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Biomedical subjects

S Imoto

Publications and source records attributed to S Imoto.

At least 91 records · Page 5Linked to original sources
PubMed1997

Fibrotic focus in invasive ductal carcinoma of the breast: a histopathological prognostic parameter for tumor recurrence and tumor death within three years after the initial operation.

We investigated whether the presence of a fibrotic focus (FF) in the primary lesion and in lymph node metastasis is a good predictor of early tumor recurrence or death in patients with invasive ductal carcinoma (IDC). Multivariate relative risk (RR) of tumor recurrence and death according to the presence of FF in the primary tumor was estimated using the Cox proportional hazards regression model with adjustment for other prognostic factors (histologic grade, T classification, nodal status, tumor necrosis, DNA ploidy, c-erbB-2 protein expression, p53 protein expression, and labeling index of proliferating cell nuclear antigen). For the evaluation of the metastatic status in the axillary lymph nodes, RR of multivariate analysis was adjusted for the presence of FF in the metastatic tumor and the number of lymph nodes involved (1-3 and > 3). The presence of FF increased the RR of tumor recurrence significantly for the cases in all stages, and especially for those in stages I and II (RR = 6.9, P < 0.05 and RR = 25.0, P < 0.005, respectively). All cases that died of disease had FF. Among IDCs with FF, 24 cases had FF in lymph node metastasis. Significantly higher RRs of tumor recurrence and death were observed in cases with FF in lymph node metastasis than in those without it (RR = 2.0, P < 0.001 and RR = 5.9, P < 0.05, respectively). It was suggested that the presence of FF is an important predictor of early tumor recurrence or death in patients with IDCs. The presence of FF in lymph node metastatic lesions is also a significant prognostic parameter.

Adult↗
PubMed1997

Significance of basic fibroblast growth factor and fibroblast growth factor receptor protein expression in the formation of fibrotic focus in invasive ductal carcinoma of the breast.

A fibrotic focus (FF) is a scar-like area within invasive ductal carcinoma (IDC) of the breast, and has been shown to be a marker of high aggressiveness of IDC. In order to investigate the mechanism of FF formation in IDC, expression of basic fibroblast growth factor (bFGF) and fibroblast growth factor receptor (FGFR) was studied. One hundred and forty-nine IDCs were divided into solid tumors and scirrhous tumors. Immunohistochemistry was used to determine the expression of bFGF and FGFR proteins in both tumor cells and fibroblasts forming FF. Scirrhous tumors with FF showed a significantly higher frequency of bFGF protein expression than those without (P = 0.017), whereas, in solid tumors, the presence of FF was not significantly associated with the frequency of bFGF protein expression (P = 0.143). In addition, scirrhous tumors showed a significantly higher frequency of FGFR protein expression than solid tumors (P = 0.001). Among IDCs having FF and expressing bFGF protein, a significantly larger number of fibroblasts expressing FGFR protein within FF was observed in scirrhous tumors than in solid tumors (P = 0.016). The results of this study suggest that in scirrhous tumors the interaction between tumor cells and stromal fibroblasts plays an important role in the formation of FF, and that there is a paracrine mechanism between bFGF protein from tumor cells and FGFR protein in fibroblasts.

Adenocarcinoma, Scirrhous↗
PubMed1997

[Simultaneous presence of macroamylase and macrolipase in a patient].

Here we report a case demonstrating simultaneous macroamylasemia and macrolipasemia. The patient showed persistently elevated serum amylase and lipase activities. On thin-layer gelfiltration, normal serum amylase migrated as a round spot behind albumin. However, serum amylase from this patient migrated slightly ahead of albumin. This finding indicated that serum amylase from this patient had a molecular weight greater than that of normal amylase. Lipase of normal serum was eluted from a Sephacryl S-300 column after the 4S protein. Lipase in the serum from this patient was eluted from the column slightly behind the 19S protein. This finding indicated that serum lipase from this patient also had a molecular weight greater than that of normal lipase. The conversion of macroamylase and macrolipase was observed when the normal serum was mixed with the patient's serum. To determine the isotypes of immunoglobulin (Ig) that was bound to amylase and lipase in the patient's serum, we investigated the effect of adding various anti-human Ig sera to the patient's serum. Amylase activity was precipitated only with anti-IgA lambda and lipase activity was precipitated both with anti-IgA lambda and anti-IgA kappa (anti-IgA kappa > anti-IgA lambda). Taken together, these data indicate that the material that enhanced amylase and lipase activities in the patient's serum was monoclonal IgA; IgA lambda for amylase and both IgA lambda and IgA kappa for lipase.

Amylases↗
PubMed1997

[Present status and advances in detecting Shiga toxin-producing Escherichia coli O157].

Currently, detection of Shiga toxin-producing Escherichia coli(STEC) in stool samples is based on the isolation method in most clinical laboratories. The procedures are as follows: i) isolation with selective agar plates, ii) biological test with differential media, iii) serological test of anti-O antisera, iv) detection of toxin or toxin gene. These procedures take 4 days, therefore more rapid method is required. In the near future, a rapid detection method that detects STEC directly from stool samples will be introduced. Polymerase-chain reaction (PCR), enzyme-linked immuno-sorbent assay (ELISA), detection of serum anti-O157 antibodies are now available in clinical laboratories. Result of PCR for detection Shiga toxin gene and serum anti-O157 antibodies are described. Fifteen stool and serum samples from patients suspected of STEC infection were examined. With the culture and PCR method, 2 patients were positive by both methods and the results were confirmed in both cases. Six patients were positive by the antibodies detection method. From these results, the PCR method using stool samples was useful as a rapid detection method in clinical laboratories. Detection of serum antibodies has been simplified and is not an expensive method. Therefore, the method is useful for clinical diagnosis of STEC infection, especially, for diagnosing HUS or after antimicrobial agents have been administered to patients.

Adolescent↗
PubMed1996

A regulatory role of c-Fos in the development of precursor B lymphocytes mediated by interleukin-7.

The proto-oncogene product c-Fos, a component of the transcription factor AP-1, plays a critical role in the expression of genes required for cellular proliferation and differentiation. The c-Fos is induced in early B lineage cells developed in the interleukin-7-dependent bone marrow (BM) cell culture from normal mice. In order to investigate a role of the c-Fos in early B cell development, we have used BM cells from two different transgenic mice carrying the exogenous c-fos gene controlled by the promoter of the H-2Kb gene (H2-c-fos) or the interferon alpha/beta (IFN)-inducible Mx gene (Mx-c-fosD). Development of B lineage cells was retarded in the BM cell culture from H2-c-fos mice. Although B lineage cells normally developed in the BM cell culture from Mx-c-fosD mice without IFN stimulation, the development was completely blocked in the Mx-c-fosD culture when transgenic c-fos was induced in BM cells by IFN stimulation. Furthermore, the IL-7-dependent proliferation of B lineage cells in Mx-c-fosD BM cells was also suppressed by the induction of c-Fos. These results suggest that the c-Fos plays a role as a negative regulator in the early B cell development.

Animals↗
PubMed1996

Refractory thrombocytopenia with chromosome 11q23 abnormality.

Although cytopenia is a common manifestation of myelodysplastic syndrome (MDS), isolated thrombocytopenia is rare. The term "refractory thrombocytopenia" (RTC) has been proposed as a counterpart of refractory anemia. We describe here a case of RTC associated with chromosome abnormality on 11q23. A 59-year-old man was admitted because of severe thrombocytopenia. A bone marrow examination revealed an increased number of micromegakaryocytes and the absence of normal-sized megakaryocytes without obvious dysplasia in either the myeloid or the erythroid lineage. A remarkable increase of GPIIb/IIIa (CD41a)-positive precursor cells in the bone marrow was observed. Cytogenetic examination detected the chromosome abnormality, an addition on chromosome 11q23. Translocation of the HRX gene was not detectable by Southern blot analysis. The diagnostic problems of isolated thrombocytopenia and possible participation of gene(s) on chromosome 11q23 in megakaryocytopoiesis as well as early hematopoiesis are discussed.

Biopsy, Needle↗
PubMed1996

A novel mutation in the ferrochelatase gene associated with erythropoietic protoporphyria.

Erythropoietic protoporphyria (EPP) is a hereditary disorder caused by mutations of the ferrochelatase gene. We investigated a Japanese patient with a dominant form of erythropoietic protoporphyria for a ferrochelatase mutation. Sequence analysis of the proband's ferrochelatase cDNA revealed a T to C point mutation at nucleotide 557. This mutation resulted in the replacement of Ile by Thr at amino acid position 186, a novel mutation in erythropoietic protoporphyria. An increase in ferrochelatase activity was not observed in the crude extract of E. coli over-expressing the mutant protein compared with the control, whereas a marked increase in activity was observed in that over-expressing the wild type. Prediction of the secondary structure of ferrochelatase suggested that the Ile186-->Thr mutation changed the original beta-sheet structure to an alpha helix in the region including amino acid residue of mutation. We conclude that, in the patient, the Ile186-->Thr mutation had abolished enzyme activity, possibly by disrupting the secondary structure, thereby causing erythropoietic protoporphyria.

Adult↗
PubMed1996

Fibrotic focus in invasive ductal carcinoma: an indicator of high tumor aggressiveness.

Histological examination of invasive ductal carcinoma of the breast often demonstrates the presence of an extensive central fibrotic focus (FF). The clinicopathological significance of the FF, or scar, in primary invasive ductal carcinoma is still ambiguous. One hundred and fifty-three cases of invasive ductal carcinoma (IDC) were classified into two groups, those with and those without FF. The differences in frequency of immunohistochemically detected overexpression of c-erbB-2 protein and nuclear accumulation of p53 protein, and the labeling index of proliferating cell nuclear antigen (PCNA), as well as histopathological parameters were compared between these two groups. IDCs smaller than 50 mm with FF showed a higher frequency of high-grade tumors, a higher frequency of lymph node metastasis, and a significantly higher frequency of c-erbB-2 protein overexpression than those without FF. In tumors of 20 mm or less, the incidence of nuclear accumulation of p53 protein was significantly higher in tumors with than those without FF. Tumors with FF showed a significantly higher PCNA labeling index than those without FF, regardless of tumor size. The present results indicate that the presence of FF is an important clinicopathological parameter associated with a higher degree of malignancy in IDCs, especially those smaller than 50 mm. Therefore, dividing IDCs into those with and those without FF appears to be meaningful clinicopathologically.

Adult↗
PubMed1995

[Study for clinical usefulness of CEA, TPA, CA15-3 and BCA225 in breast cancer].

CEA, TPA, CA15-3 and BCA225 are the most frequently assayed as tumor markers for breast cancer. The aim of the present study was to reinvestigate the clinical usefulness of these markers in patients with breast cancer (primary: 28, recurrent: 15). In the cases of primary breast cancer, including all stages, positive rates of CEA, TPA, CA15-3 and BCA225 were 18%, 25%, 11% and 18%, respectively, while in the advanced cases of stage III+IV, positive rate of both CEA and TPA increased to approximately 40%. The positive rate of combination assays using four tumor markers was 46% in the cases of primary breast cancer including all stages and was 73% in the cases of advanced primary breast cancer (stage III+IV). In the cases of recurrent breast cancer, the positive rates of CEA, TPA, CA15 3 and BCA225 were 60%, 60%, 67% and 60%, respectively. When all of those tumor markers were used for assays, all of the patients with recurrent breast cancer studied showed elevated serum levels of at least one of these tumor markers. We retrospectively analyzed serum levels of tumor markers in 15 patients who relapsed breast cancer after surgical resection. In 2 patients elevation of some of four tumor markers occurred before the recurrent tumor was detected with RI scintillation and computed tomography. These results suggested that combination assays using CEA, TPA, CA15-3 and BCA225 should be helpful for detecting the recurrence of breast cancer, and also detecting the advanced primary breast cancer.

Antigens, Tumor-Associated, Carbohydrate↗
PubMed1995

The confusion associated with breast cancer chemotherapy in Japan: the first year's experience at the Division of Oncology and Hematology, National Cancer Center Hospital East.

The current status of breast cancer chemotherapy in Japan was examined and compared with internationally accepted standard therapy, by reviewing the previous treatment of patients with advanced or metastatic breast cancer who had been referred to the National Cancer Center Hospital East. Forty patients were referred mainly from middle-sized or large hospitals between July 1992 and June 1993. The most commonly used regimen for adjuvant therapy was a combination of long-term and oral low-dose fluoropyrimidine compounds (LDFU), which is rarely used in Western countries, and tamoxifen. Some patients had received perioperative intravenous mitomycin C. The adjuvant polychemotherapy most commonly used internationally has been given to only a few patients. The first-line treatment for advanced or metastatic disease in the previous hospitals varied, but myelosuppressive chemotherapy including anthracyclines was given to half of the patients. Oral LDFU was also used for some patients alone or in combination as the first-line chemotherapy. Local therapy for metastasis to soft tissue was performed in 9 patients. Oral LDFU therapy that is frequently used for cancer treatment in Japan should be evaluated in a well designed controlled trial.

Adult↗
PubMed1994

Plasma cell leukemia with myelofibrosis.

We describe a case of plasma cell leukemia associated with myelofibrosis. A 60-year-old woman was admitted due to lumbago and monoclonal hypergammaglobulinemia. Peripheral blood showed about 40% of plasma-cell-like cells. A bone marrow aspiration was dry tap. The patient was diagnosed as having plasma cell leukemia with myelofibrosis by bone marrow biopsy. Plasma cell leukemia as well as myelofibrosis improved with combination chemotherapy using vincristine, pirarubicin, and dexamethasone. However, when plasma cell leukemia became resistant to chemotherapies, myelofibrosis also reappeared. This case strongly suggests the pathogenetic relationship between plasma cell leukemia and myelofibrosis.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1994

c-fos and jun gene expression in murine precursor B lymphocytes developed in the interleukin-7-dependent bone marrow cell culture.

We analyzed the expression of c-fos and jun family gene in murine pre-B cells developed in the interleukin-7-(IL-7) dependent bone marrow cell culture. The c-fos gene was expressed in the pre-B cells. The c-fos RNA became undetectable after IgM+ B cells were developed in the culture. The c-fos expression in the pre-B cells was IL-7-dependent. However, the c-fos RNA was not induced when the pre-B cells cultured without IL-7 for 6 h were restimulated with IL-7. The expression of c-jun RNA was slightly induced in the restimulated pre-B cells. The junB and junD RNA were the steady state level in the cells. These gene products formed AP-1 molecule in the pre-B cells. These results suggest that the AP-1 plays a role in the IL-7-dependent pre-B cell development.

Animals↗
PubMed1994

[Phase I study of CGS16949A--a new aromatase inhibitor. Cooperative Study Group for CGS16949A].

Phase I study of CGS16949A--a new aromatase inhibitor--was performed in postmenopausal women with advanced breast cancer who received either single oral administration of 4 and 8 mg, or multiple oral daily administration of 1, 2, 4, 8 and 16 mg for 5.5 days. No side effects were observed after single dose administration of 4 mg and 8 mg of CGS16949A. In the multiple administration, one patient received 1 mg/day for 3 days complained of abdominal pain (Grade 2), but administration of CGS16949 A was continued despite of the pain. In order to assess the causal relationship of the drug with the abdominal pain, the number of patients in 1 mg/day group was doubled from 3 to 6 patients, but no side effects were observed in the remaining five patients. In addition, no side effects, including abdominal pain, were noted in the other 2, 4, 8 and 16 mg/day groups. After multiple administration, plasma concentrations of estradiol at 5 hrs after the final dosage in the respective dose groups were reduced to 47.1 +/- 8.3%, 37.3 +/- 3.0%, 28.0 +/- 7.8%, 26.0 +/- 11.3% and 26.6 +/- 13.8% respectively. Similar tendencies were observed in estrone plasma levels and urinary estrogens levels. In this study, the reduction of plasma estrogen levels was confirmed following administration of CGS 16949A. The clinical usefulness of this new aromatase inhibitor remains to be studied further.

Administration, Oral↗
PubMed1993

Regulation of class II MHC gene expression by the inducible anti-sense RNA in transgenic mice.

We have established a gene regulatory system in mice by the inducible anti-sense RNA. We have generated transgenic mice carrying the anti-sense DNA composed of the class II MHC gene under the control of the human metallothionein IIa gene promoter. The detectable amount of anti-sense RNA was constitutively produced in spleen and bone marrow from transgenic mice and the amount in spleen was increased about fivefold by the stimulation of mice with heavy metal ions. We have previously reported that the reduction of class II MHC molecules on early B lineage cells by the anti-sense RNA results in delay of their development in the bone marrow culture. The early B cell development was slightly delayed in the culture from the transgenic mice. This delay was augmented in the culture by the addition of heavy metal ions in proportion to its concentration. These results suggest that the inducible anti-sense RNA reduces the expression of class II MHC molecules on B lineage cells.

Animals↗