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Biomedical subjects

Y Nishiyama

Publications and source records attributed to Y Nishiyama.

At least 19 recordsLinked to original sources

Significance of fluorodeoxyglucose PET imaging in the diagnosis of malignancies in patients with biliary stricture.

AIM: This study was performed to evaluate the significance of positron emission tomography using fluorodeoxyglucose (FDG-PET) in diagnosing malignancy in patients with biliary stricture by comparing the sensitivity and specificity of FDG-PET with those of CT scans and cytological examination of the bile. METHODS: Thirty patients who underwent FDG-PET for differential diagnosis of the disease causing biliary stricture were included in this study. The sites of the strictures were as follows: in the intrahepatic bile duct in five patients, in the peripheral extrahepatic bile duct in 17 patients, and in the distal extrahepatic bile duct in eight patients. The sensitivity and specificity (%) of FDG-PET in diagnosing malignancies were evaluated and compared with those of CT scans and cytological examination using obtained bile. Final diagnoses were based on surgical or biopsy findings. Data was collected and analysed in a retrospective fashion. RESULTS: Malignant diseases were diagnosed in 21 patients, as follows: cholangiocarcinoma including Klatskin tumour in 10 patients, gallbladder cancer in eight, duodenal and ampulla cancer in two, and pancreatic cancer in one. In diagnosing malignancy in patients with biliary stricture, overall sensitivity and specificity were 85.7 (18/21) and 55.6 (5/9), respectively, for CT, 64.7 (11/17) and 100 (7/7), respectively, for cytological examination of the bile, and 90.5 (19/21) and 77.8 (7/9), respectively, for FDG-PET. CONCLUSIONS: In diagnosing malignant diseases in patients with biliary stricture, FDG-PET was superior to CT examination in both sensitivity and specificity, and superior to cytological examination of the bile in sensitivity. However, in patients with inflammatory disease, such as primary sclerosing cholangitis and cholecystitis, false positive rates were found. Therefore, a multidisciplinary diagnostic approach using FDG-PET in conjunction with conventional modalities seems essential to a precise differential diagnosis.

Aged↗

In vitro and in vivo analysis of human herpesvirus-6 U90 protein expression.

In order to establish a reliable method for the detection of human herpesvirus-6 (HHV-6) B antigens in peripheral blood mononuclear cells (PBMCs) collected from HHV-6 infected patients, we created a polyclonal antibody against the HHV-6 B U90 protein (IEA/ex3) and used it to examine the expression of this protein in virus-infected cells and patients' PBMCs. This antibody reacted with 170 and 195 kDa proteins in HHV-6 B-infected cord blood mononuclear cells. The IEA/ex3 antigen was detected in cord blood mononuclear cells at 6 hr post-infection, and the number of infected cells reached its maximum at 48 hr post-infection. The antigen stained in a punctate pattern and partially localized to the promyelocytic leukemia (PML) protein body. We also examined 60 PBMC samples from 60 febrile children (3-19 months old) and detected IEA/ex3 antigen in the PBMCs by laser-scanning microscopy. HHV-6 was isolated from 31 of the 60 samples. The sensitivity and specificity of the antigen detection were 84% (26/31) and 97% (28/29), respectively, in the samples with virus detected. The mean number of antigen-positive PBMCs was 409/10(6) cells in 20 samples with viral isolation. A significant correlation (r = 0.566; P = 0.008) was observed between the viral load and number of antigen-positive cells. Although IEA/ex3 antigen was detected by laser-scanning microscopy in PBMCs (without cultivation) collected from six patients with isolated virus, it was detected in only one sample by conventional fluorescence microscopy. Increasing the intensity by cultivation (24 hr) resulted in a higher detection rate (5/6) even by conventional fluorescence microscopy, which is available in most hospital laboratories.

Antibodies, Viral↗

Bioconversion studies in cultured cells of Corydalis species.

Structural analysis of the metabolites of dopamine and salsolinol in cultured cells of Corydalis species was carried out using the combination of LC-MS and LC-NMR techniques. Metabolic pathways were clarified without the need to isolate the individual metabolites.

Biotransformation↗

Carrier-dependent specificity of antibodies to a conserved peptide determinant of gp120.

Amino acid residues 421-436 constitute a comparatively conserved determinant of gp120 that participates in the binding of host cell CD4 receptors by HIV-1. We compared the immunogenicity of synthetic Cys-gp120 (421-436) conjugated to KLH via the N terminal Cys residue (KLH-I) and gp120 (421-436) extended at its N terminus with a 15 residue tetanus toxoid T cell epitope (T-I) in non-autoimmune mice (BALB/cstrain) and Fas-defective autoimmune mice (MRL/lpr strain). Both immunogens elicited high titer Abs detected as the binding to gp120 (421-436) conjugated to bovine serum albumin (BSA-I) immobilized in ELISA plates. Abs from KLH-I immunized mice displayed binding to full-length gp120 but the Abs from T-I immunized mice did not. Proteins unrelated in sequence to gp120 did not bind the Abs. Soluble I and T-I failed to compete with immobilized BSA-I for binding to anti-KLH-I Abs, whereas these peptides inhibited anti-T-I Ab binding by BSA-I (rank potency order: BSA-I > T-I >> I). These results indicate the influence of the carrier protein on the specificity of Abs to synthetic I. Low level BSA-I and gp120 binding Abs were detected in sera from non-immunized MRL/lpr mice. Similar Ab binding titers and specificity profiles were evident in MRL/lpr and BALB/c mice following immunization with KLH-I and T-I, indicating that pre-existing immunity to gp120 in the former strain does not influence the magnitude or specificity of the Ab response.

Amino Acid Sequence↗

Oncolytic viral therapy using a spontaneously generated herpes simplex virus type 1 variant for disseminated peritoneal tumor in immunocompetent mice.

The present study demonstrates that a clonal derivative (HF10) of HSV-1 strain HF effectively treated disseminated peritoneal neoplasm in an immunocompetent animal model and that all of survived mice acquired resistance to rechallenge with tumor cells. The survival time of mice treated with HF10 was longer than that of mice treated with hrR3, indicating that the oncolytic effect of HF10 was more potent than that of hrR3 in this animal model. HF10 induces syncytia formation in vitro, whereas hrR3 forms rounded CPE. The sequential administration of HF10 gave a long term survival of more than 90 days after tumor injection, with no signs of disease, in 8 of the 9 treated mice. The results suggest that treatment of disseminated peritoneal tumor with HF10 induces a specific antitumor immune response. Genomic structure determination showed that HF10 has a deletion of 3.9-kilobase pair (kbp) in the right end of UL and UL/IRL junction, resulting in the loss of UL 56 expression. A 2.3 kbp deletion and extensive rearrangement were also observed in the left end of the genome.

Animals↗

99mTc galactosyl human serum albumin liver dynamic SPET for pre-operative assessment of hepatectomy in relation to percutaneous transhepatic portal embolization.

We have devised an original predictive residual index (PRI) using 99mTc diethylenetriaminepentaacetic acid galactosyl human serum albumin (99mTc-GSA) liver dynamic SPET for the pre-operative assessment of hepatectomy, including the prediction of residual liver function before hepatectomy. The aim of this study was to evaluate the usefulness of the PRI by using 99mTc-GSA liver dynamic SPET before and after percutaneous transhepatic portal embolization (PTPE) to induce compensatory hypertrophy of the remnant lobe, and to compare the results with the prognosis after hepatectomy. The subjects included eight patients with cholangiocellular carcinoma, five with gallbladder cancer, four with hepatocellular carcinoma and three with metastatic liver cancer. 99mTc-GSA liver dynamic SPET was performed immediately before and 2 weeks after PTPE. Dynamic SPET with 35 continuous rotations was performed to obtain the k-value according to the accumulation curve in each voxel (0.54 cm x 0.54 cm x 1.08 cm) of the liver immediately after a bolus injection of 185 MBq 99mTc-GSA. Each rotation consisted of 180 degrees turn in 64 steps in a 64 x 64 matrix. The acquisition time of each rotation was 35 s. We devised an original PRI by combining the k-value with functional liver volume which were measured by liver dynamic SPET. Hepatectomy was performed following the second SPET. The correlation between the PRI and post-operative patient prognosis was investigated retrospectively. The functional liver volume of the remnant lobe and the PRI significantly increased after PTPE compared with respective values before PTPE (P<0.005 and P<0.0001, respectively). Regarding the relationship between the PRI and the clinical course following surgery, post-operative complications were observed in only two patients. The PRI values of these two patients were 0.323 and 0.394. When the PRI was above 0.400, no patient had symptoms of hepatic failure. The results of this study suggest that, when the PRI value is above 0.400, there is a low probability of hepatic failure after hepatectomy. We conclude that the PRI devised in this study is useful in the pre-operative assessment of hepatectomy after PTPE.

Adult↗

Comparative whole-body 201Tl and bone scintigraphies for the detection of bone marrow involvement in multiple myeloma.

The objectives of this study were to investigate the role of whole-body 201Tl-chloride scintigraphy in comparison with bone scintigraphy in the detection of bone marrow involvement in patients with multiple myeloma and to assess the follow-up evaluation using 201Tl-chloride. Twenty-one patients with untreated multiple myeloma were evaluated. 201Tl-chloride images were acquired 10 min (early) and 2 h (delayed) after the injection of 111 MBq 201Tl-chloride. Bone images were acquired 3 h after the intravenous injection of 740 MBq 99mTc-hydroxymethylene diphosphonate (HMDP). The 201Tl-chloride scan patterns were classified as normal, diffuse (presence of bone marrow), focal (localized areas of uptake) and diffuse+focal. The bone scan patterns were classified as normal and abnormal. Eight of the 21 patients also underwent 201Tl-chloride scintigraphy after chemotherapy for the evaluation of the therapeutic response. On the early 201Tl-chloride image, two patients showed a normal, 13 a diffuse, two a focal and four a diffuse + focal pattern. On the delayed 201Tl-chloride image, nine patients showed a normal, six a diffuse, four a focal and two a diffuse + focal pattern. Bone scintigraphy showed an abnormal accumulation in only five of the 21 patients. Of the eight patients who underwent follow-up 201Tl-chloride studies, the abnormal diffuse pattern was changed to a normal pattern on post-treatment scintigraphy in three, and the degree of abnormal 201Tl-chloride accumulation decreased in comparison with the pre-treatment scan in three. These six patients were considered to be in clinical remission. In the two remaining patients, the degree of abnormal 201Tl-chloride accumulation increased in comparison with the pre-treatment scan, and they were considered to be in clinical progression. 201Tl-chloride scintigraphy is a non-invasive tool, which may be more useful than bone scintigraphy for the diagnosis of multiple myeloma, and may be helpful in the follow-up of multiple myeloma.

Aged↗

Relapse of neonatal herpes simplex virus infection.

BACKGROUND: Neonatal herpes simplex virus (HSV) infection is a severe disease with high mortality and morbidity. Recurrence of skin vesicles is common. OBJECTIVE: To determine the features of relapse and identify the factors related to relapse. DESIGN: Thirty two surviving patients with neonatal herpes virus infections were enrolled. All patients received acyclovir treatment. Clinical and virological data were analysed and compared between relapsed and non-relapsed cases. RESULTS: Thirteen (41%) had either local skin or central nervous system relapse between 4 and 63 days after completing the initial antiviral treatment. Nine patients exhibited local skin relapses, and four developed central nervous system relapses. In one skin and two central nervous system relapse cases, neurological impairment later developed. Type 2 virus infection was significantly related to relapse (odds ratio 10.4, 95% confidence interval 1.1 to 99.0). Patients with relapse had worse outcomes than those without relapse. CONCLUSION: Neonates with HSV type 2 infections have a greater risk of relapse. Relapsed patients have poorer prognoses.

Acyclovir↗

Expression of tegument protein pp65 of human cytomegalovirus (CMV) and its application to the analysis of viral-specific cellular immunity in CMV-infected individuals.

Investigations into human cytomegalovirus (CMV)-specific cellular immunity are important to better understand and manage CMV infections. CMV phosphoprotein pp65 is thought to be a major antigen for CMV-specific cellular immunity. We newly synthesized protein pp65 with a baculovirus expression system and purified it via metal affinity chromatography in a soluble form. The recombinant protein pp65 was antigenic in an enzyme immuno-linked assay for pp65-specific IgG in sera from 196 children. Traditional lymphoproliferation assays have shown that pp65 protein promotes specific lymphoproliferation in CMV-seropositive donors. Using an intracellular cytokine detection system, we showed that this recombinant protein stimulated CD4-positive T cells to express interferon-gamma. The results of these assays using protein pp65 were comparable with the use of CMV whole antigen. pp65- and CMV-specific cellular immunity, and CMV DNA load were also compared in four recipients of unrelated cord blood transplantation. The delay in re-constitution in CMV-specific cellular immunity was associated with reactivation of CMV. These results indicated that the recombinant protein pp65 can be used to study specific immunity in CMV infections.

Adolescent↗

Critical involvement of CD40 in protection against herpes simplex virus infection in a murine model of genital herpes.

We studied the requirement for CD40+ cells in the resolution of vaginal infection with avirulent herpes simplex virus type I (HSV-1) in vivo using CD40-deficient mice, which were susceptible to infection with avirulent HSV-1. Compared with wild-type mice, CD40-deficient mice could not eliminate HSV-1 virus effectively from the vaginal mucosa and produced lower amounts of interleukin-12 and interferon-gamma. These results show that the induction and activation of CD40+ cells are important for HSV prevention, facilitating the activation of T cells to induce an efficient HSV clearance from the vaginal mucosa and to prevent lethal illness due to HSV infection.

Animals↗

Comparison of 201 Tl- with 67 Ga single photon emission tomography in the diagnosis of head and neck cancer recurrence.

The purpose of this study was to evaluate the usefulness of 201Tl single photon emission tomography (SPET) in comparison with 67Ga SPET for distinguishing recurrent tumours in patients previously treated for head and neck cancer. A total of 37 patients with suspicion of recurrent cancer were investigated. SPET images with 201Tl were acquired 10min (early) and 3h (delayed) and SPET images with 67Ga were acquired 72h, after injection. The visual and semiquantitative (T/N ratio) analysis were performed. On visual analysis, results from early 201Tl SPET were the same as those from delayed 201Tl SPET. The sensitivity, specificity and accuracy of the diagnosis of local recurrence using 201Tl SPET were all 100%. The three values using 201Tl SPET for neck lymph node metastases were 73%, 100% and 91%. The corresponding values using 67Ga SPET for local recurrence were 57%, 100% and 89%, respectively, and those using 67Ga SPET for neck lymph node metastases 55%, 100% and 84%, respectively. In the semiquantitative analysis, there was a statistically higher T/N ratio obtained using 201Tl when compared with 67Ga. 201Tl early SPET, especially, has the potential to replace 67Ga SPET in the follow-up of patients with head and neck cancer.

Adult↗

99mTc-MIBI and 201Tl SPET in the detection of recurrent brain tumours after radiation therapy.

The purpose of this study was to evaluate whether Tc-hexakis-2-methoxyisobutylisonitrile ( Tc-MIBI) or Tl single photon emission tomography (SPET) could detect recurrent tumours in patients with previous radiation therapy for brain tumours. Dual SPET with Tc-MIBI and Tl was performed in 21 patients suspected of having recurrent brain tumours. SPET images were acquired 15 min (early) and 2 h (delayed) after injection. The ratio of the average counts for the region of interest in the lesion area and its mirror image in normal brain tissue was obtained. Early and delayed ratios were calculated. On the basis of histological and/or clinical findings, the final diagnosis was considered as recurrent tumours in 15 patients and radiation necrosis in six. Both ratios using Tc-MIBI and Tl were significantly higher in recurrent tumours than in radiation necrosis. Based on a cut-off of 5.89 of the early ratio using Tc-MIBI to distinguish between recurrent tumours and radiation necrosis, the accuracy was 90%. Based on a cut-off of 6.77 of the delayed ratio using Tc-MIBI, the accuracy was 86%. The corresponding values using cut-offs of 2.40 and 1.85 with Tl were 90% and 86%, respectively. However, within recurrent tumours, both ratios for Tc-MIBI were significantly higher than those for Tl. Early Tc-MIBI SPET may be especially useful for the detection of recurrent tumours in patients who have previously undergone radiation therapy for brain tumours.

Adult↗

The US11 gene product of herpes simplex virus has intercellular trafficking activity.

The US11 gene product of herpes simplex virus is an abundant virion structural protein with RNA-binding regulatory activity. Its carboxyl-terminal half consists of tandem tripeptide repeats of the sequence RXP. We demonstrate that the US11 protein has intercellular trafficking activity and accumulates in the nucleolus when singly expressed in cultured cells, and that the RXP repeats are responsible for this activity. These same properties were also observed in cells expressing a fusion protein linking US11 to the green fluorescent protein. Furthermore, exogenous US11 protein was internalized by cells at 4 degrees C, which suggests that US11 protein uptake occurs primarily through an energy-independent pathway.

Amino Acid Sequence↗

Oxidative stress inhibits the repair of photodamage to the photosynthetic machinery.

Absorption of excess light energy by the photosynthetic machinery results in the generation of reactive oxygen species (ROS), such as H2O2. We investigated the effects in vivo of ROS to clarify the nature of the damage caused by such excess light energy to the photosynthetic machinery in the cyanobacterium Synechocystis sp. PCC 6803. Treatments of cyanobacterial cells that supposedly increased intracellular concentrations of ROS apparently stimulated the photodamage to photosystem II by inhibiting the repair of the damage to photosystem II and not by accelerating the photodamage directly. This conclusion was confirmed by the effects of the mutation of genes for H2O2-scavenging enzymes on the recovery of photosystem II. Pulse labeling experiments revealed that ROS inhibited the synthesis of proteins de novo. In particular, ROS inhibited synthesis of the D1 protein, a component of the reaction center of photosystem II. Northern and western blot analyses suggested that ROS might influence the outcome of photodamage primarily via inhibition of translation of the psbA gene, which encodes the precursor to D1 protein.

Bacterial Proteins↗

Effect of the deletion of US2 and US3 from herpes simplex virus type 2 on immune responses in the murine vagina following intravaginal infection.

We investigated the effects of US2 and US3 deficiencies of herpes simplex virus type 2 (HSV-2) on host immunity in a murine model of genital herpes infection. Viral clearance from the vaginal mucosa was more rapid in mice infected with a US3-deficient mutant L1BR1 as compared with a wild-type 186 or YY2 (US2-deficient mutant) infection, although there was no significant difference among them in initial growth in the early stage of infection. Flow cytometric studies revealed that the number of vaginal mononuclear cells in L1BR1-infected mice was significantly greater than that in 186- or YY2-infected mice. Dendritic cells, macrophages and T cells were induced more rapidly and in greater numbers within the vaginas of L1BR1-infected mice. Moreover, the levels of IL-12 and IFN-gamma increased in L1BR1-infected mice over levels in 186-infected mice. These results indicate that a US3 deficiency alters the induction of the host immune response; therefore, the inactivation of US3 may be a promising strategy in the development of novel vaccines for genital herpes.

Administration, Intravaginal↗

Hydrosilylation of carbonyl compounds using a PhSeSiMe(3)/Bu(3)SnH/AIBN system.

[reaction: see text] When carbonyl compounds were allowed to react with phenyl trimethylsilyl selenide and tributylstannyl hydride in the presence of a catalytic amount of AIBN as a radical initiator, the hydrosilylation of the carbonyl compounds efficiently proceeded to give the corresponding silyl ethers in moderate to good yields.

Journal Article↗

Effect of long-term administration of JTP-2942, a novel thyrotropin-releasing hormone analogue, on neurological outcome, local cerebral blood flow and glucose utilization in a rat focal cerebral ischemia.

The effect of JTP-2942, a novel thyrotropin-releasing hormone analogue on neurological examination, local cerebral blood flow (l-CBF) and local cerebral glucose utilization (l-CGU) were examined when JTP-2942 was administered for 4 weeks after 1 week reperfusion following ischemia in a rat middle cerebral artery (MCA) occlusion. Left middle cerebral artery ischemia was induced for 90 min followed by reperfusion. JTP-2942 (0.03 or 0.003 mg/kg) or saline (vehicle) were administered for 4 weeks after 1 week ischemia, and then the drug was withdrawn. Neurological symptoms and motor disturbance based on inclined plane test were measured once a week after 1 week ischemia. l-CBF and l-CGU were measured by quantitative autoradiographic technique after 6 weeks ischemia. The adjacent sections subjected to l-CBF or l-CGU measurement were stained with Hematoxylin-Eosin, and the infarction volume was measured. JTP-2942 (0.03 mg/kg) significantly ameliorated neurological symptoms and motor disturbance at 5 weeks after ischemia as compared with vehicle, and then after completion of drug administration, amelioration effect continued. JTP-2942 (0.03 mg/kg) also significantly ameliorated the reduced l-CBF and l-CGU in the peri-infarcted areas such as the frontal cortex, motor cortex and medial caudate-putamen. No significant differences were noted in the infarction volume among MCA occlusion rats. This indicates that activating reduced metabolic turnover associated with synaptic connection changes or the activation of compensation mechanisms may result in improvement of neurological symptoms and motor disturbances. It is therefore expected that JTP-2942 may be a possible therapeutic agent for motor disturbance during the subacute or chronic cerebral infarction.

Animals↗