[Work with psychiatrically ill parents in a pediatric psychiatry treatment facility]. / Arbeit mit psychisch gestörten Eltern in einer kinderpsychiatrischen Einrichtung.

Since the new law for hospitalization has come into effect (1991) in Austria more than before children from parents who have psychoses or other serious mental disorders have to be taken into in-patient wards in psychiatric institutions for children-often according to a court decision. This article discusses the cases of 21 such children and their 16 (respective) families. The various difficulties in dealing with the mentally ill mothers and fathers as well as some first experiences with possible strategies for working with these parents, which were gathered in therapeutic practice, are described individually. Work with these parents means trying to establish reality or risking losing reality.

Reactivity of monoclonal islet cell antibodies on normal hyperplastic and neoplastic thyroid C-cells.

Thyroid C-cell reactivity to 15 monoclonal antibodies raised against a series of pancreatic islet cells (H[human]ISL,B[bovine]ISL and R[rat]ISL) was evaluated using an indirect immunoperoxidase technique on frozen thyroid sections. Of the monoclonal anti-islet cell antibodies, five reacted specifically with bovine C-cells or human hyperplastic and neoplastic C-cells but not with follicular cells. Two monoclonal antibodies of the bovine series showed strong immunoreactivity with C-cells and only a weakly positive immunostaining of follicular cells. Five monoclonal antibodies reacted with both thyroid C-cells and follicular cells, whereas 3 monoclonal anti-islet cell antibodies did not strain any cell type of the thyroid. In human medullary carcinomas, calcitonin- and somatostatin-producing neoplastic cells were immunoreactive with the same monoclonal antibodies as were normal human C-cells. The protein bands identified by the monoclonal antibodies in human medullary carcinomas had the same molecular weight as those from pancreatic islet extracts. Our study demonstrates the presence of similar differentiation antigens on thyroid C-cells and pancreatic islet cells; this further illustrates common modes of differentiation and specialisation of these embryologically different members of the dispersed neuroendocrine system. The crossreactivity of seven of the monoclonal antibodies investigated with follicular epithelium of the thyroid suggests the existence of common antigenic determinants in different endocrine organs and may partly explain the multiple organ autoimmune response found in patients with polyendocrine diseases.

Histologic tumor regression grades in squamous cell carcinoma of the head and neck after preoperative radiochemotherapy.

Forty-one patients with Stage III and IV squamous cell carcinomas (SCC) of the head and neck were treated preoperatively with mitomycin C and 5-fluorouracil and concomitant radiotherapy. Operation specimen were examined histologically, the percentage of vital tumor cells and devitalized tumor cells were graduated. The grade of regression was classified according to a four-stage scale. Tumor regression was elevated as good (Grades 1, 2) and bad (3, 4) response to combined preoperative therapy. After a follow-up of 18 to 30 months, 14 of 41 patients have experienced a locoregional recurrence; all these patients were bad responders (Grades 3, 4) to preoperative radiochemotherapy. There was a statistically significant correlation between tumor regression grade and probability of survival (P less than 0.001). The authors conclude that the prognosis of patients with pretreated SCC of head and neck depends on the histologic grade of tumor regression.

[Immunocytochemical studies in the diagnosis of pulmonary histiocytosis X]. / Immunzytochemische Untersuchungen in der Diagnostik der pulmonalen Histiocytosis X.

The diagnostic value of immunocytochemical tests was analysed for 19 cases of pulmonary histiocytosis X (PHX) and eight of other types of fibrosing pulmonary disease (sarcoidosis, 3; exogenous allergic alveolitis, 3; chronic pneumonia, 1; fibrosing alveolitis, 1). The cellular, proliferative-fibroblastic and fibrocystic stages in the course of pulmonary changes were differentiated. PHX cells reacted with anti-S 100 protein in all stages. In three cases for which unfixed tissue was available, all PHX cells reacted with antibody Leu-6, and 35% of these cells also reacted with the proliferation marker Ki-67. The few S-100 positive cells from the eight controls were limited to peribronchial tissue. Thus the antibodies Leu-6 and S-100 are useful aids in the diagnosis of PHX.

Medullary thyroid carcinomas express chromogranin A and a novel neuroendocrine protein recognized by monoclonal antibody HISL-19.

PURPOSE AND METHODS: A number of endocrine peptides and proteins are expressed by medullary thyroid carcinoma (MTC). The expression of two newly appreciated neuroendocrine tumor markers, chromogranin A (CgA) and the endocrine antigen defined by monoclonal antibody HISL-19, was determined in 14 MTCs by immunohistology to evaluate the clinical utility of these markers in the diagnosis of MTC. Papillary, follicular, and undifferentiated thyroid tumors were also evaluated along with an MTC cell line. The same tissues were evaluated with antibodies to human calcitonin. RESULTS: All human calcitonin antibodies were found to react with the MTCs. In addition, all MTCs were reactive for CgA and the antigen detected by antibody HISL-19. CgA was generally present in the human calcitonin-containing cells, whereas the HISL-19 antigen had a more distinctive distribution. The other thyroid tumors failed to show reactivity with any of the three antibodies. CONCLUSION: Our results demonstrate that, in addition to human calcitonin, MTCs commonly express CgA and the antigen defined by antibody HISL-19. Our observations thus add to the repertoire of endocrine substances produced by MTC. These studies also demonstrate the clinical value of immunohistologic procedures for two novel antigens in distinguishing MTCs from other thyroid tumors.

Immunological studies on the occurrence and properties of chromogranin A and B and secretogranin II in endocrine tumors.

We investigated a variety of endocrine tumors for the presence of chromogranins A and B and secretogranin II. These antigens were identified by one- and two-dimensional immunoblotting and in some cases by immunohistochemistry. An antigen corresponding in electrophoretic behavior to adrenal chromogranin A was present in all types of tumors, including insulinomas, oat cell carcinomas, and Merkel cell tumors of the skin. Chromogranin B had a much more limited distribution. This antigen could not be detected in parathyroid adenomas, oat cell carcinomas, or Merkel cell tumors, either by immunoblotting and immunohistochemistry. The occurrence of secretogranin II was similar to that of chromogranin B, with the exception of a positive reaction in Merkel cell tumors. In benign pheochromocytomas, all three antigens were found consistently; whereas in two of three malignant pheochromocytomas, chromogranin B was absent. Our study establishes that in most cases chromogranins and secretogranin in tumors are identical to the adrenal antigens, but that these antigens are not always stored together. Chromogranin A is the most widely distributed marker for endocrine tumors.

Immunocytochemical patterns of islet cell tumors as defined by the monoclonal antibody HISL-19.

A series of 51 islet cell tumors removed from 28 patients was investigated immunohistochemically with the monoclonal antibody HISL-19. The antibody was produced after immunization of BALB/c mice with human islet cells and was found to react with a wide range of neuroendocrine and neural cells. All tumors presented positive immunoreaction showing various combinations of 2 basic patterns. The first pattern reflected the immunostaining of the secretory granules of the tumor cells. This "granular" staining was predominantly associated with benign neoplasms and with the tumoral production of glucagon and pancreatic polypeptide (PP), while it was absent or inconsistent in most insulin-secreting tumors. The second pattern consisted of focal immunoreactive aggregates located in a peri- (and, in polarized cells, supra-) nuclear position. This "cluster-type" staining showed a good morphologic and topographic correspondence with the Golgi apparatus of the cells of the same tumors, as shown by electron microscopy. The latter pattern was well represented in all types of islet cell tumors except those producing PP. Moreover, it was more apparent in less differentiated tumors in which the granular pattern was often absent or inconsistent. Cluster-type (but not granular) immunoreactivity was frequently found in some nonendocrine, nontumoral pancreatic structures, particularly in the epithelium of small ducts. However, the immunoreactive aggregates of nonendocrine cells were distinctly less prominent than those of endocrine cells. On the basis of a comparison with other immunohistochemical markers for neuroendocrine cells, it is concluded that the HISL-19 monoclonal antibody presents specific staining characteristics useful for the cytologic analysis of islet cell tumors.

[Immunologic hormone detection in hypophyseal adenomas: correlation of serum hormone findings with immunocytochemical hormone levels in tumor tissue]. / Immunologischer Hormonnachweis bei Hypophysenadenomen: Korrelation von Serumhormonbefunden mit immunzytochemischem Hormonbefund am Tumorschnitt.

Forty-four out of 82 patients with neurosurgically removed pituitary adenomas showed preoperatively elevated plasma hormone levels of prolactin (PRL; 22 patients), of human growth hormone (hGH; 15 patients), and of adrenocorticotropic hormone (ACTH; 7 patients). Immunocytochemical detection of the hypersecreted hormone in paraffin sections of tumour tissue, was possible in all 7 patients (100%) with Cushing's disease, in 20 patients (90%) with hyperprolactinaemia, and in 10 patients (66%) with acromegaly. In a further 3 cases beta-TSH, in one case beta-LH, and in 8 cases alpha-HCG were demonstrated in sections of tumour tissue. No clinical evidence of endocrine disturbance was found in any of these latter cases. More than one anterior pituitary hormone was detected in sections of tumour tissue in 7 cases. An overall qualitative correlation of 85% was found between the elevated plasma hormone level and immunocytochemical hormone detection in tumour tissue sections. Since there is no correlation between conventional histological staining modalities (acidophilic, basophilic, chromophobic) on the one hand, and the level of plasma hormones or immunological hormone detection in tumour tissue on the other hand, modern histological diagnosis of a pituitary adenoma should include assessment of the functional state as found by immunocytochemical hormone determination.

A novel neuroendocrine cell surface glycoprotein: identification, isolation, and initial characterization.

Murine monoclonal antibodies (MAbs) HISL-5, -9, and -14, generated after immunization of mice with human pancreatic islet cell preparations, recognize a differentiation antigen expressed by the pancreatic islet cells. These MAbs react strongly with all endocrine cell subtypes of human pancreatic islets, but minimally if at all with the exocrine acinar cells, vascular cells, and stromal connective tissue cells of the pancreas. The antigen is located on the cell surface (plasma membranes), as indicated by immunofluorescence staining of viable cell preparations. Besides the pancreatic islets, HISL-5, -9, and -14 antigenic determinants are also expressed by thyroid follicular cells, parathyroid chief cells, and anterior pituitary cells, other commonly involved targets in organ-specific autoimmune disorders. Preliminary biochemical findings indicated that the MAb-defined epitope(s) is trypsin sensitive and resistant to periodate oxidation and exposure to chloroform-methanol. Further biochemical studies, including single step MAb immunoaffinity chromatographic purification, indicate that the antigen recognized by the MAbs HISL-5, -9, and -14 is a 100 K glycoprotein.

Immunochemical characterization of a novel secretory protein (defined by monoclonal antibody HISL-19) of peptide hormone producing cells which is distinct from chromogranin A, B, and C.

In this study we have investigated the biochemical properties as well as the subcellular localization of a 67 kD (35/32 kD dimer) polypeptide detected by a monoclonal antibody (HISL-19), which was generated after immunization of BALB/c mice with human islet cell preparations. This protein is expressed by neuronal and peptide hormone producing cells and shares many biochemical and molecular key features with the chromogranin proteins. As demonstrated by one-dimensional and two-dimensional gel electrophoresis, immunoblotting, monoclonal antibody HISL-19 immunoaffinity chromatography, and immunoelectron microscopy, it is a water-soluble, acidic protein stored within secretory granules of peptide hormone-producing cells, and it is released in detectable amounts into the serum of patients bearing neuroendocrine carcinomas. Differences of the HISL-19 protein and chromogranins A, B, and C are indicated by their different tissue distribution, the discrepancy of their apparent molecular weights in sodium dodecyl sulfate gels and isoelectric points, and by the lack of cross-reactivity of their specific antibodies. The protein detected by monoclonal antibody HISL-19 represents therefore a novel component of the soluble compartments of neurosecretory granules, which is distinct from chromogranin A, B, and C.

Serum neuron-specific enolase. A marker for responses to therapy in seminoma.

Neuron-specific enolase (NSE) was evaluated as a serum marker in 105 patients with testicular cancer and compared with the established tumor markers alphafetoprotein (AFP) and human chorionic gonadotropin (HCG). Increased serum NSE activity was measured in eight of 11 (73%) patients with metastatic seminoma. Serum NSE concentrations fell to within the normal range following chemotherapy. Localization of NSE in seminoma cells was demonstrated immunohistochemically. Only six of 40 (15%) patients with metastatic nonseminomatous germ cell tumors showed elevated serum NSE levels. AFP and HCG were both positive in 70% of patients in this group, and NSE determination gave no additional information. Serum NSE concentrations were normal in 53 of 54 testicular cancer patients after orchiectomy and there was no evidence of metastatic disease; only one had borderline NSE levels, indicating the specificity of serum NSE determination. NSE is a new marker of seminoma and its measurement may be of clinical value in monitoring chemotherapy in patients with metastatic seminoma.

Monoclonal antibodies to a human islet cell surface glycoprotein: 4F2 and LC7-2.

Monoclonal antibodies 4F2 and LC7-2 react with a cell surface differentiation antigen expressed by the endocrine cells of the human pancreatic islet, but not by the acinar pancreatic, ductular, vascular, or stromal connective tissue cells. Western immunoblotting procedures demonstrate the reactivity of the monoclonal antibody 4F2 with a 120 kilodalton islet cell protein in detergent-solubilized cell extracts. These two monoclonal antibodies have potential for application in many aspects of islet cell research and diabetes in general.

Aging in man. Linear increase of a novel T cell subset defined by antiganglioside monoclonal antibody 3G5.

A new human T cell subset defined by antineuronal ganglioside mAb 3G5 increases linearly with advancing age in man. The percentage of circulating 3G5+ T cells in 21 normal individuals, quantitated by cytofluorograph analysis, increases linearly from age 7 (23-30%) to age 84 (58%) (r = 0.85, p less than 0.001). The antigen on T cells has the biochemical properties of a ganglioside that migrates between GM1 and GM2 ganglioside markers on TLC. The 3G5 subset represents the first T cell subset that reflects aging in man.

Monoclonal islet antibody HISL-19 as a tool in the diagnosis of neuroendocrine carcinomas of the skin.

The monoclonal islet cell antibody HISL-19 generated after immunization of BALB/c mice with human pancreatic islet cell preparations, demonstrated specific immunoreactivity for neuroendocrine (Merkel) cells of the skin as shown by successive and simultaneous localization of neuron-specific enolase and the antigen detected by mab HISL-19 in the same cells of the bovine epidermis. Following these observations, we tested nine neuroendocrine carcinomas of the skin that were believed to be of Merkel cell origin for their immunoreactivity with mab HISL-19 using an indirect immunoperoxidase technique on formalin-fixed and paraplast-embedded tissues. In contrast to malignant lymphomas, poorly differentiated squamous cell carcinomas, and malignant melanomas, all nine neuroendocrine carcinomas reacted strongly with mab HISL-19, indicating its potential as a useful immunohistochemical probe for the distinction of neuroendocrine carcinomas of the skin from other cutaneous neoplasms with similar histological appearance.

The prevalence of immunological abnormalities in endemic simple goitre.

Thyroid growth stimulating immunoglobulins microsomal antibodies and antibodies against thyroglobulin were determined in patients with simple goitre (n = 20) and controls (n = 6) living in an iodine deficient area. In addition, lymphocytic infiltration of thyroid tissue, the amount of the various lymphocyte subsets (Leu 4+, Leu 3a+, and Leu 2a+ T-cells as well as B1+ B cells) in the thyroid gland, as well as the expression of the histocompatibility antigen HLA-DR on thyrocytes and intrathyroidal T-lymphocytes were examined. Goitrous patients were subdivided into two groups according to their individual iodine supply estimated by iodine excretion values, and immunological parameters were compared between patients with low (group A, iodine excretion less than 70 micrograms/24 h) and with higher (group B, iodine excretion greater than 100 micrograms/24 h) iodine supply. Thyroid growth stimulating immunoglobulins and antithyroid antibodies were equally prevalent in the two patient groups, but were absent in controls. Lymphocytic infiltration of thyroid tissue was present to a comparable extent in patients of groups A and B, but to a distinctly lower degree in control persons. Intrathyroidal T-lymphocyte subsets did not differ between patients and controls. B-lymphocytes, germinal centres as well as DR+ thyrocytes were detected in goitrous patients of both groups, but never in control persons. Thus, immunological abnormalities frequently occur in patients with simple goitre and do not depend upon individual iodine supply.

Monoclonal antibody HISL-19 as an immunocytochemical probe for neuroendocrine differentiation. Its application in diagnostic pathology.

The monoclonal islet cell antibody HISL-19 was generated after immunization of BALB/c mice with human islet cell preparations. Besides reactivity with all cells of the human pancreatic islet, MAb HISL-19 also reacted with other cells of the diffuse neuroendocrine system, including anterior pituitary cells, C cells of the thyroid, endocrine cells of the gut and bronchus, the adrenal medulla, and central and peripheral neurons. In this study the authors screened a series of 53 neuroendocrine and 71 nonneuroendocrine tumors for their reactivity with MAb HISL-19 using an indirect immunoperoxidase technique on formalin-fixed and Paraplast-embedded sections. MAb HISL-19 reacted strongly with all insulomas (10), carcinoids (8), C-cell carcinomas of the thyroid (8), pituitary adenomas (6), neuroendocrine carcinomas of the skin (4), paragangliomas of the carotid body (3), and pheochromocytomas (2) tested. Neuroblastomas (3), oat-cell carcinomas of the lung (2), and melanomas (4) exhibited only very few immunoreactive cells scattered throughout the tumor or remained unstained with MAb HISL-19. With the exception of one lobular carcinoma of the breast (1/3), one adenocarcinoma of the endometrium (1/4), and one adenocarcinoma of the stomach (1/6), nonneuroendocrine tumors were negative with MAb HISL-19. Biochemical findings obtained by SDS-PAGE, "Western" immunoblotting, immunoaffinity chromatography, and absorption experiments indicate that the MAb HISL-19-defined antigen is not related to neuron specific enolase. Because the epitope recognized by MAb HISL-19 is well preserved in formalin-fixed and routinely processed tissues, this monoclonal antibody finds potential applications in diagnostic pathology as an indicator for neuroendocrine cells and their neoplasms.

Islet cell proteins defined by monoclonal islet cell antibody HISL-19.

A monoclonal islet cell antibody, HISL-19, reactive with human, bovine, and porcine pancreatic islets has been used to identify and characterize a novel group of islet cell proteins (p120, p69, p67, and p56). Besides the islets, HISL-19-reactive antigenic determinants are also expressed on selected cell types, namely, gut endocrine cells, thyroid parafollicular cells (p120), anterior pituitary cells (p40 and p24), specific hypothalamic neuroendocrine cells, and a single layer of large pyramidal cells of the cerebral cortex, thus defining a new family of neuroendocrine molecules.