Biomedical subjects

Y Ito

Publications and source records attributed to Y Ito.

At least 217 records · Page 12Linked to original sources

PubMed2001

Direct measurement of HDL cholesterol: method eliminating apolipoprotein E-rich particles.

It has been reported that the existing direct method of high density lipoprotein (HDL) cholesterol measures particles enriched with apolipoprotein E (apoE). The aim of our study was to investigate a new analytical protocol to directly measure HDL cholesterol that eliminates apoE-rich particles. The interactions of four lipoproteins (HDL(3), HDL(2), LDL, and VLDL + chylomicron) with surfactants, divalent cations, sugars, and lectins were investigated. By analyzing sera, HDL(3), and HDL(2), we examined the relationships among the measurements obtained by our protocol, a precipitation method using heparin-MnCl(2), and a commercially available kit for this direct method. A significant difference was found between the direct method and the heparin-MnCl(2) method, but not between our protocol and the heparin-MnCl(2) method. Multiple regression analysis showed that the difference between the direct method and the heparin MnCl(2) method is dependent on sources of apoE-rich HDL. In conclusion, our protocol enables a direct measurement of HDL cholesterol that eliminates apoE-rich particles.

Apolipoproteins E↗

PubMed2001

Measuring the human retinal oxygenation response to a hyperoxic challenge using MRI: eliminating blinking artifacts and demonstrating proof of concept.

The retinal oxygenation response to a hyperoxic challenge measured using MRI appears to be an early and accurate marker of retinopathy risk in experimental models, with promising clinical potential. However, the application of this technique in humans is limited by blinking artifacts that can confound detection of subtle signal intensity changes. We asked subjects to refrain from blinking during a 12-s fast low-angle shot (FLASH) image, and to blink if needed during the following 3-s rest period. This no-blink blink cycle was repeated sequentially 20 times during either room-air or 100% oxygen breathing. Significant change (P < 0.05) was detected for the first time from the resultant blinking-artifact-free images in the preretinal vitreous oxygen tension (upper limit of about 13 mm Hg (1.8 KPa, N = 3)) following a 10-min hyperoxic inhalation challenge. These results provide the proof-of-concept data needed for future MRI evaluation of the retinal oxygenation response and human retinopathy, such as diabetic retinopathy.

Artifacts↗

PubMed2001

Pathology-related differential expression regulation of NGF, GDNF, CNTF, and IL-6 mRNAs in human vasculitic neuropathy.

The mRNA levels of nerve growth factor (NGF), glial cell line-derived neurotrophic factor (GDNF), ciliary neurotrophic factor (CNTF), and interleukin-6 (IL-6) were examined in sural nerves of 22 patients with acute necrotizing vasculitic neuropathies. NGF, GDNF, and IL-6 mRNAs were upregulated and CNTF mRNA was downregulated in the lesioned nerves, but their up- and down-regulation levels were not correlated with each other, showing that these mRNAs were independently expressed. The expression of NGF and CNTF mRNAs was clearly correlated with the degree of infiltrated macrophages and T cells, and myelinated fiber density, respectively. These findings indicate that these neurotrophic factors are differentially expressed temporally and spatially in the vasculitic nerve lesion by an underlying pathology-related process.

Adult↗

PubMed2001

Immunohistochemical analysis on biological markers in ductal carcinoma in situ of the breast.

BACKGROUND: The increasing use of mammographic screening has led to an increased detection of ductal carcinoma in situ (DCIS) of the breast. The detailed biological characteristics of DCIS and a new classification of DCIS based on these characteristics are needed. METHODS: Immunohistochemical studies were performed to assess the expression of c-erbB-2 (ErbB-2), estrogen receptor (ER), p53 and proliferative activity (Ki-67) in 65 patients with pure DCIS and 60 with invasive ductal carcinoma (IDC). We classified pure DCIS tumors using three classifications, the architectural, Nottingham, and Van Nuys classifications. RESULTS: ErbB-2, ER and p53 staining was positive in 34%, 66% and 21% of patients with DCIS, respectively, and 58%, 42% and 33% in patients with IDC, respectively. Ki-67 stained positively in 1.5% of patients with DCIS and 11.2% of patients with IDC. The comedo type showed a high rate of positive ErbB-2 and p53 staining. The cribriform and papillary types showed a high rate of positive ER staining. Under the Van Nuys classification, ErbB-2, p53 and Ki-67 expression were highest in the group with high nuclear grade and lowest in the group with non-high nuclear grade without necrosis. CONCLUSION: Although the biological markers of IDC tended to suggest aggressive behavior more so than those of DCIS, these differences were based on the histological sub-type, comedo or non-comedo. The Van Nuys classification best defined the subgroups of DCIS with a distinct expression pattern of biological markers, and the best candidates for breast-conserving surgery.

Adult↗

PubMed2001

A case of basal cell carcinoma of the nipple and areola with intraductal spread.

We report an 82-year-old Japanese woman with basal cell carcinoma of the left nipple and areola extending into the lactiferous duct. The patient developed a small papular lesion of the left areola about 1 year before admission. The lesion, which had slowly progressed to involve the nipple, had become symptomatic showing weeping and bleeding. Mammography revealed microcalcification in the nipple. Although Paget's disease was suspected from these clinical features, histologically basal cell carcinoma was diagnosed. There was no axillary lymphadenopathy, and no evidence of distant metastasis. The lesion of the nipple and areola was resected with a 2 cm free margin along with the underlying mammary tissue. The patient has remained well without signs of recurrence for 2 years after surgery. We reviewed cases of basal cell carcinoma of the nipple or areola and discuss considerations and problems of this rare tumor.

Aged↗

PubMed2001

Point mutations of the RUNx1/AML1 gene in sporadic and familial myeloid leukemias.

The RUNX1/AML1 gene is known to be the most frequent target for chromosomal translocation in leukemia. In addition, recent studies have demonstrated point mutations in the RUNX1 gene as an another mode of genetic lesion resulting in leukemia. Of particular interest, sporadic point mutations of biallelic type are found in a tight association with either the acute myelogenous leukemia (AML) MO subtype or trisomy 21. Germline mutations give rise to a familial platelet disorder that results in a predisposition to acute myelogenous leukemia (FPD/AML). Most of the RUNX1 mutants were defective in DNA binding but still active in beta binding, a characteristic that is consistent with the 3-dimensional structural findings and may explain the dominant inhibitory effects. Although genuine haploinsufficiency of RUNX1 was observed in some cases, a greater majority of mutant RUNX1 proteins may also act in a dominant-negative manner, possibly creating a higher propensity for leukemia development. The stronger dominant-negative effect was also deduced to be the major mechanism of the chimeric genes created by chromosomal translocations. The decrement of RUNXI activity may be a common underlying cause for RUNX1-related leukemias. However, because these RUNX1 abnormalities per se are insufficient for leukemogenesis, cooperating genetic alteration(s) should be intensively sought for further mechanistic insights and future clinical applications.

Animals↗

PubMed2001

Dose-finding phase I study of simultaneous weekly infusion with doxorubicin and docetaxel in patients with advanced breast cancer.

BACKGROUND: Combination therapy with doxorubicin (DOX) and docetaxel (DOC), given 3 weeks apart, is one of the standard regimens used for treating metastatic breast cancer, but it frequently generates febrile neutropenia. To find a safer regimen with less myelotoxicity and the appropriate dose intensity, we conducted a phase I study of simultaneous weekly infusion with DOX and DOC. METHODS: Twenty-five patients with advanced breast cancer were treated with an intravenous push-injection of DOX that was immediately followed by a 1-h infusion of DOC. This was repeated every week for at least 6 weeks. The premedication employed was three 4-mg doses of dexamethasone every week. Patients were divided into four groups for which the doses of DOX and DOC were escalated in 5-mg/m2 increments. RESULTS: In the 18 patients who were treated with DOX 15 or 20 mg/m2 and DOC 25 mg/m2, or lower, the regimen was found to be tolerable, without febrile episodes. The regimen with 20 mg/m2 of DOX and 30 mg/m2 of DOC was the maximum tolerated dose. Other indications of grade 3 toxicity included asthenia in 4% of patients, anorexia in 8%, and vomiting in 8%. Of the 25 patients, 14 had a partial response. The overall response rate was 56% (95% confidence interval [CI], 35% to 77%). The recommended dose for further trial was 20 mg/m2 of DOX and 25 mg/m2 of DOC. CONCLUSION: Simultaneous weekly infusion with DOX and DOC was feasible, with modest neutropenia and preserved dose intensity. This regimen may be helpful in the management of patients with advanced breast cancer.

Adult↗

PubMed2001

Disease resistant, NOD-related strains reveal checkpoints of immunoregulation in the pancreas.

The autoimmune diabetic NOD mouse serves as a model for human type 1 diabetes. Disease development is due to islet beta cell destruction in the context of immune cell infiltration of islets and inflammatory changes throughout the pancreas. In the present study we tried to identify immune reactivity patterns in the pancreas associated with diabetes resistance in NOD-related mouse strains. The pancreata of diabetes-prone female NOD/LtJ, NOD/Bom and of genetically related but diabetes-resistant strains; NOR, NON, NON.NOD-H2g7, NOD.NON-H-2nbl were obtained at the age of 70 days for semiquantitative analysis of insulitis and of mRNA expression by reverse transcriptase PCR. In addition, the response to a single dose of cyclophosphamide for synchronizing and accelerating the progression of insulitis was determined. The progression of insulitis and immune gene expression in response to cyclophosphamide revealed characteristic differences between the six strains. NOD/LtJ and NOD/Bom mice were found significantly to upregulate pancreatic IL-12p40 and IL-18 expression after cyclophosphamide treatment, followed by an increase in IFN-gamma mRNA levels. In contrast, the two MHC-haplotype H-2nbl expressing strains either up-regulated neither IL-12/IL-18 nor IFN-gamma gene expression. The two strains sharing MHC haplotype H-2g7 expression with NOD did respond to cyclophosphamide with IL-12p40/IL-18 gene expression. However, NON.NOD-H-2g7 mice failed to progress to IFN-gamma gene expression. NOR mice progressed to IFN-gamma expression but exhibited sustained IL-4 gene expression. Only severe intra-insulitis was associated with the expression of inducible NO synthase. The comparison of diabetes-prone and diabetes-resistant strains revealed three checkpoints of immune regulation in the pancreas. The earliest checkpoint is the induction of an IL-12p40/IL-18 response in innate immune or antigen-presenting cells. The next level of control is at the induction of IFN-gamma gene expression, and a third checkpoint is the maintenance or loss of antagonistic Th2 type reactions.

Animals↗

PubMed2001

Neck muscle responses to abrupt vertical acceleration in the seated human.

The control of neck muscle during marked changes in "g" loading must be to protect head-trunk orientation. However, little is known about the organization of reflexes. We therefore investigated the shortest latency in neck muscle evoked by abrupt ascending and descending vertical acceleration with a stroke of 20 cm and peak acceleration 0.4xg in six healthy subjects. The subjects were seated upright and restrained on a chair driven by a hydraulic servo system. Ascent induced small responses in sternocleidomastoid muscles (SCMs) with a latency of 24.0 ms (SE 1.7) from onset of head acceleration, followed by larger responses of 100 ms in duration. In comparison the responses in SCMs evoked by descent were significantly delayed, with greater interindividual variations at 44.1 ms (SE 3.1) and smaller in amplitude than responses in ascent. Latencies were consistent and showed no habituation. In order to eliminate stretch components, we measured the neck responses to vertical acceleration with the head fixed by cervical collar. The latency of the fast response of SCM evoked by ascent was not significantly different from the latency of SCMs without the collar. These results may indicate that the fast responses of SCMs to sudden ascent may be composed of a vestibular-collic reflex for making the neck and head rigid for defense to sudden gravitational change.

Acceleration↗

PubMed2001

Comparative studies on the levels of serum IgG1 and IgG2a in susceptible B10.BR mice infected with different strains of the intestinal nematode parasite Trichuris muris.

Comparative studies were carried out on the levels of serum IgG1 and IgG2a in susceptible B10.BR mice infected with different strains of Trichuris muris (E-J and S strains). As infection proceeded, levels of IgG1 and IgG2a increased in mice infected with either strain until at least day 32 post-infection (p.i.). There were no differences in the IgG1 levels on days 14, 20, and 25 p.i. between mice infected with either E-J or S strain, whereas IgG2a levels on days 20, 25, and 32 p.i. were higher in S-infected mice than those in E-J-infected mice. Isotype switching to IgG2a is entirely dependent on interferon gamma (IFN-gamma) and, according to our previous results, the period of high IFN-gamma production in S-infected B10.BR mice is long compared to E-J-infected B10.BR mice. Thus, increased levels of IFN-gamma may sustain high levels of serum IgG2a in S-infected mice. Taken together, levels of serum IgG2a are useful markers of IFN-gamma production in T. muris infection.

Animals↗

PubMed2001

Late-onset biliary leakage after laparoscopic cholecystectomy using laparoscopic coagulating shears. Report of a case.

We recently encountered a rare case of late-onset biliary leakage after laparoscopic cholecystectomy using laparoscopic coagulating shears (LCS). The patient was a 49-year-old Japanese man who had undergone a laparoscopic cholecystectomy at Hamamatsu Medical Center after a diagnosis of cholecystolithiasis associated with localized adenomyomatosis. The cystic duct and the cystic artery were closed using LCS instead of metal endoclips. The postoperative course was uneventful, and the patient was discharged on the 4th operative day. However, on the 7th day after the surgery, the patient developed severe upper abdominal pain and was readmitted to our center with the diagnosis of a late biliary leakage, which was confirmed by an endoscopic retrograde cholangiogram. We then treated the leak successfully with endoscopic nasobiliary drainage.

Bile Ducts↗

PubMed2001

High sensitivity of a novel ELISA for anti-M2 in primary biliary cirrhosis.

The use of an ELISA for the detection of anti-M2, a specific autoantibody in primary biliary cirrhosis (PBC), has been common in Japan. However, there are some problems in the sensitivity of this ELISA, especially in PBC patients showing antimitochondrial antibody (AMA)-negative sera or low AMA titers by immunofluorescence. Recently, a new ELISA for anti-M2 was developed, using porcine heart mitochondrial protein as the antigen. We report here comparative studies of the new and the former anti-M2 ELISAs. Porcine heart mitochondrial protein was prepared and used as the antigen for the new ELISA for anti-M2. Sodium dodecylsulfate-polyacrylamide gel electrophoresis (SDS-PAGE) of this protein showed three major M2 antigen proteins. As the second antibody, peroxidase-conjugated anti-human mouse monoclonal IgM, in addition to monoclonal IgG, was included. The sera of 171 PBC patients were examined. As controls, we examined the sera of 167 non-PBC patients and the sera of 115 normal controls. The cut-off index was set at 10 U/ml, based on the results for the normal controls. No sera from the non-PBC patients or the normal controls were positive for anti-M2 by either the new or the former ELISA. However, the positivity rate for anti-M2 in PBC patients with the new ELISA was 78%; in contrast, that with the former ELISA was only 54%; this difference was significant (P = 0.00001). In particular, in 65 patients showing AMA titers of 1:20 or less, the positivity rate with the new ELISA was 51%; in contrast, that with the former ELISA was only 17%. As the sensitivity of the new ELISA is significantly higher than that of the former ELISA, especially for sera from patients showing AMA-negativity or low titers of AMA, the new ELISA is considered to be more effective than the former ELISA for use in anti-M2 screening assays in patients with PBC.

Animals↗

PubMed2001

Metachronous primary hyperparathyroidism due to a parathyroid adenoma and a subsequent carcinoma: report of a case.

An extremely rare case of metachronous primary hyperparathyroidism (PHP) due to a parathyroid adenoma and subsequent carcinoma with local lymphatic spread is presented herein. A 55-year-old woman was operated on for a parathyroid adenoma in the right inferior gland. Thirteen years after the first operation, she was again hospitalized for hypercalcemia and the presence of a hard mass in the right anterior neck region. Exploratory surgery and a histological examination of the resected tumor provided evidence of a parathyroid neoplasm in the right superior gland but the malignancy was equivocal. Postoperatively, her serum parathyroid hormone (PTH) level remained at 1.5-fold the upper limit of the normal range, and hypercalcemia again gradually developed. The results of higher positive rates by Ki-67 immunohistochemical staining and an aneuploid pattern by a flow cytometric analysis of the second neoplasm were consistent with a histological diagnosis of carcinoma, and she therefore underwent further surgery. A radical neck dissection revealed two lymph node metastases which were both successfully removed. The postoperative serum PTH and calcium levels then returned to within the normal ranges. These findings indicate the usefulness of Ki-67 immunohistochemical staining and a flow cytometric analysis for differentiating malignant lesions from benign parathyroid lesions, and the importance of surgically treating cases limited to local regions without distant metastasis.

Adenoma↗

PubMed2001

A RUNX2/PEBP2alphaA/CBFA1 mutation in cleidocranial dysplasia revealing the link between the gene and Smad.

Cleidocranial dysplasia (CCD), an autosomal dominant human bone disease, is thought to be caused by heterozygous mutations in RUNX2/PEBP2alphaA/CBFA1. To understand the mechanism underlying the pathogenesis of CCD, we studied a novel mutant of RUNX2, namely CCDalphaA376, originally identified in a CCD patient. The nonsense mutation, which resulted in a truncated RUNX2 protein, severely impaired RUNX2 transactivation activity. We showed that signal transducers of transforming growth factor (TGF)-beta and bone morphogenetic protein (BMP) receptors, Smads, interact with RUNX2 in vivo and in vitro and enhance transactivation ability. The truncated RUNX2 protein failed to interact with Smads, and was unable to induce the osteoblast-like phenotype in C2C12 myoblasts following stimulation with BMP. Exogenous expression of Smads 1 and 4 in C2C12 cells stably expressing RUNX2 showed alkaline phosphatase (ALP) activity, suggesting a possible link between Smads and RUNX2, while in C2C12 stably expressing CCDalphaA376, a detectable level of ALP activity failed to be induced. The results suggest that CCDalphaA376 inhibited RUNX2 function in a dominant negative fashion.

3T3 Cells↗

PubMed2001

The original hole-in-one guide for atlantoaxial transarticular screw fixation.

Atlantoaxial fusion by transarticular screw fixation provides firm fixation, and good results have been reported. However, there are also problems, such as injury of the vertebral artery at the time of screw insertion. For accurate facet fusion, we developed a new hole-in-one guide for screw fixation and obtained good results with its use. In 60 adult subjects. we measured the antero-posterior and transverse axes and determined the center of the atlantoaxial surface and the insertion point of the screw in three dimensions on computed tomography scans. Based on these values, we measured the optimum screw insertion angle on sagittal and coronal planes, and the distance between the center and the posterior margin of the joint surface; our new hole-in-one guide was produced with these data. When the guide tip is determined to be located at the center posterior margin of the axial joint surface, and the guidewire insertion point is determined to be located at the center of the axial inferior facet immediately above the C2/3 joint, the guidewire is passed through the axial pedicle and the center of the atlantoaxial joint. Since April 1997, we have used this hole-in-one guide technique in eight patients with atlantoaxial instability. The screws passed the pars interarticularis and the center of the atlantoaxial joint in all patients with safety and accuracy. No complications associated with this technique occurred.

Adult↗

PubMed2001

Immunohistochemical localization of amelogenin in human odontogenic tumors, using a polyclonal antibody against bovine amelogenin.

In the present study, we investigated the localization of amelogenin in odontogenic tumors, using an anti-amelogenin polyclonal antibody. In order to make the antibody, antisera against an amelogenin fraction obtained from the enamel matrix of unerupted bovine tooth was raised in rabbits. By Western blot analysis, a main band of 25 kDa and six minor bands (6.8, 12, 18, 20, 23, and 27 kDa) were detected under nonreducing conditions. Immunoreactivity for the amelogenin was observed in ameloblasts and in the immature enamel matrix of 4-day-old rats. In odontogenic tumors, positive reactions for amelogenin were localized in limited areas in adenomatoid odontogenic tumor, calcifying odontogenic cyst, primary intraosseous carcinoma and odontoma. The strongest immunoreactions were shown in enamel matrices in odontomas. Small mineralized foci in epithelial nests showed positive reactions, and a few reactions were observed in epithelium adjacent to the mineralized foci. In calcifying odontogenic cysts, some ghost cells in the lining epithelium were strongly stained. The results indicate that the present antibody for amelogenin is useful for the determination of odontogenic tumors, especially in those in which small mineralized foci are present in the epithelial nests.

Amelogenin↗

PubMed2001

Colour Doppler sonographic analysis of blood-flow velocity in the human facial artery and changes in masseter muscle thickness during low-level static contraction.

Muscle oedema, which can be seen as a thickness increment by ultrasonography, is important in provoking pain and fatigue during low-level contraction. Although oedema is related to the balance of inflow and outflow of blood, there are no data on the correlation between muscle thickness change and blood-flow. Blood-flow velocities in the facial artery and the muscle thickness changes were measured by colour Doppler ultrasonography in 30 healthy volunteers during 20 min contraction with 10% of maximum force. Thickness and velocity changes both reached a peak in the initial phase of contraction. The initial change of thickness did not correlate with the velocity in the facial artery, while those immediately after exercise showed a high correlation. The velocity changes in the facial artery might depend on both the general response to contraction and local metabolic or mechanical factors in the contracted masseters.

Adolescent↗

PubMed2001

MR studies of retinal oxygenation.

In this paper, we summarize the development and application of two novel magnetic resonance based measurements of retinal oxygenation in experimental models of retinopathy, including diabetic retinopathy and retinopathy of prematurity. We use 19F-NMR and a small (microl) perfluorocarbon drop positioned in the preretinal vitreous space to make PO2 measurement of the inner retina. In addition, we use magnetic resonance imaging (MRI) to accurately and non-invasively measure the change in the preretinal PO2 (DeltaPO2) following the shift from breathing room air to a hyperoxic inhalation challenge. The advantages and disadvantages of each method are discussed. New applications of these techniques in the newborn rat and adult mouse are presented. We expect such studies to motivate future MRI oxygenation studies of human retinopathy, including diabetic retinopathy and retinopathy of prematurity.

Animals↗