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Biomedical subjects

O Ishida

Publications and source records attributed to O Ishida.

At least 19 recordsLinked to original sources

Long-term results of fractionated strontium-90 radiation therapy for pterygia.

PURPOSE: The long-term safety and effectiveness of fractionated strontium-90 radiation therapy (RT) for pterygium were reviewed retrospectively. METHODS AND MATERIALS: Between 1984 and 1996, 399 patients with 490 pterygia were treated with a strontium-90 eye applicator following surgical removal of the pterygium. The median follow-up period was 61 months (range 2-178). Of the 490 pterygia, 452 were fresh, 17 were recurrences after surgical removal alone, and 21 were recurrences after surgical removal plus postoperative RT. Fractionated RT of 31-42 Gy/4-5 fractions/22-29 days was given for 95.1% of the pterygia. RESULTS: In total, 58 (11.8%) local recurrences of pterygia were noted. The median time of local recurrences was 10 months, ranging from 2 to 93 months, and 16 recurrences (28%) were noted later than 24 months after treatment. The interval between surgery and the start of RT (1-3 days vs. >3 days) and recurrent pterygia were significant variables for local control in the multivariate analysis, while total RT dose (7-29 Gy vs. 31-50 Gy) was a marginally significant variable. Late toxicities that may be associated with strontium-90 RT were scleromalacia (scleral thinning) in 4 eyes, adhesion of eyelids in 3 eyes, and scleral ulcer in 2 eyes. CONCLUSION: Fractionated strontium-90 RT of approximately 40 Gy/4-5 fractions was safe and effective for preventing recurrence of pterygia, when RT was started within 3 days of surgery.

Adult↗

Clinical assessment of long-term safety and efficacy of a widely implanted polyacrylic intraocular lens material.

PURPOSE: To evaluate the long-term safety and efficacy, in a large series of patients, of polyacrylic intraocular lens implants 1 and 3 years after surgery, compared with polymethylmethacrylate intraocular lens implants. METHODS: This was a randomized, prospective study of 1,514 eyes of 1,202 patients that were examined for a 1-year follow-up study and 1,264 eyes of 990 patients that were examined for a 3-year follow-up study. All the patients were prospectively randomized to receive a polyacrylic or polymethylmethacrylate intraocular lens implant. A standardized surgical protocol was performed using a phacoemulsification technique and capsulorhexis. Any surgical complications were excluded, and all patients had standard postoperative medication and follow-up. Postoperative measurements included spectacle-corrected visual acuity, occurrence of postoperative sight-threatening or lens-related complications, and adverse reactions. Results were compared between the polyacrylic intraocular lens and polymethylmethacrylate intraocular lens groups. Results were also compared with standards for polymethylmethacrylate intraocular lens that were established by the US Food and Drug Administration and a previous study for silicone lens. RESULTS: The overall complete follow-up rates were 79.9% for 1-year follow-up and 69.5% for 3-year follow-up. At 1 year, the mean logarithm of the minimum angle of resolution (logMAR) of visual acuity was 0.037 +/- 0.150 and 0.042 +/- 0.154 in best case patients of the polyacrylic intraocular lens group and polymethylmethacrylate intraocular lens group, respectively. At 3 years, the mean logMAR visual acuity was 0.038 +/- 0.155 and 0.054 +/- 0.181 in best case patients in the polyacrylic intraocular lens group and polymethylmethacrylate intraocular lens group. There was no significant difference between groups at 1 and 3 years. At 1 year, 96.8% of best case patients in the polyacrylic intraocular lens group and 95.8% of those in the polymethylmethacrylate intraocular lens group achieved corrected visual acuity of 0.5 or better. At 3 years, 96.4% of best case patients in the polyacrylic intraocular lens group and 94.9% of those in the polymethylmethacrylate group achieved a corrected visual acuity of 0.5 or better; no significant difference was found at 1 and 3 years. The rate of sight-threatening complications was 1. 2% for the polyacrylic intraocular lens group of all patients and 1. 5% for the polymethylmethacrylate intraocular lens group at 1 year, and 1.6% for the polyacrylic intraocular lens group and 1.4% for the polymethylmethacrylate intraocular lens group at 3 years. No significant difference was found between the groups. The cumulative rate of Nd:YAG capsulotomy for the polyacrylic intraocular lens group (7.1%) was significantly lower than that for the polymethylmethacrylate intraocular lens group (38.1%) through 3 years (P <.0001). CONCLUSIONS: Polyacrylic intraocular lenses demonstrated safe and effective performance through long-term follow-up at a level equal to or better than polymethylmethacrylate intraocular lenses. Patients undergoing polyacrylic intraocular lens implantation achieved excellent postoperative visual acuity and experienced a low rate of postoperative complications, adverse reactions, and Nd:YAG capsulotomy. These long-term clinical results are an important outcome database for the ongoing use of this foldable optic material.

Acrylic Resins↗

Trapeziometacarpal joint arthrodesis for the treatment of arthrosis.

We undertook a retrospective follow-up study of arthrodesis of 21 trapeziometacarpal joints in 19 patients. Internal fixation was by two or three Kirschner wires and a bone graft. No joint failed to unite. Painless joints and stable grasping were achieved. Subjective estimations of improvement were excellent for 16 joints. However, some patients complained of clumsiness after the procedure. Instability was seen in six metacarpophalangeal (MP) joints of the thumb. The most common indication for trapeziometacarpal joint arthrodesis was painful arthritis in vigorous, young male labourers. However, preoperative evaluation of the function of the MP joint is necessary to determine suitability for surgery.

Adolescent↗

Surgical treatment of the cleft foot.

Between 1970 and 1997, we treated a total of 32 cleft feet in 21 patients (11 male and 10 female). We classified cases of cleft foot on the basis of the number of central ray deficiencies. Fourteen patients with 22 cleft feet were followed up for more than 1 year postoperatively (9 feet had no or one central ray deficiency, and 13 feet had two or three central ray deficiencies). The mean follow-up period was 8.8 years. The objective of this study was to evaluate the results of operative treatment of cleft foot. We evaluated the results of three methods: simple closure of the cleft, application of a double-pedicled flap, and insertion of a silicone block. Cosmetic complications, including widening of the foot, hypertrophic scarring, pigmentation of the grafted skin, and overlapping of the toes, were observed in patients with two or three central ray deficiencies. Few functional complications were observed: None of the patients experienced gait disturbances, although one patient complained of pain following walking. Roentgenography showed that the distance between the first and fifth metatarsals was 86 percent of that of the contralateral foot. When treating patients with no or one central ray deficiency, satisfactory results can be expected with simple closure of the cleft. However, in patients with two or three central ray deficiencies, it is difficult to obtain satisfactory results with simple closure of the cleft or application of a double-pedicled flap. Therefore, silicone block insertion to correct the defect is recommended when there is more than one central ray deficiency.

Child↗

Targeting chemotherapy to solid tumors with long-circulating thermosensitive liposomes and local hyperthermia.

The effectiveness of the combination of long-circulating, thermosensitive liposomes and hyperthermia is described. Small-sized, thermosensitive liposomes that encapsulate doxorubicin (DXR-PEG-TSL (SUV)) have a prolonged circulation time and are extravasated to targeted solid tumors in vivo, where they preferentially release the agent in an anatomical site subjected to local hyperthermia. Liposomes were prepared by the incorporation of amphipathic polyethyleneglycol (PEG) to prolong their circulation time. DXR-PEG-TSL (SUV) was retained longest and was accumulated most efficiently in solid tumors in Balb/c mice. The combination of DXR-PEG-TSL (SUV) and hyperthermia at the tumor sites 3 h after injection, gave high concentrations of doxorubicin in tumor tissue and resulted in more effective tumor retardation and increased survival time. A large amount of DXR-PEG-TSL (SUV) was extravasated into the tumors during circulation for 3 h after injection, suggesting that the encapsulated drug was released into the interstitial spaces of the lesions by local hyperthermia. This system is expected to be clinically valuable for the delivery of a wide range of chemotherapeutic agents in the treatment of solid tumors.

Animals↗

Thyrocyte proliferation by cellular adhesion to infiltrating lymphocytes through the intercellular adhesion molecule-1/lymphocyte function-associated antigen-1 pathway in Graves' disease.

Graves' disease (GD) is an autoimmune thyroid disease characterized by infiltration of lymphocytes into the thyroid, and intrathyroid lymphocytes are known to play an important role in the pathogenesis of GD. However, it remains to be understood how lymphocytes adhere to thyrocytes and regulate the thyrocyte function through cellular adhesion. We studied the mechanisms of T cell adhesion to thyrocytes using intrathyroid mononuclear cells (ITMC) and thyrocytes purified from the thyroids of patients with GD. The following novel features of cellular adhesion of ITMC to thyrocytes in the regulation of the thyrocyte function in GD were observed: 1) GD-ITMC expressed lymphocyte function-associated antigen (LFA)-1, which became an active adhesive configuration much higher than peripheral blood mononuclear cells (PBMC) from normal volunteers and GD patients; 2) GD-thyrocytes expressed a high quantity of intercellular adhesion molecule (ICAM)-1; 3) GD-ITMC adhered to GD-thyrocytes, whereas normal PBMC required activation stimuli by phorbol myriacetate, a pharmacological integrin-trigger, to adhere to GD- thyrocytes; 4) monoclonal antibody-blocking studies showed that the adhesion of the activated PBMC and ITMC to thyrocytes was mainly mediated by the LFA-1/ICAM-1 pathway; 5) the adhesion of GD-thyrocytes to the activated-PBMC or ITMC induced the proliferation of the thyrocytes, which was blocked by the addition of ICAM-1 and/or LFA-1 monoclonal antibodies; and 6) in GD thyrocytes of early cultures, ICAM-1 expression on GD-thyrocytes and its adhesion to LFA-1 on phorbol myriacetate-activated PBMC or ITMC were not modulated by the addition of interleukin-1beta or interferon-gamma, and proliferation of thyrocytes by the cellular adhesion via the ICAM-1/LFA-1 pathway was independent of the proliferative response of these cytokines. Taken together, these results suggest that lymphocytes infiltrating GD thyroid induce proliferation of GD-thyrocyte by the cellular adhesion to thyrocytes via ICAM-1/LFA-1, which may lead to the development of a goiter.

Cell Adhesion↗

Possibility of active targeting to tumor tissues with liposomes.

In terms of active targeting by immunoliposomes, two anatomical compartments are considerable for targeting sites. One is located a readily accessible site in intravascular, and another is a much less accessible target site located in the extravascular. However, it was made clear that the active targeting with immunoliposomes is determined by two kinetically competing processes, such as binding to the target site and uptake by the RES. To overcome these contradictions, we have designed a new type of long-circulating immunoliposome, which was PEG-immunoliposome attached antibodies at the distal end of PEG chain, so called the pendant type immunoliposome. The pendant type immunoliposome showed much higher targetability than the ordinary immunoliposomes to both targeting sites of lung endothelial cells and solid tumor tissue. This is due to the free PEG chains (not linked to the antibody) effectively avoiding the RES uptake of liposomes, resulting in elevated the blood concentration and enhanced the target binding of immunoliposomes. The presence of free PEG does not interfere with the binding of the terminally linked antibody to the antigen. For targeting to the vascular endothelial surface in the lung, 34A antibody, which is highly specific to mouse pulmonary endothelial cells, was conjugated to make the pendant type immunoliposomes (34A-PEG-ILP). 34A-PFG-ILP showed significantly higher targeting degree than the ordinary type of immunoliposomes. For targeting to the solid tumor tissue, Fab' fragment of 21B2 antibody which is anti-human CFA and transferrin (TF) were used. Both pendant type immunoliposomes (Fab'-PFG-ILP and TF-PEG-ILP) showed the low RES uptake and the long circulation time, and resulted in enhanced accumulation of the liposomes in the solid tumor. TF-PEG-ILP was internalized into tumor cells with receptor mediated endocytosis, after extravasation into tumor tissue. The pendant type immunoliposome can escape from the gaps between adjacent endothelial cells and openings at the vessel termini during tumor angiogenesis by passive convective transport much rather than ligand directed targeting. Active targeting to tumor tissue with the pendant type immunoliposome is particularly important for many highly toxic anticancer drugs for cancer chemotherapy. An ultimate goal of pendant type immunoliposome is the incorporation of a fusogenic molecule that would induce fusion of liposome following their binding to the target cells or their internalization by endocytosis. Such liposomal formulations should be useful for endocytotic internalization of plasmid DNA and other bioactive materials.

Journal Article↗

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↗