Regulation of dopamine receptors in the MtT/W15 transplantable pituitary tumor by estrogen

We investigated the effects of estrogens on the regulation of dopamine receptors in the MtT/W15 transplantable rat pituitary tumor. Diethylstilbestrol (DES) and 17[beta]-estradiol treatment in female rats significantly decreased the number of dopamine binding sites (Bmax) from 85 +/- 3.9 fmol/mg protein in untreated rats to 9.2 +/- 1.2 and 8.2 +/- 2.8 fmol/mg protein in DES and 17[beta]-estradiol-treated rats, respectively, while the binding affinities (Kd) did not change significantly. Testosterone treatment did not change the Bmax, while ovariectomy resulted in a significant increase in the Bmax (146.3 +/- 6.7 fmol/mg protein). The effects of DES on the Bmax were reversible, since removal of the DES for one week before sacrificing the animals led to a marked increase in the Bmax (54.9 +/- 3.1 fmol/mg protein).Pituitaries from normal female rats treated with DES for 6 and 9 weeks had a significant decrease in the Bmax.These results show that the number of dopamine binding sites in the membranes of MtT/W15 tumors is decreased by estrogen treatment and that this effect is reversible after removal of the estrogenic stimulus.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/26273/1/0000358.pd

Calcitonin free oat-cell carcinoma of the thyroid gland

Two cases of primary oat-cell carcinoma of thyroid, in a 63-year-old woman and a 73-year-old man, are described. Case 1 was a compound tumour with the oat-cell component merging with a papillary component. Both tumours, in addition to histological features consistent with oat-cell carcinoma, showed immunohistochemical positivity with anti-chromagranin A and anti-synaptophysin antisera. Negative results were obtained when anti-calcitonin and anti-thyroglobulin antisera were employed. Using in situ hybridization, chromogranin A and B messenger RNAs were localized with biotinylated oligonucleotide probes. In contrast, with in situ hybridization, no localization for calcitonin messenger RNA was seen using radioactive and biotinylated probes. It is concluded that these calcitonin-free, small-cell carcinomas should be considered separately from medullary thyroid carcinomas and be regarded as a distinct entity, probably the thyroid equivalent of oat-cell carcinomas of the lung.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/47516/1/428_2005_Article_BF01600144.pd

Metastatic carcinoma to the sphenoid sinus case report and review of the literature

Metastatic carcinoma to the sphenoid sinus is a rare event. A case of metastatic adenocarcinoma from the prostate gland to the sphenoid sinus and diagnosed with the aid of immunoperoxidase staining is presented. A concurrent review of the literature uncovered only 17 previously reported cases of carcinoma metastatic to the sphenoid sinus. Among these cases, adenocarcinoma from the large bowel and prostate gland predominated.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/47269/1/405_2004_Article_BF00453691.pd

Idiopathic prolactin cell hyperplasia of the pituitary mimicking prolactin cell adenoma: a morphological study including immunocytochemistry, electron microscopy, and in situ hybridization

Prolactin cell adenoma is the most frequently found lesion in surgically removed pituitaries of patients with hyperprolactinemia. However, in several instances, instead of prolactin cell adenoma, other lesions are encountered by morphological investigation. We report here the morphological findings in a patient with hyperprolactinemia who underwent transsphenoidal pituitary surgery for suspected prolactin cell adenoma. A morphological diagnosis of tumor could not be confirmed and massive diffuse prolactin cell hyperplasia was identified. The aim of this publication is to describe the lesion by histology, immunocytochemistry, electron microscopy, and in situ hybridization and to call attention to primary prolactin cell hyperplasia which can mimic prolactin cell adenoma.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/47231/1/401_2004_Article_BF00293958.pd

Tendency to Maximum Complexity in a Non-Equilibrium Isolated System

The time evolution equations of a simplified isolated ideal gas, the "tetrahe- dral" gas, are derived. The dynamical behavior of the LMC complexity [R. Lopez-Ruiz, H. L. Mancini, and X. Calbet, Phys. Lett. A 209, 321 (1995)] is studied in this system. In general, it is shown that the complexity remains within the bounds of minimum and maximum complexity. We find that there are certain restrictions when the isolated "tetrahedral" gas evolves towards equilibrium. In addition to the well-known increase in entropy, the quantity called disequilibrium decreases monotonically with time. Furthermore, the trajectories of the system in phase space approach the maximum complexity.Comment: 22 pages, 0 figures. Published in Phys. Rev. E 63, 066116(9) (2001

MALIGNANT SOMATOSTATINOMA PRESENTING WITH DIABETIC KETOACIDOSIS

High circulating levels of somatostatin (SRIF) were detected in a patient with a metastatic tumour after development of diabetic ketoacidosis (DKA). Fasting insulin and C-peptide levels were markedly suppressed, but plasma glucagon was not suppressed below normal. Progressive cachexia ensued; at autopsy a poorly differentiated non-small cell neuroendocrine carcinoma metastatic to liver was found. Small gallstones were noted. Electron microscopy of tumour tissue showed neurosecretory granules and tonofilament bundles. Immunohis-tochemical staining of tumour cells was diffusely positive for carcinoembryonic antigen, bombesin-like immunoreactivity, and calcitonin with focal immuno-reactivity for SRIF, serotonin, neuron-specific enolase, chromogranin, and epithelial membrane antigen. Column chromatography of plasma and tumour extract revealed five or more peaks of material with SRIF-like immunoreactivity (SRIF-LI): predominantly SRIF-28 and intermediates in tumour extract, and SRIF-14 and an intermediate between SRIF-28 and SRIF-14 in plasma. DKA in this case of somatostatinoma syndrome may reflect differential effects of tumour production of larger molecular weight SRIF forms on insulin and glucagon secretion.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/75579/1/j.1365-2265.1987.tb00817.x.pd

Epigenomic and somatic mutations of pituitary tumors with clinical and pathological correlations in 111 patients

Objective To profile clinically non-aggressive and aggressive pituitary adenomas (PAs)/pituitary neuroendocrine tumours (PitNETs) and pituitary carcinomas for somatic mutations and epigenetic alterations of genes involved in cell proliferation/differentiation, microRNAs (miRNA)/long noncoding RNA (LncRNA)-post-transcriptional regulators and therapy targets. Design Retrospective observational study. Patients and Measurements A total of 64 non-aggressive and 41 aggressive PAs/PitNETs and 6 pituitary carcinomas treated by endoscopic surgery with >= 1-year follow-up were included. Somatic mutations of 17 genes and DNA methylation of 22 genes were assessed. Ten normal pituitaries were used as control. Results We found at least one mutation in 17 tumours, including 6/64 non-aggressive, 10/41 aggressive PAs/PitNETs, and 1/6 pituitary carcinoma. AIP (N = 6) was the most frequently mutated gene, followed by NOTCH (4), and TP53 (3). Hypermethylation of PARP15, LINC00599, ZAP70 was more common in aggressive than non-aggressive PAs/PITNETs (p < .05). Lower levels of methylation of AIP, GNAS and PDCD1 were detected in aggressive PAs/PITNETs than non-aggressive ones (p < .05). For X-linked genes, males presented higher level of methylation of FLNA, UXT and MAGE family (MAGEA11, MAGEA1, MAGEC2) genes in aggressive vs. non-aggressive PAs/PITNETs (p < .05). In pituitary carcinomas, methylation of autosomal genes PARP15, LINC00599, MIR193 and ZAP70 was higher than in PAs/PITNETs, while X-linked genes methylation level was lower. Conclusions Somatic mutations and methylation levels of genes involved in cell proliferation/differentiation, miRNA/LncRNA-post-transcriptional regulators and targets of antineoplastic therapies are different in non-aggressive and in aggressive PAs/PitNETs. Methylation profile also varies according to gender. Combined genetic-epigenetic analysis, in association with clinico-radiological-pathological data, may be of help in predicting PA/PitNET behaviour

Sites of synthesis of chromogranins A and B in the human brain

The sites of synthesis of the chromogranins A and B, and their potential processed peptides, were examined by quantitating the levels of chromogranin A and B mRNA in various regions of the human brain by Northern blot analysis. Chromogranin A and B mRNA expression in the brain is region-specific and confined to grey matter. In situ hybridization histochemistry detected chromogranin A and B mRNA in pyramidal neurons of human cerebral cortex. Cell-specific expression in subpopulations of cerebrocortical neurons suggest that chromogranin A and B gene products may play a role in central neuronal function.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/30124/1/0000500.pd

Carcinosarcoma of bladder Evaluation by electron microscopy and immunohistochemistry

A case of carcinosarcoma of the urinary bladder characterized by electron microscopy and immunohistochemistry is described. The use of these studies in poorly differentiated bladder neoplasms and in suspected cases of carcinosarcoma is encouraged. Increased accuracy in characterizing these tumors will permit a better understanding of their natural history and response to therapy.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/24686/1/0000105.pd

MEN I pancreas: A histological and immunohistochemical study

The spectrum and extent of islet cell histopathological findings in patients with multiple endocrine neoplasia, type I (MEN I) syndrome has never been clearly defined. Although some patients have discreet tumors causing clinically evident syndromes, others may have no symptoms until metastatic islet cell carcinoma is apparent. Whether diffuse islet cell disease occurs in all patients with grossly apparent tumors is not known. This study is an attempt to define both the functional and anatomical extent of islet cell disease and its relationship with the clinical course of patients with MEN I syndrome. The resected specimens of pancreas from 14 patients with MEN I syndrome were evaluated for hyperplasia, nesidioblastosis, multiple tumors, and evidence of malignancy. In 12 cases, specimens consisted of distal pancreas and, in 2 cases, the entire pancreas was available. Multiple sections were taken from each specimen. Immunoperoxidase staining was done for gastrin, pancreatic polypeptide, glucagon, serotonin, VIP, somatostatin, and neuron-specific enolase in sections of 24 tumors from 10 patients. Five of the 10 patients with Zollinger-Ellison syndrome underwent total gastrectomy and 3 others underwent only pancreatic procedures to control their acid hypersecretion. The following is concluded. All MEN I patients with pancreatic neoplasms have diffuse islet cell involvement consisting of nesidioblastosis, micro- and macronodular hyperplasia. Some tumors produce multiple hormones and these patients are at risk to develop new tumors, but complete excision of grossly apparent tumors may result in long-term control of the endocrinopathy present. This is particularly true for patients with insulinoma and hypoglycemia. Selected patients with gastrinoma may also be considered for excision of their islet cell tumor(s) without concomitant gastrectomy, especially if transhepatic venous sampling demonstrates a single site of excess gastrin production. However, if transhepatic venous sampling demonstrates diffuse sources of hypergastrinemia, a local pancreatic procedure will invariably be unsuccessful. Total pancreatectomy in MEN I patients with disease localized to the pancreas is the only curative surgical procedure but is rarely indicated. L'histopathologie des cellules insulaires pancréatiques des malades qui présentent un syndrome MEN I n'a jamais été parfaitement définie. Si certains parmi eux sont porteurs de petites tumeurs qui se manifestent par des syndromes cliniques patents, d'autres n'accusent aucun symptôme avant que des métastases néoplasiques ne se manifestent. En particulier, on ne sait pas si les altérations des cellules insulaires sont diffuses quand les malades présentent des tumeurs évidentes. Cette étude a pour but de définir à la fois l'importance anatomique et l'importance fonctionnelle de la maladie insulaire par rapport à son expression clinique chez les sujets concernés par ce syndrome. Pour ce faire, des spécimens provenant de 14 malades atteints du syndrome MEN I ont été étudiés eu égard à l'hyperplasie, à la nésidioblastose, à la multiplicité des îlots tumoraux, à la malignité. Dans 12 cas, les spécimens répondaient au pancréas distal, dans 2 cas à la totalité du pancréas. De multiples coupes furent pratiquées au niveau de chaque pièce soumise à l'examen. L'imprégnation à l'immunoperoxidase concerna les coupes de 24 tumeurs provenant de 10 patients. Cinq des 10 malades qui présentaient un syndrome de Zollinger-Ellison avaient subi une gastrectomie totale et 3 une intervention pancréatique pour contrôler leur hypersécrétion acide. Les conclusions tirées de cette étude furent les suivantes: tous les malades accusant un syndrome MEN I et porteurs d'un néopolasme pancréatique présentaient des lésions insulaires diffuses répondant à une nésidioblastose, à une hyperplasie micronodulaire et macronodulaire. Quelques tumeurs produisaient de multiples hormones: gastrine, polypeptide pancréatique, glucagon, sérotonine, V.I.P., somatostatine, testées par la méthode. Il résulte de ces constatations que les risques de récidive tumorale après exérèse complète des tumeurs évidentes ne sont pas à écarter, encore que l'exérèse permette de contrôler longtemps l'endocrinopathie. Ceci est particulièrement vrai pour les insulinomes hypoglycémiants. En ce qui concerne les gastrinomes, leur exérèse peut être suffisante, en particulier lorsque les prélèvements veineux étagés montrent qu'ils sont uniques; la gastrectomie concomitante est alors inutile. En revanche, lorsque la gastrine est trouvée en excès au niveau de multiples échantillons veineux, l'exérèse tumorale est insuffisante et la pancréatectomie totale représente l'intervention indispensable; en fait, son indication est rare. La variedad del espectro de la histopatología de las células insulares en pacientes con sindrome de neoplasias endocrinas múltiples tipo I (NEM I) todavía no ha sido claramente definido. Aún cuando algunos pacientes poseen tumores discretos que causan síndromes clínicamente evidentes, otros pueden no exhibir sintomatología alguna hasta cuando se hace evidente un carcinoma metastásico de células insulares. No se sabe si hay enfermedad difusa de las células insulares en todo paciente con tumores macroscópicamente aparentes, ni además se conoce con qué frecuencia se desarrollan nuevos tumores en pacientes con síndrome NEM I después de resección local o de pancreatectomía parcial para tumores primarios de células insulares. El presente estudio intenta definir la extensión funcional y anatómica de la enfermedad de las células insulares y su relación con la evolución clínica en pacientes con el síndrome NEM I.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/41313/1/268_2005_Article_BF01654938.pd