Biomedical subjects

N Azumi

Publications and source records attributed to N Azumi.

At least 55 records · Page 3Linked to original sources

PubMed1991

Primary leiomyosarcoma of adrenal gland. Case report with immunohistochemical and ultrastructural study.

A primary leiomyosarcoma of the right adrenal gland is reported in a 49-year-old male who presented with progressive flank pain. This is the second case in the English language literature and the first to have documentation of malignant behavior. The tumor measured 11 cm in diameter and showed marked necrosis with prominent mitotic activity (average 15 per 10 high-power fields). Smooth muscle differentiation was apparent ultrastructurally and confirmed by positive immunostaining for muscle-specific and alpha-smooth muscle actin. Bony metastases developed; following palliative treatment with radiation and chemotherapy, the patient is alive with tumor 9 months later. Origin from smooth muscle associated with the central adrenal vein or its tributaries is proposed.

Adrenal Gland Neoplasms↗

PubMed1991

Eosinophilic pneumonia associated with reaction to radiographic contrast medium.

We have described what we believe to be the first published case of a reaction to radiographic contrast medium followed by a diffuse eosinophilic pneumonia. This association seems to confirm what is know about the immunologic mechanisms of such reactions, and though further verification of causation is needed, we found it to be the most plausible explanation.

Adult↗

PubMed1991

Undifferentiated (embryonal) sarcoma of the liver. Clinical and pathologic study of 16 cases with emphasis on immunohistochemical features.

Undifferentiated (embryonal) sarcoma of the liver is a primitive mesenchymal neoplasm with predilection for individuals in the first 2 decades of life. In this study (10 boys, 6 girls), children in the age range of 6-10 years were most commonly affected (63%). Clinical features most frequently noted on presentation were abdominal pain or a palpable mass. In two cases there was cardiac involvement caused by invasion of the inferior vena cava with extension into the right atrium and ventricle; both children died of progressive dyspnea from tumor embolization to the lungs. One patient was a member of a kindred with the cancer family syndrome (Li-Fraumeni syndrome). There were 13 tumor-related deaths (86% mortality); on child was alive with recurrent tumor in the upper abdomen. Complete surgical resection was attempted in 10 of 15 children who underwent exploratory laparotomy; 2 were alive and well 1 and 5 years later, whereas 1 patient had a recurrence in the upper abdomen 3 years after diagnosis. Ultrastructural study (five cases) and immunohistochemistry (11 cases) supported a mesenchymal origin for the tumor, but failed to identify any diagnostic immunophenotype or specific line of differentiation. Coexpression of vimentin and cytokeratin was seen in three cases. Prompt detection of this aggressive tumor with complete surgical resection is the key to a successful outcome, but this is very difficult to achieve. Recent experience suggests that aggressive adjuvant chemotherapy may improve survival in some cases.

Adolescent↗

PubMed1990

Cystic pulmonary metastatic sarcoma.

Neoplastic cavitary lesions are an unusual type of pulmonary metastases. The authors report two cases of cystic metastatic sarcoma of the lungs that illustrate the clinical, radiologic, and pathologic difficulties encountered in the diagnosis of these lesions. In one patient, multiple small, thin-walled cystic metastases from a lower leg leiomyosarcoma were the only manifestation of metastatic disease. The cystic lesions did not change over an 8-month period and a diagnosis of malignancy was not established until spontaneous pneumothorax, presumably due to rupture of the malignant blebs, prompted a thoracotomy. In the second patient, three thin-walled bullae developed after treatment of noncystic pulmonary metastases from a lower-leg synovial sarcoma. In both patients, the cystic lesions were not evident on chest radiographs, but were well visualized with computed tomography (CT), where they mimicked benign bullous disease. However, additional small cavitary lesions not seen with CT were present in resected pulmonary wedge specimens from both patients. A great degree of variability in the cellular composition of the cyst wall lining in both cases, and a lack of any solid neoplastic tissue masses in one case, led to histopathologic difficulties that required immunohistochemical studies for definitive diagnosis of the metastatic disease. These cases show that pulmonary bullae, even though thin-walled and benign-appearing on CT, may be a manifestation of pulmonary metastases. These lesions must therefore be surgically removed from patients in whom a curative resection of pulmonary metastases is warranted.

Actins↗

PubMed1990

Effects of 5-azacytidine in Syrian golden hamsters: toxicity, tumorigenicity, and differential modulation of bronchial carcinogenesis.

5-Azacytidine (AZC) was studied in a lung cancer model in outbred and syngeneic (F1D) hamsters wherein benzol[a]pyrene (BP) from sustained release implants (SRI) induces preneoplastic mucosal changes which progress to bronchogenic cancer. In pilot studies to evaluate AZC toxicity, a dose schedule of 5 mg/kg biweekly was found suitable and was then used for long-term administration in all subsequent studies. Three groups of outbred hamsters were studied: BP SRi alone (n = 60), BP SRI + AZC (n = 60), and AZC alone (n = 54). AZC treatment was begun 3-5 days after SRI placement. Sixty-one days after the start of the experiment, seven or eight hamsters were sacrificed from each group. Later sacrifices were at 3-week intervals in groups receiving BP SRI and at 6-week intervals in the AZC only group. Four groups of F1D syngeneic hamsters were studied: BP SRI alone (n = 50); BP + AZC starting 3-5 days after SRI placement and continuing until death (n = 52); BP + AZC from 3 to 5 days until 75 days after SRI placement (n = 49); BP + AZC starting 80 days after SRI placement and continuing until death (n = 52). Hamsters (n = 9-14) from each group were sacrificed at 120, 150, 180, and 220 days after SRI implantation. AZC alone was not carcinogenic under these conditions. Both outbred and F1D hamsters treated with early or continuous AZC had slower rates of neoplastic change from BP SRI than did animals receiving BP SRIs alone or BP + late AZC. The incidence of epidermoid cancer were the same for all regimens, but the tumors in those receiving AZC early in carcinogenesis were smaller than in those receiving late or no AZC. The incidences of nonepidermoid cancer were lower in those receiving AZC during early carcinogenesis, and larger tumors were noted in the absence of AZC. Thus, within the study period in this unique hamster lung cancer model, AZC given early in carcinogenesis inhibited only the later (promotional) phase of BP epidermoid carcinogenesis, but inhibited all phases of nonsquamous cancer development induced by BP. This differential modulation of bronchial carcinogenesis, which occurs from AZC given during preneoplastic stages, may prove useful for delineating molecular mechanisms underlying specific phenotypic types of bronchogenic cancers.

Animals↗

PubMed1990

Quantitative DNA alterations during 5-azacytidine-induced differential modulation of benzo(a)pyrene carcinogenesis in hamster bronchi.

Sustained release implants (SRI) containing 10% benzo(a)pyrene (BP) were placed endobronchially into outbred and syngeneic (F1D) hamsters. Randomly selected OB and F1D hamsters also received 5-azacytidine (AZC), 5 mg/kg i.p., twice weekly until death (AZC-CONT); two more groups of F1D hamsters were given the same AZC dose either for the first 75 days of SRI implantation (AZC-EARLY) or from 80 days after SRI placement until death (AZC-LATE). OB Hamsters were sacrificed at regular intervals from 62 to 189 days of SRI exposure. F1D Hamsters were sacrificed in groups after 120, 150, 180, and 220 days of SRI exposure. The bronchial mucosa at the SRI site was examined cytologically and histologically, as were the tumors that developed. Mean quantitative total cellular DNA values (QDNA) were measured by image analysis. For both varieties of hamster given AZC, QDNA values were higher in early carcinogenesis (CG) and lower in the late stage of CG than in hamsters that did not get AZC (P less than 0.001). QDNA values were lower in epidermoid than in non-epidermoid cancers (P less than 0.001); for both types of cancer, QDNA was lower in AZC-treated hamsters (P less than 0.01). Cancers induced under the influence of AZC included more epidermoid cancers (P less than 0.01) and were of a higher degree of differentiation (P less than 0.01) than those induced by BP alone, especially when AZC was given early in CG. There was no consistent relationship between QDNA and degree of differentiation in tumors. These differential effects of AZC given early during CG suggest that 1) for epidermoid bronchial CG, some of the molecular alterations involved in hyperploidy and in differentiation occur early in the sequential progression of carcinogenesis; and 2) for both epidermoid and non-epidermoid bronchial CG, the necessary changes must occur in a fixed sequence instead of as random events, until all needed changes have occurred.

Animals↗

PubMed1990

Adenomatoid tumor of the adrenal gland with ultrastructural and immunohistochemical demonstration of a mesothelial origin.

We describe an adenomatoid tumor arising in the left adrenal gland of a patient who underwent bilateral adrenalectomy for the ectopic adrenocorticotropic hormone syndrome. The mesothelial origin of the tumor was confirmed by electron microscopy and positive immunohistochemical staining for keratin. The tumor had a prominent cystic component raising the question whether adrenal cysts are derived from mesothelial inclusions. It is proposed that consideration be given to adding a new category of "mesothelial cysts" to the classification of adrenal gland cysts.

Adrenal Gland Neoplasms↗

PubMed1990

Does rapid microwave fixation improve immunohistochemistry?

Microwave fixation in dilute aldehyde solution has been reported to be superior to fixation in formaldehyde for the preservation of antigens. We studied antigen preservation among tissues which were soaked in formaldehyde, dilute aldehyde, alcohol, and saline solution with or without microwave irradiation. Microwave fixation was found to be superior to conventional formaldehyde fixation with regard to antigen preservation. However, there was no detectable difference in immunostaining between any of the irradiated and nonirradiated alcohol-, aldehyde-, or even saline-treated tissues. Microwave-irradiated tissues, regardless of the fixative employed, displayed a tendency for tissue disintegration upon protease treatment, as is commonly seen in alcohol-fixed tissues. Our results suggest that the apparent improvement in antigen preservation when microwave fixation in dilute aldehyde solution is used is largely attributable to the fixation in alcohol during the graded alcohol dehydration steps in the tissue processor, rather than to any demonstrable effect of the microwave radiation per se.

Fixatives↗

PubMed1990

Gingival granular cell tumors of the newborn. An ultrastructural and immunohistochemical study.

Gingival granular cell tumor of the newborn, or congenital epulis, is a rare congenital lesion of uncertain histogenesis located exclusively on the alveolar ridge with marked predilection for female infants. Although histologically similar to the more ubiquitous granular cell tumor or myoblastoma, ultrastructural and immunohistochemical studies support separate histogenetic pathways for the two lesions. A newborn female infant with three gingival granular cell tumors is described herein along with immunohistochemical and ultrastructural observations. There was positive immunostaining for vimentin but staining for S100 protein was uniformly negative. Immunocytochemical assay for estrogen and progesterone receptors was also negative. The findings indicate a mesenchymal origin and the demonstration of intermediate filaments with fusiform electron densities suggests that some of the granular cells have morphologic attributes of myofibroblasts.

Female↗

PubMed1988

Antigenic phenotype of Langerhans cell histiocytosis: an immunohistochemical study demonstrating the value of LN-2, LN-3, and vimentin.

In order to determine the antigenic phenotype of the proliferating cells in Langerhans cell histiocytosis (LCH), we studied 15 such examples by using formalin- and B5-fixed, paraffin-embedded tissues. We used a panel of antibodies that are known to react with lymphocyte- and histiocyte-associated antigens. These included LN-1, LN-2, and LN-3 monoclonal antibodies (MoAbs), MoAbs to leukocyte common antigen (LCA), Leu-M1 antigen, vimentin, and epithelial membrane antigen (EMA), as well as polyclonal antibodies to lysozyme and S100 protein. The antigens encountered most frequently in LCH cells were S100 protein (93% of cases), vimentin (86%), and those detected by LN-2 (80%) and LN-3 (82%). Lysozyme was detected focally in two cases and diffusely in one case. The LCH cells were negative for LN-1, LCA, Leu-M1, and EMA. There was only one specimen in which S100 protein was not demonstrated; in this case, LN-3, vimentin, and T6 on frozen section were positive. The phenotype of LCH cells is similar to that of Langerhans' cells and interdigitating histiocytes. Our results demonstrate the value of using a panel of antibodies, including anti-vimentin MoAb, LN-2, and LN-3 for the immunophenotypic diagnosis of LCH in addition to an antibody to S100 protein.

Antibodies, Monoclonal↗

PubMed1988

Non-small cell lung cancer in autogenous subcutaneous bronchial grafts in dogs.

The progression of preneoplasia into lung cancer can be serially studied in a new canine model that is simpler and more cost effective than previously reported methods of orthotopic endobronchial carcinogenesis. Short segments of bronchus, obtained by pneumonectomy, were placed on the back of 10 dogs in the form of subcutaneous bronchial autografts. These autografts (12 to 14 per dog) became vascularized and lined with normal respiratory epithelium. Four to 12 weeks after autograft implantation, 10% methylcholanthrene in crystalline form was put into 57 autografts and 10% methylcholanthrene in a silicone polymer sustained-release implant was placed into 54 autografts. Ten autografts without carcinogen (one per dog) served as controls. Serial samplings of each autograft during 9 to 97 weeks of carcinogen exposure showed the neoplastic progression from normal bronchial cells to invasive cancer through stages such as atypical squamous metaplasia and carcinoma in situ. To date, cancers have been histologically proved in 60 autografts; 36 were induced by implants and 24 by the crystalline form. Thirty-nine cancers were epidermoid, and the remainder were either adenocarcinomas (n = 3) or poorly differentiated spindle cell cancers (n = 18). The sustained-release implant method resulted in larger autografts with a greater tendency to progress to cancer than the crystalline carcinogens (p greater than 0.025). Therefore, the sustained-release implant is now considered the preferred method. Measurement of nuclear deoxyribonucleic acid by image analysis of nine histologic cancers demonstrated hyperploidy. Deoxyribonucleic acid from the L1 repeated sequence family was demonstrably hypomethylated in spindle cell tumors. Curettement of individual autografts yielded sheets of respiratory epithelium from which 43.5 to 409.5 micrograms of deoxyribonucleic acid was isolated. For the first time, deoxyribonucleic acid from each stage of the neoplastic progression in non-small cell lung cancer is available in adequate quantities for serial biochemical and therapeutic analysis.

Animals↗

PubMed1988

Immunophenotypic diagnosis of leiomyosarcomas and rhabdomyosarcomas with monoclonal antibodies to muscle-specific actin and desmin in formalin-fixed tissue.

Two fibrillary proteins, muscle-specific actin (MSA) and desmin, are found only in cells of smooth and skeletal muscle lineages. Among the monoclonal antibodies (MAbs) to these antigens which we have tested, we found several to be reactive in formalin-fixed, paraffin-embedded sections. This finding widened the possibility of using these MAbs in routine diagnostic surgical pathology for the immunodiagnosis of rhabdomyosarcomas (RMS) and leiomyosarcomas (LMS). We therefore conducted a comparative study of three such MAbs which are available commercially and which we applied to paraffin-embedded, formalin-fixed tissues from 15 patients with RMS and 19 patients with LMS. The case selection criteria included typical light-microscopic appearances as well as immunoreactivity with at least one of the MAbs. MSA was detected in all cases of RMS and LMS, whereas desmin was reactive in 12 of 13 RMS and 10 of the 19 LMS. (Desmin antigenicity was judged to be lost in two RMS, since the vascular smooth-muscle tissue present in the specimens failed to react with these antibodies.) In LMS, desmin tended to show focal positivity, whereas the MSA in the same specimens was diffusely positive. These results demonstrate the utility of MAbs for confirmation of the muscle lineage of LMS and RMS in formalin-fixed, paraffin-embedded tissue. The results also indicate that, with the MAbs tested, the antigenicity of MSA is preserved more consistently than that of desmin in formalin-fixed, paraffin-embedded tissue, and that MSA is a more sensitive marker for the detection of muscle differentiation than is desmin, especially in LMS.

Actins↗

PubMed1987

The cellular composition of adenoid cystic carcinoma. An immunohistochemical study.

To investigate the cellular differentiation of adenoid cystic carcinomas (ACC), a comparative immunohistochemical study of 12 normal salivary glands and eight specimens of ACC was performed. Antibodies were used against S100 protein (S), keratins (K) of various molecular weights, vimentin (V), muscle-specific actin (A), epithelial-membrane antigen, human milk fat globules, and collagen type IV. A panel of four of these antibodies (SKVA) was identified as the most helpful in characterizing cells in normal salivary glands and ACC. The immunophenotypes depended on the histologic patterns of ACC. Cells in morphologically recognizable duct structures in the cribriform and trabecular areas expressed a phenotype similar to that of the intercalated duct. Cell layers around pseudocysts and occasional cellular islands had an immunophenotype suggesting myoepithelial-cell differentiation. The most clear cut epithelial/myoepithelial bilaminar differentiation was present in areas with a trabecular pattern, in which the layers facing the stroma and the central ductal elements had SKVA phenotypes of myoepithelial and ductal differentiation, respectively. In areas with a reticular pattern, most of the cells showed ductal differentiation. Many of the cells in the cribriform and basaloid regions were immunophenotypically undifferentiated. These results indicate that ACC consists of undifferentiated cells and of cells that are differentiating toward ducts, predominantly intercalated ducts, and toward myoepithelium. These findings support previous observations by electron microscope.

Actins↗

PubMed1987

Differential susceptibility to bronchial carcinogenesis in syngeneic hamsters.

Previous studies of chemical carcinogenesis in the lung of Syrian golden hamsters have utilized outbred (nonsyngeneic) animals. Using the endobronchial sustained release implant technique, which causes focally originating cancers in outbred hamsters, we studied the course of bronchial carcinogenesis in two varieties of syngeneic Syrian golden hamsters, the LSH and the F1D strains (BIO 15.16 male X BIO 87.20 female). With either 10% benzo(a)pyrene or 10% methylcholanthrene sustained release implants the time course of epithelial transition from normal to neoplastic was the same for F1D hamsters as previously described for outbred hamsters. Using 10% benzo(a)pyrene sustained release implants the incidence of cancers as a function of time was significantly lower (P less than 0.001) in LSH hamsters as compared to outbred and F1D animals. Of 19 tumors transplanted into syngeneic F1D hamsters, 16 have been successfully propagated by serial transplantation. We conclude that (a) F1D hamsters are comparable to outbred animals in the response of their bronchial epithelium to endobronchial benzo(a)pyrene and methylcholanthrene, (b) there are significant differences in susceptibility to bronchial chemical carcinogenesis among hamster strains, thereby giving opportunity to study potential genetic control mechanisms during bronchial carcinogenesis, and (c) F1D hamsters are suitable for studies of lung cancer biology using tumor transplantation methods.

Animals↗

PubMed1987

The distribution of vimentin and keratin in epithelial and nonepithelial neoplasms. A comprehensive immunohistochemical study on formalin- and alcohol-fixed tumors.

Vimentin has been regarded as the intermediate filament characteristic of normal and neoplastic mesenchymal cells and keratins as typical of epithelial cells and the neoplasms derived from them. However, many epithelial cells in tissue culture or in effusion, as well as cells in some solid epithelial neoplasms such as renal, endometrial, ovarian, pulmonary, and thyroid adenocarcinomas, have been shown to coexpress vimentin and keratin. The recent availability of monoclonal antibodies that work reasonably well in paraffin-embedded tissue led us to carry out a comprehensive immunohistochemical study on formalin- and alcohol-fixed specimens of neoplasms in which we used monoclonal antibodies against vimentin. These results were compared with our previous study in which the same tumor tissues were investigated using antibodies against keratin. The antigenicity of vimentin was found to be preserved in all alcohol-fixed specimens and in 63% of formalin-fixed tissues. Vimentin was the sole intermediate filament present in virtually all sarcomas, meningiomas, schwannomas, and melanomas. In addition, variable percentages (10-57%) of carcinomas, neuroendocrine carcinomas, neuroblastomas, thymomas, and mesotheliomas were positive for vimentin, which, except in the neuroblastomas, was coexpressed with keratins. Among the adenocarcinomas, more than 50% of papillary carcinomas of the thyroid, as well as renal, endometrial, ovarian, and lung carcinomas, coexpressed keratins and vimentin. A distinctive paranuclear and basal localization of vimentin was observed in the cells of many of these tumors, in contrast to the predominantly apical distribution of the keratins. The authors conclude that coexpression of vimentin and keratin is more widespread than previously reported and that antibodies to vimentin, by themselves, are of limited value for the differentiation of epithelial from mesenchymal neoplasms.

Antibodies, Monoclonal↗

PubMed1987

Quantitation of human cytomegalovirus DNA in lungs from bone marrow transplant recipients with interstitial pneumonia.

DNA-DNA hybridization was compared with culture for virus and histopathology for the detection and quantitation of human cytomegalovirus (HCMV) in lungs from bone marrow transplant recipients. The hybridization assay detected 100 pg of HCMV DNA or greater than 520 plaque-forming unit equivalents. Compared with culture for virus, the hybridization assay had a sensitivity of 90.6% and a specificity of 77.8%. The quantity of HCMV DNA and the infectivity titer were directly correlated. Quantitation of HCMV DNA by hybridization was more reproducible than were infectivity titers for frozen specimens. Histopathologic examination of lung specimens detected HCMV inclusions in 60% (15 of 25) of patients with HCMV-associated interstitial pneumonia, whereas hybridization results were positive for 96% (24 of 25) of these patients. A significant inverse correlation was demonstrated between quantitative values for HCMV DNA and the duration of pneumonia.

Bone Marrow Transplantation↗

PubMed1987

Atypical and malignant neoplasms showing lipomatous differentiation. A study of 111 cases.

One-hundred-eleven cases of histopathologically atypical or malignant lipomatous lesions in the somatic soft tissue and retroperitoneum were studied. These consisted of 48 differentiated fatty neoplasms of the somatic soft tissues (DFT-S), 21 fatty neoplasms of the retroperitoneum (DFT-R), 33 myxoid liposarcomas from various sites and nine pleomorphic liposarcomas. DFT-S were defined as lipomatous lesions composed of mature fat and containing atypical stromal cells or lipoblasts. In the somatic soft tissues, this group included lesions that would be classified using published criteria as "atypical lipoma", "pleomorphic lipoma", "well-differentiated lipoma-like liposarcoma", and "sclerosing liposarcoma". All of the DFT-R met previously published criteria for "well differentiated liposarcoma" or "sclerosing liposarcoma". We found no consistent histologic differences between the DFT-S and DRT-R. No pure "round cell" liposarcomas were encountered although many myxoid liposarcomas had "round cell" areas. Follow-up data were available in 80 cases (72%) with a mean follow-up period of over 7 years. Among the DFT-S there were no uncontrollable recurrences, distant metastases, or tumor-related deaths. The depth of the neoplasm correlated with the tendency for local recurrence; no neoplasms primary in the subcutis recurred; 29% of the tumors recurred when they originated in the deep soft tissues or within the muscle. None of the recurrent tumors demonstrated "dedifferentiation." DFT-R had a recurrence rate of 67% and, although there were no distant metastases, nine patients (43%) died of tumor. Five retroperitoneal tumors dedifferentiated but did not metastasize. In light of this experience, we believe that the term "atypical lipoma" is warranted for the DFT-S and "well differentiated liposarcoma" is an appropriate label for the DFT-R. The overall mean survival for the 52 cases of liposarcoma (excluding DFT-S) was 13.6 years. The mean survival in "well differentiated liposarcoma" (11.25 years) was between that for myxoid liposarcoma (16.25 years) and that for pleomorphic liposarcoma (7 years). Six patients (29%) with myxoid liposarcoma developed local recurrences and 6 patients (29%) developed distant metastases and died. Metastasis was always associated with a round cell (or pleomorphic) component with increased numbers of mitotic figures in either the primary tumor or a local recurrence.

Adolescent↗

PubMed1986

Early stage head and neck non-Hodgkin's lymphoma. The effect of tumor burden on prognosis.

Treatment results were investigated in 113 previously untreated patients with clinical Stage I and II (Ann Arbor) non-Hodgkin's lymphoma of the head and neck. Fifty-six Waldeyer's ring, 34 other extranodal sites, and 23 cervical nodal lesions were included. The overall relapse-free survival at 5 years was 41%. Age and Ann Arbor stage influenced relapse-free survival. The results suggested that the tumor cell burden is a fundamental prognostic factor for patients with Waldeyer's ring disease and for patients with only cervical nodal disease. Abdominal relapse was most frequent, followed by generalized relapse. From 1981, patients were randomized in a clinical trial to receive either chemotherapy (cyclophosphamide, vincristine, and prednisone [CVP], five courses) or whole-abdominal irradiation (25 Gy/20 Fr) as an adjuvant therapy. Patients could not tolerate the whole-abdominal irradiation well. A significant improvement in survival has been obtained by adjuvant chemotherapy.

Adolescent↗