Biomedical subjects

S Ishii

Publications and source records attributed to S Ishii.

At least 37 records · Page 2Linked to original sources

PubMed2003

Reconstruction of a defect of the rotator cuff with polytetrafluoroethylene felt graft. Recovery of tensile strength and histocompatibility in an animal model.

We reconstructed defects in the infraspinatus tendon u sing polytetrafluoroethylene (PTFE) felt grafts in 31 beagle dogs and examined the mechanical responses and histocompatibility. Except for one infected specimen, all the reconstructed infraspinatus tendons healed. We examined eight specimens each immediately after surgery and at six and 12 weeks. The ultimate tensile strength of the reconstructed tendons was 60.84 N, 172.88 N, and 306.51 N immediately after surgery and at six and 12 weeks, respectively. The stiffness of the specimens at the PTFE felt-bone interface was 9.61 kN/m, 64.67 kN/m, and 135.09 kN/m immediately after surgery and at six and 12 weeks, respectively. Six tendons were examined histologically at three, six, 12 and 24 weeks. Histological analysis showed that there was ingrowth of fibrous tissue between the PTFE fibres. Foreign-body reactionswere found at the margin of the PTFE-bone interface between 12 and 24 weeks. The mechanical recovery and tissue affinity of PTFE felt to bone and to tendon support its use for reconstruction of the rotator cuff. The possible development of a foreign-body reaction should be borne in mind.

Animals↗

PubMed2002

Increased pre-therapeutic serum vascular endothelial growth factor in patients with early clinical relapse of osteosarcoma.

To investigate the clinical significance of circulating angiogenic factors, especially in association with early relapse of osteosarcoma, we quantified pre-therapeutic levels of vascular endothelial growth factor, basic fibroblast growth factor and placenta growth factor in the sera of 16 patients with osteosarcoma using an enzyme-linked immunosorbent assay. After a 1-year follow-up, the serum level of angiogenic factors was analysed with respect to microvessel density of the biopsy specimen and clinical disease relapse. The serum vascular endothelial growth factor levels were positively correlated with the microvessel density with statistical significance (P=0.004; Spearman rank correlation) and also significantly higher in seven patients who developed pulmonary metastasis than the remaining nine patients without detectable disease relapse (P=0.0009; The Mann-Whitney U-test). In contrast, the serum levels of basic fibroblast growth factor or placenta growth factor failed to show significant correlation with the microvessel density or relapse of the disease. Although there was no significant correlation between serum vascular endothelial growth factor levels and the tumour volume, the serum vascular endothelial growth factor levels were significantly higher in patients with a vascular endothelial growth factor-positive tumour than those with a vascular endothelial growth factor-negative tumour. These findings suggest that the pre-therapeutic serum vascular endothelial growth factor level reflects the angiogenic property of primary tumour and may have a predictive value on early disease relapse of osteosarcoma.

Adult↗

PubMed2002

Chloride conductance determining membrane potential of rabbit articular chondrocytes.

Membrane conductance of cultured rabbit articular chondrocytes was characterized by means of the patch-clamp technique. The resting membrane potential of the articular chondrocytes was about -42 mV. The membrane potential shifted in accordance with the prediction by the Nernst equation for Cl- when intracellular and extracellular concentrations of Cl- were changed. On the other hand, change in extracellular concentration of K+ produced no shift in the membrane potential of chondrocytes. The Cl- channel blocker 4-acetamido-4'-isothiocyanatostilbene-2'2-disulfonic acid (SITS) depolarized the membrane potential. These findings suggest that the membrane potential of the chondrocytes is determined mainly by Cl- conductance. Using the cell-attached patch-clamp method, a large unitary conductance of 217 pS was observed in the articular chondrocytes. The unitary current was reversibly blocked by SITS. Therefore, the unitary current was carried by Cl-. The Cl- channel showed voltage-dependent activation and the channels exhibited long-lasting openings. Therefore, the membrane potential of rabbit cultured articular chondrocytes was mainly determined by the activities of the large-conductance and voltage-dependent Cl- channels.

4-Acetamido-4'-isothiocyanatostilbene-2,2'-disulfo↗

PubMed2002

Effects of needle-arthroscopic lavage with different volumes of fluid on knee synovitis in rheumatoid arthritis.

To determine the appropriate volume of physiological fluid needed to effectively reduce synovitis and to determine the indications for intra-articular lavage of knee joints with rheumatoid arthritis (RA), intraarticular lavage with different volumes of physiological fluid via needle arthroscopy were performed on 102 rheumatoid knees in 98 patients (25 males, 77 females) with an average age of 46 years at the time of operation. Intra-articular lavage of a knee joint with 5 or 10 l of physiological fluid gave better clinical results than did intra-articular lavage with 0.5-1.5 l. There was no difference between the beneficial effects of intraarticular lavage using 5 1 or 10 l of fluid. The preoperative conditions (CRP, frequency of the susceptible factors of HLA-DRB1 alleles, radiological change in the knee joint) and the intraoperative chondroscopic assessments were correlated with clinical improvement. Our study demonstrated that intra-articular lavage with 5 l of physiological fluid performed using needle arthroscopy was beneficial. The following points at least should be checked before performing intra-articular lavage: (1) CRP is not elevated to a high level (> or =5 mg/dl), (2) the patient does not have susceptible factors in both HLA-DRB1 alleles, (3) the grade of rheumatoid knee is below Larsen II in preoperative X-ray findings, and (4) the degree of cartilage damage is not more than grade 3 in arthroscopic findings.

Adult↗

PubMed2002

Immunohistological indication for arthroscopic synovectomy in rheumatoid knees: analysis of synovial samples obtained by needle arthroscopy.

To determine the histological indication for arthroscopic synovectomy in rheumatoid knees, 23 patients underwent lavage and biopsy by needle arthroscopy. Eighty-one patients were treated with arthroscopic knee synovectomy after needle arthroscopy, and 51 of these patients underwent only arthroscopic synovectomy. Thirty patients who showed no improvement following arthroscopic synovectomy underwent open surgical synovectomy. Intra-articular lavage of knee joints by needle arthroscopy did not result in any clinical improvements. In the patients who underwent only arthroscopic synovectomy, two groups (only macrophages, no macrophages or B cells) showed clinical improvement (symptoms of the knee, ESR, RF). Patients in whom open surgical synovectomy was performed because of the failure of arthroscopic synovectomy showed clinical improvement. However, there was a significant loss of movement in the knee joint and more severe radiological deterioration in patients who underwent open surgical synovectomy than in those who underwent only arthroscopic synovectomy. Arthroscopic synovectomy should be used for rheumatoid patients with synovial tissue containing only macrophages or none of these two cells.

Adult↗

PubMed2002

Overexpression of granulocyte colony-stimulating factor induces severe osteopenia in developing mice that is partially prevented by a diet containing vitamin K2 (menatetrenone).

Mice transgenic for granulocyte colony-stimulating factor (G-CSF) exhibit severe osteopenia with an increase of osteoclast number and acceleration of bone resorption in adult mice. To examine the effect of G-CSF overexpression on developing bone, bone mineral density levels were examined from 4 weeks through 36 weeks after birth. Peak bone mass was observed at around 24 weeks of age irrespective of G-CSF expression. Apparent osteopenia was observed as early as 4 weeks of age without detectable developmental retardation in bone length and skeletal structure. Morphological examination confirmed a reduction of cancellous bone and cortical bone at this early stage of life, indicating that overexpression of G-CSF results in apparent osteopenia in developing mice, similar to that in adult animals. The effect of vitamin K2 (menatetrenone) (MK4) on bone phenotypes during development was then examined. Mice were fed chow containing either 0.05 mg MK-4 per 100 g or 20.0 mg MK-4 per 100 g for 12 weeks as the control and experimental diets, respectively. This treatment did not change bone length, irrespective of the type of mouse or diet. Peripheral quantitative computed tomography (pQCT) revealed an increase of in CT value bone of MK4-treated mice. Taken together, these results indicate that overexpression of G-CSF induces an apparent reduction of bone mass and results in osteopenia in developing mice. The bone reduction was partially restored by feeding the mice MK4, suggesting a choice for treatment on the osteopenia induced by G-CSF.

Animals↗

PubMed2002

Role of the platelet-activating factor (PAF) receptor during pulmonary infection with gram negative bacteria.

The lipid mediator PAF plays an important role in the phagocytosis of particles, including bacteria, and consequent production of pro-inflammatory cytokines, such as TNF-alpha and IL-8. Using a PAF receptor antagonist (UK-74,505) and PAF receptor knock-out mice, we have investigated the relevance of PAF for the inflammatory changes and lethality after pulmonary infection with the gram-negative bacteria Klebsiella pneumoniae in mice. At an inoculum of 3 x 10(6) bacteria, there was marked pulmonary (bronchoalveolar lavage and lung) neutrophilia that started early (2.5 h after infection) and peaked at 48 h. All animals were dead by day 4 of infection. The chemokine KC and the pro-inflammatory cytokine TNF-alpha increased rapidly and persisted for 48 h in the lungs. Pretreatment with UK-74,505 (30 mg kg(-1) per day, p.o.) had no significant effects on the number of infiltrating neutrophils in BAL fluid or lung tissue, as assessed by histology and measuring myeloperoxidase, or on the concentrations of KC. In contrast, concentrations of TNF-alpha and the number of bacteria inside neutrophils were significantly diminished. In order to support a role for the PAF during K. pneumoniae infection, experiments were also carried out in PAFR-deficient mice. In the latter animals, lethality occurred earlier than in wild-type controls. This was associated with greater number of bacteria in lung tissue and diminished percentage of neutrophils containing bacteria in their cytoplasm. Our results suggest that PAF, acting on its receptor, plays a protective role during infection with K. pneumoniae in mice.

Animals↗

PubMed2002

Entrapment neuropathy of the palmar cutaneous branch of the median nerve concomitant with carpal tunnel syndrome: a case report.

A case of the entrapment neuropathy of the palmar cutaneous branch of the median nerve, concomitant with carpal tunnel syndrome is presented. This report demonstrates that the Semmes-Weinstein monofilament test and nerve conduction studies can identify entrapment of the palmar cutaneous branch of the median nerve concomitant with carpal tunnel syndrome.

Carpal Tunnel Syndrome↗

PubMed2002

Valgus deformity of the ankle following harvesting of a vascularized fibular graft in children.

Progressive valgus ankle deformity is a problematic postoperative donor-site morbidity of a vascularized fibular graft in children. To prevent this complication, tibiofibular metaphyseal synostosis (the Langenskiöld procedure) has been recommended. The authors objectively evaluated the preventive and therapeutic effects of this procedure on five children who had received free vascularized fibular grafts. Their average age at the time of operation was 3 years (range: 1 to 9 years). The Langenskiöld procedure was performed primarily in four patients, and not in one patient. The anteroposterior (A-P) mortise angle and the empirical axis of the donor-site ankle were measured radiographically. With regard to the A-P mortise angle, four of five patients showed valgus with a mild lateral wedging of the distal tibial epiphysis. The patient who did not receive the operation showed the largest A-P mortise angle and mild osteoarthritic changes. The empirical axis exceeded normal range in all of the five patients. These observations indicated that valgus deformity of the ankle in children after harvesting a vascularized fibular graft is inevitable, even if the Langenskiöld procedure is performed. The procedure can delay the ankle valgus. The authors recommend close follow-up of the children who receive the Langenskiöld procedure after harvesting a vascularized fibular graft.

Adolescent↗

PubMed2002

Effects of exogenous testosterone on testicular luteinizing hormone and follicle-stimulating hormone receptors during aging.

During aging, the male Japanese quail exhibits a loss of fertility, increased morphological abnormalities in the testes, and a higher incidence of Sertoli cell tumors. Although there is a coincident loss of reproductive behavior, plasma androgen levels remain high until testicular regression occurs in association with senescence. The purpose of this study was to compare mean specific binding of chicken luteinizing hormone (LH) and follicle-stimulating hormone (FSH) as a measure of testicular receptors during identified stages during aging. Males were categorized according to age (young = 9 months, middle aged = 24 months, or old = 36+ months) and sexual behavior (active or inactive). Testicular samples were collected immediately after perfusion with 4% paraformaldehyde from the following groups: young active (n = 8), young photoregressed (n = 5), young photoregressed plus testosterone implant (n = 4), middle-aged active (n = 8), middle-aged inactive (n = 4), old inactive (n = 5), and old inactive plus testosterone implant (n = 6). A crude plasma membrane fraction was prepared from the testes of each bird and an aliquot deriving from 10 mg of testicular tissue was used for binding assay. Specific binding of labeled LH or FSH was expressed as percentage of total radioactive hormone. Results showed significant (P < 0.05) age-related decreases in both FSH and LH receptor numbers. The highest FSH binding was found in young and middle-aged active males, with low binding in old inactive males. Testicular LH binding decreased during aging, with a sharp decrease in middle-aged males, which was similar to old males. Testosterone implants weakly stimulated FSH and LH binding in old males. Both LH and FSH binding decreased in photoregressed young males. However, testosterone implants stimulated increased LH binding, but did not affect FSH binding in young photoregressed males. These results provide evidence for separate regulation of testicular LH and FSH receptors, with testosterone stimulation of LH receptor, but not FSH receptor number in young males. However, during aging there appears to be a loss of this response, potentially because of the reduced efficacy of testosterone stimulation, thereby implying a diminished capacity for response with aging.

Aging↗

PubMed2002

Characteristics of stress fractures in young athletes under 20 years.

BACKGROUND: With the popularization of organized sports among adolescents and children, the clinical cases of stress fractures in young athletes have increased. This study was carried out to investigate the characteristics of stress fractures in young athletes. METHODS: During the 18-month period between January 1996 and June 1997, new clinical cases of stress fracture due to sports activities were collected from 39 hospitals in Japan. RESULTS: We analyzed 222 stress fractures in 208 athletes under 20 years of age (108 males: 14.4+/-2.2 years, 100 females: 15.2+/-1.5 years). Among these cases, the peak age of occurrence was 16. The most common sport causing stress fracture was basketball. The tibia was the most common location. About 70% of the patients participated in the respective sport for 6 or 7 days per week. High school students trained significantly more often than the primary and junior high school students (p<0.0001). There was a statistically significant difference in the return time to the sport between the cases who visited a hospital within 3 weeks and those who waited for more than 3 weeks after the onset of symptoms (return time, 10.4 vs 18.4 wks). Several cases visited a hospital beyond 8 weeks after the onset of symptoms regardless of the continuous pain of stress fracture, and their recovery was prolonged. CONCLUSIONS: It is important to educate young athletes that continuous pain lasting over 3 weeks is a warning signal to the body, and that early diagnosis leads to early recovery.

Adolescent↗

PubMed2001

Comparison of sequences of cDNA clones obtained from oligo-capping cDNA libraries with those from unigene.

We compared in detail the characteristics of the sequences of the cDNA clones obtained by the oligo-capping method (oligo-capping clones) with that of the sequences in the UniGene database. To compare the completeness of the sequences, three new variables, "fullness-proportion of clones" (the ratio of complete clones to total clones in a library), "fullness-proportion of genes" (the ratio of complete genes to total genes in a library), and "fullness-proportion of database" (the ratio of complete genes to total genes in a database sampled from a library), were defined. The fullness-proportion of clones of oligo-capping clones was 57.3%, 2.2 times larger than that of UniGene (25.9%). The fullness-proportion of genes of oligo-capping clones was 41.8%, 2.4 times larger than that of UniGene (17.8%). When gene length was restricted to > or = 1.5 kb, the fullness-proportion of genes of oligo-capping clones was four times larger than that of UniGene. The fullness-proportion of database of oligo-capping clones was approximately the same as that of UniGene. By simulating the clone redundancy, this coincidence was found to be due to the large redundancy of the UniGene database. Consequently, the cDNA sequence database of oligo-capping clones enabled high throughput selection of full-length cDNA clones.

Algorithms↗

PubMed2001

Increased susceptibility to tumorigenesis of ski-deficient heterozygous mice.

The c-ski proto-oncogene product (c-Ski) acts as a co-repressor and binds to other co-repressors N-CoR/SMRT and mSin3A which form a complex with histone deacetylase (HDAC). c-Ski mediates the transcriptional repression by a number of repressors, including nuclear hormone receptors and Mad. c-Ski also directly binds to, and recruits the HDAC complex to Smads, leading to inhibition of tumor growth factor-beta (TGF-beta) signaling. This is consistent with the function of ski as an oncogene. Here we show that loss of one copy of c-ski increases susceptibility to tumorigenesis in mice. When challenged with a chemical carcinogen, c-ski heterozygous mice showed an increased level of tumor formation relative to wild-type mice. In addition, c-ski-deficient mouse embryonic fibroblasts (MEFs) had increased proliferative capacity, whereas overexpression of c-Ski suppressed the proliferation. Furthermore, the introduction of activated Ki-ras into c-ski-deficient MEFs resulted in neoplastic transformation. These findings demonstrate that c-ski acts as a tumor suppressor in some types of cells. The level of cdc25A mRNA, which is down regulated by two tumor suppressor gene products, Rb and Mad, was upregulated in c-ski-deficient MEFs, whereas it decreased by overexpressing c-Ski in MEFs. This is consistent with the fact that c-Ski acts as a co-repressor of Mad and Rb. These results support the view that the decreased activities of Mad and Rb in ski-deficient cells at least partly contribute to enhanced proliferation and susceptibility to tumorigenesis. Human c-ski gene was mapped to a region close to the p73 tumor suppressor gene at the 1p36.3 locus, which is already known to contain multiple uncharacterized tumor suppressor genes.

Animals↗

PubMed2001

Asymmetric synthesis with a chiral catalyst generated from asymmetric autocatalysis.

A new and efficient one-pot system of asymmetric catalysis is presented in which a chiral catalyst (5-pyrimidyl alkanol) self-improves its ee by asymmetric autocatalysis and then acts as a highly enantioselective chiral catalyst for other asymmetric synthesis (addition of dialkylzincs to aldehydes) to provide products (sec-alcohols) with very high ee (up to 99%).[reaction: see text]

Journal Article↗

PubMed2001

An electrophysiologic study of mechanoreceptors in the sacroiliac joint and adjacent tissues.

STUDY DESIGN: The somatosensory afferent units in the sacroiliac joint of an animal model were investigated using an electrophysiologic technique. OBJECTIVES: To identify the mechanosensitive receptive fields in the sacroiliac joint, and to determine their distribution and characteristics. SUMMARY OF BACKGROUND DATA: The sacroiliac joint is considered to be a source of lower back pain. Although there have been clinical studies on the diagnosis of sacroiliac joint pain, no satisfactory diagnostic method other than joint blocks has been reported. It still is not clear whether the sacroiliac joints actually transmit pain to the central nervous system. The sensory innervation of the sacroiliac joint has not been fully characterized neurophysiologically. METHODS: Experiments were performed on 10 adult cats weighing 2.6 to 4 kg. The animals were anesthetized with intravenous sodium pentobarbital. An L4-L7 laminectomy was performed. The L4-L6 dorsal roots were cut at their proximal ends, split, and draped over a bipolar recording electrode. Glass probes were used to search the sacroiliac joint and adjacent tissues for mechanosensitive units. When units were identified, they were stimulated electrically to obtain conduction velocities and by Semmes-Weinstein monofilaments to determine mechanical thresholds. RESULTS: In the sacroiliac joint and adjacent muscles, 29 discrete mechanosensitive units were identified. Of these 29 units, 26 were found in the posterior sacroiliac ligament and the remaining 3 in the adjacent muscles. Also, 16 units (55%) were identified in the proximal third of the sacroiliac joint. Conduction velocities of the units ranged from 3.1 to 22 m/second (average, 9.2 m/second), and 26 units were group III. Mechanical thresholds of the units ranged from 4.6 to 164.3 g (average, 69.7 g). Whereas 28 units (96.6%) had thresholds higher than 7 g, one unit (3.4%) had a threshold lower than 7 g. CONCLUSIONS: Group III units with mechanical thresholds higher than 7 g may serve as nociceptors, and units with thresholds of lower than 7 g may serve as proprioceptors. The current study showed that most of the units in the sacroiliac joint were high-threshold group III units that perhaps had a nociceptive function. This result suggests that the sacroiliac joint may be a source of lower back pain in humans. This study also showed that the sacroiliac joint has little proprioceptive function.

Animals↗

PubMed2001

Intracellular localization of the Ret finger protein depends on a functional nuclear export signal and protein kinase C activation.

The Ret finger protein (RFP) was identified initially as an oncogene product and belongs to a family of proteins that contain a tripartite motif consisting of a RING finger, a B box, and a coiled-coil domain. RFP represses transcription by interacting with Enhancer of Polycomb and is localized to the cytoplasm or nucleus depending on the cell type. Here, we have identified the nuclear export signal (NES) located in the coiled-coil region of RFP. Mutation of this NES or treatment with leptomycin B abrogated the nuclear export of RFP in NIH3T3 cells. In addition, fusion of this NES to other nuclear proteins, such as yeast transcription factor Gal4, resulted in their release into the cytoplasm of NIH3T3 cells. Although the NES function of RFP in HepG2 cells is masked by another domain in RFP or by another protein, 12-O-tetradecanoylphorbol-13-acetate treatment or overexpression of constitutively active protein kinase Calpha (PKCalpha) abrogated masking, leading to the cytoplasmic localization of RFP. Furthermore, treatment of NIH3T3 cells with PKC inhibitors blocked the function of NES, resulting in nuclear localization of RFP. Thus, the nuclear export of RFP is regulated positively by PKC activation. However, RFP was not a direct substrate of PKC, and additional signaling pathways may be involved in the regulation of nuclear export of RFP.

Active Transport, Cell Nucleus↗

PubMed2001

PML-RARalpha alleviates the transcriptional repression mediated by tumor suppressor Rb.

A fusion between the promyelocytic leukemia (PML) protein and the retinoic acid receptor-alpha (RARalpha) results in the transforming protein of acute promyelocytic leukemia, PML-RARalpha. PML has growth-suppressive properties and is localized within distinct nuclear structures referred to as nuclear bodies. PML participates in numerous cellular functions, including transcriptional activation, apoptosis, and transcriptional repression, whereas PML-RARalpha blocks these functions. However, the role played by PML-RARalpha in leukemogenesis remains unclear. Here we report that PML is required for transcriptional repression mediated by the tumor suppressor Rb. Rb interacts with the histone decaetylase (HDAC) complex containing co-repressors and represses the transcription of the E2F target genes. Overexpression of PML enhanced Rb-mediated repression. The degree of Rb-mediated repression was weakened by injecting anti-PML antibodies and was lower in Pml-deficient mouse embryonic fibroblasts. PML-RARalpha inhibited Rb-mediated repression, and two co-repressor-interacting sites on the PML-RARalpha molecule were required for this activity. Furthermore, PML-RARalpha blocked the interaction between Rb and HDAC. Thus, aberrant binding of PML-RARalpha to co-repressor-HDAC complexes may inhibit their association with Rb, resulting in the abrogation of Rb activity. Thus, the disruption of Rb-mediated repression may be a contributory factor in leukemogenesis.

Animals↗

PubMed2001

Single nucleotide polymorphism of human platelet-activating factor receptor impairs G-protein activation.

Various proinflammatory and vasoactive actions of platelet-activating factor (PAF) are mediated through a specific G-protein-coupled PAF receptor (PAFR). We identified a novel DNA variant in the human PAFR gene, which substitutes an aspartic acid for an alanine residue at position 224 (A224D) in the putative third cytoplasmic loop. This mutation was observed in a Japanese population at an allele frequency of 7.8%. To delineate the functional consequences of this structural alteration, Chinese hamster ovary cells were stably transfected with constructs encoding either wild-type or A224D mutated PAFR. No significant difference was observed in the expression level of the receptor or the affinity to PAF or to an antagonist, WEB2086, between the cells transfected with wild-type and mutant PAFR. Chinese hamster ovary cells expressing A224D mutant PAFR displayed partial but significant reduction of PAF-induced intracellular signals such as calcium mobilization, inositol phosphate production, inhibition of adenylyl cyclase, and chemotaxis. These findings suggest that this variant receptor produced by a naturally occurring mutation exhibits impaired coupling to G-proteins and may be a basis for interindividual variation in PAF-related physiological responses, disease predisposition or phenotypes, and drug responsiveness.

Adenylate Cyclase Toxin↗