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Biomedical subjects

H Fujii

Publications and source records attributed to H Fujii.

At least 1,387 records · Page 77Linked to original sources

Low frequency of bcl-2 expression in large non-polypoid colonic neoplasms.

Large non-polypoid colorectal adenomas that spread over the mucosa and morphologically flat lesions are included in a group called granule-aggregating tumours. These are uncommon in the West. We aimed to clarify the biological differences between granule-aggregating tumours and colorectal polypoid adenomas. We evaluated the extent of apoptotic cell loss and expression of bcl-2 and p53 oncoproteins in 26 granule-aggregating tumours and 19 polypoid adenomas. The mean apoptosis index value of granule-aggregating tumours was significantly higher than that of polypoid adenomas. Only two (7.7%) granule-aggregating tumours and 13 (68.4%) polypoid colorectal adenomas expressed bcl-2, while 12 (46.2%) granule-aggregating tumours and six (31.6%) polypoid colorectal adenomas were p53-positive. Our results show that the higher apoptosis index and frequent expression of bcl-2 oncoprotein differentiates granule-aggregating tumours from polypoid colorectal adenomas. We propose that large non-polypoid granule-aggregating tumours of the colorectum are a biologically distinct entity.

Adenoma↗

A family case of pyruvate kinase variant, PK 'Nichinan'.

A case of congenital hemolytic anemia caused by pyruvate kinase (PK) deficiency variant designated PK 'Nichinan' is presented. A 29-old patient with a history of anemia and hepatosplenomegaly had an episode of aplastic crisis associated with fever, abdominal symptoms and worsening hepatosplenomegaly. Study of the family members revealed that his mother and two of three siblings showed decreased PK activity whereas his father showed normal PK activity with a normal level of glycolytic intermediates. The patient was assumed to be a double heterozygote with two separate mutant genes from the parents despite the apparent normality of his father's erythrocyte PK.

Adult↗

Establishment of an enzyme-linked immunosorbent assay with a coated deflagellated Salmonella enteritidis antigen for detection of a specific chicken antibody.

We attempted to establish an enzyme-linked immunosorbent assay (ELISA) for field monitoring/profiling purposes for Salmonella enteritidis (SE) infection of poultry flocks. Serotyping rabbit sera, commercially obtained, specific for Salmonella identification sera to O2, O4, O7, O8, S. Vi, S. Hm, and O9, showed negative ELISA (E)-values (< 0.2) on ELISA, except the O9 identification serum (E-value > 0.5). Similar negative E-value results were obtained for antisera to Echerichia coli (E. O antigen). Field serum samples originating from SE-isolated flocks yielded similar positive ratios on both ELISAs including the present coated deflagellated SE antigen and a commercially obtained flagellated SE antigen and that of rapid plate aggregation with a pullorum antigen (PD-RPA). About 100 days after the first monitoring, no SE isolation in the same flock was observed resulting in a carrier state of SE infection. Although both the monitoring results with commercially obtained ELISA and PD-RPA showed lower positive or negative ratios, the present ELISA showed a higher positive ratio than that of the first monitoring. The present ELISA is suggested to be a suitable method to do accurate profiling on the carrier state of infection.

Animals↗

Chemosensitivity testing of irinotecan (CPT-11) in ovarian and endometrial carcinomas: a comparison with cisplatin.

BACKGROUND: The tetrazolium dye (MTT) assay is useful in predicting chemosensitivity. MATERIALS AND METHODS: Using an MTT assay, we designed an in vitro chemosensitivity test for irinotecan (CPT-11) and compared it with sensitivity to cisplatin in gynecologic carcinomas removed from 49 patients. RESULTS: The mean tumor inhibition rate (I.R.: %) for irinotecan was relatively inferior to the I.R. for cisplatin in both ovarian and endometrial carcinomas [40.2 vs 53.2 and 43.5 vs 58.0] (p < 0.05, respectively). In ovarian carcinomas, 13 (48.1%) of 27 cases were irinotecan-sensitive (I.R. > or = 50%) and 77% of the tumors were judged to be irinotecan and/or cisplatin-sensitive. There was no significant difference in the I.R. for irinotecan among the various histologic subtypes. Comparing in vitro sensitivity to irinotecan with clinical responses in 8 patients who received irinotecan, the overall accuracy of the MTT assay for evaluating clinical effectiveness was 75% (6 out of 8). In endometrial carcinomas, we found 9 (40.9%) out of 22 cases to be irinotecan-sensitive. The I.R. for irinotecan in G1 carcinomas [33.5] was significantly lower than in G2 carcinomas [59.3] (p < 0.05). CONCLUSION: Our data suggest that irinotecan appears to have moderate antitumor activity in vitro against both ovarian and endometrial carcinomas and that differences in irinotecan sensitivity among the histologic subtypes were evident in the latter but not in the former.

Adult↗

Accelerated decline of blood glucose after intravenous glucose injection in a patient with Cowden disease having a heterozygous germline mutation of the PTEN/MMAC1 gene.

The PTEN/MMAC1, a putative tumor suppressor, has been demonstrated to dephosphorylate phosphatidylinositol 3, 4, 5-triphosphate, a key molecule involved in the insulin signaling pathway. The PTEN may act, therefore, as a negative regulator of insulin signaling. The patient with Cowden disease, having a heterozygous PTEN/MMAC1 gene mutation, a C to T substitution of a single base at codon 130, was suspected to have decreased amount of PTEN protein with phosphatase signature motif. We thought that the patient might be more sensitive to insulin than normal subjects. As expected, administration of a bolus of glucose resulted in a more rapid clearance of blood glucose than was observed in 5 control subjects, indicating the presence of insulin hypersensitivity in the patient. The euglycemic hyperinsulinemic clamp study provided additional evidence.

Adult↗

Correlation between Topo II alpha expression and chemosensitivity testing for Topo II-targeting drugs in gynaecological carcinomas.

BACKGROUND: The purpose of this study was to investigate the correlation between topoisomerase II alpha (Topo II alpha) expression and the chemosensitivity to Topo II-targeting drugs in gynaecological carcinomas. MATERIALS AND METHODS: We analysed the expression of Topo II alpha, and then correlated this with the in vitro chemosensitivities of 43 gynaecological tumors using immunohistochemistry and a tetrazolium dye (MTT) assay. RESULTS: There was a significant correlation between the Topo II alpha index (the number of positive cells per 100 cells: %) and the tumor cell growth inhibition rate in culture (I.R.: %) for doxorubicin and etoposide (r = 0.631, p < 0.001 and r = 0.645, p < 0.001, respectively). The I.Rs for doxorubicin and etoposide in endometrial carcinomas were lower than those in ovarian carcinomas [38.2 +/- 22.8 vs 54.6 +/- 29.8, 37.3 +/- 19.8 vs 59.3 +/- 30.6] (p < 0.05, respectively). Furthermore, the number of high Topo II alpha index (over 30%) tumors in the ovarian carcinoma cases was higher than that in the endometrial carcinoma cases (63.1% vs 45.8%, p < 0.05). CONCLUSIONS: Our data suggest that the Topo II alpha index of a tumor is a reflection of its chemosensitivity to Topo II-targeting drugs. The use of this index may enable prediction of a clinical response to chemotherapy using Topo II-targeting drugs in gynaecological malignancies.

Antigens, Neoplasm↗

Mantle cell lymphoma of the rectum at an early stage: a case report.

We report a very rare early-stage case of mantle cell lymphoma, which arose from the rectum. A 60-year-old man presented with a small elastically hard polypoid lesion in the rectum. The lesion was 1.2 x 1.2 cm in size. As a preoperatively barium enema and endoscopy suggested a benign tumor of the rectum, he underwent local excision of a rectal polypoid mass transanally under spinal anesthesia. However, histological examination revealed a malignant lymphoma, because the lesion was histologically characterized by solid growths of small to medium-sized round cells. Furthermore, immunohistochemical tests revealed B-cell marker positivity and CD5 positivity, but cyclin D1 negativity. Since it was reported that lymphomas with a mantle cell lymphoma morphology and CD5 expression, but without cyclin D1 overexpression, exist in about 10% of mantle cell lymphoma cases, we diagnosed his disease as mantle cell lymphoma. To our knowledge, this is the first reported case of an early-stage mantle cell lymphoma, originating from the rectum.

Biomarkers, Tumor↗

Immunohistochemical expression of topoisomerase IIalpha (Topo IIalpha) and multidrug resistance-associated protein (MRP), plus chemosensitivity testing, as chemotherapeutic indices of ovarian and endometrial carcinomas.

OBJECTIVE: The purpose of this study was to investigate the chemosensitive and chemoresistant indices of gynecologic malignancies. METHODS: We studied the expression of topoisomerase II alpha(Topo II alpha) and multidrug resistance-associated protein (MRP), and then correlated them with the in vitro chemosensitivities of gynecologic tumor cells using immunohistochemistry and a tetrazolium dye (MTT) assay. RESULTS: In the 19 ovarian carcinomas examined, the mean Topo II alpha index (%) and the tumor cell growth inhibition rate (I.R.: %) for doxorubicin and etoposide in the clear cell adenocarcinomas [15.8, 21.4, 32.3] were all lower than in the endometrioid [33.9; p<0.001, 58.3, 61.9; p<0.05, respectively] and serous adenocarcinomas [43.6; p<0.001, 75.0, 79.8; p<0.01, respectively]. Comparing these markers with the clinical response to chemotherapy, the overall predictive accuracy of the Topo II alpha index and the MTT assay was 87.5% (14/16) and 81.3% (13/16), respectively. In the 24 endometrial carcinomas examined, the mean Topo II a index and the I.R for doxorubicin and etoposide in the G1 carcinomas [22.2, 26.8, 21.5] were significantly lower than in the G2/G3 carcinomas [38.4, 54.0; p<0.001, 40.5; p<0.05]. Furthermore, strong MRP expression (> or = 50%) was detected in 13 (93%) of the 14 G1 carcinomas, but in only 4 (44%) of the 9 G2/G3 carcinomas (p<0.05). CONCLUSIONS: The Topo II alpha index and the results of in vitro chemosensitivity testing may be of assistance in selecting the appropriate chemotherapeutic drugs against gynecologic malignancies based on their histological type and differentiation, along with MRP expression.

Adenocarcinoma, Clear Cell↗

Small cell carcinoma of the gallbladder: a case report and review of 53 cases in the literature.

Although small cell carcinoma of the gallbladder is rare, the prognosis of this tumor type is poorer than that of differentiated carcinomas. We report herein the case of a 62-year-old man with small cell carcinoma of the gallbladder. The operative findings showed an unresectable large tumor of the gallbladder and multiple metastases involving the liver and lymph nodes. Pathological findings revealed small sized carcinoma cells, round or oval in shape which displayed a cord-like or solid appearance. Diagnosis was confirmed by ultrastructural study that showed the presence of neurosecretory-type cored granules. He was treated by intraarterial chemotherapy with cisplatin and etoposide. Six months later, abdominal computed tomography scan confirmed loss of the large mass. A complete response to the chemotherapy was noted over a period of six months, suggesting the efficacy of intraarterial chemotherapy for this disease. Fifty-three cases of small cell carcinoma reported in the English literature are reviewed. In most cases, including ours, a radical operation was not indicated and the prognosis was extremely poor, due to the difficulty of early diagnosis and the rapid progression of the disease. Chemotherapy is effective in general and intraarterial chemotherapy performed in the present case may be particularly useful to improve survival.

Antineoplastic Combined Chemotherapy Protocols↗

Rapid inhibitory effect of tacrolimus on T cell migration by suppressing CD29-related functions.

OBJECTIVE: To clarify the direct effect of Tacrolimus (FK506) on T cell function in relation to CD29. METHODS: Human T cell line H9 and phytohemagglutinin (PHA)-activated T cells were incubated with or without Tacrolimus. The cells underwent cell migration assay by using fibronectin-coated trans-wells, and at the same time the degree of adherence by cultured cells to fibronectin-coated plastic wells was measured. For H9 cells, intracellular filamentous actin formation and the cell surface expression of CD3, CD11a, CD25, CD26, CD44, CD29 were measured by using flow cytometry. Intracellular tyrosin-phosphorylation induced by fibronectin by CD29 stimulation in H9 cells was analyzed by immunoblotting. RESULTS: The ability of H9 cells and PHA-activated T cells incubated with Tacrolimus for 2 hours (hrs) to migrate and to adhere to fibronectin was significantly suppressed. However, the inhibiton was transient, because the ability of cells incubated with Tacrolimus for 24 hrs to migrate was not affected despite the suppression of cell replication. Tacrolimus showed slight but significant reduction of cell surface expression of CD29 within 4 hrs, but CD3, CD11a, CD25, CD26 and CD44 were not affected. Tacrolimus rapidly inhibited intracellular filamentous actin formation; the maximum inhibition was within 2 hrs and the effect was not observed at 6 hrs. Intracellular tyrosin-phosphorylation induced by CD29 stimulation was also inhibited by, Tacrolimus in H9 cells. CONCLUSION: Tacrolimus appeared to have transient early phase inhibitory effects on CD29-related function that may be associated with T cell migration.

Cell Adhesion↗

Rounding of cultured human carcinoid tumor cells by forskolin.

A primary culture of carcinoid cells obtained from a metastasized brain tumor of a 30 year old man was established. Rounding of carcinoid cells was induced by the addition of 20 microM forskolin or 1 mM dibutyryl cyclic AMP to the culture medium. The cyclic AMP content in carcinoid cells was increased thirtyfold by the addition of 20 microM forskolin. The results provided evidence that cyclic AMP might also be involved in rounding of human malignant carcinoid cells.

Adult↗

The surgical management of parasternal recurrence of breast cancer.

Although parasternal recurrence of breast cancer can be adequately controlled by radiation therapy, at times, surgical excision is more effective. In this paper, a new technique for the radical resection of the parasternal portion of the chest wall, including dissection of the internal mammary and supraclavicular lymph nodes, is proposed. Between 1977 and 1984, eleven patients with parasternal recurrence were treated in our department. Five of these cases underwent this kind of operation and four of them are still alive without further recurrence; the remaining patient developed skin metastasis postoperatively. One patient refused radiation therapy but, in any case, radiation therapy failed to control the parasternal recurrences in the other five patients. This new operation is a rational and effective mode of treatment for parasternal recurrence.

Adenocarcinoma↗

Induction of differentiation of human phaeochromocytoma cells in culture by epidermal growth factor and insulin.

A primary culture of malignant phaeochromocytoma cells obtained from a left adrenal tumor of a 56 year old woman complaining of occasional palpitation and headache was established. The addition of epidermal growth factor (EGF) and insulin to the culture medium induced a profound development of network formation of axon-like processes. At the same time, the secretion of catecholamines from cultured cells was also increased. EGF and insulin were demonstrated to induce the differentiation of malignant phaeochromocytoma cells in primary culture.

Adrenal Gland Neoplasms↗

The modified extended mastectomy using the trap-door method as a staging operation.

The choice of operation for breast cancer must be directed towards giving the best chance of local control of the disease. Extended radical mastectomy may be beneficial for patients with internal mammary lymph node metastases, although it has remained controversial. The anterior chest defect created by extended radical mastectomy should be avoided in patients with no metastasis in the internal mammary lymph nodes. This paper, proposes a new technique of modified extended mastectomy using the trap-door method as a staging operation and an intermediate operation between modified radical mastectomy and extended radical mastectomy. In this operation, the axillary dissection could be performed by reflecting the pectoralis major muscle and the internal mammary lymph nodes could be dissected by reflecting the parasternal chest wall in trap-door fashion. In cases in which the metastasis is histologically found in the internal mammary content, extended radical mastectomy by sternal splitting is preferred.

Breast Neoplasms↗

Regional lymph node metastases in well-differentiated thyroid carcinoma.

The status of regional lymph node metastases was assessed in 171 patients with thyroid cancer who underwent a variety of thyroidectomy procedures with regional lymph node dissection at Kanazawa University, from January 1979 to March 1986. The rates of regional lymph node metastasis in minimal and ordinary thyroid cancer were 57% and 84% respectively. Since the rates of lymph node metastasis were high not only in the central cervical compartment but also in the lateral jugular compartment, modified radical neck dissection in the ipsilateral neck is at least recommended in patients with these thyroid cancers. Furthermore, high frequencies of bilateral regional lymph node metastases were found in patients with obviously widespread involvement of the bilateral lobes, with cancer located in the isthmus, with clinically detectable bilateral or contralateral jugular lymph node metastases and with histological involvement in the contralateral paratracheal lymph nodes. Bilateral modified radical neck dissection is recommended in these patients.

Adenocarcinoma↗

Biochemical comparison of myeloperoxidase of leukemic myeloblasts and normal neutrophilic granulocytes.

Myeloperoxidases were purified from leukemic myeloblasts (Mbl-MPO) and from normal neutrophilic granulocytes (Gra-MPO) and were compared with each other biochemically. Gel filtration studies showed that the molecular weights (Mr) of Mbl-MPO and Gra-MPO were about 70,000 and 130,000, respectively, so that the former is almost one-half the molecular size of the latter. On sodium dodecyl sulfate-polyacrylamide gel electrophoresis with 2-mercaptoethanol, both MPOs split into two major subunits, heavy and light peptide chains. However, each of these chains of Mbl-MPO seemed to be smaller than that of Gra-MPO, Mr 58,000 versus Mr 62,000 for the heavy chain and Mr 12,000 versus Mr 15,000 for the light chain. On the other hand, another band of Mr 34,000 also appeared in Mbl-MPO under nonreducing conditions and in both MPOs after being boiled. The size of this band was not different in the two MPOs, but the ratio of this band to the others was much higher in Mbl-MPO. The activity of Mbl-MPO could be demonstrated in the heavy chain of Mr 58,000, using a blotting method, and was found to be less heat stable than that of Gra-MPO. These findings indicate that Mbl-MPO may represent an incomplete, unstable half-enzyme form of Gra-MPO.

Electrophoresis, Polyacrylamide Gel↗

Effects of prophylactic irradiation of acute lymphoblastic leukemia in the central nervous system of children.

The development of prophylactic therapy for acute lymphoblastic leukemia (ALL) in the central nervous system in children has resulted in an improvement of the prognosis and prolongation of patients' lives. On the other hand, late irradiation effects have increased with the improvement of the prognosis. Therefore, there is now an important need to lessen these late effects without deteriorating the prognosis. We have investigated the recurrence rate, the survival rate and the cause of death of ALL patients who were divided into a none prophylactic irradiation group and 15 Gy, 20 Gy and 24 Gy irradiation groups. The results show that the effect of prophylactic irradiation has been more effective in the 20 Gy group than that of the 24 Gy group. Furthermore, brain atrophy and leukoencephalopathy, which were investigated by X-ray CT in long-term survivors of post-prophylactic irradiation without recurrence, have been less in the 20 Gy group than in that of the 24 Gy group. This report presents the result that the most favorable dose for prophylactic irradiation for central nervous system leukemia of ALL in children is 20 Gy by a step-up method.

Atrophy↗

Detection of P-glycoprotein in solid tumors by flow cytometry.

P-glycoprotein (P-gp) detection by FCM (flow cytometry) was correlated with P-gp detection by immunohistochemical staining or Western blotting in K562 cell lines variably resistant to doxorubicin (DOX). A strong correlation was noted between the flow cytometric data and the degree of resistance assessed by thymidine incorporation assay (TIA). Of the human carcinomas tested, 37.5% were P-gp positive by flow cytometry. The flow cytometry data correlated strongly with the immunohistochemical staining (p < 0.001). Thirteen of the 15 P-gp positive tumors were resistant to DOX and vincristine (VCR) on TIA. Thus, P-gp detection by FCM correlates strongly with tumor sensitivity to DOX and VCR (p < 0.001).

ATP Binding Cassette Transporter, Subfamily B, Mem↗