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Biomedical subjects

H Fukuda

Publications and source records attributed to H Fukuda.

At least 181 records · Page 10Linked to original sources

In vivo evaluation of carborane gadolinium-DTPA complex as an MR imaging boron carrier.

The evaluation of the Gd-carborane complex 2 as an MR imaging and boron carrier agent was carried out in vivo using tumor-bearing Donryu rats, MRI, ICP-AES, and alpha-autoradiography. The MR imaging revealed that the carborane Gd-DTPA 2 was metabolized slower in the body than Gd-DTPA 1. The results of the ICP-AES method indicated that compound 2 was incorporated into normal tissues and metabolized quickly, whereas it was not accumulated into tumor or brain tissue. The alpha-autoradiography showed that a high level of boron was obtained in the internal organs and in the necrosis of tumor tissue.

Animals↗

Improvement of productivity of active horseradish peroxidase in Escherichia coli by coexpression of Dsb proteins.

Coexpression of two classes of folding accessory proteins, molecular chaperones and foldases, can be expected to improve the productivity of soluble and active recombinant proteins. In this study, horseradish peroxidase (HRP), which has four disulfide bonds, was selected as a model enzyme and overexpressed in Escherichia coli. The effects of coexpression of a series of folding accessory proteins (DnaK, DnaJ, GrpE, GroEL/ES, trigger factor (TF), DsbA, DsbB, DsbC, DsbD, and thioredoxin (Trx)) on the productivity of active HRP in E. coli were examined. Active HRP was produced by very mild induction with 1 microM isopropyl-beta-D-thiogalactopyranoside (IPTG) at 37 degrees C, whereas the amount of active HRP produced by the induction with 1 mM IPTG was negligibly small. Active HRP production was increased significantly by coexpression of DsbA-DsbB (DsbAB) or DsbC-DsbD (DsbCD), while coexpression of molecular chaperones did not improve active HRP production. The growth of E. coli cells was inhibited significantly by the induction with 1 mM IPTG in a HRP single expression system. In contrast, when HRP was coexpressed with DsbCD, the growth inhibition of E. coli was not observed. Therefore, coexpression of Dsb proteins improves both the cell growth and the productivity of HRP.

Journal Article↗

Comparisons of effects of raw and gelatinized sago and tapioca starches on serum and liver lipid concentrations in rats.

Effects of raw and gelatinized sago and tapioca starches on serum and liver lipid concentrations were compared in rats fed a cholesterol-enriched diet. Total serum cholesterol and the atherogenic index in the rats fed raw sago starch showed a statistically significant decrease and tendency to decrease, respectively, when compared with those of rats fed raw tapioca starch. Both the serum total cholesterol and atherogenic index in the rats fed gelatinized sago starch showed a tendency to decrease when compared with those of rats fed gelatinized tapioca starch. Serum triacylglycerol concentrations in the rats fed raw sago starch were significantly lower than those in the rats fed raw tapioca starch. The apparent digestibility of raw sago starch was lower than that of tapioca starch. The oval shapes of undigested raw sago starch granules collected from feces remained almost unchanged in shape, but had some holes and scrapes on their surfaces. The shape surfaces of undigested raw tapioca starch collapsed, thereby not retaining their original granule shapes. On the other hand, the amylose contents in the raw and gelatinized sago starches were higher than those in the raw and gelatinized tapioca starches. These results suggested that a decrease or a tendency to decrease in serum total cholesterol levels and atherogenic indexes in raw or gelatinized sago starch-fed rats compared to those of raw or gelatinized tapioca starch-fed rats, and a decrease in serum triacylglycerol concentrations in raw sago starch-fed rats compared to those of raw tapioca starch-fed rats, were due to the lower digestibility and higher amylose content of sago starch.

Amylases↗

Neuropilin-2 expression affects the increased vascularization and is a prognostic factor in osteosarcoma.

Osteosarcoma is a malignant bone tumor characterized by hypervascularity. Neuropilins (NRPs), which is expressed by human tumor cells, is known to be a potent receptor for vascular endothelial growth factor (VEGF). We examined NRPs mRNA expression in 30 osteosarcomas. The osteosarcomas with NRP2 expression (n=24) showed a significantly increased vascularity (P<0.0014, Mann-Whitney U test). Osteosarcomas with NRP2 showed significantly poorer prognosis than those without NRP2 (P=0.016, Wilcoxon's test). These results suggest that NRP acts as a VEGF-amplifier in a paracrine or autocrine manner in the osteosarcoma. NRP2 expression cooperatively promotes angiogenesis and growth in osteosarcomas with VEGF expression.

Bone Neoplasms↗

Expression in hepatomas and chromosomal localization of rat protein phosphatase 5 gene.

The serine/threonine protein phosphatase type 5 (PP5) gene expression was ubiquitously observed among all the tissues examined, but being at the lowest level in the liver. The levels of PP5 mRNA were markedly elevated in rat highly malignant ascites hepatomas, while those in several rat primary hepatomas were slightly increased and those in the regenerating livers were not elevated at all compared to the control liver. The PP5 gene was mapped to rat chromosome 1q22.1. This region has been identified to have linkage homology among human, mouse and rat, and is known to be associated with several tumor types. Taken together, the present results strongly suggest important roles of PP5 in tumorigenesis.

Animals↗

[Immuno-histochemical identification of initial lymphatics: the contour and distribution pattern of initial lymphatics in the human foreskin of the penis].

PURPOSE: There has not been an established method to distinguish initial lymphatics from blood capillaries under the light microscopy. In this study, we examined the usefulness of the immuno-histochemical staining method using a monoclonal anti-desmoplakin antibody in identifying initial lymphatics under the light microscopy. The specificity of this reaction was confirmed by the immuno-electron microscopy. MATERIAL AND METHODS: The cryostat sections of the human foreskin were observed under light microscopy by indirect immunoperoxidase method with the anti-desmoplakin mouse monoclonal antibody, and compared with the hematoxylin and eosin sections. These cryostat sections were also observed under electron microscopy by pre-embedding immunoperoxidase method with the same antibody. RESULTS: Under the light microscopy, the initial lymphatics of the human foreskin were visualized by the method with anti-desmoplakin antibody. These lymphatics were mainly distributed in the dermal layer, on the other hand, rarely seen in dermal papillae. Being usually found in closed shape, the lumens of initial lymphatics were hardly recognized as initial lymphatics by the ordinary hematoxylin and eosin staining. Under the immuno-transmission electron microscopy, the peroxidase-desmoplakin antibody precipitations were located on the surface of the endothelial cells of the vasculature which lacked pericytes and basal lamina, and was composed of endothelial cells alone. By these features of the vascular structures, the vessel reacting with anti-desmoplakin antibody was identified as initial lymphatics. CONCLUSION: This study shows the reliability and specificity of the immuno-histochemical method by anti-desmoplakin antibody in identifying initial lymphatics under light microscopy, and this method will be useful in studying the fine distribution of lymphatic vessels in normal human tissue.

Animals↗

[A case of epithelioid leiomyoma (leiomyoblastoma) of the urethra].

A 25-year-old woman was admitted to our hospital because of a painless, slow growing mass arising from the external genitalia. The mass had been developing for a few years. She did not have difficulty voiding nor was there hematuria. Magnetic resonance imaging revealed a well-circumscribed, 4 cm, solid tumor between the urethra and the anterior vaginal wall. After needle biopsy confirmed a benign tumor arising from the smooth muscle, the tumor was removed by a transvaginal approach. The histopathological diagnosis was epithelioid leiomyoma (leiomyoblastoma), which often occurs in the stomach or uterus, but seldom around the urethra. The patient has remained well without recurrence for 20 months after surgery.

Adult↗

Differences between lymphocyte subsets, after allogeneic bone marrow transplantation, in patients who received tacrolimus and patients who received cyclosporin A.

The subsets of peripheral blood lymphocytes after allogeneic bone marrow transplantation were compared in 20 patients who received tacrolimus and 34 patients who received cyclosporin A (CsA) prophylactically. The phenotypes of CD3, CD4, CD8, and D8/CD57 were analyzed by flow cytometry. The percentage of CD3+ cells in the tacrolimus group (58.8% +/- 21.6%) was significantly lower than in the CsA group (77.2% +/- 12.8%) (P = .0239). The percentage of CD8+CD57+ cells in the patients receiving tacrolimus and developing acute graft-versus-host disease (GVHD) (grade I, 20.1% +/- 10.6%; grade II-IV, 13.2% +/- 6.3%) was significantly higher than in the patients receiving CsA and developing acute GVHD (grade I, 10.7% +/- 5.2%; grade II-IV, 7.7% +/- 4.0%) (grade I, P = .0036; grade II-IV, P = .0255). The absolute number of CD8+CD57+ cells in the patients with grade II-IV acute GVHD was also significantly higher in the tacrolimus group compared with the CsA group. There was no difference in the incidence of acute GVHD in the 2 groups. Recovery from acute GVHD in the tacrolimus group (16.6 +/- 13.6 days) was more rapid than in the CsA group (30.8 +/- 24.8 days) (P = .0124). These results suggest that, compared with CsA, tacrolimus administered prophylactically induces more CD8+CD57+ lymphocytes when acute GVHD occurs and accelerates the recovery from acute GVHD more rapidly.

Adolescent↗

Granular cell tumors arising nearly simultaneously in the larynx and subcutaneous cervical region.

Granular cell tumors are benign, relatively rare lesions that can occur in any organ in the body. Tumors are known to occasionally arise in two or more different organs. We report the case of a 60-year-old woman in whom granular cell tumors arose almost simultaneously in her subcutaneous cervical region and her larynx. The two tumors were surgically resected and examined histopathologically, and they exhibited the same histopathologic features. The tumor of the larynx was resected with the help of a carbon dioxide laser. Immunohistochemical staining revealed that both were positive for S-100 protein and neuron-specific enolase. Cases of the nearly simultaneous appearance of granular cell tumors in the neck and larynx are rather unusual. The results of immunohistochemical staining suggested that this tumor originates in nerve tissue.

Biopsy, Needle↗

[Crossed fused kidney with ectopic ureter: a case report].

A 5-year-old girl with a rare anomaly of a single system ectopic ureter draining into the mesonephric duct cyst and ipsilateral crossed fused kidney is presented. Both ureters were catheterized and three dimensional (3-D) images of the urinary tract were reconstructed with helical computed tomographic (CT) data. A mesonephric duct cyst, the right ureter draining into the cyst and an ectopic orifice were well depicted with these images, especially with inferior projection images. 3-D display of helical CT data with a retrograde contrast study is a promising method of obtaining anatomical detail of an ectopic ureter.

Child, Preschool↗

Hepatocyte growth factor upregulates E1AF that induces oral squamous cell carcinoma cell invasion by activating matrix metalloproteinase genes.

Hepatocyte growth factor (HGF) is thought to play a role in cell motility and invasion. Matrix metalloproteinases (MMPs) have been implicated in invasion and metastasis of tumor cells. We have previously reported that the Ets-oncogene family transcription factor E1AF positively regulates transcription of MMP genes in transient expression assays and that overexpression of the E1AF gene confers an invasive phenotype on breast cancer cells. Here we examined the effect of HGF on E1AF and MMP gene expression in terms of the invasive potential of the oral squamous cell carcinoma cell line HSC3. HGF stimulated expression of the E1AF gene. The levels of MMP-1, -3 and -9 mRNAs increased in cells treated with HGF and correlated with E1AF upregulation. In contrast, no obvious upregulation of MMP-1 and -9 mRNA was observed in ASE1AFHSC3 cells transfected with the antisense E1AF expression vector into parental HSC3 cells. The wild-type MMP-9 gene promoter was activated by endogenous E1AF in HSC3 cells, and chloramphenicol acetyltransferase (CAT) activities increased when HGF was added to transfected cells. On the other hand, CAT activity was reduced to almost two-thirds of the wild-type activity when HSC3 cells were transfected with a CAT reporter plasmid driven by a mutant MMP-9 promoter lacking the Ets-binding site, and induction of CAT activity was not observed upon addition of HGF. Analysis of organotypic raft cultures revealed that HSC3 cells invaded and degraded collagen gel actively upon addition of HGF. These results suggest that HGF induces expression of the Ets-related E1AF transcription factor gene whose product in turn activates MMP genes and leads to oral cancer cell invasion.

Adenovirus E1A Proteins↗

[A case of giant hemorrhagic adrenal pseudocyst with infection].

A 51-year-old woman was admitted with general fatigue, high fever and left upper abdominal pain. Abdominal computed tomography revealed a left adrenal mass, 15 cm in diameter with regular margins, the contents of which were not enhanced with contrast medium. The mass had heterogeneous echogenicity on the abdominal ultrasonograph. Serum hormonal levels were almost normal. Despite treatment with antibiotics, the high fever persisted. Based on these findings, the differential diagnosis was adrenal abscess or a nonfunctional adrenal tumor. Transabdominal left adrenalectomy was performed. Pathological examination revealed a hemorrhagic adrenal pseudocyst with infection. The patient's condition improved soon after the operation.

Adrenal Gland Diseases↗

[Infrastructure of cancer clinical trial cooperative groups in western countries].

Efforts for international harmonization have made it clear that Japan is far behind in Western countries in all aspects of infrastructure for clinical trials. The introduction of ICH-GCP, 1998, has promoted the rapid growth of infrastructure for investigational new drug (IND) trials; however, the infrastructure for academic cancer trials has shown no remarkable progress. There is still no governmental regulation, no agency for quality control, and no quality assurance audit system even in government-sponsored trials. The author introduces the quality control systems in cooperative groups in Western countries, such as the Southwest Oncology Group (SWOG), National Surgical Adjuvant Breast and Bowel Project (NSABP) and European Organization for Research and Treatment of Cancer (EORTC), and the quality assurance systems by the National Cancer Institute-Cancer Therapy Evaluation Program (NCI-CTEP). Key activities for quality control in cooperative groups are in-house monitoring, site visit audits, institutional performance evaluations and case report form review by study coordinators. NCI-CTEP oversees cooperative group activities through protocol review, supervision of site visit audits and a monitoring committee. Cancer cooperative groups in Western countries have taken the initiatives in advancement of trial methodology and establishment of clinical trial infrastructure. In order to improve the quality of clinical trials, there is need to invest cancer cooperative groups, thus strengthening the activities for overall clinical trials.

Clinical Trials as Topic↗

[A case of Avellis' syndrome with ipsilateral central facial palsy due to a small medullary infarction].

We report a 51-year-old man with mild left central facial palsy and left Avellis' syndrome due to a small medullary infarction. On admission, neurological examination revealed hoarseness, dysphasia, absent left gag reflex, palsies of the left vocal cord and left soft palate, and hypalgesia and thermohypesthesia on the right side of the trunk and extremities. In addition, he had a mild left central facial palsy. He had no nausea, vomiting, vertigo, hiccups, nystagmus, Horner's sign, facial numbness, or paresis or ataxia of the limbs. A T2 weighted MRI showed a small, high signal intensity area in the left dorsal region of the medulla and this lesion was presumed to involve the nucleus ambiguus and a part of the spinothalamic tract. These findings suggest that an aberrant supranuclear pathway, looping around the nucleus ambiguus to the facial nucleus exists in our patient.

Cerebral Infarction↗

Comparison of intratumoral distribution of 99mTc-MIBI and deoxyglucose in mouse breast cancer models.

UNLABELLED: The aims of this study were to evaluate the distribution of 99mTc-methoxyisobutylisonitrile (MIBI) in 3 animal models of breast cancer, the effect of radiotherapy on 99mTc-MIBI uptake, and the relationship between uptake and microvessel density. METHODS: We used syngeneic, subcutaneously transplanted FM3A, MM48, and Ehrlich mouse breast cancer. 99mTc-MIBI and FDG were injected intravenously, and tumor uptake was measured 30 min later. Double-tracer macroautoradiography (ARG) images were prepared with 99mTc-MIBI and 2-deoxy-D-[1-14C]-glucose (14C-DG), analyzed quantitatively, and compared with histology. The radiotherapeutic effects of 20 Gy x-ray irradiation were monitored by measuring tumor volume, tumor uptake, and ARG findings using 99mTc-MIBI and FDG in FM3A tumors. Microvessel density was quantified by immunohistochemical staining for CD34 and compared with ARG using 99mTc-MIBI in FM3A tumors. RESULTS: FM3A, MM48, and Ehrlich tumors showed different growth rates and radiosensitivities. Uptake of FDG, but not of 99mTc-MIBI, correlated significantly with growth rates. Compared with 14C-DG, 99mTc-MIBI accumulated more in cancer cells and less in infiltrating fibroblasts and macrophages in all tumor models. Irradiation significantly decreased 99mTc-MIBI uptake, but a rapid increase was noted at recurrence on day 7. Changes in FDG uptake were not significant at recurrence. Microvessel density in tumor tissue correlated significantly with 99mTc-MIBI uptake on ARG. CONCLUSION: Accumulation of 99mTC-MIBI in cancer cells is preferential and can be used as a sensitive marker to examine the response to radiotherapy. Angiogenesis seems to enhance accumulation of 99mTc-MIBI in tumors. These characteristics may be favorable for tumor imaging using 99mTC-MIBI.

Animals↗

[Anesthetic management of a patient with May-Hegglin anomaly].

The May-Hegglin anomaly is a rare hereditary disorder characterized by the presence of giant platelets and platelet deficiency. This report presents a successful management of a patient with May-Hegglin anomaly. A 5-year-old girl with May-Hegglin anomaly was scheduled for closure of fistulae of her ears. Although preoperative physical examination revealed platelet count of 8,000 mm-3, she had no bleeding tendency. No premedication was given. Anesthesia was induced with inhalational agents of a mixture of sevoflurane, nitrous oxide and oxygen. Neuromuscular blockade was achieved with vecuronium 0.1 mg.kg-1 and the trachea was gently intubated. Anesthesia was maintained with sevoflurane, nitrous oxide and oxygen. Five units of platelet were transfused during the operation. No bleeding tendency was observed perioperatively. It is important to plan the management of anesthesia for a patient with bleeding tendency.

Anesthesia, Inhalation↗

[A case of effective chemotherapy using CAF followed by docetaxel for advanced breast cancer].

A huge mass measuring 13 x 12 cm and wide cutaneous edema were detected in the right breast of a 51-year-old woman. Under a diagnosis of locally advanced breast cancer (T4bN2M1, stage IV) with liver metastases, we attempted sequential neoadjuvant chemotherapy. After three courses of CAF therapy (cyclophosphamide, doxorubicin (DXR), 5-FU), the primary tumor was decreased by 56% and the liver metastases had disappeared. A minor pathologic response was observed. Subsequently, three courses of docetaxel (TXT) administration were carried out. The primary tumor was then decreased by 75% and the axillary metastases had disappeared. Histopathological examination showed gross viable tumor cells in the residual tumor and positive axillary lymph nodes. The only toxic effect was nausea (grade 1) and no major adverse effects were observed. Neoadjuvant chemotherapy with sequential DXR followed by TXT is a useful treatment for locally advanced breast cancer.

Antineoplastic Agents, Phytogenic↗