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Biomedical subjects

K Ueki

Publications and source records attributed to K Ueki.

At least 91 records · Page 5Linked to original sources
PubMed1999

VHL gene inactivation in an endolymphatic sac tumor associated with von Hippel-Lindau disease.

The authors present a case of endolymphatic sac tumor, a rare adenomatous tumor of the temporal bone, in a patient with von Hippel-Lindau (VHL) disease. Sequencing and microsatellite analysis of DNA samples from the tumor showed a 1-base pair deletion in exon 1 of the VHL gene and loss of heterozygosity at chromosome 3p25.5, the locus for the VHL gene. The results indicate that VHL gene inactivation contributed to the oncogenesis of endolymphatic sac tumor and provide molecular genetic proof that this tumor is associated with VHL disease.

Adult↗
PubMed1999

Relief of hemiballism from a basal ganglia arteriovenous malformation after radiosurgery.

A patient with a 3-year history of progressive hemiballism presented with an unruptured arteriovenous malformation (AVM) in the contralateral caudate nucleus and putamen. PET demonstrated a matched reduction of cerebral blood flow (CBF) and cerebral metabolic rate of oxygen (CMRO2) in the basal ganglia and adjacent frontal lobe. The patient underwent radiosurgery for the AVM. After a period of no clinical change for 6 months, the movement disorder resolved by month 7 post-treatment. The AVM was successfully obliterated 2 years after irradiation without any significant change in the regional CBF or CMRO2.

Arteriovenous Malformations↗
PubMed1999

Correlation between tumor angiogenesis and expression of thymidine phosphorylase, and patient outcome in uterine cervical carcinoma.

The relationship between tumor angiogenesis and the expression of thymidine phosphorylase (dThdPase) in uterine cervical carcinoma tissues, as well as patient outcome, were investigated. Primary tumor specimens surgically obtained from 54 patients (stages Ib to IIIb) receiving neither chemotherapy nor radiation therapy before surgery were examined. Intratumoral microvessel density (IMVD) and dThdPase expression were evaluated immunohistochemically using anti-CD34 and anti-dThdPase antibodies and were correlated with clinicopathologic parameters and prognosis. IMVD for the 54 tumors ranged from 24.8 to 118.6, with a median value of 57.7 (number/0.7386 mm2/field). For immunoreactivity of dThdPase, 16 tumors were graded as -, 20 as 1+, and 18 as 2+. IMVD was significantly associated with the expression of dThdPase (P<.01). Both IMVD and dThdPase expression were well correlated with depth of myometrial invasion, endometrial invasion, and pelvic lymphnode metastasis (P<.05). Overall survival rates for 18 patients with strong dThdPase-staining tumors, assessed as 2+, were lower than those for 36 with weak dThdPase staining tumors (P = .0108). However, there was no statistical correlation between IMVD and patient outcome. The expression of dThdPase plays a role in the promotion of angiogenesis and affects the patient's survival in uterine cervical carcinomas.

Antigens, CD34↗
PubMed1999

A case of cimetidine-induced acute tubulointerstitial nephritis associated with antineutrophil cytoplasmic antibody.

We present a case of acute tubulointerstitial nephritis (ATIN) that developed in a 63-year-old man who had been taking cimetidine for treatment of a gastric ulcer. The constellation of clinical, laboratory, and histopathologic findings suggested drug-induced ATIN. Of interest, the patient had antineutrophil cytoplasmic antibody (ANCA) in his sera, reactive with myeloperoxidase, elastase, and lactoferrin. Prominent renal histological features included marked plasmacyte infiltration into the renal interstitium. Withdrawal of cimetidine resulted in complete resolution of renal findings, and the titers of ANCA concomitantly declined. Thus, cimetidine may have played a causative role in the development of ANCA-associated ATIN.

Anti-Ulcer Agents↗
PubMed1999

Increased insulin sensitivity and hypoglycaemia in mice lacking the p85 alpha subunit of phosphoinositide 3-kinase.

The hallmark of type 2 diabetes, the most common metabolic disorder, is a defect in insulin-stimulated glucose transport in peripheral tissues. Although a role for phosphoinositide-3-kinase (PI3K) activity in insulin-stimulated glucose transport and glucose transporter isoform 4 (Glut4) translocation has been suggested in vitro, its role in vivo and the molecular link between activation of PI3K and translocation has not yet been elucidated. To determine the role of PI3K in glucose homeostasis, we generated mice with a targeted disruption of the gene encoding the p85alpha regulatory subunit of PI3K (Pik3r1; refs 3-5). Pik3r1-/- mice showed increased insulin sensitivity and hypoglycaemia due to increased glucose transport in skeletal muscle and adipocytes. Insulin-stimulated PI3K activity associated with insulin receptor substrates (IRSs) was mediated via full-length p85 alpha in wild-type mice, but via the p50 alpha alternative splicing isoform of the same gene in Pik3r1-/- mice. This isoform switch was associated with an increase in insulin-induced generation of phosphatidylinositol(3,4,5)triphosphate (PtdIns(3,4,5)P3) in Pik3r1-/- adipocytes and facilitation of Glut4 translocation from the low-density microsome (LDM) fraction to the plasma membrane (PM). This mechanism seems to be responsible for the phenotype of Pik3r1-/- mice, namely increased glucose transport and hypoglycaemia. Our work provides the first direct evidence that PI3K and its regulatory subunit have a role in glucose homeostasis in vivo.

Animals↗
PubMed1999

Glomerular overexpression and increased tyrosine phosphorylation of focal adhesion kinase p125FAK in lupus-prone MRL/MP-lpr/lpr mice.

Much progress has been made in understanding how mammalian cells receive a diverse array of external stimuli and convert them into intracellular biochemical signals. Such efforts have identified a large number of signalling molecules. However, our knowledge is limited as to their pathophysiological role in particular diseases. We demonstrate herein that an integrin-linked signalling molecule, focal adhesion kinase p125FAK (FAK), is overexpressed in glomeruli of lupus-prone MRL/MP-lpr/lpr (MRL-lpr) mouse as compared to its congeneic MRL-+/+ strain. Increased expression was specifically demonstrated in glomeruli but not in other tissues examined. The overexpression was observed in 16-week-old MRL-lpr mice with active nephritis, as well as in younger animals at 4 weeks of age. Thus, the upregulation of FAK clearly preceded the clinical onset of nephritis. FAK in MRL-lpr glomeruli is highly tyrosine phosphorylated and is associated with adapter protein Grb2. Previous in vitro studies have shown that the association of FAK/Grb2 links cell adhesion to the Ras pathway, which ultimately stimulates mitogen-activated protein (MAP) kinase, an important regulator of cell proliferation. In accordance, we observed constitutive MAP kinase activation in MRL-lpr glomeruli. Our findings suggest that signalling pathways involving FAK are activated in MRL-lpr glomeruli, and are likely to play a role in the development and progression of autoimmune-mediated murine nephritis.

Adaptor Proteins, Signal Transducing↗
PubMed1999

Effect of Bcl-2 overexpression in human prostate cancer cells in vitro and in vivo.

BACKGROUND: Cancer cells often develop mechanisms to resist apoptosis and the extent of such anti-apoptotic ability has been shown to parallel tumor progression in various malignancies. Among various molecules implicated in regulating apoptosis pathway, bcl-2 and its family members are best characterized. METHODS: To investigate the effect of bcl-2-mediated anti-apoptotic ability on tumor growth and progression in prostate cancer, a cell line overexpressing bcl-2 (LNCaP/bcl-2) was established by genetically engineering a prostate cancer cell line LNCaP. Tumor growth of LNCaP/bcl-2 was compared with the parental cell line in vitro and in vivo. RESULTS: LNCaP/bcl-2 cells show resistance to apoptosis caused by nutrient deprivation and did not arrest when cultured in serum-free or androgen-free medium, while parental LNCaP cells or LNCaP cells transfected with the vector only (LNCaP/control) underwent extensive apoptosis on nutrient deprivation and sustained growth suppression in serum-free or androgen-free medium. When injected subcutaneously into nude mice, tumors deriving from LNCaP/bcl-2 cells grew faster compared with LNCaP/control for about 3 weeks (P = 0.02), but this effect was not evident after 5 weeks. Upon castration, the control tumors regressed but LNCaP/bcl-2-derived tumors showed resistance, as was previously reported. CONCLUSIONS: These data confirm the notion that anti-apoptotic function of bcl-2 is oncogenic and confers resistance to androgen deprivation and also indicate that it may also play a critical role in earlier stages of tumorigenesis.

Androgens↗
PubMed1999

Condylar changes after contralateral mandibular osteotomy in the rabbit.

Following orthognathic surgery undesirable changes in the temporomandibular joints (TMJs) are noted sometimes. Altered stress on the condyle and surrounding tissue frequently causes morphological changes in the TMJ. The purpose of the present study was to assess these morphologic changes in a rabbit following mandibular osteotomy and the resulting mandibular body rotation. Adult male Japanese white rabbits (3 kg, 12-16 weeks old) were applied in this study. An experimental mandibular osteotomy was performed on the right side of the body of the mandible. The surgery includes vertical mandibular body osteotomy 5 mm in width after masseter muscle reflection. Then the anterior and posterior osseous segments were fixed with wire at previously made holes. As a result, the condylar medio-lateral width on the contralateral (left) side was significantly larger than that of the ipsilateral side 2 weeks postoperatively (p < 0.05). There were significant differences in the angle between the right and the left condylar heads 4 weeks postoperatively (p < 0.05). The present experimental study demonstrated morphological changes in the contralateral TMJ caused by unilateral mandibular osteotomy. Postoperative morphological changes implied that there is a process of biological adaptation in the rabbit TMJ.

Adaptation, Physiological↗
PubMed1999

Fas ligand, Fas antigen and Bcl-2 expression in human endometrium during the menstrual cycle.

In this study, we investigate Fas ligand expression in the human endometrium during the menstrual cycle in relation to Fas antigen and Bcl-2 expression, using immunoelectron microscopy and Western blotting. Endometrial samples were obtained from 54 pre-menopausal non-pregnant women who underwent laparotomies for benign diseases. The Fas ligand, as well as the Fas antigen, were expressed on the surface of endometrial glandular cells throughout the menstrual cycle, whereas Bcl-2 showed a cyclic expression pattern, peaking during the late proliferative phase. A noteworthy finding was that both the Fas ligand and the Fas antigen were localized on Golgi apparatuses and vesicles, in addition to the cell membranes, during the late proliferative phase. These results indicate that the Fas ligand and Fas antigen which are localized on Golgi apparatus and vesicles during the late proliferative phase are incorporated into the cell membranes during the secretory phase, and are co-expressed on the cell membranes of endometrial glands throughout the menstrual cycle. The factors regulating Fas-mediated apoptosis in the human endometrium, including the level of expression of the Fas ligand and Bcl-2 are discussed.

Adult↗
PubMed1999

Snowboard head injury: prospective study in Chino, Nagano, for two seasons from 1995 to 1997.

BACKGROUND: The popularity of snowboarding has been growing rapidly throughout the world. To date, however, the risk of head injury associated with this relatively new winter sport, especially in comparison with alpine skiing, has not been well analyzed. This study was conducted to assess the risk of head injury in snowboarding and to elucidate its features in comparison with skiing head injury. METHODS: We prospectively analyzed 301 cases of head injuries related to snowboarding or skiing experienced from December of 1995 to May of 1997 at our institution, which is located close to the most popular skiing areas in Japan. Of those injuries, 143 cases were snowboard related and 158 cases were ski related. In addition to appropriate medical evaluation and medical care, detailed examination was performed on every patient to determine various factors, including sex, age, skill level, cause and mechanism of the accident, and the side of impact to the head. The data are statistically analyzed to elucidate unique features of snowboard head injury. RESULTS: During the study period, 2.2 million snowboarders and 4.2 million skiers visited the five skiing facilities that are covered by our hospital. Thus, the incidence of head injury was 6.5 per 100,000 visits for snowboarders and 3.8 per 100,000 visits for skiers. Beginning snowboarders more frequently sustained head injuries compared with beginning skiers (60 of 142 vs. 48 of 154, p = 0.022). Likewise, frequent causes of snowboarding head injuries were fall during jumping (43 of 139 vs. 2 of 147, p<0.0001), falling backward (67 of 127 vs. 49 of 144, p = 0.001), and occipital impact (67 of 126 vs. 49 of 147). More importantly, there were nine major head injury cases (6.3%) in snowboard head injuries in contrast to only two such cases found in skiing head injuries (1.3%). Of 11 major head injury cases, 10 were caused by occipital impact. CONCLUSION: These results indicate that snowboarders, particularly beginners, are at higher risk for head injury, frequently involving occipital impact, and could lead to more major head injuries. We propose that measures should be taken to protect the head, especially the occiput, in snowboarding.

Adolescent↗
PubMed1999

Biological implications of growth factors on the mechanism of invasion in gynecological tumor cells.

We investigated the effects of epidermal growth factor (EGF) and transforming growth factor-alpha (TGF-alpha) on migration, invasion and proteinase expression of gynecological cultured cancer cells (SKG-IIIb cervical squamous cell carcinoma, OMC-4 cervical adenocarcinoma, SNG-M endometrial adenocarcinoma and OMC-3 ovarian adenocarcinoma), and whether these growth factors affect thymidine phosphorylase/platelet-derived endothelial cell growth factor expression of tumor cells. Tumor cell migration along a gradient of substratum-bound fibronectin and invasion into reconstituted basement membrane were stimulated by 0.1-10 nM EGF and TGF-alpha in a concentration-dependent manner. The zymography of tumor-conditioned medium showed that the treatment of tumor cells with EGF and TGF-alpha resulted in the increase of type IV collagenases, stromelysin and urokinase-type plasminogen activator which was partly confirmed by immunoblot analysis. The expression of thymidine phosphorylase/platelet-derived endothelial cell growth factor which has angiogenic activity, was also upregulated by these growth factors. These results suggest that EGF and TGF-alpha act as positive regulators on the invasion process of gynecological tumor cells which may be associated with their stimulatory action on the motility of tumor cells, the expression of proteinases secreted by tumor cells and the angiogenic phenotype.

Adenocarcinoma↗
PubMed1999

Magnetic resonance imaging of pseudotumors of the craniovertebral junction in long-term hemodialysis patients.

BACKGROUND/AIMS: Pseudotumors of the craniovertebral junction (PTCVJ) are observed in long-term hemodialysis (HD) patients. There are neither criteria for diagnosis nor guidelines for screening. We attempted to determine magnetic resonance imaging (MRI) findings that could be used to detect PTCVJ, to determine the prevalence of PTCVJ, and to evaluate whether destructive spondyloarthropathy (DSA) might be a yardstick for selection of patients for MRI examination for PTCVJ. METHODS: MRI were examined in 19 DSA patients (8 males, 11 females, age 61.4 +/- 7.3 years, HD duration 17.0 +/- 4.4 years) and in 20 sex-, age-, and HD-duration-matched non-DSA patients (9 males, 11 females, age 57.5 +/- 6.6 years, HD duration 17.7 +/- 4.9 years). We evaluated MRI characteristics of PTCVJ according those which occur due to rheumatoid arthritis. RESULTS: PTCVJ were characterized as follows: disappearance of fat pads in the upper region (supradental PTCVJ), intensity change of the 'predental triangle' in the anterior region (predental PTCVJ), and thickening of cruciform ligaments (retrodental PTCVJ). The prevalence of PTCVJ among patients undergoing HD more than 10 years was high (26 out of 39; 66.7%). The prevalence of PTCVJ was not different between DSA and non-DSA groups. CONCLUSION: We verified that the above MRI findings might be helpful in the detection of PTCVJ. These findings were observed frequently and independently also in patients with DSA.

Amyloidosis↗
PubMed1999

Risk of subarachnoid hemorrhage after surgical treatment of unruptured cerebral aneurysms.

BACKGROUND AND PURPOSE: Recent progress in noninvasive imaging techniques has resulted in increased detection of unruptured aneurysms. Although many neurosurgeons advocate surgical intervention for such unruptured aneurysms, the long-term results of surgery for unruptured aneurysms have not been carefully investigated. METHODS: We analyzed 173 consecutive patients who had unruptured intracranial saccular aneurysm(s) detected by angiography that was performed for reasons other than subarachnoid hemorrhage (SAH). Of those, 115 cases were surgically treated and studied. All patients were followed up for either SAH, repeat treatment of aneurysms, or death. The median follow-up period was 8.8 years. RESULTS: Four of the 115 patients suffered SAH either from a de novo aneurysm (2) or from regrowth of clipped aneurysm (1), or from regrowth after wrapping (1). Additionally, 1 patient also suffered SAH from an unstudied basilar aneurysm. One patient was incidentally found to have de novo aneurysm and underwent reoperation 14 years after the first operation. The cumulative risk for SAH for the 114 cases excluding the basilar aneurysm case was 1.4% in 10 years and 12.4% in 20 years. CONCLUSIONS: Although this study confirmed the long-term efficacy of clipping unruptured aneurysms, the risk of SAH was high compared with that in the general population, even after treatment. Considering the high mortality rate of SAH, long-term follow-up by angiography may be warranted for patients with surgically treated unruptured aneurysms.

Adult↗
PubMed1999

The mechanism of insulin-induced signal transduction mediated by the insulin receptor substrate family.

Distinct from other growth factor receptors, insulin and insulin-like growth factor-I (IGF-I) receptors phosphorylate endogenous substrates on tyrosine residues which in turn associate with the SH2 domain-containing proteins transducing signals to downstream pathways. Among the cellular substrates of insulin and IGF-I receptors, insulin receptor substrate (IRS)-1 has been shown to play an important role in mediating the actions of these hormones. Recently, several proteins with similar structures and different tissue distributions were cloned as IRS-2, -3 and -4. To study the roles of these IRSs in mediating insulin actions, we analyzed liver, muscle and adipocytes, the major targets of insulin actions, from IRS-1 null mice which we previously generated, and showed that: 1) insulin-stimulated activation of PI 3-kinase, mitogen-activated protein kinase and glucose transport were impaired in muscles from IRS-1 null mice which was in contrast to the grossly normal signaling and actions in livers from these mice; 2) the difference in the degree of insulin resistance in these two major insulin targets appeared to depend on the amount of tyrosine phosphorylation of IRS-2 compensating for IRS-1 deficiency; 3) insulin-induced activation of PI 3-kinase, glucose transport and GLUT4 translocation were impaired but not abolished in adipocytes from these mice in which IRS-3 was the major tyrosine-phosphorylated protein activating PI 3-kinase and at least partially mediating some residual insulin actions in the absence of IRS-1. These data suggest that the members of the IRS family redundantly regulate insulin actions in each target organ in a distinct fashion.

Adipocytes↗
PubMed1999

Apoptosis and Bbcl-2 expression in gastric carcinomas: correlation withclinicopathological variables, p53 expression, cell proliferation and prognosis.

We investigated apoptosis and Bcl-2 expression in 221 advanced gastric carcinomas in correlation with clinicopathological variables, p53 expression, cell proliferation and prognosis, using the in situ DNA nick end labeling method and immunohistochemistry. Apoptosis was associated with high immunoreactivity of proliferating cell nuclear antigen. Bcl-2 expression correlated with a low apoptotic index and less malignant behavior of tumors. Prognostically, Bcl-2 expression was associated with a better prognosis, whereas p53 expression was the most important prognostic risk factor. Thus, apoptosis in gastric carcinomas is associated with cell proliferation, and Bcl-2 expression may have a prognostic importance as well as p53 expression.

Apoptosis↗
PubMed1999

Successful low-dose cytosine arabinoside treatment in a patient with acute leukemia from idiopathic myelofibrosis.

We report a 63-year-old male with acute leukemia developed from idiopathic myelofibrosis. Cytogenetic analysis revealed chromosomal abnormalities; 46,XY,t(3;21)(q21;q22) del(20q). Intensive chemotherapies [combination of adriamycine/vincristine/prednisolone, or idarubicine/cytosine arabinoside (Ara-C)] were unsuccessful. The patient was then treated with continuous intravenous low-dose Ara-C because of his poor physical condition and showed marked hematological improvement. Leukemic cells disappeared from the peripheral blood and the segmented neutrophil count recovered. The dysplastic morphology observed in the segmented neutrophils suggests that the recovery of the neutrophils has resulted mainly from the differentiation activity of Ara-C.

Acute Disease↗
PubMed1999

Pathological indications for conservative therapy in treating cervical cancer.

BACKGROUND: Neodymium-ytlium, argon, gadolinium (Nd-YAG) laser conization was performed in 366 patients with carcinoma in situ (CIS), and 198 with microinvasive carcinoma (MIC), and 29 with early invasive cancer (IC). The diagnostic accuracy was 72.5% in the CIS group, and 74.6% in the MIC and early IC group. RESULTS: All of the patients who obtained complete excision are now alive and doing well following the conization, with no evidence of recurrence of the disease. Incomplete excision was found in 21.7% of the MIC, 50.0% of the IC with 3 mm or less invasion, 22.2% of the IC with 3.1-4 mm, 60.0% of the IC with 4.1-5 mm invasion, 100% of the IC with 5 mm or more invasion. The residual rate of the MIC and IC with 4 mm or less invasion was 8.5%, lower than 62.5% of the IC with 4.1-5 mm invasion. The cure rate by conization in the patients with IC of 4.0 mm or less was much higher than that in the patients with IC of over 4.1 mm. CONCLUSIONS: These results suggested that the indication of laser conization for early IC was the case within 4 mm invasion, completely excised.

Adult↗