Biomedical subjects
Publications and source records attributed to Y Nanbu.
A case of primary ovarian malignant amelanotic melanoma arising in a cystic teratoma is presented with the histology, immunohistochemistry, and ultrastructure of the tumor.
A murine monoclonal antibody, 130-22, produced against a human lung adenocarcinoma cell line (PC-9) has been suggested as recognizing an antigenic determinant (CA130) which is different from an epitope recognized by OC125 on CA125 glycoprotein molecules. The immunohistochemical reactivity with the 130-22 antibody (anti-CA130) was examined in human fetal tissues, and normal and neoplastic tissues of female genital tracts, and compared to those using OC125. Among the fetal tissues, the amnion and the cells of coelomic epithelium and mullerian-derived epithelia reacted with anti-CA130. In normal adult tissues, cervical and endometrial gland cells, tubal epithelial cells, and ovarian surface cells reacted with anti-CA130. In addition, predecidual cells in the late secretory endometrium and decidual cells during gestation were positive. Among the neoplastic tissues, tubal and endometrial adenocarcinomas and epithelial ovarian tumors were positive for anti-CA130. There were no differences in the respective specimens between the immunohistochemical localization of anti-CA130 and of OC125. Therefore, anti-CA130 is considered to be useful in the immunohistochemical detection of CA125 glycoprotein molecules as well as OC125.
We generated five murine monoclonal antibodies reactive with ovarian cancer-associated antigen CA125. These monoclonal antibodies seemed to bind to separate epitopes from OC125 antibody, known to recognize CA125. A series of immunoradiometric assays for measuring serum CA125 values rapidly and sensitively were devised using these monoclonal antibodies. The antigenic determinant of a new immunoradiometric assay was different from that of a currently used CA125 kit employing OC125 both as a catcher and a tracer. However, serum antigen levels were closely correlated to each other and were elevated not only in patients with ovarian cancer, but also in patients with endometriosis and in some normal females during menstruation. These results suggest that CA125 has at least two antigenic determinants close to each other and this new rapid assay is useful, although not specific for ovarian cancer, in patients with gynecological disorders.
We examined the CA130 concentration in the amniotic fluid, maternal sera, amnion, chorion, decidua and placenta. CA130 in the maternal sera showed an initial increase during early pregnancy, remained low from the 15th weeks of pregnancy until delivery, and then increased after term delivery (249u/ml, mean, n = 27) or mid-trimester abortions (844u/ml, n = 22). The CA130, concentration in the amniotic fluid was high in the mid-trimester and remarkably low at term. Among the tissues examined, amnion and decidua contained a relatively high concentration of CA130. Immunohistochemical examination also demonstrated abundant CA130 in the cytosol of amnion and decidua tissues. The pattern of changes in CA130 in amniotic fluid was similar to that in the amnion and decidua tissue. The results suggest that the amnion cells are the source of CA130 in the amniotic fluid and that the high concentration of CA130 in maternal serum after delivery originates in decidua tissue affected by the separation of the placenta.
Bronchiectasis has come to be considered as a type of sinobronchial syndrome in Japan, but there exist some cases without chronic sinusitis. We studied the clinical features of 14 cases of bronchiectasis with definitely normal paranasal sinus roentgenogram, diagnosed during the past ten years. There were eleven middle-aged women and three men. Ten patients (71%) complained of hemoptysis, one (7%) of dry cough, one (7%) of productive cough, and the two (14%) had no complaint. In seven patients (50%) CT and bronchography showed localized cylindrical bronchiectasis in the right middle lobe and/or left upper lobe lingular division. They were considered to be middle lobe lingular syndrome. Three patients (22%) with localized varicose or cystic bronchiectasis had a history of pneumonia or pertussis in their infancy, so their bronchiectasis were considered secondary to infantile bronchopulmonary disease. Two patients (14%) had diffuse cystic bronchiectasis and were almost asymptomatic. They might be cases congenital bronchiectasis or Williams-Campbell syndrome. Pulmonary function tests were normal in most of the cases and sputum culture revealed no cases of persistent bacterial infection. These clinical features are quite different from those of bronchiectasis reported as sinobronchial syndrome, in which chronic productive cough, poor pulmonary function, persistent bacterial infection, etc. are significant. So we conclude that there are two distinct groups in bronchiectasis.
A 43-year-old man was admitted to our hospital because of cough and dyspnea. His chest X-ray showed bilateral basal infiltrative shadows. The increased eosinophils in BAL suggested chronic eosinophilic pneumonia (CEP), whereas the TBLB specimens showed findings compatible with desquamative interstitial pneumonia (DIP). The open lung biopsy specimens showed typical findings of DIP with a peripheral zone, suggestive of CEP. These two diseases may be only phasal differences of reaction to the same extrinsic stimulation.
A 43-year-old woman was admitted to our hospital because of fever and dyspnea. She had facial rash, hair-loss, arthralgia, urinary casts, thrombocytopenia, lymphocytopenia, and deposits of IgG, IgM, C3 in the epidermis. SLE was diagnosed. She also had severe dyspnea, which gradually progressed. In spite of steroid pulse therapy and cyclophosphamide, she eventually died about two months after admission. Chest X-ray film showed bilateral ground-glass shadow and volume-loss. High-resolution CT of the lung showed marked high density area with airbronchogram in the posterior part and a gradually enlarging slight high density area in the anterior area. Pathological findings of the posterior area were atelectasis and dense fibrosis. The findings of the anterior area were collapsed alveoli and dilated alveolar ducts. These findings might suggest that alveolar collapse play a major role in the course of pulmonary fibrosis of this patient.
To investigate the sources and biologic significance of CA 125 and CA 19-9 in amniotic fluid, immunohistochemical and biochemical localization of these tumor-associated glycoproteins in the decidua and fetal membranes was studied. Immunohistochemically, CA 125 and CA 19-9 were localized in the cytoplasm of decidua cells and amnion epithelial cells but not in the chorion and placental tissue. Biochemically, the 12,000 X g supernatant fractions of decidua and amnion tissues contained relatively large amounts of CA 125 and CA 19-9, 73% to 96% of which was present in the cytosolic fractions of these tissues. The CA 125 levels in the amniotic fluid decreased, whereas those of CA 19-9 increased with gestation, which correlated well with the respective levels in amnion tissues. These findings suggest that amnion cells produce and secrete these glycoproteins into the amniotic cavity. However, it is possible that the decidua also secretes CA 125 into the amniotic cavity through the chorion and amnion such as in the case of prolactin.
The amnion is believed to be derived from either cytotrophoblastic cells or embryonic ectoderm. However, it produces and secretes CA 125, which is considered a differentiation antigen of fetal coelomic epithelium derived from the mesoderm of germ cells. To verify this, the immunohistochemical localization of CA 125 in human fetal tissues (between 7 and 23 weeks of gestation) derived from the ectoderm, endoderm, or mesoderm, and in the fetal membranes and placenta was studied. Among the mesoderm-derived tissues, only the fetal coelomic epithelium-related tissues were positive for anti-CA 125 from 15 weeks of gestation. The endoderm-derived tissues did not react with anti-CA 125. However, among the ectoderm-derived tissues, only the periderm reacted with anti-CA 125 from 7 weeks until it sloughed from the stratum intermedium by 23 weeks of gestation. Among the fetal membranes and placenta, only the amnion reacted with anti-CA 125 from 9 weeks to term. These findings indicate that the amnion and the periderm, both of which constitute the epithelia covering the amniotic cavity, in addition to the fetal coelomic epithelium-related tissues, produce CA 125.
To investigate the role of the menstrual cycle in the growth of uterine leiomyomas, the mitotic count per 100 high-power fields and the relation of this to the patient's age (30 to 54 years) were examined in tissue sections of leiomyomas from 181 surgically removed myomatous uteri. The mean mitotic count in the secretory phase (12.7 per 100 high-power fields) was significantly higher than that of the proliferative phase (3.8 per 100 high-power fields) (p less than 0.01) or menses (8.3 per 100 high-power fields) (p less than 0.05). We found the highest mitotic count (54 per 100 high-power fields) in a leiomyoma at the early secretory phase. In the secretory phase, the younger age group exhibited a significantly higher mitotic count than the older group. Increased mitotic activity in leiomyomas under the hormonal milieu of the secretory phase of the menstrual cycle suggests that the growth of these tumors is affected by progesterone level. In addition, this study defined the range of mitotic counts occurring in the tissue sections of typical leiomyomas during the menstrual cycle.
A total of 210 cases of terminal pneumonia were studied out of 1183 autopsied cases at Tenri Yorozu Hospital from 1978 to 1985. Underlying diseases included lung cancer (77 patients), gastric cancer (26 patients), leukemia (24 patients). There was no statistical significance between the time from death until autopsy and the bacterial examination of autopsied lung and blood. P. aeruginosa and Klebsiella sp. were the most frequently isolated organisms. Seventy percent of isolated organisms were gram negative bacilli. In spite of administration of antibiotics, bacteria isolated from specimens before death were sometimes the same as the one isolated from specimens after death. In addition it was recognized that multiple intensive examinations of sputum are necessary for rapid diagnosis of pneumonia. It was also noted that the longer the duration of antibiotic administration, the more frequently P. aeruginosa was isolated. Finally the possibility of pneumonia should be kept in mind in compromised hosts.
A 39-year-old woman was admitted to our hospital because of dry cough. She had been quite well until 1 month before admission. She had no history of chronic sinusitis. Chest X-ray film showed a thin-walled cavity in the superior segment of the left lower lobe of the lung. Curettage biopsy of the cavity wall revealed granulomatous change. Mycobacterium intracellulare-avium complex was identified on sputum culture. Anti-tuberculous therapy was given and the cavity disappeared in 3 months. Since atypical mycobacterial infection is quite unusual for a healthy woman to contract, we performed high-resolution CT (HRCT) in search for occult abnormalities of the lung. HRCT detected a lot of thin-walled cystic lesions, and bronchography showed that they were consistent with cystic dilatation of relatively large bronchi, which ballooned up during inspiration, and collapsed during expiration. Airways peripheral to these dilatations were also visible, and were quite different from usual cystic bronchiectasis formed by acquired recurrent infections. Her bronchiectasis is most likely congenital in its etiology, and might be considered as an adult case of Williams-Campbell syndrome.
Immunohistochemical reactivities with CA 125, carcinoembryonic antigen (CEA), and CA 19-9 were studied in 15 cervixes without histologic abnormalities, ten with microglandular hyperplasia, nine adenocarcinomas in situ, ten adenocarcinomas with an invasion of less than 5 mm in depth, and 25 frankly invasive adenocarcinomas of the uterine cervix. The glandular cells of the normal cervix and microglandular hyperplasia always exhibited reactivity with anti-CA 125 in the luminal surfaces and the secretory products within the lumina, but there was usually no reactivity with either anti-CEA or anti-CA 19-9. In the neoplastic glandular cells (adenocarcinoma in situ and invasive adenocarcinoma), the reactivity with anti-CA 125 was negative or was not in the luminal surface, but in the perinuclear region of the cytoplasm as accumulations of atypical coarse granules. In addition, the positive reaction with anti-CEA and anti-CA 19-9 was seen in 78% and 0% of adenocarcinomas in situ, in 80% and 40% of adenocarcinomas less than 5 mm in depth, and in 84% and 56% of frankly invasive adenocarcinomas, respectively. Therefore, neoplastic cervical glandular cells show an unusual staining pattern with anti-CA 125, which may be associated with impaired production and/or the intracytoplasmic transport of CA 125, and they begin to produce antigens recognized by anti-CEA and/or anti-CA 9-9, which are usually negative in the normal tissue.
To verify whether analysis of the levels of CA125, carcinoembryonic antigen (CEA), and CA19-9 in the cervical mucus is effective for a detection of cervical adenocarcinomas or not, simultaneous measurement of these three tumor markers in the cervical mucus samples from women without gynecologic disorders, with leiomyoma, with cervical squamous cell carcinomas, and with cervical adenocarcinomas was performed. Extremely high levels of CA125 with low levels of both CEA and CA19-9 were demonstrated in the cervical mucus samples from women without gynecologic disorders and with leiomyoma. The cervical mucus samples from cervical adenocarcinomas showed low CA125 levels with extremely high CEA and/or CA19-9 levels. Therefore, analysis of the levels of these three tumor markers in the cervical mucus possibly helps in the diagnosis of cervical adenocarcinomas if CEA and/or CA19-9 show extremely high levels. When a ratio of (CEA + CA19-9)/CA125 was calculated, all women without gynecologic disorders and with leiomyoma showed a ratio less than 0.5, whereas ten of 11 cases of cervical adenocarcinomas had a ratio greater than or equal to 0.5. Only one case of microinvasive adenocarcinoma showed a ratio less than 0.5. Accordingly, the ratio greater than or equal to 0.5 strongly suggested an existence of cervical adenocarcinoma, although it included some cases of squamous cell carcinomas (four of 17 cases).
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Recently, normal cervical glandular cells have been reported to synthesize and secrete CA125 as a common constituent of normal cervical mucus. However, the levels of CA125 in the cervical mucus samples during the menstrual cycle and with cervical inflammatory diseases have not been determined. Therefore, we measured CA125 in cervical mucus samples in various phases of the menstrual cycle and in patients with cervical polyp or vaginitis. In addition to CA125, CEA and CA19-9 were also examined in the same samples. CA125 levels in the mucus samples of women (45 cases) without any gynecologic disorders (control) were 102,200 +/- 8,600 (M +/- S.E.) U/ml. Significantly higher levels were noted in the samples obtained in the follicular phase than in the luteal phase. CA125 levels in the mucus with atrophic vaginitis (12 cases) were significantly lower than those of controls. CEA and CA19-9 levels in the control samples were 3,400 +/- 550 ng/ml and 3,470 +/- 500 U/ml, respectively, and both of these showed no significant difference between the follicular and luteal phases. However, both CEA and CA19-9 levels in the cervical mucus with cervical polyps (15 cases) or vaginitis were much higher than in the controls. Accordingly, the present study revealed that CA125 in the cervical mucus fluctuates during the menstrual cycle, probably under the influence of ovarian sex steroids. In addition, CEA and CA19-9 in the cervical mucus samples obtained from women without any gynecologic disorders showed low levels, but those with inflammatory diseases were high, and this suggested that inflammatory diseases in the cervix and/or vagina may affect the constituent of the tumor-associated carbohydrate antigens in the cervical mucus.
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