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Biomedical subjects

T Tsuchida

Publications and source records attributed to T Tsuchida.

At least 127 records · Page 7Linked to original sources

Coregistration of FDG PET and MRI of the head and neck using normal distribution of FDG.

UNLABELLED: For better localization of head and neck structures by PET with 2-(18)F-2-deoxy-D-glucose (FDG), direct incorporation of anatomical information from MRI by the coregistration of FDG PET and MRI without external markers is proposed. METHODS: Seventeen patients with neoplasms and 16 normal subjects who had both FDG PET and MRI were studied. First, the three-dimensional normal distribution of FDG was evaluated, and then the structures of the head and neck regions with normal distribution patterns of FDG were used as internal markers for the coregistration of PET and MRI. The effectiveness of the coregistration was evaluated using focal neoplasms that were identified by both PET and MRI as fiducial internal markers. RESULTS: The normal structures selected as internal landmarks for coregistration were the tonsils, salivary glands, mucosal layers of the oral cavity and pharynx, spinal cord, inferior portion of the frontal lobe, cerebellum and nasal turbinates. These structures were more easily observed in sagittal or coronal sections than in transaxial sections. All primary neoplasms were delineated by PET, whereas 4 were missed by MRI. Thirteen primary tumors and 7 cervical lymph node metastases coregistered well, with a center-of-mass distance of <2 mm, whereas 10 lymph node metastases were slightly misregistered, with a center-of-mass distance of 7.8+/-6.5 mm (mean+/-s.d.), probably due to differences in neck positions. CONCLUSION: Normal distribution of FDG uptake in the head and neck regions delineated by multidirectional sections is important for effective coregistration of FDG PET with MRI.

Aged↗

Synthesis, photophysical properties, in vivo photosensitizing efficacy, and human serum albumin binding properties of some novel bacteriochlorins.

The synthesis, photophysical characteristics, in vivo photosensitizing efficacy, human serum albumin (HSA) binding properties, and skin phototoxicity of some stable bacteriochlorins were investigated. The novel bacteriochlorins, obtained from chlorophyll-a, have long-wavelength absorptions in the range lambda max = 734-758 nm. Preferential migration of ethyl over methyl substituents among ketobacteriochlorins obtained in the pinacol-pinacolone rearrangements of vic-dihydroxybacteriochlorins was confirmed by NOE studies. The bacteriochlorins show relatively low fluorescence quantum yields. Among all the bacteriochlorins the triplet states were quenched by ground state molecular oxygen in a relatively similar manner, yielding comparable singlet oxygen quantum yields. In preliminary in vivo studies (DBA/2 mice, transplanted with SMT/F tumors), ketobacteriochlorins were found to be more photodynamically active than the related vic-dihydroxy analogues. Replacement of the methyl ester functionalities with di-tert-butylaspartic acids enhanced the in vivo efficacy. Site specific human serum albumin (HSA) binding studies indicated a direct correlation between the ability of the compound to bind to the diazepam binding site (albumin site II) and the in vivo photosensitizing efficacy.

Animals↗

Testosterone suppresses anti-DNA antibody production in peripheral blood mononuclear cells from patients with systemic lupus erythematosus.

OBJECTIVE: To study the in vitro effect of testosterone on anti-DNA antibody production in peripheral blood mononuclear cells (PBMC) from patients with systemic lupus erythematosus (SLE) in order to elucidate its regulatory role in SLE. METHODS: PBMC from SLE patients were cultured with testosterone. IgG anti-double-stranded DNA (anti-dsDNA) antibody, total IgG, and cytokine activity in the supernatants were measured by enzyme-linked immunosorbent assay. RESULTS: Testosterone suppressed both IgG anti-dsDNA antibody and total IgG production in PBMC from SLE patients. Antibody production in B cells was also suppressed by testosterone, although the magnitude of its effect on B cells was lower than that on PBMC. Interleukin-6 (IL-6) partially restored the testosterone-induced decrease in antibody levels in PBMC. Testosterone reduced IL-6 production in monocytes. CONCLUSION: These results suggest that testosterone may directly suppress anti-DNA antibody production in PBMC from SLE patients by inhibiting B cell hyperactivity and, indirectly, by down-regulating IL-6 production in monocytes. These results support the therapeutic effects of testosterone on SLE.

Adult↗

Effects of in situ freezing and stress-shielding on the ultrastructure of rabbit patellar tendons.

The effects of in situ freezing and the combination of in situ freezing and stress-shielding on the microstructure and ultrastructure of the patellar tendon were studied with use of 20 mature rabbits. The patellar tendon was frozen in situ with liquid nitrogen to kill fibroblasts and then was completely released from stress by chronically pulling a stainless-steel wire installed between the patella and the tibial tubercle. Microstructurally, the freezing treatment induced separation of collagen fiber bundles and fibroblast necrosis at 3 weeks, although the separation disappeared at 6 weeks. Ultrastructurally, small collagen fibrils with a diameter of less than 90 nm were predominant; at 6 weeks, the area occupied by collagen fibrils had decreased. In the frozen-shielded tendon, numerous large spaces were observed in the matrix at 3 weeks. This treatment increased the number of fibrils with a diameter greater than 360 nm and decreased the number of collagen fibrils per unit of area and the area occupied by collagen fibrils at 3 weeks. This study demonstrated that in situ freezing and the combination of in situ freezing and stress-shielding leads to a smaller volume of collagen fibrils per unit of cross section of the patellar tendon by mechanisms that remain to be defined.

Animals↗

Clinical value of triple-energy window scatter correction in simultaneous dual-isotope single-photon emission tomography with 123I-BMIPP and 201Tl.

To improve the image quality in simultaneous dual-isotope single-photon emission tomography (SPET) with iodine-123 labelled 15-(p-iodophenyl)-3-methylpentadecanoic acid (BMIPP) and thallium-201, we applied the triple-energy window method (TEW) for correction of the cross-talk and scatter artifact. Seventy-one patients with coronary artery disease were included. 201Tl cross-talk into the 123I acquisition window (group 1, n = 30) and 123I cross-talk into the 201Tl window (group 2, n = 41) were studied. In group 1, 123I images were first obtained (single-isotope images), followed by 201Tl injection and SPET acquisition using dual-isotope windows (dual-isotope images). In group 2, the order was reversed. The dual-isotope SPET images with and without TEW were compared with the single-isotope images. Qualitative evaluation was performed by scoring the segmental defect pattern. Detectability of the mismatched fatty acid metabolism on dual-isotope SPET was evaluated by receiver operating characteristic (ROC) curve analysis. Segmental defect pattern agreement between dual and corrected single images was significantly improved by TEW correction (P<0.01). The agreement was particularly improved in segments with absence of uptake. There was no significant difference between TEW-corrected dual-isotope SPET and corresponding single-isotope SPET with regard to either % defect count or background activity. Mismatched fatty acid metabolism depicted by dual-isotope SPET predicted abnormal wall motion more accurately with TEW than without TEW. With TEW, a practical method for scatter and cross-talk correction in clinical settings, simultaneous dual 123I-BMIPP/201Tl SPET is feasible for the assessment of myocardial perfusion/metabolism mismatch.

Case-Control Studies↗

Effects of antitumor agents on 3H-2-deoxyglucose uptake in tumor cells and their relationship with the main targets of the antitumor agents.

To investigate the effects of antitumor drugs on 3H-2-deoxyglucose (DG) uptake in tumor cells, we performed DG uptake studies of the short-term treatment of four kinds of antitumor drugs in a cell culture system. The antitumor drugs adriamycin (ADM) and cisplatin (cDDP), which affect on DNA synthesis, did not greatly affect DG uptake, but DG uptake was lowered by antitumor drugs, actinomycin D (AcD) and cycloheximide (CHX), which target the gene expression system. To investigate the mechanism of DG uptake changes, we also tested the effects of some glucose metabolic inhibitors on DG uptake. An inhibitor of glycolytic flow (iodoacetate) lowered DG uptake whereas mitochondrial inhibition increased DG uptake. These results on the inhibition of glucose metabolism indicated that there were two types of factors affecting DG uptake directly; one affects glycolysis and the other affects oxidative phosphorylation. The two antitumor drugs with effects on gene expression were thought to act by the former. The effects of the drug treatments for tumors on DG uptake could be divided into three groups; glycolysis inhibition, mitochondrial inhibition and no relation to glucose metabolism. With the further observations of FDG uptake changes based on this prediction, the biochemical relationship between treatment effects and FDG uptake changes will be clarified.

2,4-Dinitrophenol↗

Delayed enhancement of myocardial FDG uptake on glucose loading FDG-PET in NIDDM patient.

We report a case of delayed enhancement of myocardial FDG uptake in NIDDM patient after oral glucose loading. A 65-year-old man who had a past history of NIDDM received FDG-PET examination during fasting and glucose loading. In neither condition, was an accumulation of FDG in the myocardium, and myocardial blood flow was normal. An oral glucose tolerance test (OGTT) was performed to find the best time for FDG injection and 3 hours after loading, the serum insulin concentration was increased significantly. When the interval between glucose loading and the injection of FDG was set at 3 hours, enhancement of myocardial FDG uptake was demonstrated. To know the best time for the FDG injection in advance is thought to be important in obtaining better image quality and interpreting the myocardial viability when FDG-PET examination during glucose loading is performed in NIDDM patients.

Aged↗

Intramuscular malignant granular cell tumor.

We describe a malignant granular cell tumor in the semimembranosus muscle of a 61-year-old woman. Magnetic resonance images disclosed a tumor with intermediate and low signal intensity on both T1- and T2-weighted images, measuring about 7 x 4 x 4 cm in size. The patient showed an uneventful clinical course during a 30-month follow-up period after the wide excision. The pertinent findings in making the diagnosis of malignant granular cell tumor are large size, intramuscular location, and mitosis including an atypical mitosis.

Biopsy↗

The tumor-bearing state induces augmented responses of organ-associated lymphocytes to high-dose interleukin-2 therapy in mice.

A high-dose bolus regimen for interleukin(IL)-2 administration to cancer patients frequently causes serious side-effects in which various organs are involved. In order to reveal the mechanism of toxicities associated with this regimen, we compared the augmenting effect of high-dose IL-2 on murine organ-associated lymphocytes between neoplastic and non-neoplastic states. Intraperitoneal administration of IL-2 at a dose of 10(5) JRU (Japanese Reference Units) twice daily for 3 days led to the death of all the syngeneic MH134-hepatoma- or X5563-myeloma-bearing mice, whereas it had no lethal effect on non-tumor-bearing mice. Histological and morphometric analyses demonstrated that tumor-bearing mice displayed more extensive infiltration of large granular lymphocytes and agranular lymphocytes in the liver and lungs than did the non-tumor-bearing mice. Large granular lymphocytes had the ultrastructural characteristics of lymphokine-activated killer cells. Lymphocytes often underwent extravasation into the interstitial space and exhibited local proliferation without causing any direct injury to apposed parenchymal cells. Flow-cytometric analysis of hepatic mononuclear cells demonstrated that IL-2-receptor-beta (IL-2R beta)-bearing lymphocytes, i.e., natural killer cells and intermediate CD3 cells, were increased in number in the neoplastic state before the IL-2 injection. The present study indicates that the tumor-bearing state increases the number of organ-associated IL-2R beta + lymphocytes, which are then greatly amplified by the challenge of high-dose IL-2, leading to the functional disturbance of organs. We have further demonstrated here that an intermittent low-dose IL-2 regimen has a potential therapeutic effect on tumor regression without causing lethal side-effects.

Animals↗

Complement Cls, a classical enzyme with novel functions at the endochondral ossification center: immunohistochemical staining of activated Cls with a neoantigen-specific antibody.

The secondary ossification center of 14- to 16-day-old hamster tibiae was examined immunohistochemically with active and inactive Cls-specific antibodies, RK5 and RK4, respectively. At the ossification center, chondrocytes differentiate from proliferating and hypertrophic to degenerating stages, and their site is occupied by the bone marrow. Cls was strongly immunostained in hypertrophic chondrocytes. In order to discover whether Cls is activated at a particular site, the cartilage was immunostained with RK5 and RK4. RK5 mainly reacted with degrading matrix around invading vessels. In contrast, RK4 strongly stained hypertrophic chondrocytes. Immunoelectron microscopy revealed Cls on degrading fragments of chondrocytes and fibers of cartilage matrix. Decorin, one of the major matrix proteoglycans, was dose and time dependently degraded by Cls. Type II collagen and type I gelatin were also degraded. Articular cartilage from patients with rheumatoid arthritis was positively immunostained (11/12 cases) with an anti-Cls monoclonal antibody (mAb) PG11, whereas normal articular cartilage (5/5 cases) was negative, suggesting Cls participation in the etiology of rheumatoid arthritis.

Amino Acid Sequence↗

Annular erythema associated with lupus erythematosus/Sjögren's syndrome.

BACKGROUND: Annular-polycyclic and papulosquamous lesions are associated with subacute cutaneous lupus erythematosus (SCLE). In some Asian cases, annular erythema has been associated with Sjögren's syndrome (SS). However, the relation between the two is unclear. OBJECTIVE: Our purpose was to clarify the clinical manifestations and immunologic features of patients with annular erythema. METHODS: This study included 15 patients with annular erythema. Systemic, serologic, and genetic findings were analyzed. RESULTS: Histologic examination showed perivascular and periappendageal lymphocytic infiltrates in all patients. However, LE-specific epidermal changes were observed in only three (20%). Although all patients at least partially demonstrated features of LE or SS, eight (53%) fulfilled the American Rheumatism Association criteria for systemic LE (SLE) and five (33%) were diagnosed with SS. Renal (20%) and central nervous system (7%) involvement was observed. Anti-Ro(SS-A) and anti-La(SS-B) antibodies were detected in nine (60%) and seven (47%) patients, respectively. There were no histocompatibility antigen (HLA) haplotype differences. CONCLUSION: Annular erythema in Asian patients is the counterpart of subacute skin lesions of LE in whites, except for the paucity of LE-specific histopathologic findings and HLA-DR3 tissue type.

Adolescent↗

Cutaneous lupus mucinosis: a review of our cases and the possible pathogenesis.

Cutaneous lupus mucinosis (CLM) is a rare variant of lupus erythematosus eruptions. Our 5 cases with CLM were reviewed. All were men with systemic lupus erythematosus (SLE). CLM occurred as asymptomatic cutaneous papules, nodules, or plaques on the trunk, upper and lower extremities, and face. Histopathology of CLM mainly revealed abundant mucin deposits among splayed collagen bundles throughout the dermis. However, some CLM lesions showed discoid lupus erythematosus-like epidermal and dermal changes and/or lupus profundus. Vasculitis was also revealed in the CLM lesions of 2 cases. The pathogenesis of CLM may be closely related to its two important features, the male preponderance and the association with SLE. Vasculopathy may also be involved in the development of CLM.

Adult↗

Correlation between site II-specific human serum albumin (HSA) binding affinity and murine in vivo photosensitizing efficacy of some Photofrin components.

Human serum albumin (HSA) is one of the key components in human blood that may influence drug distribution. As such, it is important to know the affinity of any drug for albumin. Previously, Photofrin, a mixture of monomeric, dimeric and oligomeric porphyrins, has been subjected to HSA binding studies. However, due to its complex nature, binding studies on Photofrin or other hematoporphyrin derivatives with HSA are inconclusive. In this report, the binding properties of some components (dimers and trimers) of Photofrin and the relationship between murine photosensitizing efficacy and those binding properties were investigated. The interaction of these porphyrins with HSA was investigated by direct ultrafiltration and fluorescent titration techniques with fluorescent probes such as dansyl-L-proline (DP), which is known to interact selectively with site II on HSA. Porphyrins also were tested for antitumor activity in a mouse model following intravenous administration and exposure to laser light. Together, the results suggest that the photosensitizers that were preferentially bound to site II of HSA were most effective at controlling murine tumor regrowth.

Animals↗

Expression and characterization of sucrose synthase from mung bean seedlings in Escherichia coli.

The cDNA fragment coding for mung bean (Vigna radiata Wilczek) sucrose synthase was introduced into the expression vector pET-20b resulting in the construction of plasmid pEB-01. After transformation of Escherichia coli strain BL21(DE3) cells by pEB-01 and induction with isopropyl thio-beta-galactoside, high level expression of the recombinant enzyme was obtained. The enzyme had a tetrameric form that conserved the activity of sucrose synthase. Although the Km and Vmax of the recombinant enzyme acting on either UDP-glucose or fructose were very close to those of the native enzyme isolated from mung bean seedlings, the Km for sucrose was higher by a factor of 10 for the recombinant enzyme. This suggests that the recombinant sucrose synthase has a tendency to synthesize sucrose, although the native enzyme catalyzes a freely reversible reaction.

Blotting, Western↗

A beta-glucosidase gene downstream of the cellulose synthase operon in cellulose-producing Acetobacter.

An open reading frame was found 214 bp downstream of the cellulose synthase operon of Acetobacter. The encoded amino acid sequence was found to be similar to some beta-glucosidases (G3ases). We detected G3ase activity in the culture medium and analysis of the N-terminal amino acid sequence showed that this gene encodes the enzyme. Therefore, it is possible that this region is a gene cluster for cellulose synthesis.

Acetobacter↗

Synthesis of asymmetrically labeled sucrose by a recombinant sucrose synthase.

About 80% of radioactivity was recovered in asymmetrically labeled sucrose from UDP-[14C]glucose or [14C]fructose with recombinant mung bean sucrose synthase expressed in Escherichia coli harboring pEB-01. This high recovery is due to the fact that the enzyme conserving the activity of sucrose synthase has a similar affinity for UDP-glucose and fructose to an intact enzyme from the mung bean, but a lower affinity for sucrose.

Carbon Radioisotopes↗

Avascular necrosis of bone in systemic lupus erythematosus. The predictive role of precipitating autoantibodies.

The association between the type of precipitating autoantibodies and occurrence of avascular necrosis of bone (AVN) was examined. We prospectively analyzed clinical and laboratory findings of our 113 patients with SLE. Seven of 113 (6%) patients developed AVN. Anti-Ro (SS-A) and anti-RNP antibodies coexisted in 3 of 7 AVN patients. The same combination of these two antibodies were observed in 1 without AVN. Antibodies to topoisomerase I were detected in 2 other patients with AVN but not in any of the patients without AVN. The coexistence of the former two or the presence of the latter one is rare in SLE. However, these (combination of) antibodies can be useful as a local ischemic marker predicting the development of AVN.

Adolescent↗