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Biomedical subjects

Y Yoshikawa

Publications and source records attributed to Y Yoshikawa.

At least 91 records · Page 5Linked to original sources
PubMed2000

Pulmonary ventricular outflow reconstruction with a size-reduced cryopreserved pulmonary valve allograft: mid-term follow-up.

Surgical reduction of pulmonary allografts is being performed because of the shortage of allografts of suitable size for pediatric use. However, the outcome of size-reduced pulmonary allografts for pulmonary conduits is unknown. In the present study, cryopreserved pulmonary allografts harvested from adults at the time of kidney donation were size-reduced and used in 4 children, 2 with pulmonary atresia and ventricular septal defect and 2 with atrioventricular discordance, pulmonary atresia and ventricular septal defect. They all had undergone right and/or left modified Blalock-Taussig shunt operations with a 5-mm synthetic graft prior to the reparative operations. They underwent definitive repair with a size-reduced cryopreserved pulmonary allograft valved conduit and were followed up for 2-5 years. Postoperative echocardiographic and cineangiographic assessments revealed excellent function of the pulmonary bicuspidalized valves with a minimal pressure gradient and no, or only trivial, regurgitation. Although the long-term result of a cryopreserved bicuspid pulmonary valved conduit remains unknown, the remodeled bicuspid pulmonary allograft conduits showed excellent hemodynamic characteristics in mid-term follow-up and appear to be a reasonable alternative to other types of conduits when an appropriate-sized allograft is not available.

Adult↗
PubMed2000

Effects of aging on bone mineral content and bone biomarkers in female cynomolgus monkeys.

Age-related changes in bone mineral content and bone biomarkers were assessed over the complete lifespan of female cynomolgus monkeys. The bone mass of the lumbar spine increased linearly from birth to about 2.5 years of age, and this increase gradually slowed thereafter until a peak bone mass was achieved at 9 years of age. The bone mass stabilized after 9 years of age, showing no sign of further reduction with age. In contrast with the significant increase in bone mass before 2.5 years of age, significant decreases occurred in the serum concentrations of the following bone formation markers: intact osteocalcin, bone-specific alkaline phosphatase and amino-terminal propeptide of type I procollagen, but the serum concentration of carboxy-terminal propeptide of type I procollagen did not change significantly throughout the entire lifespan. Concerning the bone resorption markers, the levels of tartrate-resistant acid phosphatase fluctuated throughout the entire lifespan. The skeleton of an aging female monkey undergoes changes similar to those observed in senescent humans, but did not undergo the menopausal changes seen in women. The use of female cynomolgus monkeys to model human skeletal interventions should therefore be undertaken with consideration of the similarities and differences between cynomolgus monkeys and humans.

Aging↗
PubMed2000

Localization and age-related changes in cytochrome P450 expression in APA hamster livers.

To establish the baseline data, age-related changes and the regional expression of the hepatic P450 isozymes in Syrian hamsters of the APA strain at 3, 6, 12, 18 months old were examined by immunological techniques. Immunohistochemical analysis of liver serial sections revealed that the midzonal and perivenous regions (zones 2 and 3, respectively) were stained with the anti-rat CYP1A1/2, 2B1/2 and 2E1 antibodies. These three antibodies most intensely stained the hepatocytes around the central vein. An anti-rat CYP3A2 staining section had a staining pattern with equally intense reactions in zones 2 and 3. On the other hand, CYP2C6, 2C11 and 4A1 were distributed diffusely throughout the hepatic acinus. There was no age-related difference in the expression pattern of any of the P450 isozymes examined. Total P450 content had a peak at 6 months of age and decreased to 60% of that level thereafter. Western-blot analysis revealed that the peak expressions of the isozymes detected with anti-rat CYP1A1/2, 2C6, 2E1 and 3A2 antibodies were observed in 6-month-old hamsters and declined in older ones. The CYP2B and 2C11 content reached the maximum at the age of 6 months and maintained almost the same level thereafter. The CYP4A level did not change from 3 to 6 months, and then declined to about 40% of the younger level at 12 and 18 months of age. These results suggest that the hepatic P450 isozymes of APA hamsters have region-specific expressions and most isozymes have their peaks of expression at 6 months of age, which differs from the patterns for rat P450.

Aging↗
PubMed2000

Squamous cell carcinoma of the oral cavity in an infant cynomolgus monkey.

Squamous cell carcinoma was observed in the oral cavity in a one-year-old male cynomolgus monkey. Histopathologically, the tumor consisted of various shaped cells and its assemblies infiltrated into the surrounding connective tissues. Although no obvious metaplastic keratinized cancer pearls were found in the tumor cells, the intercellular bridges were observed. Immunohistochemically, tumor cells were stained with anti-keratin, but not with anti-vimentin. On virological examinations, no papilloma virus antigen or Epstein-Barr Virus small mRNA could not be detected. Under the electron microscope, incomplete tonofibrils and desmosomes in the cytoplasm and microvillus of the cell membrane were observed, suggesting a malignancy or low differentiation of the tumor cells in the present case. This is the first case of squamous cell carcinoma observed in very young macaques, to our knowledge.

Animals↗
PubMed2000

Aortic atheromatous lesions developed in APA hamsters with streptozotocin induced diabetes: a new animal model for diabetic atherosclerosis. 1. Histopathological studies.

To develop an adequate animal model for atherosclerosis in large vessels of patients with diabetes, i.e. diabetic macroangiopathy, we induced diabetes in APA hamsters with a single injection of streptozotocin (SZ) and examined the aorta histopathologically and immunohistochemically. As a result, hyperglycemia and hyperlipidemia were continuously observed for 26 weeks after the SZ injection (WAI) in APA hamsters. Fatty streaks characterized by a subendothelial accumulation of many foam cells were observed, limited to the aortic arches as early as 6 WAI. In addition to larger fatty streaks developing with the duration of diabetes, fibrous plaques and plaques containing calcium deposits or cholesterol clefts developed at 26 WAI. These lesions are generally similar to the atheromatous lesions developed in humans. Moreover, depositions of apolipoprotein E and advanced glycation end-products immunohistochemically detected in the lesions were very similar to those found in humans. The diabetic APA hamster is therefore considered to be a useful model for studying the formation of atheromatous lesions in diabetic patients.

Alloxan↗
PubMed2000

APA hamster model for diabetic atherosclerosis. 2. Analysis of lipids and lipoproteins.

Syrian hamsters of the APA strain (APA hamsters) have recently been shown to have atheromatous lesions in the aortic arches under diabetic condition induced by a single injection of streptozotocin (SZ). In that model, fatty streaks, which are the initial lesions of atherogenesis, develop by 6 weeks after the injection (WAI). In this study, we evaluated plasma lipid concentrations and lipoprotein profiles in diabetic APA hamsters at 6 WAI to reveal the early stage of atherogenesis clinicopathologically. As a result, by biochemical analysis, hyperglycemic APA hamsters showed signs of hypercholesterolemia and hypertriglyceridemia. Low-density lipoprotein (LDL) cholesterol significantly increased, but high-density lipoprotein (HDL) cholesterol significantly decreased. Agarose gel electrophoresis showed an obvious increase in the fractions of chylomicron, LDL and abnormal lipoprotein. Plasma LDL in diabetic animals was in a state more susceptible to oxidization. In addition, a significant increase in glycated LDL was also found in the diabetic animals by enzyme linked immunosorbent assay (ELISA). Moreover, lipid peroxidation product (4-hydroxynonenal (4 HNE))-adducted proteins and advanced glycation end-products (AGE) were immunohistochemically detected in the foam cells of the fatty streaks. These results revealed that diabetic APA hamsters had hyperlipidemia characterized by increases in chylomicron, LDL and abnormal lipoprotein, and suggested that oxidized LDL and/or glycated LDL might be actively uptaken by macrophages and play an important role in the initial stage of atherogenesis.

Aldehydes↗
PubMed2000

Comparison of the effects of two fixatives for immunolocalization of testosterone in the testes of the cynomolgus monkey, mouse and rat.

We compared the effect of two fixatives, Bouin's fixative and neutralized buffered 4% formaldehyde (10% formalin), for immunolocalization of testosterone in the testes of cynomolgus monkeys, mice and rats. In the samples fixed with Bouin's fixative, immunoreactive testosterone was detected as intense deposits in the cytoplasm of Leydig cells of monkeys and mice. Immunoreactive testosterone was detected not only in Leydig cells of rats but also moderately shown within tubules. Immunoreactive testosterone could not be detected in the testes of monkeys, mice or rats fixed with neutralized buffered formalin because of the poor morphology caused by the fixative. It is concluded that Bouin's fixative is a suitable fixative for immunolocalization of testosterone in the testes of cynomolgus monkeys, mice and rats.

Acetic Acid↗
PubMed2000

[An experience with the Ross operation utilizing cryopreserved pulmonary homografts procured by and stored in our homograft valve bank].

Eight patients, 4 males and 4 females ranging in age from 10 to 54 years (mean 27 +/- 13 years) underwent the Ross operation using a cryopreserved pulmonary homograft harvested by and cryopreserved in our institutional "Tissue Bank". Seven patients had a congenital bicuspid aortic valve and 3 patients had had healed infective endocarditis of the aortic valve. Four young female patients wanted to have a baby after operation. The Ross procedure was carried out utilizing aortic root replacement techniques in all patients. All patients survived and are currently in NYHA class 1, but 2 cardiac events occurred in 2 patients during the mean follow-up term of 29 +/- 19 months. The one was the anastomic stenosis between the homograft and distal pulmonary artery treated by balloon dilatation and the other was ventricular tachycardia eventually managed by the insertion of an ICD. Pulmonary autograft valve regurgitation is present in 3 patients, but it is not progressive up to the present time. Pulmonary homograft valves function well in all patients. The Ross operation for adolescents and young adults should become more popular along with more easy availability of homograft valves based upon the establishment of the "Homograft Valve Bank" system in Japan.

Adolescent↗
PubMed2000

Replacement of the tricuspid valve in children with congenital cardiac malformations.

BACKGROUND AND AIM OF THE STUDY: When replacing the regurgitant tricuspid valve in children, the decision to use either a bioprosthesis or a mechanical valve remains controversial. METHODS: The atrioventricular valve for the pulmonary circulation was replaced in 11 young patients aged between 8 months and 13 years. Complications of congenital cardiac malformation were present in seven patients, and Ebstein's anomaly in three; tricuspid valvular regurgitation was an isolated lesion in one patient. A bioprosthesis was implanted on seven occasions, and a bileaflet mechanical valve on eight, including re-replacement of the valve in four patients. RESULTS: One patient died two years after implantation due to respiratory problems. Tricuspid stenosis due to valve calcification occurred in four bioprostheses at between four and nine years after initial replacement (57%). In three of these cases the native valve leaflets had not been removed. Thrombosis occurred in one patient with a mechanical valve; rereplacement was successful. Anticoagulant-related hemorrhage occurred in another patient. Among patients receiving a mechanical valve, 83% of valves were dysfunction-free after five and ten years. CONCLUSION: When replacing an atrioventricular valve for the pulmonary circulation in children, we prefer to use a low-profile mechanical valve, especially when extensive repair of intracardiac malformation has been carried out, but ventricular function is good. In children with poor cardiac performance, a bioprosthesis is preferred, with total resection of the native valve leaflets.

Adolescent↗
PubMed1999

T (Brachyury) is a direct target of Wnt3a during paraxial mesoderm specification.

Wnt3a encodes a signal that is expressed in the primitive streak of the gastrulating mouse embryo and is required for paraxial mesoderm development. In its absence cells adopt ectopic neural fates. Embryos lacking the T-box-containing transcription factors, Brachyury or Tbx6, also lack paraxial mesoderm. Here we show that Brachyury is specifically down-regulated in Wnt3a mutants in cells fated to form paraxial mesoderm. Transgenic analysis of the T promoter identifies T (Brachyury) as a direct transcriptional target of the Wnt signaling pathway. Our results suggest that Wnt3a, signaling via Brachyury, modulates a balance between mesodermal and neural cell fates during gastrulation.

Animals↗
PubMed1999

Relevance of ER to the Development of Endometrial Hyperplasia and Adenocarcinoma.

Estrogen has an important role in both the etiology and treatment of hormone-dependent endometrial cancers, although the mechanism remains elusive. To definethe role of estrogen-mediated signaling we investigated the biological significance of estrogen receptors (ER) in NIH3T3 cell transformation via the [ &sup12; Val ] K-Ras mutant. This mutant enhanced the steady state level and transcriptional activity of ER. In addition, overexpression of both wild type K-Ras and ER transformed NIH3T3 cells. Co-expression of the progesterone receptor (PR) with mutant K-Ras led to suppression of tumorigenicity and inhibition of ER activation. The antisense oligomers complementary to ER suppressed proliferation and transformed phenotypes of K12V cells. These observations support the importance of ER in Ras-mediated cell transformation. To address whether ER activation is also important in the development of human endometrial cancers, we investigated ER and PR expression levels in premalignant and malignant endometrial lesions. The results suggested the implication of ER abundance in endometrial hyperplasias, though modulation of PR expression by ER was retained. G1 adenocarcinoma also expressed higher levels of ER while PR modulation by ER was abrogated. These data implied the importance of ER activitiesin endometrial hyperplasia and G1 adenocarcinoma development.

Journal Article↗
PubMed1999

Binding study of semotiadil and levosemotiadil with alpha(1)-acid glycoprotein using high-performance frontal analysis.

High-performance frontal analysis (HPFA) was used to investigate the binding properties of human alpha(1)-acid glycoprotein (AGP) with semotiadil ((R)-isomer, Ca-channel blocker) and its antipode levosemotiadil ((S)-isomer, Ca- and Na-channel blockers). An on-line HPLC system consisting of a HPFA column, an extraction column, and an analytical HPLC column was used to determine the unbound concentrations of these enantiomers, and the experimental data were subsequently subjected to the Scatchard analyses to estimate their binding parameters. The binding affinity of the (R)-isomer (K = 3.17 x 10(7) M, n = 0.74) is approximately 1.2 times stronger than that of (S)-isomer (K = 2.59 x 10(7) M, n = 0.74). An enantioselective competitive binding study indicated that both enantiomers are bound at the same site on AGP molecules.

Calcium Channel Blockers↗
PubMed1999

Cloning, expression, and chromosomal mapping of a human ganglioside sialidase.

Here we report the cDNA sequence of a human ganglioside sialidase. The cDNA was isolated from a human brain cDNA library by screening with a 240 bp probe generated by polymerase chain reaction using primers based on the sequences of rat cytosolic and bovine membrane sialidases which we previously cloned. The 3.0 kb cDNA encodes an open reading frame of 436 amino acids containing a putative transmenbrane domain and an Arg-Ile-Pro and three Asp-box sequences characteristic of sialidases and showing overall 83% and 39% identities to the bovine and rat enzymes, respectively. Northern blot analysis revealed high expression in skeletal muscle and testis, but low level in kidney, placenta, lung, and digestive organs. Transient expression of the cDNA in COS-1 cells resulted in a 130-fold increase in sialidase activity compared to the control level, and the activity was found to be almost specific for gangliosides. Fluorescent in situ hybridization allowed the human sialidase gene localized to chromosome 11 at q 13.5.

Amino Acid Sequence↗
PubMed1999

Altered expression level of a systemic nuclear autoantigen determines the fate of immune response to self.

One of the hallmarks of systemic autoimmune diseases is immune responses to systemic nuclear autoantigens. We have examined the fate of the immune response against a nuclear autoantigen using human U1 small nuclear ribonucleoprotein-A protein (HuA) transgenic (Tg) mice by adoptive transfer of autoreactive lymphocytes. We obtained two Tg lines that have different expression levels of the transgene. After spleen cells from HuA-immunized wild-type mice were transferred to Tg mice and their non-Tg littermates, these recipients were injected with HuA/IFA to induce a recall memory response. HAB69, which expressed a lower amount of HuA, exhibited a vigorous increase in the autoantibody level and glomerulonephritis. Moreover, the autoreactivity spread to 70K autoantigen. Alternatively, in HAB64, which expressed a higher amount of HuA, the production of autoantibody was markedly suppressed. The immune response to HuA autoantigen was impaired as demonstrated in a both delayed-type hypersensitivity response and proliferation assay. This inhibition was Ag-specific and was mediated by T cells. These data suggest that the expression level of systemic autoantigens influences the outcome of the immune response to self.

Adoptive Transfer↗
PubMed1999

Transverse elasticity of myofibrils of rabbit skeletal muscle studied by atomic force microscopy.

Surface structure of myofibrils of rabbit skeletal muscle and their transverse elasticity were studied by atomic force microscopy. Images of myofibrils had a periodic structure characteristic of sarcomeres of skeletal muscle fibers. The transverse elasticity distribution in the sarcomere was determined based on force-distance curves measured at various loci of single myofibrils. The Z-line in rigor myofibrils was the most rigid in all the loci of myofibrils studied under various physiological conditions. The overall transverse elasticity of myofibrils decreased in the order in rigor solution > +AMPPNP solution > relaxing solution. The "apparent" transverse Young's modulus of myofibrils estimated at the overlap region between thin and thick filaments was 84.0 +/- 18.1, 37.5 +/- 14.0, and 11.5 +/- 3.5 kPa in rigor, +AMPPNP, and relaxing solution respectively.

Adenylyl Imidodiphosphate↗
PubMed1999

Molecular cloning and characterization of a plasma membrane-associated sialidase specific for gangliosides.

Gangliosides are plasma membrane components thought to play important roles in cell surface interactions, cell differentiation, and transmembrane signaling. A mammalian sialidase located in plasma membranes is unique in specifically hydrolyzing gangliosides, suggesting crucial roles in regulation of cell surface functions. Here we describe the cloning and expression of a cDNA for the ganglioside sialidase, isolated from a bovine brain cDNA library based on the amino acid sequence of the purified enzyme from bovine brain. This cDNA encodes a 428-amino acid protein containing a putative transmembrane domain and the three Asp boxes characteristic of sialidases and sharing 19-38% sequence identity with other sialidases. Northern blot and polymerase chain reaction analyses revealed a general distribution of the gene in mammalian species, including man, and the mouse. In COS-7 cells transiently expressing the sialidase, the activity was found to be 40-fold that of the control level with ganglioside substrates in the presence of Triton X-100, and the hydrolysis was almost specific to gangliosides other than GM1 and GM2, both alpha2-->3 and alpha2-->8 sialyl linkages being susceptible. The major subcellular localization of the expressed sialidase was assessed to be plasma membrane by Percoll density gradient centrifugation of cell homogenates and by immunofluorescence staining of the transfected COS-7 cells. Analysis of the membrane topology by protease protection assay suggested that this sialidase has a type I membrane orientation with its amino terminus facing to the extracytoplasmic side and lacking a signal sequence.

Amino Acid Sequence↗
PubMed1999

A two-step extraction method to measure fecal steroid hormones in female cynomolgus monkeys (Macaca fascicularis).

We developed a two-step extraction method for measuring fecal steroid concentrations. In the first step, distilled water was used to extract steroids from fecal samples. In the second step, a mixture of organic solvents (hexane and ether) was used to re-extract water extracts that had been transferred to a glass tube. A portion of the upper layer of the organic solvents was transferred to separate assay-tubes for measurement of estradiol (E2) or progesterone (P), and the organic solvents were evaporated in vacuo. After phosphate-buffered saline was added to each tube, commercially supplied radioimmunoassay (RIA) kits were used to determine the steroids. We demonstrated the advantages and reliability of this method by using it to assay the steroid hormone concentrations in fecal samples and serum samples collected on the same day from female cynomolgus monkeys who showed normal menstrual cycles and from monkeys who had induced hyperfunction of ovarian steroidgenesis. Different fecal samples from each monkey were used to determine the recovery rate of each steroid in water extraction from the fecal samples and the reproductivity of hormone concentrations in the fecal samples. The results demonstrate that this two-step method is simple and effective for measuring fecal steroids for monitoring the reproductive status of cynomolgus monkeys, without having to collect serum samples.

Animals↗