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Biomedical subjects

Naoto Takahashi

Publications and source records attributed to Naoto Takahashi.

At least 19 recordsLinked to original sources
PubMed2006

Antibodies against superantigenic exotoxins produced by Staphylococcus aureus in sera from mothers and their infants' cord blood.

A novel neonatal disease and puerperal toxic shock syndrome (TSS) induced by a superantigen, TSS toxin-1 (TSST-1), has spread throughout Japan. It is important to investigate serum titers against exotoxins in new mothers and in their infants' cord blood. We investigated antitoxin antibodies against TSST-1, staphylococcal enterotoxin (SE) A (SEA), SEB, and SEC, including immunoglobulin G (IgG) subclass specificity by enzyme-linked immunosorbent assay, in sera from 221 mothers and 97 cord blood samples. The rate of mothers with negative anti-TSST-1 antibody titer was high (more than 40%). Although antitoxin antibody titers in the sera of cord blood were well correlated with those in the sera of the mothers for every toxin, the tendencies of antibody transmission differed between toxins. Anti-TSST-1 antibody consisted mainly of IgG1 and IgG4 subclasses. Anti-TSST-1 IgG1- and IgG4-specific antibody titers in cord blood were well correlated with those in the sera of the mothers. The low frequency of pregnant women with positive anti-TSST-1 antibody titers could be one reason for the spread of TSS in Japan. Neonates whose mothers have positive IgG titers against TSST-1 should be protected because the antibody is composed of the subclasses transferred well through the placenta.

Adult↗
PubMed2006

TNF-alpha and phosphorylation of ERK in DRG and spinal cord: insights into mechanisms of sciatica.

STUDY DESIGN: Characterize extracellular signal-regulated kinase (ERK) and its phosphorylation (pERK) in neural tissues after topical application of tumor necrosis factor-alpha (TNF-alpha) to L5 nerve root. OBJECTIVE: Identify time-course, localization, and expression of pERK. SUMMARY OF BACKGROUND DATA: TNF-alpha has a key role in disc herniation and sciatica as an inflammatory component of the nucleus pulposus. ERK is associated with neuronal signal transduction and nociception. METHODS: We studied tissue from naive rats, vehicle-treated rats, and rats receiving rat recombinant TNF-alpha using Western blots of total and phosphorylated ERK (pERK). We used immunohistochemistry of pERK with neuronal nuclear (NeuN) antibody to identify its cellular distribution. RESULTS: Topical application of TNF-alpha to rat nerve root increased pERK in ipsilateral dorsal root ganglion (DRG) neurons and glia within 5 hours. pERK was not expressed in DRG during the first hour after TNF-alpha application, nor was it seen at anytime in spinal cord dorsal horn. DRG satellite cells had increased pERK 5 hours after TNF-alpha or vehicle treatment. TNF-alpha treatment increased pERK in small- and medium-sized DRG neurons and to a lesser degree in large neurons. CONCLUSIONS: These findings suggest that ERK signaling plays a role in the activation of DRG cells following inflammatory injuries to nerve roots and further documents the importance of inflammation in the pathogenesis of painful spine disorders.

Administration, Topical↗
PubMed2006

Quantification of left ventricular regional functions using ECG-gated myocardial perfusion SPECT--validation of left ventricular systolic functions--.

OBJECTIVE: We have developed a program to quantify regional left ventricular (LV) function and wall motion synchrony using ECG-gated myocardial perfusion SPECT (MPS). This preliminary study was undertaken to validate the use of this program for estimating regional LV systolic function. METHODS: Patients were subjected to MPS by 99mTc-sestamibi at rest. The study included 20 patients who were confirmed to have a low probability of coronary artery disease (LPG; low probability group), 19 heart disease patients who were examined by MPS and equilibrium radionuclide angiography (ERNA) (ERG; ERNA group), and 24 patients who were examined by MPS and 2-dimensional echocardiography (2DE) (2DEG; 2DE group). The values of the ejection fraction (EF) and peak ejection rate (PER) were estimated. The global functions evaluated by this program were compared with those obtained by ERNA in the ERG. For regional assessment, the reference values of the functional indices were obtained for 17 LV segments in LPG. The Z score, (reference average value of the segment--patient's value of the segment)/reference standard deviation of the segment, was used for the evaluation of regional functions; a score equal to or greater than 2 was defined as abnormal. Semiquantitative visual interpretation of 2DE was used as the standard to assess wall motion. The sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of these criteria and the relationship between 2DE grading and Z scoring were validated in 2DEG. RESULTS: The values of the global EF and PER evaluated by this program correlated with those determined by ERNA (r = 0.76 and 0.58, respectively; p < 0.005 and 0.01, respectively). The sensitivities of regional EF and PER for segmental wall motion abnormalities were 86.7% and 68.7%, respectively; their specificities were 86.7% and 95.5%, respectively; their PPVs were 64.3% and 79.2%, respectively; and their NPVs were 96.0% and 91.7%, respectively. The Z scores of these indices significantly correlated with the scores determined by 2DE (rs = 0.70 and 0.68, respectively; p < 10(-10)). CONCLUSION: The potential of this program to quantify the regional systolic function was validated.

Aged↗
PubMed2006

Late-onset fatal Epstein-Barr virus-associated hemophagocytic syndrome following cord blood cell transplantation for adult acute lymphoblastic leukemia.

A 43-year-old Japanese woman underwent unrelated cord blood transplantation (CBT) during remission for acute lymphoblastic leukemia with t(4; 11)(q21;q23). Tacrolimus was given for prophylaxis of graft-versus-host disease. The posttransplantation clinical course was mostly uneventful, and the leukemia remained in remission. Fourteen months after CBT, the patient developed pancytopenia and hepatic dysfunction with persistent high-grade fever. The bone marrow was hypocellular with increased numbers of macrophages and hemophagocytes. The numbers of Epstein-Barr virus (EBV) copies in peripheral blood samples were remarkably high. Although the patient showed complete donor-type hematopoiesis, the titer of viral capsid antigen immunoglobulin G was low, and the results of a test for EBV nuclear antigen were negative. There was no clinical response to the reduction of immunosuppressive therapy or to the administration of high-dose methylprednisolone, human immunoglobulin, or acyclovir. The patient died 466 days after CBT of massive gastrointestinal hemorrhage due to bone marrow and hepatic failures. This case demonstrates that fatal EBV-associated hemophagocytic syndrome (HPS) can occur more than 1 year after CBT. This report is the first of a case of late-onset EBV-associated HPS following CBT.

Acyclovir↗
PubMed2006

[S-1 combined with lentinan in patients with unresectable or recurrent gastric cancer].

Lentinan (LNT) is a beta-glucan known to have a life-prolonging effect in combination with chemotherapy for patients with unresectable or recurrent gastric cancer. Thus, a multi-center trial of chemo-immunotherapy using S-1 combined with LNT may benefit patients with unresectable or recurrent gastric cancer with acceptable toxicity. With such a regimen, the median survival time in 32 patients was 559 days. Regardless of change to second-line chemotherapy, the mean period of using S-1+LNT for patients with long NC above 400 days was 725 days. In subset analyses, the survival period of the patients with G/L ratio of equal to or less than 2 was significantly better than that of the higher one (p<0.0001). The incidence of hematological toxicity (grade 3 leukopenia and thrombocytopenia) was 6.3% (2/32), and non-hematological toxicity (grade 2 dysgeusia) was 6.3% (2/32), while no grade 4 toxicity was observed. S-1 and LNT combination immunotherapy was carried out safely with high QOL and allowed a prolonged administration. S-1+LNT regimen may prolong NC periods in patients with unresectable or recurrent gastric cancer.

Adenocarcinoma↗
PubMed2005

Cytogenetic features of de novo CD5-positive diffuse large B-cell lymphoma: chromosome aberrations affecting 8p21 and 11q13 constitute major subgroups with different overall survival.

De novo CD5-positive diffuse large B-cell lymphoma (CD5(+)DLBCL) is regarded as a different clinicopathological entity from CD5-negative DLBCL (CD5(-)DLBCL) and mantle cell lymphoma (MCL). Because only a few published cytogenetic studies of de novo CD5(+)DLBCL are available, we investigated chromosomal changes in 23 Japanese patients who had de novo CD5(+)DLBCL. A characteristic of cytogenetic abnormalities in de novo CD5(+)DLBCL was a high incidence of chromosomal aberrations affecting 8p21 and 11q13. Major chromosomal breakpoints were concentrated at 8p21, 11q13, and 3q27. Patients with 8p21 aberrations showed aggressive clinical features, including advanced stage of disease, elevated serum LDH level, poor performance status, and an inferior survival curve compared with patients who had 11q13 changes (P = .043). Chromosomal abnormalities of both 8p21 and 11q13 were not observed in the same patient, and each abnormality showed different chromosomal gains and losses. These results indicate that de novo CD5(+)DLBCL may occur in previously unidentified subgroups that differ in their chromosomal abnormalities. The conflicting results of previous studies on prognosis may thus be explained in part by the differences in chromosomal changes.

Adult↗
PubMed2005

Phase I study of a weekly schedule of fixed-dose paclitaxel and escalating doses of cisplatin for recurrent or unresectable gastric cancer in Japan.

The authors objective was to determine the toxicities and maximum tolerated dose of a dose-dense schedule of fixed-dose paclitaxel and escalating doses of cisplatin in patients with recurrent or unresectable carcinoma of the stomach. On days 1, 8, 15, 29, 36, and 43, patients received a fixed dose of paclitaxel (80 mg/m2 over 1 hour after a short premedication) followed by a 30-minute infusion of cisplatin at dose levels of 7, 15, 20, and 25 mg/m2. Six patients were treated at each dose level, except for the dose of 25 mg/m2 cisplatin. All the patients were assessed for toxicity and 17 patients (81%) were evaluated for response. The cisplatin dose could be escalated to 25 mg/m2. At the dose of 80 mg/m2 paclitaxel and 25 mg/m2 cisplatin, all 3 patients developed dose-limiting toxicity of the gastrointestinal tract. There were no treatment-related deaths. Leukopenia grades 3 or 4 was seen in 5 patients (11.1%), but infectious complications were not encountered. Other toxicities were mild and easily managed. Weekly paclitaxel at a dose of 80 mg/m2 infused over 1 hour, followed by an infusion of 20 mg/m2 cisplatin is recommended for further study in patients with recurrent or unresectable gastric cancer.

Adult↗
PubMed2005

Cerebral ventricular volume assessment by three-dimensional ultrasonography.

We assessed ventricular volume with three-dimensional ultrasonography. The study group consisted of 54 infants admitted to the neonatal intensive care unit (NICU). Gestational age was 32.9+/-3.5 weeks and birth weight was 1774+/-623 g. To obtain images, the transducer was placed on the anterior fontanel. Sagittal sections were serially and automatically scanned from left to right. The angle of scanning was 60 degrees and five seconds were spent on e scanning. Two hundred fifty B-mode images were stored in the built-in computer for later retrieval. We chose the parasagittal sections from the midline to the lateral portion and traced manually an area of the lateral ventricle in each section at intervals of 1 mm. The built-in computer integrated them and measured the ventricular volume. The lateral ventricular size became larger during the first two weeks after birth. The left ventricle was larger than the right one. There was no correlation between lateral ventricular volume and birth weight. Our study shows the normal value of the lateral ventricular volume in neonates.

Cerebral Ventricles↗
PubMed2005

Utility of a Doppler-derived index combining systolic and diastolic performance (Tei index) for detecting hypoxic cardiac damage in newborns.

The purpose of this study was to assess cardiac function of newborns with mild asphyxia by a Doppler-derived index combining systolic and diastolic performance (Tei index). We studied 20 preterm infants with mild asphyxia. A control group consisted of 20 gestational age-matched preterm infants without asphyxia. Echocardiograms were performed during the fourth and seventh days after birth. Peak velocities of an early filling wave (E) and an atrial contraction wave (A) were measured from the mitral inflow velocity profile and the ratio of peak E to A was calculated. Ejection time was measured from the left ventricular outflow Doppler signal. The sum of isovolumetric times was obtained by subtracting the ejection time from the interval between cessation and onset of mitral inflow. The index was the sum of isovolumetric times divided by ejection time. Ejection fraction was also calculated. The ratio of peak E to A and ejection fraction were the same in both groups. The myocardial performance index in patients with asphyxia was higher than that in patients without asphyxia. We concluded that patients with mild asphyxia have a mild cardiac dysfunction and this change can be detected by a myocardial performance index.

Asphyxia Neonatorum↗
PubMed2005

Fluorescence in situ hybridization monitoring of BCR-ABL-positive neutrophils in chronic-phase chronic myeloid leukemia patients during the primary stage of imatinib mesylate therapy.

We describe a method for monitoring chronic myeloid leukemia (CML) patients treated with imatinib that uses fluorescence in situ hybridization (FISH) to detect BCR-ABL in peripheral blood (PB) granulocytes. First, we compared this method, termed Neutrophil-FISH, with interphase FISH (i-FISH) analysis of bone marrow (BM), i-FISH analysis of PB mononuclear cells, and conventional cytogenetic analysis (CCA) of BM in 30 consecutive CML patients. We found the percentage of BCR-ABL-positive neutrophils as determined by Neutrophil-FISH to correlate best with the percentage of Philadelphia chromosome-positive metaphases in the BM determined by CCA (y = 0.8818x + 5.7249; r(2) = 0.968). We then performed a serial Neutrophil-FISH study of 10 chronic-phase CML patients treated with imatinib and found that the technique could clearly separate imatinib responders from nonresponders within 12 weeks of drug administration. There was a significant difference in the percentages of BCR-ABL-positive neutrophils between responder (mean 3 SD, 18.2% 3 11.8%) and nonresponder (82.4% 3 5.1%) groups at 12 weeks (P < .0001, Student t test).Together with real-time quantitative polymerase chain reaction analysis, Neutrophil-FISH represents another useful method for monitoring CML patients during the primary myelosuppressive stage of imatinib therapy because it is a quick, simple, and reliable method for assessing cytogenetic response.

Antineoplastic Agents↗
PubMed2005

Percutaneous transhepatic mechanical thrombectomy for acute mesenteric venous thrombosis.

PURPOSE: To present the management of symptomatic acute mesenteric venous thrombosis using a percutaneous thrombectomy device followed by resection of necrotic intestine. CASE REPORT: A 60-year-old woman developed acute abdomen and melena. Diffuse and extensive mesenteric and portal vein thromboses were diagnosed by computed tomography. Percutaneous transhepatic mechanical thrombectomy with an Oasis thrombectomy device removed approximately 80% of the thrombus in the portal and superior mesenteric veins. The patient underwent laparotomy immediately after thrombectomy, in which 100 cm of necrotic intestine was resected. Catheter-directed urokinase thrombolysis was performed for 3 days to address residual thrombi. The result was excellent, and the patient recovered without short bowel syndrome. CONCLUSIONS: The hydrodynamic thrombectomy system is a quick, reliable, efficient device that may offer an alternative to thrombolysis and surgical thrombectomy. Combining mechanical thrombectomy devices and surgery can be used to treat symptomatic acute mesenteric venous thrombosis.

Abdominal Pain↗
PubMed2003

Pathomechanisms of nerve root injury caused by disc herniation: an experimental study of mechanical compression and chemical irritation.

STUDY DESIGN: An electrophysiologic and histologic study on nerve roots after mechanical compression and/or local application of nucleus pulposus (NP) was performed. OBJECTIVE: To assess the effects of mechanical compression and/or chemical irritation caused by NP. SUMMARY OF BACKGROUND DATA: It has been shown that application of NP to nerve roots without compression induces histologic and functional changes in nerve roots and the dorsal root ganglia. In clinical situations, however, mechanical compression has also been considered an important factor in disc herniation. METHODS: Eighteen dogs (9-15 kg) were used in this study. Four groups were used to assess the effect of each factor: 1) sham group (n = 3); 2) NP group (NP applied under the S1 lamina) (n = 5); 3) comp group (a plastic balloon placed under the S1 lamina) (n = 5); and 4) comp+NP group (a balloon and NP placed under the S1 lamina) (n = 5). Ascending cauda equina action potentials (CEAPs) and cauda equina-sensory nerve conduction velocity (SCV) were recorded before, immediately after, and 1 week after treatment. Histologic changes were also assessed by light microscopy. RESULTS: There were no significant differences in CEAP and SCV among the four groups immediately after the treatment. However, 1 week after treatment, the amplitudes in the NP group, comp group, and comp+NP group were statistically significantly lower compared with those in the sham group. The comp+NP group showed significantly lower amplitude than did the NP group and comp group. Immediately after treatment, SCV in the NP group and comp group did not show significant differences compared with that in the sham group. However, 1 week after treatment, SCV in the comp+NP group was significantly lower compared with that in the sham group. Histologic changes such as intraneural edema, Schwann cell edema, and nerve fiber injury seemed to be more pronounced in the comp+NP group than in the other groups. CONCLUSIONS: It was shown that each of the assessed factors induces nerve dysfunction. However, the combination of mechanical compression (mass effect of herniated NP) and chemical irritation (inflammation around nerve root) may induce more nerve root injury than each factor per se.

Animals↗
PubMed2003

A histologic and functional study on cauda equina adhesion induced by multiple level laminectomy.

STUDY DESIGN: A histologic and functional study on cauda equina adhesion induced by multiple-level laminectomy was performed using rats. OBJECTIVE: To assess the relation between the extent of laminectomy and histologic and functional changes of the cauda equina induced by laminectomy. SUMMARY OF BACKGROUND DATA: It has been demonstrated that laminectomies may induce cauda equina adhesion, transiently or permanently. However, the relation between the extent of laminectomy and histologic and functional changes of the cauda equina induced by laminectomy is still unclear. METHODS: Sprague-Dawley rats (250-300 g) were used. They were divided into four groups: no-laminectomy group (n = 5) and single, double, and triple level laminectomy groups (n = 20, respectively). At 24 hours and 1, 3, and 6 weeks after laminectomy, rats in each group were killed, and specimens were obtained from L4 to L6. The histologic changes were assessed using the classification of Yamagami. Walking durations on treadmill test and ascending spinal nerve-evoked potential were assessed in laminectomy groups before laminectomy, then weekly for 1 to 6 weeks after laminectomy. RESULTS: With the greater extent of laminectomy, the decrease in cauda equina adhesions was more delayed. There was no difference in walking durations and ascending spinal nerve-evoked potential between pre- and postlaminectomy. CONCLUSIONS: The extent of laminectomy was related to recovery time of induced cauda equina adhesion. However, a delay in recovery from cauda equina adhesion may not produce a recognizable delay in recovery from clinical symptoms.

Animals↗
PubMed2003

Neonatal toxic shock syndrome-like exanthematous disease (NTED).

The author and colleagues recently discovered an emerging neonatal infectious disease: neonatal toxic shock syndrome-like exanthematous disease (NTED), which is induced by the superantigen toxic shock syndrome toxin-1 (TSST-1), produced by methicillin-resistant Staphylococcus aureus (MRSA). The massively expanded Vbeta2+ T cells were rapidly deleted in the peripheral blood of patients with NTED. A marked depletion of Vbeta2+ T cells was also observed in the peripheral blood before the expansion of these T cells. Anergy is specifically induced in the TSST-1 reactive T cells of patients with NTED. Rapid recovery from NTED without complications is expected to be related to the induction of immunologic tolerance in neonatal patients. Anti-TSST-1 IgG antibody of maternal origin was found to play a protective role in preventing the development of NTED. The number of hospitals that have experience caring for patients with NTED has increased threefold in the past 5 years. Most MRSA isolates from neonatal intensive care units in Japan were found to be a single clone of coagulase type II and to possess TSST-1 and staphylococcal enterotoxin C genes. The timing and increased incidence of NTED suggest the emergence of a new MRSA clone. By recognizing that TSST-1 can induce NTED, healthcare providers may give increased attention to this disease in neonatal wards.

Antilymphocyte Serum↗
PubMed2003

Staphylococcal exanthematous disease in a newborn due to a virulent methicillin-resistant Staphylococcus aureus strain containing the TSST-1 gene in Europe: an alert for neonatologists.

We report a case of staphylococcal exanthematous disease in a newborn due to a toxic shock syndrome toxin 1- and SEC-producing methicillin-resistant Staphylococcus aureus strain and alert neonatologists to the probable emergence in France of the neonatal toxic shock syndrome-like exanthematous disease in newborns previously described in Japan. We advise neonatologists to pay careful attention to clinical parameters and to prescribe appropriate tests: platelet count, serum C-reactive protein concentration, and Vbeta2-positive T-cell counts.

Bacterial Toxins↗