Effective D-penicillamine treatment of an early diagnosed patient with Wilson's disease.
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Hepatolenticular Degeneration↗
Biomedical subjects
D J Ruiter
Publications and source records attributed to D J Ruiter.
Improvements and limitations of the subrenal capsule assay for determining tumour sensitivity to cytostatic drugs.
Cyclophosphamide (CY) prevented the host response from occurring in treated animals, and we therefore evaluated CY and other immunosuppressive forms of pretreatment in normal mice using the subrenal capsule assay initially for transplanted and later also for primary tumours. CY pretreatment, 4 or 4.5 Gy whole-body irradiation and cortisone were superior to silica in reducing host cell infiltration, and irradiation as pretreatment has become our routine technique. The addition of cortisone acetate to irradiation was of minor benefit in only 1/3 transplanted lines. When primary tumours were tested, the irradiation was only rarely able to completely prevent cellular infiltration. Only 7/11 ovarian tumours and 3/9 lung tumours were evaluable as tumour specimens (greater than 50% tumour) in preirradiated mice. The degree of infiltration and fibrosis was similar in transplants in irradiated normal mice or in athymic nude mice, suggesting that these phenomena are largely due to properties of the tumours rather than of the host. The limitations of the technique to some cell lines and occasional primary tumours is obvious.
Animals↗
Immunohistochemical demonstration of the cytoplasmic copper-associated protein in the liver in primary biliary cirrhosis: its identification as metallothionein.
Metallothionein was isolated from the liver of rats pretreated with cadmium. Monospecific anti-metallothionein antibodies were produced in rabbits. Twenty-six primary biliary cirrhosis (PBC) liver samples and three control liver samples were stained for metallothionein by an indirect immunoperoxidase technique. Nineteen of the PBC samples and the control samples were also stained for copper by Timm's silver sulphide method. In all PBC samples the copper concentration was determined. In addition, the zinc, cadmium, and mercury concentrations were measured in some samples. Eighteen of the PBC samples stained for metallothionein showed marked diffuse cytoplasmic and nuclear staining of a varying number of periportal hepatocytes. In none of them was granular staining detected. None of the control samples showed staining. Fourteen of the PBC samples stained for copper showed diffuse cytoplasmic and granular staining of the periportal hepatocytes. In none of them was nuclear staining detected. None of the control samples showed staining. No elevated zinc, cadmium, or mercury concentrations were found but the copper concentration was increased in 21 of the 26 PBC samples. The number of cells staining for copper and metallothionein was assessed semiquantitatively. Significant correlations were found between the grade of metallothionein staining and the liver copper concentration; the grade of Timm's staining and the liver copper concentration; and the grades of metallothionein staining and Timm's staining. The data suggest that the accumulation of copper induces synthesis of cytoplasmic and nuclear metallothionein, and that the increased amount of cytoplasmic copper is bound to a similarly increased amount of metallothionein.
Adult↗
The lysosomal copper concentration in the liver in primary biliary cirrhosis.
The copper concentration in the lysosomes of periportal hepatocytes of nine patients with primary biliary cirrhosis was determined by X-ray microanalysis in ultrathin sections, the chlorine concentration of the embedding medium being taken as internal standard. A positive correlation was found between the lysosomal and the total liver copper concentration. No correlation was found between the lysosomal copper concentration and the grade of orcein staining for lysosomal copper-associated protein in paraffin sections. It is concluded that in contrast to the grade of orcein staining, the lysosomal copper concentration is a reliable measure of the total liver copper concentration in primary biliary cirrhosis.
Copper↗
Monoclonal antibodies with different specificities against cytokeratins. An immunohistochemical study of normal tissues and tumors.
Monoclonal antibodies against cytokeratins, isolated from human callus, were prepared. Here we describe the characterization of three of these monoclonal antibodies (Clones 77, 78, and 80) with special emphasis on the staining characteristics of a number of normal epithelial tissues and a series of tumors. On thin sections and in immunoblotting experiments our monoclonal antibodies showed different specificities. In immunoblots Clone 80 stained more bands in preparations of cytokeratin from callus, cultured keratinocytes, and a metastasis of a lung carcinoma than Clones 77 and 78. In this last cytokeratin preparation Clones 77 and 78 each stained a separate band not stained by Clone 80. In normal tissues Clone 80 stained all types of epithelia except myoepithelium and podocytes of glomeruli. Clone 78 stained mainly squamous epithelium. Clone 77 stained differentiated squamous epithelium, transitional epithelium, ductal epithelium, and parenchymatous epithelium. These results confirm the heterogeneity of cytokeratins. In neoplasms Clone 77 was positive with adenocarcinoma and squamous cell carcinoma. Clone 78 stained squamous cell carcinoma and well-differentiated adenocarcinoma. Clone 80 stained all epithelial tumors, including anaplastic carcinoma, and is therefore useful in tumor diagnosis.
Animals↗
Immunohistochemical analysis of malignant melanomas and nevocellular nevi with monoclonal antibodies to distinct monomorphic determinants of HLA antigens.
Using an indirect immunoperoxidase technique, 20 nevocellular nevi, 5 dysplastic nevi, 14 primary cutaneous melanomas, and 24 metastatic melanomas were tested with a panel of monoclonal antibodies to monomorphic determinants of Class I (HLA-A,B,C) and Class II (la-like) major histocompatibility complex antigens. Class I HLA and beta 2-microglobulins were not detected on the majority of nevus cells but were expressed by 3 of 5 dysplastic nevi, by the majority of tumor cells in 12 of 14 primary cutaneous melanomas, and in 13 of 24 metastases. The different expression of Class I HLA and beta 2-microglobulins in primary and metastatic lesions suggests that loss of these antigens may be associated with progression of malignancy. Class II HLA were not detected in common nevi but were locally present in 1 of 5 dysplastic nevi, 7 of 14 cases of primary cutaneous melanoma, and all 24 cases of metastatic lesions tested. These findings suggest that increase in Class II HLA expression may be associated with progression of malignancy. The staining patterns obtained with monoclonal antibodies to distinct determinants of Class I HLA and Class II HLA were superimposable within each type of antigen. Therefore, the discrepancies in the literature about the expression of histocompatibility antigens by lesions of melanocytic origin are not likely to reflect the different specificity of the antibodies used by the various investigators.
Adolescent↗
Cytokeratin and neurofilament in lung carcinomas.
Three monoclonal antibodies, one directed against cytokeratin (clone 80) and two directed against neurofilament (clones 2F11 and 3G6), were used in the study of a series of 77 lung carcinomas by immunohistochemical staining. The anti-cytokeratin antibody, a very broadly reacting antibody directed against an antigenic determinant common to a great number of cytokeratins, was applicable on frozen sections. The two anti-neurofilament antibodies, directed against the 70 kD protein (clone 2F11) and the 160 kD and 200 kD proteins (clone 3G6) of neurofilament, were applicable on both frozen sections and paraffin sections. The staining results on the lung carcinomas indicate that all types of tumors studied, including small-cell anaplastic carcinoma, are markedly positive for cytokeratin. Frozen sections of five and formalin-fixed and paraffin-embedded sections of six other small-cell anaplastic carcinomas were negative with both anti-neurofilament monoclonal antibodies. One poorly differentiated squamous cell carcinoma positive with anti-neurofilament clone 2F11 but negative with clone 3G6. This distribution of cytoskeletal proteins demonstrates the epithelial differentiation of all types of lung carcinomas. Neuroendocrine differentiation of lung carcinomas as found in the small-cell anaplastic types does not result in expression of neurofilament proteins.
Adenocarcinoma↗
Methods in laboratory investigation. Immunoelectron microscopic methods for demonstration of antigens on normal human melanocytes and other epidermal cells.
Different procedures for fixation and processing were evaluated in order to examine the antigenic profile of melanocytes and other epidermal cells for immunoelectron microscopy. For this purpose the monoclonal antibodies anti-HLA-A, B, C, anti-HLA-DR, anti-T6, and the melanoma-associated monoclonal antibody NKI /C-3 were used as markers. Fixation with periodate-lysine-paraformaldehyde yielded better antigenic and ultrastructural preservation than 3% paraformaldehyde or picric acid-paraformaldehyde did. Skin was further processed by five different methods: (a) 15-micron frozen sections; (b) 75-micron agar-embedded, tissue chopper sections; (c) 15-micron polyethylene glycol-embedded sections; (d) epidermal cells in suspension; and (e) epoxy sections (postembedding staining) were prepared for the immunoperoxidase procedure. Antigenicity was best preserved in the cell suspension method and somewhat less, but with a similar staining distribution, with the first three methods. Staining with the polyethylene glycol-embedded sections was only achieved if they were left free-floating in buffer; no staining was observed when the sections were mounted on glass slides and left to dry overnight at 37 degrees C. Epidermal cells remained unreactive in the postembedding method, even after etching. Ultrastructural preservation of the agar-embedded sections and the cells in suspension was superior to the other preembedding methods. Melanocytes mostly showed moderate staining for HLA-A, B, C and slight staining for the antigen that is recognized by NKI /C-3. The latter was further demonstrated on Langerhans cells and indeterminate cells which also expressed HLA-A, B, C, T6, and HLA-DR antigens.
Antibodies, Monoclonal↗
[Thyroid gland carcinoma as a late sequel of irradiation of the neck region].
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Adult↗
Heterogeneity of primary and metastatic human malignant melanoma as detected with monoclonal antibodies in cryostat sections of biopsies.
Monoclonal antibodies were generated against established melanoma cell lines and characterized by their reactivity with various sublines. The antibodies selected for their reaction with melanoma-associated antigens were tested on cryostat sections of melanoma tissue from various stages and on other tumors. The reactivity with normal tissues was also determined. Of 30 antibodies reacting with melanoma cell lines 11 did not react with melanoma biopsies. Of the remaining 19 antibodies nine displayed broad cross-reactivity with normal cells and structures and other benign or malignant tumor cells. Among the remaining antibodies five types were defined that detected antigens (nevocellular I, nevocellular II, neural, endothelial, basal cell) found on certain normal tissues and structures and on certain tumor phenotypes. Even though there seems to be a tendency for some antigens to be preferentially associated with certain stages of melanoma, it has not yet been possible to establish any clear-cut correlation between the expression of one of the differentiation antigens and a particular stage or malignancy potential of melanoma.
Antibodies, Monoclonal↗
Cholescintigraphy with 99mTc-diethyl-IDA for the detection of rejection of auxiliary liver transplants in pigs.
In 15 pigs an auxiliary liver was transplanted and cholescintigraphy with 99mTc-diethyl-IDA was performed to study the function of the livers separately. Serial scintigraphy of the recipient and donor liver was performed on days 3, 8 and 18 after transplantation and time-activity curves over 1 h after injection of the radio-tracer were generated for each liver. From these data the time at which the maximal activity was present in the liver (Tmax) and the time at which during the excretion phase half of this activity was still present in the organ (T1/2) were determined. Liver biopsy material from the recipient liver and the donor liver was obtained at (approximately) the day of one of the scintigraphic examinations and at autopsy. In all cases no histological abnormalities were found in the recipient liver. In 4 pigs there were no histological signs of rejection of the donor liver, in which cases the values for Tmax and T1/2 were normal. In 11 pigs histological signs of rejection were noticed and in all of these cases T1/2 was significantly prolonged, whereas no changes in Tmax were observed. Cholescintigraphy revealed an abnormal value for T1/2 a few days before the biopsy was taken in 10 of these 11 cases. Normal functioning or the prediction of rejection of the auxiliary liver transplant in pigs correlated significantly (P less than 0.01) with normal or prolonged T1/2 values. It is concluded that cholescintigraphy may be helpful in establishing the diagnosis of rejection of liver transplants.
Animals↗
Radiation-induced head and neck tumours: is the skin as sensitive as the thyroid gland?
Six hundred and five persons, randomly selected from a cohort of 2400 patients who had been irradiated 16-46 yr previously for benign diseases in the head and neck region, were traced, recalled and examined for radiation-associated tumours. Three hundred and sixty-seven patients were alive, 179 had died and 66 had emigrated. Two hundred and fifty-seven patients were clinically examined, 87 refused or were not able to participate and 16 could not be contacted. Eighteen of the clinically examined patients had been or were being treated for 20 skin carcinomas with a mean latency of 37 yr. In this group only 7 carcinomas of the thyroid gland were observed, with a mean latency of 38 yr. Eleven carcinomas of the skin and 3 of the thyroid gland were reported in the group which was examined by means of questionnaires. The observed number of carcinomas of the skin is higher than expected according to the dose-effect relationship of UNSCEAR, whereas the number of carcinomas of the thyroid gland is lower. It is concluded that there might be less difference in susceptibility for the induction of tumours by ionizing radiation between the skin and the thyroid gland than is commonly assumed.
Dose-Response Relationship, Radiation↗
Location of HLA-A,B,C antigens in dendritic cells of normal human skin: an immunoelectron microscopic study.
The distribution of the major histocompatibility antigens HLA-A,B,C, (HLA) on dendritic cells of normal human skin was studied by immunoelectron microscopy and a 4-step immunoperoxidase technique utilizing monoclonal antibodies. Light microscopy revealed peripheral staining for HLA of epidermal and pilar infundibular keratinocytes. In the epidermis, the staining was present from the basal layer to the upper stratum spinosum. In the follicles below the level of the infundibulum, HLA was detected only on rare intraepithelial dendritic cells. These dendritic cells could not be identified in the epidermis due to the HLA staining of the surrounding keratinocytes. Similar cells stained diffusely with anti-T6 antibody; the keratinocytes did not. Immunoelectron microscopy demonstrated: (1) the presence of HLA staining of keratinocyte membranes from the stratum basalis to the level of the upper stratum spinosum and in the pilar infundibulum, (2) the possible absence of HLA on melanocytes, (3) the presence of focal HLA staining of the membranes of epidermal and follicular dendritic cells that contained Birbeck granules and were, therefore, Langerhans cells, (4) dendritic mononuclear cells within the follicular epithelium, which although devoid of Birbeck granules, exhibited similar reactivity with anti-HLA antibody. These findings suggest that HLA antigens are present on the membranes of Langerhans cells, but are not demonstrable on melanocytes in normal human skin.
Antibodies, Monoclonal↗
Distribution of major histocompatibility antigens in normal skin.
The distribution of major histocompatibility antigens HLA-A,B,C (HLA), beta 2-microglobulin (beta 2m), and Ia-like antigens (HLA-DR; Ia) in normal skin was studied in frozen tissue sections by a four-step immunoperoxidase method and an avidin-biotin method employing monoclonal antibodies. HLA and beta 2m were present on the basal and spinous keratinocytes of the epidermis, on the outer root sheath epithelium in the infundibulum of the hair follicle, and on the excretory sebaceous duct epithelium. Ia-positive dendritic cells were found in the epidermis and hair follicles, but they were more frequent in the infundibulum and isthmus of the hair follicle than in its inferior portion or in the epidermis. In the straight eccrine duct, HLA and beta 2m-positivity was most striking in its lower portion. In the superficial duct, there was a less intense staining using the four-step procedure, but when an avidin-biotin method was used, the difference was less apparent. In contrast, the acrosyringial epithelium was markedly Ia-positive with decreasing intensity of staining as the duct penetrated the dermis. No HLA or Ia antigens were identified in eccrine glands and apocrine glands. Eccrine glands were slightly beta 2m-positive. HLA and beta 2m were uniformly present in non-dilated and dilated intradermal apocrine ducts.
Adult↗
Immunological, cytochemical and ultrastructural studies in lymphomatoid papulosis.
In lymphomatoid papulosis two histological types can be distinguished, i.e. type A and type B. In the present study various immunological, enzyme-histochemical and ultrastructural techniques were used to investigate the cellular infiltrate in both types of lymphomatoid papulosis. The type A lesions showed a predominance of large atypical cells, relatively few T cells and few or no Langerhans or related cells, as defined by a positive staining for OKT6 and NA I/34 antisera. The immunological, cytochemical and ultrastructural characteristics of these large atypical cells resembled those of the Langerhans cell/interdigitating reticulum cell series. The morphology and marker profile of these large cells resembled those of Reed-Sternberg cells, which suggests a relationship between lymphomatoid papulosis type A and Hodgkin's disease. The type B lesions showed a predominance of small, medium-sized and large cerebriform mononuclear cells with the phenotype of activated T helper cells, and numerous Langerhans and/or related cells. Their cellular composition was similar to that observed in the early stages of mycosis fungoides.
Antibodies, Monoclonal↗
A staining procedure for melanin in semithin and ultrathin epoxy sections.
Staining for melanin at the ultrastructural level may act as an important diagnostic aid by helping to identify apparently amelanotic melanomas. A modified Warthin-Starry (WS) procedure for melanin has therefore been adapted for direct application to epoxy sections. Minute amounts of melanin can thus be demonstrated in individual melanosomes, indicating a high sensitivity. Using the usual types of fixation, specificity for melanin at the ultrastructural level is high. Primary osmium tetroxide (OsO4) fixation probably induces false positive staining of lipofuscin and should not be used prior to the WS procedure, but it does not influence the results of the procedure when employed as a post-fixative. It is not improbable, however, that the positive staining of lipofuscin and also of mast cell granules is due to the presence of melanin in these structures. The WS procedure yields additional diagnostic information, especially in suboptimally preserved material, as expressed by an increase in the number of convincingly identifiable melanosomes in one completely and four partly amelanotic melanomas.
Epoxy Resins↗
Reticulum cell sarcomas (large cell lymphomas) presenting in the skin. High frequency of true histiocytic lymphoma.
The clinical and histologic data from 12 patients with "reticulum cell sarcoma" (large cell lymphoma) presenting in the skin were reviewed. Moreover, when appropriate material was available additional immunological, cytochemical and ultrastructural techniques were used to define the nature of the neoplastic cells. Eight tumors were found to be of true histiocytic origin (histiocytic sarcoma), three of B-cell origin (two B-immunoblastic lymphomas and one centroblastic or large noncleaved follicle center cell lymphoma) and one case could not be classified. Possible explanations for the discrepancy between the current report and other studies as to the frequency of true histiocytic tumors will be discussed. The differentiation into T-cell, B-cell and true histiocytic lymphomas appears to be important, not only because of different clinical behaviour, but possibly also from a therapeutical point of view.
Adult↗
Dendritic reticulum cell sarcoma: a rare tumor of the follicular compartment.
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Adult↗