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Biomedical subjects

Y Nanbu

Publications and source records attributed to Y Nanbu.

At least 37 records · Page 2Linked to original sources

[A study on the dosage of carboplatin for bronchial arterial infusion in combination with radiation therapy].

Radiation therapy holds an important position as one of the multidisciplinary methods of treating lung cancer (non-small cell carcinoma). As a result of the development of platinum preparations such as cisplatin (CDDP) and wide use of digital subtraction angiography (DSA), selective bronchial arterial infusion (BAI) therapy made possible more effective use of anti-lung cancer drugs. The use of radiation therapy in combination with BAI is now recommended as a more effective method. Meanwhile carboplatin (CBDCA) has recently been developed as a second generation platinum preparation with less side effects, and is being used for BAI, too. However, the maximum tolerated dose (MTD) of CB DCA for BAI to be used in combination with radiation therapy is not known yet. We, therefore, carried out a phase-study to determine MTD of CBD CA for combination with radiation therapy. The results show that the MTD of CBDCA is 400 mg/m2, and that clinically recommendable infusion limit is 350 mg/m2. In an angiographic study performed at the same time, a plural number of tumor affected blood vessels were found in 81.3% of the patients with lung cancer. Therefore, infusion of a drug for such patients should be carefully applied.

Aged↗

Expression of c-erbB-2 protein and epidermal growth receptor in endometrial carcinomas. Correlation with clinicopathologic and sex steroid receptor status.

BACKGROUND: The c-erbB-2 (HER-2/neu) protein is a membrane glycoprotein growth factor receptor showing molecular homology with the epidermal growth factor receptor (EGFR). In endometrial carcinomas, little is known about the relationship between the expression of c-erbB-2 protein and that of EGFR. METHODS: The immunohistochemical reactivity of monoclonal antibodies against both of these proteins was examined in 34 endometrial carcinomas, and the presence or absence of correlation with the clinicopathologic features or with the immunohistochemical expression of sex steroid receptors (estrogen receptor [ER] and progesterone receptor [PR]) was analyzed. RESULTS: Of the 34 patients, 22 (64.7%) had c-erbB-2 protein-positive and EGFR-negative tumor, and 8 (23.5%) had tumor positivity for both proteins. Four patients had tumors negative for both proteins. ER or PR positivity was found in 24 (70.6%) of the 34 patients. Intense immunostaining for c-erbB-2 protein was found in 5 (14.7%) of the 34 patients but was not correlated with the stage or grade of differentiation in endometrial carcinoma. However, expression of EGFR in addition to c-erbB-2 protein was more frequently observed with advancing stage of disease and was inversely correlated with the grade of differentiation and with the expression of ER or PR of the tumor. CONCLUSION: The expression of EGFR, in addition to that of c-erbB-2 protein, is an important event that presumably is linked with progression or with a poorly differentiated state of endometrial carcinomas.

Adult↗

[A case of hypersensitivity pneumonitis in Pholiota nameko's manufacturer].

A 58-year-old female was admitted to our hospital because of fever and dyspnea on exertion. She has been working in the factory making Pholiota nameko for 8 years. Her chest X-ray revealed diffuse linear and fine nodular shadows in both lower lung fields. Hypoxemia was seen on blood gas analysis. Bronchoalveolar lavage (BAL) and transbronchial lung biopsy (TBLB) were performed. Differential cell count of the BAL fluid showed lymphocytosis and CD4/8 was decreased. TBLB specimens revealed bronchioloalveolitis. Precipitins against Trichosporon cutaneum were detected by Ouchterlony method. These findings are compatible with hypersensitivity pneumonitis, and Trichosporon cutaneum may have been causative antigen in this case. Trichosporon cutaneum is often detected in the Japanese summer-type hypersensitivity pneumonitis. This case suggests that Trichosporon cutaneum is one cause of hypersensitivity pneumonitis in workers at factories making Pholiota nameko.

Alveolitis, Extrinsic Allergic↗

Expression and growth-promoting effect of adult T-cell leukemia-derived factor. A human thioredoxin homologue in hepatocellular carcinoma.

Adult T-cell leukemia-derived factor (ADF), originally defined as an interleukin-2 receptor inducer, is a human thioredoxin homologue. ADF is detected in many malignant tissues and has a growth-promoting effect on transformed cells. In this study, ADF expression was examined immunohistochemically in human liver cell lines and liver tissues, and its growth-promoting effect was tested on human hepatoma cells. On three liver cell line--PLC/PRF/5, HepG2, and Chang liver cells--ADF stained positively and also was detected by immunoblotting. ADF had strong staining in the fetal liver (n = 8), although it was faint in the normal adult liver (n = 6). In hepatocellular carcinoma (n = 25), ADF expression generally was enhanced and was very strong in 52% (13 of 25) of the cases, although it was moderate in cases of chronic hepatitis or cirrhosis. ADF augmented the growth of PLC/PRF/5 cells and showed an additive effect with epidermal growth factor. These results indicate possible involvement of ADF in cell activation and growth of hepatocytes, as is the case with lymphocytes.

Carcinoma, Hepatocellular↗

Expression of adult T-cell leukaemia-derived factor, a human thioredoxin homologue, in the human ovary throughout the menstrual cycle.

An immunohistochemical study of the expression of adult T-cell leukaemia-derived factor (ADF), a human thioredoxin homologue, was performed in the normal human ovary throughout the menstrual cycle. Primordial follicles were negative for ADF. Both granulosa cells and theca interna cells at the stages of preantral and antral follicles contained ADF. The staining intensity of these cells was very strong in the preovulatory dominant follicle. After ovulation, both granulo-lutein and theca-lutein cells were positive for ADF. During pregnancy, the theca-lutein cells revealed very intense ADF staining. The theca interna cells of the atretic follicles showed ADF staining, while the granulosa cells of such follicles did not. These results suggest that ADF localizes in the ovarian steroidogenic cells which have the binding sites of either luteinizing hormone or follicle-stimulating hormone, and that ADF expression is closely associated with the activity of the ovarian steroidogenic cells.

Adult↗

Expression of c-erbB-2 protein and epidermal growth factor receptor in normal tissues of the female genital tract and in the placenta.

The c-erbB-2 (HER-2/neu) protein is a membrane glycoprotein growth factor receptor that has molecular homology with the epidermal growth factor receptor (EGFR). To investigate the relationship between the expression of c-erbB-2 protein and EGFR in the tissues of the human female genital tract and in the placenta, we examined the immunohistochemical reactivity of monoclonal antibodies against both of these proteins. In the müllerian-derived genital tract, epithelial cells of the fallopian tube, endometrium, and endocervix showed reactivity for c-erbB-2 protein, whereas reactivity for EGFR was distributed mainly in the stromal cells throughout the menstrual cycle and during pregnancy. In addition, the staining intensity for EGFR in the endometrial stroma increased with its decidualization. In the exocervical squamous epithelium, basal cells were c-erbB-2 protein-negative and EGFR-positive, but the more differentiated squamous cells of the intermediate layer were c-erbB-2 protein-positive and EGFR-negative. In the placental tissues, cytotrophoblasts and syncytiotrophoblasts of the chorionic villi were c-erbB-2 protein-negative and EGFR-positive. In contrast, intermediate trophoblasts in the extravillous space were c-erbB-2 protein-positive and EGFR-negative. Thus, there is an inverse relationship between the expression of c-erbB-2 protein and EGFR in the tissues of the female genital tract and in the placenta. This suggests that there may be a regulatory mechanism(s) for the expression of both proteins that is associated with the differentiation and/or function of cells in the female genital tract and the placenta.

ErbB Receptors↗

Immunohistochemical localization of c-erbB-2 protein and epidermal growth factor receptor in normal surface epithelium, surface inclusion cysts, and common epithelial tumours of the ovary.

The c-erbB-2 (HER-2/neu) protein is a membrane glycoprotein growth factor receptor showing molecular homology with the epidermal growth factor receptor (EGFR). We examined the immunohistochemical reactivity of monoclonal antibodies against both of these proteins in normal surface epithelium, surface inclusion cysts, and common epithelial tumours of the ovary. The ovarian tumours were classified as benign (16), borderline malignant (2), and malignant (19). Normal surface ovarian epithelium was weakly positive for both c-erbB-2 protein and EGFR. In surface inclusion cysts, however, the epithelial cells lining the lumen exhibited stronger staining for c-erbB-2 protein, but no staining for EGFR. All 16 benign ovarian tumours and the 2 borderline malignant ovarian tumours were positive for c-erbB-2 protein and negative for EGFR. Of the ovarian carcinomas, 13 of the 19 (68.4%) were positive for c-erbB-2 protein and negative for EGFR, while 4 showed positivity for both c-erbB-2 protein and EGFR. Two cases were negative for both proteins. Expression of both c-erbB-2 protein and EGFR was found in endometrioid carcinoma with squamous differentiation and in clinically advanced poorly differentiated serous carcinomas. Expression of c-erbB-2 protein appears to be increased and that of EGFR is reduced in the early stage of epithelial ovarian oncogenesis. The expression of EGFR with c-erbB-2 protein in ovarian carcinoma is related both to histological differentiation and/or advanced clinical stage.

Adolescent↗

Coexpression of adult T-cell leukemia-derived factor, a human thioredoxin homologue, and human papillomavirus DNA in neoplastic cervical squamous epithelium.

Adult T-cell leukemia-derived factor (ADF) is an autocrine interleukin-2 receptor-inducing factor produced by human T-lymphotropic virus-1 (HTLV-1)-transformed lymphocytes, which has a high structural homology with an endogenous dithiol reducing coenzyme, thioredoxin. Its localization was investigated immunohistochemically in the cervix, using normal tissue (27 samples) and squamous neoplastic tissue (three condylomas, 42 cervical intraepithelial neoplasia [CIN] samples, 34 invasive squamous cell carcinoma samples). The expression of human papillomavirus (HPV) DNA was also studied in serial sections of the same subjects. Normal squamous cells and glandular cells of the cervix were negative for ADF. However, intracytoplasmic and/or intranuclear ADF-positive cells were usually found in the intermediate and superficial layers of the neoplastic squamous epithelium of condylomas (three of three cases) and CIN (35/42 cases). HPV DNA was detected in all condylomas and in 27 of 42 CIN specimens. HPV DNA-positive cells were usually localized in the intermediate and superficial layers of the neoplastic squamous epithelium. These HPV DNA-positive cells were also positive for ADF. Invasive squamous cell carcinoma was also positive for ADF (24/34 cases) and HPV DNA (11/34 cases). The coexpression of HPV DNA and ADF was observed in all HPV DNA-positive cases. Coexistence of HPV DNA and ADF immunopositivity in neoplastic squamous cells of the cervix suggests that ADF expression closely reflects the intracellular event on HPV DNA replication.

Adult↗

Immunohistochemical analysis of estrogen receptors, progesterone receptors, Ki-67 antigen, and human papillomavirus DNA in normal and neoplastic epithelium of the uterine cervix.

To investigate the relationship between the sex steroid receptor (estrogen receptor [ER] and progesterone receptor [PR]) status and the cell proliferation kinetics during the menstrual cycle in normal and neoplastic epithelium of the uterine cervix, immunohistochemical localization of ER, PR, and cell proliferation-associated antigen, Ki-67, was investigated in 35 normal cervical specimens, 3 condylomas, 26 cervical intraepithelial neoplasia (CIN) samples, and 22 invasive squamous carcinoma samples. The presence of human papillomavirus (HPV) DNA was also studied. In the normal cervix, basal cells were usually ER positive, PR negative, and Ki-67 negative throughout the menstrual cycle. Parabasal cells were ER positive and PR negative in the follicular phase, but ER negative and PR positive, and Ki-67 positive in the luteal phase, and Ki-67-positive cells increased in number in the luteal phase. In contrast, PR positivity was observed in the cells of condyloma (2 of 2 cases), CIN (19 of 26 cases), and invasive squamous carcinoma (13 of 22 cases) irrespective of the menstrual phase. Moreover, most neoplastic cells containing HPV DNA type 16/18 were ER negative, whereas several lesions containing HPV DNA type 31/33/35 were weakly ER positive. Many Ki-67-labeled cells were observed in the neoplastic lesions. These results suggest that reduced ER expression and increased PR expression are associated with the proliferation of normal cervical squamous epithelium, and this proliferation-related receptor status, which is probably induced by HPV infection, is usually expressed in neoplastic cervical squamous cells.

Adult↗

Immunohistochemical analysis of oestrogen receptors, progesterone receptors and Ki-67 in leiomyoma and myometrium during the menstrual cycle and pregnancy.

Immunohistochemical distribution of oestrogen receptors (ER), progesterone receptors (PR), and the cell proliferation-associated antigen Ki-67 was investigated in leiomyomas and the myometrium during the menstrual cycle and pregnancy. In the myometrium, ER expression was observed in the proliferative phase, but was suppressed in the secretory phase and during pregnancy. In leiomyomas, ER expression was observed throughout the menstrual cycle, but was suppressed during pregnancy. However, PR was expressed both in the myometrium and leiomyomas throughout the menstrual cycle and pregnancy. In both the myometrium and leiomyomas, a higher number of Ki-67-positive cells was observed during pregnancy than in the secretory phase, and Ki-67 was negative during menopause. The Ki-67-positive cell count in leiomyomas was significantly higher than that in the myometrium throughout the menstrual cycle and pregnancy. Thus both myometrium and leiomyomas have high growth activity under the hormonal milieu of high progesterone levels. The growth potential of leiomyomas is apparently higher than that of myometrium throughout the menstrual cycle and during pregnancy.

Adult↗

Immunohistochemical localization of adult T-cell leukaemia-derived factor, a human thioredoxin homologue, in human fetal tissues.

An immunohistochemical study of the expression of adult T-cell leukaemia-derived factor (ADF), a human thioredoxin homologue, was performed using a rabbit antibody against the C-terminal peptides of ADF. Tissues were obtained from human fetuses between 9 and 23 weeks of gestation. It was revealed that ADF was widely distributed in different organs and tissues during the fetal period. The ADF antibody reacted selectively with medullary cells of the thymus, lung epithelium, the epithelium of the digestive tract, hepatocytes, bladder epithelium, peripheral nerve cells, hair follicles, sebaceous glands, osteoblasts and the proximal tubules of the kidney. It also reacted with cells destined to differentiate into ciliated cells in the fallopian tube and efferent ductules of the testis, interstitial cells in the ovary, Leydig cells of the testis, and dendritic cells in the spleen and lymph nodes. This is the first report on the thioredoxin system in human cells during the early fetal period. The selectivity of ADF staining in fetal tissues suggests that, during early fetal life, ADF expression correlates well with the cellular function of certain tissues.

Cytokines↗

Serial changes of serum CA125 levels during menstrual cycles.

Serial changes of serum CA125 levels during 32 menstrual cycles were examined in 32 healthy young women (19-21 years of age) charting basal body temperature (BBT) and measuring serum estradiol and progesterone levels. Analysis of BBT charts and serum progesterone levels revealed that the 32 menstrual cycles could be classified into either an ovulatory cycle with a sustained BBT temperature increase for at least 10 days (type I: 9 cycles), an ovulatory cycle with a sustained BBT temperature increase for less than 10 days (type II: 17 cycles), or anovulation (type III: 6 cycles). All 32 cycles exhibited basal CA125 levels of less than 35 u/ml throughout the cycle, except during the period of menstruation. At menstruation, 7 of the 9 cycles of type I showed a marked, transient elevation of CA125 levels from previous basal levels (a mean net increase). On the other hand, 12 of 17 cycles of type II showed only a slight elevation of CA125 levels during the period of menstruation. None of the 6 cycles of type III showed any apparent increase in CA125 levels during the period of menstruation. The mean net increase of CA125 levels during the period of menstruation in the cycles of type I was significantly higher than that of the cycles of type II (p less than 0.05) and type III (p less than 0.05). These results imply that a transient elevation of serum CA125 levels during the period of menstruation occurs in cycles with ovulation, and the levels of elevation seem to be closely associated with the duration of the sustained BBT temperature increase.

Adult↗

Effect of human chorionic gonadotropin on the expression of progesterone receptors and estrogen receptors in rabbit ovarian granulosa cells and the uterus.

To investigate whether LH/human CG (hCG) or progesterone acts as a regulator of estrogen receptors (ER) and progesterone receptors (PR) in granulosa cells, we studied the immunohistochemical expression of both ER and PR in the ovary and the uterus of mature rabbits, during the induction of ovulation by FSH followed by administration of hCG, progesterone, or a progesterone antagonist (RU486) and hCG. Granulosa cells pretreated with FSH for 3 days showed ER staining, but negligible PR staining. The staining pattern for ER and PR changed in animals pretreated with FSH followed by hCG injection; by 6 h after hCG injection, we observed the disappearance of ER and the appearance of PR, and by 3 days after hCG injection, we observed the reappearance of ER and the disappearance of PR. However, the expression of ER and PR in the granulosa cells of animals pretreated with FSH followed by progesterone administration instead of hCG was almost the same as that of animals pretreated with FSH alone. In addition, the expression of ER and PR in the granulosa cells of animals pretreated with FSH followed by RU486 and hCG was almost the same as that of animals pretreated with FSH followed by hCG administration. The uterine glandular epithelium, in contrast, began to show decreased appearance of ER and PR by 48 h after hCG injection, and we observed the disappearance of both receptors by 3 days after hCG administration. These results suggest that the expression of ER and PR in granulosa cells is not regulated by the action of progesterone, but by that of LH/hCG.

Animals↗

[Clinico-pathological study of cervical carcinoma with massive infiltration of eosinophils].

Eight patients with cervical carcinoma with massive stromal infiltration of eosinophils were selected for a clinicopathological study among 474 patients with cervical carcinoma at stages Ib-IIIb who underwent radical hysterectomy between 1971 and 1989 at Kyoto University Hospital. The 8 patients ranged in age from 28 to 48 years and had menstrual cycles. The peripheral leucocyte count in 5 patients showed eosinophilia of the peripheral blood. Histologically, the cervical carcinoma was a locally advanced tumor with invasion of more than 2/3rds the depth of the cervical wall in 6 cases, and with parametrial involvement in 4 cases. Massive infiltration of eosinophils was observed not only around the cancer nests but also within the regional lymph nodes. Mast cells expressing immunoreactivity for histamine were scarce around the tumor. Consequently, the production of an eosinophil chemotactic factor by the tumor cells was strongly suggested. PAS and Alcian-blue staining as well as electron microscopy revealed that the tumor cells in most cases had the histological characteristics of both squamous carcinoma and adenocarcinoma. Collectively, these clinicopathological characteristics of cervical carcinoma with massive infiltration of eosinophils distinguish this tumor from conventional cervical carcinomas.

Adenocarcinoma↗

Estrogen receptor localization in normal and neoplastic epithelium of the uterine cervix.

To investigate the estrogen receptor (ER) status of cells during carcinogenesis of the uterine cervix, the immunohistochemical reactivity for a monoclonal anti-ER antibody (H 222) was studied in 26 normal cervical specimens, 21 cases of cervical intraepithelial neoplasia (CIN), and 21 cases of invasive cervical carcinoma. In addition, the presence of human papillomavirus (HPV) DNA (types 6/11, 16/18, or 31/33/35) was analyzed by in situ hybridization. In the normal cervix, basal cells of the squamous epithelium, metaplastic cells, and endocervical glandular cells were ER positive. In contrast, neoplastic cells of CIN (17 of 21 cases) and invasive carcinoma (19 of 21 cases) were ER negative. The remaining four cases of CIN and two cases of invasive carcinoma were focally ER positive. The HPV DNA analysis revealed that HPV DNA in ER-negative cases was either types 16/18 or undetectable, but all ER-positive neoplasms contained HPV DNA types 31/33/35. These results suggest that most neoplastic cells in CIN and invasive cervical carcinoma lose their ER expression and that this may be related to the HPV DNA types which they possess.

Adenocarcinoma↗

Mucin leakage into the cervical stroma may increase lymph node metastasis in mucin-producing cervical adenocarcinomas.

The relationships between the histologic feature of mucin leakage into the cervical stroma, lymph node metastasis, and the levels of serum carcinoembryonic antigen (CEA), CA 19-9, and CA 125 were analyzed in 35 cases of cervical adenocarcinoma. Histologically, mucin leakage was identified in 14 (40%) cases as amorphorous materials dissecting the connective tissues and permeating the lymphatic channels, associated with or without cancer cells. The cases with mucin leakage showed a significantly higher incidence of lymph node involvement than those without mucin leakage (71.4% versus 23.8%; P less than 0.01). In addition, when the mucin leakage was immunohistochemically positive for CEA or CA 19-9, elevated serum levels of these antigens were frequently observed. These results suggest that the mucin leakage into the cervical stroma represents not only stromal invasion, but also a means that frequently conducts cancer cells into the lymphatic channels. Clinically, this is reflected in an elevation of serum CEA or CA 19-9 levels in cervical adenocarcinoma patients.

Adenocarcinoma, Mucinous↗

Immunohistochemical localization of oestrogen receptors and progesterone receptors in the human ovary throughout the menstrual cycle.

Immunohistochemistry was used to determine the distribution of oestrogen receptors (ER) and progesterone receptors (PR) in the human ovary during folliculogenesis. Primordial and preantral follicles did not contain ER or PR. The granulosa cells of antral follicles had ER, but negligible PR, before the LH surge. In contrast, at the time of LH surge, these cells of the dominant follicle contained PR, but not ER. On the other hand, granulosa cells of the non-dominant follicles had ER, but not PR. After ovulation, the PR persisted in the luteinized granulosa cells and in the corpus luteum during early pregnancy. The theca interna and surrounding stromal cells were ER-negative and PR-positive throughout the menstrual cycle. Thus, the results show that ER and PR are not expressed simultaneously in the granulosa cells, the thecal cells, or the stromal cells during folliculogenesis. Mechanisms controlling the expression of steroid receptors during the normal menstrual cycle and in early pregnancy are discussed.

Adult↗