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Biomedical subjects

M Uno

Publications and source records attributed to M Uno.

At least 19 recordsLinked to original sources

Anti-HER2-antibody enhances irradiation-induced growth inhibition in head and neck carcinoma.

To explore the antiproliferative effects of rhumAbHER2 on head and neck squamous carcinoma cell (HNSCC) lines and breast cancer cell lines (BCCLs) and to evaluate the combined effects with irradiation, 2 human HNSCC lines and 2 BCCLs were exposed to rhumAbHER2 with or without irradiation. The results showed that combined treatment enhanced the growth and colonization inhibitory effects of rhumAbHER2 or irradiation. Interestingly, the apoptotic cell fraction produced by irradiation disappeared on combined treatment. This disappearance was associated with repression of p53 and Bax upregulation induced by irradiation, but conservation of the upregulation of p27. Based on these results, rhumAbHER2 and irradiation may be a new strategy for treating HNSCC and breast cancers. In addition, the upregulation of cyclin-dependent kinase inhibitors by rhumAbHER2 may occur upstream of irradiation-induced p53 upregulation.

Apoptosis↗

Multivariate analysis of regional metabolic differences in normal ageing on localised quantitative proton MR spectroscopy.

We performed multivariate analysis of regional differences and normal age-related changes in metabolites in the lentiform nucleus and frontal lobe, as measured by proton MRS. The cerebrospinal fluid (CSF) in the measurement area was estimated and the metabolite concentration adjusted. The concentration of N-acetylaspartate (NAA) in the lentiform nucleus decreased with ageing (F = 4.11, P < 0.01), but that in the frontal lobe did not change (F = 0.93, P = 0.45). This is in marked contrast with pathological dementia, such as Alzheimer's disease. In this multivariate analysis, the normal change in metabolism with ageing differed depending on the cerebral region, suggesting that metabolite concentrations, especially that of NAA may be useful metabolic indices for discriminate normal ageing from pathological dementia.

Adult↗

Guglielmi detachable coil embolization for ruptured lower-midbasilar trunk aneurysms--a report of five cases.

Detachable coil embolization currently plays an essential role for patients with ruptured basilar artery aneurysms, even though it may have an unfavorable outcome and there may be some technical problems of embolization. We describe Guglielmi detachable coil (GDC) embolization for five ruptured lower-mid basilar trunk aneurysms, using a variety of techniques. The patients' ages ranged from 61 to 78 years; Hunt and Kosnik grade was distributed from 2 to 4, and three patients were found to have fenestrations of the lower basilar arteries. All patients underwent aneurysmal embolization at the subacute or chronic stage. The transfemoral route was used in three patients--one of whom, with a wide-necked aneurysm, was treated by the balloon remodeling technique. The transbrachial approach was chosen for the fourth patient, while vertebral artery origin exposure followed by a direct puncture was achieved in the fifth. All patients were assessed with 80-100% aneurysmal obliteration. No patient re-bled after the embolization. Small cerebellar infarction, possibly due to embolism from the obliterated aneurysmal sac, occurred 11 days after the treatment. Of the five patients, four achieved a good recovery, and one became severely disabled. Ruptured basilar trunk aneurysms can be successfully treated with GDC embolization. In addition to the routine transfemoral route, the transbrachial route, direct vertebral artery puncture, and balloon remodeling technique are also useful for the embolization of this location of aneurysm.

Aged↗

Synergistic effect of polymorphisms of uncoupling protein 1 and beta3-adrenergic receptor genes on autonomic nervous system activity.

OBJECTIVE: To investigate the association of the promoter region -3826 A to G polymorphism of the uncoupling protein 1 (UCP1) gene with autonomic nervous system (ANS) activity and the interaction of the polymorphism with the Trp64Arg polymorphism of the beta3 adrenergic receptor (beta3AR). SUBJECTS: Three-hundred and forty-nine young (mean age 20.4+/-2.1 y old), healthy Japanese males. MEASUREMENTS: DNA was extracted from whole blood and genotyped by polymerase chain reaction restriction fragment length polymorphism. Plasma glucose, plasma insulin and body mass index (BMI) were measured. Frequency of family history of diabetes or obesity was determined by interview. Subjects randomly chosen from each genotype were examined for ANS activity during supine rest and standing by electrocardiogram power spectral analysis of heart rate variability. RESULTS: UCP1 or beta3AR polymorphism was not associated with BMI, plasma glucose, plasma insulin and frequency of family history of diabetes or obesity. The inhibitory effect of UCP1 polymorphism on ANS activity was observed only with occurrence of the variant of beta3AR. The very low frequency component associated with thermoregulation in the sympathetic nervous system of homozygotes of UCP1 (GG) at supine rest was significantly lower than normal (AA, 203.2+/-50.3 vs 462.2+/-83.6 ms(2); mean+/-s.e., P=0.021). A higher response to postural change to standing was also observed in both sympathetic and parasympathetic nervous activities of AA than of GG. CONCLUSION: While UCP1 polymorphism alone does not affect ANS activity, it has a synergistic effect with beta3AR polymorphism in decreasing sympathetic nervous system activity.

Adult↗

In vitro induction of apoptosis for nasal angiocentric natural killer cell lymphoma-derived cell line, NK-YS, by etoposide and cyclosporine A.

Epstein-Barr virus (EBV)-associated nasal T/natural killer (NK) cell lymphoma has often been reported in Asian countries and has been recently confirmed as a novel clinicopathological entity. The prognosis of advanced stage disease is quite poor and an effective chemotherapeutic modality is strongly advocated. We have established the novel cell line NK-YS, which preserves the original characteristics of EBV-associated nasal angiocentric T/NK cell lymphoma. Using this cell line, we investigated the induction of apoptosis by apoptosis-inducing agents, and expression of P-glycoprotein (P-gp), p53 and bcl-2 proteins. NK-YS showed resistance towards apoptosis-inducing agents and expressed bcl-2 and P-gp but not p53. To overcome this drug resistance, we added cyclosporine A (CsA) and these agents to culture media as a P-gp antagonist. The combination of CsA and etoposide or CsA and doxorubicin induced apoptotic cell death. These results indicated that P-gp-mediated drug resistance is an essential mechanism of drug resistance of the NK-YS cell line. Combined therapy of conventional anti-cancer agents with CsA may have an important place in the establishment of a curative therapy for disseminated nasal angiocentric NK cell lymphoma.

ATP Binding Cassette Transporter, Subfamily B↗

Cell cycle analysis and expression of cell cycle regulator genes in myeloma cells overexpressing cyclin D1.

Among the recently discovered myeloma-specific gene alterations associated with chromosomal translocations, cyclin D1/PRAD1/Bcl-1 overexpression caused by t(11;14)(q13;q32) is considered to be the most frequent in myeloma patients and cell lines, and may be a prognostic factor clinically. To elucidate the cellular biological role of overexpressed cyclin D1 in myeloma cells, we examined the mRNA expression levels of cell cycle regulators including three cyclin Ds, cyclin-dependent kinase inhibitors (CDK-Is) and accelerators. Cyclin D1 overexpression was clearly demonstrated in the lines with abnormal 11q13 and associated with overexpression of S and G2 accelerator genes. The cyclin D1-overexpressing lines tended to have a shortened G1 phase compared with the non-expressing lines. In addition, artificial silencing using antisense oligonucleotides for cyclin D1 suppressed the growth rate of some but not all cyclin D1-overexpressing cells. These results indicate that overexpression of cyclin D1 caused by cytogenetic abnormalities may make cells progress through the cell cycle rapidly, but it seems that other factors such as cyclin D2 and translocation-related genes affect the cell cycle progression in myeloma cells.

Cell Cycle↗

Combined therapeutic approach of intra-arterial thrombolysis and carotid endarterectomy in selected patients with acute thrombotic carotid occlusion.

PURPOSE: The feasibility and clinical outcome of intra-arterial thrombolysis followed by carotid endarterectomy (CEA) for acute thrombotic occlusion of the internal carotid artery (ICA) were evaluated. METHODS: Intra-arterial thrombolysis and CEA were performed in four patients with acute thrombotic ICA occlusion. Computed tomography scans, cerebral angiograms, and the severity of carotid plaques were examined, and the patients' clinical outcome was evaluated. RESULTS: All 4 patients had severe hemiparesis; 3 patients were alert, and 1 patient was lethargic at the time of hospital admission. New lesions were not shown by means of the initial computed tomography scan. ICA occlusion was indicated in all four patients by means of cerebral angiograms; in three patients, middle cerebral artery occlusion was noted. Collateral circulation was manifested in all patients. Partial recanalization of the occluded ICA was obtained in all patients. Two patients with severe residual ICA stenosis underwent an emergency CEA soon after thrombolysis; the other two patients were treated by means of CEA in the subacute or chromic stage. Plaque rupture and intraplaque hemorrhage were seen in all four patients. All four patients recovered completely, and restenosis of the ICA was not shown by means of follow-up angiograms. CONCLUSION: Intra-arterial thrombolysis followed by CEA may be an effective therapeutic approach for treating acute thrombotic ICA occlusion. The optimal timing of CEA remains controversial.

Acute Disease↗

Carotid endarterectomy with external shunt: a new device and indication for use: technical note.

OBJECTIVE: We designed a new external shunt system and evaluated its indications and efficacy in patients undergoing carotid endarterectomy (CEA). METHODS: In 8 of 332 CEA procedures, external shunts were placed between the common carotid artery and the internal carotid artery (ICA). This procedure was implemented for one of two indications: 1) a change in electroencephalographic and/or somatosensory evoked potential readings immediately after ICA occlusion, or 2) elongation of the ICA made safe insertion of an internal shunt impossible. In addition, a shunt was placed between the common carotid artery and the external carotid artery to establish collateral circulation from the external carotid artery to the intracranial circulation, which is essential during ICA occlusion. RESULTS: All external shunts were functional, and electroencephalography and somatosensory evoked potentials demonstrated no significant abnormalities during the CEAs. All patients awoke from surgery without manifestation of new neurological deficits. CONCLUSION: Our new external shunt device proved safe and efficacious in cases that did not permit the placement of an internal shunt.

Aged↗

Measurements of both hippocampal blood flow and hippocampal gray matter volume in the same individuals with Alzheimer's disease.

We evaluated both hippocampal blood flow and hippocampal gray matter volume using single photon emission tomography and magnetic resonance imaging in the same individuals with Alzheimer's disease (AD) and in age-matched controls. The hippocampal blood flow was not significantly lower in mild AD patients (n = 21, Mini-Mental State Examination (MMSE) 23.3+/-2.1) than in controls (n = 16) with a 57% overlap. The hippocampal blood flow was significantly lower in advanced AD patients (n = 22, MMSE 15.4+/-3.2) than in controls. The hippocampal gray matter volume was significantly smaller in mild AD patients than in controls, although a 43% overlap was present. There was no significant difference in the hippocampal gray matter volume between the mild and advanced AD patients. The combination of measurements of hippocampal blood flow and gray matter volume discriminated 71% of mild AD patients from controls. These results suggest the usefulness of a combined analysis of hippocampal blood flow and gray matter volume for the early diagnosis of AD.

Aged↗

Helicobacter pylori seropositivity among 963 Japanese Brazilians according to sex, age, generation, and lifestyle factors.

Seropositivity of anti-Helicobacter pylori antibody (HP + ) was examined among Japanese Brazilians. The study was announced through 18 Japanese community culture associations in São Paulo, Curitiba, Mogi das Cruzes, and Mirandopolis in 2001. Among 969 participants, 963 individuals aged 33 - 69 years were analyzed. The overall HP + % was 48.1% (95% confidence interval, 44.9 - 51.3%). There was no difference in HP + % between 399 males and 564 females (49.6% and 47.0%, respectively). The HP + % increased with age; 35.3% for those aged 33 - 39 years, 46.2% for those aged 40 - 49 years, 46.5% for those aged 50 - 59 years, and 56.9% for those aged 60 - 69 years, but no differences were observed among the generations (Issei, Nisei, and Sansei) for each 10-year age group. Mogi das Cruzes, a rural area, showed a higher HP + %. Length of education was inversely associated with the positivity; the odds ratio (OR) relative to those with eight years or less of schooling was 0.61 (0.42 - 0.89) for those with 12 years or more. The associations with smoking and alcohol drinking were not significant. Fruit intake was associated with the HP + %; the OR relative to everyday intake was 1.38 (1.05 - 1.83) for less frequent intake, while intake frequencies of green tea, miso soup, and pickled vegetables (tsukemono) were not. Multivariate analysis including sex, 10-year age group, residence, education, and fruit intake showed that all factors except sex were significant. This is the largest study of HP infection among Japanese Brazilians, and the results indicated a similar pattern of age-specific infection rate to that for Japanese in Japan.

Adult↗

Quantitative evaluation of cerebral metabolites and cerebral blood flow in patients with carotid stenosis.

We examined the metabolic and hemodynamic status of patients with severe carotid stenosis and evaluated the effectiveness of carotid endarterectomy (CEA) by comparing pre- and post-operative results of quantitative proton magnetic resonance spectroscopy (1H-MRS) and single-photon emission computed tomography (SPECT). Quantitative 1H-MRS and SPECT were performed in 17 patients with severe carotid stenosis before CEA; in 10 patients the examinations were repeated after CEA. There was a significant correlation between the degree of internal carotid artery (ICA) stenosis and the N-acetyl-aspartate (NAA) concentration, and between CBFand NAA in the basal ganglia. In 10 of the 17 patients (58.8%) we noted a decrease of NAA on 1H-MRS. After CEA in these patients, NAA was significantly increased, and in 7 of 8 patients whose pre-operative SPECT had indicated impairment of cerebral vasoreactivity, it was improved. Quantitative 1H-MRS and CBF measurements can indicate the severity of metabolic and hemodynamic impairment in patients with severe carotid stenosis, and can help to assess the effectiveness of CEA.

Adult↗

Expression and in vitro modification of parathyroid hormone-related protein (PTHrP) and PTH/PTHrP-receptor in human myeloma cells.

To elucidate the role of PTHrP in myeloma, we examined the expression levels of PTHrP and its receptor in human myeloma cell lines and clinical specimens from 13 myeloma cases. In vitro modification of PTHrP expression and production induced by TGF-beta and PMA in PTHrP expressing myeloma cell lines was also investigated. PTHrP expression was detected in six out of seven myeloma cell lines with an inverse correlation with the expression of its receptor, and in 10 out of 13 clinical specimens in varying degrees. The PTHrP expression and secretion into culture medium were enhanced by supplemental TGF-beta and PMA. PMA also seemed to affect PTHrP upregulation via TGF-beta activation. The fundamental role of PTHrP in bone lesions and hypercalcemia in myeloma may be important to consider even during the initial phase of the disease and particularly in the progression of bone complications with hypercalcemia.

Aged↗

[An elderly case of lung cancer presenting with symptoms of orbital metastasis].

An 88-year-old woman was first referred to an eye clinic in mid-May 2000 because of limitation of ocular movement. A right orbital tumor was recognized on orbital CT scans and she was referred to our hospital. A chest X-ray film showed an abnormal mass in the right middle lung field, so she was admitted for further investigations. Adenocarcinoma was diagnosed by transbronchial lung biopsy. The right orbital tumor was thought to be a metastasis from the lung cancer. She received radiation therapy for the metastatic orbital tumor. However, two months after the onset of symptoms, she died due to progressive systemic metastasis. In summary, we report an elderly lung cancer patient whose initial symptoms were related to orbital metastasis.

Adenocarcinoma↗

[Findings of bedside swallowing assessment and brain computerized tomography in patients with chronic cerebral infarction, and their outcome].

To estimate the usefulness of the bedside swallowing assessment proposed by Smithard et al and neuroimaging findings characteristic for dysphagia, we studied the outcome of 102 patients with chronic cerebral infarction after assessment of swallowing by this test with brain computerized tomography (CT). All patients had a variety of motor disturbance and were admitted on a long-term medicare basis. They were divided into two groups according to the findings: the positive group (n = 33), who showed any of the listed types of difficulty in swallowing water, and the negative group (n = 69). Followed up to 2.2 years, their outcomes were studied. CT findings were studied on type of infarction, number and laterality of infarction, grade of periventricular lucency (PVL), presence of ventricular dilatation (VD), and severity of cortical atrophy (CA). The mean age was 76.4 years at registration and 61 were men. The frequency of severe dementia and disturbed ADL were significantly higher in the positive group. Eighteen patients died during the observation period and 15 of those were in the positive group, indicating higher annual death rate (29.9% vs 2.2% in the negative group). All of the 15 patients in the positive group died of pneumonia. CT findings showed high incidence of multiple infarction, bilateral hemispheric lesion, severe PVL, VD, and severe CA in the positive group. These findings indicated that this evaluation method was useful in screening swallow function for patients with cerebral infarction in the chronic phase. Furthermore, CT findings suggested that severe white matter lesion, VD, and severe CA as well as multiple infarction seen in bilateral hemisphere was related to dysphagia, probably due to multiple factors involving pyramidal- and extrapyramidal-tracts with higher brain function.

Adult↗

[Automated analysis for determination of PCBs in fish].

An automated analytical method for determination of polychlorinated biphenyls (PCBs) in fish was developed using supercritical fluid extraction (SFE) in combination with an automated sample preparation instrument (Prep) and GC/MS. By incorporating basic alumina with the sample in the extraction process, and optimizing the amount of carbon dioxide used, fish lipid was selectively reduced. The extract was cleaned up on a Florisil cartridge with Prep. The method was evaluated using naturally contaminated tissues and by comparison of automated analytical method results with those obtained by the conventional method. Mean recovery of PCBs from 3 kinds of fish including hairtail, mackerel and yellowtail were 69.8%, 90.2% and 81.1%, respectively. This method is less laborious and requires far less organic solvent than the conventional method, but produced comparable results.

Animals↗

Association of Epstein-Barr virus with tumor cell proliferation: clinical implication in nasopharyngeal carcinoma.

Nasopharyngeal carcinoma (NPC) is characterized by its association with Epstein-Barr virus (EBV) infection. Unlike other upper aerodigestive tract squamous cell carcinomas, clinical and pathologic features are unable to predict outcome in NPC. EBV has been demonstrated to have transforming potential in B-cell systems so that its infection can rapidly and efficiently induce sustained lymphocyte proliferation in vitro. However, the relationship between cell proliferation and EBV infection in NPC has not been previously reported. This study was designed to determine the association of EBV infection and NPC tumor cell proliferation. Cell proliferation index, as measured by two markers, PCNA and Ki-67, were moderately correlated (r=0.534, p=0.033). Quantitative analysis of EBV positivity was highly correlated with both cell proliferation indices (r=0.802, p=0.0039 and r=0.720, p=0.0174 for PCNA and Ki-67, respectively). TNM staging did not demonstrate prognostic significance. NPC patients whose tumors were EBV positive demonstrated increased survival compared with patients whose tumors were EBV negative (p=0.043). These results indicate that EBV infection may regulate cell proliferation in NPC and the presence of EBV can be used as a positive prognostic factor.

Adult↗

Donepezil hydrochloride preserves regional cerebral blood flow in patients with Alzheimer's disease.

UNLABELLED: The aim of this SPECT study was to investigate the effects of donepezil on regional cerebral blood flow (rCBF) in patients with mild to moderate Alzheimer's disease (AD) using statistical parametric mapping. METHODS: rCBF was noninvasively measured using (99m)Tc-ethyl cysteinate dimer in 35 AD patients with a Mini-Mental State Examination score > 16 on initial evaluation. Baseline and follow-up SPECT studies with a mean interval of 12 mo were performed on these patients. We used the adjusted rCBF images in the relative flow distribution (normalization of global cerebral blood flow for each patient to 50 mL/100 g/min with proportional scaling) to compare these groups through statistical parametric mapping. RESULTS: In the follow-up study, the adjusted rCBF was significantly preserved in the right and left anterior cingulate gyri, right middle temporal gyrus, right inferior parietal lobules, and prefrontal cortex of donepezil-treated AD patients, compared with placebo-treated AD patients. CONCLUSION: Treatment with donepezil for 1 y appears to reduce the decline in rCBF, suggesting preservation of functional brain activity.

Aged↗

Changes in brain morphology in Alzheimer disease and normal aging: is Alzheimer disease an exaggerated aging process?

BACKGROUND AND PURPOSE: Whether Alzheimer disease (AD) represents exaggerated aging rather than a disease is controversial. Data about the effects of normal aging on the human brain are essential for clarifying this issue; however, whether coherent common patterns of regional morphologic brain changes emerge in the normal aged brain is unclear. Clarification of regional morphologic changes in the brain associated with normal aging and AD was sought using MR imaging. METHODS: Ninety-two healthy volunteers and 26 mildly to moderately impaired patients with AD participated. Images were anatomically normalized, and voxel-by-voxel analyses were done. RESULTS: In healthy volunteers, an age-related decline in the volume of the prefrontal cortex, insula, anterior cingulate gyrus, superior temporal gyrus, inferior parietal lobule, and precuneus was found. These decreases might contribute to the cognitive changes during normal aging. In patients with AD, a significant reduction of gray matter volume in the hippocampal formation and entorhinal cortex bilaterally was noted. CONCLUSION: Morphologic changes associated with normal aging are clearly different from those seen with AD.

Adolescent↗