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Biomedical subjects

S Yoshida

Publications and source records attributed to S Yoshida.

At least 955 records · Page 53Linked to original sources

Herbimycin A inhibits phorbol ester-induced morphologic changes, adhesion, and megakaryocytic differentiation of the leukemia cell line, MEG-01.

12-O-Tetradecanoylphorbol 13-acetate (TPA) induces rapid changes in the morphology of the human megakaryoblastic leukemia cell line, MEG-01, as well as changes in adhesion and megakaryocytic differentiation. To investigate the signal transduction pathway of these three phenomena, we studied the effect of herbimycin A, an inhibitor of tyrosine kinase (TK) and the effects of calphostin C, a specific inhibitor protein kinase C (PKC) on TPA treated MEG-01 cells. Both herbimycin A and calphostin C inhibited all three TPA-induced phenomena, suggesting that both pathways are required for these phenomena. Herbimycin A but not calphostin C blocked the tyrosine phosphorylation of cellular proteins. Immunohistochemical staining of PKC using an anti-PKC monoclonal antibody showed that herbimycin A did not interfere with the translocation and subsequent down regulation of PKC induced by TPA, suggesting that the TPA-induced effect on PKC (translocation and probably its activation) is not dependent on TK. Induction of c-fos and c-jun expression by TPA was inhibited by both herbimycin A and calphostin C, suggesting that both PKC and TK pathways are necessary for the induction of the TPA-induced transcription factor AP1, which is a known TPA-inducible early immediate gene product. Taken together, our results show that the tyrosine kinase signal transduction system as well as the PKC pathway is indispensable for the TPA-induced phenomena of morphologic change, cell attachment, early immediate gene expression, and lineage-specific phenotypic expression in the MEG-01 cell line.

Benzoquinones↗

[Therapeutic efficacy of zinc picolinate in patients with taste disorders].

We studied the therapeutic efficacy of zinc picolinate in patients with zinc-deficient and idiopathic taste disorders. Efficacy was assessed in a double-blind study. The following findings were obtained: 1. There was a significant difference between the zinc picolinate and placebo groups in the grade of improvement shown by the filter-paper disk method. 2. There was a significant difference between the zinc picolinate and placebo groups in the serum zinc concentration. 3. There was no significant difference between the two groups in the degree of total subjective recovery or the grade of improvement, as shown by in the whole mouth method. 4. We conclude that the administration of zinc picolinate is effective for patients with zinc-deficient and idiopathic taste disorders.

Double-Blind Method↗

Effect of modified LDL on the release of NO and PGI2 from rat peritoneal macrophages.

Nitric oxide (NO) and prostacyclin (PGI2) have vasodilative and anti-proliferative effects on smooth muscle cells (SMC) and an anti-aggregating action on platelets. The present study was designed to elucidate the influence of modified low density lipoprotein (LDL) on the release on NO and PGI2 from rat peritoneal macrophages. Cholesteryl ester (CE) content in macrophages markedly increased on incubation with acetylated LDL (ac-LDL), while NO release did not change. Although incubation with mildly oxidized LDL (m-ox-LDL) and highly oxidized LDL (h-ox-LDL) increased CE content in macrophages, only incubation with h-ox-LDL reduced NO release. PGI2 release from macrophages was not affected by incubation with ac-LDL, m-ox-LDL or h-ox-LDL. These results indicate that the degree of suppression of NO release in macrophages by modified LDL is related to the extent of oxidative modification of LDL itself, but not to the extent of the accumulation of CE in macrophages. Although the role of NO released from macrophages in atherosclerosis is still unclear, the observation of reduced production of NO from macrophages in response to ox-LDL may provide new insight into the role of ox-LDL in the pathogenesis of atherosclerosis.

Animals↗

[Development of apoptosis induced by whole-body irradiation in murine liver].

Apoptosis is known to be induced by radiation. However, the correlation between radiation-induced apoptosis and radiation injury in tumors in vivo has been unclear. In this paper, we report the study of apoptosis induced by whole-body irradiation using an immunohistochemical technique to detect DNA fragmentation in murine liver. A dose of 7 Gy was employed as LD50/30. DNA fragmentation was observed 30 min after radiation, and it peaked between 1 and 6 hours. DNA fragmentation could be detected 48 hours after radiation in capillary endothelium. This study was able to reveal the development of radiation-induced apoptosis in the liver by detecting DNA fragmentation in situ.

Animals↗

Differential effects of TGF-beta 1 on normal and leukemic human hematopoietic cell proliferation.

We evaluated the effects of transforming growth factor-beta 1 (TGF-beta 1) on the growth of hematopoietic progenitors in normal donors and in patients with hematologic malignancies now designed as clonal disorders of multipotential stem cells. TGF-beta 1 at 80 pM exhibited differential effects on the normal hematopoietic progenitors when cells were stimulated with different growth factors, such as G-CSF, GM-CSF, interleukin-3 (IL-3), or stem cell factor (SCF). The suppressive effect by TGF-beta 1 was increased for growth with GM-CSF, IL-3, and SCF, and growth with G-CSF was unaffected in hematologic malignancies, TGF-beta 1 suppression for growth with G-CSF was increased for essential thrombocythemia (ET) and polycythemia vera; chronic myelogenous leukemia (CML) in chronic phase; CML in accelerated phase; CML in myeloid crisis; myelodysplastic syndrome (MDS) in refractory anemia; MDS in refractory anemia with an excess of blasts; and acute myeloblastic leukemia (AML). In CML-myeloid crisis and AML, TGF-beta 1 almost completely abolished the growth, with some patient-to-patient variation. The mean ED50s for the growth of leukemic blast progenitors were 1.6, 1.2, 0.7, and 0.2 pM in the presence of G-CSF, GM-CSF, IL-3, and SCF, respectively, c-myc and c-myb antisense oligonucleotides significantly suppressed the growth of leukemic blast progenitors, but not that of clonogenic cells from normal donors and patients with ET. We also demonstrated that TGF-beta 1 inhibits mRNA expression by AML blasts for c-myc and/or c-myb. When the data are taken together, growth suppression by TGF-beta 1 appears to increase with the progression of clonal evolution in hematologic malignancies.

Base Sequence↗

Dual-isotope SPECT of skull-base invasion of head and neck tumors.

UNLABELLED: Skull-base invasions of head and neck tumors were examined by simultaneous bone and tumor dual-isotope SPECT (S-SPECT) with 99mTc-hydroxy-methylene-diphosphonate (99mTc-HMDP) and 201Tl-chloride. The effectiveness and reliability of tumor diagnosis by this method was the primary interest in this study. METHODS: Before S-SPECT imaging, a phantom experiment using dried skull-bone specimens was performed to establish anatomical details of the skull base with the SPECT camera. Radionuclide crosstalk, window widths and control patients were also examined prior to S-SPECT imaging. Twenty patients with suspected tumor invasion of the skull base underwent S-SPECT. RESULTS: Preliminary experiments revealed that crosstalk effects could be disregarded with adequate window width and routine administrative doses of the radionuclides. S-SPECT detected bone destruction and the extent of tumor invasion for all 12 patients in whom skull-base involvement was diagnosed by CT or MRI. For the three patients in whom CT or MRI revealed no tumor invasion, the S-SPECT images did not show any abnormal accumulation in similar regions. In the remaining five patients without CT and MRI confirmation of skull-base invasion, the S-SPECT findings showed skull-base abnormalities in three. Tumor invasion was confirmed surgically or by clinical follow-up. The remaining two patients had negative S-SPECT images. CONCLUSION: S-SPECT is an effective and reliable diagnostic technique for detecting tumor invasion in the complex bony regions of the skull base.

Adult↗

Incidence and characteristics of clonal hematopoiesis in remission of acute myeloid leukemia in relation to morphological dysplasia.

We studied 34 patients in remission of acute myeloid leukemia (AML) by performing clonal analysis of peripheral blood polymorphonuclear (PMN) cells and mononuclear (MN) cells, using X-linked DNA polymorphisms, in conjunction with the assessment of morphological myelodysplastic changes, performed by a scoring method. Nine patients demonstrated a non-random or skewed X-chromosome inactivation pattern in PMN cells. Three of these nine patients had an apparently random pattern in MN cells (group A), whereas the remaining six patients demonstrated no difference between the inactivation patterns of PMN and MN cells (group B). The PMN cells of the other 25 patients showed a random X-chromosome inactivation pattern, and the patterns of the PMN cells did not differ from those of the MN cells (group C). The scores for myelodysplasia were high (> or = 4) in all three patients in group A, intermediate (2-3) in two patients and low (score < 2) in four patients in group B, and intermediate in five patients and low in 20 patients in group C. The duration of remission in patients with a myelodysplasia score of > or = 2 was significantly shorter than that of patients with a score of < 2 (P < 0.01). We conclude that clonal remission actually occurs with myelodysplastic features in some patients with AML (around 10%, group A). It is possible that this clonal analysis may not be sensitive enough to detect the preleukemic clone with myelodysplastic features when this clone constitutes only a minor population of remission hematopoiesis. To further elucidate the biology of such preleukemic clones it is essential to develop more sensitive molecular methods for the detection of genetic abnormalities specific to preleukemic hematopoiesis.

Adolescent↗

[A study of chemotherapy for patients with severely advanced gastric cancer--comparison of chemotherapy and route].

We analyzed the clinical response, toxicities, ambulatory and overall survival time among 51 patients with inoperable gastric cancer, to evaluate chemotherapies and drug delivery routes. Twenty-nine patients were treated by Methotrexate/5-FU (FMTX) therapy and 22 by 5-FU/CDDP (FP) therapy. Twenty-five patients were treated by intra-arterial (IA) route and 26 by intra-venous (IV). The response rate of IA therapy was higher than that of IV therapy (p < 0.05), 48% and 19%, respectively. Median survival times of FMTX and FP were 361 and 289 days, respectively, and the 1-year survival rates of FMTX and FP were 44% and 33%, respectively, with no significant differences. Duration of home chemotherapy with FMTX was longer than that with FP, at 130 and 85 days, respectively. There was no difference between duration of home chemotherapy of IA and that of IV. IA chemotherapy showed a higher response rate than IV, but there were no differences in the incidence of side effects and ambulatory and overall survival time.

Antineoplastic Combined Chemotherapy Protocols↗

Immunohistochemical study of p53 expression in cancer tissues from patients undergoing radiation therapy.

Immunostaining using p53 monoclonal antibodies (p53(Ab-3) recognizes mutant type and p53(Ab-6) the wild type of p53 protein) was performed on frozen sections of biopsy specimens obtained before and during preoperative radiotherapy from 23 patients with head and neck squamous cell carcinoma. The positive staining rates of p53(Ab-3) before radiotherapy and at radiation doses of 4Gy, 10Gy and 20Gy were 30.0%, 38.9%, 25.0% and 6.25%, and those of p53(Ab-6) 10.5%, 11.8%, 5.0% and 0% respectively. The relationship between the immunohistochemical findings and antitumor effect at radiation dose of 20Gy was examined on the correspondent haematoxylin-eosin sections. In patients whose p53(Ab-3) stainings were positive at any doses of radiotherapy, the antitumor effect at the cumulative dose of 20Gy waas either remarkable or effective. Moreover, the frequency of the expression of mutant type p53 protein tended to increase in rather radiosensitive tumors. As for wild type p53 protein, there was no remarkable relationship between the staining of p53(Ab-6) and the antitumor effect.

Adult↗

External radiotherapy for biliary decompression of hilar cholangiocarcinoma.

Obstructive jaundice due to hilar cholangiocarcinoma is difficult to decompress because of the location of the tumor. We used external radiation alone for biliary decompression and reviewed its efficacy in this study. Subjects comprised 14 patients diagnosed as having inoperable hilar cholangiocarcinoma by ultrasonography, percutaneous transhepatic cholangiography, and CT scanning. The total bilirubin level on admission ranged from 0.4 to 34.6 mg/dl (mean: 11.0 mg/dl). These patients were irradiated with a 4MeV linear accelerator using parallel opposing fields measuring from 7 x 7 cm to 8 x 10 cm. The total radiation dose ranged from 50 Gy to 60 Gy and in fractions of 1.8-2.0 Gy per day. No patient underwent further biliary decompression after percutaneous transhepatic cholangiography, and irradiation was performed immediately after diagnosis. Eleven of the 14 patients received the full dose of external radiation. Three patients discontinued radiotherapy because of severe vomiting and nausea, pneumonia, and a hemorrhagic gastric ulcer. In 10 of the 11 patients, the serum total bilirubin level returned to normal (p < 0.005) and no cholangitis occurred. Obstructive jaundice recurred in one patient, and serum total bilirubin returned to normal again after further irradiation. Eight of the 11 patients could be discharged from hospital and returned to society. The survival time of the 11 patients ranged from 3 to 25 months and the 12-month survival rate was 50% (Kaplan-Meier method). This study suggests that external radiation therapy is an effective treatment for biliary decompression in patients with unresectable hilar cholangiocarcinoma.

Aged↗

[Intravesical instillation of epirubicin hydrochloride in superficial bladder tumor--prophylactic and therapeutic instillation for carcinoma in situ].

Between May 1990 and May 1993 we performed intravesical instillation of epirubicin hydrochloride (EPI) to 52 patients with superficial bladder tumor after transurethral resection. Indications of these instillations were classified into 3 groups. Group 1 was for carcinoma in situ (CIS) or the CIS other than the original tumor, group 2 was for multiple tumors, and group 3 was for pT1G3 tumor. Intravesical instillations of the drug were given weekly for 10 weeks and close follow-up examinations were performed routinely. Group 1 was treated for CIS, whereas group 2 and group 3 were prophylactic instillations. The disease-free rate in group 1 was 67%, and that in group 2 and group 3 was 77% at 12 months, and 42% at 24 months according to the Kaplan-Meier method. The major side effects of the instillations were bladder irritation, hematuria and pyuria. However, we experienced 5 patients with severe side effects; 2 of atrophic bladder and 3 of hemorrhagic cystitis. Although this study was conducted retrospectively, these findings suggest that intravesical instillations of EPI can be as effective as other drugs, such as mitomycin C, and doxorubicin, by adding the maintenance instillation or by elevating the drug density and shortening the instillation time.

Administration, Intravesical↗

[Primary oculomotor nerve palsy due to head injury: analysis of 10 cases].

Ten cases of primary oculomotor nerve palsy due to head injury are presented. All ten patients had a dilated, non reactive pupil. Seven had complete oculomotor palsy. Two had partial extraocular palsy or blepharoptosis and one had neither extraocular palsy nor blepharoptosis. The initial ophthalmoplegia was recognized immediately after trauma. Nine patients had severely impaired consciousness on admission, but eight patients recovered fully within two months after the traumatic event, while one patient remained disoriented. Emergency CT scan on admission showed mass lesions in no patients except one who had a hematoma measuring 3 cm in the frontal lobe, but had no herniation sign. Patients with complete oculomotor palsy had a high incidence of traumatic SAH (71%) or skull fracture (57%). Recovery from third nerve palsy was not so good. The follow-up period extended from 3 months to 18 months. Of the 10 patients, none recovered completely from third nerve palsy. The prognoses of blepharoptosis, external ophthalmoplegia and internal ophthalmoplegia were analyzed separately. The recovery rates were 78%, 44% and 20%, respectively, the internal ophthalmoplegia showing poorest recovery. We discuss the mechanism of direct injury to the oculomotor nerve.

Adult↗

[Effect of low dose CDDP/5-fluorouracil therapy on PCNA labeling index and TS inhibition rate of gastric cancer].

The response of gastric cancer to intravenous application of low-dose CDDP plus 5-fluorouracil (FP) was assessed by changes in DNA indices (DIs) and PCNA labeling indices (LIs) by flow cytometry, and by the thymidylate synthetase inhibition rate (TSIR). Pretherapy samples were compared to specimens resected at operation. FP therapy was performed in 10 of 26 specimens and not in the others (C). There was no difference between change in DIs of FP group and that of C group. In FP group, PCNA LI of resected specimen was higher than that of biopsy, although they showed almost the same values in C group. Change in PCNA LIs correlated to TSIR in FP group. These results suggest that FP therapy affects gastric cancer cells in PCNA LIs and TSIR, and that PCNA LIs could be an indicator of the effect of FP therapy as TSIR.

Antineoplastic Combined Chemotherapy Protocols↗

Expression and activity-dependent changes of a novel limbic-serine protease gene in the hippocampus.

A novel murine cDNA which encodes a protein designated neuropsin was cloned. Northern and in situ hybridization analyses demonstrated that neuropsin mRNA is expressed specifically in the limbic system of mouse brain and is localized at highest concentration in pyramidal neurons of the hippocampal CA1-3 subfields. Direct hippocampal stimulation and kindling induced by amygdaloid stimulation caused a significant bilateral change in neuropsin mRNA level in the hippocampal pyramidal neurons. The activity-dependent changes and the specific localization indicate that neuropsin is involved in hippocampal plasticity.

Amino Acid Sequence↗

[Leiomyosarcoma metastatizing to the sphenoid bone presenting exophthalmos: a case report].

A rare subcutaneous leiomyosarcoma metastatizing to the sphenoid bone and presenting exophthalmos is reported. A 56-year-old female presented with protrusion of the right eye and a slowly growing lump on the right temporal region. Six years previously, she had undergone removal of a subcutaneous mass in the back, which was histologically diagnosed in another hospital as leiomyosarcoma. She had undergone four other operations, including removal of local recurrences and a right renal metastasis. On admission, physical examination showed no neurological deficits. Craniogram revealed an osteolytic lesion without marginal sclerosis in the right sphenoid bone. CT showed an inhomogeneously enhanced mass with irregular expansion of the diploic space, which was partly invading the right orbit. MRI demonstrated an extradural mass in the right sphenoid region, which was slightly low-intense in T1-weighted image, high-intense in T2-weighted image, and inhomogeneously enhanced by Gd-DTPA. Right external carotid angiogram showed a highly vascular stain fed by meningeal arteries. Radionuclide bone scintigram showed multiple high-uptake areas in the left femoral head, the ribs, and the sphenoid bone. Preoperative embolization of the tumor vessels fed by the external carotid artery was performed. Following this procedure, the tumor stain disappeared completely. The tumor was totally excised with minimal bleeding through an orbitozygomatic approach. The tumor was loosely adherent to the dura and periorbit. The bone defect was covered with a methylmethacrylate resin plate. the histological examination demonstrated fascicular arrangement of the spindle shaped cells with mitotic figures. Immunohistochemical studies showed that most tumor cells were positive for actin and myosin, but negative for desmin.(ABSTRACT TRUNCATED AT 250 WORDS)

Exophthalmos↗