5 X 10(-5) and 2 X 10(-4) M) significantly potentiated the contractile response to PGF2alpha and E2 but did not alter the relaxation induced by PGE1. In contrast, contractions induced by serotonin were attenuated. It is concluded that dog cerebral, coronary, mesenteric and femoral arteries relaxed differently in response to PGE1. It appears that arterial responses to vasoconstricting PGs, but not to the vasodilating PG, are significantly attenuated by polyphloretin phosphate and potentiated by aspirin.

Aged↗

Prostaglandin E1 for renal papillary necrosis in a patient with diabetes mellitus.

We report a case of renal papillary necrosis with diabetes mellitus which was treated with prostaglandin E1. An intravenous infusion of 40 mg/day prostaglandin E1 was given for 14 days in an attempt to improve renal circulation. Treatment resulted in an improved creatinine clearance, renal plasma flow and renogram, and proteinuria was decreased. The administration of prostaglandin E1 produced an improvement in renal haemodynamics and can be considered as a possible therapy for renal papillary necrosis in diabetic patients.

Aged↗

Epidemiological characteristics on human immunodeficiency virus infection and acquired immunodeficiency syndrome in Japan.

The first case of human immunodeficiency virus (HIV) infection/acquired immunodeficiency syndrome (AIDS) in Japan was diagnosed in a homosexual male in 1985. The Ministry of Health and Welfare formed the AIDS Surveillance Committee, which published HIV seropositive and AIDS data at 2-month intervals. Excluding persons infected through blood products there were 971 HIV seropositives by April 1993, and 204 reported cases of AIDS. One of the epidemiological characteristics of HIV infection and AIDS in Japan is the rapid increase of cases of transmission through heterosexual contact since 1991. Before this, homosexual transmission was the commonest reported mode of transmission. Sporadic cases of mother-to-child transmission and some cases due to injecting drug use were also reported. It is predicted that heterosexual contact will be the primary mode of transmission of HIV in the future. Virtually all the diagnosed AIDS cases so far have been reported to this surveillance network, and it will be an important task of the network to monitor the HIV seropositive cases.

Acquired Immunodeficiency Syndrome↗

Epidemiological characteristics of human immunodeficiency virus type-2 infection in Africa.

There are things yet to be clarified about African HIV-2 infection, compared to HIV-1 infection. However, the epidemiological characteristics have gradually been elucidated through various studies. HIV-2 infection is believed to have existed in the 1960s in Africa and is presently epidemic in West Africa. The HIV-2 seropositive rate for the general population is higher in urban regions than in rural areas. The peak age of persons infected with the HIV-2 tends to be higher than that of persons infected with the HIV-1, but no sex difference was recognized between the HIV-2 and HIV-1 seropositive rates. Sexual contact, mother-to-child transmission and blood transfusion have been confirmed as HIV-2 transmission modes. Prostitutes and patients with other STD are recognized as being high-risk groups for the HIV-2 infection. Patients who are infected with both HIV-1 and HIV-2 have also been identified, but it is suggested that the pathogenicity of HIV-2 is lower than that of HIV-1.

Africa↗

Treatment of surgically induced acute liver failure with transplantation of highly differentiated immortalized human hepatocytes.

Primary human hepatocytes are an ideal source of hepatic function in bioartficial liver (BAL), but the shortage of human livers available for hepatocyte isolation limits this modality. To resolve this issue, primary human fetal hepatocytes were immortalized using simian virus 40 large T antigen. One of the immortal cell lines, OUMS-29, showed highly differentiated liver functions. Intrasplenic transplantation of OUMS-29 cells protected 90% hepatectomized rats from hyperammonemia and significantly prolonged their survival. Essentially unlimited availability of OUMS-29 cells supports their clinical use for BAL treatment.

Ammonia↗