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Biomedical subjects

Y Hara

Publications and source records attributed to Y Hara.

At least 145 records · Page 8Linked to original sources
PubMed2000

[Carotid artery disease in patients with retinal vein and artery occlusion].

To evaluate carotid artery disease in patients with retinal vein occlusion (RVO) and with retinal artery occlusion (RAO), 41 RVO patients (male 21, female 20, mean age 63 +/- 12 years) and 59 RAO patients (male 39, female 20, mean age 66 +/- 12 years) were investigated. All patients were examined neurologically and underwent carotid ultrasound examination. Using carotid ultrasound, carotid artery disease was evaluated in terms of presence of plaque, echogenicity of the plaque, degree of stenosis, or presence of ulceration. Carotid plaque or occlusion of the carotid artery was observed more frequently in RAO patients than in RVO patients (ipsilateral side: p < 0.01, contralateral side: p < 0.001; Fisher's exact test). Heterogeneous plaque was found more frequently in RAO patients compared to RVO patients (ipsilateral side: p < 0.01, contralateral side: p < 0.02; Fisher's exact test). Ulcerated plaque was found only in patients with RAO. In conclusion, carotid artery disease was more frequently found in patients with RAO than in patients with RVO.

Aged↗
PubMed2000

[Clinical evaluation of cases with massive ascites accumulation after discontinuation of CAPD: an attempt to establish the concept of the pre-sclerosing encapsulating peritonitis(pre-SEP) state].

Sclerosing encapsulating peritonitis(SEP) is a most serious complication of continuous ambulatory peritoneal dialysis(CAPD). Although the criteria of diagnosis and guidelines for therapy of SEP have been proposed by the Japanese SEP Study Group already, SEP is refractory to treatment when the disease process is complete. It is important to detect the latent phase of SEP(pre-SEP state) in order to treat patients at an early stage. We evaluated the characteristics of ascites in four patients with massive ascites accumulation after discontinuation of CAPD. Age and the duration of CAPD of the subjects were 53.3 +/- 9.7 years and 126.5 +/- 6.8 months, respectively. However, the patients were withdrawn from CAPD because of peritonitis or ultrafiltration failure. We also followed cytokines and parameters of collagen metabolism of ascites in two patients during adrenocorticosteroid therapy and conducted a histopathological evaluation of the peritoneum of an autopsy case who had died of pneumonia. Ascites seems to be exudative because of the high concentration of protein, cytokines and parameters of collagen metabolism such as interleukin-1 beta, interleukin-6, transforming growth factor-beta 1, procollagen 3 peptide, and type IV collagen 7S, the levels of which were 21.3 +/- 9.3 pg/ml, 8,153 +/- 7,327 pg/ml, 6.7 +/- 3.6 ng/ml, 89.3 +/- 67.8 U/ml, and 59.0 +/- 36.2 ng/ml, respectively. The histopathological findings of the peritoneum from the autopsy case showed dense fibrous tissue permeated with inflammatory infiltration and widespread infiltration of fibrin. These findings suggested that the peritoneum was inflamed when massive ascites accumulated. The amount of ascites and concentration of cytokines and parameters of collagen metabolism of ascites diminished during adrenocorticosteroid therapy. We concluded that massive and refractory accumulation of ascites appearing after the discontinuation of CAPD should be regarded as a sign of the pre-SEP state, and prophylactic treatment should be started at this stage of disease.

Adult↗
PubMed2000

Molecular mechanism of doxorubicin-induced anticholinergic effect in guinea-pig atria.

The molecular mechanisms of anticholinergic actions of doxorubicin were examined by electrophysiological methods in atria and myocytes isolated from guinea-pig heart. A direct anticholinergic action of doxorubicin was confirmed with antagonistic action on carbachol-induced negative inotropic effect in atria. Both carbachol and adenosine produced shortening of action potential duration in atria measured by a microelectrode method. Doxorubicin (10-100 microM) inhibited the carbachol-induced action potential shortening in a concentration-dependent manner. However, doxorubicin did not antagonize the shortening elicited by adenosine. The whole-cell voltage clamp technique was performed to induce the muscarinic acetylcholine-receptor-operated K+ current (IK.ACh) in atrial myocytes loaded with GTP or GTPgammaS, a nonhydrolysable analogue of GTP. Doxorubicin (1-100 microM) suppressed carbachol-induced IK.ACh in a concentration-dependent manner (IC50 = 5.6 microM). In contrast, doxorubicin (10 and 100 microM) suppressed neither adenosine-induced IK.ACh nor GTPgammaS-induced IK.ACh. These results indicate that doxorubicin produces a direct anticholinergic effect through the muscarinic receptors in atrial myocytes.

Adenosine↗
PubMed2000

[Supplementary motor area epilepsy associated with ADHD in an abused history].

A 6-year-old girl with attention-deficit hyperactivity disorder (ADHD) who had been abused by her mother in infancy developed supplementary motor area (SMA) epilepsy. The seizure was characterized by bilateral tonic seizure of the upper and lower extremities, speech arrest, preserved consciousness and a lack of postictal confusion. The duration of the seizure was usually 10-60 seconds. The seizures sometimes clustered. She was diagnosed as having SMA epilepsy based on the characteristic clinical symptoms, interictal EEG, ictal video-EEG and ictal SPECT. Though her seizure was initially improved by anti-epileptic drugs, the symptoms appeared again after discharge. Since her clinical course indicated that her seizure was aggravated by her mental state, treatment included both medication with anti-epileptic drugs and the adjustment of her living environment in cooperation with a child guidance clinic. Thereafter both her epileptic seizure and ADHD symptoms improved. These changes may be related to each other, because both conditions are associated with frontal lobe dysfunction. It was interesting that the adjustment of the environment improved frontal lobe epilepsy, which in turn ameliorated ADHD symptoms.

Attention Deficit Disorder with Hyperactivity↗
PubMed2000

Early tumor growth in metastatic organs influenced by the microenvironment is an important factor which provides organ specificity of colon cancer metastasis.

We have previously demonstrated that liver metastases in nude mice and lung metastases in nude rats occurred specifically, when KM12SM human colon carcinoma cells were inoculated orthotopically into the cecal wall of nude mice and rats. To clarify the relationship between the tumor growth potential in the metastatic organs and the metastatic organ preference in these two metastatic models, we have evaluated the in vitro cell growth activities affected by the organ conditioned medium (CM) from the liver and lung, and the in vivo growth activities of the ectopic implanted tumors in the liver and lung. The tumorigenicity of the ectopic implanted tumors was 100% in mouse liver, 33% in rat liver, 50% in mouse lung, and 75% in rat lung. The crude liver CM of the animals showed inhibitory activities for KM12SM cell growth in a dosage-dependent manner, and the crude lung CM stimulated KM12SM cell growth. The liver CM of nude mice inhibited the KM12SM cell growth more strongly compared with the CM of nude rats, and the lung CM of nude rats was more strongly stimulated compared with the CM of nude mice. The liver CM of nude mice had non-heparin binding factors, which stimulated or inhibited KM12SM cell growth, in a molecular weight range of 50 to 100 kDa. By contrast, the liver CM of nude rats showed no growth stimulating activity for KM12SM cells. These results suggest that the metastatic organ specificity of KM12SM cells may depend on the early tumor growth influenced by the microenvironment in metastatic organs.

Animals↗
PubMed2000

Structural requirements of muramylpeptides for induction of Toll-like receptor 2-mediated NF-kappaB activation in CHO cells.

We previously demonstrated that Gram-positive bacteria activated immune cells via CD14 and Toll-like receptor 2 (TLR2). Although peptidoglycan, a major constituent of the bacterial cell wall, substituted for whole organisms, the essential structure of muramylpeptides required to stimulate the cells is not clear. We further investigated the critical determinant for recognition by CD14 and TLR2. Chinese hamster ovary (CHO) fibroblasts, which do not express a functional TLR2 transcript, were transfected with TLR2 or TLR4. These cells were exposed to freeze-dried Staphylococcus epidermidis and were subsequently subjected to the pro-inflammatory transcription factor nuclear factor-kappaB (NF-kappaB)-dependent CD25 expression assay. Heterologous expression of human TLR2, but not TLR4, in CHO cells conferred immune responsiveness to freeze-dried S. epidermidis. A preparation of peptidoglycan from S. epidermidis substituted for whole organisms. Staphylococcus aureus lytic enzyme-digested product (SEPS) from peptidoglycan retained the activity, but hydrolysis of the glycan backbone in SEPS by M-1 endo-N-acetylmuramidase resulted in loss of the activity. These findings showed that cellular activation by Gram-positive cell wall components was mediated by TLR2, but not TLR4, and indicated that the glycan backbone of peptidoglycan is critical for TLR2-mediated NF-kappaB activation.

Acetylmuramyl-Alanyl-Isoglutamine↗
PubMed1999

Clinical Significance of Estrogen Receptor Àin Breast Cancer.

To estimate the clinical significance of estrogen receptor (ER) beta in breast cancer we reviewed some reports and compared them with our preliminary results. The structure of ERbetais similar to that of ER alpha. The DNA binding domain of ER beta is 96% conserved compared with ER alpha, and the ligand binding domain shows 58% conserved residues, suggesting that both receptors can bind estrogen responsiveelements on target genes and that they may also bind similar ligand. The targettissues of ER beta such as testis, prostate, lung, brain, thymus, and ovary, are different from those of ER alpha, ovary, uterus, endometrium, and breast. Although the function of ER beta in breast cancer progression is not well understood, 30-50% of breast cancers may express ER beta mRNA signals. Additionally, ER beta may be auseful prognostic factor in patients with breast cancer, because tumors that co-expressed ER alpha and ER beta might be node positive and tend to be of higher grade.Further characterization of the function of ER beta and its isoforms in breast cancer is warranted.

Journal Article↗
PubMed1999

Glycogen storage disease type Ib: structural and mutational analysis of the microsomal glucose-6-phosphate transporter gene.

Glycogen storage disease type Ib is caused by a mutation in the gene encoding microsomal glucose-6-phosphate (G6P) transporter. We determined the exon/intron organization of the G6P transporter gene. Four overlapping genomic fragments containing the entire coding region of the gene were amplified by polymerase chain reaction (PCR) using exonic primers, and their nucleotide sequences were determined. The gene spans 4.5 kb and has eight exons. All exon/intron boundaries adhered to the canonical AG/GT rule. We then designed eight pairs of PCR primers to amplify all coding exons for a mutational analysis and studied five Japanese patients with the disease. Two novel homozygous mutations were identified in two families: a three-base deletion (delV235) in exon 2 in a consanguineous family and a splicing mutation (IVS7+1G-->T) in intron 7 in a nonconsanguineous family. Patient 3 was a compound heterozygote of W118R and IVS1+1G-->A, both of which we previously identified [Kure et al., 1998: Biochem Biophys Res Commun 248:426-431]. Patients 4 and 5 were homozygotes of W118R. Including our previous study, we found a total of ten W118R alleles in nine Japanese patients. The results support our previous suggestion that W118R is prevalent among Japanese patients. The genomic sequence data and mutation spectrum obtained from the Japanese patients will facilitate genetic diagnosis of glycogen storage disease type Ib.

Antiporters↗
PubMed1999

Mode of action of a new indolocarbazole anticancer agent, J-107088, targeting topoisomerase I.

J-107088 [6-N-(1-hydroxymethyl-2-hydroxy)ethylamino-12,13-dihydro-2,10-dihydroxy- 13-(beta-D-glucopyranosyl)-5H-indolo[2,3-a]-pyrrolo[3,4-c]-carb azo le-5,7(6H)-dione] is a new derivative of NB-506, an indolocarbazole antitumor agent. J-107088 induced single-strand DNA cleavage only in the presence of topoisomerase I (top1) more effectively than NB-506 or camptothecin. The preferable sequences of the DNA cleaved by J-107088 were C/T / G as in the case of NB-506. This base-preference of J-107088 in top1-mediated cleavage was different from that of camptothecin, which was T / G/A. top1 poisons stabilize the complex between DNA and top1 (cleavable complex). This cleavable complex is released on addition of a high concentration of monovalent cation or removal of top1 poisons. The complex induced by J-107088 was quite stable; it was scarcely released on the addition of NaCl or dilution of J-107088, contrary to the case with camptothecin and NB-506. J-107088-inducing complexes were also stable in cultured cells, when the compound was added to the culture medium. These unique in vitro activities of J-107088 on top1 that differed from those of camptothecin and NB-506 may be relevant to its more potent in vivo antitumor efficacy in a human tumor xenographted nude mouse model.

Animals↗
PubMed1999

Consecutively Occurring Multiple Fibroadenomas of the Breast Distinguished from Phyllodes Tumors by Clonality Analysis of Stromal Tissue.

We present a woman with consecutively occurring multiple fibroadenomas of thebreast distinguished from phyllodes tumor by clonality analysis of stromal tissue. Fifty-three masses developed in her right breast in an 11.5 year period since first onset. A clonality analysis, performed by polymerase chain reaction (PCR), focused on the Hpa II site within exon 1 of the androgen receptor (AR) gene. Estrogen receptor (ER) alpha immunohistochemistry was performed with a specific polyclonal antibody against the hormone binding domain of the protein. Since all of the nodules were polyclonal in stromal tissues, they were hyperplastic rather than true neoplasms such as phyllodes tumors. The co-existence of abundant adenosisfoci and numerous sub-clinical small nodules in the adjacent breast tissue alsosuggested proliferative stimuli throughout the breast. ER alpha protein was expressed only in the nuclei of epithelial cells. The possible influence of ER positive epithelial cells on stromal cell growth is discussed.

Journal Article↗
PubMed1999

Down regulation of the prepro-orexin gene expression in genetically obese mice.

The gene expression of prepro-orexin, the precursor of orexin-A and orexin-B which are hypothalamic pepetides that are associated with feeding behavior, were examined in control (C57B1/6J) and obese (ob/ob and db/db) mice using in situ hybridization histochemistry. Orexins are identical with hypocretins that have been identified by directional tag PCR subtractive hybridization method. In situ hybridization histochemistry revealed that the expression of the prepro-orexin gene was significantly decreased in ob/ob and db/db mice compared with control mice. The gene expression of neuropeptide Y (NPY), a potent feeding stimulant, is known to be increased in ob/ob and db/db mice. The expression of the NPY gene in the arcuate nucleus was increased remarkably in ob/ob and db/db mice compared to that of control mice. An immunohistochemical study showed that orexin-A and orexin-B immunoreactive neurons exhibited in the lateral and posterior hypothalamic areas and the perifornical nucleus were distributed similarly in control, ob/ob and db/db mice. These results suggest that the regulatory mechanism of orexins/hypocretins may be different from that of NPY in genetically obese mice.

Animals↗
PubMed1999

Novel splice site mutation at IVS8 nt 5 of HEXB responsible for a Greek-Cypriot case of Sandhoff disease.

Sandhoff disease is caused by abnormalities in HEXB gene encoding the beta-subunit of beta-hexosaminidase. In this study, we analyzed the HEXB gene of a Sandhoff carrier in the Greek-Cypriot community. A G to C transversion was identified in one allele of her HEXB gene at position 5 of the 5'-splice site of intron 8 (IVS8 nt5). One of 13 cDNA clones derived from her lymphocyte HEXB mRNA lacked the last four nucleotides "GTTG" of exon 8, which created a premature termination codon at 11 codons downstream. In vivo transcription of the mutant HEXB gene fragment in CHO cells resulted in deletion of the "GTTG." The mutation has not been found in 40 DNA samples from anonymous donors, indicating that this is not a polymorphism in the Cypriot population. These results clearly indicate that the splice site mutation at IVS8 nt5 is responsible for this case of Sandhoff disease.

Bacterial Proteins↗
PubMed1999

Determination of corneal gel dynamics.

From observations of the dynamics of light scattered by the cornea, intensity autocorrelation functions that revealed two independent diffusion coefficients, D (fast) = 2.4 +/- 0.2 x 10(-7) cm2/s and D (slow) = 9.4 +/- 1.3 x 10(-9) cm2/s, were obtained. The diffusion coefficients were found to be statistically independent of the position and depth on the lateral surface of the cornea from which the scattered light was sampled. The slow diffusion coefficients obtained from light sampled from within cross-sections of the cornea were, however, measurably different. Diffusion coefficients obtained independently from observations of the kinetics of corneal swelling for comparison were found to be several orders of magnitude greater than those obtained from light scattering. The large disparity in the diffusion coefficients obtained from the two independent methods invoked the possibility that the lamellar layers within the cornea behave as individual gel sheets. Irrespective of this additional hypothesis, divergent behavior in the measured total scattered light intensities and diffusion coefficients upon varying external conditions, such as temperature or pressure (stretching), was observed. Namely, a slowing down of the dynamic modes accompanied by increased "static" scattered light intensities was observed. Although the slowing down of the dynamic modes is possibly indicative of the reduced affinity of protein binding to the gel matrix that "softens" the gel, the divergent behavior in the scattered light intensities and diffusion coefficients is, however, more characteristic of a phase transition. In addition, the divergent behavior in the scattered light intensities and diffusion coefficients was reversible up to a critical temperature (approximately 50 degrees C) or stretching (approximately 16%).

Animals↗
PubMed1999

Prominent medial hypertrophy of renal arterioles in an infant with hyporeninemic hypoaldosteronism.

We describe an 11-month-old boy who presented clinically with hyperkalemic renal tubular acidosis due to hyporeninemic hypoaldosteronism. Persistent hyperchloremic acidosis and mild azotemia were present. All abnormal laboratory values were corrected by the administration of fludrocortisone. Renal biopsy showed prominent medial hypertrophy of renal arterioles and interstitial fibrosis, which closely resemble those of the gene-targeted mice with disruption of the renin angiotensin system. This is the first case report raising the possibility that a defective renin angiotensin system in infancy may lead to tubulointerstitial damage with medial hypertrophy of intrarenal arterioles.

Arterioles↗
PubMed1999

Preparation of specific antisera to 15alpha-hydroxyestrogen 15-N-acetylglucosaminides.

3-(1-Carboxypropyl) ether derivatives of 15alpha-hydroxyestradiol 15-N-acetylglucosaminide (15alpha-OHE2 15NAG) and 15alpha-hydroxyestriol (E4) 15NAG were synthesized and conjugated with bovine serum albumin. Antisera elicited in rabbits possessed high affinity and specificity for the 15alpha-hydroxyestrogen (15alpha-OHEs) 15NAG, exhibiting no significant cross-reactivity with 15alpha-OHEs and their positional isomers such as 16NAG and 17NAG. Enzyme immunoassay methods developed by using the purified antisera and horseradish peroxidase-labeled antigens were applied to the measurement of 15alpha-OHEs 15NAG and E4 15NAG in normal pregnancy urine. We demonstrated for the first time that the conjugation of N-acetylglucosamine to E4 occurs at the C-15alpha position.

Animals↗
PubMed1999

Preparation of specific antisera to 15alpha-hydroxyestrogens.

The synthesis of haptens of 15alpha-hydroxyestrone, 15alpha-hydroxyestradiol, and 15alpha-hydroxyestriol (estetrol) was undertaken, to obtain specific antisera required for enzyme immunoassay. 3-(1-Carboxypropyl) ethers of these 15alpha-hydroxyestrogens were prepared and conjugated with bovine serum albumin and horseradish peroxidase. The specificity of antisera elicited against bovine serum albumin conjugates was checked by the enzyme immunoassay by using horseradish peroxidase-labeled antigen, and proved to be satisfactory in terms of cross-reactivities to related compounds.

Animals↗