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Biomedical subjects

H Fujii

Publications and source records attributed to H Fujii.

At least 361 records · Page 20Linked to original sources

Effects of sex steroids and growth factors on invasive activity and 5'-deoxy-5-fluorouridine sensitivity in ovarian adenocarcinoma OMC-3 cells.

Effects of sex steroids (estradiol-17 beta, E2; progesterone, Prog) and growth factors (epidermal growth factor, EGF; transforming growth factor-alpha, TGF-alpha) on invasive activity and 5'-deoxy-5-fluorouridine (5'-dFUrd) sensitivity of ovarian adenocarcinoma OMC-3 cells were investigated. Tumor cell migration along a gradient of substratum-bound fibronectin and invasion into reconstituted basement membrane were inhibited by 10 microM Prog, but stimulated by 0.1-10 nM EGF and TGF-alpha in a concentration-dependent manner. E2 did not have any effect on tumor cell migration or invasion. The zymography of tumor conditioned medium showed that the treatment of OMC-3 cells with EGF and TGF-alpha resulted in increases of type IV collagenase, stromelysin and urokinase-type plasminogen activator (uPA). EGF and TGF-alpha up-regulated thymidine phosphorylase (dThdPase) expression of tumor cells and consequently enhanced the antiproliferative action of 5'-dFUrd, which is converted to 5-fluorouracil by dThdPase. E2 and Prog did not have significant effects on the expression of proteolytic enzymes and dThdPase, or on the 5'-dFUrd sensitivity of tumor cells. The inhibitory effect of Prog on tumor cell invasion may depend on its inhibitory action on the motility of tumor cells. These results suggest that EGF and TGF-alpha simultaneously up-regulate the potential of ovarian adenocarcinoma cells to invade extracellular matrices and their dThdPase expression, both of which are associated with the specific action of 5'-dFUrd selectively to kill tumor cells with high invasive and metastatic potential.

Basement Membrane↗

Oral administration of a Kampo (Japanese herbal) medicine Juzen-taiho-to inhibits liver metastasis of colon 26-L5 carcinoma cells.

We have investigated the inhibitory effect of oral administration of Juzen-taiho-to, a Kampo Japanese herbal medicine, on liver metastasis by the inoculation of a liver-metastatic variant (L5) of murine colon 26 carcinoma cells into the portal vein. Oral administration of Juzen-taiho-to for 7 days before tumor inoculation resulted in dose-dependent inhibition of liver tumor colonies and significant enhancement of survival rate as compared with the untreated control, without side effects. We also found that liver metastasis of L5 cells was enhanced in BALB/c mice pretreated with anti-asialo GM1 serum or 2-chloroadenosine, and in BALB/c nu/nu mice, compared to normal mice. This indicates that NK cells, macrophages, and T-cells play important roles in the prevention of metastasis of tumor cells. Juzen-taiho-to significantly inhibited the experimental liver metastasis of colon 26-L5 cells in mice pretreated with anti-asialo GM1 serum and untreated normal mice, whereas it did not inhibit metastasis in 2-chloroadenosine-pretreated mice or T-cell-deficient nude mice. Oral administration of Juzen-taiho-to activated peritoneal exudate macrophages (PEM) to become cytostatic against the tumor cells. These results show that oral administration of Juzen-taiho-to inhibited liver metastasis of colon 26-L5 cells, possibly through a mechanism mediated by the activation of macrophages and/or T-cells in the host immune system. Thus, Juzen-taiho-to may be efficacious for the prevention of cancer metastasis.

2-Chloroadenosine↗

Abscess-forming neutrophilic dermatosis: report of three cases associated with hemopathies.

BACKGROUND: The development of different types of neutrophilic dermatosis is reported to occur in the course of malignant hemopathies. These concern mainly Sweet's syndrome, pyoderma gangrenosum, erythema elevatum et diutinum and neutrophilic eccrine hidradenitis. OBSERVATIONS: We have recently encountered the cases of 3 patients who presented all with multiple acneiform papules and dome-shaped aseptic abscesses leaving scars. Pus was sterile in all except case 3 in which slight Staphylococcus aureus growth was shown. However, in this patient, only steroids were effective demonstrating that this bacterium was not responsible for the disease. Histopathology disclosed a dense dermal polymorphonuclear neutrophil infiltrate and some mononuclear cells. Two of these patients had myelodysplastic syndromes while one had IgA myeloma. CONCLUSION: Abscess-forming neutrophilic dermatosis seems to be another type of neutrophilic dermatosis associated with hematological malignancies.

Abscess↗

Anti-metastatic and immunomodulating properties of the water extract from Celosia argentea seeds.

We have investigated the anti-metastatic effect of Celosia argentea seed extracts (CAE), which have traditionally been used as a therapeutic drug for eye and hepatic diseases in China and Japan. Intraperitoneal (i.p.) administration of CAE for 7 d before tumor inoculation significantly inhibited liver metastasis caused by intraportal injection of colon 26-L5 carcinoma cells in a dose-dependent manner. CAE also showed concentration dependent mitogenic activity on BALB/c whole splenocytes, whereas incubation of the non-adherent fraction of splenocytes with CAE did not induce this activity. CAE has the ability to induce interleukin (IL)-12 production from macrophages in vitro. Following i.p. administration of CAE the maximal levels of IL-12 and interferon (IFN)-gamma production in serum were achieved at 2-3 and 6 h, respectively. Experiments using macrophage- or NK cell-deficient mice revealed that CAE-induced IL-12 in serum was not mediated by macrophages and that IFN-gamma production was mainly dependent on natural killer (NK) cells. Since CAE was inactive when the contributions of macrophages were removed in our system, its inhibitory mechanism is likely to be mainly associated with the activation of macrophages to an anti-metastatic state rather than NK cells. CAE administration resulted in increased production of IL-2, IFN-gamma and decreased production of a Th2 cytokine (IL-4) from splenocytes stimulated by PMA and A23187. Thus, the anti-metastatic effect by CAE is based on its immunomodulating properties including induction of cytokines such as IL-12, IL-2 and IFN-gamma leading to a Th1 dominant immune state and activating macrophages to the tumoricidal state. This may provide a basis for the inhibition of cancer metastasis.

2-Chloroadenosine↗

Primary pulmonary artery sarcoma.

A 66-year-old woman with a history of mitral valve replacement with a Starr-Edwards ball valve 25 years ago was treated for refractory heart failure but died of right heart failure. At autopsy, primary pulmonary artery sarcoma was found in the right ventricular outflow tract, main pulmonary trunk, and bilateral pulmonary artery, and had invaded the aortic arch. The pathohistologic diagnosis was osteosarcoma. Echocardiography, chest computed tomography and right ventriculography performed 1 year before death did not reveal the presence of a tumor in the pulmonary artery. The history of this patient shows that primary pulmonary artery sarcoma grows rapidly, with, in this case, the patient dying within 1 year of its appearance.

Aged↗

Serous cystadenoma of the pancreas with atypical cells. Case report.

CONCLUSION: Serous cystadenomas of the pancreas may have the biologic ability to undergo malignant transformation. BACKGROUND: It is generally recognized that: serous cystadenomas of the pancreas are benign and that their malignant potential is low. METHODS: A serous cystadenoma of the pancreas was resected from a 53-yr-old woman. In the central portion of the tumor, papillary structures were found on the cyst wall. Immunohistologic studies using antibodies to carbohydrate antigen 19-9, carcinoembryonic antigen, and proliferating cell nuclear antigen were performed to determine the malignant potential of this tumor. RESULTS: On histology, most tumor cells were positive for periodic acid-Schiff but were negative for periodic acid-Schiff after diastase digestion and Alcian blue, a staining pattern typical of serous cystadenomas. The cells found in the papillary structure of the cyst wall were mildly atypical. These cells were stained with antibodies to carbohydrate antigen 19-9, carcinoembryonic antigen, and proliferating cell nuclear antigen, indicating that the cells comprising the papillary structure were proliferating more rapidly than cells in other parts of the tumor and strongly suggesting that the cells are premalignant.

CA-19-9 Antigen↗

Detection of estrogen receptor alpha, carbonic anhydrase II and tartrate-resistant acid phosphatase mRNAs in putative mononuclear osteoclast precursor cells of neonatal rats by fluorescence in situ hybridization.

Increasing evidence suggests that estrogen deficiency in women promotes the expansion of populations of bone marrow cells that differentiate into osteoclasts under the influence of osteotropic hormones and local factors. A progressive cytoplasmic accumulation of osteoclastic bone resorbing enzymes, such as tartrate-resistant acid phosphatase (TRACP) and carbonic anhydrase II (CA II), characterizes osteoclast differentiation. To evaluate the possibility that estrogen may have a direct effect on osteoclast precursor cells, we investigated the mRNA levels of estrogen receptor a (ERa), TRACP and CA II genes in neonatal rat bone imprints by fluorescence in situ hybridization and confocal microscopy. Morphological assessment of bone imprints has shown that the putative mononuclear osteoclast precursor cells (MOPC) display strongly basophilic cytoplasm and a low nuclear/cytoplasmic ratio, while some of these cells possess pale-staining ruffled border regions similar to those observed in osteoclasts. Both CA II and TRACP mRNAs were detected in putative MOPC as well as multinuclear osteoclasts. The gene transcripts were mainly located in the cytoplasm of these cells. To determine whether these putative MOPC possess ER mRNA, a 637 base pair antisense ER riboprobe was used. The results indicated that MOPC which show TRACP reactivity express high levels of ER gene transcripts in their cytoplasm. In contrast, only a few multinuclear osteoclasts in the bone imprints possessed ER gene transcripts. Interestingly, the levels of ER mRNA in these multinuclear osteoclasts were very low compared with those in the putative MOPC. Treatment with RNase prior to hybridization resulted in a significant loss of signal in these cells. The results of these studies suggest that estrogen may have a direct role in modulating the recruitment of osteoclast precursor cells during osteoclastogenesis.

Acid Phosphatase↗

Effects of levofolinate calcium on subacute intravenous toxicity of 5-fluorouracil in rats.

To clarify whether levofolinate calcium (1-LV) enhances 5-fluorouracil (5-FU) toxicity, a 4-week toxicity study of 5-FU (10 mg/kg/day) in combination with 1-LV (6, 20 or 60 mg/kg/day) was conducted in rats. In the 5-FU alone group, a decrease in body weight gain, food consumption, RBC parameter and WBC counts were detected. Histopathologically, lymphoid depletion of lymphatic organs, hematopoiesis enhancement of the spleen and myelosuppression were observed. In the group for which 5-FU was combined with 1-LV, the RBC counts decreased, extramedullary hematopoiesis increased and the suppression of lymphatic organs was enhanced. Changes in the lymphatic organs were observed at 20 mg/kg/day of 1-LV and above. In monitoring of blood drug concentrations of 1-LV, 5-methyl tetrahydrofolic acid, a metabolite of 1-LV, and 5-FU after the 1st and 14th dosings, there was no apparent difference between 5-FU alone and 5-FU combined with 1-LV in Cmax and AUC0-infinity. The potentiation induced by 1-LV in the toxicity of 5-FU appeared to be mainly immuno-suppression and myelosuppression, which were related to the anti-tumor activity of 5-FU. Plasma concentrations of 5-FU and 1-LV in this study overwhelmed the concentrations that enhancement of thymidylate synthetase (TS) inhibition due to 5-FU was observed by addition of 1-LV in vitro. Therefore toxic potentiation of 5-FU due to simultaneous 1-LV dosing is presumed to be concerned with an increased ternary complex (FdUMP-TS-5,10-methylenetetrahydrofolate) formation and a greater extent of TS inhibition.

Animals↗

A heterozygous germline mutation of the PTEN/MMAC1 gene in a patient with Cowden disease.

Cowden disease, or multiple hamartoma syndrome, is an autosomal dominant inherited cancer syndrome with a high risk of thyroid and breast cancers. Its susceptibility gene has been mapped to chromosome 10q22-23. Because a newly found tumor suppressor gene, PTEN/MMAC1, often mutated in glioblastoma and in prostatic and breast cancers, has been mapped to the same chromosomal locus, it is suspected that it may be the gene responsible for Cowden disease. germline mutations of the gene have been reported in 4 of 5 families with Cowden disease. We performed a genetic analysis of the PTEN/MMAC1 gene in a sporadically found patient with the disease who had no apparent family history of the disease. We found a germline heterozygous mutation of the PTEN/MMAC1 gene in a patient with Cowden disease. The mutation, a C to T substitution of a single base at codon 130, leads to a formation of stop codon, generating a truncated protein lacking both protein phosphatase signature motif and tensin-like domain. Our finding supports the hypothesis of the PTEN/MMAC1 gene as being responsible for Cowden disease even in a sporadic case.

Adult↗

A heterozygous frameshift mutation of the PTEN/MMAC1 gene in a patient with Lhermitte-Duclos disease - only the mutated allele was expressed in the cerebellar tumor.

Lhermitte-Duclos disease is a rare disorder of the cerebellum which exhibits a focally indolent growth of the cerebellar cortex. The disease is sometimes associated with multiple hamartoma syndrome, or Cowden disease, an autosomal, dominantly inherited cancer syndrome. Germline mutations of the PTEN/MMAC1 gene, a gene recently discovered to be a tumor suppressor, have been documented in four families with Cowden disease. A family member in one of these families have had Lhermitte-Duclos disease, indicating that mutations of the gene are responsible for the development of Lhermitte-Duclos disease. However, the occurrence of Lhermitte-Duclos disease is mostly sporadic. It is unknown whether the PTEN/MMAC1 gene is involved in these cases. We performed a genetic analysis on a patient with Lhermitte-Duclos disease, as well as analyses on his family members, and found a germline mutation of the PTEN/MMAC1 gene. An insertion of A at nucleotide 83 in codon 28 was apparent in both the patient and members of his family. This mutation caused a frame shift that generated a premature stop codon in codon 43. The mutation was heterozygous, although only the mutated allele was expressed in the cerebellar tumor of the patient. A monoallelic expression of the mutated PTEN/MMAC1 gene may have been responsible for the development of a cerebellar tumor in the patient.

Adolescent↗

Factors influencing physiological FDG uptake in the intestine.

The intestine is a well-known site of physiological 18F-fluorodeoxyglucose (FDG) accumulation in positron emission tomography (PET). To identify factors influencing physiological FDG uptake in the intestine, the intensity of FDG uptake was evaluated in a total of 1,068 healthy adults. Non-attenuation-corrected whole-body PET images were obtained for all subjects and visually evaluated. Subjects were then classified into two groups according to the intensity of intestinal FDG uptake. Sex, age, presence or absence of constipation, and serum glucose, hemoglobin A1c, and free fatty acid levels were compared between the two groups. High intestinal FDG uptake was observed at an overall rate of 11.0%. Sex (female), age, and bowel condition (constipation) were found to affect intestinal FDG uptake. The factors we identified lead to further questions regarding the relationship between intestinal motility and glucose uptake that warrant further study.

Adult↗

Allelic loss of chromosomal arm 8p in breast cancer progression.

Loss of heterozygosity (LOH) of chromosomal arm 8p has been reported to occur at high frequency for a number of common forms of human cancer, including breast cancer. The objectives of this study were to define the regions on this chromosomal arm that are likely to contain breast cancer tumor suppressor genes and to determine when loss of chromosomal arm 8p occurs during breast cancer progression. For mapping the tumor suppressor gene loci, we evaluated 60 cases of infiltrating ductal cancer for allelic loss using 14 microsatellite markers mapped to this chromosomal arm and found LOH of 8p in 36 (60%) of the tumors. Whereas most of these tumors had allelic loss at all informative markers, five tumors had partial loss of 8p affecting two nonoverlapping regions. LOH for all but one of the tumors with 8p loss involved the region between markers D8S560 and D8S518 at 8p21.3-p23.3, suggesting that this is the locus of a breast cancer tumor suppressor gene. We then studied LOH of 8p in 38 cases of ductal carcinoma in situ (DCIS) with multiple individually microdissected tumor foci evaluated for each case. LOH of 8p was found in 14 of the DCIS cases (36%), including 6 of 16 cases of low histological grade and 8 of 22 cases of intermediate or high histological grade. In four of these DCIS cases, 8p LOH was seen in some but not all of the multiple tumor foci examined. These data suggest that during the evolution of these tumors, LOH of 8p occurred after loss of other chromosomal arms that were lost in all tumor foci. Thus, LOH of 8p, particularly 8p21.3-p23, is a common genetic alteration in infiltrating and in situ breast cancer. Although 8p LOH is common even in low histological grade DCIS, this allelic loss often appears to be preceded by loss of other alleles in the evolution of breast cancer.

Breast Neoplasms↗

[Perioperative management of two patients with severe dilated cardiomyopathy].

We report perioperative management of two patients with severe dilated cardiomyopathy belonging to the group IV of classification of Inoh (ejection fraction 18% and 30%). In the preoperative period, they developed severe congestive heart failure. Dopamine, dobutamine, and furosemide were given to improve cardiac function. Anesthesia was performed safely under continuous cardiac output and mixed venous saturation monitoring. We consider that preoperative evaluation and management are very important to prevent intraoperative and postoperative complications in patients with severe dilated cardiomyopathy.

Aged↗

[Recurrent nerve palsy after endotracheal intubation].

We encountered left recurrent nerve palsy in four patients who had undergone surgery unrelated to the course of the vagus nerve or recurrent nerve, during which they had received endotracheal anesthesia. They were intubated without difficulty and underwent surgery without trouble, but postoperatively they all complained of hoarseness. We used a disposable ENTRASOFT endotracheal tube with high volume, low-pressure cuff in three patients and a disposable PORTEX endotracheal tube with low volume, standard cuff in one patient. In three patients recurrent nerve palsy healed completely within two months after the operation, and one patient was recovering from the palsy on the twentieth day after the operation. We believe that the most plausible explanation of recurrent nerve palsy is the excessive pressure from the inflated endotracheal tube cuff on the intralaryngeal course of the anterior branch of the recurrent nerve. Monitoring cuff pressure is most important to prevent recurrent nerve palsy after endotracheal intubation.

Adult↗

[Clinical study on the inhibitory effect of a 5-HT3 antagonist, granisetron, for nausea and vomiting induced by chemotherapy (CHOP, VEPA, high-dose ETP) for non-Hodgkin's lymphoma].

The antiemetic effect of granisetron on nausea and vomiting induced by cancer chemotherapy (CHOP, VEPA, VEPA-B, massive dose of ETP) was studied in fifty patients with non-Hodgkin's lymphoma. There was almost no difference in the inhibitory effect by regimen, with the rates of perfect inhibition of nausea and vomiting standing at 55.6% to 60%. Nausea and vomiting was perfectly controlled in 60% of 35 patients receiving CHOP therapy. As a part of this study, a comparison was made of perfect inhibitory effect on nausea and vomiting by potency of chemotherapy under the potency scale of 750 mg/m2 of CPA as 1, revealing no significant difference in the rates of complete inhibition as 71.4% for a drug potency of less than 0.8 vs 52.4% for 0.8 or above (p = 0.26). However, it was clear that the higher the dose of chemotherapy, the lower the rate of complete inhibition. The results confirmed the high efficacy and safety of granisetron in the treatment of nausea and vomiting induced by cancer chemotherapy.

Adult↗

[Successful double peripheral blood stem cell transplantation for patient with malignant lymphoma of primary induction failure].

Three patients with non-Hodgkin's lymphoma of intermediate-grade histologies, who had failed to achieve a complete remission (CR) after more than several courses of conventional chemotherapy were treated with two cycles of high-dose chemotherapy with autologous peripheral blood stem cell transplantation (double PBSCT). All patients received regimen A with carboplatin 1g/m2, etoposide 1.2g/m2 and cyclophosphamide 120mg/kg prior to 1st PBSCT and obtained a partial remission. One patients received regimen A and two patients received regimen B with MCNU 500mg/m2, etoposide 750mg/m2 and L-PAM 140mg/m2 prior to 2nd PBSCT and all patients obtained CR. Second PBSCT was performed 3 to 5 months after the 1st PBSCT. At a median follow-up of 36 (range; 29 to 54) months, all patients remained in continuous CR. The period after reinfusion of PBSCT to achieve a neutrophil count more than 500/microliters ranged between 7 and 9 days and to achieve a platelet count more than 5 x 10(4)/microliters ranged 12 and 22 days. Grade 3 nonhematologic toxicity (mucositis) was seen in one patient after 2nd PBSCT. Double PBSCT could be well tolerated with a high response rate in patients with malignant lymphoma of primary induction failure.

Adult↗

[A comparison of a 3 day course with a 2 week course of oral prednisolone in patients with chronic asthma].

To investigate an appropriate duration of short course of a oral prednisolone (PSL), we compare the results of a 3 day course of PSL (3D) with those of a 2 week course of PSL (2W) in 20 patients with chronic asthma. All subjects had been inhaling beclomethasone dipropionate (BDP, mean daily dose: 1325 micrograms), and had been self-monitoring their peak expiratory flow rate (PEF) for at least 6 months. Mean +/- SE of the best PSL-induced PEF in 2W (2W-best) was not different from that in 3D (397 +/- 29 and 356 +/- 23 L/min, respectively, p = 0.26). Mean weekly morning PEF/2W-best before and 1, 2, 3 and 4 weeks after PSL was 60, 76, 80, 76 and 76% in 2W, and 63, 73, 67, 67 and 65% in 3D, respectively. Both changes over the course of time were significant. The frequency of emergency room visits and/or unscheduled hospital visits was not significantly different between 2W and 3D. However, both the frequency of use of inhaled beta 2 agonists and the symptom score significantly decreased only in 2W. Seven patients (35%) did not need additional oral PSL during the 4-week period after initiating 3D, and among these patients, emergency room visits and/or unscheduled hospital visits were completely controlled. In conclusion, although the effect of 3D was inferior than that of 2W, it was a sufficient duration in 35% of the patients, and thus, may be appropriate as a initial duration of rescue course of oral steroids.

Administration, Oral↗