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Biomedical subjects

Y Sakurai

Publications and source records attributed to Y Sakurai.

At least 163 records · Page 9Linked to original sources

[A case of interstitial nephritis induced by a super antigen produced by methicillin-resistant Staphylococcus aureus (MRSA) presenting as acute renal failure].

We report the case of a 21-year-old man who had been developing acute renal failure with Methicillin-resistant Staphylococcus aureus (MRSA) colitis and sepsis. He was admitted for consciousness disturbance, nausea, vomiting, and diarrhea. Oliguria was also observed and his serum creatinine level was elevated to 10 mg/dl. Urinary protein was positive and an abundance of hyaline cast were seen in urinary sedimentation. Diarrhea and pyrexia were prolonged and serum C-reactive proteins were elevated, but lymphocyte and leukocyte counts temporarily decreased from the 3rd to the 6th hospital day and remained low until normalizing after the 14th day. His clinical symptoms improved with hemodialysis (HD) and effective antibiotic therapies. An MRSA strain producing toxic shock syndrome toxin-1 (TSST-1), a super antigen which specifically stimulates human V beta 2-positive T cells, was separated from his feces and blood. To ascertain the cause of his renal dysfunction, a renal biopsy was performed on the 8th day. His renal histology revealed acute interstitial nephritis with severe inflammatory cell infiltration around the medullary areas without glomerular changes. Most of the infiltrated cells were small monocytes, and lymphoid cells were rich in the interstitium. With immunohistochemical staining, over 70% of T-cells were V beta 2-positive. TSST-1-producing MRSA was detected in his blood specimen. Furthermore, V beta 2-positive T cells were accumulated in the renal intersititium, and transient lymphocytopenia was observed. These data suggested the following possible pathogenesis for interstitial nephritis: TSST-1 acts as a super antigen in the renal interstitium where major histocompatibility complex (MHC) is class-2-positive, thereby resulting in interstitial nephritis with T cell migration.

Acute Kidney Injury↗

Identification of the binding site for an alloantibody to von Willebrand factor which inhibits binding to glycoprotein Ib within the amino-terminal region flanking the A1 domain.

An alloantibody to von Willebrand factor (vWF) which developed in a Japanese boy with type 3 von Willebrand disease has been characterized. The antibody was non-precipitating IgG and the main subclasses were IgG2 and IgG4. The antibody inhibited completely ristocetin-induced platelet aggregation (RIPA) and high shear stress-induced platelet aggregation (SIPA). Its predominant inhibitory role was focused, therefore, on the interaction between vWF and platelet gycoprotein Ib. The antibody reacted with a 52/48 kDa tryptic fragment of vWF (residues 449-728). No reaction was seen, however, with either a 39/34 kDa dispase fragment (480-718) or a recombinant vWF fragment (residues 465-728). These findings suggested that the essential epitope resided in the amino-terminal flanking region of the Al domain. We synthesized overlapping peptides corresponding to the region containing D3/A1 boundary. A peptide, residues 458-472, bound to the antibody and dose-dependently blocked the antibody binding to the 52/48 kDa fragment. The same peptide neutralized the inhibitory effect of the alloantibody on SIPA. The data are consistent with the presence of an epitope within residues 458-472 which reacted with the 52/48 kDa fragment. Furthermore, the specific component of the antibody, directed against residues 458-472, blocked vWF binding to GPIb in absence of exogenous agonist. Our results suggest that the region flanking the Al domain plays an important role in regulating vWF binding to GPIb.

Antibody Specificity↗

[A case report of emergent CABG after left main trunk occlusion as complication of direct PTCA].

A 38-years-old man was transferred to our hospital because of cardiogenic shock following acute left main trunk (LMT) occlusion as a complication of direct percutaneous transluminal coronary angioplasty (PTCA), and then underwent emergent coronary artery bypass grafting. We successed his life salvage, but he suffers from very severe heart failure following extensive myocardial infarction. Though acute LMT occlusion as a complication of PTCA is rare, a proper treatment has to be started as soon as possible if it occurs. We must make the systems of support for the emergencies among the surrounding hospitals.

Adult↗

[A case of frequent intracerebral hemorrhage from mixed vascular malformation in a child].

We reported a rare case of frequent intracerebral hemorrhage from mixed vascular malformation in an infant. A 1-year and 4-month-old girl was admitted with seizure. She had been diagnosed as having febrile convulsion at the age of 8 months. Computed tomography (CT) indicated a multicystic mass without perifocal edema in the right frontal lobe. The mass was not enhanced by contrast media, but T1-weighted magnetic resonance imaging (MRI) revealed a multicystic mass with mixed signal intensity, while T2-weighted image demonstrated a heterogenous high signal intensity mass with a marginal low intensity rim. These findings suggested a cavernous angioma causing intracerebral hematomas. Because of this, total resection was achieved via a right fronto-temporal craniotomy without neurological deficits. Histologically, numerous dilated venous-type blood vessels interspersed within the normal brain parenchyma were seen. In parts, the vessel walls were abnormally thickened and the lesion coalesced with capillary-like vessels. We diagnosed mixed vascular malformation, mainly composed of venous malformation along with telangiectasia. The number of reports for this so-called mixed vascular malformation have thus been increased. The histopathological criteria for classification of vascular malformation should be reinvestigated carefully.

Cerebral Hemorrhage↗

Inverse association between coffee drinking and serum uric acid concentrations in middle-aged Japanese males.

Consumption of caffeine-rich beverages, which have diuretic properties, may decrease serum uric acid concentrations. We examined cross-sectionally the relationship of coffee and green tea consumption to serum uric acid concentrations in 2240 male self-defence officials who received a pre-retirement health examination at four hospitals of the Self-Defence Forces between 1993 and 1994. The mean levels of coffee and green tea consumption were 2.3 and 3.1 cups/d respectively. There was a clear inverse relationship between coffee consumption and serum uric acid concentration. When adjusted for hospital only, those consuming less than one cup of coffee daily had a mean serum uric acid concentration of 60 mg/l, while that of those drinking five or more cups of coffee daily was 56 mg/l (P < 0.0001). No such relationship was observed for green tea, another major dietary source of caffeine in Japan. The relationship between coffee consumption and serum uric acid concentration was independent of age, rank in the Self-Defence Forces, BMI, systolic blood pressure, serum creatinine, serum total cholesterol and serum HDL-cholesterol concentrations, smoking status, alcohol use, beer consumption and intake of dairy products. These findings suggest that coffee drinking may be associated with lower concentrations of serum uric acid, and further studies are needed to confirm the association.

Alcohol Drinking↗

Incorporation of water-insoluble anticancer drug into polymeric micelles and control of their particle size.

A water-insoluble anticancer drug, KRN 5500 (KRN), was incorporated into polymeric micelles forming from poly(ethylene glycol-poly(amino acid) block copolymers by physical entrapment utilizing hydrophobic interactions between this drug and the poly(amino acid) chain block of the block copolymers. Three block copolymers were examined for this incorporation; poly(ethylene glycol)-poly(beta-benzyl l-aspartate) (PEG-PBLA) and its two derivatives obtained by partial hydrolysis at the beta-benzyl l-aspartate (BLA) units (PEG-P(Asp, BLA)) and by partial cetyl ester substitution at the BLA units (PEG-P(C16, BLA)), respectively. Among these block copolymers, considerable effects of the cetyl esterification were seen on KRN yield and particle size. Considerable differences in the KRN incorporation yield and particle size were also observed between DMF and DMS used as solvent to dissolve KRN and the block copolymers. Sonication was turned out to be an effective method to obtain a polymer micelles fraction in high efficiency, and sonication was considered to work for separating intermicellar associates into dispersed micelles. A KRN incorporation procedure by dialysis using PEG-P(C16, BLA) and DMSO (as solvent) followed by sonication brought about polymeric micelles of 71 nm in weight-average diameter. This shows successful incorporation of a water-insoluble drug into polymeric micelles by optimizing block copolymer structure and incorporation conditions.

Antibiotics, Antineoplastic↗

Preparation and characterization of thermally responsive block copolymer micelles comprising poly(N-isopropylacrylamide-b-DL-lactide).

The thermally sensitive block copolymer, poly(N-isopropylacrylamide-b-dl-lactide) (PIPAAm-PLA), was synthesized by ring-opening polymerization of dl-lactide initiated from hydroxy-terminated poly (N-isopropylacrylamide) (PIPAAm). A PIPAAm bearing a single terminal hydroxyl group was prepared by telomerization using 2-hydroxyethanethiol as a chain-transfer agent. Successful preparation of PIPAAm and the PIPAAm-PLA block copolymer was verified by gel permeation chromatography (GPC) and 1H-NMR spectroscopy. Polymeric micelles were prepared from block copolymers using a dialysis method. Their solutions showed reversible changes in optical properties: transparent below a lower critical solution temperature (LCST) and opaque above the LCST. Dynamic light scattering measurements were used to observe the formation of micellar structures approximately 40 nm in diameter, which do not change between 20 degreesC and 30 degreesC. Above the LCST, polymer micelles aggregated, a phenomenon found to be reversible since the aggregates dissociated again by cooling below the LCST. Further observations using atomic force microscopy (AFM) confirmed this behaviour. The properties of this block copolymer system are interesting from both applied and fundamental perspectives, particularly for active targeting as drug carriers.

Acrylamides↗

Monoclonal antibody 14F7, which recognizes a stage-specific immature oligodendrocyte surface molecule, inhibits oligodendrocyte differentiation mediated in co-culture with astrocytes.

Cells at an intermediate stage of oligodendrocyte lineage are not only well characterized by biochemical studies but also are likely to relate to the outcome of physiological events. To elucidate the molecular events leading to the development of oligodendrocyte lineage cells, we have raised monoclonal antibodies against stage-specific immature oligodendrocytes, which have previously been isolated by a novel oligodendrocyte-lineage cell culture technique (Sakurai et al.: J Neurosci Res 52:17-26, 1998). We have isolated a mouse monoclonal antibody termed 14F7 which predominantly labels stage-specific immature oligodendrocytes and have found that the expression of 14F7 immunoreactivity in the developing neonatal rat forebrain is closely associated with cells expressing the oligodendrocyte progenitor marker A2B5 and to immature oligodendrocyte expressing O4 antigen. 14F7+ cells were distributed in the ventricular and subventricular zone and the nearby forming corpus callosum as non-myelinating cells. In contrast to cell culture observations, 14F7+ cells were seen only in oligodendrocyte lineage cells. For instance, dissociated cell culture studies indicated that 14F7 labels a cell surface molecule, and its cellular distribution is coincident with all of O4+ cells and A2B5+ cells, and even A2B5- cells. By contrast, 14F7-positive cells did not label astrocytes and, furthermore, did not label myelin basic protein (MBP)-positive oligodendrocytes. 14F7 recognized a 48-kDa protein on sodium dodecyl sulfate polyacrylamide gel electrophoresis. 14F7 immunoreactivity was detectable in rat brain as early as embryonic day 18. Furthermore, in these cells, the total time for differentiation was extended, and on maturation, these cells subsequently expressed an array of myelin-specific proteins, which normally occurs by direct contact with type-1 astrocytes. However, in the presence of 14F7, stage-specific oligodendrocytes co-cultured with astrocytes completely failed to express MBP. These data suggest that the 14F7 antigen is a novel cell surface molecule that is expressed in the intermediate stage of oligodendrocyte-lineage cells, and it is expected that it regulates the differentiation of oligodendrocyte throughout development.

Animals↗

Progressive aphemia in a patient with Pick's disease: a neuropsychological and anatomic study.

We describe a patient with progressive aphemia with agrammatism that was later overlaid with buccofacial apraxia and pseudobulbar palsy. Pathological findings were consistent with those of classic Pick's disease with argyrophilic inclusions and neuronal achromasia, except for restricted cortical atrophy in the frontal operculum posterior to the pars opercularis (Brodmann Area 44). In addition, major neuronal loss was confined to the premotor cortex and the anterior half of the precentral gyrus (Area 6), which apparently explained the aphemia. The present case demonstrated that classic Pick's disease can show quite limited cortical atrophy in a patient who clinically presents with progressive aphemia. Also, our patient differed from the progressive non-fluent aphasia patients reported as having Pick's disease, who were all Pick variants, revealing that classic Pick's disease can be included in the spectrum of progressive aphasia syndrome.

Aphasia, Broca↗

Response of quiescent and total tumor cells in solid tumors to neutrons with various cadmium ratios.

PURPOSE: Response of quiescent (Q) and total tumor cells in solid tumors to neutron irradiation with three different cadmium (Cd) ratios was examined. The role of Q cells in tumor control was also discussed. METHODS AND MATERIALS: C3H/He mice bearing SCC VII tumors received continuous administration of 5-bromo-2'-deoxyuridine (BrdU) for 5 days using implanted mini-osmotic pumps to label all proliferating (P) cells. Thirty minutes after intraperitoneal injection of sodium borocaptate-10B (BSH), or 3 h after oral administration of dl-p-boronophenylalanine-10B (BPA), the tumors were irradiated with neutrons, or those without 10B-compounds were irradiated with gamma rays. This neutron irradiation was performed using neutrons with three different cadmium (Cd) ratios. The tumors were then excised, minced, and trypsinized. The tumor cell suspensions were incubated with cytochalasin-B (a cytokinesis-blocker), and the micronucleus (MN) frequency in cells without BrdU labeling (Q cells) was determined using immunofluorescence staining for BrdU. The MN frequency in total (P + Q) tumor cells was determined from tumors that were not pretreated with BrdU. The sensitivity to neutrons was evaluated in terms of the frequency of induced micronuclei in binuclear tumor cells (MN frequency). RESULTS: Without 10B-compounds, the MN frequency in Q cells was lower than that in the total cell population. The sensitivity difference between total and Q cells was reduced by neutron irradiation. Relative biological effectiveness (RBE) of neutrons compared with gamma rays was larger in Q cells than in total cells, and the RBE values for low-Cd-ratio neutrons tended to be larger than those for high-Cd-ratio neutrons. With 10B-compounds, MN frequency for each cell population was increased, especially for total cells. This increase in MN frequency was marked when high-Cd-ratio neutrons were used. BPA increased the MN frequency for total tumor cells more than BSH. Nevertheless, the sensitivity of Q cells treated with BPA was lower than that in BSH-treated Q cells. This tendency was clearly observed in high-Cd-ratio neutrons. CONCLUSION: From the viewpoint of enhancing the Q-cell sensitivity, tumors should be irradiated with high-Cd-ratio neutrons after BSH administration. However, normal tissue reaction remains to be examined because of its low tumor-to-normal tissue and tumor-to-blood biodistribution ratios.

Animals↗

Design of compact absorbers for high-heat-load X-ray undulator beamlines at SPring-8.

A compact and high-heat-load absorber for the SPring-8 X-ray undulator beamline has been developed and installed. It consists of an upper heat-absorber part and a lower photon duct part, which are configured together in a water-cooled GlidCop body. The absorber part has a horizontal notch shape and the photon duct part forms a rectangular open channel under the absorber part. Two types of absorber are designed: one, with wire mesh channels, is 486 mm long, 70 mm high and 64 mm wide; the other, with smooth-bore channels, is 610 mm long, 75 mm high and 70 mm wide. Thermal and stress analyses show that they withstand the 12.3 kW heat load and the maximum heat flux of 940 W mm(-2) at normal incidence.

Journal Article↗

Present status and performance of SPring-8 front ends.

SPring-8 front ends have a novel structure which makes it easy to rearrange them and exchange the components. The structure has a common support for all the components except X-ray beam-position monitors and lead collimators. The alignment of the common support as well as the components was carried out with an accuracy of 0.25 mm in the vertical and horizontal directions. Replaceable pumping systems have also been placed on the common support and have achieved a vacuum of 2 x 10(-8) Pa at the upstream part of the front ends without synchrotron radiation. During the commissioning with synchrotron radiation, the pumping systems displayed good pumping-down characteristics. Commissioning has been successfully performed for four standard in-vacuum X-ray undulators and three bending-magnet-beamline front ends up to July 1997. Measurements of temperature rise show that absorber, pre-slits and XY slits can handle the anticipated maximum heat load at a ring current of 100 mA.

Journal Article↗

Novel thermally reversible hydrogel as detachable cell culture substrate.

A novel UV crosslinkable co-polymer of 4-(N-cinnamoylcarbamide)methylstyrene (CCMS) and N-isopropylacrylamide (IPAAm) was partially entrapped in traditional tissue-culture-treated polystyrene and crosslinked by UV light irradiation. Dishes modified by this method showed a change in contact angle with respect to temperature as compared to tissue culture polystyrene controls. Surface chemical analysis indicated that the crosslinked hydrogel does not detach from the surface after successive rinsing in ethanol and water, keeping the cells or cell construct free of unwanted soluble polymer after detachment. Cultures of both bovine endothelium and human retinal pigmented epithelium were confirmed to be able to attach and grow on the polymer-modified surfaces morphologically identical to that on control tissue culture polystyrene surfaces. Corresponding to a change in temperature, these cultures would detach and could be transplanted to another culture surface without functional and structural changes. These results show that the new, photo-crosslinkable hydrogel system can utilize the hydrophobic/hydrophilic change of the surface for cell culture detachment while being permanently applicable to any tissue culture geometry.

Acrylic Resins↗

Insulin therapy in burn patients does not contribute to hepatic triglyceride production.

Lipid kinetics were studied in six severely burned patients who were treated with a high dose of exogenous insulin plus glucose to promote protein metabolism. The patients were 20+/-2-yr-old (SD) with 63+/-8% total body surface area burned. They were studied in a randomized order (a) in the fed state on the seventh day of a control period (C) of continuous high-carbohydrate enteral feeding alone, and (b) on the seventh day of enteral feeding plus exogenous insulin (200 pmol/h = 28 U/h) with extra glucose given as needed to avoid hypoglycemia (I+G). Despite a glucose delivery rate approximately 100% in excess of energy requirements, the following lipid parameters were unchanged: (a) total hepatic VLDL triglyceride (TG) secretion rate (0.165+/-0.138 [C] vs. 0.154+/- 0.138 mmol/kg . d-1 [I+G]), (b) plasma TG concentration (1.58+/-0.66 [C] vs. 1. 36+/-0.41 mmol/liter [I+G]), and (c) plasma VLDL TG concentration (0. 68+/-0.79 [C] vs. 0.67+/- 0.63 mmol/liter [I+G]). Instead, the high-carbohydrate delivery in conjunction with insulin therapy increased the proportion of de novo-synthesized palmitate in VLDL TG from 13+/-5% (C) to 34+/-14% (I+G), with a corresponding decreased amount of palmitate from lipolysis. In association with the doubling of the secretion rate of de novo-synthesized fatty acid (FA) in VLDL TG during insulin therapy (P > 0.5), the relative amount of palmitate and stearate increased from 35+/-5 to 44+/-8% and 4+/-1 to 7+/-2%, respectively, in VLDL TG, while the relative concentration of oleate and linoleate decreased from 43+/-5 to 37+/-6% and 8+/-4% to 2+/-2%, respectively. A 15-fold increase in plasma insulin concentration did not change the rate of release of FA into plasma (8.22+/-2.86 [C] vs. 8.72+/-6.68 mmol/kg.d-1 [I+G]. The peripheral release of FA represents a far greater potential for hepatic lipid accumulation in burn patients than the endogenous hepatic fat synthesis, even during excessive carbohydrate intake in conjunction with insulin therapy.

Adolescent↗

Design of a pre-slit for SPring-8 undulator beamlines.

A volumetric heating method is applied to the pre-slit placed on the SPring-8 standard-undulator beamline front ends in order to handle the very intensive photon beam. A graphite block is used as the radiation-absorbing body, which is brazed to a cooling holder made of oxygen-free high-conductivity copper. Various experiments and calculations have been carried out on the strength of the brazed joint. Comparisons between the experiments and calculations show that static fracture of the joint would not occur even under the highest heat load. The outgassing properties of the graphite blocks are also presented here.

Journal Article↗