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[Hypertrophic pulmonary osteoarthropathy with paraneoplastic secretion of four hormones. Considerations on pathogenesis (author's transl)].

The case of a patient with small-cell carcinoma of the lung, bone marrow metastases, and hypertrophic pulmonary osteoarthropathy is reported. Normal growth hormone serum concentrations contrasted with significant increases in ACTH, beta-MSH, calcitonin, and gastrin. A hormonal etiology has previously been suggested for hypertrophic pulmonary osteoarthropathy. Our findings indicate that the hormone responsible for hypertrophic pulmonary osteoarthropathy may be an APUD polypeptidic substance, that differs from immunoreactive GH but is related to somatomammotropins.

Adrenocorticotropic Hormone↗

[Alveolar soft tissue sarcoma].

Clinical and morphological manifestations of alveolar soft tissue sarcoma (ASTS) are presented on the basis of 19 examinations performed by the authors and data available in the literature. ASTS has been found to be more common in young women and to be usually located in the thick layers of the proximal parts of the extremities. The tumor generally shows slow growth and late occurrence of metastases. It has been demonstrated that ASTS has an organoid structure, namely alveolar grouping of cells, abundance of capillaries, and its cells contain PAS-positive inclusions. In atypical ASTS, the prognosis has been found to be less favourable. The crystalloid inclusions that are absent in other soft tissue neoplasms are a characteristic ultrastructural sign of ASTS. The genesis of ASTS remains controversial but it cannot be ruled out that it is related to the elements of the APUD-system.

Adult↗

GABAergic control of anterior pituitary hormone secretion.

Anatomical and biochemical studies have identified a hypothalamic tubero-infundibular GABAergic system, which plays a functional role on anterior pituitary hormone secretion. Experimental and clinical evidence support the presence of a dual component in the action of GABA; one mediated via the central nervous system and the other exerted directly at the anterior pituitary level. The two sites of action may be responsible for the excitatory and inhibitory effects of GABA on pituitary hormone and especially prolactin secretion. The future characterization of this system will provide a better understanding of the involvement of GABA in the physiology of anterior pituitary hormone secretion and will contribute to the development of new pharmacological agents for the therapy of neuroendocrine disorders.

Adrenocorticotropic Hormone↗

[Bronchial carcinoid tumor].

The present knowledge concerning bronchial carcinoid tumour (BCT) of the lung is described on the basis of two case histories. BCT belongs to the group of APUD tumours which are better known in the intestine. Patients with BCT are younger than patients with malignant pulmonary tumours. The incidence is less than 6% of all pulmonary tumours. The symptoms are similar to those of malignant pulmonary tumours but the duration is longer. The carcinoid syndrome is rare. It is frequently difficult to differentiate between BCT and small cell carcinoma. Radical surgery is indicated on account of the potential malignancy of BCT. The relapse frequency is less than 5% over a period of five years.

Adult↗

Prolactin control by the tubero-infundibular GABAergic system: role of anterior pituitary GABA receptors.

Anterior pituitary (AP) GABA receptors have been shown to play a functional role in the inhibitory control of prolactin (PRL) secretion by this amino acid. However, the physiological significance and the pharmacological characteristics of these receptors have yet to be determined. In normal male rat AP's incubated in vitro, GABA (10(-6) M) is effective in decreasing PRL release only when incubated in the presence of ethanolamine-O-sulphate (EOS), a potent GABA-transaminase (GABA-T) blocker. The failure of GABA alone to inhibit PRL release in vitro could be explained by the rapid degradation of the amino acid when added to the medium by AP-GABA-T. Central nervous system (CNS)- and AP-GABA receptors present similar affinity constants when evaluated by Scatchard analysis. However, displacement studies show that AP-GABA receptors have 10- and 100-times less affinity for muscimol (M), a GABA agonist, and for bicuculline, a GABA antagonist, respectively, than have GABA receptors. The low affinity of the agonist towards the AP receptors could also account for the relatively poor sensitivity of lactotrophs to GABA-mimetic compounds. Failure of chronic treatment with aminooxyacetic acid, a GABA-T inhibitor, to modify the PRL-lowering effect of GABA-mimetic compounds, despite the decrease in the number of AP-GABA receptors, indicates that in normal conditions only a reduced number of receptors are operative. These studies of AP-GABA receptors provide insight for a better understanding of the mechanisms involved in the regulation of PRL secretion by the hypothalamic GABAergic system.

Animals↗

[Pathology of endocrine polyneoplasms (polyadenomatoses) (author's transl)].

The term "endocrine polyadenomatoses" includes two types of pathological entities in which there are an association of at least two endocrine tumors having no physiological relationships, and hereditary familial characteristics: Wermer's syndrome (Type I): pancreatic endocrine tumor, pituitary adenoma, and hyperplasia or adenoma of the parathyroids. Sipple' syndrome (Type II): medullary thyroid cancer, one of two pheochromocytomas, and parathyroid hyperplasia. The multifocal character of the pancreatic D-cell lesions in the first type, and the bilateral nature of the thyroid and adrenal lesions in the second type are particular features of each of them. Apart from some parathyroid lesions, for which the origin is still debatable, these endocrine tumors enter into the framework of the apudomes and are derived therefore from the neural crest. The association of other tumoral varieties of the APUD (carcinoid) type with nervous tissue tumors, and with dysmorphic anomalies suggests that these syndromes are the expression of a dysgenesis affecting more or less completely, structures derived from the neural crest.

Adrenal Gland Neoplasms↗

[A rare variety of polyendocrine neoplasms: the MEN IIb and MEN III syndrome].

The MEN IIb syndrome is a rare form of multiple endocrine neoplasia, clearly defined more than 15 years ago, since which time more than 100 cases have been identified. It has a characteristic phenotype appearance which is unique and should permit more frequent diagnosis. The patient who is the subject of this study had passed through several different hospital departments without his very characteristic appearance being recognized or a diagnosis established. The marfanoid aspect of such patient is however very obvious, with kyphosis, skeletal asymmetry and funnel chest. The facial appearance of blunt features and thick lips is even more specific. The tongue and digestive mucosa are covered with small polypoid lesions which are submucosal ganglioneuromas. The visible presence of fine hyperplastic nerve fibres on the cornea is pathognomonic. This syndrome occurs sporadically but is generally transmitted genetically in an autosomal dominant manner. A medullary thyroid carcinoma, followed or preceded by pheochromocytoma (often bilateral), is associated with these dysmorphic signs. The tumours are themselves preceded by C-cell hyperplasia or adrenal medullary hyperplasia. The ganglioneuromas which predominate in the digestive tract exist from birth. The accompanying symptoms may, initially, be mistaken for inflammatory bowel disease. The prognosis is poor, since it relates to the evolution of the medullary thyroid carcinoma which is particularly malignant and presents at an early age. We have been following the course of this unusual disease of the APUD system in a young man, now aged 26 years, for over 2 years.

Adrenal Gland Neoplasms↗

"Aging bull'.

An old bull, it is said by those who know, can have his troubles. Included among these are vertebral osteosclerosis and ankylosing spondylosis; this stiffening up limits, rather than accentuates, the value and reproductive potential of a stud bull past his prime. Associated with these abnormalities, however-and not seen in age-matched cows of comparable breeds-are fascinating endocrine neoplasms suggestive of a pattern that could be productive as a model of human hereditary endocrine abnormalities. Adjacent to the thyroid gland in other vertebrates are ultimobranchial bodies that are incorporated into the lateral thyroid lobes in primates as the parafollicular "C cells' of the thyroid. These are the cells in man that give rise to medullary thyroid cancer and are associated with calcitonin secretion, useful as a tumor marker. In aging bulls of whatever breed, nearly half exhibit abnormality of these ultimobranchial bodies: 20% show hyperplasia, and 30% have frank neoplasia. These ultimobranchial tumors appear in bulls passing 6 1/2 years in age, and are absent in young bulls and all cows of any age. Calcitonin can be demonstrated in the ultimobranchial tumors from bulls, and secretion is stimulated by calcium infusion, though serum calcium remains normal. The ultimobranchial tumors themselves can range from hyperplasia through adenoma to metastasizing carcinoma-in fact, representing one of the commoner cattle cancers. Parathyroid glands taken from bulls with these ultimobranchial tumors initially show evidence of inhibited secretory activity and morphologic atrophy, but later go on to develop hyperplasia and, eventually, autonomy. Cattle forage on calcium-rich diets. Bulls appear to respond to this calcium excess from the positive balance, but breeding cows have the unique calcium deficits of the high net loss of calcium through lactation and the large requirements of calcifying a fetal skeleton. Chronic stimulation of the APUD-derived ultimobranchial bodies by high calcium intake, not counterbalanced by calcium losses in the bulls, may account for the development over time of the ultimobranchial neoplasms. Further, a number of the bulls who have the ultimobranchial tumors are found to have multiple endocrine tumors in other glands-bilateral pheochromocytomas and pituitary acidophil adenomas.

Aging↗

[Histology of cerebellar metastasis of bronchial oat cell carcinoma].

Anatomo-pathological examination of 28 bronchic oat-cell carcinoma, all with cerebellar metastases and which are very often cerebral. In half of the cases, these localized cerebellar metastases contain palisades. These formations which haven't been described until now within intracranial metastases, can't be considered as artefacts as their frequency approaches 50% of the cases. Neither the primitive tumor nor the extracerebral metastases of the series reveal palisades; sometimes some of them exist in their cerebral metastases. As far as the epidemiology, the clinical evolution, the survival time and the extracerebral localization are concerned, these 28 cases are not different from those described in medical literature. The morphological, hormonal and biochemical knowledge we possess about this type of cancer tends to prove its neuroectodermic origin as well as its close relation with both the APUD- and the "endocrinien diffus" systems. The described palisading elements represent another very specific morphological point which tends to support this theory: they appear principally in the tumors of the central and peripheral nervous system. Although the author is not able to explain the reason of palisades' genesis in cerebellar metastases, he insists on the fact that it iw very important - as far as every days' biopsy's study is concerned - to proceed to a differential histological diagnosis in regards to certain primitive tumors of the nervous system (among these the medulloblastoma) and a cerebellar metastasis of this type of bronchic carcinoma.

Aged↗

Carcinoid of the ileocaecal valve: a case report.

The authors present a case of carcinoid of the ileocaecal valve. The patient complained for over one year of mild pain in the right lower quadrant of the abdomen. Colonoscopy had shown hyperaemia on the colic side of the ileocaecal valve which appeared substenotic and biopsy revealed micronodules formed by chromogranin-A-positive neuroendocrine cells. Roentgenography of the small bowel and barium enema revealed a specular filling defect in the caecum and in the terminal ileum near the ileocaecal valve. Right hemicolectomy was performed and the definitive diagnosis was carcinoid of the ileocaecal valve. The tumour had spread to all layers of the intestinal wall and 4/19 lymph nodes were metastatic. The patient refused an oncological examination; however, three years after surgery there are no signs of recurrence. Carcinoids have been included in the APUD system and usually present endocrine activity. The 5-year survival of patients with gastrointestinal carcinoids is 80% when located in the appendix and rectum as against 50% in the stomach, jejunum and colon, because the localisation in the appendix and rectum is marked by clinical signs of appendicitis and rectal bleeding, which suggest diagnostic examinations useful for an early diagnosis. Radical operations according to the rules of oncologically correct surgery are the treatment of choice, while complementary treatments have yet to be codified.

Aged↗

Chemical features of monoaminergic and non-monoaminergic neurons in the brain of laboratory shrew (Suncus murinus) are changed by systemic administration of monoamine precursors.

5-Hydroxy-L-tryptophan (5-HTP) and L-3,4-dihydroxyphenylalanine (L-DOPA) were injected intraperitoneally (i.p.) into the laboratory shrew (Suncus murinus). Immunocytochemical and immunofluorescence studies were carried out on serial or same sections of the brain, which were reacted with specific antisera to dopamine (DA) or serotonin (5-HT) produced in our laboratory. We observed that cell bodies and nerve terminals of many catecholaminergic (CAnergic) neurons exhibited 5-HTP uptake and conversion of the precursor into 5-HT. However, the locus ceruleus showed scarcely any 5-HT immunoreactivity. This suggests that the precursor uptake mechanism may be different among various CAnergic groups. In contrast to these findings on CAnergic neurons, all serotoninergic (5-HTnergic) neurons after L-DOPA administration showed DA immunopositive reaction in their cell bodies and nerve terminals, suggesting that 5-HTnergic neurons may have the same capacity for precursor uptake. On the other hand, we observed that all aromatic L-amino acid decarboxylase (AADC)-only-positive neuron groups showed both DA and 5-HT immunoreactions after L-DOPA and 5-HTP administration, respectively, in the double-staining immunofluorescence method. From these results, AADC-only-positive neurons may be considered to belong to the amine precursor uptake and decarboxylation (APUD) system.

5-Hydroxytryptophan↗

[Syndrome of inappropriate antidiuretic hormone secretion. A report of two cases with hyponatremia and hypouricemia].

Two cases of Schwartz-Bartter syndrome are reported. Both were due to malignant anaplasic tumours of the APUD type with multiple abnormal endocrine secretion, and both were accompanied with hypouricaemia of uncertain significance. The authors believe that the association of hypernatraemia with hypouricaemia should alert clinicians to the possibility of a syndrome of inappropriate antidiuretic hormone secretion (SIADH) of malignant origin.

Apudoma↗

[Amyloidosis. II. Current pathogenetic and clinico-nosographic aspects].

Amyloidosis is due to the overproduction of a precursor protein and its conversion into products capable of polymerisation into fibrils. The primary form, or that associated with multiple myeloma or Waldenström's macroglobulinaemia, marked by the presence of protein AL, includes the overproduction of Ig light chains followed by conversion on the part of lysosome enzymes. The forms can thus be classified as immunoproliferative diseases (plasma-cell dyscrasias). Secondary amyloidosis is primarily associated with neoplasia or chronic inflammation. Its biochemical label is the AA protein. Initially, there is overproduction of protein SAA, while the formation of AA-amyloid fibrils may theoretically be attributed to a variety of factors: changes in the amount of circulating SAA, the presence of amyloidogenetic SAA, variations in the activity of SAA catabolic systems, insufficient removal of acculated fibrils. The way in which the immunocompetent system intervenes is a controversial subject. Lesser froms of amyloidosis are known in which there are local deposits of amyloid: APUD-amyloidosis, amyloidomas. In some forms, the features of systemic accumulation are maintained, but only one organ is primarily involved. They are rarely of clinical significance (e.g. senile amyloidosis). Current biochemical techniques enable a clinical and nosographic distinction to be drawn between an Ig (AL)-amyloidosis and non-Ig (AA, APUD and AS) forms.

Amyloid↗

Iodine-131 MIBG scintigraphy of neuroendocrine tumors other than pheochromocytoma and neuroblastoma.

Metaiodobenzylguanidine (MIBG) locates most pheochromocytomas and neuroblastomas. The tracer is concentrated in intracellular storage vesicles by an active process. Many other neuroendocrine tumors of the amine precursor uptake and decarboxylation (APUD) series have hormonal storage vesicles and, thus, the potential to take up [131I]MIBG. A variety of neuroendocrine tumors in 57 patients were studied 1, 2, and 3 days after 0.5 mCi [131I]MIBG. Views from skull to pelvis were obtained. Results of MIBG scans were compared with all available imaging modalities (including plain radiography, liver scan, ultrasound, computed tomography, and angiography) and surgical exploration. The neuroendocrine nature of the tumor was determined by histology, immunohistochemistry, electron microscopy, and the assay of appropriate biogenic amines and peptide hormones. Results were (positive/total cases): carcinoids (four of ten), nonsecreting paragangliomas (three of three), sporadic medullary carcinomas of the thyroid (MCT) (one of five), familial MCT (one of 26), chemodectomas (two of five), oat cell carcinomas (zero of four), choriocarcinoma (one of one), atypical schwannoma (with storage granules) (one of one), Merkel cell skin cancer (one of one), islet cell carcinoma (zero of one). We conclude that a wide range of neuroendocrine tumors show [131I]MIBG uptake; tumors other than pheochromocytomas and neuroblastomas are less often seen scintigraphically, but in certain cases (e.g., carcinoid and nonsecreting paragangliomas) scintigraphy may be useful in depicting the extent and location of disease and may indicate therapeutic potential. Iodine-131 MIBG shows promise in the diagnosis and staging of tumors of varied types.

3-Iodobenzylguanidine↗

[Ectopic production of chorionic gonadotropin in apudomas (author's transl)].

Two pheochromocytomas, two carcinoid tumours of the ileum and one pancreatic vipoma showed APUD-system properties and formed electron-dense secretory granules indicating synthesis and storage of proteohormones. Besides catecholamines, 5-hydroxytryptamine and vasoactive intestinal polypeptide, all five tumours contained immunoreactive chorionic gonadotropin and also its free, protomeric beta chain as a sign of de-differentiation. Plasma of the tumour patients also contained immunoreactive chorionic gonadotropin and the free protomeric beta chain, both of which are useful tumour markers.

Acute Kidney Injury↗

Biochemical and functional aspects on the control of prolactin release by the hypothalamo-pituitary GABAergic system.

A growing body of biochemical, immunohistochemical, and autoradiographic evidence indicates the presence of two different GABAergic systems in the mediobasal hypothalamus: one intrinsic, the tuberoinfundibular GABAergic system, and the other extrinsic, whose cell bodies are located outside the mediobasal hypothalamus and which projects to this area and establishes synaptic contacts with aminergic and peptidergic neurons involved in endocrine function. This particular anatomical configuration provides a rational basis to explain the dual action of GABA (inhibitory and stimulatory) on prolactin release. Different studies aimed at identifying the precise role of GABA on prolactin function have demonstrated that this system can be modulated, at the pre- and/or post-synaptic level, by different experimental maneuvers in which prolactin secretion is physiologically and pharmacologically altered. GABA mainly appears to be involved in feedback mechanisms preventing an exaggerated prolactin output during specific physiological situations. The ability of clinically tested, direct GABAmimetic compounds to lower prolactin secretion in the rat points towards a clinical usefulness of these drugs in particular spontaneous or induced neuroendocrine disorders. However, the possibility of a widespread use of this type of compounds is hampered by the lack of potent, specific and non-toxic GABA agonists suitable for clinical purposes.

Animals↗

Factors affecting production of mold mycelium and protein in synthetic media.

The effects of certain cultural conditions on the yield of dry mycelium, protein, and total amino acid content of Rhizopus oligosporus Saito (NRRL 2710), Rhizopus rhizopodiformis (Cohn apud Lichtheim) Zopf (NRRL 6246), and Absidia corymbifera (Cohn) Sacc. et Trotter (NRRL 6247) were studied. The yield of mycelium was found to significantly increase as the spore inoculum was increased from 187,500 to 2,250,000 spores. But the total amino acids (grams/liter) did not change significantly, whereas the percentage of crude protein decreased. An inoculum containing approximately 750,000 spores/ml was used in all of the other experiments. Mycelial production was highest at 37 degrees C for all three molds. However, the best temperature for percentage of crude protein and total amino acids varied with the organism. The mycelial yield and total crude protein of R. oligosporus showed some significant changes as the C/N ratio was increased in 3% glucose medium. In a synthetic medium having a 15:1 C/N ratio, the strains of R. oligosporus, R. rhizopodiformis, and A. corymbifera had better yields from falactose than glucose, not only in dry mycelium but also in total crude protein (grams/liter) and total amino acids (grams/liter). R. oligosporus grew very well on several ammonium salts. but the maximum yield of dry mycelium, total crude protein (grams/liter), and total amino acids (grams/liter) occurred with ammonium sulfate. The optimum pH for both Rhizopus species was 4.0, although R. oligosporus grew equally well at pH 3.0 and slightly less at pH 5.0. The highest yield of mycelium for A. corymbifera was obtained in a medium with an initial pH of 8.0. It was calculated that a fermenter chanrged with an adequate medium and 1,000 lb (about 450 kg) of R. oligosporus or A. corymbifera cells could produce 88 or 90 lb of protein (on a dry-weight basis) per h if the product was removed continuously.

Amino Acids↗

[The enterochromaffin-serotonin system and Helicobacter infection in the mechanisms of the staged development of peptic ulcer].

Submitted in this article are scientific propositions and problems concerning the way ulcer disease (UD) of the gastroduodenal system (GDS) develops through its particular stages, and pathosanogenous role which the enterochromaffin-serotonin system (ECSS), a part of the diffusive neuroendocrine APUD-system of the organism, has in it, along with etiopathogenetic role Helicobacter infection plays in the gastroduodenal mucosa (M). Experience gained by the authors with prospective comprehensive evaluation and treatment of 310 patients with chronic gastroduodenitis (CGD), 198 UD GDS patients and 350 of those surgical patients who had undergone resection of the stomach for complicated UD GDS, indicates that all above pathological states share common etiopathogenetic, clinical, histomorphological and microbiological (Helicobacter infection) features, which facts suggest a common pathomorphogenesis of CGD, erosive GD, UD GDS and postgastroresectional UD, and a staged character of erosive-ulcerous transformation in the GDS M, with the hypercoagulative sings being present at the level of hemomicrocirculation. Progressing structural and functional changes in ECSS parallel to stages of development and severity of the UD GDS course suggest their interrelationship to pathosanogenesis during all stages of erosive-ulcerous transformation. At the molecular level, this may reflect directly the course of staged ulceration and a point of activation of processes of physiological defence, this being of diagnostic as well as prognostic value. The enterochromaffin-serotonin conception of pathosanogenesis of staged erosive-ulcerous transformation in GDS M supplements, rather than contradicts to a current infectious Helicobacter hypothesis of ulcerogenesis. Thus, evaluation of ECSS structural and functional status in UD GDS is to be part of a diagnostic algorithm testing severity of the course as well as of a monitoring of treatment and prognostication.

Adult↗