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Takahiro Goto

Publications and source records attributed to Takahiro Goto.

At least 19 recordsLinked to original sources
PubMed2006

Novel mucosal insulin delivery systems based on fusogenic liposomes.

PURPOSE: Fusogenic liposomes (FLs) are unique delivery vehicles capable of introducing their contents directly into the cytoplasm with the aid of envelope glycoproteins of Sendai virus (SeV). The objective of this study was to evaluate the potential of FL to improve the mucosal absorption of insulin from rat intestinal membranes. METHOD: The FLs containing insulin were prepared by fusing insulin-loaded liposomes with inactivated SeV particles and were administered directly into the ileal, the colonic, and the rectal loops (10 IU/kg). RESULTS: The FL successfully enhanced the insulin absorption and induced a significant hypoglycemic effect following the colonic and the rectal administration without detectable mucosal damage. This enhancing effect of insulin absorption was further improved by increasing the amount of insulin loaded in the FL and by coencapsulating insulin-degrading enzyme inhibitor. In contrast, the insulin absorption was not increased by the ileal administration of FL because the mucous/glycocalyx layers overlaid on the ileal epithelium impede the fusion of FL to the intestinal mucosa. CONCLUSION: Our results indicated that FL is a useful carrier for improving the absorption of poorly absorbable drugs, such as insulin, via the intestinal tract.

Animals↗
PubMed2006

Gastrointestinal transit and mucoadhesive characteristics of complexation hydrogels in rats.

The aim of this study was to investigate the gastrointestinal (GI) transit and mucoadhesive properties of complexation hydrogels, poly(methacrylic acid-grafted-ethylene glycol). The fluorescent labeled complexation hydrogels containing different molar ratios of methacrylic acid/ethylene glycol and different particle diameters were synthesized by free radical solution polymerization. The GI transit profiles of microparticles after oral administration to rats were evaluated by determining the polymer remaining in the stomach and the small intestine. Moreover, the mucoadhesion to the duodenal mucosa was evaluated by an in situ perfusion method. The ethylene glycol content and particle size of the hydrogels influenced significantly the GI transit and mucoadhesive capacities. The microparticles composed of polymers prepared from 1:1 ratio of methacrylic acid/ethylene glycol and having diameters of <53 microm showed the strongest mucoadhesive capacity. These findings indicated that the hydrogels may be a promising tool for improving oral bioavailability of various drugs, which are poorly absorbed from the GI tract.

Adhesiveness↗
PubMed2006

Induction of heat shock proteins in a rat composite tissue allotransplantation model of acute rejection.

BACKGROUND: Clinical cases of composite tissue allotransplantation have been reported, but the exact mechanisms of allograft rejection remain unclear. The current study examined the possible involvement of heat shock proteins in major histocompatibility complex-compatible minor-mismatch composite tissue allotransplantation rejection. METHODS: Allotransplantation (Fisher 344 to Lewis) and isotransplantation (Lewis to Lewis) of rat lower extremities were performed. Temporal profiles of 70-kDa and 60-kDa heat shock proteins (heat shock protein 70 and heat shock protein 60) were conducted by quantitative Western blot analysis and immunohistochemistry. Analyses were performed immediately after reperfusion (day 0) and on postoperative days 1, 3, 7, and 12 (n = 5 for quantitative Western blot analysis and n = 5 for immunohistochemistry). RESULTS: The expression levels of the inducible forms of heat shock protein 70 and heat shock protein 60 were uniformly and significantly augmented until postoperative day 7 in the allografts, compared with the isografts (p < 0.001 for each protein). Immunoreactivities to heat shock protein 70 and heat shock protein 60 in keratinocytes, hair follicular cells, and endothelial cells of the subdermal vascular plexus were enhanced in the allografts early on postoperative day 1. Positive staining of hair follicles extended to deeper parts of the hair follicles and hair bulbs in the allografts on postoperative day 3. Although dendritic cells were positive for both heat shock protein 70 and heat shock protein 60, infiltrating lymphocytes were positive only for heat shock protein 60. CONCLUSIONS: These results suggest the possible involvement of heat shock proteins in the process of major histocompatibility complex-compatible minor-mismatch composite tissue allotransplantation rejection. Thus, modulation of the function of heat shock proteins might be an important therapeutic option for improving the outcome of minor-mismatch allografts.

Animals↗
PubMed2005

Novel oral insulin delivery systems based on complexation polymer hydrogels: single and multiple administration studies in type 1 and 2 diabetic rats.

Insulin-loaded polymer microparticles (ILP) composed of crosslinked poly(methacrylic acid) and poly(ethylene glycol) are multi-functional carriers showing high insulin incorporation efficiency, a rapid insulin release in the intestine based on their pH-dependent complexation properties, enzyme-inhibiting effects and mucoadhesive characteristics. Thus, they are potential carriers for insulin delivery via an oral route. Recent studies suggest that the polymer composition and particle size of ILP strongly influenced insulin bioavailability. Therefore, the present study aimed at finding an optimal formulation and designing carriers for oral insulin delivery using in vivo experiments. Various types of ILPs were prepared and administered orally to healthy and type 1 and 2 diabetic rats. The most promising formulation was subsequently used for in vivo multiple oral administration studies using diabetic rats. The microparticles of diameters of <53 microm (SS-ILP) composed of a 1:1 molar ratio of methacrylic acid/ethylene glycol units showed the most pronounced hypoglycaemic effects following oral administration to healthy rats, achieving a 9.5% pharmacological availability compared to subcutaneous insulin injection. Their usefulness was also confirmed with both type 1 and 2 diabetic rat groups. In a multiple administration study, SS-ILP significantly suppressed the postprandial rise in blood glucose and showed continuous hypoglycaemic effects following 3 times/day oral administration to both diabetic rat groups in the presence of foods. These results indicate that the blood glucose levels of diabetic rats can be effectively controlled by oral SS-ILP administration, and thus SS-ILP would be a promising delivery carrier of insulin via the oral route.

Administration, Oral↗
PubMed2005

Proteus syndrome with giant myelolipoma in the pelvis.

Proteus syndrome is a very rare and complex disorder with malformations and overgrowth of multiple tissues. This disorder was designated Proteus syndrome by Wiedemann et al. to denote its variable clinical expression. Our patient presented with macrodactyly, cerebriform appearance and a huge abdominal mass. A biopsy under laparotomy was performed, and histopathological examination revealed myelolipoma. Tumor resection was performed. To our knowledge, no case of Proteus syndrome presenting a myelolipoma in the retroperitoneal cavity has been reported before.

Humans↗
PubMed2004

Mucosal insulin delivery systems based on complexation polymer hydrogels: effect of particle size on insulin enteral absorption.

Insulin-loaded polymer (ILP) microparticles composed of poly(methacrylic acid) and poly(ethylene glycol), which have pH-dependent complexation and mucoadhesive properties have been thought to be potential carriers for insulin via an oral route. Nevertheless, further optimization of the polymer delivery system is required to improve clinical application. Therefore, the effect of particle size of the ILP (L-ILP: 180-230 microm, S-ILP: 43-89 microm, SS-ILP: <43 microm) on insulin absorption was studied in the in situ loop system, hypothesizing smaller particle sizes of ILP could induce bigger hypoglycemic effects due to increase mucoadhesive capacity. To verify the hypothesis, the adhesive capacities of differently sized ILPs to the mucosal tissues were evaluated. Additionally, the intestinal site-specificity of ILP for insulin absorption was investigated. Intra- and inter-cellular integrity and/or damage were also examined by lactate dehydrogenase leakage and membrane electrical resistance change to ensure the safety of ILP as a carrier for oral route. As hypothesized, the smaller sized microparticles (SS-ILP) showed a rapid burst-type insulin release and higher insulin absorption compared with the microparticles having larger sizes, resulting in greater hypoglycemic effects without detectable mucosal damage. In fact, SS-ILP demonstrated higher mucoadhesive capacity to the jejunum and the ileum than those of L-ILP. Moreover, SS-ILP's enhancement effect of insulin mucosal absorption showed a site-specificity, demonstrating maximum effect at the ileal segment. These results imply that the particle size and delivery site are very important factors for ILP with respect to increasing the bioavailability of insulin following oral administration.

Animals↗
PubMed2004

Simple curettage without bone grafting for enchondromas of the foot.

BACKGROUND: Simple curettage without bone grafting for enchondromas of the hand and its good clinical results have been reported. Yet, there have been no reports regarding simple curettage without bone grafting for enchondromas of the foot. The purpose of this study is to elucidate the clinical results of this method for enchondromas of the foot. METHODS: We studied eight patients (ten bones) with enchondromas of the foot treated with simple curettage without bone grafting. After making an oval or round fenestration, the enchondroma was curetted. The cortical window of the fenestration was excised in five bones, whereas it was replaced at the fenestration site in the other five bones. RESULTS: The affected toe was immobilized with a tape in two patients. All patients began to walk on the day of surgery or the next day without crutches. Sclerotic changes on the plain radiographs were seen 6.4 weeks (range: 4-10 weeks) postoperatively. The patients returned to their normal daily activity including occupation and sport in 8.6 weeks (range: 0-12 weeks) postoperatively. The radiographic appearance was almost normalized in 8.4 months on average (range: 3-14 months). Function was classified as excellent in all bones according to a modified Tordai classification. CONCLUSION: We conclude that simple curettage without bone grafting can be one of the standard surgical treatments for enchondromas of the foot.

Adult↗
PubMed2004

Effects of antithrombin III on spinal cord-evoked potentials and functional recovery after spinal cord injury in rats.

STUDY DESIGN: From the view of motor function, spinal cord-evoked potentials, and histology, we evaluated the effects of antithrombin III on a spinal cord injury resulting in incomplete paraplegia. OBJECTIVES: To investigate the effect of antithrombin III on the recovery process after acute incomplete rat spinal cord injury. SUMMARY OF BACKGROUND DATA: Antithrombin III is used for treating disseminated intravascular coagulation by its anticoagulant effect and is also reported to reduce organ damage by the release of prostaglandin I2 from endothelial cells, induced by antithrombin III. Therefore, antithrombin III has potential as a therapeutic agent for spinal cord damage. METHODS: The spinal cord injury was induced by placing a 25 g weight on the dorsal surface of the spinal cord at the 10th thoracic spine level for 20 minutes. Antithrombin III (250 U/kg) was administered intravenously 5 minutes before the compression, whereas 2 mL of physiologic saline solution was administered to the control group. We recorded the spinal cord-evoked potentials at the T13 level after stimulation of the brain and C7 level. For 12 weeks after the injury, we observed the recovery course of waveform and motor function. The recovery of motor function was evaluated by using inclined table and modified Tarlov scores. We also examined the histology of the compressed site in the spinal cord. RESULTS: There were statistically significant differences in the motor recovery process between the two groups. Evoked potentials of the antithrombin III group recovered earlier than those of the control group. Histologically, hemorrhage and tissue defects in the spinal cord were less in the antithrombin III group. CONCLUSION: Because antithrombin III facilitated the recovery of behavior and evoked potentials, these findings suggest that antithrombin III may have a positive effect on the recovery of incomplete spinal cord injury.

Animals↗
PubMed2004

Spindle cell lipoma of the knee: a case report.

A rare case of spindle cell lipoma of the knee in a 58-year-old woman is presented. A soft tissue mass on the lateral aspect of the knee, measuring 5 x 6 cm in size, that had been noticed 1 year previously showed slightly lower signal intensities both on T1- and T2-weighted magnetic resonance images than those of subcutaneous adipose tissue. Because pathological findings of the tiny specimen obtained by needle biopsy showed lipogenic tumor and the possibility of well-differentiated liposarcoma could not be ruled out, wide excision was performed. Histopathological examination revealed that the tumor consisted of spindle cells, collagen fibers, and lipocytes. In addition, immunohistochemical study showed positive staining for CD34. From these histological findings, diagnosis of spindle cell lipoma was made. Although expected sites of spindle cell lipoma are the posterior neck, shoulder region, and upper back, it may also arise in the lower extremity. Therefore, when radiological findings suggest lipogenic tumor but are different from those of lipoma, spindle cell lipoma as well as well-differentiated liposarcoma should be considered for differential diagnoses.

Antigens, CD34↗
PubMed2004

Development of acrylic-based copolymers for oral insulin delivery.

We developed nanospheres of crosslinked networks of methacrylic acid grafted with poly(ethylene glycol), and acrylic acid grafted with poly(ethylene glycol) nanospheres for use as oral insulin delivery devices. The copolymer nanospheres were synthesized via free-radical precipitation/dispersion. The average particle diameter of the copolymer gel nanospheres at various physiologically relevant pH values was characterized using photon correlation spectroscopy. Their size increased dramatically as the surrounding pH rose above the pK(a) of the network. The nanospheres ranged in diameters from 200 nm at pH of 2.0 to 2 microm at pH around 6.0. Insulin was loaded into the copolymers at levels of 9.33 and 9.54 mg per 140 mg solid sample, by partitioning from concentrated insulin solutions. In vitro studies were performed to study the passage of the insulin-loaded copolymer samples in the gastrointestinal tract. Insulin was entrapped at low pH (pH=3.0) but released at more neutral pH (pH=7.0). Animal studies were performed to investigate the abilities of insulin-loaded copolymer samples to influence the serum glucose levels of rats. In studies with diabetic rats, the serum glucose level was lower than control values for the animals that received the insulin-loaded copolymers and lasted for at least 6 h. The insulin loaded copolymer nanospheres caused a significant reduction of serum glucose with respect to that of a control animal.

Acrylates↗
PubMed2004

[Ewing's sarcoma].

Ewing's sarcomas account for 6.8% of all primary malignant bone tumors and are probably a neurogenic, undifferentiated, high-grade malignancy, which usually affects the bones of children 5-15 years of age. Pain and swelling are the most common symptoms. Increase of CRP and erythrocyte sedimentation rate, leucocytosis, and anemia are frequently seen. Radiologically, they show permeative bone destruction on plain radiographs. When arising in the diaphysis of long bones, laminated, "onion-skin" periosteal reaction is seen. The tumor shows muscle density on CT, iso-signal intensity on T1-weighted MR images, and high signal intensity on T2-weighted MR images. Intramedullary invasion and skip lesions can be detected on MR images. Histologically, the tumor is uniformly composed of sheets of small round cells closely packed and without any matrix product. Glycogen granules are demonstrated in the cytoplasm by periodic acid-Schiff (PAS) and diastase reactions. Immunohistochemically, Ewing's sarcomas are positive for vimentin and MIC-2 gene product (CD99). Reciprocal translocation, i.e., t(11;22) (q24;q12), is seen in the tumor cells. EWS/FLI-1 fusion gene can be demonstrated, which can be a complementary method in diagnosing this tumor. Because Ewing's sarcomas are chemosensitive and radiosensitive, they are treated by a combination of chemotherapy, surgery, and radiotherapy. Neoadjuvant chemotherapy consists of preoperative chemotherapy and postoperative chemotherapy. Preoperative chemotherapy aims at eradicating distant micrometastasis, reducing the primary tumor volume, and evaluating the efficacy of the chemotherapeutic agents. Surgery is performed as a local treatment by excising the tumor using the wide procedure. If surgery is impractical, curative radiotherapy is performed instead of excision. When surgery is performed without complete wide procedure, adjuvant radiotherapy is carried out to eradicate the residual tumor cells. Postoperative chemotherapy aims to eradicate the distant micrometastasis. Recently, myeloablative, high-dose chemotherapy followed by autologous bone marrow transplantation is being attempted for poor-prognosis patients and good results have been reported.

Adult↗
PubMed2004

[Soft tissue sarcoma: postoperative chemotherapy].

In high-grade musculoskeletal sarcomas, adjuvant chemotherapy is often performed to prevent distant metastases. The efficacy of chemotherapy varies according to the histological type of sarcoma. Prognoses are poor in patients with osteosarcoma, Ewing's sarcoma, or rhabdomyosarcoma, when surgery alone is performed. However, because these sarcomas are chemosensitive, their prognoses are improved with adjuvant chemotherapy. On the other hand, the efficacy of chemotherapy is not statistically demonstrated in non-round cell sarcomas, e. g., malignant fibrous histiocytoma. Nowadays, several kinds of antitumor agents are usually used for adjuvant chemotherapy, and many authors have reported various kinds of regimens and their clinical results. Commonly used drugs include adriamycin, ifosfamide, cisplatin, methotrexate, cyclophosphamide, dacarbazine, vincristine, and actinomycin-D. Recently, high-dose chemotherapy combined with autologous peripheral blood or bone marrow stem cell transplantation has been begun in patients who do not respond to standard chemotherapy, and a better prognosis is expected.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed2003

Expression of cyclooxygenase-2 in chondroblastoma: immunohistochemical analysis with special emphasis on local inflammatory reaction.

To investigate the frequency and mechanism of the peritumoral inflammatory reaction in chondroblastoma, we evaluated the relationship between clinicoradiological findings and immunohistochemical expression of cyclooxygenase-2 (COX-2) in excised tumors. Twenty-one cases of chondroblastoma were studied. Imaging analysis was performed with radiographs and T1- and T2-weighted magnetic resonance images in all cases and with computed tomography scan and bone scintigraphy in some cases. Immunohistochemical study for COX-2 was carried out using formalin-fixed paraffin-embedded tissues. Periosteal reaction was observed in 6 cases (29%) and bone marrow edema in 15 cases (71%). Soft-tissue edema, joint effusion, and synovitis were found in 10 cases (48%), in 7 cases (33%), and in 9 cases (43%), respectively. Immunohistochemical expression of COX-2 in chondroblastoma cells was found in 15 of 21 cases (71%). The intensity of COX-2 immunoreactivity was correlated statistically with the presence of periosteal reaction, bone-marrow edema, soft-tissue edema, and synovitis. Our results indicate that activation of eicosanoid synthesis by COX-2 expression in the tumor itself is probably an important factor, inducing peritumoral inflammatory changes in chondroblastomas.

Adolescent↗
PubMed2002

Chondrosarcoma of the hand secondary to multiple enchondromatosis; report of two cases.

Although malignant transformation to chondrosarcoma may occur in some patients with multiple enchondromatosis, this event rarely occurs in the hand. We encountered two patients with chondrosarcoma of the hand secondary to multiple enchondromatosis. One patient was a 27-year-old man and the other, a 76-year-old man. Both patients manifested multiple osteolytic lesions in the hand on the plain radiographs. Severe bone destruction associated with a large soft-tissue swelling of the proximal and middle phalanges of the little finger was seen in case 1. In case 2, tremendous expansion and bone destruction of the middle phalanx of the ring finger was seen. Magnetic resonance images of the tumour in both patients showed low signal intensity on T1-weighted and high signal intensity on T2-weighted images. Amputation was performed in each patient. Histological examination revealed that the tumour was a grade 2 chondrosarcoma in case 1 and a grade 1 chondrosarcoma in case 2 accompanied by enchondromata. From these findings, the diagnosis of chondrosarcoma secondary to multiple enchondromatosis was made. Because quite a few patients with multiple enchondromatosis develop secondary chondrosarcoma, although rarely in the hand, the enchondromata should be curetted, unless impractical, before malignant transformation occurs.

Adult↗
PubMed2002

Intracortical chondromyxoid fibroma of humerus.

The clinicoradiologic and pathologic aspects of an intracortical, diaphyseal chondromyxoid fibroma of the humerus are reported. Because of the location of the lesion, the possibility of chondromyxoid fibroma was not considered radiologically. The diagnosis was made only after histologic examination of tissue obtained via an open biopsy, which led to the appropriate treatment, surgical curettage.

Adult↗
PubMed2002

Intracortical chondroblastoma mimicking intra-articular osteoid osteoma.

We report a case of intra-articular intracortical chondroblastoma of the femoral condyle which radiologically appeared to be osteoid osteoma. A 19-year-old woman presented with a 3-year history of gradually increasing pain in the right knee and had been on nonsteroidal anti-inflammatory drugs for pain relief. Laboratory data were within normal limits. Radiographs showed a well-demarcated lucent lesion in the medial condyle of the right femur. A nidus-like lesion with calcifications and a sclerotic rim located in the cortex was imaged by computed tomography scan. Magnetic resonance imaging revealed bone marrow edema and soft tissue swelling around the lesion, with low signal intensity of the nidus-like lesion on both T1- and T2-weighted images. The lesion was excised en bloc and the histological diagnosis of chondroblastoma was made. A mild inflammatory reaction was observed in the bone marrow and synovium around the tumor. The chondroblastoma cells were shown to express cyclooxygenase-2 with immunohistochemistry.

Adult↗
PubMed2002

Primary leiomyosarcoma of the femur.

Leiomyosarcoma usually arises in the uterus, gastrointestinal tract, retroperitoneum, or soft tissue. Primary leiomyosarcoma of bone is rare. We encountered two patients with primary leiomyosarcoma of the femur; one was a 24-year-old woman and the other, a 41-year-old woman. Bone destruction observed on plain radiographs was minimal in both patients. Magnetic resonance imaging (MRI) showed low signal intensity on T1-weighted images and high signal intensity on T2-weighted images, with these areas being much larger than the findings to be expected from the plain radiographs. Histological examination revealed spindle-cell sarcoma, with an interlacing pattern, acidophilic cytoplasm and blunt-ended or "cigar-shaped" nuclei, in both patients. In both patients, immunohistochemical examination showed positive staining for vimentin, desmin, and alpha-smooth muscle actin. Extensive examination of the gastrointestinal tract and uterus revealed no primary lesion. Therefore, the leiomyosarcoma in the femur was considered to be primary rather than metastatic. Histological examination, including immunohistochemistry, and the exclusion of an extraskeletal primary lesion, is necessary in diagnosing primary leiomyosarcoma of bone.

Adult↗