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Biomedical subjects

S Imoto

Publications and source records attributed to S Imoto.

At least 73 records · Page 4Linked to original sources

Defective human T-lymphotrophic virus type I provirus in T-cell prolymphocytic leukaemia.

T-cell prolymphocytic leukaemia (T-PLL) is a rare form of post-thymic T-cell neoplasm, the aetiology of which remains unknown. We examined human T-lymphotropic virus (HTLV) provirus in five HTLV-I/II seronegative patients with T-PLL. Southern blotting did not show monoclonal integration of the HTLV-I genome in any of the DNA samples. However, two of the five DNA samples contained an HTLV-I tax sequence. Other sets of oligonucleotide primers for HTLV-I gag, pol, env and LTR regions were all negative. HTLV-I tax gene expression and p40tax antibody were not detected in samples from cases with HTLV-I tax sequence. Our findings suggest that there may be alternative mechanisms involved in HTLV-associated leukaemogenesis, in which HTLV-I genome insertion triggers T-PLL but the deletion of various regions of the integrated provirus subsequently prevents active replication and the expression of the virus.

Adult↗

Optimizing microvessel counts according to tumor zone in invasive ductal carcinoma of the breast.

We calculated microvessel counts (MVCs) by analyzing CD31-stained sections in three tumor zones (central, intermediate, and peripheral) in 147 cases of invasive ductal carcinoma (IDC). The purpose of the study was to discover whether there is a difference in MVC in the different zones of tumor, which zone contains the highest MVC within the tumor, from which zone the MVCs best correlate with tumor recurrence or tumor death, and which histologic factors correlate with the MVC of the tumor. Sections were scanned to assess the highest number of microvessels in any single 200 x field (0.384 mm2). In all of our cases, the average MVCs of the central, intermediate, and peripheral zones of the IDCs were 34.4, 39.4, and 51.5 per 200x field, respectively. The MVC significantly increased from the central to the peripheral zones (P < .001). In the univariate analysis, in at least one tumor zone, the MVC was correlated with T classification, tumor necrosis, fibrotic focus (a scar-like area within IDCs), and c-erbB-2 protein expression. The only factor significantly correlated with a higher MVC in all of the three zones was fibrotic focus. Moreover, in the multivariate analysis, tumors having high MVCs in the peripheral zone were significantly associated with higher hazard ratios for tumor recurrence (P < .05). This study showed that the MVC of an IDC significantly increases from the central to the peripheral zones, and it showed that angiogenesis in the peripheral zone is associated with prognosis. Therefore, estimation of angiogenesis should be performed in the peripheral zone for reliable prediction of outcome in breast cancer patients. As a surrogate for angiogenesis, fibrotic focus seems to be a useful marker for malignant potential in breast cancer.

Adult↗

Pharmacokinetic study of low- versus high-dose medroxyprogesterone acetate (MPA) in women.

The present study was conducted to compare the pharmacokinetics (PK) of low-dose versus high-dose medroxyprogesterone (MPA) as a once-daily oral administration. Of 32 patients, all women, enrolled in this PK study, 18 received 600 mg MPA daily and 14 received 1200 mg daily. Detailed PK data were obtained on day 1 and after more than 4 weeks of MPA treatment. In addition, multiple data for the minimum steady-state concentration (Css min) were analyzed. The MPA serum concentrations were measured by high-performance liquid chromatography. Wide interpatient variability was found in the PK parameters obtained both on day 1 and after more than 4 weeks. There were no clear relationships between the oral dose and the MPA peak concentration (Cmax), area under the time versus concentration curve (AUC), or mean Css min. Weight gains of 10% or more were demonstrated more frequently in the high-dose group (P < 0.01). Liver dysfunction (n = 5) did not influence the PK of MPA. Five patients demonstrated extremely low AUC and Cmax (< 10 ng/ml) values on day 1. Phenobarbital, dexamethasone and betamethasone were being taken concomitantly with the MPA each by one patient. The serum MPA concentrations were markedly increased after the discontinuation of phenobarbital in that patient, suggesting a drug interaction. At present we cannot recommend the high dose of MPA, except in clinical studies, from a PK or a pharmacodynamic points of view.

Adult↗

Malignant phyllodes tumour with a noninvasive ductal carcinoma component.

A malignant phyllodes tumour with a noninvasive ductal carcinoma component is reported. The patient was an 80-year-old Japanese woman with a breast tumour detected by routine physical examination. A simple mastectomy was performed. The excised tumour was 10.5 x 9.4 x 5.4 cm in size and bulged into the skin with ulceration. The macroscopic appearance was that of a phyllodes tumour. Histologically the tumour consisted mainly of stromal components with a leaf-like structure lined by atypical ductal epithelium. The epithelial component showed gradual evolution to intraductal papillary carcinoma in a few areas. The stromal component was composed mainly of fibrosarcoma with areas of osteosarcoma and rhabdomyosarcoma. Neither stromal invasion of intraductal carcinoma nor transition between the stromal and epithelial elements was seen. Three months after the operation, death occurred, with multiple pulmonary and subcutaneous metastases. This case probably represents malignant change in both the stromal and the epithelial components of a phyllodes tumour. Since the two elements were independent, the possibility that a phyllodes tumour may be one of the origins of true carcinosarcoma is raised.

Aged↗

Proliferative reaction of myelogenous leukemia cells with cytokines G-CSF, GM-CSF, M-CSF, SCF and TPO.

In recent years, many cytokines have been defined and some of them used clinically. In hematological malignancies, cytokines, including granulocyte colony-stimulating factor (G-CSF), have been widely used for leukopenia after chemotherapy. However, in acute myelogenous leukemia (AML), some leukemic cells may be induced to proliferate by these cytokines and they must be used with care. In this study, we have investigated cell reactivity and proliferation with G-CSF, granulocyte-macrophage colony-stimulating factor (GM-CMF), macrophage colony-stimulating factor (M-CSF), stem cell factor (SCF) and thrombopoietin (TPO) in cases of AML. We have also investigated the reactivity of some myeloid leukemia cell lines to TPO. G-CSF, GM-CSF, M-CSF, SCF and TPO caused proliferation of leukemic cells in 25%, 58.3%, 8.3%, 21.1% and 0% of cases, respectively. Because of this result, the use of G-CSF in AML should be regarded as potentially hazardous. TPO did not cause proliferation of leukemic cells in any case of AML, or in cell lines except MO7E, which is a megakaryocytic cell line. This result suggests that TPO might cause proliferation of some megakaryocytic leukemia cells. We cannot conclude that TPO does not cause proliferation of other AML cells, as the number of cases was small and it has been reported elsewhere that leukemia cells may proliferate when exposed to TPO in 50% of AML cases. Reactivity of AM L cells to TPO is an important factor when deciding the indications of TPO in AML and myelodysplastic syndrome.

Cell Division↗

14q11 abnormality and trisomy 8q are not common in Japanese T-cell prolymphocytic leukemia.

We studied ten cases of Japanese T-cell prolymphocytic leukemia (T-PLL) collected over the last 9 years. Median age was 61 years with a male predominance (M:F, 8:2). The main disease features were splenomegaly, lymphadenopathy, hepatomegaly, skin lesions and serous effusions. The clinical course was progressive with a median survival of 10 months. Immunophenotyping showed that the prolymphocytes had a post-thymic phenotype (TdT-, CD1a-, CD2+, CD3+, CD5+, CD7+) with a predominant CD4+ immunophenotype. Cytogenetic analysis showed no consistent abnormalities. 14q abnormality and trisomy 8q, which are frequently seen in T-PLL of Western countries, were found in only two and zero cases, respectively. We conclude that the clinical and biological characteristics of T-PLL in Japan are almost the same as those in Western countries. However, the cytogenetic findings of T-PLL in Japan might be different.

Adult↗

Coagulation abnormalities and thrombotic microangiopathy following bone marrow transplantation from HLA-matched unrelated donors in patients with hematological malignancies.

Thrombotic microangiopathy is a well-known heterogeneous disorder that occurs as a complication of allogenic bone marrow transplantation (BMT). We evaluated 12 consecutive patients receiving HLA-matched unrelated BMT and 12 consecutive recipients of HLA-identical related BMT for the development of bone marrow transplantation-associated thrombotic microangiopathy (BMT-TM) on days 30 and 60 following BMT. A diagnosis was made in four of 12 (33.3%) unrelated compared to none of 12 (0%) HLA-identical cases. Levels of serum lactic dehydrogenase (LDH), fibrin degraded products (FDP) and de novo thrombocytopenia were elevated in eight of 12 patients (66.7%) receiving unrelated donor BMT, and none of the patients receiving related donor BMT. Our findings suggest clinical or subclinical microangiopathic changes may occur frequently in unrelated donor BMT. FDP elevation is possibly an important marker of microangiopathic changes as early complications of BMT.

Adolescent↗

Detection of the first recurrence during intensive follow-up of breast cancer patients.

BACKGROUND: Breast cancer patients are routinely followed after primary treatment. Many intensive diagnostic methods (tumor markers, chest X-ray, mammography, liver echography, bone scans) are performed periodically. However, it remains to be determined how often attempts should be made to detect the first recurrence of breast cancer by these methods. METHODS: To evaluate the effect of imaging diagnosis and tumor markers, we analyzed methods of detection of first recurrence sites during intensive follow-up of breast cancer patients. RESULTS: Of 550 female patients who had been surgically treated between July 1992 and December 1996, 65 recurrent cases had been diagnosed as of December 1997. Thirty cases (46%) had been found as a result of symptoms related to the site of recurrence and 14 cases (22%) were detected by physical examination. In the remaining 21 cases (32%), detection was by other methods: in eight cases by imaging diagnosis, in three cases based on abnormal tumor markers and in 10 cases by imaging diagnosis and abnormal tumor markers. Twenty-nine cases (45%) followed every 1-3 months had presented with symptoms at routine or interval appointments. There was a significant difference between first recurrence sites (loco-regional, bone and viscera) and the methods of detection (symptoms, physical examination and other diagnostic methods) (P < 0.0001). However, no statistical difference in overall survival after operation was observed between the 30 cases found as a result of symptoms and the 35 cases detected by physical examination or other diagnostic methods. CONCLUSIONS: Taken together with ASCO's surveillance guidelines (J Clin Oncol 1997;15:2149-56), intensive follow-up of breast cancer patients should be limited to high-risk breast cancer patients, especially those who enter randomized clinical trials. A careful history and physical examination are in practice indicated every 3-6 months for 3 years and then every 6 months for the following 2 years.

Adult↗

Determination of cytosol c-erbB-2 protein in breast cancer by sandwich enzyme immunoassay.

We determined cytosol c-erbB-2 protein levels using a sandwich enzyme immunoassay in benign breast disease and primary and recurrent breast cancer and analyzed the relationship between c-erbB-2 protein levels and clinicopathological factors. Overexpression of c-erbB-2 protein, the cut-off value being set at 18 ng/mg protein, was observed in 26 of the 139 cases of stages I-IIIB breast cancer (18.7%), four of the 12 cases of stage IV breast cancer (33.3%) and seven of the 13 recurrent breast cancer cases (53.8%). The levels of c-erbB-2 protein were significantly different between the stages. Overexpression of c-erbB-2 protein in stages I-IIIB breast cancer was associated with histological grade and serum CEA level, but not with other clinicopathological factors. In addition, there was an inverse correlation in the group of stages I-III plus IV breast cancer between c-erbB-2 protein expression and estrogen receptor status. Overexpression of c-erbB-2 protein can be easily determined in the cytosol fraction together with hormonal receptor by this method. The prognostic importance will be evaluated in ongoing adjuvant trials for operable breast cancer patients.

Breast Diseases↗

Intracystic papillary carcinoma of the breast in male: case report and review of the Japanese literature.

We report a case of intracystic papillary carcinoma of the breast in a 62-year-old Japanese man, who came to our hospital complaining of a right subareolar mass. Imaging diagnosis was a cyst with an intracystic component. Since repeated aspiration biopsy cytology was interpreted as a borderline lesion, no additional treatment had been given. Because he wanted the removal of the mass 14 months after his first visit, an excisional biopsy was performed under local anesthesia. Pathological examination revealed the intracystic component to be non-invasive papillary carcinoma. Although the incidence of male breast cancer is approximately 1% of all breast cancer, intracystic papillary carcinoma in the male is very rare. From a review of the literature on this disease in Japanese men, an intracystic component can often be demonstrated by ultrasound. However, it is difficult to confirm malignant cells by aspiration biopsy cytology of cyst fluid. Since some cases have a local relapse, excisional biopsy and long-term follow-up are indicated.

Biopsy↗

A proposal for a new histological classification scheme for predicting short-term tumor recurrence and death in patients with invasive ductal carcinoma of the breast.

Tumor recurrence rate (TRR) and mortality rate (MR) of invasive ductal carcinoma (IDC) of the breast in short-term follow-up are relatively low. Nevertheless, it is extremely important to identify patients at risk of early recurrence or death after surgery. The aim of this study was to establish a new histological prognostic classification scheme for IDC in order accurately to predict the short-term outcome. The following histological parameters were analyzed in 201 IDCs: 1) tumor size, 2) structural atypia, 3) nuclear atypia, 4) number of mitotic figures, 5) fibrotic focus (FF), 6) vascular invasion, 7) tumor necrosis, 8) skin invasion, 9) muscle invasion, 10) nodal status and 11) extramammary fat invasion. Multivariate analysis showed that nuclear atypia, presence of FF, and the invasive length of fat invasion (ILFI) were the most important histological parameters correlated with TRR or MR of IDCs. Accordingly, a new histological classification based on nuclear atypia, FF and ILFI (Nucleus-Fibrotic focus-Fat invasion, NFF) was devised. Comparative studies were performed with the following existing prognostic classifications: 1) histological grade, 2) modified Scarff-Bloom-Richardson histological grade, 3) prognostic index and 4) pathological TNM (pTNM) stage classifications. Patient grouping defined by NFF classification significantly correlated with tumor recurrence or death of IDCs in all cases, cases at stages I and II, those without lymph node metastasis and those who were estrogen receptor (ER)-positive after adjustment for the other four classifications, using multivariate analysis. NFF classification appeared superior to existing prognostic classifications for the accurate prediction of the short-term outcome for patients with IDCs in low risk groups.

Adipose Tissue↗

A case of well-differentiated minute hepatocellular carcinoma with extrahepatic metastasis.

A rare case of well-differentiated minute hepatocellular carcinoma (HCC) metastasizing to distant sites in a 77-year-old man with hepatitis C virus (HCV)-related cirrhosis is presented. Ultrasonography (US) disclosed a 9 mm hypoechoic lesion in segment seven (S7) of the liver, although computed tomography (CT), magnetic resonance imaging (MRI) and angiography did not reveal any space-occupying lesion. Ultrasound-guided biopsy showed the histological features of well-differentiated HCC. A plain film of the abdomen and CT revealed osteolytic changes in the sacrum and the lumbar vertebra. Ultrasound-guided biopsy of the sacrum revealed well-to-moderately differentiated HCC metastasizing from the liver. Percutaneous ethanol injection therapy (PEIT) effected complete response and completely eliminated the abnormal findings on US. Three months after PEIT, metastasis to the thoracic vertebra was revealed by CT, despite negative alpha-fetoprotein-mRNA in serum. This is the first report describing a well-differentiated HCC with metastatic potential. Further studies may provide insights into metastasis of well-differentiated HCC.

Aged↗

Prediction of efficacy of interferon treatment of chronic hepatitis C by multivariate analysis and a new classification.

One hundred and fifteen patients with chronic hepatitis C were administered interferon (IFN) and classed into two groups: (i) complete responders (CR), HCV-RNA continuously negative 1 year after treatment; and (ii) non-responders (NR), positive 1 year after treatment. Multivariate analysis comprised eight variables: age, sex, transfusion history, alanine aminotransferase level, viral genotype, level of viremia, type of IFN, and total amount of IFN. The HCV-RNA level was correlated with complete response (P = 0.0175). Liver biopsy specimens were classified into four grades and stages according to the measure of severity and the extent of fibrosis, respectively. There was no correlation between the efficacy rate and grading. However, in staging there was a difference in the efficacy of IFN between stages 1 or 2, and stage 3 (0.05 < P < 0.1 and 0.01 < P < 0.025, respectively). Of the CR patients, 0% (0/5) were at stage 0 (no fibrosis); 27.5% (22/80) at stage 1 (mild); 42.9% (6/14) at stage 2 (moderate); and 6.3% (1/16) at stage 3 (severe fibrosis). Thus the new classification would be useful in predicting roughly the efficacy of IFN.

Adolescent↗

[Multicentric Castleman's disease with lymphoid interstitial pneumonia and polyneuropathy].

A 51-year-old woman was admitted to a local hospital because of pneumonia, and received a diagnosis of cervical lymphadenopathy, anemia, and hyperimmunoglobulinemia with suspected multicentric Castleman's disease (MCD). At the age of 53 she was transferred to our hospital because of numbness and muscle weakness. Polyclonal hyperimmunoglobulinemia was observed, and biopsy specimens of lymph node tissue revealed infiltration of plasma cells in the interfollicular areas, thus leading to a diagnosis of MCD. A chest computed tomography scan revealed diffuse nodular shadows in all lung fields, and a transbronchial lung biopsy disclosed infiltration of plasma cells in the alveolar septa. Together, these findings indicated lymphoid interstitial pneumonia (LIP). Polyneuropathy was diagnosed by neurological examination and nerve conduction studies. Treatment with prednisolone and cyclophosphamide was ineffective against LIP probably because the patient had coexising pulmonary fibrosis. Since pulmonary complications of MCD determine its prognosis, their early detection and treatment are essential.

Castleman Disease↗

Influence of estrogen metabolism on proliferation of human breast cancer.

In order to investigate the influence of estrogen metabolism on human breast cancer, estradiol 2- and 16 alpha-hydroxylase (2- and 16 alpha-OHase) activities were determined in the microsomal fractions of cancer tissues by using reverse phase HPLC. 2-OHase activity was detected in most cancer tissues and noncancerous tissues, but the activity was significantly lower in cancer tissues than in the paired noncancerous tissues (0.01 < p < 0.02). Interestingly the patients without lymph node metastasis had significantly higher 2-OHase activity in cancer tissues than those with lymph node metastasis (0.02 < p < 0.05). No correlation was observed between ER status and 2-OHase activity in cancer tissues. On the other hand, 16 alpha-OHase activity was detected only in one third of the breast cancer tissues examined. The activity was not significantly different from that in noncancerous tissues, although it was relatively higher in ER-positive cancer tissues when compared with that in ER-negative ones (0.05 < p < 0.1). Estrone sulfatase activity measured simultaneously in the cytosol fractions of some specimens was much higher in cancer tissues than in noncancerous tissues (0.02 < p < 0.05). We found, however, no correlation between estrone sulfatase activity and estradiol hydroxylase activity. Taken together, our results suggest that the increase in 2-OHase activity prevents the proliferation of breast cancer and that estradiol metabolism is regulated independently of the local biosynthesis of estrogen.

Aryl Hydrocarbon Hydroxylases↗

Idiopathic granulomatous mastitis: case report and review of the literature.

We report a case of idiopathic granulomatous mastitis in a 35-year-old Japanese woman, who came to our hospital complaining of a tender mass in her right breast. Because the results of initial aspiration cytology were considered highly suspicious for carcinoma, modified radical mastectomy was performed. However, the final histological diagnosis was granulomatous lobular mastitis with no evidence of malignancy. Idiopathic granulomatous mastitis is a rare inflammatory breast disease of unknown etiology. Since the clinical manifestations are similar to those of mammary carcinoma, this condition has been misdiagnosed as carcinoma and treated as such. A review of the literature revealed that idiopathic granulomatous mastitis has tended to occur in young patients with a history of childbirth or oral contraceptive usage. Clinical or imaging diagnosis has often been difficult. Complete resection or corticosteroid therapy can be recommended as the optimal treatment. Since 38% of patients experience recurrence, long-term follow-up is indicated.

Adrenal Cortex Hormones↗

Feasibility of adjuvant chemotherapy for breast cancer patients.

To evaluate the feasibility of adjuvant chemotherapy, we analyzed the toxicities of chemotherapy for primary breast cancer in Japanese women. Since the opening of the National Cancer Center Hospital East, 180 female breast cancer patients have received adjuvant chemotherapy or chemo-hormonal therapy following surgical treatment between June 1992 and December 1995. On the basis of informed consent about prognosis and adjuvant therapy, most patients decided to choose the type of cytotoxic chemotherapy themselves. Adjuvant chemotherapy consisted of oral fluoropyrimidine compounds (OFP), cyclophosphamide + adriamycin +/- 5-fluorouracil [CA(F)] or cyclophosphamide + methotrexate + 5-fluorouracil (CMF). Toxicity was determined using the Toxicity Grading Criteria of the Japan Clinical Oncology Group (JCOG). Sixty-six patients received OFP, 59 CA(F) and the rest 55 CMF. The toxicity grading of leukocytes and neutrophils was significantly higher in patients treated with CA(F) or CMF than in those treated with OFP. Similar results were also seen relating to the toxicity of nausea/vomiting and alopecia. There was no statistical difference in the toxicity grading of hemoglobin, glutamic oxaloacetic transaminase/glutamic pyruvic transaminase (GOT/GPT) and stomatitis/ gastritis between the three groups of patients. Interestingly, the number of patients that were forced to discontinue chemotherapy was higher in those receiving OFP than in those receiving CA(F) or CMF. Cytotoxic chemotherapy of CA(F) or CMF results in greater toxicity than OFP, but is tolerated and feasible in the adjuvant setting used in Japanese breast cancer patients from the viewpoint of toxicities by anticancer chemotherapy.

Administration, Oral↗