Biomedical subjects

H Yoshikawa

Publications and source records attributed to H Yoshikawa.

At least 109 records · Page 6Linked to original sources

PubMed2001

Immunohistochemical detection of parathyroid hormone-related peptide, Indian hedgehog, and patched in the process of endochondral ossification in the human.

Parathyroid hormone-related peptide (PTHrP), Indian hedgehog (Ihh), and patched (Ptc; a receptor for Ihh) were immunolocalized in tissue undergoing endochondral ossification in the human. PTHrP, Ihh, and Ptc were immunolocalized in prehypertrophic and hypertrophic chondrocytes in mature cartilage matrix. PTHrP and Ptc were immunostained in proliferating chondrocytes and perichondrial cells, whereas Ihh was not. PTHrP, Ihh, and Ptc showed positive immunostaining in osteoblasts in the bone-forming area. In the bone resorption site, PTHrP was immunolocalized in osteoclasts, whereas Ihh and Ptc were not. The present findings indicated that PTHrP, Ihh, and Ptc were associated with the process of endochondral ossification, and suggested the possible involvement of Ihh and PTHrP signaling in the regulation of proliferation and hypertrophy of chondrocytes in human chondrogenesis.

Bone Neoplasms↗

PubMed2001

Localization and expression of osteopontin in the rotator cuff tendons in patients with calcifying tendinitis.

Calcifying tendinitis of rotator cuff tendons is a common and painful condition caused by ectopic calcification in humans. To examine the involvement of osteopontin (OPN), a potent regulator of calcium deposition on connective tissues, localization and expression of OPN protein and messenger (m)RNA were investigated in human tissue samples of calcified rotator cuff tendons. Immunohistochemistry demonstrated that OPN was localized in cells surrounding the calcified area. OPN was localized in two distinct cell types, i.e., fibroblast-like cells negative for CD68 and tartrate-resistant acid phosphatase (TRAP) and multinucleated macrophages positive for CD68 and TRAP. In situ hybridization revealed that the mRNA expression of OPN in these cells coincided with the immunohistochemistry results, and these results were supported by reverse transcriptase polymerase chain reaction analysis using human OPN-specific oligonucleotides. Cells located away from the calcified area did not express OPN. The present findings indicate the involvement of OPN in the process of calcification of rotator cuff tendons and suggest that OPN plays a role in such painful disorders through the actions of at least two cell types.

Acid Phosphatase↗

PubMed2001

Activation and localization of cartilage-derived morphogenetic protein-1 at the site of ossification of the ligamentum flavum.

Localization and expression of cartilage-derived morphogenetic protein (CDMP)-1 in tissues at the site of ossification of the ligamentum flavum (OLF) were examined by immunohistochemistry and in situ hybridization. The CDMP-1 protein and messenger ribonucleic acid (mRNA) were localized in spindle-shaped cells and chondrocytes in the OLF tissues. CDMP-1 was not detected in cells in non-ossified sites. These data indicate that CDMP-1 is locally activated and localized in spindle-shaped cells and chondrocytes at the site of OLE. Given the previously reported promoting action of CDMP-1 for chondrogenesis, the current results suggest that CDMP-1 may be involved in the progression of OLF, leading to the narrowing of spinal canal and thus causing severe clinical manifestations.

Aged↗

PubMed2001

Hypophosphatemic rickets accompanying McCune-Albright syndrome: evidence that a humoral factor causes hypophosphatemia.

McCune-Albright syndrome (MAS) is sometimes complicated by hypophosphatemia. However, it remains unclear whether a humoral factor is associated with the cause of hypophosphatemia. We isolated cells with mutations of the Gsalpha gene from fibrous bone dysplasia tissues of two MAS patients (MAS cells). Severe combined immunodeficiency (SCID) mice were subjected to experiments using from one of these cells patients. Effects of conditioned media (CM) isolated from MAS cells (MAS-CM) on phosphate transport were investigated by using rat renal slices, the renal cell line OK-B, rat intestinal rings and the human intestinal cell line Caco-2. In addition, the effects of MAS-CM on human sodium-dependent phosphate transporter (NPT2) gene promoter activity expression were investigated in the renal cell line OK-B2400 and were compared with the effects of CM isolated from a patient with oncogenic hypophosphatemic osteomalacia (OHO). MAS cells caused significant hypophosphatemia (P < 0.05) and elevated serum alkaline phosphatase activity (P < 0.05) in SCID mice. The MAS-CM significantly inhibited phosphate uptake in everted intestinal rings (P < 0.01), whereas it had no effect on glucose uptake. The MAS-CM had no effect on either phosphate uptake in the kidney or NPT2 gene promoter activity. In contrast, the CM of the OHO patient significantly inhibited phosphate uptake and NPT2 gene promoter activity. These results indicate that the humoral factor derived from fibrous dysplasia cells of the MAS patient is different to that from OHO patients, because the humoral factor from the MAS patient inhibited phosphate transport not in the kidney but in the intestine.

Adolescent↗

PubMed2001

A myxoid liposarcoma in the lower leg, with a large intra-abdominal metastasis.

We report a patient with a large intra-abdominal metastasis of myxoid liposarcoma. The patient first noticed an asymptomatic mass in her left leg in 1985, when she was 20 years old. The mass was left untouched until she realized its rapid growth and consulted a local doctor in 1994. After needle biopsy, she was histologically diagnosed as having a myxoid liposarcoma. She disagreed with the recommendation for an amputation below the knee, made at another hospital. A marginal resection was performed as an alternative treatment. She subsequently underwent three more marginal resections and four intra-lesional resections for repeated local recurrences. In 1997, an abdominal computed tomography scan revealed the presence of multiple intra-abdominal metastases, and the lesions were judged to be inoperable. Ileus and respiratory distress, caused by compression by the abdominal mass, gradually worsened, and she died in 1999, at the age of 34. The girth of her abdomen was 135 cm at the time of death.

Abdominal Neoplasms↗

PubMed2001

Myelin-associated oligodendrocytic basic protein modulates the arrangement of radial growth of the axon and the radial component of myelin.

Myelin-associated oligodendrocytic basic protein (MOBP) is abundantly expressed in central nervous system myelin, and shares several characteristics with myelin basic protein (MBP), in terms of regional distribution and function. MOBP causes experimental allergic encephalomyelitis (EAE) and is associated with multiple sclerosis. MOBP has several isoforms, and the carboxy termini that are unique to each isoform contain a cluster of positively charged amino acids residues. These residues are considered to facilitate myelin sheath compaction, as does MBP. MOBP-deficient mice had compact myelin of a normal appearance. The myelin periodicity in MOBP-deficient mice was equal to that in wild-type mice. When mice were exposed to hexachlorophene, a known dysmyelinating agent, however, the myelin showed widening of the major dense lines. By morphometric analysis of the optic nerve in MOBP-deficient and MBP/MOBP-double-deficient mice, we demonstrated that MOBP played a role in controlling axonal diameter. After glutaraldehyde and tannic acid fixation, a radial series of rod-like electron enhancements in the intraperiod line in the CNS myelin, the so-called "radial component", was found arrayed in a straight radial direction in MOBP-deficient mice, while these components were scattered in an oblique zigzag direction in wild-type mice. Thus, it can be concluded that MOBP is essential for normal arrangement of the radial component.

Animals↗

PubMed2001

Bilateral abducens nerve paresis associated with anti-GQ1b IgG antibody.

PURPOSE: To describe two cases with bilateral abducens nerve paresis associated with serum anti-GQ1b IgG antibody. METHODS: Case reports. RESULTS: Two boys, aged 12 and 10 years, experienced acute onset of diplopia after preceding symptoms and signs of infection. In both boys, examination showed only bilateral abducens nerve paresis. Although routine laboratory data and magnetic resonance imaging demonstrated no pathologic findings, titer of anti-GQ1b IgG antibody in the sera of both patients was increased. Diplopia and signs of bilateral abducens nerve paresis disappeared in 6 weeks without any specific treatment. CONCLUSION: The anti-GQ1b IgG antibody in the sera of both patients probably contributed to the bilateral abducens nerve paresis.

Abducens Nerve Diseases↗

PubMed2001

Early MRI findings of rapidly destructive coxopathy.

To diagnose rapidly destructive coxopathy (RDC) in its early stages and understand the pathomechanism of associated joint destruction, ten cases of RDC were followed by periodic MRI from onset of the disease. In the initial stage (stage 1) of RDC, when radiographs revealed slight narrowing of the joint space, a small subchondral area of low signal intensity was observed on T(1)-weighted images (T1WI) and inhomogeneous high intensity was observed on T(2)-weighted images (T2WI) in the antero-lateral portion of the femoral head. When radiographs showed obliteration of the joint space (stage 2), MRI revealed a diffuse area of low intensity on TIWI and high intensity on T2WI in the proximal femur, including the femoral neck and head, suggesting extensive bone marrow edema. The femoral head and acetabulum were aggressively destroyed (stage 3) in all cases 3 to 6 months after the diffuse abnormal pattern was observed on MRI. MRI in stage 3 cases showed low intensity areas on both T1WI and T2WI. RDC did not show the band-like pattern of low intensity on T1WI and high intensity on T2WI that typify MRI findings in cases of osteonecrosis. When joint space narrowing is observed radiographically, the diffuse abnormal pattern of low intensity on T1WI and high intensity on T2WI induced by a subchondral small lesion might be an early sign of RDC.

Aged↗

PubMed2001

Involvement of BMP-2 signaling in a cartilage cap in osteochondroma.

This study describes the distributions of bone morphogenetic protein (BMP)-2 as well as mRNAs for BMP receptor type IB (BMPRIB). collagen types II (Col II) and III (Col III) in a growing "cartilage cap" of osteochondroma. In situ hybridization and immunohistochemical study were performed using histological sections obtained during surgery. BMP-2 was detected in mesenchymal cells in the outer fibrous layer and chondrocytes in the inner cartilaginous matrix, positive for Col III and Col II, respectively. BMPRIB mRNA was distributed in chondrocytes. This is the first study to provide observational evidence of the involvement of BMP-2 signaling in the pathogenesis of cartilage cap of osteochondroma. and suggests the role of BMP-2 in the growth of cartilage cap in osteochondroma.

Bone Morphogenetic Protein 2↗

PubMed2001

In vivo inhibition of tumour growth by dexamethasone in murine osteosarcomas.

This study was performed to determine whether glucocorticoid (GC) is an effective inhibitor of tumour growth in murine osteosarcoma (OS) in vivo. The effects of dexamethasone (DEX) on the growth of this tumour were studied in male C3H/He mice. The animals received a dose of 1.25 or 5 microg/g of DEX in 0.1 ml of steroid solution daily intraperitoneally (i.p.) for 14 days. In each DEX-treated group, significant inhibition of the tumour growth curve was seen in a dose- dependent manner compared with the control group (P<0.0001). The percentage of proliferative cell nuclear antigen (PCNA)-positive cells was 22.7% in the 5 microg/g DEX treatment group compared with 67.6% in the control group (P=0.009). Furthermore, mifepristone, a GC receptor antagonist, blocked the inhibition of tumour growth induced by DEX. In the control group, tumour cells showed positive reactivity for nuclear glucocorticoid receptors (GR) by immunohistochemistry. The results of this study indicate that tumour growth inhibition by DEX in murine osteosarcoma may be via GR.

Animals↗

PubMed2001

Involvement of mitochondrial permeability transition and caspase-9 activation in dimethyl sulfoxide-induced apoptosis of EL-4 lymphoma cells.

We observed that dimethyl sulfoxide (DMSO) induced apoptotic changes in the EL-4 murine lymphoma cell line and that effect was dependent on the concentration and time period. Incubating cells over a period of 18 h, 2.5% DMSO was found to induce sub-G1 peak in DNA histograms analyzed by flowcytometer and nucleosomal ladder formation in DNA gel electrophoresis. We also found down-regulation of Bcl-2, collapse of mitochondrial membrane potential (delta psi m) occurred following DMSO treatment, and release of cytochrome c from the mitochondria to cytosol. These observations suggest that DMSO converted its pro-apoptotic signal at the mitochondria. In the involvement of caspases, caspase-9 and -3, but not caspase-8, were found to be activated responding to DMSO treatment. Inhibitory experiments demonstrated that caspase cascade of mitochondrial apoptotic pathway was indispensable for DMSO-induced apoptosis. In the caspase cascade, caspase-9 was an upstream initiator and its primary signal could be transduced and amplified by caspase-3, -6 and -7. Kinetic study of these data showed mitochondrial dysfunction and caspase activation occurred at 12 h and apoptotic change of nuclear DNA at 18 h, providing another support for the transduction of DMSO pro-apoptotic signal via the mitochondrial pathway.

Animals↗

PubMed2001

Multidimensional profiles of welfare and work dynamics: development, validation, and associations with child cognitive and mental health outcomes.

This prospective longitudinal study addresses the research gap in the literature regarding multidimensional variation in welfare use and employment patterns, and relationships of such variation with parent earnings and child development outcomes. This study also aims to address the limitations of welfare dynamics studies that do not examine how multiple dimensions of welfare receipt and employment co-occur Cluster analysis was utilized, using monthly welfare and employment data from the National Longitudinal Survey of Youth, to examine variation within the welfare population in their welfare and work patterns across the first 5 years of children's lives. Six cluster profiles of welfare and work dynamics were found: Short-Term, Short-Term Work Exit, Working Cyclers, Nonworking Cyclers, Cycle to Long-Term Exit, and Long-Term. The clusters were validated using mother's 6th-year earnings as the criterion. The clusters' associations with child development outcomes in the cognitive and mental health domains (at ages 6 and 7) were then explored. Work following short-term welfare use was associated with higher child reading scores than that following long-term use (a moderate-size effect). Cycling on and off welfare in the context of high levels of employment was associated with higher child internalizing symptoms than cycling accompanied by low levels of employment (a moderate-size effect). Implications for evaluation of TANF welfare-to-work policies are discussed.

Adolescent↗

PubMed2001

Analysis of immunoglobulin secretion by lymph organs with myasthenia gravis.

OBJECTIVES: To investigate in vitro anti-acetylcholine receptor (AChR) antibody secretion by lymph organs with myasthenia gravis (MG) with special attention to clinical status and stages. MATERIALS AND METHODS: Twenty MG patients before therapy were included in this study. Four patients were negative for serum anti-AChR antibodies (AChRAb). All patients received extended thymectomy. Thymic cells, bone marrow (BM) cells and peripheral blood mononuclear cells (PBMC) were cultured for 1 week. AChRAb secretion and IgG secretion in the culture medium were determined by immunoprecipitation assays and ELISA respectively. RESULTS: PBMC secreted AChRAb and IgG most efficiently, followed by BM cells, and then thymic cells. Even in patients whose diseases were of short duration (less than 2 months), the tendency was not changed. AChRAb secretion by BM cells and PBMC significantly correlated with serum AChRAb levels. Thymectomy did not change AChRAb or IgG secretion by PBMC within 3 months. AChRAb secretion by PBMC paralleled the clinical status. Some seronegative patients turned positive by culturing PBMC. CONCLUSION: PBMC is the most efficient site at producing AChRAb, even in patients of short duration (equal to, or less than, 2 months). Monitoring AChRAb secretion by PBMC is useful to estimate the autoimmune activity of MG.

Adolescent↗

PubMed2001

Tumor cell spillage to the vaginal cavity and vaginal stump during the surgery of endometrial carcinoma.

BACKGROUND: Our purpose was to investigate the spillage of the endometrial carcinoma cells to the vaginal cavity and vaginal stump during the surgery. METHODS: Cytologic examination of specimens obtained from the vaginal cavity and vaginal stump during surgery performed on 15 patients with endometrial carcinoma. And the risk factors of carcinoma cell spillage to the vaginal cavity were investigated. RESULTS: Carcinoma cells from the vaginal cavity were negative for nine patients and positive for six patients. Those from the vaginal stump were negative for l4 patients and positive for one patient. In one patient, both were positive. Total abdominal hysterectomy might be one risk of carcinoma cell spillage to the vaginal cavity compared with modified radical hysterectomy and radical hysterectomy. CONCLUSIONS: Endometrial carcinoma cells were spilled into the vaginal cavity in not a few cases and their spillage from there to the vaginal stump could follow during the surgery.

Adenocarcinoma↗

PubMed2001

Overexpression of the granulocyte colony-stimulating factor gene impairs bone morphogenetic protein responsiveness in mice.

Granulocyte colony-stimulating factor (G-CSF) is the major hematopoietic growth factor regulating the production and differentiation of neutrophils. We previously demonstrated that permanent overexpression of G-CSF in transgenic mice produces a dramatic enlargement of the bone cavity and reduction of bone mass. This phenotype was shown to be associated with an increase of osteoclast-mediated bone resorption. As a way of determining the role of G-CSF in bone formation in vivo, an ectopic bone was induced subcutaneously into G-CSF transgenic mice by bone morphogenetic protein (BMP)-2, a potent initiator of bone and cartilage from undifferentiated mesenchymal cells. A BMP-2/atelocollagen pellet containing recombinant human BMP-2 was implanted into a dorsal subfascial pocket. At one week after implantation, proliferation of mesenchymal cells around the implant was significantly decreased in transgenic mice compared with control mice. At three weeks, an ectopic bone containing bone marrow was formed both in transgenic and control mice. However, the ectopic bones of the transgenic mice were smaller and less consistent than those of control mice, and the calcium contents were reduced to 56.2% of those of controls. The ectopic bone in the G-CSF mice showed poor development of both lamellar and trabecular bone. Semiquantitative reverse transcription-polymerase chain reaction analysis of the ectopic bone at 3 weeks disclosed no significant differences in the mRNA levels of type I collagen, osteopontin, and osteocalcin between G-CSF mice and control mice. Immunohistochemical study in G-CSF mice showed reduced staining of osteocalcin in the bone matrix surrounding the reduced number of osteoblasts. The half-life of BMP in the implants was prolonged to 7 to 9 days in the G-CSF mice, whereas it was 5 days in the control mice. Collectively, the permanent expression of G-CSF may retard the differentiation process of osteoblasts by impairing the initial induction of mesenchymal cells, resulting in reduction of bone mass, suggesting that G-CSF regulates the bone metabolism by modulating both osteoclast and osteoblast function. Furthermore, it is suggested that G-CSF is a potent modulator of the BMP-2 signal pathway in vivo.

Animals↗

PubMed2001

SOCS-1, a negative regulator of the JAK/STAT pathway, is silenced by methylation in human hepatocellular carcinoma and shows growth-suppression activity.

Hepatocellular carcinoma (HCC) is a major cause of cancer death, but the molecular mechanism for its development beyond its initiation has not been well characterized. Suppressor of cytokine signaling (SOCS-1; also known as JAB and SSI-1) switches cytokine signaling 'off' by means of its direct interaction with Janus kinase (JAK). We identified aberrant methylation in the CpG island of SOCS-1 that correlated with its transcription silencing in HCC cell lines. The incidence of aberrant methylation was 65% in the 26 human primary HCC tumor samples analyzed. Moreover, the restoration of SOCS-1 suppressed both growth rate and anchorage-independent growth of cells in which SOCS-1 was methylation-silenced and JAK2 was constitutively activated. This growth suppression was caused by apoptosis and was reproduced by AG490, a specific, chemical JAK2 inhibitor that reversed constitutive phosphorylation of STAT3 in SOCS-1 inactivated cells. The high prevalence of the aberrant SOCS-1 methylation and its growth suppression activity demonstrated the importance of the constitutive activation of the JAK/STAT pathway in the development of HCC. Our results also indicate therapeutic strategies for the treatment of HCC including use of SOCS-1 in gene therapy and inhibition of JAK2 by small molecules, such as AG490.

Antineoplastic Agents↗

PubMed2001

A member of the YER057c/yjgf/Uk114 family links isoleucine biosynthesis and intact mitochondria maintenance in Saccharomyces cerevisiae.

BACKGROUND: Two paralogs, YIL051c and YER057c, in the Saccharomyces cerevisiae genome are members of the YER057c/Yigf/Uk114 family, which is highly conserved among Eubacteria, Archaea and Eukarya. Although the molecular function of this protein family is not clear, previous studies suggest that it plays a role in the regulation of metabolic pathways and cell differentiation. RESULTS: Yil051cp is 70% identical in amino acid sequence to Yer057cp, and differs in that the former is longer by 16 amino acids containing, in part, the mitochondrial targeting signal at the N-terminus of the protein. An HA-tagged protein of Yil051cp is localized strictly in mitochondria, while that of Yer057cp is found in both cytoplasm and nucleus. Disruption of YIL051c (yil051cDelta) resulted in severe growth retardation in glucose medium due to isoleucine auxotroph, and no growth in glycerol medium due to the loss of mitochondria. An extract prepared from yil051cDelta cells showed no transaminase activity for isoleucine, while that for valine or leucine was intact. Haploid yil051cDelta cells newly isolated from the YIL051c/yil051cDelta hetero-diploids gradually lost mitochondrial DNA within 24 h in the absence of, but not in the presence of, an isoleucine. Mutants either requiring leucine (leu2-112) or isoleucine-valine (bat1Delta, bat2Delta) in a YIL051c background showed no changes in mitochondrial DNA maintenance in the absence of requirements. CONCLUSIONS: Based on these results, we named Yil051c as Ibm1 (Isoleucine Biosynthesis and Mitochondria maintenance1) and concluded that: (i) Ibm1p determines the specificity of isoleucine biosynthesis, probably at the transamination step, (ii) Ibm1p is required for the maintenance of mitochondrial DNA when isoleucine is deficient, and (iii) Isoleucine compensates for the lack of Ibm1p. Taken together, Ibm1p may act as a sensor for isoleucine deficiency as well as a regulator determining the specificity for branched amino acid transaminase.

Amino Acid Sequence↗

PubMed2001

Involvement of platelet activation in experimental osteonecrosis in rabbits.

Osteonecrosis (ON) was produced experimentally in rabbits by intravenous injection of platelet activating factor (PAF) in combination with lipopolysaccharides (LPS) on two occasions separated by a week-long interval. Eleven of 15 rabbits (73%), with administration of both LPS (50 microg/kg) and PAF (10 microg/kg), exhibited microcirculatory injuries including extravasation of erythrocytes into sinusoidal spaces and formation of microthrombi in arterioles near regions of erythrocyte extravasation. Seven of 15 rabbits (47%), which received both LPS (50 microg/kg) and PAF (10 microg/kg), exhibited necrosis of trabeculae and 8 of 15 (53%) exhibited bone marrow necrosis. In addition, PAF receptor antagonist (0.3 and 3.0 mg/kg) significantly reduced the incidence of trabecular necrosis (0%) in this model. The findings of the present study suggest that platelet activation may play an important role in inducible ON, and that suppression of platelet activation may contribute prevention of ON.

Animals↗