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Biomedical subjects

Y Iida

Publications and source records attributed to Y Iida.

At least 127 records · Page 7Linked to original sources

Beta 2-microglobulin modified with advanced glycation end products induces interleukin-6 from human macrophages: role in the pathogenesis of hemodialysis-associated amyloidosis.

Recently, we demonstrated that beta 2-microglobulin (beta 2M) of amyloid deposits in hemodialysis-associated amyloidosis (HAA), a serious complication leading to hemodialysis arthropathy, is modified with advanced glycation end products (AGEs) of the Maillard reaction. In the present study, to elucidate the possible involvement of AGEs-modified beta 2M (AGE-beta 2M) in the pathogenesis of HAA, we examined the effect of AGE-beta 2M on macrophage production of interleukin-6 (IL-6), an important cytokine for osteoclastogenesis and bone resorption. Purified AGE-beta 2M from long-term hemodialysis patients, but not normal beta 2M, stimulated synthesis and secretion of IL-6 from macrophages. Similar effects were also induced by in vitro-prepared AGE-beta 2M (normal beta 2M incubated with glucose for 60 days in vitro). These findings suggested a potential role of AGE-beta 2M in the pathogenesis of HAA.

Amyloidosis↗

Characterization of genomic PIG-A gene: a gene for glycosylphosphatidylinositol-anchor biosynthesis and paroxysmal nocturnal hemoglobinuria.

Paroxysmal nocturnal hemoglobinuria (PNH) is an acquired hemolytic anemia characterized by the presence of abnormal subpopulations of blood cells that are deficient in surface expression of glycosylphosphatidylinositol (GPI)-anchored proteins. Recent studies showed that the gene termed PIG-A, which participates in the first step of GPI-anchor biosynthesis, is mutated in the abnormal blood cells from patients with PNH. In this study the genomic PIG-A gene was cloned and characterized to obtain nucleotide sequence information for analyzing somatic mutations of PIG-A in patients with PNH. The PIG-A gene is at least 17 kb long and has six exons. The exon-intron boundaries and 583 bp of the 5' flanking region were sequenced. The 5' flanking region has no TATA-like sequence, but includes four CAAT boxes, two AP-2 sequences, and a CRE sequence, some of which are present in regions necessary for the promoter activity. We report pairs of oligonucleotide primers for polymerase chain reaction that should be useful to amplify and analyze various regions of the PIG-A gene in patients with PNH.

Base Sequence↗

Abnormalities of PIG-A transcripts in granulocytes from patients with paroxysmal nocturnal hemoglobinuria.

BACKGROUND: Paroxysmal nocturnal hemoglobinuria (PNH) is an acquired disorder in which there is a deficiency in the synthesis by hematopoietic cells of the glycosyl-phosphatidylinositol molecules that anchor proteins to the cell membrane. Recently, we demonstrated that a gene termed PIG-A (for phosphatidylinositol glycan class A), a component of glycosyl-phosphatidylinositol biosynthesis, was responsible for PNH in two patients. The present study was undertaken to elucidate whether PIG-A is the gene responsible for all cases of PNH and to characterize further the somatically acquired abnormalities of this gene. METHODS: We studied granulocytes from 15 patients with PNH. The cell content of CD55 and CD59 was assessed by fluorescence-activated flow cytometry. PIG-A transcripts were reverse-transcribed, amplified by the polymerase chain reaction, and cloned into plasmids. The structure of the cloned complementary DNA was analyzed by nucleotide sequencing, and its function was assessed on the basis of its ability to restore to normal the abnormal phenotype of a PIG-A-deficient cell line after transfection. RESULTS: Three patients had size abnormalities of PIG-A transcripts with different patterns, and in one patient a very low level of the PIG-A transcript was found. Eleven patients had transcripts of normal size, but the transfection assay revealed that in each patient some of them were nonfunctional. The percentage of nonfunctional PIG-A transcripts was correlated with the percentage of affected granulocytes (P < 0.001). Sequence analysis demonstrated somatic mutations in two of the patients. CONCLUSIONS: PIG-A is the gene responsible for PNH in all patients studied to date.

Base Sequence↗

Magnetic resonance imaging of the olfactory apparatus.

The magnetic resonance imaging visualization of the olfactory apparatus is reported in this article. We used a superconductor-type magnetic resonance device (Siemens Magnetom H15 (1.5 T) with a surface coil. The subjects were patients with posttraumatic anosmia. The olfactory bulbs were clearly visualized in the frontal plane magnetic resonance images, the olfactory bulbs and the foramina of the cribriform plate were visualized in the sagittal section, and the olfactory bulbs, tracts, and other structures were visualized in the coronal sections. The olfactory nerves could not be seen.

Brain Diseases↗

Scintigraphic findings of the thyroid in hypothyroid patients with blocking-type TSH-receptor antibodies.

The present study was designed to analyse the scintigraphic appearance of the thyroid in hypothyroid patients with blocking-type TSH receptor antibodies (TRAbs). Eleven hypothyroid patients with autoimmune thyroiditis positive for TSH binding inhibitor immunoglobulins (TBII) [80% +/- 12 (SD)%; normal < 11%] and for thyroid stimulation-blocking antibodies (TSBAbs) (90% +/- 9%: normal < 32%) were studied. Thyroid scanning was performed using technetium-99m or iodine-123, when the patients were hypothyroid. Analysis of the scan images revealed the presence of localized functioning areas in six patients (group 1), and no visualization of the thyroid in the remaining five patients (group 2). Patients in group 1 showed significantly higher uptake of 99mTc than those in group 2 (P < 0.05). Interestingly, three patients in group 1 were positive for thyroid-stimulating antibodies (TSAbs) (249% +/- 17%; normal < 145%), which were not detected in the remaining eight patients. Antibodies against thyroglobulin and microsomal antigens were detected in nine nine (81.8%) and 11 (100%) patients, respectively, but neither of these titres correlated with the scan image. Three patients in group 1 underwent scintigraphy again after treatment with thyroxine, at which time the functioning lesion was not noted. Fourteen hypothyroid patients with negative TBII displayed no such scintigraphic findings. Chronic stimulation of the thyroid by TSAbs and/or TSH might be responsible for the presence of the functioning lesion, but clarification of the mechanism requires further studies. In summary (1) TSAbs were detected in three (27.3%) of 11 hypothyroid patients with blocking TRAbs; (2) thyroid scintigraphy revealed the presence of localized functioning area(s) in approximately half of these cases.

Adolescent↗

Endoscopic resection of large colorectal polyps using a clipping method.

PURPOSE: In conventional endoscopic snare polypectomy, bleeding and perforation are the principal concerns. To prevent these complications, we employ an endoscopic clipping technique using the HX-3L clipping apparatus. METHODS: With this method, clips are used to clamp the base of a polyp. A snare is hung peripheral to the clips. The polyp is then resected by coagulating and cutting with an electric current. RESULTS: Neither bleeding nor perforation during or after polypectomy has occurred, nor have complications related to the use of clips developed. Gigantic polyps were not resected piecemeal, but rather were resected en bloc facilitating a clear determination of cancer on the surface of the resected site. Endoscopic clipping permitted site marking for colonoscopic surveillance. CONCLUSION: We conclude that the clipping method has many advantages and is a useful technique in colonoscopic polypectomy.

Adult↗

11C-labeled 2'-iododiazepam for PET studies of benzodiazepine receptors: synthesis and comparison of biodistribution with its radioiodinated compound.

For PET studies of benzodiazepine receptors, N-11C-methyl-2'-iododiazepam (2'-IDZ) was synthesized by N-methylation of its desmethyl derivative with 11C-methyl iodide, and was subsequently purified by HPLC. The labeling and purification procedures were completed within 45 min after 11C-methyl iodide trapping, and the radiochemical yield (corrected for decay) was approximately 40% based on the initial trapped radioactivity of 11C-methyl iodide. Biodistribution studies in mice demonstrated that 11C-2'-IDZ was rapidly and noticeably accumulated in the brain, and subsequently decreased with time. Accumulation was greater in the cortex than in other brain regions. When compared with 125I-2'-IDZ, the distribution was almost the same until 5 min after injection, but levels were low after 20 min. Metabolic studies indicated that the difference between these two compounds in the time course of brain radioactivity distribution may be due to N-demethylation in vivo.

Animals↗

Radioiodinated nordiazepam analog for in vivo assessment of benzodiazepine receptors by single photon emission tomography.

2'-Iodo-nordiazepam (2'-IND), a nordiazepam analog iodinated at the 2'-position of the C-5 phenyl ring, was synthesized and evaluated as a potential radiopharmaceutical for investigating brain benzodiazepine receptors by SPECT. [125I]2'-IND was synthesized by the halogen exchange reaction and purified by HPLC. In an in vitro competitive binding study using [3H]diazepam and rat cortical synaptosomol membranes, 2'-IND showed an almost equal affinity for benzodiazepine receptors as diazepam. In a saturation binding study using rat cortical synaptosomal membranes, 2'-IND displayed a Kd of 1.10 nM and a Bmax of 1.87 pmol/mg protein. Biodistribution and metabolism studies in mice showed that [125I]2'-IND exhibited rapid and high accumulation in the brain, and that the cerebral uptake and distribution of this compound occurred in the intact form. Furthermore, the administration of diazepam and flumazenil reduced cortical uptake by approx. 20%, suggesting that the uptake of 2'-IND occurred at least partly in association with benzodiazepine receptors.

Animals↗

Stimulated iodide uptake in FRTL-5 cells preincubated with Graves' immunoglobulins in NaCl-free medium: a sensitive assay for thyroid-stimulating antibodies.

The present study was designed to increase the sensitivity of iodide uptake assay for detecting thyroid-stimulating antibodies (TSAb). Based on the previous observations that TSAb are more active to increase cAMP levels in the NaCl-free condition, we improved the assay procedure and defined the optimum conditions: FRTL-5 cells were incubated with immunoglobulin (IgG) in NaCl-free medium for 3 days, and then 125I uptake in the cells was determined after 60 min. The sensitivity of iodide uptake assay for TSAb increased 3-fold by the modification, when assessed by the IgG concentration required to elicit the same response. The described assay is as sensitive as that using cAMP measurement in NaCl-free buffer. Thus, it could detect TSAb in all 21 patients with active Graves' disease and in 7 of 8 with ophthalmic Graves' disease but not in 29 of 30 control subjects. Thyroid stimulating activities assessed by these two assays correlated with each other (n = 29, r = 0.707, p < 0.001). False positive results obtained in 4 hypothyroid patients with Hashimoto's thyroiditis (serum TSH concentrations, 11-171 mU/L) could be prevented using anti-TSH antibodies. In summary, the described assay allows evaluation of stimulated thyroid function directly without affecting the detection of TSAb.

Animals↗

Quantitative analysis of genomic polymorphism of herpes simplex virus type 1 strains from six countries: studies of molecular evolution and molecular epidemiology of the virus.

Using the presence or absence of 63 variable restriction endonuclease (RE) sites selected from 225 sites with six REs, genomic polymorphism of 242 herpes simplex virus type 1 (HSV-1) strains from six countries (Japan, Korea, China, Sweden, U.S.A. and Kenya) was quantitatively analysed. Twenty-five of the 63 sites were found to differ between Korean and Kenyan strains. In contrast, only three and six sites were found to differ between isolates from Sweden and the U.S.A. and between those from Korea and China, respectively, suggesting that they are closely related to each other. In this way, characterization of 63 sites enabled us to categorize 186 distinct HSV-1 genotypes from 242 individuals. Some strains from Japan, Korea and China shared the same genotypes, indicating that they are phylogenetically closely related. Many significant correlation coefficients (magnitude of > 0.42; P < 0.01) between pairs of sites were found in isolates from the three Asian countries (Japan, Korea and China) as well as in those from Sweden and the U.S.A., suggesting that HSV-1 strains from within the same ethnic groups are evolutionarily closer. The average number of nucleotide substitutions per nucleotide, as defined by nucleotide diversity (pi), was estimated for HSV-1 genomes within (pi x or pi y) and between (pi xy) countries. On the basis of 225 sites, nucleotide diversity for Kenyan isolates was 0.0056, almost three times higher than that for Korean isolates, implying that Kenyan HSV-1 genomes are much more diverse than those from Korea. In addition, the diversity between HSV-1 isolates from different countries (pi xy) was highest between isolates from the three Asian countries and Kenya (0.0075 to 0.0081) and lowest among those from the three Asian countries (0.0032 to 0.0040). The mutation rate (lambda) for HSV-1 was estimated to be 3.5 x 10(-8)/site/year. All these findings show that the evolution of HSV-1 may be host-dependent and very slow.

Biological Evolution↗

Involvement of beta 2-microglobulin modified with advanced glycation end products in the pathogenesis of hemodialysis-associated amyloidosis. Induction of human monocyte chemotaxis and macrophage secretion of tumor necrosis factor-alpha and interleukin-1.

beta 2-Microglobulin (beta 2M) is a major constituent of amyloid fibrils in hemodialysis-associated amyloidosis (HAA), a complication of long-term hemodialysis. However, the pathological role of beta 2M in HAA remains to be determined. Recently, we demonstrated that beta 2M in the amyloid deposits of HAA is modified with advanced glycation end products (AGEs) of the Maillard reaction. Since AGEs have been implicated in tissue damage associated with diabetic complications and aging, we investigated the possible involvement of AGE-modified beta 2M (AGE-beta 2M) in the pathogenesis of HAA. AGE- and normal-beta 2M were purified from urine of long-term hemodialysis patients. AGE-beta 2M enhanced directed migration (chemotaxis) and random cell migration (chemokinesis) of human monocytes in a dose-dependent manner. However, normal-beta 2M did not enhance any migratory activity. AGE-beta 2M, but not normal-beta 2M, increased the secretion of TNF-alpha and IL-1 beta from macrophages. Similar effects were also induced by in vitro prepared AGE-beta 2M (normal-beta 2M incubated with glucose in vitro for 30 d). When TNF-alpha or IL-1 beta was added to cultured human synovial cells in an amount equivalent to that secreted from macrophages in the presence of AGE-beta 2M, a significant increase in the synthesis of collagenase and morphological changes in cell shape were observed. These findings suggested that AGE-beta 2M, a major component in amyloid deposits, participates in the pathogenesis of HAA as foci where monocyte/macrophage accumulate and initiate an inflammatory response that leads to bone/joint destruction.

Adult↗

[A case of unilateral brain-stem tumor and impaired ventilatory response].

A 44-year-old man with a unilateral brain-stem tumor (ganglioglioma) presented with marked hypoventilation and irregular breathing. His respiratory muscle strength was impaired slightly, and his ventilatory responses to chemical stimuli were markedly diminished. Magnetic resonance imaging of the brainstem revealed that the tumor was located in the left superior cerebellar peduncle and the medulla, and involved the left lateral portion of the medullary reticular formation, ambiguous nucleus, and solitary nuclear complex. From these findings, we conclude that the abnormality of ventilatory control may have been caused by damage to both the unilateral respiratory neuron group in the medulla and the afferent pathway to the respiratory motor unit on the opposite side.

Adult↗

[Surgical treatment of distal aortic arch aneurysm combined with mitral regurgitation--a case using "elephant trunk" technique and concomitant mitral valvuloplasty].

We present a surgical case of a 63-year-old male with distal aortic arch aneurysm combined with mitral regurgitation. Through a median sternotomy, a mitral valvuloplasty was performed with McGoon's procedure and Carpentier's ring. Then with the aid of deep hypothermia and circulatory arrest, the aortic arch was opened. A long woven velour graft was anastomosed only proximally to the distal end of the aortic arch and was allowed to float down the descending aorta ("Elephant Trunk" technique). Anti-coagulant therapy was continued only for 4 weeks after the operation. Postoperative left ventriculogram showed no residual regurgitation. The aneurysm was confirmed fully thrombosed around the graft on computed tomogram. It is concluded that "Elephant Trunk" technique for distal arch aneurysm is useful when combined other cardiac surgery without anti-coagulant therapy, such as mitral valvuloplasty, is needed.

Aortic Aneurysm, Thoracic↗

Scintigraphic findings of the thyroid in euthyroid ophthalmic Graves' disease.

UNLABELLED: The scintigraphic findings of the thyroid were analyzed in patients with euthyroid ophthalmic Graves' disease known to have some thyroid-related abnormalities. METHODS: Technetium-99m-pertechnetate images of the thyroid from 38 euthyroid ophthalmic Graves' disease patients with small, soft or nonpalpable goiter were analyzed. RESULTS: Scan images showed homogeneous (even) and nonhomogeneous (uneven) 99mTc uptake in 20 and 16 patients respectively. Poor images due to low uptake were observed in two patients. Six patients displayed alterations in scintigraphic appearance from even to uneven patterns after T3 suppression test. Statistical analysis revealed that the uneven pattern was more frequently observed in euthyroid ophthalmic Graves' disease patients than in 26 patients with hyperthyroid Graves' disease who were euthyroid during antithyroid drug therapy (p < 0.005). The scintigraphic heterogeneity was correlated with reduced uptake as well as a higher ratio of the uptake values after T3 treatment to the pretreatment values. Scintigraphically, hot or warm lesions were observed in most cases showing the uneven pattern (16/22; 73%). Rather low titers of antithyroglobulin, antimicrosomal antibodies and TSH-binding inhibitor immunoglobulins were detected in only 4 (10.5%), 7 (18.4%) and 12 (31.6%) patients respectively, while the prevalence of thyroid-stimulating antibodies (TSAb) was as high as 86.8% (33/38). The scintigraphic heterogeneity did not correlate with the detection of these antibodies but did correlated with the severity and duration of ophthalmopathy. CONCLUSIONS: The presence of functioning follicular cells with some autonomy that were heterogeneously distributed in the thyroid was observed in about half the euthyroid ophthalmic Graves' disease patients. Chronic stimulation by TSAb may be the underlying mechanism for these findings.

Adolescent↗

Change in impulse response of heart rate to instantaneous lung volume.

A method is presented that relates the heart rate variability (HRV) to the change in instantaneous lung volume (ILV) under non-stationary conditions. Methods utilizing a recursive least squares (RLS) algorithm and a modified Widrow LMS algorithm are proposed to keep track of changes in impulse response of HRV to ILV. Results are presented of real data analysis and a dedicated system is proposed utilizing DSP chips for the real time data processing.

Algorithms↗

Increased uptake of iodine-131 in metastases of differentiated thyroid carcinoma associated with less severe hypothyroidism following total thyroidectomy.

BACKGROUND: In an attempt to determine possible factors affecting the efficacy of iodine-131 (I-131) treatment for metastatic thyroid carcinoma, the authors focused their efforts on thyroid functions after total thyroidectomy. METHODS: Between 1980 and 1991, 47 patients with lung metastases of differentiated thyroid carcinoma were treated with I-131. Relationships of the images on post-therapy scans with various clinical features were studied. RESULTS: Among them, 28 (59.6%) showed I-131 uptake in the metastases on post-therapy scans. Younger patients had lesions that concentrated more radioactive iodine than did those of older patients. The amount of I-131 concentrated in the metastatic lesions correlated with serum triiodothyronine (T3), thyroxine (T4), and thyroglobulin levels and inversely with serum thyroid-stimulating hormone (TSH) levels determined at the time of therapy. Serum T3 and T4 levels were significantly higher in 28 patients with positive scans than in 19 patients with negative scans. Most patients who had metastases with markedly increased radioactivity were euthyroid or mildly hypothyroid, suggesting that thyroid hormones produced by tumor masses compensated for severe hypothyroidism after total thyroidectomy, and showed favorable responses to the treatment. In three patients successfully treated, decreases in serum thyroglobulin levels and the size of metastatic lesions were accompanied by the development of severe hypothyroidism. CONCLUSIONS: The presence of a large amount of metastatic functioning thyroid tissues responsive to I-131 treatment can be suspected in patients with less severe hypothyroidism after total thyroidectomy.

Adenocarcinoma↗