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Biomedical subjects

H Takayama

Publications and source records attributed to H Takayama.

At least 163 records · Page 9Linked to original sources

[Retroperitoneal mucinous cystadenocarcinoma associated with horseshoe kidney: a case report].

We report a case of retroperitoneal mucinous cystadenocarcinoma in a patient with a horseshoe kidney. A 61-year-old woman was admitted to our hospital for examination and therapy of an abdominal mass. Various examinations revealed, a retroperitoneal tumor and a horseshoe kidney. Open surgery was performed. Pathological findings revealed mucinous cystadenocarcinoma. We review and discuss 17 cases of retroperitoneal mucinous cystadenocarcinoma, which have been reported in Japan.

Cystadenoma, Mucinous↗

[Tumor enucleation for intrapelvic schwannoma: a report of two cases].

A 65-year-old man and a 35-year-old woman were diagnosed with intrapelvic tumors originating from the sacral nerves by computed tomographic (CT) scan, magnetic resonance imaging (MRI) and angiography. These tumors were tightly adhered to the iliac arteries and veins and could not be resected completely. Since the cryostat sections revealed benign schwannomas histopathologically, we enucleated the tumors without the pseudocapsules. All of the 57 intrapelvic schwannomas previously reported in Japan were resected with pseudocapsules. Both of our patients showed improvement of subjective symptoms, but should be followed up and examined for the presence of regrowth of tumors.

Adult↗

Hepatocyte growth factor/scatter factor overexpression induces growth, abnormal development, and tumor formation in transgenic mouse livers.

To investigate the in vivo role of hepatocyte growth factor/scatter factor (HGF/SF) in liver function, we generated transgenic mice using a mouse HGF/SF cDNA under the control of the mouse metallothionein gene promoter and 5'/3' flanking sequences. In adult HGF/SF transgenic mice, liver weight as a percentage of total body weight was at least twice that of wild-type mice. Comparison of transgenic and control liver morphology revealed dramatic heterogeneity in the size and appearance of hepatocytes as a distinctive feature of HGF/SF overexpression. Transgenic livers exhibited a significant increase in the number of small hepatocytes with a 2N DNA content, accounting for the observed increase in liver mass. The DNA labeling index of hepatocytes increased 11-fold at 4 weeks of age, when liver enlargement first became apparent, and was still elevated about 5-fold in adult HGF/SF transgenic mice. Moreover, hepatocytes isolated by perfusion of transgenic livers doubled every 2 days in culture, whereas little or no growth was observed with isolated control hepatocytes. The mechanistic basis of hepatocyte proliferation was elucidated as the chronic activation of the c-met proto-oncogene product. Met and substrates such as phosphatidylinositol 3-kinase, Src homology and collagen-like, pp60c-src, focal adhesion kinase p125FAK, and paxillin were associated with tyrosine-phosphorylated complexes in a hepatocyte cell line established from the transgenic liver. This proliferative stimulus triggered the formation of hepatocellular adenomas and/or carcinomas in most transgenic mice > or = 1.5 years of age. Finally, the rate of transgenic mouse liver regeneration was increased 3-fold over control livers following partial hepatectomy.

Adaptor Proteins, Signal Transducing↗

[Prostatic cancer with cystic formation: a case report].

A 60-year-old man was admitted to our hospital with the chief complaints of dysuria and sense of abdominal fullness. On digital rectal examination, an enlarged prostate with a smooth surface and elasticity was palpated. The concentration of prostate specific antigen (PSA) was elevated to 78 ng/ml. Pelvic computed tomographic (CT) scan and magnetic resonance imaging (MRI) revealed a large prostate, 8 cm in diameter, with a cystic mass, and extra-iliac lymph node swelling. On needle biopsy of the prostate and cyst, the histology was poorly differentiated adenocarcinoma, and the aspirate comprised bloody fluid with a negative test for cytology. He was diagnosed with prostatic cancer of T4N3M0. This is the 19th case of prostatic cancer with cystic formation reported in Japan.

Adenocarcinoma↗

Cyclic AMP-insensitive activation of c-Src and Syk protein-tyrosine kinases through platelet membrane glycoprotein VI.

Platelet glycoprotein (GP) VI is a so-far uncharacterized 62-kDa membrane protein, whose deficiency results in selective impairment in collagen-induced platelet aggregation. Our group previously reported a human polyclonal antibody (anti-p62 IgG) that induces activation of normal, but not of GPVI-deficient, platelets in an Fc-independent manner. The F(ab')2 fragments of this antibody (F(ab')2-anti-p62) stimulated tyrosine phosphorylation of numerous proteins, which was not prevented even in the presence of cAMP-increasing agents such as prostacyclin. Pretreatment of platelets with the protein-tyrosine kinase (PTK) inhibitor tyrphostin A47 completely abolished F(ab')2-anti-p62-induced platelet aggregation in parallel with dose-dependent inhibition of protein-tyrosine phosphorylation, indicating an essential requirement of PTK activity for generating GPVI-mediated signaling. We found that two cytosolic PTKs, c-Src and Syk, became rapidly activated in response to F(ab')2-anti-p62 in a way insensitive to elevation of cAMP. In contrast, in the presence of prostacyclin, F(ab')2-anti-p62 did not stimulate tyrosine phosphorylation of the focal adhesion kinase. cAMP-insensitive activation of c-Src and Syk was also observed in collagen but not thrombin-stimulated platelets. Moreover, either F(ab')2-anti-p62 or collagen stimulated cAMP-insensitive tyrosine phosphorylation of phospholipase C-gamma 2. These results indicate that the receptor-mediated activation of several PTKs in platelets is regulated through a cAMP-sensitive or -insensitive mechanism depending on the nature of each stimulus, and also suggest that GPVI engagement is coupled to cAMP-insensitive activation of c-Src and Syk accompanied by tyrosine phosphorylation of numerous substrates including phospholipase C-gamma 2 in a manner similar to collagen stimulation.

Adult↗

Thrombopoietin, c-Mpl ligand, induces tyrosine phosphorylation of Tyk2, JAK2, and STAT3, and enhances agonists-induced aggregation in platelets in vitro.

We investigated in vitro effects of recombinant human thrombopoietin (TPO), or c-Mpl ligand, on human platelets. TPO induced rapid dose-dependent tyrosine phosphorylation of several proteins. We identified Janus tyrosine kinases, Tyk2 and JAK2, and a member of STAT (signal transducers and activators of transcription) family, STAT3, as the tyrosine-phosphorylated proteins in response to TPO. TPO by itself did not cause platelet aggregation and shape change, but augmented ADP-induced aggregation in a dose-dependent manner. Acetylsalicylic acid inhibited the secondary aggregation enhanced by TPO, but not the TPO-induced potentiation of the primary aggregation. TPO modulates platelet activation possibly through protein-tyrosine phosphorylation.

Aspirin↗

Differential regulation of protein-tyrosine phosphatases by integrin alpha IIb beta 3 through cytoskeletal reorganization and tyrosine phosphorylation in human platelets.

The major platelet integrin alpha IIb beta 3 (glycoprotein IIb-IIIa) has been implicated in the regulation of tyrosine phosphorylation and dephosphorylation in activated platelets. To investigate the mechanisms of the alpha IIb beta 3-dependent tyrosine dephosphorylation, normal platelets or thrombasthenic platelets lacking alpha IIb beta 3 were stimulated with thrombin and fractionated into Triton X-100-soluble or -insoluble subcellular matrices. We then examined the kinetics of the tyrosine-phosphorylated proteins and distribution of protein-tyrosine phosphatases in these fractions and whole cell lysates. First, alpha IIb beta 3-dependent tyrosine dephosphorylation was recovered mainly in the cytoskeleton with similar kinetics to the whole cell lysate. Second, protein-tyrosine phosphatase (PTP) 1B and its cleaved 42-kDa form were associated with the cytoskeleton in an aggregation-dependent manner, whereas association of PTP1C with the cytoskeleton was regulated differentially both by thrombin stimulation and by alpha IIb beta 3-mediated aggregation. Several calpain inhibitors did not affect either tyrosine phosphorylation and dephosphorylation or relocation of PTP1B, but they did inhibit cleavage of PTP1B. Cytochalasin D blocked relocation of both PTP1B and PTP1C but not PTP1B cleavage. SH-PTP2 was distributed in the other fractions than the cytoskeleton and showed no relocation on thrombin stimulation. Finally, the cytoskeleton-associated PTP1C became tyrosine-phosphorylated in an alpha IIb beta 3-mediated aggregation-dependent manner. Thus, integrin alpha IIb beta 3 was involved differentially in the regulation of PTP1B and PTP1C.

Adult↗

Dinoflagellate Alexandrium tamarense as the source of paralytic shellfish poison (PSP) contained in bivalves from Hiroshima Bay, Hiroshima Prefecture, Japan.

In April 1993, a phytoplankton dinoflagellate was isolated from Hiroshima Bay, Hiroshima Prefecture, Japan, and unambiguously identified as Alexandrium tamarense on the basis of the morphological characteristics. The dinoflagellates, cultures in modified SW-2 medium at 15 degrees C for 15 days, showed a specific toxicity of 30.7 x 10-6 MU/cell. HPLC analysis demonstrated that the toxin was composed mainly of gonyautoxin-4 (GTX4) and protogonyautoxin-2 (PX2 or GTX8)(27.6 and 37.0 mole%, respectively). Total toxin concentration of this strain was 39.5 fmole/cell. Short-necked clams, mussels, and oysters contaminated by the dinoflagellate showed a more complicated composition, with GTX1 as the major component (61.8 mole% for short-necked clams, 60.5 mole% for mussels, 42.5 mole% for oysters), and PX2 was only present in trace amounts.

Animals↗

Functional significance of platelet membrane glycoprotein p62 (GP VI), a putative collagen receptor.

We previously suggested that platelet 62 kDa protein (p62, GP VI) is a putative collagen receptor by the studies on platelets and antiplatelet antibody in a patient (YA) with idiopathic thrombocytopenic purpura (ITP) who showed defective collagen-induced platelet function. Herein, we confirm that p62/p57 (reduced/unreduced conditions) is a specific membrane protein recognized by YA antibody using an improved immunoprecipitation technique. To further study the functional role of this protein, a crude p57 fraction ('p57') was obtained from human platelets by serial chromatography including DEAE-Sepharose CL-6B and WGA-agarose followed by preparative sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE). This 'p57' diminished the platelet-aggregating activity of collagen and of YA immunoglobulin G (IgG). N-terminal amino acid sequence analysis of 'p57' showed that it contained intercellular adhesion molecule 2 (ICAM-2). Immunoprecipitation experiments using platelet lysates and anti-ICAM-2 monoclonal antibody demonstrated that ICAM-2 molecules had a molecular weight similar to p62 on SDS-PAGE. However, ICAM-2 was also expressed on YA's p62-deficient platelets both on immunoprecipitation and flow cytometric analysis. Thus, ICAM-2 seems to be different from p62.

Amino Acid Sequence↗

Basic fibroblast growth factor increases dopaminergic graft survival and function in a rat model of Parkinson's disease.

The clinical use of fetal neural grafts as an intracerebral source of dopamine for patients with Parkinson's disease has met with limited success. Since basic fibroblast growth factor (bFGF) enhances the survival and growth of dopaminergic neurons in vitro, we explored whether cells genetically modified to produce bFGF would improve the functional efficacy of dopaminergic neurons implanted into rats with experimental Parkinson's disease. Results show that bFGF-producing cells grafted together with fetal dopamine neurons have potent growth-promoting effects on the implanted neurons in vivo. Moreover, rats implanted with such co-grafts display the most pronounced behavioural improvements post-grafting. These findings not only provide insight into the function of bFGF in situ, but also suggest an approach for enhancing the survival and function of dopamine neurons grafted into the damaged brain.

Animals↗

Expression of biologically active basic fibroblast growth factor by genetically modified rat primary skin fibroblasts.

Basic fibroblast growth factor (FGF-2) is normally expressed as a cell-associated protein, and accordingly it is not clear how it exerts its action on target cells in vivo. It has been proposed that cells release, by death or other mechanisms, small amounts of FGF-2 that then acts in an autocrine manner. To address the question of whether it is necessary that FGF-2 remain cell associated or needs to be secreted from cells to have biological activity, we expressed the 18-kDa form of FGF-2 in primary fibroblasts as a cell-associated (FGF-2-B) or as a secreted (FGF-2-S) protein. FGF-2 protein is detected in cell lysates and membrane fractions of both cell types, whereas it is present in significant amounts only in the conditioned medium of FGF-2-S cells. No FGF-2 is detected in control (untransfected) cells. FGF-2-S cells also grow faster than the control of FGF-2-B cells. Yet, when evaluated for their ability to promote the survival of embryonic hippocampal neurons in vitro, both the cell types are active, establishing the activity of the transgene product. We conclude that FGF-2 is active when engineered to be expressed as a cell-associated form or secreted from cells.

Animals↗

Potent and specific inhibition of human immunodeficiency virus type 1 replication by 4-(2,6-dichlorophenyl)-1,2,5-thiadiazol-3-Y1 N,N-dialkylcarbamate derivatives.

4-(2,6-Dichlorophenyl)-1,2,5-thiadiazol-3-yl N,N-dialkylcarbamate (TDA) derivatives were found to be highly potent and specific inhibitors of human immunodeficiency virus type 1 (HIV-1) replication in a variety of cell cultures. The most potent congener of TDA derivatives, RD4-2024, inhibited HIV-1 replication by 50% at concentrations of 12.5 and 4.8 nM in MT-4 cells and peripheral blood mononuclear cells, respectively. These concentrations were more than 2,000- and 30,000-fold lower than its 50% cytotoxic concentrations, respectively. Although the TDA derivatives were active against 3'-azido-3'-deoxythymidine-resistant HIV-1, no antiviral activities were observed against HIV-2 and nonnucleoside reverse transcriptase inhibitor-resistant mutants of HIV-1. The TDA derivatives inhibited recombinant HIV-1 reverse transcriptase activity, depending on the template-primer used for the assay. However, they did not interact with HIV-2 reverse transcriptase. Thus, the TDA derivatives belong to the family of nonnucleoside reverse transcriptase inhibitors. Because of their potent anti-HIV-1 activities in vitro and their low levels of toxicity in mice, the TDA derivatives deserve further evaluation as candidate drugs for the treatment of patients with AIDS.

Antiviral Agents↗

Effects of alkaloids extracted from the stem bark of Hunteria zeylanica on acute inflammation in experimental animals.

The effects of crude alkaloids extracted from the stem bark of Hunteria zeylanica GARD. (H. zeylanica) on acute inflammatory responses such as carrageenin-induced paw edema in rats and croton oil- and arachidonic acid-induced ear edema in mice were investigated. Oral administration of H. zeylanica alkaloid extract (200-400 mg/kg) significantly suppressed the paw swelling induced by carrageenin. In the croton oil-induced ear edema, topically applied H. zeylanica alkaloid extract, at doses of 200 and 400 mg/ml, also significantly reduced ear edema. Moreover, the extract (50-200 mg/kg, p.o.) reduced in a dose-dependent manner the ear swelling induced by topically applied arachidonic acid (2 mg/ear). These results suggest that the inhibitory effects of H. zeylanica alkaloid extract on acute edema formation are partly due to inhibition of 5-lipoxygenase and cyclooxygenase activity.

Alkaloids↗

Inhibitory effect of alkaloids extracted from the stem bark of Hunteria zeylanica on 5-lipoxygenase activity in vitro.

The effects of alkaloid extract from the stem bark of Hunteria zeylanica Gard. (H. zeylanica) on the activities of cyclooxygenase and 5-lipoxygenase in A23187-stimulated rat mast cells were investigated. H. zeylanica alkaloid extract (0.3-300 micrograms/ml) inhibited leukotriene C4 (LTC4) production by 5-lipoxygenase in a concentration-dependent manner and it blocked the production by 50% at 300 micrograms/ml. On the other hand, the extract had no effect on prostaglandin D2 (PGD2) production by cyclooxygenase. Neither (-)-eburnamine nor pleiomutinine, major constituents of H. zeylanica alkaloid extract, inhibited the production of PGD2 and LTC4 in the A23187-stimulated mast cells. The inhibition of arachidonic acid metabolism via 5-lipoxygenase pathway may be due to minute amounts of other components as stated in the Discussion.

Alkaloids↗

[A case of bladder cancer producing alpha-fetoprotein (AFP)].

The high incidence of increased level of AFP in association with primary hepatoma and embryonic tumors of the ovary and testis is well recognized, but elevated AFP is very uncommon in bladder cancer. A 74-year-old man, diagnosed with transitional cell carcinoma of the bladder, showed an increased level (410 ng/ml) of circulating AFP. After partial cystectomy, the high level of AFP returned to the normal value. The AFP level remained normal for 4.5 years after surgery and no recurrence of bladder cancer was seen by the cystoscopy. X-ray and ultrasound examination has revealed no evidence of neoplasm in the other organs. AFP producing localization was detected in bladder cancer cells by the use of immunocytochemical technique with the avidin-biotin method.

Aged↗

[Giant schwannoma in the pelvic cavity presenting as renal failure: a case report].

A case of giant schwannoma in the pelvic cavity detected with renal failure is reported. A 50-year-old man was referred to another clinic with chief complaints of general fatigue and edema of the face and dorsa of the feet. On March the 4th 1994, he was hospitalized in the clinic because of renal failure. Bilateral hydronephrosis and a giant pelvic tumor were found by computed tomography (CT) and ultrasonography. Because bilateral percutaneous nephrostomies failed to recover his renal function, he was referred to our clinic for the purpose of hemodialysis and the further examination of the tumor on March 16, 1994. The pelvic angiography showed that the tumor was fed by the vessel from the left internal iliac artery. After the chemo-embolization from the feeding artery, tumor resection was performed on May 9, 1994. The tumor was 16x13x10 cm in size, and 1,110 g in weight. The histological findings of the tumor revealed the mixed type schwannoma of Antoni A and B. Six months after the operation, he has had no tumor recurrence. This is a rare case of pelvic schwannoma which was detected with renal failure. We reviewed and discussed 56 cases of schwannoma in the pelvic cavity, including our case, in the Japanese literature.

Humans↗