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.

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.

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.

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.

Immunological features of nonimmunogenic hyperthyroidism.

Blood lymphocyte subpopulations (Leu 4+ cells = pan-T cells, Leu 3a+ cells = helper/inducer cells, and Leu 2a+ cells = suppressor/cytotoxic cells), thyroid-stimulating immunoglobulins, microsomal antibodies and antibodies against thyroglobulin were determined in 10 patients with hyperthyroidism due to single autonomously functioning thyroid nodules (ATN), 11 patients with hyperthyroidism due to Graves' disease (GD) and in 20 normal subjects. Thyroidectomy was performed in 8 of the patients with ATN and in 6 of those with GD after 3 weeks of antithyroid drug treatment with methimazole. Lymphocytic infiltration of thyroid tissue, the amount of the various lymphocyte subsets (Leu 4+, Leu 3a+, and Leu 2a+ T cells as well as B+ B cells) in the thyroid gland, as well as the expression of the histocompatibility antigen HLA-DR on thyrocytes and intrathyroidal lymphocytes were examined. Blood Leu 4+ cells were reduced due to a lack of Leu 2a+ cells in patients with ATN and GD when compared to normal subjects. Thyroid-stimulating immunoglobulins were detected in all patients with ATN and GD, but in none of the normal subjects. Lymphocytic infiltration of thyroid tissue was present in patients with ATN and GD. The various lymphocyte subsets in the thyroid gland did not differ between the two patient groups. DR expression on thyrocytes was seen in 6 of the patients operated for ATN and in 5 of those who underwent surgery for GD. Infiltration with DR+-T lymphocytes was found in all thyroid glands investigated. Thus immunological findings usually classified as proof for the autoimmune origin of GD exist also in patients with ATN. An overlap in the pathogenetic background of both diseases seems possible.

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.

Demonstration of secretory component, IgA, and IgM by the peroxidase-antiperoxidase technique in inverted papillomas of the nasal cavities.

Fifteen inverted papillomas were examined by the peroxidase-antiperoxidase method for their ability to synthesize secretory component (SC) and to take up IgA and IgM. In each case, SC and IgA could be localized to the apical cytoplasm of some tumor cells. In addition, secretory component, IgA, and IgM were observed as the main constituents of hyaline globules lying in the intracytoplasmic lumina of one columnar cell variant of inverted papilloma, suggesting an intact transepithelial transport mechanism of polymeric immunoglobulins. Goblet cells, found only in the transitional cell variant of inverted papilloma, did not react with anti-SC, anti-IgA, or anti-IgM. Since SC can be utilized as a marker to differentiate columnar cells from goblet cells, transitional cell papillomas may originate from undifferentiated reserve cells, which retain their capacity to differentiate into both columnar cells and goblet cells. In contrast, in columnar cell papillomas only differentiated columnar cells are integrated into the neoplastic process.

Hemangioendothelioma of the thyroid gland--true endothelioma or anaplastic carcinoma?

After a critical histological re-examination of 26 cases of malignant hemangioendothelioma of the thyroid, and a comparison with 51 cases of anaplastic spindle and giant cell carcinoma, it becomes obvious that traumatic and shrinkage artefacts due to fixation, as well as superimposition of neoplastic and repair processes due to regressive changes--almost always seen in malignant hemangioendothelioma associated nodular goiter--may be misinterpreted as neoplastic vascular spaces (and therefore angioblastic tumour differentiation). Focal epithelial arrangements of tumour cells often observed in these malignant hemangioendotheliomas and the lack of objective light microscopic differential diagnostic criteria of anaplastic spindle and giant cell carcinoma make the high incidence of endotheliomas of the thyroid in European endemic goiter regions very questionable. Compared with anaplastic spindle and giant cell carcinoma, the incidence for (1) extrathyroid tumours that infiltrate into the trachea or the oesophagus, (2) lymph node metastases and (3) distant metastases is not statistically different in malignant hemangioendothelioma. Therefore we conclude that the tumours classified as malignant hemangioendothelioma in goitrous areas represent a special growth pattern of anaplastic spindle and giant cell carcinoma within adenomatous glands rather than a distinct tumour type.

[Serum methotrexate determination by microbiological assay in patients receiving high-dosage methotrexate (author's transl)]. / Zur Methotrexatbestimmung im Serum mit einem mikrobiologischen Test nach hochdosierter Methotrexatbehandlung.

Microbiological assay according to Burchenal (modified by Mehta) is used for the determination of the serum methotrexate (MTX) level. Fifty cycles of high-dose MTX therapy were monitored in 11 patients with osteogenic sarcoma. The results showed close correlation with the clinical course of the therapy. The serum level of MTX was elevated in patients with symptoms of toxicity.

[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.

[Androgen-producing adrenal adenoma in an 18 year-old woman: diagnosis by gas-chromatographic steroid analysis, histology and postoperative course]. / Androgen-produzierendes Nebennierenadenom bei einer 18jährigen Patientin: Diagnostik mittels gaschromatographischer Steroidanalyse, Histologie und postoperativer Verlauf.

Gas-chromatographic analysis of the urinary steroids in an 18 year-old girl with primary amenorrhoea and hirsutism revealed markedly elevated excretion of androsterone, etiocholanolone, dehydroepiandrosterone, and androstendiole, both under basal conditions and after oral dexamethasone (0.5 mg q.i.d. for three days). Adrenal scintigraphy revealed the presence of a tumour of the right adrenal gland, which was subsequently removed by unilateral adrenalectomy. Histologically, the tumour showed marked anisocytosis, but since there was no evidence of capsular or angioinvasion or of mitotic activity, it was classified as an adrenocortical adenoma. Postoperatively the patient showed regression of the virilizing syndrome and normal menstrual bleeding. Urinary steroid excretion has remained normal for four years after adrenalectomy. Androgen-producing tumours must be considered as a possible cause of hirsutism in young females and should, thus, be excluded in each case. Analysis of urinary steroids by gas chromatography is a valuable tool in accomplishing this task.

[Papillary carcinoma of the thyroid gland (author's transl)]. / Das papilläre Schilddrüsenkarzinom.

Records were examined of 174 patients with papillary thyroid carcinoma operated on at the 1st Department of Surgery of the University Hospital in Vienna between 1948 and 1976. The overall mortality rates amount to 20 +/- 8% after 5 years, rising to 70 +/- 21% after 20 years. Clear relationships are demonstrated between lymph node metastases, distant metastases, extrathyroid tumours and higher mortality rates. An older age correlates in the extrathyroid tumour group only with a higher risk of death. In our material reclassified by the criteria of the WHO classification (1974) between 1965 and 1976 the incidence of papillary carcinoma is 25% of all thyroid carcinomas. The incidence of this tumour subgroup varies in the literature between 25 and 90% and is influenced by regional differences in the use of childhood radiation on the one hand and iodine uptake on the other hand, different methods of thyroid examination and the subjectivity of the pathologist.

[Sipple syndrome (bilateral phaeochromocytoma medullary C-cell carcinoma of the thyroid gland) with exceptionally prolonged clinical course]. / Sipple-Syndrom (bilaterale Phäochromozytome und medulläres C-Zell-Karzinom der Schilddrüse) mit besonders protrahiertem Verlauf.

The sporadic occurrence of the Sipple syndrome with bilateral phaeochromocytoma and medullary thyroid carcinoma is a well-known pathological entity. The present report refers to a patient with medullary thyroid carcinoma, initially misdiagnosed as Hurthle-cell adenoma after partial resection of the thyroid gland. 5 and 8 years later the patient underwent bilateral adrenalectomy for phaeochromocytoma. 4 years after the second phaeochromocytoma a palpable thyroid nodule developed, thyroidectomy was performed and the tumour diagnosed as a medullary thyroid carcinoma. This diagnosis was confirmed by reexamination of the histological specimens obtained during the first surgical intervention. We were prompted to report the current case history, because of the protracted course of the medullary thyroid carcinoma in this patient and to point out the value of the determination of pentagastrin stimulated calcitonin values in patients with medullary thyroid carcinoma for diagnosis, postoperative follow-up and in family screening studies.

[Anaplastic spindle and giant cell carcinoma of the thyroid (author's transl)]. / Das anaplastische Spindel- und Riesenzellkarzinom der Schilddrüse.

77 cases of spindle and giant cell carcinoma of the thyroid were reviewed. This rapidly fata neoplasm extended beyond the capsule of the thyroid gland in all cases but one, with infiltration of the trachea or oesophagus in 3/4 of these cases at the time of diagnosis. 60% of the patients had lymph node metastases and 26% distant metastases. Due to the advanced stage of the primary tumour at the time of presentation, total resection was feasible in 13% of cases only. The prognosis is very poor; all patients died within 18 months. Correlations were demonstrated between lymph node metastases, distant metastases, tumour infiltration of trachea or oesophagus and shorter survival times. The survival time is prolonged in patients with partial tumour resection by adjuvant radiotherapy. 28% of all thyroid carcinomas seen at the 1st Department of Surgery of the University Hospital in Vienna between 1965 and 1976 were anaplastic. The high incidence in Austria is caused, in our opinion, by the higher rate of anaplastic transformation of long-standing, differentiated carcinomas in adenomatous goitres, which remain undetected clinically for years in this endemic goitre region because of their slow rate of growth.

[The biological classifications of malignant thyroid tumours (author's transl)]. / Zur biologischen Klassifikation der Struma maligna.

Carcinomas of the thyroid gland display large pathological and clinical variation. Favourable prognostic factors accompary well-differentiated tumours, whereas poorly differentiated or anaplastic carcinomas tend to invade early and are usually rapidly fatal. Experience has demonstrated the difference in rate of growth, subsequent recurrence and late spread even in identically well-differentiated thyroid carcinomas. Biological difference must be the underlying reason for the clinical difference in behaviour of histologically similar cancers. This report demonstrates the correlation between in vivo radioactive iodine uptake, tumour staging and recurrence-free interval in 30 thyroid carcinomas. The uptake by well-differentiated carcinomas staged T2N0M0 is significantly higher than that by tumours staged T3N1M0, whereas the latter show a higher uptake than those tumours staged T3N1M0. A high tumour uptake rate is correlated with long recurrence-free interval (up to 24 months) within all groups of staging and vice versa.

[Controlled ultra-high dosage methotrexate therapy in three patients with metastatic osteosarcoma (author's transl)]. / Ultrahochdosierte Methotrexattherapie mit plasmaspiegelgesteuerter Verabreichung bei 3 Pateiten mit metastasierendem Osteosarkom.

9 HDMTX infusions with 30 to 55 g MTX and leucovorin rescue were given to 3 patients with multifocal osteosarcoma. Resistance to standard MTX infusions with up to 12 g/m2 body surface in 4 hours indicated the administration of these higher doses (27 g/m2 body surface on average) over a shorter period of time (160 min on average). MTX input was controlled by the increase in plasma MTX levels which were determined by EMIT enzyme assay within a few minutes of sampling. The plasma MTX levels were found to be up to 10 times (average 4 times) higher than those achieved by the standard infusion. All infusions proved to be relatively well tolerated in all 3 cases, although, thrice after 36 hours an increased leucovorin rescue had to be made for 12 hours, because of delayed renal methotrexate excretion; the usual leucovorin rescue (15 mg every 6 hours) was given for an average of five days. No therapeutic effects were seen either clinically, radiologically, or histologically. The resistance to HDMTX in these three patients could not be broken by HDMTX PLRD infusions.

[Importance of the intracellular detection of alpha-fetoprotein and beta-human chorionic gonadotropin in a testicular tumor using immunoperoxidase]. / Die Bedeutung des intrazellulären Nachweises von alpha-Fetoprotein und beta-Humanchoriongonadotropin im Hodentumor mittels Immunperoxydase.

30 patients with testicular cancer (20 seminoma, 10 non-seminomatous tumours) were investigated with respect to the determination of alpha-fetoprotein and beta-human chorionic gonadotropin in formalin-fixed slices by means of the indirect immunoperoxidase technique. The immunohistochemical method detected HCG-producing cells in 8 seminoma, whereas routine histology revealed syncytiotrophoblastic giant cells in 4 cases only. The immunohistochemical results and the serum AFT, and/or HCG values obtained by radioimmunoassay corresponded well in all patients with non-seminomatous tumours. Direct evidence of HCG production in the primary tumour can be important in therapeutic decisions, especially in patients with seminoma. The direct proof of AFP in the primary tumour might answer in the future the question of the incidence and the prognostic impact of yolk sac tumour parts in malignant teratomas.

[The significance of bilateral diagnostic lymphadenectomy in thyroid cancer. Tactical operative procedure in the 1st intervention]. / Die Bedeutung der beidseitigen diagnostischen Lymphadenektomie beim Schilddrüsencarcinom. Operationstaktisches Vorgehen beim Ersteingriff.

In 101 patients with differentiated (papillary n = 74, follicular n = 20, or medullary n = 7) thyroid cancer and lymph node metastases a modified radical neck dissection (unilateral or bilateral) had been performed. After the examination of the lymph nodes in several stations the retrospective analysis showed positive nodes within the internal jugular vein (= central reservoir) in 96% of all cases independent of the tumor site. Only tumors in dorsal parts of the thyroid or in the isthmus (4%) showed other modes of lymphatic spread. Therefore during the first exploration the bilateral excision of the lymph nodes of the internal jugular vein (= diagnostic lymphadenectomy) by Kocher' incision is representative whether an extensive lymphatic spread has occurred.

[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.