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Biomedical subjects

Y Ando

Publications and source records attributed to Y Ando.

At least 109 records · Page 6Linked to original sources
PubMed2000

Mechanism of anemia associated with autonomic dysfunction in rats.

The aim of this study was to elucidate the mechanism of anemia associated with autonomic dysfunction in rats. Using 6-hydroxydopamine (6-OHDA)-treated sympathectomized rats, changes in systolic blood pressure, plasma catecholamine levels, hemograms, erythropoietin (EPO) secretion, and beta-adrenergic receptors on erythrocytes were monitored, and compared with desipramine- and 6-OHDA-treated, and control rats. In 6-OHDA-treated rats, systolic blood pressure and plasma catecholamine levels significantly decreased from 7 days after 6-OHDA administration, returning to the control values on day 28. Hemoglobin (Hb), hematocrit (Hct) and red blood cell (RBC) levels significantly decreased from day 14 to day 28, and reached normal values after day 35, but neither corpuscular constants nor white blood cell (WBC) levels changed after anemia occurred. Administration of desipramine 1 day before 6-OHDA injection prevented anemia. EPO levels did not elevate, even after bloodletting to load anemia, and the EPO circadian rhythm was irregular in 6-OHDA-treated rats. beta-adrenergic receptors measured using 125I-cyanopindolol (CYP) significantly decreased from day 7 to day 28, and reached normal values after day 35. These results suggest that irregular EPO secretion via disordered autonomic nerves may induce anemia in patients with autonomic disorders.

Adrenergic beta-Antagonists↗
PubMed2000

Loss of heterozygosity and microsatellite instability in ductal carcinoma in situ of the breast.

To investigate the alterations of genetic instabilities in carcinogenesis of the breast, we analyzed the allelotypic profile of 65 ductal carcinomas in situ (DCIS), compared with that of 207 invasive ductal carcinomas (IDC) of the breast. These studies were performed by means of examining microsatellite-length polymorphisms at seven loci (AluVpa, ESR, D11S988, D13S267, D16S398, D17S1159, and D17S855) from microdissected paraffin sections. Allelic loss or imbalance, considered a loss of heterozygosity (LOH), tended to be more frequently seen in IDC than in DCIS. In particular, the frequency of LOH at the 17p locus was significantly higher in IDC than in DCIS (42 vs. 23%, P=0.022). LOH in DCIS was most frequently seen at D16S398 (26%). LOH frequency at D16S398 in low- and intermediate-grade DCIS was higher than that in high-grade DCIS, while LOH frequencies at D11S988 and D17S1159 in low- and intermediate-grade DCIS was lower than those in high-grade DCIS. LOH frequency at D11S988 in non-comedo type DCIS was lower than that in comedo type DCIS. Furthermore, the frequency of microsatellite instability (MSI) at only one locus in DCIS (28%) was statistically higher than that in IDC (6%) (P<0.001), while there was no difference between the frequency of MSI at multiple loci in DCIS (6%) and that in IDC (3%). Together, these observations indicate that chromosomal losses of 16q may occur in low- and intermediate-grade DCIS and those of 11p and 17p may occur high-grade DCIS, and that MSI occurring at only one locus is not yet clear and MSI at multiple loci is uncommon in not only IDC but also DCIS of the breast.

Adult↗
PubMed2000

Metal-to-insulator crossover in the low-temperature normal state of Bi(2)Sr(2-x)La(x)CuO(6+delta).

We measure the normal-state in-plane resistivity of Bi(2)Sr(2-x)La(x)CuO(6+delta) single crystals at low temperatures by suppressing superconductivity with 60 T pulsed magnetic fields. With decreasing hole doping, we observe a crossover from a metallic to an insulating behavior in the low-temperature normal state. This crossover is estimated to occur near 1/8 doping, well inside the underdoped regime, and not at optimum doping as reported for other cuprates. The insulating regime is marked by a logarithmic temperature dependence of the resistivity over two decades of temperature, suggesting that a peculiar charge localization is common to the cuprates.

Journal Article↗
PubMed2000

Enhancement of AA-amyloid formation in mice by transthyretin amyloid fragments and polyethylene glycol.

The mechanism behind amyloid formation is unknown in all types of amyloidosis. Several substances can enhance amyloid formation in animal experiments. To induce secondary systemic amyloid (AA-type amyloid) formation, we injected silver nitrate into mice together with either amyloid fibrils obtained from patients with familial polyneuropathy (FAP) type I or polyethylene glycol (PEG). Mice injected with silver nitrate only served as controls. Amyloid deposits were detectable at day 3 in animals injected with amyloid fibrils and in those injected with PEG, whereas in control mice, deposits were not noted before day 12. Our results indicate that amyloid fibrils from FAP patients and even a non-sulfate containing polysaccharide (PEG) have the potential to act as amyloid-enhancing factors.

Amyloid↗
PubMed2000

Comparative studies of two transthyretin variants with protective effects on familial amyloidotic polyneuropathy: TTR R104H and TTR T119M.

Recently, a new nonpathogenic transthyretin (TTR) variant-TTR R104H (TTR H104)-has been described in heterozygotic and compound heterozygotic individuals from a Japanese family with familial amyloidotic polyneuropathy (FAP). The compound heterozygotic individual, a carrier of TTR V30M (TTR M30) and TTR R104H (TTR M30/H104) presented a very mild form of FAP with slow progression of the disease. TTR and retinol binding protein (RBP) levels were found to be increased in serum from TTR H104 carriers. These characteristics are very similar to those found in compound heterozygotic carriers of TTR V30M-T119M (TTR M30/M119). To structurally compare these variants, we performed stability and thyroxine (T(4)) binding studies. TTR M30/H104 showed an increased resistance to dissociation into monomers similar to TTR M30/M119. This suggests that the His104 substitution has the same stabilizing effect on tetrameric TTR as the Met119 substitution. Concerning T(4) binding, TTR H104 presents a T(4) binding affinity lower than that of TTR M119, but still higher than normal TTR. However, TTR from the compound heterozygotic carrier of TTR M30/H104 presented a T(4) binding affinity lower than normal. The results indicate that the His 104 substitution induces structural alterations that increase the stability of the tetramer in compound heterozygotes for TTR M30 despite a lower affinity for T(4) binding. Thus, stability of TTR and binding affinity for T(4) may not be related. More detailed characterization of these variants is needed to clarify the structural alterations responsible for their increased stability.

Amino Acid Substitution↗
PubMed2000

Oxidative injury is present in Purkinje cells in patients with olivopontocerebellar atrophy.

To verify the presence of lipid peroxidation products in spinocerebellar degeneration (SCD), the cerebella from eight patients with olivopontocerebellar atrophy (OPCA) and six non-OPCA patients were immunohistochemically investigated with 4-hydroxy-2-nonenal (HNE) antibody. On average, 84.6% of Purkinje cells were positively or strongly positively immunostained in OPCA patients while only 15.5% were positive in non-OPCA patients. Other cells in the molecular and granular layers showed no obvious immunoreactivity. These data suggest that a lipid peroxidation product is present in Purkinje cells of OPCA patients and that oxidative stress may play an important role in the degeneration process of SCD.

Aged↗
PubMed2000

Effect of sildenafil citrate (Viagra) on erectile dysfunction in a patient with familial amyloidotic polyneuropathy ATTR Val30Met.

A 34-year-old male patient with familial amyloidotic polyneuropathy (FAP) amyloidogenic transthyretin (ATTR) Valine30Methionine (Val30Met), who underwent a liver transplantation in Sweden in 1994, was treated with sildenafil citrate (Viagra) to ameliorate his erectile dysfunction (ED). Some clinical symptoms and the examination data for autonomic functions were improved after liver transplantation, but ED was never improved after the operation. Five years after liver transplantation, he requested a sildenafil citrate therapy to enhance his erectile potential. One and a half hours after the administration of 25 mg of sildenafil citrate, the skin surface temperature around the pelvic area increased and the penis became erect, though the postdose hemodynamic parameters did not significantly change from the respective baseline or predose values. He was able to have sexual intercourse, though ejaculation did not occur. This case report appears to suggest that sildenafil citrate is an effective drug to treat ED in patients with an organic impairment of the autonomic nervous system without altering systemic circulation.

Adult↗
PubMed2000

A new diagnostic procedure to detect unknown transthyretin (TTR) mutations in familial amyloidotic polyneuropathy (FAP).

Two patients with amyloidosis caused by transthyretin (TTR) were investigated by immunohistopathologic, mass spectrometric, and molecular genetic methods. After confirming the immunoreactivity of TTR in the amyloid deposits using anti-TTR polyclonal antibody, a new method: centrifugal concentration and electrospray ionization mass spectrometry (ESI-MS) was employed to detect the variant TTR in the serum. Only 50 microl of the serum and 30 microl of the anti-TTR antibody were needed for the analysis. After incubation with the antibody, the samples were passed through a 1000 kDa cut off centrifugal concentrator to retain the antibody, thereafter, the filtrate was analyzed by ESI-MS. Several forms of normal and variant TTR were detected in the serum samples: unconjugated TTR, cysteine and cysteine-glycine conjugated TTR. In the patients, a variant form of TTR was detected with a 26.0 Da higher molecular weight than that of normal TTR. Single-strand conformation polymorphism (SSCP) and direct sequence analysis confirmed the presence of a one-base substitution situated at the codon 50 from AGT (Ser) to ATT (Ile) in both patients, that corresponded to the increased molecular weight of 26.0. The present diagnostic procedure demonstrates the usefulness of both ESI-MS and SSCP to screen for TTR related amyloidosis rapidly. Moreover, the DNA samples obtained from the band showing abnormal electrophoretic migration pattern in SSCP, facilitate the direct sequence analysis to detect the unknown mutation, and the observed shift in molecular weight of the variant TTR in ESI-MS confirms the base substitution.

Amino Acid Substitution↗
PubMed2000

Endothelium-dependent vasodilatation in patients with familial amyloidotic polyneuropathy.

We examined endothelium-dependent vasodilatation in 15 familial amyloidotic polyneuropathy (FAP) amyloidogenic transthyretin (ATTR) Valine30Methionine (Val30Met) patients and 12 healthy volunteers. Using ultrasonography, we measured the radial artery diameters under both baseline and hyperemic conditions. Endothelium-dependent vasodilatation was expressed as a percent increase in the diameters of the radial artery after induced hyperemia. Endothelium-dependent vasodilatation tended to decrease in the patients, compared with healthy volunteers. Responses were not elicited at all in patients with disease of more than 9 years' duration. Linear negative correlation was observed between endothelium-dependent vasodilatation and disease duration (P < 0.01). Correlation between endothelium-dependent vasodilatation and degree of autonomic dysfunction was significant (P = 0.0524) and for age was close to significance (P = 0.051). These results suggest that the peripheral vasomotor dysfunction in FAP patients may predominantly depend on the amount of amyloid deposition around the vessels through the course of illness.

Adult↗
PubMed2000

Expression of estrogen receptor alpha exon 5 and 7 deletion variant in human breast cancers.

BACKGROUND: An exon deletion variant of estrogen receptor (ER) mRNA has been reported, as one of the possible mechanisms of loss of ER function. METHODS: We examined the expression of exons 3, 5, and 7 in ER alpha mRNA and the frequency of exon deletion variant expression in 64 cases of human breast cancers and in 8 non-cancerous breast tissues using reverse transcriptase polymerase chain reaction (RT-PCR). RESULTS: Approximately the same amount of wild-type (wt) mRNA was detected in all the non-cancerous breast tissues. In cancers, expression of wild-type exon 3 (w3), exon 5 (w5), and exon 7 (w7) was detected in 93.5%, 93.5%, and 91.3% of ER alpha protein (pER) positive cases, respectively, and 27.8%, 38.9%, and 44.4% in negative cases, respectively (p < 0.0001, p = 0.0035, and p = 0.0002). Although the variants for exon 5 (d5) and 7 (d7) were detected in both non-cancerous and cancerous tissues respectively, the variant for exon 3 was not detected at all. Comparatively, the ratio of d5/w5 was significantly higher in pER positive and progesterone receptor protein (pPgR) negative cases. CONCLUSIONS: We suspect that the exon 5 deletion does not work as a dominant positive.

Breast↗
PubMed2000

Comparison of five different antibodies in the immunohistochemical assay of estrogen receptor alpha in human breast cancer.

BACKGROUND: Estrogen receptor alpha (ER) expression is the best prognostic and predictive factor of hormone dependency of human breast cancers. Unlike enzyme immunoassay (EIA), which has been widely used to evaluate ER status in breast cancer, immunohistochemical assay (IHC) can detect ER in a small amounts of tissue with detailed localization. Although there is a sufficient number of ER antibodies against various regions of the protein, the reliability of IHC staining is only well understood for a few. IHC and EIA for the evaluation of the ER status of human breast cancer, therefore, should be compared using the same breast cancer tissues. METHODS: Five different ER antibodies (1D-5, C-314, G-20, C-311 and HC-20) that identify different amino acid sequences were used. The evaluation of ER status by IHC using these antibodies was compared with EIA concomitantly in 97 primary human breast cancer tissues RESULTS: The positivity rate for EIA was 68%. That of IHC for antibodies 1D-5, C-314, G-20, C-311 and HC-20 was 50.5%, 47.4%, 46.4%, 44.3% and 57.7%, respectively. The concordance between EIA was 76.3% for 1D-5 and 77.3% for HC-20, which is statistically highly significant (p<0.0001); Other antibodies were not. CONCLUSIONS: HC-20 is most suitable in the evaluation of the ER status of human breast cancers using the IHC method. Although antibody 1D-5 is also available, C-314, G20 and C-311 are unreliable in such an evaluation.

Antibodies↗
PubMed2000

Role of ultrasonography in the detection of intraductal spread of breast cancer: correlation with pathologic findings, mammography and MR imaging.

The purpose of this study was to assess the role of US in the detection of intraductal spread of breast cancer in comparison with mammography (MMG) and MRI. In 46 patients with breast cancer, US features of the intraductal component were classified as ductal type or distorted type. Histopathologically, 29 of 46 (63%) cases had intraductal components, and the sensitivity, specificity, and accuracy rates in detection of intraductal spread were 89, 76, and 85%, respectively. Each US pattern demonstrated good correspondence to the histologic components, and the distorted type correlated well with comedo-type carcinoma. Mammography was performed in all cases, and the sensitivity, specificity, and accuracy rates in detection of intraductal spread were 55, 100, and 72%, respectively. In comedo type, MMG could diagnose the extent of intraductal spread more accurately compared with US examination. Magnetic resonance imaging comparison was available in 25 cases. Magnetic resonance imaging depicted intraductal extension as an enhanced area during the early phase of a contrast enhancement study with a sensitivity of 93%. Ultrasound and MRI were closely related in terms of morphologic characteristics: the ductal type of US image correlated well with linear enhancement on MRI, whereas the distorted type correlated with regional or segmental enhancement. Current US examination is useful in depicting the intraductal spread of breast cancer; however, US has a tendency to underestimate intraductal component of comedo type compared with MMG and MRI.

Breast↗
PubMed2000

The missing fundamental phenomenon in temporal vision.

Subjective flicker rates were measured for compound waveforms consisting of five harmonics without a fundamental component. It was found that observers perceived a rate at the fundamental frequency, although energy at this frequency was not included in the signals. In auditory pitch sensation this is called the missing fundamental phenomenon, and an analogous finding is known to occur in spatial vision. Moreover, observers perceived the flicker rates at the fundamental frequency even in the random-phase conditions, in which the period of the fundamental component is unclear in the real waveforms. The results indicate that the perceived flicker rates are not detected from the temporal waveforms per se. One possible mechanism for extracting such a periodicity in the signal is an auto-correlation function to the real temporal waveforms.

Adult↗
PubMed2000

Familial amyloidotic polyneuropathy (ATTR Ser50Ile): the first autopsy case report.

We report an autopsy case of a pedigree of familial amyloidotic polyneuropathy (FAP) with a mutation of isoleucine-50 transthyretin (ATTR Ser50Ile). A 47-year-old man started developing severe diarrhea and weight loss at age 41 years, followed by urinary incontinence, autonomic-nervous-system abnormalities and serious heart failure; the diagnosis of FAP (ATTR Ser50Ile) was made on the basis of genetic, histochemical and immunohistochemical analysis. Six years after the initial symptoms, he died of septic shock. Autopsy revealed suppurative peritonitis, perforation of the sigmoid colon and marked systemic amyloid deposition. The total amount of amyloid deposited in the heart was greatly increased and was much lower in the thyroid gland and kidneys compared with amyloid deposits in ordinary FAP (ATTR Val30Met). Amyloid deposition in peripheral vessel walls was prominent, particularly in lymphatics and veins. His elder sister, 54 years old, started to develop orthostatic hypotension at age 49 years, followed by dysesthesia, diarrhea and severe congestive heart failure. Endomyocardial biopsy revealed severe TTR-amyloid deposition; ultrastructural examination demonstrated that amyloid fibrils were deposited disproportionately and extended radially around microvessels.

Aged↗
PubMed2000

Reinvestigation of positional distribution of fatty acids in docosahexaenoic acid-rich fish oil triacyl-sn-glycerols.

Positional distribution of fatty acids in triacyl-sn-glycerols of docosahexaenoic acid (DHA)-rich tuna orbital and bonito head oils has been reanalyzed by a method based on chromatographic separation of isomeric and enantiomeric monoacyl-sn-glycerol (MAG) derivatives. When boric acid thin-layer chromatography (TLC) was used for separation of 1(3)- and 2-MAG analytical intermediates, the stereospecific analysis showed the preferential association of DHA to the sn-2 position followed by the sn-3 position. This distribution pattern differed from that obtained by silicic acid TLC of their bis-3,5-dinitrophenylurethane (DNPU) derivatives. Reversed-phase high-performance liquid chromatography elution profiles of 1(3)- and 2-MAG intermediates revealed that 1(3)- and 2-MAG made up of both short- and long-chain lengths cannot be clearly resolved by TLC after preparation of the DNPU derivatives. The 1(3)- and 2-MAG must be resolved by boric acid TLC prior to derivatization.

Animals↗