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Biomedical subjects

Hiroshi Yoshioka

Publications and source records attributed to Hiroshi Yoshioka.

At least 19 recordsLinked to original sources

Production of infectious hepatitis C virus particles in three-dimensional cultures of the cell line carrying the genome-length dicistronic viral RNA of genotype 1b.

We show that a dicistronic hepatitis C virus (HCV) genome of genotype 1b supports the production and secretion of infectious HCV particles in two independent three-dimensional (3D) culture systems, the radial-flow bioreactor and the thermoreversible gelation polymer (TGP), but not in monolayer cultures. Immunoreactive enveloped particles, which are 50-60 nm in diameter and are surrounded by membrane-like structures, are observed in the culture medium as well as at the endoplasmic reticulum membranes and in dilated cytoplasmic cisternae in spheroids of Huh-7 cells. Infection of HCV particles is neutralized by anti-E2 antibody or patient sera that interfere with E2 binding to human cells. Finally, the utility of the 3D-TGP culture system for the evaluation of antiviral drugs is shown. We conclude that the replicon-based 3D culture system allows the production of infectious HCV particles. This system is a valuable tool in studies of HCV morphogenesis in a natural host cell environment.

Cell Culture Techniques↗

High-resolution MR imaging of the proximal zone of the lunotriquetral ligament with a microscopy coil.

OBJECTIVE: To evaluate high-resolution MRI of the proximal zone of the lunotriquetral ligament (LTL) using a microscopy surface coil with a 1.5 T scanner. DESIGN AND SUBJECTS: The proximal zone of the LTL was reviewed in 90 subjects (23 asymptomatic normal volunteers and 67 patients with suspicion of triangular fibrocartilage complex injury) with high-resolution MRI using a 47-mm microscopy surface coil. High-resolution MR images were obtained with gradient recalled echo (GRE) T2*-weighted sequence and short tau inversion recovery imaging, with a 1- to 1.5-mm slice thickness, a 50-mm field of view, an imaging matrix of 140-224x512 using zero fill interpolation, and 3-4 excitations. As a qualitative analysis, the LTL was classified in shape and signal intensity. RESULTS: The triangle-shaped low-signal-intensity LTL was identified in 77 of 90 subjects (85.6%) on GRE images. The triangle was classified as regular (41.1%), broad-based (20.0%), narrow-based (6.7%), or asymmetrical (17.8%). The bar-shaped ligament was seen in one patient, and unclassified ligaments were seen in 12 patients. All volunteers showed triangle-shaped LTL. The MR signal intensity of the proximal zone in the LTL was characterized as homogeneously low intensity (type 1; 33.8%), linear intermediate or high signal intensity traversing the distal surface of the LTL (type 2; 45.5%), and linear intermediate or high intensity traversing both distal and proximal surfaces of LTL (type 3; 20.8%). CONCLUSION: The proximal zone of the LTL showed a broad spectrum of normal variations in shape and signal intensity on high-resolution MR images with a microscopy coil.

Adolescent↗

Low-field compact magnetic resonance imaging system for the hand and wrist in rheumatoid arthritis.

PURPOSE: To investigate the feasibility of an originally developed compact MRI system for evaluating rheumatoid arthritis (RA), and determine its advantages and disadvantages as an imaging modality for evaluating RA. MATERIALS AND METHODS: We prospectively studied 13 healthy controls with no clinical symptoms of arthritis, and 13 patients with hand and wrist pains (including pain from RA) with a 0.2 T permanent-magnet compact MR imager. All MR images were obtained while the subjects were in a sitting position. Coronal three-dimensional spin-echo T1-weighted images and coronal two-dimensional short tau inversion recovery (STIR) images were obtained with image matrix = 256 x 128 and field of view (FOV) = 20.48 cm. Plain radiograph findings and MRI findings of patients were compared. RESULTS: In three of the patients with suspected early RA (N = 7), early RA was evaluated based on STIR images. All RA patients showed morphologic or signal intensity changes that allowed an evaluation of RA from MR findings. Four of five RA patients showed high signal intensity on STIR images in the wrist, proximal interphalangeal (PIP) joint, or metacarpophalangeal (MCP) joint that suggested synovitis. Multiple erosions in the hand and wrist were seen in four RA patients, with low signal intensity on T1-weighted images. CONCLUSION: RA was correctly evaluated, and early RA could be identified with the compact MRI system. However, the current system has limitations, such as the nonselective STIR sequence used and magnetic field inhomogeneity.

Adult↗

Novel drug delivery system using thermoreversible gelation polymer for malignant glioma.

Many approaches to local tumor treatment have been reported and their efficacy demonstrated in patients with malignant glioma. We studied thermoreversible gelation polymer (TGP) as a novel drug delivery system (DDS) for treating this type of tumor. TGP exhibits sol-gel transition i.e., is water-soluble in the sol phase below the chosen sol-gel transiting temperature and water-insoluble in the gel phase above this temperature. We conjugated doxorubicin with TGP to prepare doxorubicin-TGP (DXR-TGP), then studied the kinetics of doxorubicin release from TGP and the antitumor activity of DXR-TGP in vitro and in vivo. The diffusive speed of doxorubicin from TGP was 9.4x10(-7) cm(2)/s and doxorubicin was reliably released from TGP. DXR-TGP showed antitumor activity against the human glioma cell lines T98G and U87MG and in a subcutaneous tumor model in nude mice. Pathologically, detection of the proliferation marker Ki-67 was considerably lower in the DXR-TGP group than in the control group (30-40% vs. 60-70%, respectively). This is to the best of our knowledge the first report of TGP as a novel drug delivery system, and further we provide evidence that TGP exhibits potential for use as a novel DDS for malignant glioma.

Animals↗

Comparison between high-resolution MRI with a microscopy coil and arthroscopy in triangular fibrocartilage complex injury.

PURPOSE: To determine whether high-resolution magnetic resonance imaging (MRI) could detect injuries to the triangular fibrocartilage complex (TFCC). METHODS: Eleven patients who showed both a positive sign during the ulnocarpal stress test and tenderness at the distal end of the ulna had a high-resolution MRI using a 47-mm diameter microscopy coil. Six regions of the TFCC were investigated for injury: the radial attachment, disc, ulnar attachment of the triangular fibrocartilage (TFC), ulnotriquetral ligament, palmar radioulnar ligament (PRUL), and dorsal radioulnar ligament (DRUL). Arthroscopy was performed subsequently on each patient. RESULTS: For injuries to the radial attachment or the disc of the TFC, a high-resolution MRI showed 100% sensitivity and 100% specificity compared with arthroscopy. In 3 cases in which injury to the ulnar attachment of the TFC was detected with MRI and examination showed a positive piano-key sign and distal radioulnar joint instability, only 1 injury was confirmed with arthrotomy. For MRI diagnosis of an ulnotriquetral ulnolunate attachment injury, the sensitivity was 100% and the specificity was 70%; however, 3 cases had false-positive results. Finally MRI had 100% sensitivity for detecting DRUL and PRUL injuries, although specificities were 75% and 83%, respectively. With MRI there were 2 false-positive DRUL injury diagnoses and 1 false-positive PRUL injury diagnosis. CONCLUSIONS: High-resolution MRI using a microscopy surface coil allowed assessment of each TFCC component and showed a higher accuracy for diagnosing injuries to the radial attachment and the disc of the TFC compared with previous studies. High-resolution MRI, however, was not able to diagnose DRUL, PRUL, or ulnolunate ligament injuries accurately. TYPE OF STUDY/LEVEL OF EVIDENCE: Diagnostic III.

Adolescent↗

In vitro culture of chondrocytes in a novel thermoreversible gelation polymer scaffold containing growth factors.

In this study we examined the potential of a novel thermoreversible gelation polymer (TGP) to act as a 3-D hydrogel scaffold and deliver both chondrocytes and growth factors. Chondrocytes obtained from bovine articular cartilage were studied as a suspension in TGP chilled to 4 degrees C, in the presence or absence of the growth factors IGF-1 and/or TGF beta2. The cold cell/aqueous suspensions were injected into a cylindrical mold and cultured at 37 degrees C for up to 16 weeks. Specimens obtained at 12 and 16 weeks were semitranslucent and elastic. The matrices surrounding the chondrocytes were histologically positive to Safranin-O staining and type II collagen staining. The glycosaminoglycan and hydroxyproline contents in the specimens increased as a function of time and because of the presence of growth factors; those cultured with growth factors produced significantly more of these substances than those cultured without. We have concluded that TGP has potential as a scaffold material in the generation of tissue-engineered cartilage in vitro.

Animals↗

MR imaging of articular cartilage: current state and recent developments.

Osteoarthritis is the most common type of arthritis and a frequent cause of pain and disability. A number of exciting surgical treatment modalities have been introduced recently, including autologous chondrocyte transplantation and osteochondral allografting or autografting. MR imaging offers the distinct advantage of visualizing the articular cartilage directly. MR imaging can detect signal and morphologic changes in the cartilage and has been used to detect cartilage surface fraying, fissuring, and varying degrees of cartilage thinning.

Cartilage Diseases↗

Cerebral thrombotic complications in adolescent leukemia/lymphoma patients treated with L-asparaginase-containing chemotherapy.

We described the cerebral thrombotic complications developed in 2 adolescent patients treated with L-asparaginase-containing regimens. For determining risk factors, we retrospectively analysed hemostatic markers in 19 pediatric patients with leukemia or lymphoma who were treated with either 1 of the 2 L-asparaginase-containing regimens; 11 were treated with VLP1 and the remaining 8 were treated with the VLAD protocol. The data indicated that low coagulation factors in association with increased plasma D-dimer levels during or post-L-asparaginase administration combined with fresh frozen plasma infusion might have activated coagulation processes in these patients. Careful management is required to prevent such episodes in patients with markedly decreased coagulation factors and increased D-dimer levels following L-asparaginase administration.

Adolescent↗

Triple arterial phase dynamic MRI with sensitivity encoding for hypervascular hepatocellular carcinoma: comparison of the diagnostic accuracy among the early, middle, late, and whole triple arterial phase imaging.

OBJECTIVE: We assessed and compared the diagnostic accuracy of the early, middle, late, and whole triple arterial phase MRI with sensitivity encoding (SENSE) for the detection of hypervascular hepatocellular carcinoma (HCC). MATERIALS AND METHODS: Thirty-one patients with 102 HCCs underwent dynamic MRI with SENSE. The findings of CT examinations, combined with those of visceral angiography or histopathologic examination, were used as the gold standard. After acquisition of T1- and T2-weighted images, gadolinium-enhanced triple arterial, portal, and delayed phase images were obtained. Acquisition of the triple arterial phase imaging was started at the timing of peak aortic enhancement and completed within a single breath-hold. Acquisition time for each phase was 8.4 sec. Four image sets including the early, middle, late, and whole triple arterial phase imaging were interpreted separately by four observers. The mean values of area under alternative-free-response receiver operating characteristic (AFROC) curve and of sensitivity were compared among the four image sets. RESULTS: The mean values of area under AFROC curve were 0.52, 0.66, 0.53, and 0.68 and of sensitivity were 45%, 64%, 48%, and 65% for the image sets with the early, middle, late, and whole triple arterial phase imaging, respectively. Both mean values were significantly higher for the image sets with the middle and whole triple arterial phase imaging than for those with the early and late arterial phase imaging. CONCLUSION: The middle arterial phase imaging with k-space centered at 12.6 sec after the peak aortic enhancement was optimal for detecting HCC and showed diagnostic accuracy equivalent to that of the whole triple arterial phase imaging.

Aged↗

Gene expression profile of human mesenchymal stem cells during osteogenesis in three-dimensional thermoreversible gelation polymer.

This study attempted to characterize the ability of thermoreversible gelation polymer (TGP) to induce differentiation of human mesenchymal stem cells (hMSC) into osteoblasts. Using a long oligo microarray system consisting of 3760 genes, we compared the expression profiles of the cells in 2-dimensional (2D) culture, 3D culture in collagen gel, and 3D culture in TGP with or without osteogenic induction. Compared to 2D culture, the gene expression profile of hMSC showed almost the same pattern in TGP without osteogenic induction, but 72% of genes (2701/3760) were up-regulated in collagen gel. With osteogenic induction, hMSC showed higher ALP activity and osteocalcin production in TGP as compared to 2D culture. Moreover, up-regulation and down-regulation of osteogenic genes were augmented in 3D culture in TGP as compared to 2D culture. As TGP is chemically synthesized and completely free from pathogen such as prion in bovine spongiform encephalopathy, these results suggest that TGP could be applied clinically to induce osteogenic differentiation of hMSC.

Alkaline Phosphatase↗

High-resolution MR imaging of the elbow using a microscopy surface coil and a clinical 1.5 T MR machine: preliminary results.

OBJECTIVE: To obtain high-resolution MR images of the elbow using a microscopy surface coil with a 1.5 T clinical machine and to evaluate the feasibility of its use for elbow injuries. DESIGN AND PATIENTS: Five asymptomatic normal volunteers and 13 patients with elbow pain were prospectively studied with MR imaging using a microscopy surface coil 47 mm in diameter. High-resolution MR images using a microscopy coil were obtained with fast spin echo (FSE) proton density-weighted sequence, gradient recalled echo (GRE) T2*-weighted sequence, and short tau inversion recovery (STIR) sequence, with a 1-2 mm slice thickness, a 50-70 mm field of view, an imaging matrix of 140-224 x 512 using zero fill interpolation, and 2-6 excitations. RESULTS: High-resolution MR images of normal volunteers using a microscopy coil clearly showed each structure of the medial and lateral collateral ligaments on GRE T2*-weighted images and FSE proton-density weighted images. Partial medial collateral ligament injury, a small avulsion of the medial epicondyle, and osteochondritis dissecans were well demonstrated on high-resolution MR images. CONCLUSION: High-resolution MR imaging of the elbow using a microscopy surface coil with a 1.5 T clinical machine is a promising method for accurately characterizing the normal anatomy of the elbow and depicting its lesions in detail.

Adolescent↗

Magnetic resonance imaging evaluation of cooling on blood flow and oedema in skeletal muscles after exercise.

This study assessed the effects of cooling on blood flow and intramuscular water content in human skeletal muscles after exercise using magnetic resonance imaging. In six male subjects, their legs were randomly assigned to be control or to be cooled. All subjects performed ankle dorsiflexion exercise inside an imaging magnet and after exercise, an ice bag was placed on the ankle dorsiflexors of the cooled leg. Flow-sensitive images, which reflect both perfusion and intramuscular water, were obtained before and up to 270 s post-exercise at 30-s intervals. The flow-sensitive alternating inversion recovery (FAIR) images, which extract only the perfusion change, were also obtained. Signal intensity (SI) in the ankle dorsiflexors was estimated before and after exercise in both flow-sensitive and FAIR images. On the flow-sensitive images, the control leg increased SI 30-270 s after exercise (P<0.05), but the cooled leg showed no significant change. On the FAIR images, the control leg increased SI 30-270 s post-exercise (P<0.05), while the cooled leg increased SI 30-150 s and 210 s after exercise (P<0.05). The findings suggest that cooling attenuates the perfusion elevation and prevents the oedema formation in skeletal muscle immediately after exercise.

Adult↗

Magnetic resonance imaging of articular cartilage of the knee: comparison between fat-suppressed three-dimensional SPGR imaging, fat-suppressed FSE imaging, and fat-suppressed three-dimensional DEFT imaging, and correlation with arthroscopy.

PURPOSE: To compare signal-to-noise ratios (S/N) and contrast-to-noise ratios (C/N) in various MR sequences, including fat-suppressed three-dimensional spoiled gradient-echo (SPGR) imaging, fat-suppressed fast spin echo (FSE) imaging, and fat-suppressed three-dimensional driven equilibrium Fourier transform (DEFT) imaging, and to determine the diagnostic accuracy of these imaging sequences for detecting cartilage lesions in osteoarthritic knees, as compared with arthroscopy. MATERIALS AND METHODS: Two sagittal fat-suppressed FSE images (repetition time [TR] / echo time [TE], 4000/13 [FSE short TE] and 4000/39 [FSE long TE]), sagittal fat-suppressed three-dimensional SPGR images (60/5, 40 degrees flip angle), and sagittal fat-suppressed echo-planar three-dimensional DEFT images (400/21.2) were acquired in 35 knees from 28 patients with osteoarthritis of the knee. The S/N efficiencies (S/Neffs) of cartilage, synovial fluid, muscle, meniscus, bone marrow, and fat tissue, and the C/N efficiencies (C/Neffs) of these structures were calculated. Kappa values, exact agreement, sensitivity, specificity, positive predictive value, and negative predictive value were determined by comparison of MR grading with arthroscopic results. RESULTS: The synovial fluid S/Neff on fat-suppressed FSE short TE images, fat-suppressed FSE long TE images, and fat-suppressed three-dimensional DEFT images showed similar values. Fat-suppressed three-dimensional DEFT images showed the highest fluid-cartilage C/Neff of all sequences. All images showed fair to good agreement with arthroscopy (kappa, 0.615 in FSE short TE, 0.601 in FSE long TE, 0.583 in three-dimensional SPGR, and 0.561 in three-dimensional DEFT). Although the sensitivity of all sequences was high (100% in FSE short TE, FSE long TE, and DEFT; 96.7% in SPGR), specificity was relatively low (67.6% in FSE short TE and FSE long TE; 85.3% in SPGR; 58.3% in DEFT). The peripheral area of bone marrow edema or whole area of bone marrow edema on fat-suppressed FSE images was demonstrated as low or iso-signal intensity on fat-suppressed three-dimensional DEFT images. CONCLUSION: Fat-suppressed three-dimensional SPGR imaging and fat-suppressed FSE imaging showed high sensitivity and high negative predictive values, but relatively low specificity. The Kappa value and exact agreement was the highest on fat-suppressed FSE short TE images. Fat-suppressed three-dimensional DEFT images showed results similar to the conventional sequences.

Adult↗

Development of a compact MRI system for trabecular bone volume fraction measurements.

A compact MRI system for measuring trabecular bone volume fraction (TBVF) of the calcaneus was developed with the use of a 0.21 T permanent magnet and portable MRI console. The entire system weighed < 600 kg and was installed in a 2 m x 2 m space. Two cross-sectional spin-echo images of a heel acquired with external reference phantoms (total measurement time = 5 min) were used to quantify the TBVF of the calcaneus. The linearity and reproducibility of the measurements were evaluated by means of proton density-adjusted phantoms. Comparative measurements with quantitative ultrasound (QUS) in groups of healthy female volunteers showed a relatively high positive correlation (R(2) = 0.4539, 0.2693) between TBVF and the speed of sound (SOS). These results demonstrate the potential of this new system for measuring bone density. Magn Reson Med 52:440-444, 2004.

Adolescent↗

Bone scintigraphic and CT evaluation of chondrosarcoma of the rib: correlation with histological grade in 6 cases.

OBJECTIVE: The objective of this study is to assess the value of CT and bone scintigraphic findings for grading of rib chondrosarcoma. METHODS: Included in this study were six cases of histologically proven chondrosarcoma of the rib, in which bone scintigraphy and/or CT was performed. Correlation of histologic grade (I-III), tumor size on CT, CT grading (modified Brown's system), the pattern (nodular or peripheral, presence or absence of extended uptake pattern) and the intensity (Simon and Kirchner's grade, 0-4) of scintigraphic uptake were assessed. RESULTS: CT grade was III, except for one case of dedifferentiated chondrosarcoma. Scintigraphic grade was 3 or 4 in all the cases. CONCLUSION: The patterns of CT and bone scintigraphic findings more likely reflect the size of the mass and ossification, and are not well correlated with the histological grading.

Adult↗

Three-dimensional fast field echo MR myelography using water excitation.

The purpose of this study is to determine if 3D FFE MRM using WE provides better image quality in comparison with that using SPIR. Twenty subjects were referred for the MRM images using SPIR, and WE with different TR. SNR and CNR were measured in the ganglions and adjacent tissues, in addition, the uniformity of the fat tissues was scored on a three-point scale by two radiologists with consensus. The WE sequence showed the higher SNR and CNR values than that using SPIR, in addition, the WE technique was helpful to achieve the shorter acquisition time of MRM.

Adolescent↗

Dual double arterial phase dynamic MR imaging with sensitivity encoding (SENSE): which is better for diagnosing hypervascular hepatocellular carcinomas, in-phase or opposed-phase imaging?

The purpose of this study was to investigate the efficacy of sensitivity encoding (SENSE) dynamic magnetic resonance imaging (MRI) with the dual (in-phase and opposed-phase) double arterial phase to detect hypervascular hepatocellular carcinomas (HCCs). MR images of the liver from 44 consecutive patients were obtained. Dynamic MRI with SENSE was performed six times (precontrast, early arterial, late arterial, 1 min, 3 min and 5 min after contrast injection) at 11 s per scan using the gradient recalled echo sequence (TR/TE/flip angle = 168/2.3 and 4.6/70). In-phase and opposed-phase images were obtained simultaneously each scan. For the quantitative analysis, the signal-to-noise ratio (S/N) of HCC and tumor-to-liver contrast-to-noise ratio (C/N) were analyzed for 55 HCCs. The mean S/N of HCCs on in-phase images showed significantly higher values than that on opposed-phase images regarding all phases (P < 0.001). In arterial phases, the mean tumor-to-liver C/N for in-phase images was significantly higher than that for opposed-phase images (P < 0.05). In portal and delayed-phase images, the mean tumor-to-liver C/N in opposed-phase images showed a negative value. In six HCCs with fatty metamorphosis, the mean tumor-to-liver C/N on arterial phase images approached zero in opposed-phase, while it showed a positive value in-phase. In dual double arterial phase dynamic MRI of the liver, in-phase images were superior to opposed-phase images for detecting early enhancement of hypervascular HCCs, while the latter were superior for detecting washout of contrast media from HCCs in the portal and delayed phase. The combination of both images overcomes the difficulty of diagnosing hypervascular HCCs with fatty metamorphosis.

Aged↗

Articular cartilage of knee: normal patterns at MR imaging that mimic disease in healthy subjects and patients with osteoarthritis.

PURPOSE: To evaluate normal magnetic resonance (MR) imaging findings that may mimic articular cartilage diseases in healthy subjects and patients with osteoarthritis of the knee. MATERIALS AND METHODS: Sagittal fat-suppressed intermediate-weighted fast spin-echo (FSE) (repetition time msec/echo time [TE] msec, 4,000/13), sagittal T2-weighted FSE (4,000/39), and sagittal fat-suppressed three-dimensional (3D) spoiled gradient-echo (SPGR) (60/5, 40 degrees flip angle) MR images were acquired in 28 patients and four volunteers. FSE images with a TE of 13 msec were considered "short-TE images"; those with a TE of 39 msec were considered "long-TE images." Presence of normal MR imaging appearance of articular cartilage was determined by one author. Contrast between cartilage and adjacent structures (meniscus, joint capsule, synovial fluid, muscle) was calculated in posterior regions of the femoral condyle on images obtained with each sequence; Wilcoxon signed rank testing was performed. RESULTS: The following appearances were observed in patients with knee osteoarthritis (on short-TE FSE, long-TE FSE, and SPGR MR images, respectively): (a) ambiguity of surface contour in posterior region of the femoral condylar cartilage (in zero, zero, and 20 patients), (b) linear area of high signal intensity in deep zone adjacent to subchondral bone of femoral condyle (in zero, zero, and 26 patients), (c) pseudolaminar appearance in posterior region of femoral condylar cartilage (in seven, nine, and 24 patients), (d) truncation artifact in patellofemoral compartment (in seven, six, and 27 patients), (e) susceptibility artifact on cartilage surface caused by air or metal (in three, three, and 11 patients), (f) decreased signal intensity in distal part of trochlear cartilage (in 28, 28, and 28 patients), (g) cartilage thinning adjacent to the anterior horn of the lateral meniscus (in 19, 19, and 21 patients), and (h) focal cartilage flattening in posterior region of femoral condyle (in 16, 16, and nine patients). Cartilage-meniscus and cartilage-synovial fluid contrast was significantly higher on fat-suppressed FSE than on fat-suppressed 3D SPGR MR images (P <.001). CONCLUSION: Fat-suppressed FSE and 3D SPGR MR images showed nonuniform signal intensity arising from articular cartilage and cartilage thinning, both of which could mimic disease.

Adult↗