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Biomedical subjects

O Yamada

Publications and source records attributed to O Yamada.

At least 109 records · Page 6Linked to original sources

Telomeric DNA in normal and leukemic blood cells.

We studied telomeric DNA in leukemic cells as well as in normal T cells, B cells, monocytes, polymorphonuclear leukocytes, and bone marrow hematopoietic progenitor cells. No marked differences were observed in the sizes of the telomeric repeats in the various populations of normal blood cells obtained from donors in their twenties to sixties, and the telomere length ranged between 8.5 and 9.0 kb. The leukemic cells of 12 patients with acute leukemia (seven with myeloid and five with lymphoid leukemia) showed a variable reduction in the length of telomeric DNA, ranging from 2.7 to 6.4 kb. The average telomere length was 4.8 and 4.7 kb in myeloid and lymphoid leukemia, respectively, while the telomere length in peripheral blood mononuclear cells obtained from the same patients during complete remission was 8.5 and 7.9 kb, respectively. When the same Southern blots were hybridized with Alu or alphoid sequences, no marked changes in the sizes of the repetitive DNA sequences were observed, indicating that the DNA abnormality in the leukemic cells was specific to the telomere region. Investigation of telomeric DNA changes may be helpful in determining the biological properties of leukemic cells.

Adult↗

Fine structure of podocytes in the bovine renal corpuscle.

Thick primary processes issued from the hemispherical or plate-like cell bodies of podocytes in bovine renal corpuscles. These processes branched into secondary and tertiary ones, but no fine pedicels were observed on the outer surface of the podocytes by scanning electron microscopy, because each primary process closely interdigitated with those of adjacent cells. Many pedicels, however, were observed under the processes by using the freeze-fractograph and a transmission electron microscope.

Aging↗

Microvascular changes in the bovine corpus luteum during pregnancy.

The microvasculature of bovine corpora lutea during pregnancy was studied by scanning electron microscopy using corrosion casts. Only one spiral arteriole branched directly from the ovarian artery entered the blood vascular bed of the pregnant corpora lutea. The bed consisted of numerous lobular sinusoidal capillary plexuses during pregnancy, and were characteristic to the microvasculature of a large corpus luteum. At the late stage of pregnancy, arteriovenous anastomoses were situated within the lobular sinusoidal capillary plexus composed of thin sinusoidal capillaries. These anastomoses may induce a decrease in blood flow to the lobular sinusoidal capillary plexus, suggesting that they may have an important role to induce the initial degeneration of the bovine pregnant corpora lutea.

Animals↗

Microvascular changes during the development of follicles in bovine ovaries: a study of corrosion casts by scanning electron microscopy.

Microvascular changes during the development of follicles in bovine ovaries were studied by scanning electron microscopy of corrosion casts. A clear vascular plexus of ovarian follicles appeared at the stage when secondary follicles were 200-400 microns in diameter. The plexus consisted initially of a thin, roughly structured and single-layered capillary network. During follicular development, the microvascular architecture of antral follicles was arranged as two independent vascular plexuses. The inner plexus, which received a spiral arteriole, consisted of a dense sinusoidal capillary network with an arterial and a venous layer; it functioned as an independent microcirculatory unit. The inner plexus developed from the capillary plexus of the theca interna of the secondary follicles. The outer plexus, which anastomosed with several stromal capillaries, consisted of a thin, coarse and basket-like capillary plexus. The outer plexus was formed from the stromal capillary plexus as a consequence of the rapid enlargement of developing antral follicles.

Animals↗

[Computed tomography with continuous transport and continuous scanner rotation for laparoscopic cholecystectomy].

We investigated the 58 cases of cholecystolithiasis including 8 cases of choledocholithiasis treated with laparoscopic cholecystectomy. All patients received spiral CT scanning with drip infusion cholangiography (DIC-SCT), and 1.6 patients received endoscopic retrograde cholangiography (ERC), and the detection rates of the gallbladder, the bile duct and the cystic duct were compared. The gallbladder could be seen in 86.2% of cases with DIC-SCT and in 63.8% of cases with conventional DIC. The junction between the cystic duct and the common bile duct could be seen in 18 of 58 cases with DIC and in 49 of 58 cases with DIC-SCT. The DIC-SCT showed significantly superior anatomical details compared with images with conventional DIC. A comparison of DIC, ERC and DIC-SCT revealed that the junction between the cystic duct and the common bile duct could be identified in 14 of 16 cases undergoing ERC, in 13 of 16 cases receiving DIC-SCT and in 4 of 16 cases receiving DIC. Significant differences were noted among DIC-SCT, ERC and conventional DIC. We concluded that DIC-SCT is easy, non-invasive and useful for the preoperative assessment of laparoscopic cholecystectomy and also helpful for avoiding damage to the bile duct.

Adolescent↗

Activity and cleavage site specificity of an anti-HIV-1 hairpin ribozyme in human T cells.

Human CD4+ T cells (Molt-4) were transduced with retroviral vectors containing a hairpin ribozyme which targets the rev/env coding region of HIV-1 RNA (HXB2: 8629-8644). This target sequence is conserved among many HIV-1 clones, including the prototype virus HXB2, but the infectious clone SF2 contains a single nucleotide substitution at the cleavage site (from N*GUC to N*UUC). Cells stably expressing the ribozyme or its disabled counterpart were challenged with HXB2 or SF2 and the amount of p24 antigen produced was monitored. While this ribozyme was effective in inhibiting the replication of HXB2 in Molt 4 cells, it showed only marginal inhibitory effect on SF2 replication. The same level of virus production was observed with cells transduced by the disabled ribozyme, which functions essentially as an antisense molecule. Expression of the ribozyme was comparable in HXB2- or SF2-infected cells as detected by reverse transcription-polymerase chain reaction. These data provide in vivo evidence that the antiviral activity of the hairpin ribozyme is strictly dependent on the presence of the cleavage site in the target RNA and supports the conclusion that the ribozyme acts as catalytic RNA rather than as antisense RNA in vivo.

Base Sequence↗

Surgical outcome of aortic arch aneurysms using selective cerebral perfusion.

The surgical results observed in 80 patients with aneurysms of the aortic arch who underwent an operation between January 1986 and the end of August 1992 were analyzed by multivariate analysis to identify predictors of high operative risk. All operations were performed using a cardiopulmonary bypass technique, blood cardioplegia for myocardial protection, and selective cerebral perfusion to prevent cerebral ischemia during aortic arch repair. The overall early (30-day) mortality rate was 16.3%. A severe stroke occurred postoperatively in 1 patient (1.3%). The 5-year survival rate was 73% +/- 5%, as determined by the Kaplan-Meier method. Multivariate analysis revealed that the presence of critical cardiopulmonary dysfunction preoperatively and the need for reoperation were significant independent predictors. Of the 63 (79%) patients who were free of these risks, only 3 (4.8%) died. The findings from the present study indicate that, currently, early mortality is relatively low for all patients who undergo operations for aneurysm of the aortic arch, unless they are in a critical condition preoperatively or unless they are undergoing a reoperation.

Actuarial Analysis↗

Total arch graft replacement in patients with acute type A aortic dissection.

Treatment of acute type A aortic dissection with emergency total aortic arch graft replacement remains controversial. Between December 1988 and July 1993, 30 patients with this fatal disease underwent graft replacement of both the ascending aorta and total aortic arch on an emergency basis. All operations were performed with the aid of extracorporeal circulation, blood cardioplegia, selective cerebral perfusion, and open distal anastomosis. The overall early mortality rate was 23.3% (7 patients), but that in patients with complications with shock and renal/mesenteric ischemia was 57% and 66.7%, respectively. On the other hand, the mortality rate in the 23 patients (77%) in whom neither of these two risk factors was present was low (8.7%). The overall 4-year survival rate was 66.5% +/- 8.7%, and that for patients without these two risk factors was 87.0% +/- 7.0%. The present data suggest that simultaneous total arch replacement may be justified in selected patients with acute type A aortic dissection.

Adult↗

Ultracytochemistry of glycoconjugates in pig duodenal gland.

To elucidate the ultrastructure, glycoprotein profile and site of glycosylation of glandular cells in relation to the functional polarity of the organelles, swine duodenal tissue was embedded in glycol methacrylate and subsequently stained for periodic acid thiocarbohydrazide silver proteinate (PA-TCH-SP), high iron diamine (HID)-TCH-SP, low iron diamine (LID)-TCH-SP, ninhydrin T-TCH-SP and five peroxidase-labeled lectins. The secretory granules in the duodenal gland cells were electron lucent with a 200 nm to 500 nm electrondense core. Glycoconjugates were confined to the secretory granules and elements of the Golgi complex. Protein activity was located only in the electron dense core. Achivementestic staining pattern for Concanavalin A (Con A), peanut agglutinin (PNA), Ulex europaeus agglutinin-I (UEA-I), wheat germ agglutinin (WGA) and soybean agglutinin (SBA) was observed in stained secretory granules and the Golgi apparatus. A few cis cisternae were stained with SBA and UEA-I. Trans cisternae were stained with WGA and PNA. Con A reacted with seromucous granules and rough endoplasmic reticulum. These observational findings suggest that these are seromucous cells. The Golgi apparatus is the site of glycosylation and can be divided into two distinct compartments.

Animals↗

Transfer of an anti-HIV-1 ribozyme gene into primary human lymphocytes.

We reported previously that human CD4+ T cell lines stably expressing a hairpin ribozyme targeted to the human immunodeficiency virus type 1 (HIV-1) U5 leader sequence were resistant to challenge with diverse HIV-1 viral clones and clinical isolates (Yamada et al., 1994). To simulate more closely the in vivo infection process for investigations of anti-HIV-1 ribozyme gene therapy, we developed a system to transfer this ribozyme gene into freshly isolated human peripheral blood lymphocytes (PBLs) using a murine retrovirus vector. Following transduction and G418 selection, human PBLs from multiple donors expressed the ribozyme and resisted challenge by HIV-1 viral clones and clinical isolates, while control vector-transduced PBLs remained fully permissive for HIV-1 infection. No inhibition of an HIV-2 clone lacking the target was seen in ribozyme-expressing PBLs. Ribozyme expression had no effect on viability or proliferation kinetics of the primary lymphocytes. This study is the first demonstration in primary human T cells of resistance to HIV-1 infection conferred by gene transfer. A human clinical trial is in development to test further the safety and efficacy of this ribozyme in PBLs of HIV-1-infected patients in vivo.

Base Sequence↗

Scanning electron microscopical observation of the intramitochondrial body in the bovine corpus luteum during pregnancy and after parturition.

Large luteal cells of the bovine pregnant luteum can be characterized as steroid-producing cells. Mitochondria of these cells contained intramitochondrial bodies (IMB). The three-dimensional structure of the IMB and the degenerative process of luteal cells were as follows: 1) The IMBs were globular or oval, 0.1 to 1.5 microns in diameter. Their outer surfaces were coarse but their cut surfaces were uniform. Their outer surfaces changed from rough to smooth during pregnancy. 2) At the late stage of pregnancy, the large luteal cells lost their cytoplasmic processes, showing the first sign of degeneration at the cell level in such a way that their mitochondrial cristae transformed from tubular to laminar, and that they contained accumulated lipid droplets. 3) After parturition, the IMBs came out from degenerating large luteal cells, and were conveyed by lymphatic capillaries.

Animals↗

Intracellular immunization of human T cells with a hairpin ribozyme against human immunodeficiency virus type 1.

T-cell lines (Jurkat and Molt-4) were transduced with retroviral vectors containing a hairpin ribozyme that targets a conserved sequence in the 5' transcribed leader sequence of human immunodeficiency virus (HIV) type 1. Stable cell lines were generated which constitutively and persistently expressed the ribozyme gene driven by either the Moloney retroviral long terminal repeat (LTR) or an internal human tRNA(val) promoter. There was no apparent deleterious effect of long-term ribozyme expression on cell proliferation or viability. Cells expressing ribozyme were resistant to challenge from diverse strains of HIV, including an uncloned clinical isolate. No reverse transcriptase activity or virus infectivity was detectable in the culture supernatants of Jurkat cells expressing the ribozyme driven by the tRNA(val) promoter up to 35 days after challenge with HIV-1/HXB2. Expression of the ribozyme also significantly decreased (by approximately 50- to 100-fold) the efficiency of incoming virus to synthesize viral DNA. These and previously reported results indicate that transfer and expression of the ribozyme gene interfere with both early and late events in the HIV replication cycle and confer long-term resistance to HIV-1 infection.

Base Sequence↗

Uniquely higher incidence of isolated or combined deficiency of band 3 and/or band 4.2 as the pathogenesis of autosomal dominantly inherited hereditary spherocytosis in the Japanese population.

To clarify the pathogenesis of hereditary spherocytosis (HS), red cell membrane protein components were analyzed by sodium dodecylsulfate-polyacrylamide gel electrophoresis (SDS-PAGE) with a 3.5-17% exponential gradient according to the method of Fairbanks et al. and of Laemmli in 47 HS cases from 32 unrelated Japanese families. The relative contents of each membrane protein fraction, which was stained by Coomassie blue, were expressed as their ratios to those of total membrane proteins. The density of each band of red cell membrane proteins in 47 HS patients was compared to that in 10 normal controls or in 4 high-reticulocyte controls. Various isolated or combined deficiencies of membrane proteins in these HS patients were detected by identifying the amounts of membrane proteins, which were > 1 S.D. (91%) or 2 S.D. (53%) of the mean values of normal controls, and > 1 S.D. (100%) or 2 S.D. (98%) of those of high-reticulocyte controls. Contrary to the commonly held belief that most of the autosomal dominantly-inherited HS demonstrate isolated or combined deficiency of ankyrin (ANK) and/or spectrin (SP), a much lower incidence of isolated or combined deficiency of SP and/or ANK was observed in these Japanese HS patients; 19% (> 1 S.D.) or 12% (2 S.D.) compared to normal controls, or 2% (1 S.D.) or 4% (2 S.D.) compared to high-reticulocyte controls. Instead, the incidence of isolated or combined deficiency of band 3 (B3) and/or band 4.2 (B4.2) was markedly elevated in these Japanese HS patients; 50% (1 S.D.) or 39% (2 S.D.) compared to normal controls, or 78% (1 S.D.) or 88% (2 S.D.) compared to high-reticulocyte controls. Other combined deficiencies were also observed, but the incidence was much lower. Therefore, distinct characteristics, i.e., higher incidence of isolated or combined deficiency of B4.2 and/or B3 with much lower incidence of ANK and/or SP deficiency, were observed in Japanese HS patients.

Anion Exchange Protein 1, Erythrocyte↗

Red cell membrane disorders in the Japanese population: clinical, biochemical, electron microscopic, and genetic studies.

Based on studies on 610 cases of hereditary red cell membrane disorders, the characteristic features of the incidence of these disorders in the Japanese population are described. These patients were screened by a protocol on red cell morphology (scanning electron microscopy), on red cell membrane proteins (sodium dodecylsulfate polyacrylamide gel electrophoresis, and kinetics of membrane proteins), biophysical studies (ektacytometry, mechanical stability and fluorescence recovery after the photobleaching method), membrane transport (sodium influx and efflux, and anion transport), gene analysis (spectrins, band 4.2 and band 3), surface markers (blood type antigens and sialic acid content), and development and expression of membrane proteins (using a two-phase liquid culture system). Among the molecular abnormalities detected, alpha-spectrin mutation appeared rare (only one family with spectrin alpha I/74), as opposed to two beta-spectrin mutations in Japan out of seven worldwide cases. Two unrelated kindreds with a chromosomal abnormality; that is, del (8) (p11.2-p21.1), were found that involved the possible contribution of ankyrin to the pathogenesis of hereditary spherocytosis. Anomalies of a transmembrane domain of band 3 were detected in two independent kindreds with impaired anion transport. Among 16 HE patients, 13 cases were partially band 4.1 deficient. Complete band 4.2 deficiency of the Nippon type (GCT-->ACT at codon 142 in band 4.2 gene) was observed in 17 cases of 13 unrelated kindreds. Other forms of band 4.2 deficiency without the mutation were also detected in three kindreds. Band 7 deficiency was found in seven cases with hereditary stomatocytosis independent of the presence or absence of cation transport abnormalities. A relatively high incidence of hereditary high red cell membrane phosphatidylcholine hemolytic anemia was disclosed by the analysis of red cell membrane lipids.

Anemia, Hemolytic, Congenital↗

[Concordant improvement of progressive systemic sclerosis and chronic myelogenous leukemia with interferon-alpha treatment].

A 44-year-old woman with progressive systemic sclerosis (PSS) visited our clinic because of leukocytosis and thrombocytosis. She was diagnosed as having chronic myelogenous leukemia (CML) with PSS, and was treated with interferon-alpha 2b (IFN-alpha) after pretreatment of hydroxyurea as a cytoreduction. Complete hematological remission was obtained two months later, and four months later minimal cytogenetic response was achieved by IFN-alpha. Her PSS symptoms were also improved to some extent as judged by Rodnan's total skin score, maximal opening distance of oral cavity, and range of motion of wrists. Our results suggest that IFN-alpha is probably beneficial not only for CML itself but also for PSS, too.

Adult↗

Electron microscopic and physicobiochemical studies on disorganization of the cytoskeletal network and integral protein (band 3) in red cells of band 4.2 deficiency with a mutation (codon 142: GCT-->ACT).

The role of band 4.2 deficiency in the pathogenesis of red cell membrane dysfunctions was studied in seven unrelated patients with complete band 4.2 deficiency with a point mutation (142 GCT-->ACT; 142 Ala-->Thr) on the cDNA of the band 4.2 gene. Two major types of abnormalities were detected in these patients; (A) abnormalities of the cytoskeletal network in the horizontal dimension, and (B) abnormalities of band 3 in the vertical dimension. Electron microscopy by the surface replica method and the quick-freeze deep-etching method demonstrated the markedly impaired cytoskeletal network (a disorganized cobblestone pattern, uneven distribution of junctional units, and the appearance of bulky aggregates after heat treatment). Ektacytometry showed a markedly decreased red cell deformability especially at 48 degrees C, although the cytoskeletal proteins themselves were essentially normal with normal mechanical stability of the Triton-shells. Electron microscopy by the freeze fracture method revealed a decreased number and a random distribution of intramembrane particles (IMPs) with a shift of the IMPs to a larger size. Fluorescence recovery after photobleaching studies on band 3 indicated the marked increase of its mobile fraction. The extractability of band 3 by Triton X in vitro was markedly enhanced, although the physico-biochemical properties of band 3 itself (the cleavage pattern of band 3 fragments, and the binding properties of band 3 to band 4.2 or ankyrin) were basically normal. These findings demonstrate that band 4.2 plays a crucial role in the maintenance of the normal structure and functions of both the cytoskeletal and integral proteins (band 3).

Anion Exchange Protein 1, Erythrocyte↗

[Co-operative study of all-trans retinoic acid as a differentiation induction therapy of acute promyelocytic leukemia].

Efficacy and safety of tretinoin (all-trans retinoic acid, ATRA, Ro01-5488) for refractory and relapsed acute promyelocytic leukemia were studied by multi-institutional study in Japan. 22 out of 27 (81.5%) patients with previously untreated who were intolerable to chemotherapy, relapsed and refractory were achieved CR. And 4 out of 11 (36.4%) in relapsed patients who received ATRA remission induction therapy previously responded. Side effects, such as dryness of the lip and skin, headache, increase of triglyceride, beta-lipoprotein and lactate dehydrogenase, were observed in 36 of 41 eligible patients (87.8%) but these were well tolerated. In addition to these, hyperleukocytosis in 4 cases and retinoic acid syndrome in 3 cases were observed. However, all patients were prescribed tretinoin again by adequate management.

Administration, Oral↗

[A successful case report of redo composite graft and total aortic arch replacement for active prosthetic graft endocarditis].

A successful redo composite graft and total aortic arch replacement for active prosthetic graft endocarditis is reported in the 31-year-old female with Marfan syndrome who had undergone Bentall procedure and proximal aortic arch replacement for type A acute aortic dissection 21 months previously. Echocardiography revealed massive vegetation in the composite graft and left ventricular outflow tract, and blood culture suggested Candida endocarditis. The composite graft and arch grafts were completely removed, and the reconstruction was carried out with a new composite graft using Piehler's technique. Finally, the total aortic arch was replaced and the all branches were reconstructed. The post-operative course has been uneventful, and she is now doing well 12 months after the operation without any evidence of recurrence of endocarditis.

Adult↗