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Atsuko Nakagawa

Publications and source records attributed to Atsuko Nakagawa.

18 recordsLinked to original sources

Infant eye and head movements toward the side opposite the cue in the anti-saccade paradigm.

BACKGROUND: The anti-saccade task, when people must respond in the direction opposite to a visual stimulus, has been used as a marker of operation of the frontal cortical oculomotor area. However, early development of oculomotor control has been little studied with the infant anti-saccade paradigm, and a few studies did not recognize anti-saccades in infants in light of the results of adult anti-saccade. Since the characteristics of infant eye movements are little known, applying the criteria used in adult study is by no means the best way to study infant anti-saccade. As it is indicated that coordinated eye and head movements often enable infants to control the direction of their gaze, head movements should be examined as an infant orienting response. The aim of this study was to address how infants used eye and head movements during the anti-saccade paradigm. To distinguish infants' responses, we also investigated eye and head movements during a task for an inhibition of return. Inhibition of return, in which delayed responses occur in the direction to which attention had previously been oriented, has been thought to mark activity of the superior colliculus. Since the superior colliculus is thought to develop much earlier in life than the frontal lobes, we thought it useful to compare these task performances during infancy. METHODS: Infants were divided into three groups according to age. Anti-saccade and inhibition-of-return tasks were given. Their eye and head movements during tasks were independently recorded by the corneal reflection method in the head-free condition. RESULTS: Younger infants tended to initiate eye movement less than older ones in both tasks. In the anti-saccade task, responses opposite to the cue tended to show longer latency than responses to the cue. Infants made faster responses toward the side opposite the cue when it was to the right than when it was left of fixation. Regarding the comparison of responses toward the side opposite the cue between two tasks, the leftward eye movement was faster than the leftward head movements in the inhibition-of-return task, while no difference of latency was observed between eye and head movements in the anti-saccade task. A qualitative analysis of the trajectory of these responses revealed that head movement trajectories were steeper in the anti-saccade than in the inhibition-of-return task. CONCLUSION: Younger infants move head and eyes together, with head movements frequently starting first. On the other hand, both the leftward latency difference between eye and head and gentle trajectories of head in inhibition of return indicate that eye movements are more predominant over head movements in the inhibition-of-return task than in the anti-saccade task. This would suggest an earlier developing inhibition-of-return mechanism.

Journal Article↗

Mechanisms of development and progression of cyanotic nephropathy.

Cyanotic nephropathy (CN) is often accompanied by congenital cyanotic heart diseases (CCHD). The purpose of this study was to clarify the risk factors and the mechanisms of involved in the development and progression of CN. Thirty patients with CCHD were examined. We analyzed the risk factors for the development of CN on the basis of the clinical and laboratory findings. We also examined ten renal biopsy specimens obtained from patients with CN. Patients with CN showed significantly higher hematocrit levels than those without CN (P=0.025), although there was no difference between the two groups in terms of oxygen saturation. The renal plasma flow (RPF) in patients both with and without CN was low. However, the filtration fraction (FF) was significantly lower in patients with CN than in those without CN (P=0.001). The glomeruli of biopsy specimens with significant proteinuria (n=7) were larger than those of biopsy specimens without significant proteinuria, and there were more capillaries per glomerulus in the former than in the latter (n=3) and the control specimens (n=6) (glomerular size: P<0.01; number of glomerular capillaries: P<0.01). In conclusion, hyperviscosity by polycythemia may be responsible for the development of CN. This pathological condition may induce an angiogenic increase in the glomerular capillary beds, in turn leading to glomerulomegaly. In addition, the failure of a compensatory mechanism to respond to reduced RPF by hyperfiltration may be accompanied by the development and progression of CN.

Adolescent↗

Prognostic significance of immunohistochemical expression of the HER-2/neu oncoprotein in bone metastatic prostate cancer.

OBJECTIVES: To investigate the usefulness of the overexpression of the human epidermal growth factor receptor (HER-2) oncoprotein in patients with bone metastatic prostate cancer as a marker for the time to recurrence and outcome after endocrine therapy. METHODS: We studied 50 patients who had been diagnosed with bone metastatic prostate cancer. HER-2 overexpression in the prostatic tissue by biopsy was evaluated by immunohistochemistry using the Hercep test. The results were scored into four levels by two pathologists; scores greater than 1+ were considered positive. RESULTS: The HER-2 staining score was 0, 1+, 2+, 3+, and indeterminate in 28, 4, 11, 6, and 1 case, respectively. HER-2 was overexpressed (greater than 1+) in 21 patients (42%). The cause-specific survival and nonrecurrence rates were significantly lower in the HER-2-positive group than in the negative group (P = 0.0084 and P = 0.0485, respectively). Furthermore, the cause-specific survival rate after recurrence was significantly greater in the HER-2-negative group than in the positive group (P = 0.0247). CONCLUSIONS: We consider that HER-2 overexpression, as measured by immunohistochemistry, may be useful as a marker of an unfavorable prognosis by predicting the interval until relapse and outcome after endocrine therapy in patients with bone metastatic prostate cancer.

Aged↗

Is neuroendocrine cell differentiation detected using chromogranin A from patients with bone metastatic prostate cancer a prognostic factor for outcome?

We evaluated the usefulness of overexpression of neuroendrocrine (NE) cell differentiation determined by immunohistochemical staining for chromogranin A (Cg A) in diagnostic needle biopsy specimens of bone metastatic prostate cancers. A total of 50 patients diagnosed as having bone metastatic prostate cancer were studied. The period of observation was between 6.9 and 79.4 months (median 48.7 months). Cg A was detected by immunostaining using the labeled streptavidin biotin method. Cg A-positivity was defined as the presence of immunostained cells in 10% or more of the tumor. All statistical analyses were carried out using the Statistical Package for Social Sciences Software, version 10.0 for Windows. Eleven patients (22%) were classified into the Cg A-positive group. There were no significant differences in clinical data between the Cg A-positive and Cg A-negative groups. The 5-year cause-specific survival rate was 34.1% for the Cg A-positive group and 55.2% for the Cg A-negative group (p=0.3763). The 3-year non-recurrence rate was 9.1% for the Cg A-positive group and 35.9% for the Cg A-negative group, and this difference was significant (p=0.0253). The 3-year cause-specific survival rates after recurrence were 38.4% and 42.3% respectively (p=0.8125). We consider that NE cell differentiation of the primary tumor in cases of bone metastatic prostate cancer is not a prognostic factor for outcome.

Aged↗

Rituximab treatment for posttransplant lymphoproliferative disorder (PTLD) induces complete remission of recurrent nephrotic syndrome.

A 12-year-old Japanese boy who underwent kidney transplantation with a kidney from his mother developed severe proteinuria immediately after the operation. Because his original disease was nephrotic syndrome (focal segmental glomerulosclerosis, or FSGS) and electron microscopic examination of the renal biopsy showed foot process fusion, we diagnosed this as a recurrence of nephrotic syndrome to the transplanted kidney. Four months after the transplantation, posttransplant lymphoproliferative disorder (PTLD) developed, which was pathologically diagnosed as diffuse large B cell lymphoma. Treatment consisting of a reduction in immunosuppression resulted in improvement in PTLD a month after the start of treatment. However, relapse occurred 2 months after the first onset of PTLD, which we treated with rituximab (CD-20 monoclonal antibody 375 mg/m2) once weekly for a total of four doses. The PTLD resolved immediately after the rituximab treatment was started, and, interestingly, urinary protein levels also improved at the same time. Three years later, the boy shows no signs of PTLD, and no proteinuria has been detected. These findings suggest that rituximab may be an effective treatment for recurrence of nephrotic syndrome after transplantation and that activated B cells may play a pivotal role in the recurrence of nephrosis after renal transplantation.

Antibodies, Monoclonal↗

A case of idiopathic sclerosing mediastinitis in a 7-year-old Japanese boy.

UNLABELLED: Sclerosing mediastinitis is a very rare benign disorder characterised by the development of dense fibrous tissue within the mediastinum. Affected patients are typically young adults with infant cases being uncommon especially in areas without endemic histoplasmosis. We report a Japanese boy with markedly elevated serum inflammatory markers for more than 1 year in the absence of any clinical manifestations. 67Ga-scintigraphy demonstrated an accumulation in the mediastinal region and an open biopsy revealed a hard fibrous mass in the anteriosuperior mediastinum. Thus, a diagnosis of idiopathic sclerosing mediastinitis was made. CONCLUSION: To the best of our knowledge, this case is the youngest patient reported with this disorder. In patients with mediastinal mass lesions the diagnosis of sclerosing mediastinitis should be considered as well as infectious, autoimmune or neoplastic disease even in children.

Anemia↗

Expression profiling using a tumor-specific cDNA microarray predicts the prognosis of intermediate risk neuroblastomas.

To predict the prognosis of neuroblastoma patients and choose a better therapeutic protocol, we developed a cDNA microarray carrying 5340 genes obtained from primary neuroblastomas and examined 136 tumor samples. We made a probabilistic output statistical classifier that provided a high accuracy in prognosis prediction (89% at 5 years) and a highly reliable method to validate it. Kaplan-Meier analysis indicated that the patients in an intermediate group defined by existing markers are divided by microarray into two further groups with 5 year survivals for 36% and 89% of patients (p < 10(-4)), i.e., with unfavorably and favorably predicted neuroblastomas, respectively. According to these results, we developed a gene subset chip for a clinical tool, for which our classifier exhibited 88% prediction accuracy.

Algorithms↗

Immunohistochemical study of chromogranin A in Stage D2 prostate cancer.

OBJECTIVES: To study the clinical and pathologic factors that affect the time to recurrence after hormonal therapy in patients with Stage D2 prostate cancer and to determine whether cells positive for chromogranin A (CgA) in tissue biopsied at diagnosis is a useful marker for predicting the duration to recurrence after hormonal therapy. METHODS: A total of 50 patients diagnosed with Stage D2 prostate cancer at our institution from January 1998 to December 2001 were studied. The needle prostate biopsy specimens obtained at diagnosis were stained by immunohistochemistry using the labeled streptavidin biotin method, and the results were considered positive if CgA-positive cells constituted 10% or more of the tumor area. RESULTS: No significant differences were found between patients on the basis of the time to recurrence of less than 2 years versus 2 years or more with respect to prostate-specific antigen level, patient age, Gleason score, or extent-of-disease grade. Of the 50 patients, 11 (22.0%) had positive cell staining for CgA. No significant differences were found between the CgA-positive group and the CgA-negative group in age, prostate-specific antigen level, Gleason score, extent-of-disease grade, T stage, or N stage. The rate of freedom from recurrence after 2 years as analyzed by the Kaplan-Meier method was 18.2% for the CgA-positive group and 47.4% for the CgA-negative group, and the CgA-positive group had a significantly shorter time to recurrence (P < 0.0122). CONCLUSIONS: The results of our study have shown that patients with overexpression of CgA-positive cells in the prostate have a significantly shorter time to recurrence after hormonal therapy than patients with CgA-negative cells; thus, CgA expression may be a useful marker predictive of the time to recurrence.

Aged↗

Biological role of anaplastic lymphoma kinase in neuroblastoma.

Anaplastic lymphoma kinase (ALK) is a tyrosine kinase receptor originally identified as part of the chimeric nucleophosmin-ALK protein in the t(2;5) chromosomal rearrangement associated with anaplastic large cell lymphoma. We recently demonstrated that the ALK kinase is constitutively activated by gene amplification at the ALK locus in several neuroblastoma cell lines. Forming a stable complex with hyperphosphorylated ShcC, activated ALK modifies the responsiveness of the mitogen-activated protein kinase pathway to growth factors. In the present study, the biological role of activated ALK was examined by suppressing the expression of ALK kinase in neuroblastoma cell lines using an RNA interference technique. The suppression of activated ALK in neuroblastoma cells by RNA interference significantly reduced the phosphorylation of ShcC, mitogen-activated protein kinases, and Akt, inducing rapid apoptosis in the cells. By immunohistochemical analysis, the cytoplasmic expression of ALK was detected in most of the samples of neuroblastoma tissues regardless of the stage of the tumor, whereas significant amplification of ALK was observed in only 1 of 85 cases of human neuroblastoma samples. These data demonstrate the limited frequency of ALK activation in the real progression of neuroblastoma.

Anaplastic Lymphoma Kinase↗

Identification of specific autoantigens in Sjögren's syndrome by SEREX.

We carried out SEREX (serological analysis of antigens by recombinant cDNA expression cloning) using sera from patients with Sjögren's syndrome (SjS) and investigated the frequencies of autoantibodies against autoantigens identified by SEREX in the sera of healthy individuals (HI) and patients with SjS, rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE). IFI16 and two kelch-like proteins, KLHL12 and KLHL7, were found to be novel autoantigens in SjS by SEREX. A markedly high frequency of anti-IFI16 autoantibodies was observed in the sera of SjS (SjS, 70%; RA, 13%; SLE, 33%; HI, 0%). Interestingly, all serum samples from SjS demonstrated immunoreactivity against one or both of IFI16 and SS-B/La. The presence of autoantibodies against KLHL12 and KLHL7 in the sera was significantly specific to SjS (23% and 17%, respectively), as they were not detected in RA, SLE or HI. Furthermore, we confirmed that transcripts of these autoantigens were expressed preferentially in the salivary glands and immuno-privileged testes. Our results suggest these autoantigens may be useful as serological markers for the clinical diagnosis of SjS and may play a crucial role as organ-specific autoantigens in the aetiopathogenesis of SjS. This study warranted clinical evaluations of autoantibodies against IFI16, KLHL12 and KLHL7 in combination with anti-SS-B/La autoantibodies.

Adolescent↗

Low expression of human tubulin tyrosine ligase and suppressed tubulin tyrosination/detyrosination cycle are associated with impaired neuronal differentiation in neuroblastomas with poor prognosis.

Neuroblastoma (NBL), one of the most common childhood solid tumors, has a distinct nature in different prognostic subgroups. However, the precise mechanism underlying this phenomenon remains largely unknown. To understand the molecular and genetic bases of neuroblastoma, we have generated its cDNA libraries and identified a human ortholog of tubulin tyrosine ligase gene (hTTL/Nbla0660) as a differentially expressed gene at high levels in a favorable subset of the tumor. Tubulin is subjected to several types of evolutionarily conserved posttranslational modification, including tyrosination and detyrosination. Tubulin tyrosine ligase catalyzes ligation of the tyrosine residue to the COOH terminus of the detyrosinated form of alpha-tubulin. The measurement of hTTL mRNA expression in 74 primary neuroblastomas by quantitative real-time reverse transcription-PCR revealed that its high expression was significantly associated with favorable stages (1, 2 and 4s; p = 0.0069), high TrkA expression (p = 0.002), a single copy of MYCN (p < 0.00005), tumors found by mass screening (p = 0.0042), nonadrenal origin (p = 0.0042) and good prognosis (p = 0.023). The log-rank test showed that high expression of hTTL was an indicator of favorable prognosis (p = 0.026). Immunohistochemical analysis using specific antibodies generated by us demonstrated that tyrosinated tubulin (Tyr-tubulin), detyrosinated tubulin (Glu-tubulin) and hTTL as well as Delta2-tubulin were positive in favorable tumors, whereas only Delta2-tubulin was positive in the tumors with MYCN amplification. In an RTBM1 neuroblastoma cell line, hTTL was increased after treating the cells with bone morphogenetic protein 2 (BMP2) or all-trans retinoic acid (RA), which induced neuronal differentiation. These results suggest that the deregulated tubulin tyrosination/detyrosination cycle caused by decreased expression of hTTL is associated with inhibition of neuronal differentiation and enhancement of cell growth in the primary neuroblastomas with poor outcome.

Amino Acid Sequence↗

TrkA expression in peripheral neuroblastic tumors: prognostic significance and biological relevance.

BACKGROUND: This study was conducted to investigate the prognostic significance and biologic relevance of trkA expression levels in peripheral neuroblastic tumors (pNTs) (i.e., neuroblastoma, ganglioneuroblastoma, and ganglioneuroma). METHODS: Levels of trkA expression from a total of 265 pNTs were determined by quantitative polymerase chain reaction analysis with Genescan software. The results were analyzed according to histopathology (favorable histology [FH] vs. unfavorable histology [UH] according to the International Neuroblastoma Pathology Classification) and MYCN tumor status (amplified vs. nonamplified) along with clinical stage and outcomes of the patients. RESULTS: The levels of trkA expression differed significantly between the group of patients who were alive and well (n = 170 patients) and the group that had progressed or died (n = 95 patients) and between the group that was alive (n = 188 patients) and the group that died (n = 77 patients). However, the trkA expression levels were not independent predictors of clinical outcome when the proportional hazards model contained the known prognostic variables of clinical stage, histopathology, and MYCN status (all tests were done in 196 patients). In the neuroblastoma category (n = 173 tumors), tumors in the FH/nonamplified MYCN subset (n = 112 tumors) expressed higher levels of trkA and showed an age-dependent neuroblastic differentiation: They were classified into either a poorly differentiated subtype (n = 91 tumors; all patients age < 1.5 years at diagnosis) or a differentiating subtype (n = 21 tumors; 57% of patients ages 1.5-5.0 years). Tumors in the UH/amplified MYCN subset (n = 30 tumors) expressed significantly lower levels of trkA and showed very limited neuroblastic differentiation. Tumors in the FH/amplified MYCN subset were very rare (n = 3 tumors) and expressed higher levels of trkA. Tumors in the UH/nonamplified MYCN subset (n = 28 tumors) had trkA levels in a wide range and showed limited neuroblastic differentiation. CONCLUSIONS: For patients with pNTs, levels of trkA expression did not add significant information to prognostic grouping, as defined by the combination of clinical stage, histopathology, and MYCN status. There was a biologically relevant correlation between molecular properties (trkA expression and MYCN status) and histopathologic features of the tumors in the neuroblastoma category.

Biomarkers, Tumor↗

[Membranous nephropathy following allogeneic peripheral blood stem cell transplantation in a boy with anaplastic large cell lymphoma].

We report the case of 13-year-old boy who had been diagnosed as having anaplastic large cell lymphoma (ALCL) when he was 11 years old. He suffered a relapse despite the chemotherapy regimens he had been subjected to. Since anaplastic lymphoma kinase (ALK), one of the important prognostic factors of ALCL, was not expressed in the tumor cells, allogeneic peripheral blood stem cell transplantation (PBSCT) from his HLA-matched elder brother was performed. Eleven months after PBSCT, the patient developed nephrotic syndrome as a consequence of chronic graft-versus-host disease (GVHD). He was diagnosed as having membranous nephropathy (MN) based on the results of histological examinations. Soluble interleukin-2 receptor and anti-nuclear antibody closely reflected the clinical course of MN, therefore some immune mechanisms closely related to chronic GVHD seemed to contribute to the occurrence of MN after PBSCT.

Adolescent↗

The temporal relationship between reduction of early imitative responses and the development of attention mechanisms.

BACKGROUND: To determine whether early imitative responses fade out following the maturation of attentional mechanisms, the relationship between primitive imitation behaviors and the development of attention was examined in 4-month-old infants. They were divided into high and low imitators, based on an index of imitation. The status of attention was assessed by studying inhibition of return (IOR). Nine-month-old infants were also tested to confirm the hypothesis. RESULTS: The IOR latency data replicate previous results that infants get faster to produce a covert shift of attention with increasing age. However, those 4-month-olds who showed less imitation had more rapid saccades to the cue before target presentation. CONCLUSION: The cortical control of saccade planning appears to be related to an apparent drop in early imitation. We interpret the results as suggesting a relationship between the status of imitation and the neural development of attention-related eye movement.

Age Factors↗

Asian variant of CD5+ intravascular large B-cell lymphoma with splenic infarction.

A 57-year-old man was admitted with fever and epigastralgia, and presented with splenomegaly and pancytopenia. A CT scan revealed splenic infarctions. There were no lymphadenopathies, skin lesions, or neurological abnormalities. A splenectomy was performed. Bone marrow involvement with hemophagocytosis was noted. The diagnosis of Asian variant of intravascular diffuse large B-cell lymphoma was based on intravascular and sinusoidal distribution of large CD5+ B cells. The patient died of the disease 11 months after onset. To our knowledge, this is the first report of AIVL that presented with splenic infarction. This distinct lymphoma should be included in the differential diagnosis of splenic infarction.

Asia↗

Fatal cytotoxic T-cell proliferation in chronic active Epstein-Barr virus infection in childhood.

Histopathologic features of 5 cases (4 boys and 1 girl; 4-9 years old) with severe chronic active Epstein-Barr virus (EBV) infection are discussed. All patients died within 3 years after disease onset without developing hematolymphoid malignant neoplasms. The pathology specimens (autopsy, 2 cases; multiple organs and tissues obtained by surgery or biopsy, 3 cases) showed polymorphic lymphocytic proliferation in the lymph nodes (4/5) and spleen (3/3), and systemic lymphocytic infiltration of the liver (4/4), lung (2/2), bone marrow (3/4), and kidney (2/2). Skin lesions were noted clinically in 3 of 5 cases. Two cases had coronary artery aneurysm due to lymphocytic vasculitis. The lymphocytes had a characteristic phenotype of cytotoxic T cells expressing CD3, CD8, and cytotoxic molecules, and were negative for CD4. EBV-encoded small nonpolyadenylated RNAs were detected in the nuclei of the lymphocytes, but latent membrane protein 1 and EBNA2 were not seen. In 4 of 4 cases, an oligoclonal growth pattern of EBV was determined after detecting terminal repetitive sequences by Southern blot. In 3 of 3 cases, the lymphocytes did not have T-cell receptor beta or J(H) gene rearrangement.

Antibodies, Viral↗