Biomedical subjects

Yuka Sasaki

Publications and source records attributed to Yuka Sasaki.

At least 19 recordsLinked to original sources

PubMed2024

Activated NAD+ biosynthesis pathway induces olaparib resistance in BRCA1 knockout pancreatic cancer cells.

PARP inhibitors have been developed as anti-cancer agents based on synthetic lethality in homologous recombination deficient cancer cells. However, resistance to PARP inhibitors such as olaparib remains a problem in clinical use, and the mechanisms of resistance are not fully understood. To investigate mechanisms of PARP inhibitor resistance, we established a BRCA1 knockout clone derived from the pancreatic cancer MIA PaCa-2 cells, which we termed C1 cells, and subsequently isolated an olaparib-resistant C1/OLA cells. We then performed RNA-sequencing and pathway analysis on olaparib-treated C1 and C1/OLA cells. Our results revealed activation of cell signaling pathway related to NAD+ metabolism in the olaparib-resistant C1/OLA cells, with increased expression of genes encoding the NAD+ biosynthetic enzymes NAMPT and NMNAT2. Moreover, intracellular NAD+ levels were significantly higher in C1/OLA cells than in the non-olaparib-resistant C1 cells. Upregulation of intracellular NAD+ levels by the addition of nicotinamide also induced resistance to olaparib and talazoparib in C1 cells. Taken together, our findings suggest that upregulation of intracellular NAD+ is one of the factors underlying the acquisition of PARP inhibitor resistance.

Humans↗

PubMed2006

Greater disruption due to failure of inhibitory control on an ambiguous distractor.

Considerable evidence indicates that a stimulus that is subthreshold, and thus consciously invisible, influences brain activity and behavioral performance. However, it is not clear how subthreshold stimuli are processed in the brain. We found that a task-irrelevant subthreshold coherent motion led to a stronger disturbance in task performance than did suprathreshold motion. With the subthreshold motion, activity in the visual cortex measured by functional magnetic resonance imaging was higher, but activity in the lateral prefrontal cortex was lower, than with suprathreshold motion. These results suggest that subthreshold irrelevant signals are not subject to effective inhibitory control.

Adult↗

PubMed2006

The radial bias: a different slant on visual orientation sensitivity in human and nonhuman primates.

It is generally assumed that sensitivity to different stimulus orientations is mapped in a globally equivalent fashion across primate visual cortex, at a spatial scale larger than that of orientation columns. However, some evidence predicts instead that radial orientations should produce higher activity than other orientations, throughout visual cortex. Here, this radial orientation bias was robustly confirmed using (1) human psychophysics, plus fMRI in (2) humans and (3) behaving monkeys. In visual cortex, fMRI activity was at least 20% higher in the retinotopic representations of polar angle which corresponded to the radial stimulus orientations (relative to tangential). In a global demonstration of this, we activated complementary retinotopic quadrants of visual cortex by simply changing stimulus orientation, without changing stimulus location in the visual field. This evidence reveals a neural link between orientation sensitivity and the cortical retinotopy, which have previously been considered independent.

Animals↗

PubMed2006

[Clinical review of patients with pulmonary tuberculosis who were detected by the screening of homeless persons admitted in the shelter facilities].

PURPOSE AND METHODS: There has been a recent increase in the number of non-profit facilities that provide shelter for the homeless. These social service facilities aim to assist the social rehabilitation of homeless persons. The Public Health Center of Chiba City screened 1,054 residents of these homeless shelters between November 2002 and August 2004 and found 17 individuals (1.6%) with active pulmonary tuberculosis. We clinically reviewed these cases. RESULTS: All 17 individuals were male, and their ages ranged from 44 to 70 years (mean 54.9 years). Four cases were smear positive and three cases were smear negative but culture positive by sputum examination for acid-fast bacilli. Nine cases had cavitary lesions on chest X-ray. There were three cases complicated with hepatitis C, two cases with diabetes mellitus and two cases with past history of gastrectomy. Of the 17 individuals, 13 were treated as inpatients, and four as outpatients. The mean hospitalization duration was 146.7 days excluding two patients who were discharged by themselves. Of the 11 inpatients, four remained hospitalized until the completion of treatment. Final outcome of the treatment was the following; 12 patients were cured, while five patients dropped out or discontinued treatment. CONCLUSION: The screening performed by the Public Health Center of Chiba City revealed a very high prevalence of tuberculosis among shelter residents. Thus, in the future, public health centers and medical institutions must work in collaboration to actively screen and provide treatment for residents of homeless shelters. This study also revealed that in spite of recommended hospitalization or long-term treatment, patients often self-discharged or discontinued regular outpatient treatment. Health centers and other public agencies must therefore work in close cooperation to help the homeless to continue hospitalization and subsequent medication and treatment even after their discharge from hospital.

Adult↗

PubMed2006

[Case of disseminated tuberculosis complicated with tuberculous meningitis while investigating an abdominal lymphadenopathy].

In February 2005, a 33-year-old man visited A hospital complaining of fever. The blood screening test revealed the liver dysfunction, then computed tomography showed swelling of abdominal lymph nodes. In April, headache and disorientation appeared. He was diagnosed as disseminated tuberculosis and tuberculous meningitis based on chest X-ray and computed tomography findings and examination of cerebrospinal fluid. After admission to our hospital, anti-tuberculous drugs were prescribed, but the cerebral infarction happened. The disturbance of consciousness and the left half of his body paralysis appeared. They did not improve and hydrocephalus was complicated in August, though he was treated by steroids. He needed all helps because of the left half of his body paralysis and an advanced sequelae was left. It was thought that the abdominal lymph adenopathy preceded as one of symptoms of the disseminated tuberculosis in this case. It is said to be rare that abdominal lymph node swelling is seen in the early stage of disseminated tuberculosis. But, we think that it is necessary to keep in mind that the possibility of disseminated tuberculosis as one of the diseases in differential diagnosis, when we examine enlargement of abdominal lymph nodes with symptoms suggesting the presence of infection such as fever.

Abdomen↗

PubMed2005

Separate processing of different global-motion structures in visual cortex is revealed by FMRI.

The visual system has the remarkable ability to extract several types of meaningful global-motion signals, such as radial motion, translation motion, and rotation, for different visual functions and actions. In the monkey brain, different groups of cells in MST respond best to different types of global motion [1, 2] whereas in lower cortical areas including MT, no such differential responses have been found. Here, we show that an area (or areas) lower than MST in the human brain [3] responds to different types of global motion. A series of human functional magnetic resonance imaging (fMRI) experiments, in which attention was controlled for, indicated that the center of radial motion activates the corresponding location in the V3A representation, whereas translation motion activates mainly in a more peripheral representation of V3A. These results suggest that in the human brain, V3A is an area that differentially responds according to the type of global motion.

Adult↗

PubMed2005

Serum immunoglobulin levels do not affect antibody responses to influenza HA vaccine in preterm infants.

Antibody responses to two doses of influenza hemagglutinin (HA) vaccine were evaluated in 45 previously unimmunized preterm infants aged 6-11 months before the 2003/2004 influenza season. Twenty-three (51.1%), 21 (46.6%) and 2 (4.4%) of the subjects acquired protective (>or=1:40) hemagglutination inhibition (HI) antibody titers after vaccination for A/New Caledonia (H1N1), A/Panama (H3N2) and B/Shandong, respectively. Antibody responses to A (H1N1), A (H3N2) appeared to be comparable to those reported on full-term infants of similar ages vaccinated with the identical vaccine. Serum IgG levels at vaccination had no positive association with antibody responses on univariate or multivariate analysis, indicating that prolonged hypogammaglobulinemia after 6 months of age in preterm infants was not a factor to affect antibody responses to influenza HA vaccine.

Antibodies, Viral↗

PubMed2005

A neutralizing anti-fibroblast growth factor 8 monoclonal antibody shows potent antitumor activity against androgen-dependent mouse mammary tumors in vivo.

PURPOSE: Fibroblast growth factor 8b (FGF8b) has been implicated in oncogenesis of sex hormone-related malignancies. A murine monoclonal anti-FGF8 antibody, KM1334, has been raised against a FGF8b-derived peptide and shown to neutralize FGF8b activity in an androgen-dependent mouse mammary cell line (SC-3) in vitro growth. The purpose of this study was to evaluate KM1334 as a therapeutic agent for FGF8-dependent cancer. EXPERIMENTAL DESIGN: Specificity and neutralizing activity of KM1334 were examined in vitro. In vivo therapeutic studies were done in nude mice bearing SC-3 tumors s.c. RESULTS: KM1334 recognized FGF8b and FGF8f specifically out of four human FGF8 isoforms and showed little binding to other members of FGF family. Neutralizing activity of KM1334 was confirmed by both blocking of FGF8b binding to its three receptors (FGFR2IIIc, FGFR3IIIc, and FGFR4) and FGF8b-induced phosphorylation of FGFR substrate 2alpha and extracellular signal-regulated kinase 1/2 in SC-3 cells. The in vitro inhibitory effect could be extended to in vivo tumor models, where KM1334 caused rapid regression of established SC-3 tumors in nude mice. This rapid regression of tumors after KM1334 treatment was explained by two independent mechanisms: (a) decreased DNA synthesis, as evidenced by a decrease in uptake of 5-bromo-2'-deoxyuridine, and (b) induction of apoptosis as shown by the terminal deoxynucleotidyl transferase-mediated nick end labeling assay. CONCLUSIONS: KM1334 possesses strong blocking activity in vitro and antitumor activity in vivo and therefore may be an effective therapeutic candidate for the treatment of cancers that are dependent on FGF8b signaling for growth and survival.

Animals↗

PubMed2005

Symmetry activates extrastriate visual cortex in human and nonhuman primates.

Humans often create and appreciate visual symmetry in their environment, and the underlying brain mechanisms have been a topic of increasing interest. Here, symmetric versus random dot stimuli produced robust functional MRI (fMRI) activity in higher-order regions of human visual cortex (especially areas V3A, V4, V7, and LO) but little activity elsewhere in brain. This fMRI response was found both with and without attention controls. Moreover, it was highly correlated with the psychophysical perception of symmetry. Similar symmetry responses were found by using line-based and dot stimuli and were found at a wide range of stimulus sizes and geometric configurations. Weaker symmetry responses were found in analogous regions of macaque visual cortex by using fMRI techniques with higher sensitivity. This evidence suggests that visual symmetry is specifically enhanced in the human brain, but that the underlying neural mechanisms may nevertheless be resolvable in nonhuman primates.

Adult↗

PubMed2005

Survey of human immunodeficiency virus (HIV)-seropositive patients with mycobacterial infection in Japan.

OBJECTIVE: To assess DNA polymorphisms in mycobacterial isolates obtained from human immunodeficiency virus (HIV)-seropositive patients with tuberculosis in Japan from 1996 to 2003. METHODS: Restriction fragment length polymorphisms (RFLP) from Mycobacterium tuberculosis and Mycobacterium avium isolates obtained from individual seropositive patients with tuberculosis (n=78) were analysed with the use of IS6110 and (CGG)(5) or IS1245 and IS1311, respectively, as markers. As a control, the same procedures were applied to isolates from HIV-seronegative tuberculosis patients (n=87). RESULTS: Of 86 mycobacterial strains, M. tuberculosis, M. avium and Mycobacterium chelonae were identified in 48 (55.8%), 36 (41.9%) and 2 (2.3%) isolates, respectively. The obtained RFLP patterns of M. tuberculosis isolates from both the HIV-seropositive and -seronegative groups were variable, suggesting no obvious clustering among the isolates. Similar results were obtained in isolates of M. avium. CONCLUSIONS: This is the first report on the molecular epidemiology of Mycobacterium spp. isolated from HIV-seropositive patients in Japan. The results indicate that no particular clones of M. tuberculosis or M. avium prevail in HIV-seropositive patients in Japan. Further monitoring of mycobacterial infection associated with HIV infection in Japan should be continued.

Adolescent↗

PubMed2005

[A case of esophageal tuberculosis which developed during the treatment for tuberculous lymphadenitis].

A 23-year-old man was admitted to the other hospital complaining of fever and lymph node swelling in the left neck. Computed tomography showed swollen mediastinal lymph nodes without intrapulmonary lesions. Mycobacterium tuberculosis were identified by sputum culture and cervical lymph node biopsy and the case was diagnosed as tuberculous lymphadenitis. Three weeks after starting treatment with four anti-tuberculous drugs, he complained chest pain while eating and chest X-ray showed a new infiltrative shadow in the right cardiophrenic angle, then he was admitted to our hospital. Esophagoscopy revealed a deep ulceration with fistulas at 30 cm from the incisor and he was diagnosed as esophageal tuberculosis by histological examination of the biopsy specimen showing remarkable leukocytes infiltration and epithelioid cell granulomas with a few multinucleated giant cells. After antituberculous chemotherapy for six months, the mediastinal and cervical lymphadenopathy were reduced in size and the esophageal ulceration almost disappeared. Although esophageal tuberculosis is rare, the disease might develop during or after mediastinal or periesophageal tuberculous lymphadenitis.

Adult↗

PubMed2005

[Current situation of contacts examination and chemoprophylaxis for persons exposed to multi-drug resistant tuberculosis in ordinance-designated cities in Japan].

PURPOSE: To evaluate the current situation of contacts examination and chemoprophylaxis for those who were exposed to multi-drug resistant tuberculosis (MDR-TB) in Japan. OBJECT AND METHOD: The questionnaire survey was conducted about the MDR-TB patients and their contacts examination enforced in the ordinance-designated cities in Japan from 1998 to 2002. RESULT: Nine cities out of total 13 ordinance-designated cities replied to the questionnaire (69.2%). The cases newly diagnosed as MDR-pulmonary tuberculosis were 189 cases from 1998 to 2002. Out of 189 cases, 34 MDR pulmonary tuberculosis patients were the source of MDR-TB infection. Among 659 individuals who were exposed to 34 MDR-TB, 58 persons (8.8%) were diagnosed as the contacts who were infected with MDR-TB. Out of 58 persons, 41 had chemoprophylaxis; 18 with isoniazid (INH), 3 with Ethionamide (TH), 2 with INH + Rifampin (RFP) + Ethambutol (EB), and each one with EB + Pyrazinamide (PZA) + TH, PZA + TH, PZA + Levofloxacin, PZA + EB. In 6 persons, INH was changed to other medicines, and 8 persons were treated with unknown prescription. Thirteen contacts developed MDR-TB, and out of them, 9 cases had several problems when they developed MDR-TB. Those problems were the delay in detection, infection from hospitalization refused cases, infection at the time of bacteriological relapse, and no use of chemoprophylaxis. CONCLUSION: MDR-TB bacilli produce the tuberculosis infection similarly as the sensitive tubercle bacilli, and it is necessary to re-examine the action plan of contacts examination including chemoprophylaxis.

Adolescent↗

PubMed2004

The primary visual cortex fills in color.

One of the most important goals of visual processing is to reconstruct adequate representations of surfaces in a scene. It is thought that surface representation is produced mainly in the midlevel vision and that area V1 (the primary visual cortex) activity is solely due to feedback from the midlevel stage. Here, we measured functional MRI signals corresponding to "neon color spreading": an illusory transparent surface with long-range color filling-in, one of the important mediums in reconstructing a surface. The experiment was conducted with careful controls of attention, which can send feedback signals from higher visual areas. Activity for filling-in was observed only in V1, whereas activity for illusory contours was observed in multiple visual areas. These results indicate that surface representation is produced by multiple rather than single processing.

Color↗

PubMed2004

Identification of a novel type 1 diabetes susceptibility gene, T-bet.

The gene encoding interferon (IFN)-gamma, IFNG, is known as one of the candidate susceptibility genes for type 1 diabetes. In addition, cytokines, including IFN-gamma, play important roles in the pathogenesis of type 1 diabetes. Therefore, we focused on the Th1-specific T-box transcription factor gene (T-bet), which contributes to the induction of the hallmark Th1 cytokine, IFN-gamma. We first screened for polymorphisms in the T-bet gene and detected two microsatellite repeat polymorphisms located in intron 1 and the 3'- flanking region, and two single nucleotide polymorphisms, including a His33Gln substitution within the coding region. By association studies, the Gln-positive phenotype and (CA)14 allele in 3'-flanking region of T-bet were found to be associated with type 1 diabetes in the Japanese population. Furthermore, Gln33 T-bet showed a significantly higher transcriptional activity of the IFNG gene via a dual luciferase reporter assay. Our study suggests the first evidence of an association between type 1 diabetes and polymorphisms in the T-bet gene, and that variation in T-bet transcriptional activity may play a role in the development of type 1 diabetes, possibly through the effect on IFN-gamma production in Th1 cells.

Adolescent↗

PubMed2004

Specific detection of tuberculosis infection: an interferon-gamma-based assay using new antigens.

The tuberculin skin test for immunologic diagnosis of Mycobacterium tuberculosis infection has many limitations, including being confounded by bacillus Calmette-Guérin (BCG) vaccination or exposure to nontuberculous mycobacteria. M. tuberculosis-specific antigens that are absent from BCG and most nontuberculous mycobacteria have been identified. We examined the use of two of these antigens, CFP-10 and ESAT-6, in a whole blood IFN-gamma assay as a diagnostic test for tuberculosis in BCG-vaccinated individuals. Because of the lack of an accurate standard with which to compare new tests for M. tuberculosis infection, specificity of the whole blood IFN-gamma assay was estimated on the basis of data from people with no identified risk for M. tuberculosis exposure (216 BCG-vaccinated Japanese adults) and sensitivity was estimated on the basis of data from 118 patients with culture-confirmed M. tuberculosis infection who had received less than 1 week of treatment. Using a combination of CFP-10 and ESAT-6 responses, the specificity of the test for the low-risk group was 98.1% and the sensitivity for patients with M. tuberculosis infection was 89.0%. The results demonstrate that the whole blood IFN-gamma assay using CFP-10 and ESAT-6 was highly specific and sensitive for M. tuberculosis infection and was unaffected by BCG vaccination status.

Adolescent↗

PubMed2004

Biotin enhances ATP synthesis in pancreatic islets of the rat, resulting in reinforcement of glucose-induced insulin secretion.

Previous studies showed that biotin enhanced glucose-induced insulin secretion. Changes in the cytosolic ATP/ADP ratio in the pancreatic islets participate in the regulation of insulin secretion by glucose. In the present study we investigated whether biotin regulates the cytosolic ATP/ADP ratio in glucose-stimulated islets. When islets were stimulated with glucose plus biotin, the ATP/ADP ratio increased to approximately 160% of the ATP/ADP ratio in islets stimulated with glucose alone. The rate of glucose oxidation, assessed by CO(2) production, was also about 2-fold higher in islets treated with biotin. These increasing effects of biotin were proportional to the effects seen in insulin secretion. There are no previous reports of vitamins, such as biotin, directly affecting ATP synthesis. Our data indicate that biotin enhances ATP synthesis in islets following the increased rate of substrate oxidation in mitochondria and that, as a consequence of these events, glucose-induced insulin release is reinforced by biotin.

Adenosine Diphosphate↗

PubMed2004

[A study on cases developed pulmonary tuberculosis after receiving gastrectomy].

OBJECTIVE: Patients who had undergone gastric resection are considered to be high risk of developing tuberculosis. We investigated the factors leading to pulmonary tuberculosis after gastrectomy. MATERIALS AND METHODS: We retrospectively examined 654 pulmonary tuberculosis patients discharged from Chiba-East National Hospital from January 1999 to December 2001. RESULTS: Fifty-five patients (31-84 years old, mean 63.5 +/- 12.5 years, 48 males and 7 females) had the history of gastric resection. The proportion of patients receiving gastrectomy among patients with pulmonary tuberculosis was 8.4 percent. The mean age of patients received gastric resection was 50.2 +/- 16.6 years, and the mean interval from gastrectomy to the development of pulmonary tuberculosis was 13.6 +/- 11.0 years. On admission to our hospital, 34 out of 55 cases were smear positive by sputum examination for acid-fast bacilli and 39 cases had cavitary lesions on chest X-ray. Gastrectomy was done due to carcinoma of the stomach in 31 cases, peptic ulcer in 21 cases, adenomatous polyp in two cases, and accidental injury in one case. Out of total 55 cases, 52 patients improved, but three cases died of pulmonary tuberculosis. None had the recurrence of carcinoma of the stomach. Body weight, Body mass index, Prognostic nutritional index (PNI; 10 x serum albumin concentration + 0.005 x peripheral lymphocyte count) which was proposed by Onodera, serum albumin level and serum total cholesterol level were lower in the gastrectomy group than in the non-gastrectomy group. The odds ratio of developing tuberculosis among gastrectomy patients compared with the appropriate controls in 30 to 59 year-old-men was 3.8. CONCLUSION: This study confirms that gastrectomy is one of the risk factors of developing tuberculosis in 30 to 59 year-old-men. However, whether gastrectomy in itself is a risk factor or whether it is secondarily associated with another risk factor such as underweight status and/or inadequate nutrition following surgery remains unclear.

Adult↗

PubMed2003

Comparison of perivascular astrocytic structure between white matter and gray matter of rats.

Regional differences in perivascular glial structures were investigated between the white matter (hippocampal fimbria, corpus callosum, cerebellar medulla) and the gray matter (cerebral cortex) of adult rats. Sparser vascular distribution, perivascular glial rows and cylinder-like segmented astrocytic endings were characteristic in the white matter. The perivascular astrocytic processes covered microvessels extensively in the white matter. Comparison of transverse microvessel sections by transmission electron microscopy (TEM) between the two sites revealed significantly larger perivascular astrocytic spaces in the white matter.

Animals↗