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Biomedical subjects

Y Miyake

Publications and source records attributed to Y Miyake.

At least 127 records · Page 7Linked to original sources

Retinal dysfunction in basigin deficiency.

PURPOSE: To examine the retina of basigin (Bsg) knockout mice by electrophysiological and histologic methods and thereby to determine the possible function of Bsg in phototransduction and retinal development. METHODS: Scotopic and photopic electroretinograms (ERGs) were recorded from 11 wild-type, 12 heterozygous, and 8 homozygous Bsg gene knockout mice of different ages. The retinas were also examined by histologic and immunolabeling methods. RESULTS: Bsg knockout mice of 5 to 41 weeks of age showed a decrease in the amplitude of all components of both the photopic and scotopic ERGs. In contrast, the fundus and the fluorescein fundus angiography and morphology of the retina at the light microscopic level appeared to be normal until 8 weeks of age in Bsg knockout mice. Thereafter, the length of outer segment and outer nuclear layers decreased with increasing age. Immunohistochemical analysis localized Bsg protein in a variety of cells in the retina, especially in the pigment epithelium, the upper outer plexiform layer and the inner segments of photoreceptor cells. CONCLUSIONS: The results demonstrated that both rod and cone function were severely affected from an early age by the targeted disruption of the Bsg gene. In spite of abnormal ERGs, the photoreceptor cells maintained normal morphology up to 8 weeks. Thereafter, the photoreceptor cells degenerated gradually and were almost ablated by 41 weeks.

Animals↗

A high association with cone dystrophy in Fundus albipunctatus caused by mutations of the RDH5 gene.

PURPOSE: To analyze the RDH5 gene in patients with fundus albipunctatus with and without cone dystrophy and to determine whether the disease is stationary or progressive and whether the cone dystrophy is a part of fundus albipunctatus or a separate disease. METHODS: Fourteen patients from 12 separate Japanese families with fundus albipunctatus were examined. Six of the patients from 6 families also had a cone dystrophy. Genomic DNA was extracted from leukocytes of the peripheral blood, and exons 2, 3, 4, and 5 of the RDH5 gene were amplified by polymerase chain reaction and were directly sequenced. A complete ophthalmic examination was performed including best-corrected visual acuity, slit-lamp examination, indirect ophthalmoscopy, fundus photography, and electroretinography. RESULTS: In all the patients, either a homozygous mutation or compound heterozygous mutations in the RDH5 gene were identified. The identified mutations were nucleotide position (nt) 103 G to A (Gly35Ser), nt 319 G to C (Gly107Arg), nt 394 G to A (Val132Met), nt 719 G insertion (frame shift), nt 839 G to A (Arg280His), nt 841 T to C (Tyr281His), and nt 928 C to GAAG (Leu310 to GluVal). All these mutations except the Arg280His were new. The nt 928 C to GAAG mutation was detected in patients with and without cone dystrophy. Cone dystrophy was most frequently seen in patients over 40 years old. CONCLUSIONS: Fundus albipunctatus either with or without cone dystrophy is caused by mutations of the RDH5 gene. Cone dystrophy is frequently observed in elderly patients with fundus albipunctatus. The conclusion was reached that the mutations of the RDH5 gene caused a progressive cone dystrophy as well as night blindness.

Adolescent↗

[Effectiveness of home help service for psychiatric patients. The results of a model project in S city].

PURPOSE: The purpose of this study was to evaluate the effectiveness of a home help service project for psychiatric patients in S city. METHODS: To assess the effectiveness of the home help service, home help service providers at S city in 1997 were invited to hearings and the transcripts were examined qualitatively. Based on the results, interview questions were developed. We then interviewed 28 home help providers who were providing or had completed the service project, as well as care managers as of July 1998. Home help providers divided their patient stories retrospectively into three time frames: before starting home care, one month after starting providing care and at the present. Amount of care provided and patients' self care level were scored and averages ere compared for the three time frames. RESULTS: The analysis of the hearing data revealed parameters for the effectiveness of home help service for psychiatric patients to be as follows: 1) enhanced ability of daily living, such as taking meals, maintaining hygiene and shopping, (primary effectiveness: 5 items); and 2) developing social function, such as being motivated, maintaining personal relationship, extending social life, and decreasing family burden, (secondary effectiveness: 9 items). The amount of care needed was found to be significantly decreased and social function was significantly enhanced on comparisons between before starting home care and one month later, as well as between before starting home care and the present. DISCUSSION: Home help service for psychiatric patients is not only useful for enhancing patients' ability to succeed in daily living tasks, but also for developing their social functioning. Effectiveness was also identified in the level of patients' behavior. The results provide reasonable grounds for extended use of the home help service.

Home Care Services↗

Low density lipoprotein (LDL) binding affinity for the LDL receptor in hyperlipoproteinemia.

We measured the binding affinity of low density lipoprotein (LDL) for the LDL receptor in patients with various types of hyperlipoproteinemia and investigated the effects of LDL lipid composition and particle size on receptor affinity. LDL (1.019 < d < 1.063) was isolated by sequential ultracentrifugation from the serum of normolipidemic controls and patients with hyperlipoproteinemia. Patients with type IIa hyperlipoproteinemia had LDL with a similar receptor affinity to that of normal LDL. However, patients with hypertriglyceridemia (type IIb and type IV hyperlipoproteinemia) had LDL with a low receptor affinity, and the degree of the reduction in affinity paralleled the severity of the hypertriglyceridemia. The LDL of hypertriglyceridemic patients was rich in protein and triglycerides, had a low content of cholesterol and phospholipids, and was smaller than normal, thus resembling the atherogenic lipoprotein known as small, dense LDL. These abnormalities were observed even in patients with mild hypertriglyceridemia regardless of their serum cholesterol levels. The degree of alteration in LDL lipid composition and particle size was strongly associated with the reduction of LDL receptor affinity. We also examined the effects of two lipid-lowering agents (bezafibrate and probucol) on the characteristics of LDL. LDL receptor affinity was only improved when the lipid composition and particle size were normalized by drug therapy. Although it has been reported that decreased cholesteryl ester transfer protein (CETP) activity results in the formation of small LDL, plasma CETP activity was normal in the hyperlipoproteinemic patients and the normalization of LDL characteristics by drug therapy was not accompanied by an increase of CETP activity. Our results suggested that an abnormal lipid composition and/or small particle size might cause a decrease in the receptor affinity of LDL. These structural and functional abnormalities were reversed by drug therapy, underlining the importance of treating hypertriglyceridemia for the prevention of atherosclerosis.

Adult↗

Detailed localization of photoreceptor guanylate cyclase activating protein-1 and -2 in mammalian retinas using light and electron microscopy.

Guanylate cyclase activating proteins, GCAP-1 and GCAP-2, have a pivotal role in the activation of guanylate cyclase in phototransduction. Previous studies on the localization of GCAP-1 and GCAP-2 are contradictory. In this study, we tried to avoid possible artifacts accompanied by immunocytochemistry. Immunolabeling of a GCAP was carried out using antibodies pre-adsorbed with a different type of GCAP. In addition, immunolabeling was performed using three different animal species under different fixation and embedding. Electron microscopic immunocytochemistry was also performed to reveal subcellular localization of GCAPs as well as confirming data obtained by light microscopy. All data indicate that anti-GCAP-1 antibody binding sites were found predominantly in cone outer segments, in particular, in disk membrane regions. Sparse labeling was observed in rod outer segments, but the labeling was much lower than that seen in cone outer segments. Less labeling is also found in synaptic regions and inner segments of cones. No labeling was detected in connecting cilia and its cytoplasmic extensions. Such labeling patterns were similar among human, monkey and bovine retinas. The localization of GCAP-1 is consistent with the pattern of a recently reported human cone-specific degeneration. Anti-GCAP-2 antibody binding sites were detected in both inner and outer segments of rods and cones of all three animals although the labeling density was slightly different among species. Cryo-immuno-labeling of GCAP-2 in bovine retinas revealed that labeling sites were more concentrated in rods than those of cones, and that synaptic regions were also labeled. The different localization of GCAPs suggest that roles of GCAP-1 and GCAP-2 may be different.

Animals↗

A new method to evaluate ischemic heart disease: combined use of rest thallium-201 myocardial SPECT and Tc-99m exercise tetrofosmin first pass and myocardial SPECT.

We developed a new diagnostic method for simultaneously evaluating myocardial ischemia, myocardial viability and ventricular function in less than 90 minutes by combined use of rest thallium-201 (Tl) SPECT and exercise Tc-99m tetrofosmin (TF) first pass and SPECT. The subjects were 9 healthy controls, 19 angina pectoris patients, and 19 old myocardial infarction patients, in all of whom coronary angiography had been performed. Rest Tl myocardial SPECT was performed first, and was followed by exercise TF myocardial SPECT. We also performed first pass radionuclide angiography by TF during maximum exercise on a bicycle ergometer to assess the left ventricular ejection fraction (LVEF). The total examination time was less than 90 minutes. SPECT diagnosis was performed by semi-quantitative analysis. LVEF below 55% was regarded as abnormal. In the patients with angina pectoris, analysis according to the coronary artery showed that the diagnostic accuracy of SPECT was 85.0% for ischemia in the region of the left anterior descending branch (LAD), 87.5% for the left circumflex branch (LCX) and 77.8% for the right coronary artery (RCA). The accuracy of diagnosis for angina pectoris was 82.1%, as determined by SPECT alone, and rose to 89.3% when the LVEF levels were also taken into consideration. In the patients with old myocardial infarction, the diagnostic accuracy of SPECT was 84.2% for the LAD, 92.3% for the LCX and 85.0% for the RCA. Analysis by patients showed that the accuracy of diagnosis for myocardial infarction was 85.7%, as determined by SPECT alone. The diagnostic accuracy, however, rose to 89.3% when the LVEF levels also were taken into consideration. In conclusion, it was demonstrated that this combined diagnostic method was highly reliable for evaluating ischemic heart disease within a short time.

Aged↗

Open reduction for congenital dislocation of the hip: comparison of the long-term results of the wide exposure method and Ludloff's method.

We compared the long-term clinical and radiographic results of two methods of open reduction for congenital dislocation of the hip; a wide exposure method (360-degree circumferential capsulotomy) versus Ludloff's method (limited capsulotomy via the medial approach). Thirty-one hips in 24 patients assigned to group A received the wide exposure method and 32 hips in 27 patients assigned to group B had the Ludloff reduction. All patients were surgically reduced at less than 3 years of age. The follow-up averaged 16 years. None of the hips in group A required additional operations; however, 34.4% of the hips in group B did. At the latest review, 26 (83.9%) of the hips in group A were rated as Severin class I or II. Except for one patient, none had pain or a limp. Of the hips in group B, 18 (56.3%) were rated as Severin class I or II. Three patients had pain or Trendelenburg gait. Avascular necrosis occurred in 3.2% of hips in group A and in 21.9% of hips in group B. The wide exposure method is capable of completely releasing the posterosuperior tightness resulting from capsular adhesion to the ilium and the contracted short external rotators. Releasing the posterosuperior tightness from these structures seemed to provide a better chance of achieving an anatomically and functionally satisfactory hip.

Acetabulum↗

Abnormal focal macular electroretinograms in eyes with idiopathic epimacular membrane.

PURPOSE: To study the functional state of the retina beneath an epimacular membrane by means of focal macular electroretinography. METHODS: Focal macular electroretinograms of 30 consecutive patients (age 25 to 75 years) with unilateral idiopathic epimacular membrane were recorded prospectively. The amplitudes and implicit times of the a and b waves and the oscillatory potentials (O1, O2, O3) recorded from the eye with idiopathic epimacular membrane were compared with those of the normal fellow eye. RESULTS: There was a statistically significant reduction in the amplitude of the a wave (P < .001), the b wave (P < .001), and the oscillatory potentials (O1 + O2 + O3; P < .001) of the affected eyes. The reduction of the b-wave amplitude was significantly greater than that of the a wave, resulting in a lower b/a wave ratio (P = .003) in the affected eyes. The reduction in the amplitude of the oscillatory potentials was significantly greater than that of the other two components (P < .001). The implicit times were significantly prolonged for the a wave (P < .001), the b wave (P = .004), and 03 (P < .001). There was a significant correlation between relative b-wave amplitude (affected/normal fellow eye) and the visual acuity (r = -0.50, P = .007). These findings were similar to those we reported for eyes with aphakic cystoid macular edema. CONCLUSIONS: The focal macular electroretinograms in eyes with epimacular membrane disclosed abnormalities that were similar to those of eyes with cystoid macular edema. This suggests that the epimacular membrane probably induced damage to the neurons in the inner retinal layers. Dysfunction of these neurons is one possible cause of visual impairment in this disease.

Adult↗

Retinal ganglion cell response properties in the transcorneal electrically evoked response of the visual system.

To identify the retinal origin of a cortical evoked potential elicited by transcorneal electrical stimulation of the visual system (EER), the response properties of retinal ganglion cells (RGCs) of cats to transcorneal electrical stimuli were studied. The discharge latency of RGCs to transcorneal stimulation had two peaks with a high temporal resolution. The latency of early components of the EER is associated with the discharge latency of RGCs. Some RGCs showed prominent oscillatory discharges after transcorneal stimulation. Discharges of ON-bipolar cells responding to transcorneal stimulation were significantly inhibited by intravitreal injection of DL-2-amino-4-phosphonobutyrate (APB), which blocks the ON-pathway. These findings indicate that the EER has far-field potentials that might relate to oscillatory discharges of RGCs, and that ON bipolar cells and their related synaptic sites are involved in transcorneal electrical stimuli. The far-field potentials of the EER may have clinical applications, similar to those of somatosensoric evoked potentials and auditory brain stem potentials.

Aminobutyrates↗

Age-related changes in intraocular pressure in a large Japanese population: a cross-sectional and longitudinal study.

OBJECTIVE: To assess the influence of aging, blood pressure, and body mass index (BMI) on intraocular pressure (IOP) in a large Japanese population. DESIGN: Cross-sectional and longitudinal study. PARTICIPANTS: The participants in this study were 69,643 Japanese men and women 20 to 79 years of age. They were office workers and their family members who had received annual health examinations from 1989 to 1997. The records of the participants who received health examinations were reviewed retrospectively. Each participant was examined according to a standard protocol, including tonometry with a noncontact tonometer, anthropometric measurements, and blood pressure measurements. The data from the subjects' most recent visit were analyzed cross-sectionally. The data from the 68,998 men and women of the total participants who were born between the 1920s and 1960s were used in longitudinal analysis. TESTING: Tonometric and anthropometric measurements. MAIN OUTCOME MEASURES: Mean values of IOP, systolic blood pressure, diastolic blood pressure, and BMI were determined. The relationship among IOP, age, systolic blood pressure, diastolic blood pressure, and BMI was studied using the multiple linear regression model with cross-sectional analysis. In longitudinal analysis, regression coefficients of IOP against age, systolic blood pressure, diastolic blood pressure, and BMI were calculated using the mixed effect model. RESULTS: The mean (+/-standard deviation) IOP values for men and women were 11.9+/-2.5 and 11.5+/-2.4 mmHg, respectively. In cross-sectional analysis, IOP decreased significantly with age (P < 0.001). However, longitudinal analysis showed that IOP increased significantly with age in both men and women (P < 0.001). Systolic blood pressure and BMI were positively correlated to IOP in both the cross-sectional and longitudinal studies. CONCLUSION: The authors found an inconsistency in the change in IOP against age between cross-sectional and longitudinal analysis. It is suspected that birth cohort differences in ocular characteristics influence IOP in the Japanese population.

Adult↗

Relationship of coffee consumption with serum lipids and lipoproteins in Japanese men.

PURPOSE: To examine the relationship of instant coffee and brewed coffee with serum lipids and lipoproteins in Japanese men. METHODS: Study subjects were 4587 male self-defense officials aged 48-56 years who had a preretirement health examination at one of the three hospitals of the Self-Defense Forces from October 1986 to December 1992. A self-administered questionnaire ascertained lifestyle characteristics including consumption of a limited number of foods and beverages by all of the men. Serum concentrations of total cholesterol (TC), triglycerides (TG), and high density lipoprotein (HDL) cholesterol were measured, and low density lipoprotein (LDL) cholesterol levels were calculated from the values of TC, TG, and HDL cholesterol. RESULTS: While the consumption of brewed coffee was unrelated to any parameter of serum lipids and lipoproteins, instant coffee consumption showed a highly significant positive association with serum LDL cholesterol levels and an inverse association with serum TG levels. After adjustment for body mass index, smoking, alcohol use, green tea consumption, rank, and hospital, for each cup of instant coffee per day, LDL cholesterol levels were 0.82 mg/dl (95% confidence interval (CI) 0.29-1.35) higher, and TG levels in a natural log-scale were 0.014 mg/dl (95% CI 0.006-0.022) lower. There was also a tendency for a positive association between instant coffee intake and serum TC levels (trend p = 0.09). HDL cholesterol levels were unrelated to instant coffee consumption. These associations did not change after additional adjustment for selected foods and beverages associated with serum lipids and lipoproteins. CONCLUSIONS: The findings suggest that instant coffee, not brewed coffee, may be associated with raised levels of serum LDL cholesterol and decreased levels of serum TG.

Coffee↗

Identification of coumarins from lemon fruit (Citrus limon) as inhibitors of in vitro tumor promotion and superoxide and nitric oxide generation.

Three coumarins were isolated as siginificant inhibitors of tumor promoter 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced Epstein-Barr virus (EBV) activation in Raji cells from the peel of lemon fruit. They were identified as 8-geranyloxypsolaren (LE-1), 5-geranyloxypsolaren (bergamottin, LE-2), and 5-geranyloxy-7-methoxycoumarin (LE-3), respectively, by spectroscopic analysis. Three isolates had no potential O(2)-scavenging and markedly suppressed TPA-induced superoxide (O(2)(-)) generation in differentiated human promyelocytic HL-60 cells. Furthermore, LE-1 and LE-3 reduced both lypopolysaccharide (LPS) and interferon-gamma (IFN-gamma)-induced nitric oxide (NO) generation in mouse macrophage RAW 264.7 cells. Similarly, they were found to be NO generation inhibitors rather than scavengers by measuring the extracellular L-citrulline levels. The occurrence of these coumarins in a lemon fruit was abundant in the flavedo of the peel based on quantitative analysis using high-performance liquid chromatography (HPLC). The present study suggests that the coumarins in lemon fruit are promising chemopreventive agents by inhibiting radical generation.

Animals↗

Iridal-type triterpenoids with ichthyotoxic activity from belamcanda chinensis

Ichthyotoxic activity-guided fractionation of the hexane and ether extracts of Belamcanda chinensis (Iridaceae) has resulted in the isolation of eleven iridal-type triterpenoids including six new compounds, 3-O-tetradecanoyl-16-O-acetylisoiridogermanal (4), 3-O-decanoyl-16-O-acetylisoiridogermanal (5), belachinal (7), anhydrobelachinal (9), epianhydrobelachinal (10), and isoanhydrobelachinal (11). Structures of the new iridals were determined by spectral and chemical methods. The absolute configuration of isoiridogermanal (1) at C-16 was determined to be R by the modified Mosher's method. Of these compounds, 16-O-acetylisoiridogermanal (3), 7, and spiroiridal (12) exhibited potent ichthyotoxic activity against killie-fish (Oryzias latipes).

Journal Article↗

A novel minor histocompatibility antigen recognized by HLA-A31 restricted cytotoxic T lymphocytes generated from HLA-identical bone marrow donor lymphocytes.

Bulk cytotoxic T lymphocytes (CTL) were generated by in vitro stimulation of BMT donor lymphocytes with Philadelphia chromosome (Ph)-positive leukemic cells from an HLA-identical sibling patient. CTL were cytotoxic against the patient's leukemic cells as well as the EBV-lymphoblastoid cell line (EBV-LCL) generated from the patient's cells, suggesting that they recognize a minor histocompatibility antigen (mHAg). Subsequently, several CTL lines were established by a limiting dilution method and analyzed. One of these CTL lines, 16C12 CTL which used a single TCRbetaV3S1 for CD8 cells, lysed HLA-A31-positive leukemic cells and EBV-LCL, but not fibroblasts. The cytotoxicity against the patient's leukemic cells and EBV-LCL was blocked by anti-HLA-A31 moAb, anti-HLA-class I moAb, and anti-CD8 moAb, suggesting that this mHAg was presented with HLA-A31. The antigen recognized by 16C12 CTL seemed to be a novel mHAg, since HLA-A31 restricted antigen has not been reported to date and 16C12 CTL showed no cytotoxicity against EBV-LCL which probably express known mHAgs. CTL detecting this mHAg may play an important role in the GVL effect in HLA-A31-positive BMT patients.

Bone Marrow Transplantation↗