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Biomedical subjects

C Tanaka

Publications and source records attributed to C Tanaka.

At least 37 records · Page 2Linked to original sources
PubMed2001

Study on the Progression of Visual Field Defect and Clinical Factors in Normal-Tension Glaucoma.

Purpose: We investigated the relationship between the progression of visual field defect and clinical factors in patients with normal-tension glaucoma (NTG).Subjects and Methods: Forty-eight eyes of 48 NTG patients undergoing more than 5-year follow-up were enrolled in this study. Their visual field defects ranged between Aulhorn's classification stage 2 and 4, and mean deviation (MD) more than -10 dB measured by Humphrey Field Analyzer (HFA). End points of this follow-up study were defined as follows: in HFA STATPAC 2 glaucoma change probability analysis, more than 5 points which significantly deteriorated at P <.05 were found at 2 consecutive examinations (Criterion 1) or a significant decrease in MD value at P <.025 was encountered at one examination or in MD value at P <.05 at consecutive examinations (Criterion 2).Results: During the follow-up period, 18 eyes of 48 patients satisfied Criterion 1 and 21 eyes Criterion 2. There were no significant differences in clinical factors between patients with progression and without progression. By multiple logistic regression analysis, minimum flow velocity of central retinal artery (CRA) showed significant relation (odds ratio for a 1 cm/sec rise = 0.2215; 95% confidence interval: 0.0530-0.9253) to progression of visual field defect in Criterion 1, and minimum flow velocity of CRA (odds ratio for a 1 cm/sec rise = 0.2099; 95% confidence interval: 0.0506-0.8712) and cholesterol (odds ratio for a 1 cm/dl rise = 1.0332; 95% confidence interval: 0.4096-2.6064) showed significant relation in Criterion 2.Conclusion: These results suggests that vascular risk factors of ocular blood flow may play a role in the progression of visual field defects in NTG patients.

Journal Article↗
PubMed2001

Amyloid beta protein activates PKC-delta and induces translocation of myristoylated alanine-rich C kinase substrate (MARCKS) in microglia.

The increased accumulation of activated microglia containing amyloid beta protein (Abeta) around senile plaques is a common pathological feature in subjects with Alzheimer's disease (AD). Much less is known, however, of intracellular signal transduction pathways for microglial activation in response to Abeta. We investigated intracellular signaling in response to Abeta stimulation in primary cultured rat microglia. We found that the kinase activity of PKC-delta but not that of PKC-alpha or -epsilon is increased by stimulation of microglia with Abeta, with a striking tyrosine phosphorylation of PKC-delta. In microglia stimulated with Abeta, tyrosine phosphorylation of PKC-delta was evident at the membrane fraction without an overt translocation of PKC-delta. PKC-delta co-immunoprecipitated with MARCKS from microglia stimulated with Abeta. Abeta induced translocation of MARCKS from the membrane fraction to the cytosolic fraction. Immunocytochemical analysis revealed that phosphorylated MARCKS accumulated in the cytoplasm, particularly at the perinuclear region in microglia treated with Abeta. Taken together with our previous observations that Abeta-induced phosphorylation of MARCKS and chemotaxis of microglia are inhibited by either tyrosine kinase or PKC inhibitors, our results provide evidence that Abeta induces phosphorylation and translocation of MARCKS through the tyrosine kinase-PKC-delta signaling pathway in microglia.

Amyloid beta-Peptides↗
PubMed2001

Early and delayed neuroprotective effects of FK506 on experimental focal ischemia quantitatively assessed by diffusion-weighted MRI.

The immunosuppressive drug FK506 (tacrolimus) has been reported to be a powerful neuroprotective agent in the focal ischemia of animals. However, no report has been published concerning neuroprotective effect of this compound on the morphology in superacute stage. The separate analysis between early and delayed effects of FK506 on the morphology may be helpful in the study of the compound's mechanism of action which is still unknown. The goal of this study was to determine early and delayed effects of pharmacological treatment with FK506 in permanent MCA occlusion using magnetic resonance imaging (MRI). Nineteen rats were subjected to permanent MCA occlusion, and given either intravenous injection of placebo or 1 mg/kg FK506 immediately after occlusion. DWI and T(2)-weighted MRI were performed 3 and 24 h after MCA occlusion, and postmortem histological analysis was also performed. FK506 drastically reduced the ischemic damage in 3-h apparent diffusion coefficient (ADC) map. This is the first report to demonstrate the neuroprotective effects of FK506 on focal cerebral ischemia in superacute stage. In addition, postmortem ischemic damage tended to be smaller than ischemic area indicated by 3-h ADC map in the FK506 group, whereas there was an excellent equality between them in the placebo group, suggesting the possible effect of FK506 on the later ischemic period. Our findings provide direct evidence for the neuroprotective effect of FK506 on ischemic cell damage in both early stage and possibly later stage.

Animals↗
PubMed2001

Lumbar posterolateral fusion with biphasic calcium phosphate ceramic.

The authors conducted a retrospective observational study of patients who needed lumbar posterolateral fusion (PLF) using a biphasic calcium phosphate ceramic implant as a substitute for bone graft. The findings of clinical, radiographic, and histologic examinations were reviewed. Thirty-two patients underwent single-level PLF with instrumentation. In all cases, to decrease the occurrence of donor-site complications and morbidity, locally harvested morselized bone from the decompressive site was mixed with hydroxyapatite and beta-tricalcium phosphate (HAP-TCP) granules and sticks and used for fusion at the posterolateral aspect of the lumbar spine. The histologic findings of three biopsy specimens obtained during second operations for metallic implant removal were reviewed. The minimum follow-up period was 26 months. There was no evidence of instrument loosening or breakage. However, bone-graft incorporation was difficult to evaluate radiographically, because image quality was inferior to that with conventional autogenous iliac bone graft. Partial graft bone resorption was revealed on radiographs in 75% of cases. The results showed clinical improvement in all but one case. Solid fusion was observed during the second operation in all three cases. Histologic analysis showed excellent bone incorporation around the HAP-TCP granules. These findings suggest that, although the bulk of the fusion mass with HAP-TCP was smaller than that with autogenous bone, this technique combined with rigid instrumentation is a safe and effective procedure.

Adult↗
PubMed2001

Autistic children: experience and severity of dental caries between 1980 and 1995 in Kagoshima City, Japan.

The present study indicates that experience and severity of dental caries in 1995 showed a clear decrease from observations in 1980 in Kaogsima City, Japan. This decline may be attributed to several factors such as the qualitative and quantitative improvements in treatment of caries, more regular visits to dental clinics, improved daily oral hygiene, and changes in dietary pattern.

Adolescent↗
PubMed2001

Frequent allelic loss/imbalance on the short arm of chromosome 3 in tongue cancer.

Frequent allelic imbalances including loss of heterozygosity (LOH) and microsatellite instability (MSI) on the short arm of chromosome 3 (3p) have been found in several types of human cancer. This study was designed to identify the tumor suppressor locus (or loci) on 3p associated with tongue squamous cell carcinoma (SCC). Among 16 patients with tongue SCC tested, 7 (44%) of 16 informative cases showed LOH at one or more loci. Deletion mapping of these 16 tumors revealed two discrete, commonly deleted regions on the chromosome arm. Our data support the notion that tumor suppressor gene(s) contributing to the progression of tongue squamous cell carcinoma reside on 3p24 and 3p25.

Carcinoma, Squamous Cell↗
PubMed2001

Analysis of a role for p16/CDKN2 expression and methylation patterns in human oral squamous cell carcinoma.

The p16/CDKN2 (cyclin dependent kinase number 2) gene is known to be one of the negative regulators of the cell cycle. Aberrant 5'CpG island methylation is one of the most important mechanisms of p16/CDKN2 gene promoter region alteration. We studied 8 oral squamous cell carcinoma cell lines and 25 primary tumor tissues for the p16/CDKN2 gene and its expression by PCR-SSCP, MSP, RT-PCR, and immunohistochemical methods to determine the mechanism and the potential biological significance of p16/CDKN2 gene inactivation. In primary tumors, no p16/CDKN2 gene mutations were found by PCR-SSCP. However, hypermethylation of the CpG sites of p16/CDKN2 gene was observed in 48% (12/25) cases of primary tumors and in 50% (4/8) of cell lines. To verify the p16 mRNA expression, we employed RT-PCR and observed decreased or lacked p16 mRNA in 44% (11/25) of primary tumor tissues. In addition, hypermethylation was observed in 6 of the above 11 cases (55%). An immunohistochemistry assay was also performed with the primary tumor tissues, and a semi-quantitative method was used to evaluate the staining intensity of p16 protein. We observed 52% (13/25) negative nuclear staining. When we compared these results with clinicopathological stages, there was no statistical significance. These findings suggest that hypermethylation of p16/CDKN2 promoter region may be associated with p16/CDKN2 gene alteration.

Aged↗
PubMed2001

Clinical significance of plasma nucleosome levels in cancer patients.

The nucleosome is the primary repeating unit of DNA organization in chromatin, and cell death may lead to increased levels of circulating nucleosomes in plasma (PNLs) in various circumstances such as inflammation, pulmonary embolism, autoimmune disease, and cancer. Cell death can also be induced by chemotherapeutic agents. We investigated PNLs in 99 patients with primary breast cancer, 26 with recurrent disease, 11 with benign breast disease, and 27 with other histological types of cancer. In 18 patients with recurrent breast cancer who received docetaxel (D, 60 mg/m2) every 3 weeks as second line therapy after an anthracycline-based regimen, PNLs were investigated before and during the administration of D. One hundred and seventy-four healthy controls (111 females, 63 males) without any evidence of disease were also investigated. PNLs were detected using the cell death detection ELISAplus kit. PNLs were significantly higher in patients with primary breast cancer (mean +/- SD: 0.135 +/- 0.213) and in recurrent breast cancer (0.182 +/- 0.196) as compared with healthy female controls (0.010 +/- 0.012) (p < 0.01). In patients with primary breast cancer, no correlation was found between PNLs and clinicopathological characteristics. On the other hand, PNLs were decreased after mastectomy (p < 0.05). Patients with other histological types of cancer (0.244+/-0.383) also showed significantly higher PNLs as compared to healthy controls (p < 0.01), and PNLs were elevated independently of the histological type of cancer. In patients with recurrent breast cancer, PNLs showed a transient increase 24 h after the administration of D, and these increases correlated with the degree of subsequent leukopenia. In a follow-up study, pretreatment baseline PNLs decreased markedly when a response was obtained, whereas there was no decrease in either stable disease or progressive disease. Thus, increased PNLs were found in cancer patients, and PNLs seem to be a sensitive marker of cell death that could be predictive of both leukopenia and response to chemotherapy.

Adolescent↗
PubMed2001

[Efficacy of weekly docetaxel therapy for advanced or recurrent breast cancer].

To evaluate the safety and efficacy of weekly docetaxel (weekly TXT) in cases of advanced or recurrent breast cancer, 31 patients were enrolled in this pilot study of weekly TXT given at 25 mg/m2/w. Each cycle consisted of 3 weeks of therapy followed by a 1-week treatment break in an outpatient setting. Patients received a median of 15 infusions with a median cumulative dose of 680 mg. The median time to treatment failure was 8 months. The overall response rate was 32.3%, and 22.6% of patients had stable disease for at least 6 months. The response rate was consistent regardless of prior chemotherapy with anthracycline. There was no grade 3 or 4 toxicity, and the regimen was generally well tolerated. Although 37.5% of patients had grade 1 or 2 nail change, myelosuppression, fatigue, nausea, vomiting and fluid retention were mild. Weekly TXT seems to be an effective and feasible treatment for advanced or recurrent breast cancer patients.

Adult↗
PubMed2001

[Correlation between blue chromatic macular sensitivity and optic disc change in early glaucoma patients].

PURPOSE: To investigate the relationship between morphological changes of the optic nerve head (ONH) and macular sensitivity(MS) determined with blue-on-yellow(B on Y) and white on white (W on W) perimetry in normal subjects and patients with glaucoma. METHODS: One randomly chosen eye was evaluated in each of 28 normal subjects, 23 patients with ocular hypertension(OH), and 23 patients with early primary open-angle glaucoma(POAG). Mean values for MS by B on Y and W on W perimetry were obtained with the macular program using a modified Humphrey Field Analyzer(HFA). The Heidelberg Retina Tomograph(HRT) with software version 2.01 was used to evaluate the topographic parameters of temporal sector in ONH. RESULTS: There was no significant difference in temporal topographic parameters of ONH among the three clinical groups. Mean values for MS of B on Y and W on W perimetry in early POAG were significantly lower than in normal subjects and OH. Mean values for MS of W on W perimetry showed no significant correlation with ONH parameters of the temporal sector. In early POAG, mean values for MS of B on Y perimetry significantly correlated with cup area, cup/disc area ratio, cup volume, and rim volume in the temporal sector of ONH. CONCLUSION: The measurement of mean MS of B on Y might be able to detect the glaucomatous optic nerve damage due to increased intraocular pressure prior to the morphological changes of ONH in early stages of glaucoma.

Eye Proteins↗
PubMed2001

Sticks and stones: racism as experienced by adolescents in New Brunswick.

The purpose of the study was to describe both the nature of racism as experienced by adolescent self-described victims in the province of New Brunswick and their response to the perceived racist incidents. A qualitative methodology based on the constructivist paradigm was used. In-depth interviews were conducted with non-White adolescent victims of racism and with parents of victims. Although the study was initiated in response to an eruption of publicity about teenage racial violence, the findings indicate that racist incidents were not a new phenomenon for the participants. They described a low-key but long-term problem that had begun when they entered the public school system. Name-calling was by far the most common form of racism identified and it played a part in most of the other incidents described; dismissed as harmless by authority figures, it appeared to have long-term consequences for its targets. The participants' response to racism was found to have three phases: splintered universe, spiralling resistance, and disengagement. The results suggest that nurses working in the field of school health should address issues of racism among children and adolescents.

Adolescent↗
PubMed2000

Phosphorylation of tau is regulated by PKN.

For the phosphorylation state of microtubule-associated protein, tau plays a pivotal role in regulating microtubule networks in neurons. Tau promotes the assembly and stabilization of microtubules. The potential for tau to bind to microtubules is down-regulated after local phosphorylation. When we investigated the effects of PKN activation on tau phosphorylation, we found that PKN triggers disruption of the microtubule array both in vitro and in vivo and predominantly phosphorylates tau in microtubule binding domains (MBDs). PKN has a catalytic domain highly homologous to protein kinase C (PKC), a kinase that phosphorylates Ser-313 (= Ser-324, the number used in this study) in MBDs. Thus, we identified the phosphorylation sites of PKN and PKC subtypes (PKC-alpha, -betaI, -betaII, -gamma, -delta, -epsilon, -zeta, and -lambda) in MBDs. PKN phosphorylates Ser-258, Ser-320, and Ser-352, although all PKC subtypes phosphorylate Ser-258, Ser-293, Ser-324, and Ser-352. There is a PKN-specific phosphorylation site, Ser-320, in MBDs. HIA3, a novel phosphorylation-dependent antibody recognizing phosphorylated tau at Ser-320, showed immunoreactivity in Chinese hamster ovary cells expressing tau and the active form of PKN, but not in Chinese hamster ovary cells expressing tau and the inactive form of PKN. The immunoreactivity for phosphorylated tau at Ser-320 increased in the presence of a phosphatase inhibitor, FK506 treatment, which means that calcineurin (protein phosphatase 2B) may be involved in dephosphorylating tau at Ser-320 site. We also noted that PKN reduces the phosphorylation recognized by the phosphorylation-dependent antibodies AT8, AT180, and AT270 in vivo. Thus PKN serves as a regulator of microtubules by specific phosphorylation of tau, which leads to disruption of tubulin assembly.

Amino Acid Sequence↗
PubMed2000

A Japanese patient with frontotemporal dementia and parkinsonism by a tau P301S mutation.

The authors report a patient carrying a missense mutation in exon 10 of tau that causes a substitution at codon 301 (P301S). Although the patient shares the rapidly progressive frontotemporal dementia of the other reported pedigrees with P301S, the clinical phenotype is unique in that parkinsonism was a major symptom in the early stage and because behavioral symptoms with dementia became prominent 2 years after the onset of the disease. This study substantiates the notion that tau mutations at codon 301 can show various phenotypes.

Adult↗
PubMed2000

Missing anterior cervical plate and screws: a case report.

STUDY DESIGN: A case report of an anterior cervical plate and screws that disappeared completely. OBJECTIVES: To present a case of a missing anterior cervical plate and screws, this being quite a rare complication of a cervical implant. SUMMARY OF BACKGROUND DATA: No mention of this complication was found in the literature. METHODS: Methods in the literature and clinical presentation are reviewed. RESULTS: Dislodgment of an anterior cervical plate occurred in association with an methicillin-resistant Staphylococcus aureus infection. Three months later the implants had disappeared, presumably passing without notice through the gastrointestinal tract. Whole body fluoroscopy could not identify any residual plate or screws. No esophageal fistula could be detected by barium meal swallow study. CONCLUSIONS: The plate and screws became dislodged, eroded through the posterior wall of the esophagus, then traversed the limit of the gastrointestinal tract, passing with feces without significant morbidity. Whether the methicillin-resistant Staphylococcus aureus infection contributed to this unique circumstance or is coincidentally related to it remained a matter of speculation.

Aged↗
PubMed2000

Rapamycin and FK506 induce long-term potentiation by pairing stimulation via an intracellular Ca(2+) signaling mechanism in rat hippocampal CA1 neurons.

Immunophilin-CsA and -FK506 complexes bind to calcineurin (CaN) and inhibit its phosphatase activity leading to enhancement of neuronal activities. However, inhibition of CaN activity is not the mediator of modulatory activity for IP3 and ryanodine receptors and does not mediate the neurotrophic actions of FK506. FK506 binding protein (FKBP)-12 also binds rapamycin, another immunosuppressant which does not affect CaN activity. Using whole-cell patch clamp techniques, excitatory postsynaptic currents (EPSCs) were recorded and we analyzed the effect of immunosuppressants on the synaptic potentiation induced by pairing weak presynaptic stimulation with postsynaptic depolarization in CA1 neurons of rat hippocampal slices. We found that postsynaptic application of rapamycin or FK506, at low concentrations, but not cyclosporin A, in conjunction with weak pairing stimulation, induced NMDA-dependent long-term potentiation (LTP). The rapamycin-induced LTP was blocked by chelating intracellular Ca(2+) or by inhibiting the intracellular Ca(2+) release. Thus, Ca(2+) release from intracellular Ca(2+) stores is required for the induction of LTP by weak pairing stimulation in the presence of rapamycin or FK506 at postsynaptic sites. We propose that postsynaptic FKBP-12 regulates synaptic transmission by stabilizing the postsynaptic Ca(2+) signaling mechanism in rat hippocampal CA1 neurons.

Animals↗
PubMed2000

Dual effects of PKNalpha and protein kinase C on phosphorylation of tau protein by glycogen synthase kinase-3beta.

We analyzed the effects of PKNalpha and protein kinase C (PKC) on phosphorylation of tau protein by glycogen synthase kinase (GSK)-3beta using monoclonal antibodies (AT8, AT180, and AT270). These antibodies are highly specific for phosphorylated tau in Alzheimer paired helical filaments, and recognize phosphorylated Ser202/Thr205, Thr231, and Thr181 of tau protein, respectively. Immunoblot analysis demonstrated that PKNalpha and PKC did not directly phosphorylate their sites, whereas GSK-3beta efficiently did so. Incubating GSK-3beta with PKNalpha or PKC subtypes inhibited subsequent GSK-3beta-induced AT8 and AT270 immunoreactivity. However, the constitutive active form of the GSK-3beta(S9A) mutant was almost totally inert to each enzyme. Incubating tau with PKNalpha increased the GSK-3beta-induced AT180 immunoreactivity, which was further enhanced when the S9A mutant was used instead of the wild type GSK-3beta. These results suggest that PKNalpha and PKC directly inhibit GSK-3beta activity at least in part by phosphorylating Ser9 of GSK-3beta, and that they indirectly suppress GSK-3beta-stimulated phosphorylation of tau at amino acids Ser202/Thr205 and Thr181, but enhanced phosphorylation at Thr231 through phosphorylation at other sites of tau.

Amino Acid Sequence↗