Search PubMed⌕ Search

Biomedical subjects

Y Yoshikawa

Publications and source records attributed to Y Yoshikawa.

At least 181 records · Page 10Linked to original sources
PubMed1997

[One-stage replacement of the entire thoracic aorta with aortic valve reimplantation technique--a reoperation for a Marfan patient with annulo-aortic ectasia and chronic aortic dissection of DeBakey type I].

A 23-year-old man with Marfan syndrome, who had annulo-aortic ectasia and chronic aortic dissection of type I, was successfully treated. He underwent one-stage replacement of the entire thoracic aorta using a retrograde pull-through technique with aortic valve sparing reimplantation (David procedure). The descending aorta was replaced with a Hemashield graft, and then the graft was passed through within the descending aortic aneurysm in the retrograde fashion. Thus, the graft was inserted inside the descending aortic aneurysm without ligation of some of the intercostal arteries. Postoperative MRI showed complete clotting of the space between the graft and the aneurysm. David's reimplantation procedure which spares own aortic valve, requires no anticoagulant therapy in the post operative period. Neither aortic regurgitation nor pressure gradient between the left ventricle and the aorta were observed postoperatively. We conclude that the replacement of the entire thoracic aorta using a retrograde pull-through technique with an aortic valve sparing reimplantation by the single stage is useful for the selected patients with aneurysm of the entire thoracic aorta and annulo-aortic ectasia.

Adult↗
PubMed1997

Biological behaviour of 6-chloro-2',3'-dideoxyguanosine and 6-chloro-2',3'-dideoxyinosine in the brains of mice.

By using tissue and blood from mice and mice themselves, biological behavior of 6-chloro-2',3'-dideoxyguanosine (6-Cl-ddG) and 6-chloro-2',3'-dideoxyinosine (6-Cl-ddI) was examined in vitro and in vivo. Both compounds resemble each other in chemical structure. They are converted to ddG and ddI, respectively, by adenosine deaminase in the cells, and express their anti-HIV activity in vitro. According to our recent data about their biological behaviour in vivo; however, it was revealed that they are fairly different especially as the agent working in the brain. After injection of each drug into the body of mice, ddG, or metabolite of 6-Cl-ddG, was observed in the brain, while ddI was not found there.

Adenosine Deaminase↗
PubMed1997

Morphological variation in folded duplex DNA chains.

I have monitored the packaging process of giant DNA chains with various condensing agents, such as polyamines, polyethylene glycol having pendant aminogroups and a lipospermine, under fluorescence microscopy. The detail morphological structure of the compacted DNA has been observed using electron microscopy. It has become clear that the difference in the folding process results in a large polymorphism of compacted DNA. I discuss the biological importance of controlling the compacted structure.

Bacteriophage T4↗
PubMed1996

Daunomycin unfolds compactly packed DNA.

Daunomycin is an antitumor antibiotic known to inhibit DNA replication and transcription. Although the inhibition is assumed to be caused by a direct interaction of the drug with DNA, the exact effect of daunomycin on the higher order DNA structure remains uncertain. We studied the effect of daunomycin on DNA compacted states using fluorescence and electron microscopies. Structural changes in individual DNA molecules were examined under the following conditions. T4 phage DNA (166 kbp) was first compacted by spermidine followed by the addition of daunomycin to the compacted DNA. A direct observation of individual single duplex DNAs by fluorescence microscopy indicated that daunomycin induced unfolding of the compacted DNA. Electron microscopic observation of the morphological changes of the higher order DNA structure supported the results obtained by fluorescence microscopy. We discuss here the mechanisms of the unfolding of the compacted structure following intercalation of daunomycin into DNA particularly in terms of the free energy.

Antibiotics, Antineoplastic↗
PubMed1996

Folding and aggregation of DNA chains induced by complexation with lipospermine: formation of a nucleosome-like structure and network assembly.

Dioctadecylamidoglycylspermine (DOGS) is a cationic lipid vector capable of efficiently introducing DNA into various eukaryotic cells. We investigated the higher-order structure of the DNA/DOGS complex using fluorescence and electron microscopy. Our results show that the DNA/DOGS complex exhibits a nucleosome-like structure in which DNA wraps around an aggregate of DOGS molecules. In addition, DNA/DOGS complexes tend to associate with each other to form network structures. The resulting network assembly may play a role in effective gene transfection.

Animals↗
PubMed1996

In vitro immortalization of Old World monkey T lymphocytes with Herpesvirus saimiri: its susceptibility to infection with simian immunodeficiency viruses.

Peripheral blood T lymphocytes of Old World monkeys, rhesus and cynomolgus monkey (Macaca mulatta and Macaca fascicularis, respectively), were successfully immortalized by infection with Herpesvirus saimiri subtype C. The T cell lines were stably cultured without addition of exogenous IL-2. The STP-C488 protein, the oncogene product of subtype C strain 488-77, was detected in these cells by Western blotting. They also expressed some markers of activated or matured T cell phenotypes such as CD2+, monkey Pan-T+, CD25+,CD29+ and MHC-II DR+. Interestingly, not only CD4+CD8- or CD4-CD8+ single positive subpopulations but also CD4+CD8+ double positive ones were present in all of them. Furthermore, they were productively infected with both SIVmac and SIVagm. The levels of the viral replication were comparable to those in human T cell lines. Thus, Herpes Virus Saimiri-immortalized Old World monkey T lymphocytes will be suitable for further studies of immune system in Old World monkeys and cell-virus interactions in SIV infection.

Animals↗
PubMed1996

The bioavailability of oral dosage forms of a new HIV-1 protease inhibitor, KNI-272, in beagle dogs.

The bioavailability (BA) of a tripeptide protease inhibitor, KNI-272, which has a strong pharmacological potential for treating human immunodeficiency virus type 1 (HIV-1), has been studied in beagle dogs by administering several oral dosage forms. The tested dosage forms were form 1, plain gelatin capsules; forms 2 and 3, gelatin capsules of which the inner and outer surfaces were coated with 7G ethylcellulose (EC, 30 mu m thickness) and an enteric coating material, hydroxypropyl methylcellulose phthalate (HP-55), respectively; and form 4, gelatin capsules of which the inner surface is coated with 10G EC (60 mu m thickness). The difference between forms 2 and 3 was the amount of citric acid contained in the capsule, namely 100 mg in form 2 and 200 mg in form 3. One hundred milligrams of KNI-272 was placed in each capsule after being dissolved with propylene glycol (PG). These capsules were used to deliver KNI-272 to the stomach for form 1, to the upper part of the small intestine for forms 2 and 3, and to the middle part of the small intestine for form 4. As a reference, 50.0 mg of KNI-272 was administered to the same dogs by intravenous (IV) infusion for 15 min. By measuring the plasma drug levels with the HPLC method, BAs were estimated for each test dosage form. Form 1 showed the highest BA of 26 center dot 2 +/- 7 center dot 0% (mean +/- SE), though the other capsules showed BAs of approximately 10%, namely 6 center dot 6 +/- 0 center dot 4% for form 2, 10 center dot 3 +/- 1 center dot 1% for form 3 and 14 center dot 2 +/- 1 center dot 0% for form 4. Therefore, as the site where KNI-272 is released from the capsule becomes higher, the BA increases. In addition, as the amount of citric acid contained in a capsule increases, the BA value tends to increase. These results suggest that KNI-272 is stable and not extensively hydrolysed in the gut after oral administration, that the dissolution process into GI fluids is important for the BA of KNI-272, and that the most appropriate absorption site of KNI-272 in dogs is the duodenum. The potential of this new tripeptide compound as an orally active anti-AIDS drug has been confirmed.

Administration, Oral↗
PubMed1996

Studies on the mechanism of early onset macular degeneration in cynomolgus (Macaca fascicularis) monkeys. I. Abnormal concentrations of two proteins in the retina.

Cynomolgus (Macaca fascicularis) monkeys from three families, which showed symptoms of early onset macular degeneration was studied. Two proteins, albumin and glyceraldehyde 3-phosphate dehydrogenase, were found to have markedly altered concentrations in whole retina of the monkeys with early onset macular degeneration, compared with normal controls. SDS-polyacrylamide gel patterns detected a 40-70% increase in the concentration of albumin and about 65% decrease in the concentration of glyceraldehyde 3-phosphate dehydrogenase in these affected retinas. There was however no significant difference in the relative concentrations of albumin in the plasma samples of affected and normal monkeys belonging to the three families studied and to an unrelated family. These initial findings suggest that degradative as well as antioxidant enzymes might be involved in the mechanisms leading to macular degeneration. In addition, the results also correlate with a possible role of these two proteins in H2O2 toxicity and appear to indicate that oxidative stress is significant in the etiology of early onset macular degeneration.

Albumins↗
PubMed1996

Studies on the mechanism of early onset macular degeneration in cynomolgus monkeys. II. Suppression of metallothionein synthesis in the retina in oxidative stress.

Initial investigations done in this laboratory detected increased albumin and decreased glyceraldehyde 3-phosphate dehydrogenase concentrations in the retina of an animal model manifesting early onset macular degeneration. Both glyceraldehyde 3-phosphate dehydrogenase and albumin are markers of oxidative stress in cells. In this study, we used the same animal model to study further biochemical and physiological processes which may be involved in the pathogenesis of early onset macular degeneration in monkeys. We detected 60% lower catalase and glutathione peroxidase activities in the affected retinas suggesting lower antioxidant activities and oxidative stress. One of the consequences of oxidative stress is the production of metallothionein, a low molecular weight protein also induced by high concentrations of heavy metals such as zinc. Metallothionein was detected by RT-PCR in these monkey retinas. However initial quantitative PCR studies on this protein showed that the synthesis of metallothionein in affected retinas appears to be less than in normal controls. The affected retinas also showed a fourfold lower zinc concentration compared with the normal controls. No significant difference, however, could be detected in the zinc concentrations in plasma samples. Since induction of metallothionein synthesis is mediated by transcription factors which require heavy metals such as zinc for binding to specific sites in the DNA, the lowered zinc concentration may, thus, correlate with the lowered metallothionein expression. And since metallothionein is suggested to function as a free radical scavenger, the lowered metallothionein synthesis may consequently contribute to increased peroxidation reactions in the affected retinas. It appears therefore, that oxidative stress and the decreased metallothionein synthesis may be involved in the pathogenesis of early onset macular degeneration in this animal model.

Amino Acid Sequence↗
PubMed1996

Functional restoration of rat bladder after subtotal cystectomy: in vivo cystometry and in vitro study of whole bladder.

Functional restoration of the rat urinary bladder following subtotal cystectomy was studied via in vivo infusion cystometry and an in vitro whole bladder model. After the bladder had been separated from the prostate, subtotal cystectomy was achieved by ligating the bladder completely at a level just above the insertion of the ureters into the bladder. Bladder function was investigated immediately and 7, 14, and 28 days after surgery. Bladder weight was reduced to 17% that in sham-operated controls immediately after surgery, but recovered to 76% of that in controls 28 days after the operation. In vivo capacity also increased after surgery from 13% that of controls to 59% 28 days later. However, voiding pressure remained low (34% of control) 28 days later. An in vitro whole bladder study showed that the response to field stimulation decreased significantly on day 7, but had recovered considerably by day 28. The maximal response to bethanechol decreased significantly 7 days after surgery, but recovered thereafter. The response to phenylephrine increased significantly immediately after surgery, but gradually returned to the control level. An in vitro volume-pressure study showed that passive compliance of the cystectomized bladder decreased after surgery, but improved with time. The peak of the active pressure increase to field stimulation occurred at a low infusion volume immediately after surgery, but bladder capacity increased gradually until 28 days later, when the maximal active pressure was obtained. Our results suggest that restoration of the bladder following subtotal cystectomy may not derive simply from an expansion of the bladder wall. Functional alteration involving the bladder base was also observed.

Animals↗
PubMed1996

Effect of the expression of DR alpha E beta NOD molecule on the development of insulitis and diabetes in the non-obese diabetic (NOD) mouse.

Previous studies have shown that a transgenic I-E alpha gene, the mouse homologue of human DR alpha gene, prevents the development of insulitis and hence of diabetes in NOD mice. To investigate the mechanism of this prevention, we generated two strains of NOD mice expressing DR alpha E beta molecule: DR alpha-24-NOD expressing DR alpha E beta molecule on thymic epithelial cells (TEC) and bone marrow-derived cells (BDC), and DR alpha-30-NOD expressing DR alpha E beta molecule only on the TEC, and these mice were monitored for disease development. Because the DR alpha E beta molecule reconstituted I-E controlled immune regulation, it would become clear which cell type, TEC or BDC, was responsible for the I-E-mediated disease protection. To our surprise, however, DR alpha-24-NOD developed insulitis and diabetes comparably to non-transgenic littermates. This suggested that the difference in structure between DR alpha and E alpha molecules contributed to the difference in preventive effect on the development of insulitis and diabetes between DR alpha-24-NOD and E alpha-NOD. In an analysis of the T cell proliferative responses to glutamic acid decarboxylase (GAD) 65-derived peptides which were known to be diabetogenic autoantigens, it was shown that DR alpha-24-NOD and NOD acquired comparable level of T cell response to GAD 509-528 but 5-10-fold higher response was observed in E alpha-NOD. This suggested that I-ANOD and E alpha E beta NOD molecules could present GAD 509-528 peptide to T cells, while DR alpha E beta NOD could not. Furthermore, T cells from DR alpha transgenic mice showed proliferative response to antigen-presenting cells from E alpha transgenic mice in primary mixed lymphocyte reaction. This also suggested that the E alpha E beta molecule does differ in structure and peptide binding from the DR alpha E beta molecule. Present data suggested a possibility that the T cell repertoire selection, or the T cell response to GAD 65 and/or other unknown antigens specifically mediated by I-E molecule, may contribute to the prevention of disease development in E alpha-NOD.

Amino Acid Sequence↗
PubMed1996

Human monoclonal rheumatoid factors augment arthritis in mice by the activation of T cells.

In order to investigate the in vivo role of rheumatoid factor (RF), the effects of the administration of human monoclonal (m) IgM-RF and IgG-RF on the development of arthritis in mice were examined. The administration of human mRFs into mice immunized with type II collagen (CII) markedly enhanced the clinical score and paw swelling. The severity of arthritic joint disease with a marked infiltration of lymphoid cells, proliferation of synovial membrane, pannus formation and destruction of articular cartilage was significantly enhanced in both groups receiving RF (RF-enhanced arthritis). Skin ulcers were also observed in some of these RF-enhanced arthritis mice, whereas no such signs were observed in CII-immunized mice without mRFs. Both IgM-RF and IgG-RF increased CII-specific IgG antibodies in circulation, and the severity of arthritis correlated with the production of high titres of anti-CII antibodies. In vivo treatment of RF-enhanced arthritis mice with an anti-CD4 MoAb or an anti-CD8 MoAb inhibited the induction and progression of arthritis in these mice. Administration of RF to severe combined immunodeficient (SCID) mice with arthritis developed by the transfer of spleen cells from CII-immunized mice, prolonged the arthritis and enhanced the severity. This murine model of RF-enhanced arthritis may provide a useful tool for analysing the pathogenesis of rheumatoid arthritis in RF-positive patients.

Adoptive Transfer↗
PubMed1996

A case of alpha-fetoprotein-producing gastric cancer showing an exogastric growth pattern.

A case of alpha-fetoprotein (AFP)-producing gastric cancer, which showed a huge abdominal mass due to an exogastric growth, is here described. A 69-year-old Japanese woman with a huge abdominal mass, measuring 22 x 15 cm in size, had a serum AFP level that was exceptionally high (155 x 10(3) ng/ml). CT, barium meal studies, and gastrointestinal fiberoscopy revealed a gastric tumor with an exogastric growth pattern. The patient underwent a partial gastrectomy. The histological examination revealed that the tumor consisted of anaplastic carcinoma with positive staining for AFP. Although no liver metastasis was observed at operation, she died of multiple liver metastases 8 weeks after the operation. A gastric cancer that shows both AFP production and an exogastric growth pattern is quite rare and may be virulent.

Aged↗
PubMed1996

Transient expression of CD20 antigen (pan B cell marker) in activated lymph node T cells.

In contrast to the case of peripheral T cells, the surface expression of CD20 antigen and the expression of CD20 mRNA in monkey lymph node (LN) T cells underwent a noticeable increase when they were cultured with mitogen and interleukin-2 (IL-2). To confirm in vivo regulation of CD20 expression during the activation of LN T cells, we examined LNs derived from monkeys experimentally inoculated with simian immunodeficiency virus (SIV). Significant expression of CD20 antigen was detected in the T cells of the LNs at the stage of lymphadenopathy. These findings suggest that lymphocyte activation in the LNs induced expression of the CD20 molecule in some T cells.

Animals↗
PubMed1996

Immunohistochemical characteristics of the constituents of senile plaques and amyloid angiopathy in aged cynomolgus monkeys.

In this study, we immunohistochemically examined the several constituents of senile plaques (SPs) and cerebral amyloid angiopathy (CAA) in aged cynomolgus monkeys. Apolipoprotein E (apoE) deposited in all mature plaques and CAA, and in half of the diffuse plaques. Alpha-1-antichymotripsin (alpha ACT) deposited in half of the mature plaques and in one third of the CAA. Amyloid precursor protein (APP), ubiquitin (Ub), and microtubule-associated protein-2 (MAP-2) accumulated in the swollen neurites of mature plaques. Glial fibrillary acidic protein (GFAP) was detected in the astrocytes and their processes surrounding the mature plaques. Tau was detected in neither the SPs nor CAA. Therefore, mature plaques involved extracellular A beta, apoE, and alpha ACT, and also astrocytes and swollen neurites. However, diffuse plaques involved only extracellular A beta and apoE. Since these features, except for tau, were consistent with those in humans, this animal model will be useful for studying the pathogenesis of cerebral amyloid deposition.

Aging↗
PubMed1996

Oral sustained-release cisplatin capsule.

An oral sustained-release cisplatin preparation was prepared by combining microporous water-insoluble pharmaceutical polymer, ethylcellulose, a membrane and a gel-forming polymer, poly(acrylic) acid (Carbopol). As cisplatin is an extremely hydrophilic and small compound, it was difficult to control the release rate solely by the micropores on the ethylcellulose capsule. To retain cisplatin within the capsule, gel-forming polymer was formulated inside the capsule. The release rate of cisplatin was dependent both on the number of micropores of the capsule and the formulated amount of Carbopol. The number of micropores ranged from 20 and 30 to 60, and the formulated amount of Carbopol varied from 15 to 100 mg. In-vitro release experiments suggested that the release rate decreased as the formulated amount of Carbopol increased when the pore number was 60 and 30. However, when pore number was decreased to 20, the effect of the amount of Carbopol was not clearly observed. In the in-vivo study using rabbits, the sustained-release cisplatin capsule was evaluated in comparison with solution after oral administration of 20 mg drug. With the pore number of 60, Cmax was 0.46 +/- 0.02 microgram mL-1 at 4 h and thereafter serum concentrations declined rapidly. When the pore number was 30, serum cisplatin level-time profiles showed long-acting patterns and AUC was reversely correlated with the formulated amount of Carbopol. Cmax and tmax were 0.41 +/- 0.02 microgram mL-1 and 3.33 +/- 0.88 h, respectively and 0.23 +/- 0.01 microgram mL-1 was obtained at 24 h after oral administration of capsule having 30 pores and 15 mg of Carbopol. We conclude that the possibility of developing an oral sustained-release cisplatin preparation is feasible.

Acrylic Resins↗
PubMed1996

Immunohistochemical study on the deposition of apolipoprotein E in cerebral and islet amyloidoses in cynomolgus monkeys (Macaca fascicularis).

To investigate the role of apolipoprotein E (apo E) in amyloidoses of cynomolgus monkeys, the localization of apo E in cerebral amyloid, including senile plaques and cerebrovascular amyloid, and in islet amyloid was examined immunohistochemically. Mature types of senile plaques with amyloid deposits and cerebrovascular amyloid showed intense immunoreactivity to both antisera to apo E and amyloid beta protein (A beta). In contrast, diffuse plaques without obvious Congophilic amyloid showed weak immunoreactivity to antiserum to apo E, but intense reactivity to antiserum to A beta. In addition, the number of these apo E-positive diffuse plaques was small compared with that of A beta-positive plaques. On the other hand, diabetic islet amyloid that was negative with A beta, reacted intensely with antiserum to apo E. These findings suggest that apo E plays an important role in amyloid fibril formation in several types of amyloidoses.

Amyloid↗