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O Ishida

Publications and source records attributed to O Ishida.

At least 37 records · Page 2Linked to original sources

Size-dependent extravasation and interstitial localization of polyethyleneglycol liposomes in solid tumor-bearing mice.

We have examined the size dependence of extravasation and interstitial localization of polyethyleneglycol-coated liposomes (PEG-liposomes) in the solid tumor tissue by means of electron microscopic observation. Liposomes composed of distearoyl phosphatidylcholine, cholesterol and distearoylphosphatidylethanolamine derivative of polyethyleneglycol (PEG) were prepared in various size ranges. PEG-liposomes with an average diameter of 100-200 nm showed the most prolonged circulation time and the greatest tumor accumulation in all the solid tumors employed in this experiment. Although large PEG-liposomes with a diameter of 400 nm showed a short circulation time in normal mice, the results in splenectomized mice indicated that they do have an intrinsic prolonged circulation character in vivo. However, large PEG-liposomes could not extravasate into solid tumor tissue. These results indicate that the size of liposomes is critical for extravasation. The electron microscopic observations revealed the almost exclusive engulfment of extravasated liposomes by tumor-associated macrophages; very few were taken up by tumor cells.

Animals↗

Rejection and regeneration in peripheral nerve homografts in rats after withdrawal of cyclosporin: morphological and immunohistochemical assessment.

Peripheral nerve homografts 35 mm long were inserted in rats to study rejection and regeneration of nerves after suspension of an immunosuppressant (cyclosporin), and the correlation between the Schwann cells of the host and the donor during the course of regeneration. Sciatic nerve homografts from 36 ACI-RT1a rats were transplanted into Lewis-RT1(1) rats. Isografts were taken from 24 Lewis rats. Cyclosporin 5 mg/kg/day was given subcutaneously for 12 weeks. In the homograft group the myelinated axons that regenerated while the immunosuppressant was being given were covered mainly with Schwann cells from the donor, and after the immunosuppressant was withdrawn both Schwann cells of the donor and axons were rejected. However, while the cyclosporin was being given the Schwann cells of the host migrated into the nerve graft together with a few myelinated axons that escaped rejection, and unmyelinated axons that regenerated after rejection were myelinated by the Schwann cells of host.

Animals↗

Appearance of normal brain maturation on fluid-attenuated inversion-recovery (FLAIR) MR images.

BACKGROUND AND PURPOSE: Fluid-attenuated inversion-recovery (FLAIR) MR imaging is widely accepted for brain diagnoses, though to our knowledge no description of the MR FLAIR appearance of the normal infantile brain has been published. The purpose of this study was to investigate the appearance of normal infantile brain maturation on FLAIR MR images. METHODS: FLAIR images were obtained in 52 children between the ages of 1 day and 4 years who had clinically suspected brain disease but no neurologic abnormality or growth retardation. T1- and T2-weighted images were also obtained in all the children, and these images were compared with the FLAIR sequences for the appearance of brain maturation. A grading system for the differences in signal intensity between gray and white matter on FLAIR images was introduced to make detailed profiles of maturation in each brain region, including the posterior limb of the internal capsule, the cerebellar peduncle, the frontal deep white matter, the occipital deep white matter, and the centrum semiovale. These grades were plotted against patients' ages. RESULTS: On the FLAIR images, the myelinated white matter, including the cerebellar peduncle and the posterior limb of the internal capsule, showed high signal intensity relative to gray matter at birth. Thereafter, the white matter lost signal intensity with time and showed low signal intensity at 50 weeks and beyond. The unmyelinated white matter, including the frontal deep white matter, the occipital deep white matter, and the centrum semiovale, showed low signal intensity at birth. The white matter showed high signal intensity at 20 to 30 weeks, and low signal intensity again at 100 to 160 weeks and after. CONCLUSION: The dynamics of brain myelination can be accurately delineated and evaluated on FLAIR images without other spin-echo (SE) sequences. The FLAIR appearance of infantile white matter can be divided into two phases, reflecting development of the myelination process: the first phase is similar to that seen on SE T1-weighted images and the second phase is similar to that seen on SE T2-weighted images.

Brain↗

Identification and characterization of a novel protein interacting with Ral-binding protein 1, a putative effector protein of Ral.

Ral-binding protein 1 (RalBP1) is a putative effector protein of Ral and exhibits a GTPase activating activity for Rac and CDC42. To clarify the function of RalBP1, we isolated a novel protein that interacts with RalBP1 by yeast two-hybrid screening and designated it POB1 (partner of RalBP1). POB1 consists of 521 amino acids, shares a homology with Eps15, which has been identified as an epidermal growth factor (EGF) receptor substrate, and has two proline-rich motifs. The POB1 mRNA was expressed in cerebrum, cerebellum, lung, kidney, and testis. POB1 interacted with RalBP1 in COS cells and the C-terminal region of POB1 was responsible for this interaction. The binding domain of RalBP1 to POB1 was distinct from its binding domain to Ral. Ral and POB1 simultaneously interacted with RalBP1 in COS cells. The binding of POB1 to RalBP1 did not affect the GTPase activating activity of RalBP1. Furthermore, POB1 bound to Grb2 but not to Nck or Crk. POB1 was tyrosine-phosphorylated in COS cells upon stimulation with EGF and made a complex with EGF receptor. These results suggest that RalBP1 makes a complex with POB1 and that this complex may provide a link between tyrosine kinase, Src homology 3 (SH3)-containing protein, and Ral.

Adaptor Proteins, Signal Transducing↗

Results of treatment of chronic dorsal fracture-dislocations of the proximal interphalangeal joints of the fingers.

We reviewed 20 cases of chronic dorsal fracture-dislocation of the proximal interphalangeal joint, with a mean follow-up period of 74 months. In patients without comminuted palmar fragments, open reduction and internal fixation or osteotomy of the malunited fragment provided good results. In treating patients with damaged articular cartilage or with comminuted palmar fragments by palmar plate arthroplasty, poor results were obtained because of secondary osteoarthritic changes.

Adolescent↗

MR imaging of meniscal tears with discoid lateral meniscus.

OBJECTIVE: To study MR findings of meniscal tears with discoid lateral menisci (DLMs) and to evaluate the incidence and accuracy of MRI compared to arthroscopical surgery. MATERIAL AND METHODS: MR appearances of surgically proved torn discoid lateral menisci (DLM) were studied in 57 knees (40 patients). They were all performed with a 1.5T MR before surgery. MR sequences included T1- and T2* weighted images on both coronal and sagittal planes and 3D-axial images with a slice thickness of 0.7 mm. RESULT: Of 57 DLMs, there were 32 complete DLMs and 25 incomplete DLMs. Twenty-five of 32 complete DLMs had tears; including seven with intrasubstance tear, five with radial tear, five with other kinds of tears and eight with severe tears involving whole meniscus. On the other hand, 13 of 25 incomplete DLMs had tears; including two with intrasubstance tear, six with radial tear, four with other kinds of tears and one with severe tears. All DLMs were correctly diagnosed on MR images. Twenty-seven of 38 tears with DLM were correctly identified on conventional 2D MR images. This yielded 71.1% sensitivity, 100% specificity and 80.7% overall accuracy. When adding axial 3D MR images to 2D MR images, 36 of 38 tears were correctly diagnosed. A combination of both techniques yielded a sensitivity of 94.7% and a specificity of 100%. Ten of 11 radial tears with DLM were correctly identified on 3D axial images, where only three of them could be diagnosed on conventional 2D images. Eight of nine intrasubstance tears were correctly identified on 3D axial images, where six of them could be diagnosed on conventional 2D images. CONCLUSION: DLMs had a much higher incidence of meniscal tears than normally shaped lateral menisci and MR is the only modality of choice to evaluate them before surgery. Especially 3D axial MR images were quite useful in the detection of intrasubstance and radial tears often associated with DLMs.

Adult↗

Genotype-phenotype correlation of patients with multiple endocrine neoplasia type 2 in Japan.

BACKGROUND: Multiple endocrine neoplasia type 2 (MEN 2) is a hereditary syndrome characterized by medullary thyroid carcinoma (MTC), pheochromocytoma and hyperparathyroidism. MEN 2 is caused predominantly by germ-line mutations of the RET proto-oncogene. This study aimed to clarify the genotype-phenotype correlation in MEN 2 patients in Japan in order to modify the clinical management according to the genotype. METHODS: Constitutive DNA of 64 MEN 2 patients (48 kindreds) were searched for mutations at exons 10, 11, 13, 14 and 16 of the RET proto-oncogene using polymerase chain reaction-single strand conformation polymorphism (PCR-SSCP), direct sequencing and restriction enzyme digestion. The clinical characteristics of the patients were obtained from a previous nationwide questionnaire survey. RESULTS: Overall, 62 (96.9%) out of 64 patients had a germ-line point mutation at the hot spots. MTC and pheochromocytoma occurred equally in every genotype except C630S. Specific genotype had a correlation between tumor size and age at the operation for MTC or extent of MTC, i.e. C618S developed late onset type of MTC as compared with that of C634R, C634Y and M918T. Small MTC in C634R may be less aggressive than those in C634Y and M918T. CONCLUSIONS: DNA testing has good clinical implications for the management of patients with MEN 2 and the timing and operative procedures of thyroidectomy can be modified according to the genotype.

Adrenal Gland Neoplasms↗

Long-term results of surgical treatment for macrodactyly of the hand.

A retrospective review was performed for 23 patients who were surgically treated for macrodactyly of the hand between 1964 and 1995. Treatment regimens varied among the patients, and more than two operative procedures were performed in 65 percent of the patients. At final follow-up, the average length of the affected digits was 102 percent of that of the normal contralateral side. The average circumference of the digits was 121 and 124 percent at the proximal interphalangeal and distal interphalangeal joints, respectively. The average range of motion was 65, 57, and 37 degrees at the metacarpophalangeal, proximal interphalangeal, and distal interphalangeal joints, respectively. Although it is difficult to compare treatment regimens, epiphysiodesis/epiphysectomy was quite effective in the prevention of longitudinal overgrowth of the digits, but resection of the hypertrophic nerves was unsuccessful in preventing finger overgrowth.

Female↗

[Transferrin conjugated PEG-liposomes as intracellular targeting carrier for tumor therapy].

For the purpose of intracellular targeting carrier by systemic administration, PEG-liposomes conjugating transferrin (TF) at the distal ends of PEG chain were newly prepared. Biodistribution of TF-PEG liposome was examined in the colon 26 bearing mice. TF-PEG liposome were prolonged in the circulation and highly accumulated into the tumor tissue. After extravasation, TF-PEG liposome retains the specific binding ability to tumor cell surface. Uptake of TF-PEG liposome was examined by electron microscopy. TF-PEG liposome was localized at the cell surface, coated pits and endosome. These results show TF-PEG liposome was bound and internalized by endocytosis. Such liposomes should be useful for intracellular targeting carrier at the way of systemic administration.

Animals↗

[Three-dimensional MR angiography of HCC and portal and hepatic veins using superparamagnetic iron oxide].

We examined a new MR technique for obtaining 3D-MRA images of the liver that simultaneously depicts HCC and the portal and hepatic veins. Five patients with clinically suspected HCC were studied with superparamagnetic iron oxide (SHU-555A) used as a negative contrast medium for the liver. In our study, a 3D-rotational display was provided on the CTR monitor from 2D-TOF images by computed reconstruction, clearly showing HCC and portal and hepatic veins on the same image. Our method was found to be of great value in planning surgery of the liver.

Aged↗

Characterization of Ral GDP dissociation stimulator-like (RGL) activities to regulate c-fos promoter and the GDP/GTP exchange of Ral.

Ral GDP dissociation stimulator-like (RGL) has been identified to be a possible effector protein of Ras. RGL shares 50% amino acid identity with Ral GDP dissociation stimulator and contains the CDC25-like domain in the central region and the Ras-interacting domain in the C-terminal region. Since the modes of activation and action of RGL have not yet been clarified, in this paper we have analyzed the functions of RGL. In COS cells, RGL interacted with RasG12V/E37G (a Ras mutant in which Gly-12 and Glu-37 were changed to Val and Gly, respectively) which failed to bind to Raf, but not with RasG12V/T35S which bound to Raf. Raf did not inhibit the binding of RGL to RasG12V/E37G under the condition that Raf inhibited that of RGL to RasG12V. Expression of either RGL or Raf into NIH3T3 cells slightly activated c-fos promoter, while coexpression of both proteins greatly stimulated the c-fos promoter activity. RGL stimulated the GDP/GTP exchange of Ral and this action was enhanced by the post-translational modification of Ral. However, RGL was not active on Ras, Rac, CDC42, Rap, or Rho. Furthermore, this action of RGL to stimulate the GDP/GTP exchange of Ral was dependent on Ras in COS cells. These results suggest that RGL constitutes another Ras-signaling pathway which is distinct from the Raf pathway and indicate that the RGL pathway regulates the c-fos promoter activity and the GDP/GTP exchange of Ral.

Animals↗

MRI of head injury using FLAIR.

We studied the utility of fluid-attenuated inversion-recovery (FLAIR) MRI in the investigation of head injury. We examined 56 patients with head injuries with T2-weighted spin-echo (SE) and FLAIR sequences. In all cases, the sensitivity of FLAIR images to equal or superior to that of conventional SE images to the traumatic lesions. In 9 cases, central diffuse axonal injury of the fornix and corpus callosum could be seen only on sagittal FLAIR images.

Adult↗

Chondrocytes are regulated by cellular adhesion through CD44 and hyaluronic acid pathway.

The articular cartilage consists of resident chondrocytes embedded within the extracellular matrix which contains several components such as collagen and hyaluronic acids (HA). CD44 is a major cell surface receptor for HA and is homologous to cartilage-link proteins. Although CD44 is present in cartilage, it is not clear if chondrocytes adhere to HA through CD44 or whether such adhesion changes the function of chondrocytes. We studied the molecular mechanisms of CD44-related chondrocyte adhesion to HA and the effects of such adhesion on chondrocyte function. Experiments were performed using the human chondrosarcoma-derived chondrocyte-like cell line HCS-2/8. Our results showed that (a) HCS-2/8 cells highly expressed CD44; (b) HCS-2/8 cells efficiently adhered to HA without any stimuli; (c) monoclonal antibody (mAb)-blocking studies indicated that adhesion of HCS-2/8 cells to HA was mainly mediated by the CD44/HA pathway; (d) cellular adhesion to HA increased the proliferation of HCS-2/8 cells, independent of transforming growth factor-beta (TGF-beta), but this was inhibited by CD44 mAb; (e) the adhesion of chondrocytes to HA also induced c-myc mRNA expression and this was also inhibited by CD44 mAb; and (f) the adhesion of cells to HA augmented TGF-beta mRNA expression, a process also reduced by CD44 mAb. Thus, HCS-2/8 cells effectively adhered to HA through cell surface CD44. The adhesion was also involved in cellular signaling which induced cellular proliferation and expression of c-myc mRNA as well as TGF-beta mRNA expression within the cells. Our results indicate that CD44 on chondrocytes plays an important role in normal and abnormal functions of cartilage through its adhesion to HA, which induces a variety of stimulatory signals to regulate chondrocyte proliferation as well as matrix synthesis in cartilage microenvironment.

Antibodies, Monoclonal↗

High signal intensity of the infundibular stalk on fluid-attenuated inversion recovery MR.

PURPOSE: To determine the MR imaging characteristics of the pituitary stalk with a fluid-attenuated inversion recovery (FLAIR) technique. METHODS: We retrospectively studied the prevalence of a high-signal infundibular stalk on FLAIR MR images of the brain in 133 patients and compared this finding with the patients' ages. To understand the cause of the high signal intensity of the pituitary stalk on FLAIR images, we calculated the T1, T2, and proton-density values in regions of gray matter, white matter, and the pituitary stalk in nine cases. RESULTS: FLAIR images showed the pituitary stalk as having high signal intensity in 97 (73%) of 133 cases; however, in 11 of 16 patients less than 10 years old, the infundibular stalk was not of high signal intensity. In patients with a high-signal pituitary stalk on FLAIR images, the T2 value of the pituitary stalk was longer than that of gray or white matter. CONCLUSION: High signal intensity of the infundibular stalk was frequently seen on FLAIR MR images of the brain at all ages. A prolonged T2 value of the pituitary stalk caused the high signal intensity, presumably reflecting the fluid component of the pituitary stalk.

Adolescent↗

Benign fibrous histiocytoma of the femur: review of three cases.

OBJECTIVE: Benign fibrous histiocytoma is a tumor with histologic features similar to those of xanthofibromas, which include fibrous cortical defects and nonossifying fibromas, but with different clinical features. This study investigated the findings of benign fibrous histiocytoma on various imaging modalities. It emphasized the importance of clinical and imaging features as well as histologic findings in establishing the diagnosis. DESIGN: We reviewed three cases of benign fibrous histiocytoma of the femur that had been diagnosed histologically as (fibro)xanthoma during a retrospective analysis of 187 primary benign and malignant bone lesions. PATIENTS: All the patients were middle-aged women with various knee complaints. RESULTS AND CONCLUSIONS: Radiologically, the lesions were all lytic with well-defined geographic margins and sclerotic rims. The tumors arose within the medullary cavity in the distal metaphysis of the femur and involved the epiphysis. CT showed lytic destruction with well-defined marginal sclerosis. T1-weighted MR images showed that the lesions had predominantly the same signal intensity as that of skeletal muscle. The lesions were hypovascular on angiography. Bone scintigraphy showed moderately increased uptake. It was concluded that multiple images as well as clinical features can be useful in differentiating benign fibrous histiocytoma from fibroxanthoma, giant cell tumor, and other fibrohistiocytic tumors of bone.

Aged↗

Soluble interleukin-6 receptor levels in pleural effusions.

Generation of soluble cytokine receptors is a general phenomenon, and the roles of several such receptors have been investigated in clinical settings. Unlike other soluble cytokine receptors, soluble interleukin-6 receptor (sIL-6R) can act as an agonist and thus is implicated as an important modulator in the acute-phase reaction of prolonged inflammation. The purpose of the present study was to determine the roles of pleural sIL-6R in both differential diagnosis of pleural diseases and in the induction of acute-phase protein. Specific sandwich enzyme-linked immunosorbent assays were used to determine sIL-6R and IL-6 in 19 tuberculous, 48 malignant and 10 transudative effusions. Although IL-6 levels in pleural effusions were strikingly different, no significant differences in pleural sIL-6R levels were found between the groups. Pleural levels of IL-6 were invariably much higher, whereas those of SIL-6R were invariably lower than serum levels. Furthermore, IL-6, but not sIL-6R, levels in effusions correlated significantly with serum C-reactive protein levels. These results suggest that: (1) pleural levels of sIL-6R are not increased even in strong inflammation such as tuberculous pleurisy, nor significantly different among pleural diseases; and (2) the local levels of sIL-6R are not as important as expected for the induction of acute-phase proteins in patients with pleural diseases.

Antigens, CD↗

Penile replantation after self-inflicted complete amputation: case report.

A case of penile replantation is reported in which a 37-year-old man suffered a self-inflicted complete penile amputation. Replantation was successfully performed; at 3 months after surgery, a urethrocystogram demonstrated the absence of urethral stricture. Although complete erection has yet to be obtained, no other functional impairments have been encountered at 7 months after replantation. Reconstruction of the venous system is considered to be one of the most important factors in achieving a successful penile replantation.

Adult↗