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Biomedical subjects

Y Ikuta

Publications and source records attributed to Y Ikuta.

At least 37 records · Page 2Linked to original sources

The state of the articular cartilage at the time of surgery as an indication for rotational acetabular osteotomy.

We have studied whether the state of the articular cartilage at the time of rotational acetabular osteotomy for dysplasia of the hip affects the outcome 2 to 5.5 years after surgery. Arthroscopy in 57 patients (59 joints) at the time of the operation showed grade-0 changes in seven, grade-1 in nine, grade-2 in 17, grade-3 in 14 and grade-4 in 12 joints, according to the classification of Outerbridge. There was radiological evidence of the progression of arthritis in four joints which were classified at arthroscopy as grade 4. Stepwise regression analysis showed that damage to acetabular or femoral articular cartilage significantly affected the progression of arthritis. We conclude that the short-term results of successful rotational acetabular osteotomy for dysplasia are affected by the state of the articular cartilage.

Acetabulum↗

Targeted systemic chemotherapy using magnetic liposomes with incorporated adriamycin for osteosarcoma in hamsters.

To control the growth of primary tumors effectively with systemic chemotherapy, we recently developed intravenously administered small-sized magnetic liposomes as an anticancer drug carrier. We previously reported that intravenously administered magnetic liposomes with incorporated adriamycin (magnetic ADR liposomes) effectively delivered ADR to the target site where a permanent magnet was implanted. In the present study, the therapeutic efficacy of this novel treatment approach, which involves a combination of magnet implantation at the target site and intravenous administration of magnetic liposomes, was further evaluated by comparing tumor growth rates among different administration modalities and by histological examination of treated tumors. Small-sized magnetic ADR liposomes with a mean diameter of 146 nm were prepared by the reverse-phase evaporation method. Syrian male hamsters inoculated with osteosarcoma, Os515, in the right hind limb were studied 7 days after inoculation. One day prior to the animal study, either a permanent magnet (with magnetic force) or non-magnetic alloy (without magnetic force) was implanted in the center of the tumors. Treatment with magnetic ADR liposomes under magnetic force showed significantly greater antitumor activity than intravenous administration of ADR solution or that of magnetic ADR liposomes without magnetic force. ADR administered as magnetic liposomes eliminated weight loss of hamsters, one of the side effects produced by ADR. Interestingly, magnetic liposomes (without incorporated ADR) given under magnetic force also suppressed the tumor growth. The selective accumulation of magnetite particles in the tumor blood vessels was observed by histological examination. These results suggest that this systemic chemotherapy can effectively control the primary tumor without significant side effects, due to the targeting of magnetic ADR liposomes.

Animals↗

Effect of thermosensitive liposomal doxorubicin with hyperthermia on primary tumor and lung metastases in hamster osteosarcoma.

We evaluated the effect of intravenous thermosensitive liposomal doxorubicin (TL-DOX) together with local hyperthermia on primary tumors in highly metastatic hamster osteosarcoma. This combination resulted in higher DOX concentrations in plasma, primary tumors and lungs than standard DOX under the same conditions. Tumor growth and lung metastasis were also inhibited more by TL-DOX and hyperthermia than by hyperthermia alone, DOX with or without hyperthermia, and TL-DOX without hyperthermia. In addition, gains in hamster body weight were not suppressed. These results suggest that the combination of TL-DOX and hyperthermia can control primary tumors and suppress lung metastasis in hamsters.

Animals↗

[Anesthetic management of a patient with pheochromocytoma and cerebral ischemic attacks].

A 15-year-old girl with history of two cerebral ischemic attacks possibly caused by cerebral vascular spasm was diagnosed as having a pheochromocytoma, and was scheduled for laparoscopic removal of the adrenal tumor. Epidural catheterization was performed at Th 12/L 1. General anesthesia was induced with thiamylal and vecuronium, and maintained with nitrous oxide-oxygen-isoflurane and continuous epidural infusion of 1.5% lidocaine. Phentolamine and thiamylal were continuously administrated into the vein. While operating on the tumor, abnormal hypertension did not occur. Just after removal of the tumor, the systolic blood pressure fell to 50-70 mmHg. The hypotension continued for about 75 min, despite administration of dopamine, norepinephrine and epinephrine. After the emergence from anesthesia, the blood pressure recovered to normal level. No neurocerebral abnormality was found. In patients like this one, we have to prevent cerebral vascular spasm and cerebral infarction caused by excessive secretion of catecholamines.

Adolescent↗

Repair of articular cartilage on the surface of heat-treated bone by transplantation of cultured chondrocytes.

The present study addresses clinical problems associated with the degeneration of articular cartilage, which occurs when heat-treated bone with articular cartilage is used for re-implantation after resection of malignant bone tumors adjacent to the joints. We therefore evaluated the effect of transplantation of chondrocytes embedded in collagen gel on the surface of heat-treated bone. A cylindrical complex of bone and articular cartilage 6 mm in diameter was resected from rabbits' patellar grooves and treated in saline at 60 degrees C for 30 min. In Group A, articular cartilage was resected from the complex and the remaining bone was returned to the patellar groove. Then, autologous chondrocytes cultured in collagen gel were transplanted and covered with periosteum. As controls, the original complex of heat-treated bone and articular cartilage (Group B) and heat-treated bone directly covered with periosteum (Group C) was returned to the patellar groove. In Group A, histological study showed that round cells were mainly observed and the matrix was well stained with Safranin O in the repair tissue after 24 weeks. The repair tissue was as thick as the adjacent normal cartilage. Immunohistological study detected type-II collagen and chondroitin-6-sulphate (3B3+) in the matrix of the repair tissue, but not type-I collagen. The repair tissue was consequently cartilaginous in Group A. The repair tissue was not cartilaginous or was degenerative in the control groups. We believe that this modality of heat-treated joints will contribute to limb salvage reconstruction after resection of malignant bone tumors adjacent to the joints.

Animals↗

A HER2/NEU-derived peptide, a K(d)-restricted murine tumor rejection antigen, induces HER2-specific HLA-A2402-restricted CD8(+) cytotoxic T lymphocytes.

We have identified an H-2K(d)-binding peptide, HER2p780 (PYVSRLLGI), derived from murine HER2/neu (HER2), that can induce HER2-specific murine cytotoxic T lymphocytes (CTL). Weekly vaccination of BALB/c mice by syngeneic dendritic cells pulsed with HER2p780 peptide, entirely common to murine and human HER2, suppressed growth of pretransplanted HER2-expressing syngeneic tumors. A HER2-expressing human cancer cell line SKOV3 transfected with murine H-2K(d) cDNA could also be lysed by HER2p780-specific murine CTLs, indicating that human HER2-expressing cancer cells can process and present the cognate peptide in the context of H-2K(d). Since H-2K(d) and HLA-A2402 molecules have similar anchor motifs, the possibility of inducing HER2-specific CTL activity with HER2p780 in HLA-A2402 individuals was examined. CD8(+) CTL clones specific for HER2-expressing cancer cell lines were established from peripheral blood lymphocytes with HLA-A2402 by repeatedly sensitizing with peptide-pulsed autologous dendritic cells as well as peripheral blood mononuclear cells. Detailed analysis of their specificity revealed that the cytotoxicity of CTL clones is specific for the cognate peptide with HLA-A2402 restriction. The results suggest that HER2p780 is a unique peptide that may function as a tumor rejection antigen peptide in HLA-A2402 individuals, as it was directly proven here to function in a murine tumor system.

Animals↗

The anatomic relation among the nerve roots, intervertebral foramina, and intervertebral discs of the cervical spine.

STUDY DESIGN: An anatomic study of the cervical intervertebral foramina, nerve roots, and intradural rootlets performed using a surgical microscope. OBJECTIVES: To investigate the anatomy of cervical root compression, and to obtain the anatomic findings related to cervical foraminotomy for the treatment of cervical radiculopathy. SUMMARY OF BACKGROUND DATA: Cervical foraminotomy is a procedure performed frequently for the management of cervical radiculopathy. However, anatomic studies of cervical foraminotomy have not been fully elucidated. METHODS: In this study, 18 cadavers were obtained for the study of the cervical spine. All the soft tissues were dissected from the cervical spine. Thereafter, laminectomy and facetectomy were performed on C4 through T1 using a surgical microscope. The nerve roots and surrounding anatomic structures, including intervertebral discs and foramina, were exposed. In addition, the intradural rootlets and their intersegmental connections were observed. RESULTS: The shape of the intervertebral foramina approximated a funnel, the entrance zone being the most narrow part and the root sleeves conical, with their takeoff points from the central dural sac being the largest part. Therefore, compression of the nerve roots occurred at the entrance zone of the intervertebral foramina. Anteriorly, compression of the nerve roots was caused by protruding discs and osteophytes of the uncovertebral region, whereas the superior articular process, the ligamentum flavum, and the periradicular fibrous tissues affected the nerve posteriorly. The C5 nerve roots were found to exit over the middle aspect of the intervertebral disc, whereas the C6 and C7 nerve roots were found to traverse the proximal part of the disc. The C8 nerve roots had little overlap with the C7-T1 disc in the intervertebral foramen. The C6 and C7 rootlets passed two disc levels in the dural sac. Also, a high incidence of the intradural connections between the dorsal rootlets of C5, C6, and C7 segments was found. CONCLUSIONS: This study demonstrated the anatomy of the nerve roots, rootlets, and intervertebral foramina, and may aid in understanding the pathology of cervical radiculopathy. The presence of intradural connections between dorsal nerve roots and the relation between the course of the nerve root and the intervertebral disc may explain the clinical variation of symptoms resulting from-nerve root compression in the cervical spine. To perform cervical foraminotomy for cervical radiculopathy, it is necessary to understand the detailed anatomy of the intervertebral foramina thoroughly.

Aged↗

Pathogenesis of retinoic acid-induced abnormal pad patterns on mouse volar skin.

BACKGROUND: Abnormal dermatoglyphs on human volar skin have been reported in many syndromes, but little is known about the pathogenesis. Patterns of pads on rodent limb volar skin are homologous to human dermatoglyphs. METHODS: In previous studies, we showed that transplacental exposure to teratogens induced abnormal pads in mouse fetuses. Moreover, teratogens caused abnormal pad patterns at levels below those that caused skeletal malformations. In this study, we examined morphology and cytokinetics in developing abnormal pads. Pregnant mice were treated with all-trans-retinoic acid at 20 mg/kg orally at embryonal day (E) 12.5 (vaginal plug = E0). The hindlimbs of the embryos were harvested and observed under a light microscope and by scanning electron microscopy. Cell proliferation and cell death were estimated by 5-bromo-2'-deoxyuridine (BrdU) labeling, Nile blue A vital staining, and terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL). RESULTS: Retinoic acid induced aplasia of the fibular tarsal pad and supernumerary interdigital pads on hindlimbs. Cell proliferation was observed in the area of developing pad, but cell death was very rarely seen in either normal or abnormal pads. CONCLUSIONS: Retinoic acid disturbed pad patterning as a whole rather than individual pad formation.

Abnormalities, Drug-Induced↗

A novel human HER2-derived peptide homologous to the mouse K(d)-restricted tumor rejection antigen can induce HLA-A24-restricted cytotoxic T lymphocytes in ovarian cancer patients and healthy individuals.

A mouse HER2-derived peptide, HER2p63 (A) (TYLPANASL), can induce K(d)-restricted mouse cytotoxic T lymphocytes (CTL) and also function as a tumor rejection antigen in an in vivo assay. Since the anchor motif of mouse K(d) for peptide binding has much similarity to that of human HLA-A2402, we asked if human HER2p63 (T) (TYLPTNASL) could induce HER2-specific CTL in HLA-A2402-positive individuals. Peripheral blood mononuclear cells (PBMC) of HLA-A2402-positive individuals were sensitized in vitro with HER2p63-pulsed autologous dendritic cells prepared from PBMC. CTL clone derived from these specifically lysed HER2-expressing cell lines bearing HLA-A2402. Cytotoxic activity of the CTL clone against the HER2-expressing cell line bearing HLA-A2402 was blocked by antibodies against CD3, CD8, HLA-A24 or MHC class I, and was also inhibited by the addition of excess HER2p63-pulsed C1R bearing HLA-A2402. Killer cells were generated from PBMC of seven healthy individuals and five ovarian cancer patients, all of HLA-A2402 type, by in vitro sensitization with HER2p63-pulsed autologous antigen presenting cells. These killer cells selectively lysed HER2-expressing SKOV3 transfected with HLA-A2402 cDNA, indicating high immunogenicity of HER2p63 in all 12 individuals examined.

Animals↗

Development of a cancer vaccine: peptides, proteins, and DNA.

Genetic changes leading to protooncogene activation qualitatively and/or quantitatively alter their gene products and are exclusively or largely restricted to transforming cells and their precursors. The overexpression of HER2 is among those changes and is often detected in adenocarcinomas such as breast, ovarian, lung, and gastric cancer. This provides a rationale for exploring the possibility that HER2 is a target of host immune responses against cancer cells. We have recently demonstrated that HER2 can be a target for tumor-rejecting immune responses against syngeneic murine HER2+ tumor cells. We defined two different peptides, HER2p63-71 and HER2p780-788, with a Kd anchor motif that can induce CD8+ cytotoxic T lymphocytes (CTLs). The growth of HER2+ syngeneic tumors was suppressed in mice immunized with HER2p63-71 or p780-788. Since murine Kd and human HLA-A24 share a similar anchor motif for peptides, HER2p63 71 and HER2p780-788 were examined for induction of CTLs in HLA-A24+ individuals. CD8+ CTL clones specific for these peptides were established and they lysed HER2+ tumor cells in a human leukocyte antigen (HLA)-A24-restricted manner. To elicit specific CD8+ T cell immune responses against cancer, the development of efficient devices to deliver tumor antigen peptides to the major histocompatibility complex (MHC) class I pathway constitutes a central issue. We have developed a novel formula of hydrophobized polysaccharide nanoparticles which can deliver a HER2 oncoprotein containing an epitope peptide to the MHC class I pathway. We designed a simple protein delivery system: cholesteryl group-bearing polysaccharides, mannan or pullulan (CHM or CHP, respectively), complexed with the truncated HER2 protein containing the 147 N-terminal amino acids. These complexes were able to induce CD8+ CTLs against HER2+ tumors. CTLs were MHC class I restricted and specifically recognized HER2p63-71, a part of a truncated HER2 protein used as an immunogen. The complete rejection of tumors also occurred when CHM-HER2 was applied early after tumor implantation. In the effector phase of in vivo tumor rejection, CD8+ T cells played a major role. The results suggest that this unique hydrophobized polysaccharide may help soluble proteins to induce cellular immunity. Such a novel vaccine may be of potential benefit in cancer prevention and cancer therapy.

Animals↗

Transtrochanteric rotational osteotomy for osteonecrosis of the femoral head with preoperative superselective angiography.

A prospective radiologic and scintigraphic study was made of 15 joints in 12 patients who underwent transtrochanteric rotational osteotomy of the femoral head after identifying by preoperative superselective angiography which arteries should be preserved during surgery. The preoperative superselective angiography revealed that the blood supply to the femoral head was provided by the medial femoral circumflex artery in 12 joints and a branch of the internal iliac artery in 3 joints. These nutrient arteries were preserved during surgery. At the follow-up examination made after at least 2 years, there were no cases of collapse of the new femoral head weight-bearing site, and also there were no cases with a large cold area in the femoral head on the scintigram obtained 2 months postoperatively. For this operative procedure, the nutrient arteries of the femoral head should be confirmed by preoperative superselective angiography, and it is essential that these arteries be preserved during surgery.

Adolescent↗

Changes in serum tissue inhibitor of matrix metalloproteinase-1 after interferon alpha treatment in chronic hepatitis C.

BACKGROUND/AIMS: The aim of this study was to evaluate the effect of interferon alpha on the metabolism of hepatic fibrosis in chronic hepatitis C, monitoring serum tissue inhibitor of matrix metalloproteinase-1(TIMP-1) and N-terminal propeptide of type III procollagen (PIIINP) reflecting fibrolysis and fibrogenesis, respectively. METHODS: Serum levels of TIMP-1 and PIIINP were serially measured in 112 treated and 31 untreated patients with chronic hepatitis C during and after interferon alpha treatment. Furthermore, the relationships between these serum markers and the grades of hepatic fibrosis after interferon therapy were also investigated. RESULTS: Serum pretreatment levels of TIMP-1 and PIIINP in non-responders were significantly higher than those in sustained and transient responders, but these levels were not different in the latter two groups. Serum TIMP-1 levels decreased significantly during and after treatment in sustained responders, and decreased temporarily at the end of treatment in transient responders, although these levels were unchanged during and after treatment in non-responders and untreated patients. In contrast, serum PIIINP levels decreased significantly during and after treatment in all treated groups, but were unchanged in untreated patients. Histological examination 12 months after interferon was completed demonstrated that hepatic fibrosis improved in sustained responders and was unchanged in transient and non-responders, but progressed in untreated patients. CONCLUSION: These results suggest that interferon alpha treatment of chronic hepatitis C may improve hepatic fibrosis in sustained responders by the acceleration of fibrolysis as well as the inhibition of fibrogenesis, and that it may suppress the progression of hepatic fibrosis in non-sustained responders by the inhibition of fibrogenesis.

Antiviral Agents↗

Pretibial cyst formation after anterior cruciate ligament reconstruction using auto hamstring grafts: two case reports in a prospective study of 89 cases.

Eighty-nine cases after anterior cruciate ligaments (ACL) reconstruction were followed prospectively with magnetic resonance imaging (MRI). The patients were examined using axial and sagittal MRI at least twice during the postoperative evaluation of reconstructed ACL. Two cases of pretibial cyst formation were observed. At the time of cyst formation, neither patient had any subjective or objective evidence of knee instability. The cyst of one case communicated with the intra-articular. The minimum follow-up period after the surgical excision was 9 months, with no evidence of recurrence. We might speculate that the critical period for cyst formation in both patients occurred at less than 12 months after their ACL reconstruction. We concluded that the cyst formation was most likely due to incomplete graft tendon incorporation within the osseous tunnel.

Adolescent↗

Two Alangium alkaloids from Alangium lamarckii.

Two new Alangium alkaloids, 1',2'-dehydrotubulosine (1) and alangine (2), were isolated from the dried fruits of Alangium lamarckii along with tubulosine (3), isotubulosine (4), deoxytubulosine, cephaeline, isocephaeline, psychotrine, neocephaeline, 10-O-demethylcephaeline, 2'-N-(1"-deoxy-1" -beta-D-fructopyranosyl)cephaeline, protoemetine, protoemetinol, salsoline, and alangiside. The structures of the new alkaloids (1 and 2) were determined by spectroscopic and chemical means.

Alkaloids↗

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↗

The current perception thresholds vary between horizontal and 70 degrees tilt-up positions.

UNLABELLED: We investigated the influence of posture on current perception threshold (CPT). The subjects consisted of 20 healthy male volunteers (23-31 yr old). At both the horizontal and the 70 degrees tilt-up position (TUP), the CPTs (5, 250, and 2000 Hz) of the middle finger were determined by using the Neurometer CPT/C (Neuropteran, Baltimore, MD). Autonomic nervous activities were evaluated by heart rate variability (HRV) analysis and spontaneous baroreflex sensitivity analysis at the two postures previously mentioned. The three CPTs at the 70 degrees TUP were significantly lower than those at the horizontal posture (5 Hz, P < 0.05; 250 Hz, P < 0.001; 2000 Hz, P < 0.05). The changes in HRV and spontaneous baroreflex sensitivity at the 70 degrees TUP indicated decreasing parasympathetic tone. The CPTs of 5 and 250 Hz were significantly correlated with mean systolic blood pressure at the 70 degrees TUP. The CPT of 2000 Hz was significantly correlated with the 0.15-0.4 Hz component in HRV at both postures. The regression analysis of the difference of 5 Hz CPT with that of the mean systolic blood pressure showed a significant correlation (P < 0.001). To evaluate the clinical course of peripheral nerve disorders, the comparison of CPTs measured during the same posture is important. This suggests that CPTs must be measured at the horizontal posture. IMPLICATIONS: Current perception thresholds at the 70 degrees tilt-up posture were significantly lower than those at the horizontal posture. When the compensatory mechanism for preserving blood pressure was emphasized, the current perception thresholds would have a relational connection to mean systolic blood pressure, similar to the concept of hypertension-induced hypoalgesia.

Adult↗

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↗