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Annals of Surgery Oct 1975Foregut endocrine polypeptide-secreting APUD cells (Amine-Precursor-Uptake and Decarboxylation), in their embryologic migration from neural crest to foregut may become...
Foregut endocrine polypeptide-secreting APUD cells (Amine-Precursor-Uptake and Decarboxylation), in their embryologic migration from neural crest to foregut may become "arrested" in the mesoderm or in other ectopic locations. They may become hyperplastic, adenomatous or malignant. Eight illustrative patients are reported. One patient had "pancreatic hyperparathyroidism" with hypercalcemic crises, pancreatic apudocarcinoma, normal parathyroids, biologically active parathormone, but inert immunochemically to the usual parathyroid antisera. Two had gastrin-secreting malignancies in the mesoderm. Remission after excision, but eventual recurrence of the syndrome due to islet cell hyperplasia required total gastrectomy. One patient had a gastric corpus apudocarcinoma found prospectively with hypergastrinemia which required excision of the tumor. One patient had acromegaly with hypergastrinemia and antral gastrinosis treated by pituitary irradiation, One patient had the antral or intermediary type of the Zollinger-Ellison syndrome with moderate hypergastrinemia, duodenal ulcer and antral gastrinosis, treated by vagotomy and antrectomy. One patient had hyperparathyroidism with antral gastrinosis, treated by parathyroidectomy. One patient had malignant Zollinger-Ellison syndrome and developed associated thyroid parafollicular cell hyperplasia and parathyroid chief cell hyperplasia, treated by total gastrectomy and multiple endocrine excisions. These investigative observations demonstrate ectopic loci and associated hyperplasias which support the concept of migration and bizarre potentiality of polypeptide-secreting cells of the foregut.
Topics: Adenoma; Adult; Aged; Amines; Child; Decarboxylation; Endocrine System Diseases; Endoderm; Female; Gastrins; Humans; Hyperplasia; Male; Middle Aged; Multiple Endocrine Neoplasia; Neoplasms; Pancreatic Neoplasms; Parathyroid Diseases; Parathyroid Hormone; Peptides; Stomach Neoplasms; Zollinger-Ellison Syndrome
PubMed: 241302
DOI: 10.1097/00000658-197510000-00003 -
The Journal of Physiology Mar 2001
Topics: APUD Cells; Amines; Animals; Hormones
PubMed: 11251039
DOI: 10.1111/j.1469-7793.2001.0581h.x -
Gut Apr 1973Indirect immunofluorescence studies using an antiserum to purified porcine gastric inhibitory polypeptide indicate, in the gastrointestinal tract of dog and man, that...
Indirect immunofluorescence studies using an antiserum to purified porcine gastric inhibitory polypeptide indicate, in the gastrointestinal tract of dog and man, that this polypeptide is present in cells situated predominantly in the mid-zone of the glands in the duodenum and, to a lesser extent, in the jejunum. Absolute correlation of the gastric inhibitory polypeptide cell with one or other of the known endocrine-like cells identified by electron microscopy awaits confirmation by electron immunocytochemistry. It is here identified as an endocrine polypeptide cell of the APUD series and, provisionally, as the D(1) cell. While the hormonal status of a given polypeptide depends ultimately on physiological experiments the present results strengthen the view that gastric inhibitory polypeptide is indeed a hormone.
Topics: Animals; Dogs; Duodenum; Fluorescent Antibody Technique; Gastrointestinal Hormones; Humans; Jejunum; Methods; Microscopy, Electron; Peptides; Swine
PubMed: 4574902
DOI: 10.1136/gut.14.4.284 -
Thorax Aug 1977Our studies show that the apparent number of Feyrter cells in the lung declines during the neonatal period in normoxic rabbits, and that in hypoxic animals a uniformly...
Our studies show that the apparent number of Feyrter cells in the lung declines during the neonatal period in normoxic rabbits, and that in hypoxic animals a uniformly and significantly lower number of cells occurs as compared with the normoxic rabbits. There is some indication of degranulation of cells in the hypoxic groups. It is suggested that environmental and/or physiological factors associated with the start of extrauterine life, or lung development, may affect the apparent number and probable level of activity of these cells. These changes seem to be enhanced by hypoxia. Mast cells are scarce, and Feyrter cells are relatively more numerous along the airways. These cell types could possibly represent storage sites for 5-hydroxytryptamine, as suggested also by other investigators. Intraepithelial nerve fibres in bronchi and bronchioles were found but they were not limited to innervations of Feyrter cells or related cell bodies.
Topics: APUD Cells; Animals; Animals, Newborn; Bronchi; Cell Count; Hypoxia; Lung; Rabbits
PubMed: 22136
DOI: 10.1136/thx.32.4.449 -
Gut Apr 1971An indirect immunofluorescence technique, using the globulin fraction of rabbit antihuman gastrin serum, was applied to formalin-fixed material obtained by suction...
An indirect immunofluorescence technique, using the globulin fraction of rabbit antihuman gastrin serum, was applied to formalin-fixed material obtained by suction biopsy from the fundic mucosa of nine cases of pernicious anaemia. Cytochemical tests for endocrine polypeptide cells of the APUD series, in which the G cell is included, were carried out in parallel with immunofluorescence and with ultrastructural observations.G cells were present, in large numbers, in five of the nine cases studied. In the remaining four cases the predominantly intestinalized glands contained only enterochromaffin in cells. Because of their low gastrin content (immunofluorescence), low secretion granule content (cytochemistry), and the associated ultrastructural findings, it is suggested that the G cells of the fundic mucosa are in a state of high synthetic and high secretory activity.
Topics: Anemia, Pernicious; Animals; Fluorescent Antibody Technique; Gastric Mucosa; Gastrins; Histocytochemistry; Humans; Microscopy, Electron; Peptides; Rabbits
PubMed: 4930156
DOI: 10.1136/gut.12.4.319 -
British Journal of Cancer Jan 1995We performed a phase II study with mitoxantrone in patients with carcinoid tumours, islet cell tumours and medullary carcinomas of the thyroid. Thirty-five eligible... (Clinical Trial)
Clinical Trial
We performed a phase II study with mitoxantrone in patients with carcinoid tumours, islet cell tumours and medullary carcinomas of the thyroid. Thirty-five eligible patients received mitoxantrone 12 mg m-2 i.v. every 3 weeks. Among 18 previously untreated patients, three responded (17%, 95% CI = 4-41%); no responses were achieved in 17 previously treated patients. Of the 21 patients who had carcinoid tumours, 11 were previously untreated and two achieved a response (18%, 95% CI = 2-52%). Overall response rate was 9% (95% CI = 2-23%). At a median follow-up of 43 months, median overall survival was 16 months. The median survival of 21 patients with a normal alkaline phosphatase was 29 months and 9 months for 14 patients with elevated serum levels (P = 0.005). A similar observation was noticed for gamma-glutamyltransferase (P = 0.007). We concluded that mitoxantrone is not active in APUD tumours. Elevated alkaline phosphatase and gamma-glutamyltransferase are associated with a poor prognosis.
Topics: Adenoma, Islet Cell; Adult; Aged; Alkaline Phosphatase; Apudoma; Carcinoid Tumor; Carcinoma, Medullary; Female; Humans; Male; Middle Aged; Mitoxantrone; Neoplasm Metastasis; Pancreatic Neoplasms; Survival Rate; Thyroid Neoplasms
PubMed: 7819024
DOI: 10.1038/bjc.1995.21 -
The Yale Journal of Biology and Medicine 1981WE HAVE DEVELOPED THREE TYPES OF EXPERIMENTAL SYSTEMS FOR THE STUDY OF SCCL: (1) serially heterotransplanted tumors in athymic nude mice; (2) continuous, clonable cell...
WE HAVE DEVELOPED THREE TYPES OF EXPERIMENTAL SYSTEMS FOR THE STUDY OF SCCL: (1) serially heterotransplanted tumors in athymic nude mice; (2) continuous, clonable cell cultures; and (3) direct clonogenic assays for tumor specimens. These systems have their own individual advantages, applications, and limitations, but these are interrelated and complementary. The study of these systems has greatly aided our understanding of the biology of SCCL, and its relationship to other lung cancers and the APUD cell system. In addition, new markers for SCCL have been identified, such as a creatine kinase and its BB isoenzyme (CK-BB). These cellular markers may have clinical applications, as serum levels of CK-BB are an indicator of tumor burden. Assays for clonogenic tumor cells may permit selection of optimal drug combinations for the treatment of individual tumors. Variant cultures having the morphology of SCCL, but lacking some or all of the other features, have been identified. While our systems have been used primarily for biological studies, they have clinical applications for both diagnostic and therapeutic purposes.
Topics: Animals; Carcinoma, Small Cell; Cells, Cultured; Creatine Kinase; Culture Media; Humans; Lung Neoplasms; Mice; Mice, Nude; Neoplasm Transplantation
PubMed: 6270917
DOI: No ID Found -
Clinical and Experimental Immunology Jul 1980The presence of autoantibodies detected by immunofluorescence to single endocrine cells, of human duodenum is described in three groups of patients and two control...
The presence of autoantibodies detected by immunofluorescence to single endocrine cells, of human duodenum is described in three groups of patients and two control groups. Of 173 coeliac cases, four had GIP cell antibodies, one had secretin cell antibodies and twenty-one reacted with both cell types. Of twelve tropical sprue sera, four reacted with the same two cells. Among fifty elderly diabetics treated with hypoglycaemic drugs, seven sera gave a positive cytoplasmic IFL on duodenal substrate. Four were identified as GIP cells by use of the appropriate hormone antiserum and three reactions were against cells distinct from those stained by anti-GIP, -secretin, -somatostatin, -glucagon and -gastrin. Additional gut hormone antisera will have to be tested to identify these APUD cells. Thirty blood donors and seventy-three sera from autoimmune endocrine patients gave entirely negative results on unfixed cryostat sections of duodenal mucosa. Although impaired GIP and secretin responses have been reported in coeliac disease, and abnormal GIP values were found in Type II diabetes, there is as yet no data to correlate these metabolic dificiencies with the presence of endocrine cell antibodies in the serum. These studies are in progress.
Topics: Adult; Autoantibodies; Celiac Disease; Child; Diabetes Mellitus; Duodenum; Fluorescent Antibody Technique; Gastric Inhibitory Polypeptide; Gastrointestinal Hormones; Humans; Intestinal Mucosa; Secretin; Sprue, Tropical
PubMed: 7002390
DOI: No ID Found -
The American Journal of Pathology Dec 1981A highly significant correlation is demonstrated between the presence in older persons of medullary renal interstitial cell nodules (RICNs) containing amyloid and... (Comparative Study)
Comparative Study
A highly significant correlation is demonstrated between the presence in older persons of medullary renal interstitial cell nodules (RICNs) containing amyloid and increased heart weight indicative of chronic arterial hypertension. By contrast, the population with amyloid-free RICNs 1) showed heart weights comparable to those of controls and 2) had a mean age about 11 years less (56.7 +/- 9.6 vs 68 +/- 12 years) than the group with amyloid-containing RICNs. In a series of 55 autopsy cases presenting with RICNs, no individual was younger than 30 years. In two cases, in which fresh material was available, histochemical reactions suggested that the RICNs contained APUD amyloid. It is speculated that fully functional RICNs may evolve on a compensatory base counteracting an increase in mean arterial blood pressure and that the deposition of amyloid within RICNs could be associated with, or be an expression of, a reduced endocrine function of these structures, finally resulting in the development of arterial hypertension.
Topics: APUD Cells; Adult; Age Factors; Aged; Amyloid; Cardiomegaly; Chronic Disease; Humans; Hypertension; Kidney Medulla; Male; Microscopy, Electron; Middle Aged; Organ Size
PubMed: 6119030
DOI: No ID Found -
Neuropsychopharmacology : Official... Aug 2014Neurexins are presynaptic neuronal adhesion molecules that interact with postsynaptic neuroligins to form an inter-synaptic complex required for synaptic specification...
Neurexins are presynaptic neuronal adhesion molecules that interact with postsynaptic neuroligins to form an inter-synaptic complex required for synaptic specification and efficient neurotransmission. Deletions and point mutations in the neurexin 1 (NRXN1) gene are associated with a broad spectrum of neuropsychiatric and neurodevelopmental disorders, including autism, intellectual disability, epilepsy, developmental delay, and schizophrenia. Recently, small nucleotide polymorphisms in NRXN1 have been associated with antipsychotic drug response in patients with schizophrenia. Based on previous suggestive evidence of an impact on clozapine response in patients with schizophrenia, we conducted an association study of NRXN1 polymorphisms (rs12467557 and rs10490162) with antipsychotic treatment response in 54 patients with schizophrenia in a double blind, placebo-controlled NIMH inpatient crossover trial and examined for association with risk for schizophrenia in independent case-control and family-based clinical cohorts. Pharmacogenetic analysis in the placebo controlled trial revealed significant association of rs12467557and rs10490162 with drug response, whereby individuals homozygous for the A allele, at either SNP, showed significant improvement in positive symptoms, general psychopathology, thought disturbance, and negative symptoms, whereas patients carrying the G allele showed no overall response. Although we did not find evidence of the same NRXN1 SNPs being associated with results of the NIMH sponsored CATIE trial, other SNPs showed weakly positive signals. The family and case-control analyses for schizophrenia risk were negative. Our results provide confirmatory evidence of genetically determined differences in drug response in patients with schizophrenia related to NRXN1 variation. Furthermore, these findings potentially implicate NRXN1 in the therapeutic actions of antipsychotic drugs.
Topics: Adult; Antipsychotic Agents; Calcium-Binding Proteins; Case-Control Studies; Cell Adhesion Molecules, Neuronal; Cohort Studies; Cross-Over Studies; Double-Blind Method; Family; Female; Genotyping Techniques; Humans; Male; Nerve Tissue Proteins; Neural Cell Adhesion Molecules; Pharmacogenetics; Polymorphism, Single Nucleotide; Psychiatric Status Rating Scales; Risk; Schizophrenia; Treatment Outcome
PubMed: 24633560
DOI: 10.1038/npp.2014.65