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Biomedical subjects

Y Toda

Publications and source records attributed to Y Toda.

At least 55 records · Page 3Linked to original sources

Bilateral macular atrophy in blue cone monochromacy (BCM) with loss of the locus control region (LCR) and part of the red pigment gene.

PURPOSE: To describe unusual macular abnormalities in a family with blue cone monochromacy (BCM, or X-linked incomplete achromatopsia) and deletion of about 9.5 kb comprising part of the red pigment gene and the region upstream of the red pigment gene. METHODS: The molecular structure of the red and green pigment genes and the locus control region (LCR) upstream of the red gene were studied for deletions, rearrangements and point mutations by Southern blot analysis and PCR. Four affected males (ages 33, 45, 51, and 59) and a carrier female (age 58) were examined by funduscopy and fluorescein angiography. Extensive color vision testing as well as rod and cone electroretinography (ERG) were performed on two of them. RESULTS: Analysis showed that the 6 kb proximal red gene region, exon 1 and about 3.1 kb of intron 1 of the red gene are deleted in this family. Exons 2-6 of the red gene, all the exons of the green gene and the Tex 28 gene were present. Four affected males had bilateral macular changes, including three with overt atrophy. All had visual acuity of 20/200 and their color vision was typical for BCM, with the absence of long- and middle-wavelength sensitive cone function. The ERG showed normal rod responses, whereas the photopic cone and 30-Hz flicker responses were >95% reduced. CONCLUSIONS: We report the unusual association between macular atrophy and BCM resulting from the loss of an approximately 9.5 kb region encompassing the LCR, proximal red gene promoter elements and exon 1 of the red gene. However, loss of the LCR and promoter is not sufficient to explain the phenotype since we have observed other BCM families with similar deletions who do not exhibit macular changes.

Adult↗

Sequence patterns observed in 5' flanking regions of primate Alu elements.

Retrotransposons have generally been known to integrate randomly into host genomes. Jurka, however, showed some consensus sequence patterns at insertion sites of some mammalian retrotransposons and proposed enzymatic involvement that mediates integration. Jurka used about 400 complete human Alu and rodent ID sequences which retain full length with identical flanking sequences at both ends. In our study, more than 25,000 Alu sequences longer than 250 bp were used for comprehensive analysis to identify any consensus sequence(s) preceding the 5' end of Alu elements. "Entropy" at each nucleotide position within 500 bases of the 5' Alu end was computed. Significant drop of entropy was observed between position -20 and -10 of the 5' end of Alu, suggesting the existence of certain consensus sequence(s) in the region. Frequencies of all possible triplets (total of 64) were measured in the same region. Observation that frequencies of triplets "aaa," "taa," and "tta" in the 5' flanking sequences were high is consistent with Jurka. However, frequencies of triplets "att" and "aca" were also significantly high, which are not the primary candidates for nick site in Jurka.

Alu Elements↗

Study of the cause of the temperature rise at the muscle-bone interface during ultrasound hyperthermia.

Undesirable temperature rise at the muscle-bone interface has been one of the major problems during ultrasound hyperthermia treatment. In this study, we examined by both computer calculation and phantom experiment the cause of this problem. Ultrasound penetrates a bone in two different waveforms, longitudinal and transversal. The transmission coefficient of these two waves vary greatly with the incident angle. From both theoretical and experimental results, the incident angle dependency of the interface heat was confirmed. When the incident angle is less than the critical angle of the longitudinal wave, the main cause of the temperature elevation is the absorption of the longitudinal wave in the bone. When the incident angle is larger than the critical angle of the longitudinal wave, the transversal wave becomes the major cause of the heat generation. At the incident angles larger than the critical angle of the transversal wave, no temperature rise is produced by the absorption of the ultrasound at the bone; the incident longitudinal wave, strengthened by the reflected wave, is absorbed in the muscle just in front of the bone. The heat generated in the muscle is transported to the interface so that the temperature of the interface and bone increases slightly.

Bone and Bones↗

Ultrasonographic arterial portography with second harmonic imaging: evaluation of hepatic parenchymal enhancement with portal venous flow.

Ultrasonographic arterial portography was evaluated with second harmonic and conventional gray scale imaging after the administration of 0.001 to 0.1 ml/kg of FS069 (Optison) in 10 dogs (four dogs with ligation of the portal vein branch) and two woodchucks with hepatocellular carcinomas. Harmonic imaging was required to obtain good liver parenchymal enhancement for ultrasonographic arterial portography to be useful. The tumors were visible as regions of greater enhancement after intravenous injection and as hypoechoic regions after superior mesenteric artery injection. The segments with portal vein ligation were not detected after intravenous injection but were clearly seen after superior mesenteric artery injection. Doppler signal measurement verified a significant difference between the portal vein and hepatic vein after superior mesenteric artery injection and in the femoral artery after intravenous versus superior mesenteric artery injection, demonstrating that minimal levels of FS069 pass through the liver.

Albumins↗

Cold milk accelerates oro-cecal transit time during the luteal phase but not the follicular phase in women.

The effect of the menstrual cycle on oro-cecal transit time (OCTT) has been controversial. Since poor reproducibility of OCTT measurements by lactulose might be responsible for this controversy, we measured OCTT with either milk or a solid test meal during the luteal and follicular phases of the menstrual cycle. Nine healthy young women (21.9 +/- 0.42 years old) with regular menstruation were studied for 4 consecutive menstrual cycles. Control (37 degrees C) or cold (10 degrees C) milk was used as a liquid meal, and the OCTT measurements were taken 3 times at each milk temperature during each of the 2 phases for 3 consecutive menstrual cycles. OCTT after a solid test meal (cooked rice, miso soup, a boiled egg, and cooked soybeans with mixed vegetables) was studied twice in 1 menstrual cycle. Breath hydrogen was determined every 15 min for 6 h. OCTT was defined as the time when breath hydrogen showed a sustained rise of 3 ppm or more from baseline. OCTT was not different between the luteal and follicular phases when the test meal was control milk or the solid meal. When cold milk was used as the test meal, OCTT was significantly shorter during the luteal phase (134 +/- 15 min) than during the follicular phase (165 +/- 21 min). In conclusion, cold milk accelerates OCTT during the luteal phase but not the follicular phase of the menstrual cycle in women.

Administration, Oral↗

Circadian rhythm of breath hydrogen in young women.

Breath hydrogen levels, which reflect colonic fermentation of undigested starches, are usually low in the fasted state. Fasting levels of breath hydrogen are important for estimation of oro-cecal transit time and diagnosis of lactase deficiency. In young women, however, fasting levels of breath hydrogen are high. To clarify the reason for this, we studied the circadian pattern of breath hydrogen and the effect of alpha-D-galactosidase on fasting breath hydrogen in one study, and the effect of sleep deprivation on fasting breath hydrogen in another study, in 13 women students aged 21-23 years. In the first study, two breath samples were collected, one in the evening and the other the next morning. On another occasion, alpha-D-galactosidase was given before dinner and breath samples were collected the next morning. In the second study, the circadian rhythm of breath hydrogen was assessed for 3 days and the subjects were deprived of sleep on the second night. Breath samples were collected every 30 min, except during the second night when samples were collected at 1-h intervals. Fasting breath hydrogen was 24 +/- 3.9 ppm (mean +/- SE), which did not differ from the value for the previous night. Alpha-D-galactosidase significantly decreased fasting breath hydrogen levels, to 17 +/- 2.4 ppm (P < 0.05). There was a clear circadian pattern of breath hydrogen, high in the morning and decreasing to the nadir by 16:00. After dinner, the level increased again and stayed high during the night. Sleep deprivation did not affect fasting levels of breath hydrogen. High fasting breath hydrogen levels in young women followed a circadian pattern and this may have been due, in part, to an high intake of dietary fiber on the previous day.

Adult↗

The homozygote of HLA-DRB1*0901, not its heterozygote, is associated with rheumatoid arthritis in Japanese.

To assess the association between HLA-DRB1*0901 and Japanese rheumatoid arthritis (RA) patients, we analyzed the frequency of HLA-DRB1*0901 in 852 Japanese RA patients. We found that the homozygote of DRB1*0901 was associated with Japanese RA patients, while the heterozygote of DRB1*0901 was not. These findings suggest that DRB1*0901 is a weakly susceptible allele of RA, which in our investigation was not associated with RA by a single allele, but can be by a homozygote. DRB1*0901 does not have the shared epitope, and it is suggested that there may be some mechanism ofthe association between HLA-DRB1 and RA other than the shared epitope, which was not strong.

Alleles↗

Elderly-onset rheumatoid arthritis and its association with HLA-DRB1 alleles in Japanese.

To assess the association between HLA-DRB1 and elderly-onset rheumatoid arthritis (RA) (EORA) in Japanese people, we analysed the HLA-DRB1 antigen frequencies of EORA patients. The age at onset distribution of 852 Japanese RA patients was analysed, and EORA was defined as an age at onset of 60 yr or older. Among the 852 RA patients, 120 (14.1%) were EORA patients. Their HLA-DRB1 antigen frequencies were assessed for significant deviation from those of the control (n = 652) and adult-onset RA (AORA; disease onset between 16 and 59 yr; n = 732) groups. The Japanese EORA patients were positively associated with DRB1*0101, *0405 and *1502, and the relative risks were 2.7, 1.9 and 2.2, respectively. The frequency of DRB1*1502 was also significantly higher among the EORA patients than in the AORA patients. The EORA patients showed different trends from the AORA patients in their frequency of HLA-DRB1 alleles, which suggests that EORA may be a different subset from AORA in light of its immunogenetic background.

Adolescent↗

Visualization of sulfated glycoconjugates in the chicken embryonic heart by whole-mount alcian blue staining.

In the atrioventricular canal (AVC) and outflow tract (OT) of the developing heart, endothelial cells transform specifically to mesenchymal cells. The mesenchymal cells migrate into the underlying acellular matrix termed cardiac jelly and form endocardial cushion tissue. It is believed the that the highly hydrated nature of cardiac jelly is ascribed to sulfated glycoconjugates in the components of jelly matrix. In the present study, we have visualized the distribution and its temporal changes of sulfated glycoconjugates in the embryonic heart from stage 12 to 26 using whole mount alcian blue (AB) histochemistry. Atrial matrix was AB-negative in all the stages examined. Cardiac jelly in the AVC and OT were positive and the staining intensity increased as heart development proceeded, while AB-positive staining in the matrix of the ventricle became negative by stage 19. At stages later than 19, AB-positive matrix was localized in only the AVC and OT where endothelially-derived mesenchymal cells populated.

Alcian Blue↗

Endothelial outgrowth and the subsequent cell transition in the culture of embryonic atrioventricular canal placed in an inverted polarity.

Endothelial cells in the atrioventricular (AV) segment of the developing chicken heart undergo a transition into mesenchymal cells. When the AV segment is explanted onto a hydrated collagen gel, endothelial cells grow out and reproduce in vivo cell transition regardless of the precise orientation of the explant on a gel. Our results showed that when the luminal side of an explant was placed towards a gel surface, the inverted polarity of endothelium was not adjusted by direct reorganization of polarity, but that the endothelium crawled down so as to settle on a gel surface in the correct original cell polarity. Subsequently, endothelial cells showed cytoplasmic hypertrophy, formed microvillous projections and then extended filopodial migratory appendages. These cellular changes were quite similar to those in vivo. However, the continuity of the endothelial layer was specifically disrupted in AV explant cultures. Such disruption was never observed in ventricle explant cultures in which endothelial-mesenchymal cell transition did not occur. The disintegration of AV endothelial outgrowth must be closely related to its capability to transform into mesenchymal cells and mitotic activity to keep a depository of endothelial cells.

Animals↗

Comprehensive Sequence Analyses of 5' Flanking Regions of Primate Alu Elements.

Retrotransposons have been generally known to integrate randomly into host genomes. Jurka (Proc. Natl. Acad. Sci. USA 94: 1872-1877, 1977), however, showed consensus sequence patterns at integration sites of certain mammalian retrotransposons, and suggested involvement of sequence specific enzymes that mediate integration. We have conducted comprehensive sequence analyses of 5' flanking regions of primate Alu elements. In contrast to the small but clean data set Jurka (1977) used, (1) larger number of samples were used, (2) wider region of 5' end of Alu elements was analyzed, and (3) comparisons were made among different subfamilies for comprehensive analyses in order to identify characteristic sequence pattern(s) preceding 5' end of Alu elements. The nucleotide occurrences at each position within 500 bases of 5' end of Alus were counted to obtain profiles. Information content at each nucleotide position in the same region was, then, computed. Distinctive difference in the nucleotide composition and information content values that divides the region into two was observed. The region between -20 and 5' end of Alu elements is found to be highly adenine-rich and shows significantly higher information content values compared to the rest of the region, implying the existence of certain characteristic sequence pattern in this region. Also, younger subfamilies of Alu elements show higher information content values than older subfamilies. This implies that certain characteristic sequence pattern already existed in the region between -20 and 5' end of Alu elements at the time of Alu integration, and accumulation of mutation in the course of time resulted in the less distinctive sequence pattern in older sequences. Frequencies of all possible triplets (total of 64) were measured in the same region in order to identify characteristic sequence pattern(s). Observation that frequencies of triplets aaa, taa and tta in the 5' flanking sequences were high is consistent with Jurka (1977). Frequencies of some other triplets such as gaa, caa, aac, ctt, gtt, atg, etc. which do not comprise the primary candidates for the nick site in Jurka (1977) also show significantly high frequencies.

Journal Article↗

[HR-CT evaluation of lung parenchymal alterations in patients following breast conservation therapy].

Twenty patients with early-stage breast cancer treated with breast conservation surgery and definite radiation, underwent computed tomography (added HR-CT) of the lungs before, immediately after, and at one, six, and twelve months after radiotherapy. During the follow-up period, 17 (85%) of the patients developed parenchymal alterations in the irradiated lung volume. We classified the parenchymal alterations into seven patterns: pattern 1 = septal line, 2 = nodular opacity, 3 = ground-glass opacity, 4 = consolidation, 5 = curvilinear opacity, 6 = aircyst accumulation, and 7 = irregularity of pleural surface. From one to six months after radiotherapy, 14 patients developed nodular opacities and ground glass opacities in the irradiated lung field. At 12 months after radiotherapy, fourteen patients were found to have aircyst accumulation and irregularity of the pleural surface. In this study, none of the patients presented any abnormal findings immediately after irradiation. There was no relationship between central lung distance or boost irradiation and the parenchymal alterations in the lung. On the other hand, there was a close relationship between oral anti-cancer agents and lung lesions. In conclusion, HR-CT was useful to evaluate morphologic changes in the irradiated lung.

Breast Neoplasms↗

Change in body fat, but not body weight or metabolic correlates of obesity, is related to symptomatic relief of obese patients with knee osteoarthritis after a weight control program.

OBJECTIVE: To determine the variable most closely related to symptomatic relief of osteoarthritis (OA) of the knee in response to a weight control program. METHODS: Twenty-two patients diagnosed with knee OA whose body mass index (BMI) was more than 26.4 were treated with a low calorie diet, an appetite suppressant, and nonsteroidal antiinflammatory drugs for 6 weeks. The patients were instructed to follow a walking program. We analyzed BMI, percent body fat, the average number of steps per day by pedometer, and the metabolic correlates of obesity (blood pressure, fasting blood serum glucose, total cholesterol, triglycerides, and serum insulin) at the beginning and end of therapy. The correlation between the change in each variable and the remission score (delta score) using the Severity Index of Lequesne, et al was evaluated. RESULTS: Delta score of knee OA was more strongly associated with reduction in percent body fat (p= 0.0013, r=0.62) than other variables. Significant correlation was also observed between the number of steps per day and delta score (p=0.0031, r=-0.58). No other variable, including weight loss, was significantly correlated with delta score. There was a significant correlation between delta percent body fat and the number of steps per day (p=0.012, r=-0.62). CONCLUSION: In a weight control program, decreasing body fat and increasing physical activity are more important than body weight loss or decreasing other indices of obesity in producing symptomatic relief of knee OA, although there is not necessarily a cause and effect relationship between body fat and OA score.

Adipose Tissue↗

Alu elements as an aid in deciphering genome rearrangements.

Genomic rearrangements result in genomic duplications that lead to the generation of more complex genomes. Some attempts have been made to trace duplication histories of different loci using Alu elements because of their large population in primate genomes (Chen et al., 1989; Mnuková-Fajdelová et al., 1994). In this short report, using the human growth hormone locus as an example, we demonstrate the usefulness of Alu repetitive elements in computer sequence analyses when tracing duplication histories. Information on subfamily classification, direction, arrangements, Poly(A) tails and direct repeats can aid our understanding of genome rearrangements.

Chromosome Mapping↗

Cyclin-D1-gene amplification is a more potent prognostic factor than its protein over-expression in human head-and-neck squamous-cell carcinoma.

To evaluate the prognostic significance of cyclin D1 protein/gene expressions in human head-and-neck squamous-cell carcinoma (HNSCC), we examined amplification of the cyclin-D1 gene (CCND1) by the differential PCR method and over-expression of cyclin-D1 protein by immunohistochemistry in 45 paraffin-embedded sections from HNSCC. Amplification of CCND1 was found in 10 (22%) cases and over-expression of cyclin D1 was found in 24 (53%) cases. CCND1 amplification was also found in 3 (25%) of 12 cases of dysplastic lesions adjacent to HNSCC. The overall 5-year survival of patients with CCND1 amplification or with protein over-production was significantly lower than that of patients without (p < 0.0001 and p < 0.05, respectively). However, with multivariate analysis, only amplification of CCND1 retained an independent prognostic value (p = 0.0018). These suggest that CCND1 amplification occurs at early stages of HNSCC tumorigenesis and is a more useful prognostic factor than over-expression of cyclin D1 in HNSCC.

Adult↗

Small bowel transit time and colonic fermentation in young and elderly women.

Small bowel transit time (SBTT) in 15 young and 13 elderly women was assessed by measuring breath hydrogen concentrations after they had consumed a solid test meal. The meal consisted of 200 g cooked rice, 50 ml miso (made from fermented soy bean curd) soup, a boiled egg, and 95.5 g of cooked soy beans with mixed vegetables. This meal provided 17 g protein, 14.1 g fat, 92.9 g carbohydrate, 7 g dietary fiber, and 565 kcal total energy. The SBTT, calculated by a mean 3 ppm increase in breath hydrogen, was 191 +/- 14.9 (mean +/- SE) min in the young and 188.1 +/- 16.8 min in the elderly group; the difference was not significant. Breath hydrogen levels, however, were higher in the young than in the elderly group (39.1 +/- 6.3 ppm, vs 22.2 +/- 4.3 ppm, P < 0.05). There was an initial peak of hydrogen concentration, reached almost immediately after the ingestion of the meal, and then a decline to baseline within 60 min. This initial peak was not as pronounced in the elderly subjects. A second peak, indicating the entry of the test meal into the cecum, was more pronounced in the young than in the elderly group. SBTT did not differ significantly between the two groups, but colonic fermentation was more pronounced in the young, both in the fasting and the postprandial state.

Adult↗

The relationship between HLA-DRB1 alleles and disease subsets of rheumatoid arthritis in Japanese.

To assess the association between HLA-DRB1 and the pathogenesis of rheumatoid arthritis (RA) in the Japanese population, we typed for HLA-DRB1 alleles in 852 Japanese patients. An analysis of HLA-DRB1 allele associations was performed on the overall group and in three disease subsets of adult-onset RA, classified according to the extent of joint destruction evident on plain radiograms, i.e. least erosive subset (LES), more erosive subset (MES) and most erosive subset with mutilating disease (MUD). The Japanese RA patients with positively associated with DRB1*0101 and *0405, and negatively associated with DRB1*0701, *0802, *1302 and *1405. DRB1*0101 was associated more strongly with a milder disease subset and the relative risk (RR) was 1.9, 1.5 and 1.2 for LES, MES and MUD, respectively. On the other hand, DRB1*0405 was associated more strongly with a more severe disease subset, the RR being 1.8, 4.0 and 4.3 for LES, MES and MUD, respectively. These findings suggest that RA is a heterogeneous disease, not only clinically, but also in terms of its immunogenetic background, and that HLA-DRB1 can be a useful prognostic factor for RA.

Adolescent↗