Endocrine Cell Content Research Articles

Morphological Characteristics of Colon Tumors in Mice with Different Tolerance to Hypoxia.

In adult male C57BL/6 mice with high (HR) and low (LR) resistance to hypoxia, morphological features of colon tumors and blood parameters were evaluated 70 days after intraperitoneal injection of azoxymethane and subsequent consumption of 3 cycles of dextran sulfate sodium. On macroscopic analysis, tumors were found in the distal colon in 35% (7 of 20 animals) of HR and 31% (4 of 13 animals) of LR animals. Microscopic analysis of the distal colon revealed tumors in 75% (15 of 20 animals) of HR and 69% (9 of 13 animals) of LR mice. The tumors were presented by areas of glandular intraepithelial neoplasia and adenocarcinomas; the incidence and the area of the tumors did not differ in groups of HR and LR mice. The number of neuroendocrine and goblet cells in the distal colon mucosa in the areas of tumors was similar in the compared groups. However, in both HR and LR mice of the experimental groups, the content of goblet cells in tumors was lower and the content of endocrine cells was higher than in the corresponding control groups. In the peripheral blood, the erythrocyte count and hemoglobin content decreased in HR and LR mice of the experimental groups; the relative number of monocytes increased only in HR mice and the absolute number of lymphocytes and monocytes decreased in LR mice. Thus, 70 days after azoxymethane administration and dextran sulfate sodium consumption, the tumors in mice were presented by glandular intraepithelial neoplasia and adenocarcinomas, and their incidence and area did not differ between animals with different tolerance to hypoxia.

Mucosal Hallmarks in the Alimentary Canal of Northern Pike Esox lucius (Linnaeus).

Simple SummaryIn vertebrates, mucous cells are one of the main cellular components of the gut mucosal system, which secrete different mucin types involved in several functions. Endocrine cells are scattered in the epithelium of the gut mucosa, and they produce and release regulatory molecules affecting food intake and nutrition. The goal of this study was to obtain data on quantitative distribution of mucous and endocrine cell types in the alimentary canal of the northern pike (Esox lucius), using histochemistry and immunofluorescence. In the stomach of pike, there is a high abundance of mixed mucins, with the acid component contributing to the lubrication of mucosae, where they are associated with the rapid passage of digesta through the intestine. Neutral mucins increase in the intestine aborally. The distribution of endocrine cells of the diffuse endocrine system shows the presence of somatostatin and catecholamine-secreting endocrine cells and the lack of gastrin-secreting endocrine cells. We show a close regulatory relation between endocrine and mucous cells of the gut mucosal system involved in the physiology of fish nutrition. Results confirmed the relationship between the carnivorous diet and the gut mucins distribution of northern pike; indeed, our data provide very important information to ichthyologists who study dietary behavior of species.On the basis of trophic behavior, fish are classified as herbivores, carnivores, omnivores, or detritivores. Epithelial mucous cells secrete mucin types specific to diet and digestive function. Mucus secretion is regulated mainly by molecular modulators produced by epithelial endocrine cells in response to luminal or tissue stimuli. These modulators are involved in control of food intake and digestive functions. Immunohistochemical and immunofluorescence studies were conducted on 10 adult northern pike (Esox lucius Linnaeus, 1758) from Lake Piediluco (Central Italy) to quantify distribution of sub-types of mucous and endocrine cells in alimentary mucosal epithelium. Neutral mucins predominated in the esophagus, and mixed and acidic mucins predominated in stomach and intestine. The gastric epithelium contained endocrine cells secreting somatostatin, tyrosine hydroxylase, and substance P. Mucous cells secreting neutral mucins increased in number from proximal to distal intestine, with endocrine cells containing substance P in the proximal intestine and those containing Leu-enkephalin throughout the intestine. Lectin histochemistry of gut sections revealed an abundance of N-acetyl-glucosamine and N-acetyl-galactosamine as carbohydrate residues on the mucin chain. The quantity and content of endocrine and mucous cells in the alimentary canal of E. lucius showed a direct relationship with its diet.

Protective effect of necrostatin-1 on the damage of pancreas islet cells induced by TNF-α.

To investigate whether necrostatin-1 (Nec-1) can protect islet cells from the damage induced by TNF-α. After isolation and purification, the neonatal porcine islet cell clusters (NICCs) were divided into 3 groups (islets 10 000 IEQ/group): a Nec-1 group (Nec-1+TNF-α was added to the culture medium), a TNF-α group (TNF-α was added to the culture medium), and a control group (pure medium). The number of cells was observed after 48 h of co-culture. The cell death was evaluated by AO/EB staining. Insulin secretion and DNA of islets were detected by chemiluminescence and nucleic acid quantitative analysis. RT-PCR assay was used to examine the mRNA expressions of insulin gene, glueogan gene and somatostatin gene. Flow cytometry analysis was used to detect the viability of B cells. The number of islets in Nec-1 group, TNF-α group and the control group were (8 425±2 187), (4 325±778), and (7 122±1 558) IEQ, respectively. Compared to the other two groups, the number of dead cells in TNF-α group was greatly increased. The insulin/DNA values in the Nec-1 group, TNF-α group and blank control group were (13.21±3.15), (2.47±0.45), and (7.44±0.97) mIU/mg, respectively. Compared to the TNF-α group and the control group, the mRNA relative expression levels of insulin gene (6.73±1.07), glucagon gene (10.13±1.98), somatostatin gene (8.57±1.11) were significantly increased in the Nec-1 group (all P<0.05), the rate of live cells (97.32±1.87)% and live B cells (90.86±3.68)% were increased significantly in the Nec-1 group (all P<0.05). TNF-α can induce neonatal porcine islet cells damage, which is attenuated in the presence of Nec-1. Nec-1 can increase the content of endocrine cells in NICCs.

Microscopic and submicroscopic structure of the heart atria and auricles in condition of the experimental thermal trauma

Burns is the damage of the skin or mucous membranes (often with underlying tissues), because of high-temperature influence (thermal burns), chemical, electrical, radiation, combined, thermochemical and electrothermal factors influence. According to the investigations, burns rank third among other injuries, and in some countries, second, second only to transport injuries. Although the level of survival after burns is increasing, the problem of their treatment remains relevant in modern medicine and pharmacy. The aim was to study the peculiarities and the patterns of morphofunctional changes in the structural components of the heart atria and auricles in case of the experimental thermal trauma. The study involves 30 adult guinea pigs with a bodyweight of 630-670 g. The burn was applied under general ether anesthesia with water vapor at a temperature of 96-97 0C on the surface of the skin of the animal's back for 60 seconds. The size of the lesion area was 18-20% of the body surface. The depth of the lesion corresponded to the degree ІІІА -IIIB. The experimental animals were divided into two groups: the first - intact guinea pigs (6 heads); second - animals with thermal trauma (24 heads). Were used a number of methods of investigation, including macrometric and massometric - to establish the structural restructuring of the heart and its parts, microscopic and electron microscopic to detect changes in the structural components of the atrium and auricle of the heart; morphometric - to obtain quantitative parameters of the morphological components of the heart; mathematical and statistical - to ensure the analysis of the reliability of the research results. In intact guinea pigs, the morphological organization of the heart auricles differs from the atria by the direction of the muscle fibers, the ratio of morphometric parameters of their structural components and the content of muscle endocrine cells. Submicroscopically, endocrine myocytes of the auricles of the heart contain more hormonal granules than atria. In the ears of the heart, the relative volume of connective tissue is 1,34 times greater, and the relative volume of muscle fibers is 1,03 times smaller than in the atria. Submicroscopically, endocrine muscle cells of the heart auricle contain more hormonal granules than atria. It has been established that thermal trauma causes significant morphofunctional changes in the atria and auricles of the heart at different levels of their structural organization. The degree of damage depends on the duration of the experiment and develops against the background of increased plasma toxicity. In the stages of burn shock and early toxemia, adaptive-compensatory processes develop in the structures of the heart, and irreversible destructive changes occur in the stages of late toxemia and septicotoxemia.

Морфофункциональные изменения ободочной кишки и иммунные реакции при холодовом стрессе у самцов и самок мышей C57BL/6

Introduction. Stress is one of the factors contributing to the gastrointestinal tract diseases development and exacerbating the course of diseases of the gastrointestinal tract. The cold factor is the most common stress factor in Russia. Therefore, the aim of our work was to characterize the immune responses and colon morphological and functional changes during cold stress in male and female C57BL/6 mice. Materials and methods. We studied alterations in the subpopulation composition of peripheral blood lymphocytes and morphofunctional changes in the thymus, spleen, and colon in response to a course intermittent cold exposure during 35-minute sessions for 14 days at –20° in adult male and female C57BL/6 mice. Results. The volume fraction of the PALS zone of the spleen and the content of endocrine cells in the colon decreased in animals of both sexes in the cold stress conditions. In females, the number of platelets and leukocytes in the peripheral blood increased, the width of the subcapsular zone of the thymus decreased, and the volume fraction of the red spleen pulp increased. In males, in the peripheral blood, the absolute and relative content of T-regulatory lymphocytes decreased, and the relative content of activated T-helpers increased, the volume fraction of the light centers of lymphoid nodules in the spleen decreased, the length of the crypts increased in the colon. A number of differences between males and females of control groups were also revealed: in the peripheral blood, males had more platelets and the absolute content of T-regulatory lymphocytes and less absolute content of T-cytotoxic. In the colon of males, the content of proliferating epithelial cells in the colon was higher than the one in females, and the bulk density of goblet cells was lower in males. Conclusion. Under the cold stress factor exposure in animals, physiological stress develops. Immune reactions and colon morphofunctional changes in the colon during cold stress differ between males and females. Keywords:cold stress, sex differences, colon, immune system

Diabetes Caused by Elastase-Cre-Mediated Pdx1 Inactivation in Mice.

Endocrine and exocrine pancreas tissues are both derived from the posterior foregut endoderm, however, the interdependence of these two cell types during their formation is not well understood. In this study, we generated mutant mice, in which the exocrine tissue is hypoplastic, in order to reveal a possible requirement for exocrine pancreas tissue in endocrine development and/or function. Since previous studies showed an indispensable role for Pdx1 in pancreas organogenesis, we used Elastase-Cre-mediated recombination to inactivate Pdx1 in the pancreatic exocrine lineage during embryonic stages. Along with exocrine defects, including impaired acinar cell maturation, the mutant mice exhibited substantial endocrine defects, including disturbed tip/trunk patterning of the developing ductal structure, a reduced number of Ngn3-expressing endocrine precursors, and ultimately fewer β cells. Notably, postnatal expansion of the endocrine cell content was extremely poor, and the mutant mice exhibited impaired glucose homeostasis. These findings suggest the existence of an unknown but essential factor(s) in the adjacent exocrine tissue that regulates proper formation of endocrine precursors and the expansion and function of endocrine tissues during embryonic and postnatal stages.

Abnormal rectal endocrine cells in patients with irritable bowel syndrome

Irritable bowel syndrome (IBS) is a common gastrointestinal disorder. In a previous study the total number of endocrine cells in the rectum of IBS patients, as detected by chromogranin A, did not differ from that of healthy controls. While the total endocrine cell content of the rectum appears to be unchanged in IBS patients, changes in particular endocrine cells cannot be excluded. This study was undertaken, therefore, to investigate the cell density of different rectal endocrine cell types in (IBS) patients. Fifty patients with IBS (41 females and 9 males) were included in the study. Thirty patients had diarrhoea (IBS-D) and 20 had constipation (IBS-C) as the predominant symptom. Twenty-seven subjects were included as controls (19 females and 8 males). Rectal biopsy specimens were immunostained using the avidin–biotin-complex method for serotonin, peptide YY (PYY), pancreatic polypeptide (PP), and oxyntomodulin and somatostatin cells. The cell densities were quantified by computerised image analysis. The serotonin cell density did not differ significantly, although a type II statistical error cannot be excluded, due to the small size of the sample. The densities of PYY and Oxyntomodulin cells were significantly lower and that of somatostatin were significantly higher in IBS patients than controls. These abnormalities were observed in both IBS-D and IBS-C patients. The abnormalities in the endocrine cells observed in this study in the rectum differed considerably from those seen in the colon of IBS patients. This indicates that caution in using the rectum to represent the large intestine in these patients. These abnormalities could be primary (genetic) or secondary to changes in the gut hormones found in other segments of the gut and/or other pathological processes. Although the-cause-and effect relationship of the abnormalities found in rectal endocrine cells is difficult to elucidate, they might contribute to the symptoms associated with IBS. The densities of PYY and somatostatin cells are potential biomarkers with good sensitivity and specificity for the diagnosis of IBS.

Chromogranin A cell density in the rectum of patients with irritable bowel syndrome

In a previous study, chromogranin A (CgA) cell density in the colon of patients with irritable bowel syndrome (IBS) was found to be reduced. It has been suggested that intestinal CgA cell density may be used as a marker for the diagnosis of IBS. The rectum harbours a larger number of large intestinal endocrine cells and is more accessible for biopsies than the colon. The present study aimed at determining the CgA cell density in the rectum of IBS patients. A total of 47 patients with IBS that fulfilled the Rome Criteria III (39 females and 8 males; average age, 38 years) were included. A total of 28 patients had diarrhea (IBS-D) and 19 had constipation (IBS-C) as the predominant symptom. A total of 27 subjects that underwent colonoscopy with rectal biopsies were used as the controls. These subjects underwent colonoscopy due to gastrointestinal bleeding (the source of which was identified as haemorrhoids or angiodysplasia; 19 females and 8 males; average age, 49 years), or health worries. The rectal biopsies were immunostained for CgA and quantified by computer image analysis. The CgA density in the controls was 206.3±22.2 (mean ± SEM), in all IBS patients 190.2±14.3, in IBS-D patients 188.8±14.7 and in IBS-C patients 195.3±34.1. There was no statistically significant difference between the controls, IBS, IBS-D or IBS-C patients (P=0.5, 0.5 and 0.7, respectively). The present study showed that although the rectum comprises the same endocrine cell types as the colon, attention must be paid when drawing conclusions regarding the whole large intestine from studies carried out on the rectum. This particularly applies when endocrine cells are investigated. As CgA cell density represents the total endocrine cell content of the rectum, changes in specific endocrine cells in IBS patients cannot be excluded.

A novel tissue for islet transplantation in diabetics

BackgroundIslet transplantation for diabetes therapy has remained a challenge. None of the currently used transplantation sites have provided satisfactory results as islets seem to require a specific tissue for survival and growth. Since the submandibular gland (SMG) shares physiological and anatomical similarities with the pancreas, we attempted to use this tissue as the transplantation site. MethodsIn Experiment 1, a group of 10 female Syrian Golden hamsters’ (SGH) received isolated and purified homologous islets transplanted into their right SMG. In Experiment 2, 15 female SGH received islet transplant into their left SMG as above, except that the recipient hamsters were made diabetic by streptozotocin (STZ) before islet transplantation. In Experiment 3, isolated and purified human islets were transplanted into the SMG of 10 female hamsters. ResultsIn 8 out of 10 hamsters in Experiment 1 the islets survived and showed the same morphological structure and endocrine cell content, as intrapancreatic islets and presented signs of rapid growth and distribution. Also, as in Experiment 1, well-established islets were present in Experiment 2. Ten of the 15 hamsters pretreated with STZ had blood glucose values between 96 and 125 mg/dl, whereas three hamsters remained hyperglycemic (glucose levels between 194 and 417 mg/dl). Remarkably, the islets in the pancreas of 10 STZ-treated hamsters with functioning SMG islets remained atrophic even after 12 weeks. In two hamsters transplanted islets showed degeneration and remained diabetic until their pancreatic islets regenerated. In Experiment 3, transplanted human islets were completely destroyed. ConclusionsSMG appears to be the most suitable site for islet transplantation for the treatment of diabetes.

Small-molecule inducers of insulin expression in pancreatic α-cells

High-content screening for small-molecule inducers of insulin expression identified the compound BRD7389, which caused alpha-cells to adopt several morphological and gene expression features of a beta-cell state. Assay-performance profile analysis suggests kinase inhibition as a mechanism of action, and we show that biochemical and cellular inhibition of the RSK kinase family by BRD7389 is likely related to its ability induce a beta-cell-like state. BRD7389 also increases the endocrine cell content and function of donor human pancreatic islets in culture.

Adaptive changes of gastro-entero-pancreatic system endocrine cells in the black-spotted pond frog Rana nigromaculata after fasting

Abstract Changes in distribution density, morphology and secretory content of endocrine cells in the gastro- entero-pancreatic system of black-spotted frogs Rana nigromaculata before and after fasting were investigated using immunohistochemistry and antisera to six gut hormones. Six types of endocrine cells were detected in the digestive tract of Rana nigromaculata, including 5-hydroxytryptamine (5-HT), gastrin (GAS), somatostatin (SOM), glucagon (GLU), pancreatic polypeptide (PP) and vasoactive intestinal polypeptide (VIP) cells. After fasting, the density of 5-HT cells in the esophagus, cardia and fundus, GAS cells in the fundus and pylorus, PP cells in the fundus decreased significantly (P &lt; 0.01), while SOM cells in the cardia, GLU cells in the rectum increased significantly (P &lt; 0.01). The cytoplasmic processes of 5-HT cells became shorter or not detectable. The secretory content of GAS cells reduced in the cardia. The positive immunostaining reaction in the perinuclear region of SOM cells in the cardia, fundus and pylorus became weaker, while the staining intensity in the periphery of these cells became stronger. VIP cells were not detectable in the whole digestive tract after fasting. Five types of endocrine cells were found in the pancreas of Rana nigromaculata, including 5-HT, GAS, SOM, GLU and PP cells. After fasting, the density of 5-HT cells decreased slightly (P &gt; 0.05), while SOM, GAS, GLU and PP cells increased significantly (P &lt; 0.01). Furthermore, the secretory content of GLU cells increased significantly. Considering their functionalities, our results indicate that the changes of GEP endocrine cells in Rana nigromaculata responded adaptively to starvation-induced stress.

Endocrine cells in gastric carcinoma and adjacent mucosa. An immunohistochemical and ultrastructural study.

Endocrine cells are often found in human gastric carcinoma and may be recognized by the immunoreactivity of their chromogranin A, peptides and biogenic amines content. Anti-chromogranin A was used to investigate the morphology of endocrine cells using light and electron microscope immunohistochemical techniques. The hormone content of endocrine cells was examined in both tumour tissue and tumour-adjacent mucosa. It was found that the endocrine cells in tumour tissue were malignant, often had amphocrine differentiation and did not resemble a normal cell type. The hormone content of endocrine cells in tumour tissue seldom corresponded to the hormonal content of endocrine cells in tumour-adjacent mucosa. In intestinal-type carcinoma and in some parts of diffuse-type gastric carcinomas, endocrine cell hyperplasia and an alteration of the differentiation in the tumour-adjacent mucosa were discovered. The distribution of endocrine cells in the tumour tissue was different in both types of gastric carcinoma. The results reported here suggest that endocrine cell differentiation of malignant endocrine cells in human gastric carcinoma develops in a different way from that of endocrine cells in tumour-adjacent mucosa, and as a result, diverse hormonal products may appear in tumour tissue.

Liver transplantation restores endocrine cells in patients with familial amyloidotic polyneuropathy.

The aim of this study was to investigate familial amyloidotic polyneuropathy, Portuguese type patients' endocrine cell content in the stomach and duodenum before and after liver transplantation, and to relate the findings to the patients' gastrointestinal disturbances. Ten liver-transplanted familial amyloidotic polyneuropathy, Portuguese type patients and 10 healthy controls were seen. Endocrine cells were identified by immunohistochemistry and quantified with computerized image analysis. The activity of the cells was appraised by measurements of the cell secretory index and nuclear area. Clinical symptoms were obtained from the patients' medical records. After transplantation, a significant increase of several endocrine cell types were noted, and the pretransplant depletion of several types of endocrine cells disappeared. For no type of endocrine cell was any difference compared with controls noted after transplantation. There was no significant decrease of the amount of amyloid in the biopsies after liver transplantation. The patients' symptoms remained generally unchanged after transplantation, although a substantial time lapse between pretransplant evaluation and transplantation was present. Liver transplantation restores the endocrine cells in the upper part of the gastrointestinal tract. The restoration was not correlated with an improvement of the patients' symptoms. No decrease of the amyloid deposits was noted.

Colonic endocrine cells in patients with familial amyloidotic polyneuropathy.

To establish whether the endocrine cell number is affected in the colon in Japanese FAP patients. Department of Medicine, Umeå University Hospital and Department of Internal Medicine and Pathology, University Hospital, Kumamoto, Japan. Autopsy colon tissue specimens from 11 FAP patients and nine controls as well as 12 control biopsy specimens were included in the study. Endocrine cells in the colon were detected by immunohistochemistry and quantified by computerized image analysis. The autopsy material showed a slight autolysis. Neither enteroglucagon nor pancreatic polypeptide positive cells could be detected in the autopsy material, but were present in biopsy material. There was no statistical difference between autopsy and biopsy specimens regarding the number of peptide YY (PYY), somatostatin and serotonin cells. No significant differences were noted in PYY, somatostatin and serotonin immunoreactive cells in FAP patients compared to autopsy controls, though PYY cells tended to be decreased and serotonin and somatostatin cells tended to be increased in FAP patients. The difference between the Swedish and Japanese patients in the endocrine cell content points to the possibility of involvement of other factors than the endocrine cell depletion of the colon might be involved in the pathogenesis of gastro-intestinal dysfunction in FAP. The tendency of PYY to decrease in Japanese FAP might contribute to the development of diarrhoea in these patients.

Endocrine cells in the upper gastrointestinal tract in relation to gastrointestinal dysfunction in patients with familial amyloidotic polyneuropathy

Gastrointestinal (GI) dysfunction is a common complication of familial amyloidotic polyneuropathy (FAP). In previous reports, a decreased content of small and large intestinal endocrine cells has been found in patients with FAP and it has been suggested that this may contribute to the development of GI disturbances. The aim of the present study was to investigate the endocrine cell content in the stomach and duodenum of FAP patients, and to correlate the findings with gastric emptying.Fifteen patients with FAP were included in the study. Twenty-eight subjects with macroscopically and histologically normal mucosa were used as controls for endocrine cell contents and 14 healthy subjects for gastric scintigraphy. The endocrine cells were identified by immunohis-tochemistry and quantified with image analysis. Gastric emptying time was detected by scintigraphy andendoscopy.The number of chromogranin A-immunoreactive (IR) cells was reduced in all investigated parts of the GI tract except bulbus duodeni. Gastrin/CCK cell content was reduced in duodenum, but tended to be increased in antrum of the stomach (P=0.07). Otherwise, the content of all other endocrine cells types in the upper GI tract was reduced compared with controls. A correlation with malnutrition was found for gastric inhibitory polypeptide and secretin cell content in bulbus duodeni. Gastric scintigraphy disclosed delayed gastric emptying of solid food, but the finding was not correlated to the decreased content of neuroendocrine cells. The severity of endocrine cell depletion was not correlated to duration of GI disturbances.The present study showed that the endocrine cells of the stomach are affected in FAP patients and that the abnormalities in the upper GI endocrine cells occur early during the course of the disease.

Pulmonary endocrine cells in anthracosilicotic lungs.

It has been suggested by some studies of human and animal lungs that the products of pulmonary endocrine cells, particularly gastrin-releasing peptide, might play a role in fibrogenesis, but more recent detailed studies of fibrotic human lungs have failed to confirm this. We have made a detailed quantitative examination of a series of fibrotic human lungs to see if we could determine whether there was any relationship between endocrine cells and fibrosis. Using immunocytochemistry, we investigated the morphology, content, distribution and number of pulmonary endocrine cells in 15 pairs of fibrotic lungs from coal miners, and compared their features with those of equivalent cells in age-matched controls. Proliferation of endocrine cells was seen in the lungs of just two miners, in which it was focal and associated with acute bronchitis and bronchopneumonia. There was no difference between the miners and controls in the appearance (mostly solitary cells), content (predominantly gastrin-releasing peptide and calcitonin), distribution (mainly in small bronchi and bronchioles), or number (4.5 vs 4.1 cells per 10,000 epithelial cells, respectively) of endocrine cells. It seems unlikely that the substances secreted by these cells play any role in stimulating fibrosis in human lungs, but rather that they have a function in the inflammatory response to pulmonary injury.

Endocrine cells in tumour-bearing lungs.

When hormones are detected in the serum of patients with bronchial carcinoma they are generally considered to originate from the tumour, but this may be not the only explanation. Pulmonary endocrine cells proliferate in lungs affected by non-neoplastic disease and their products are often demonstrable in the serum. The aim of this study was to examine the pulmonary endocrine systems of a series of tumour-bearing lungs to see whether any changes in them could possibly account for raised levels of pulmonary peptides in the blood. The morphology, number, distribution, and content of pulmonary endocrine cells in 30 pairs of tumour-bearing lungs from patients coming to necropsy with bronchial carcinoma were examined. These features were related to the pathology of the tumour and to other pathological changes present in the lungs, and compared with pulmonary endocrine cells in 10 pairs of control lungs from patients without pulmonary disease. Increased numbers of endocrine cells, often in the form of large abnormal aggregates, were present in 17 pairs of tumour-bearing lungs where they were associated not with the tumour but with non-tumoral pathology, especially inflammation and changes associated with cardiac failure. Appropriate and inappropriate peptides were identified within them. The possibility is raised that, in some subjects with bronchial carcinoma who have raised serum hormone levels, the source of these substances might be the endocrine cells in the diseased lung around the tumour.

Effects of inhaled lignocaine and adrenaline on capsaicin-induced cough in humans.

The hypothesis that adrenaline can augment and/or prolong the antitussive effect of nebulised lignocaine was examined. The effect of inhaled lignocaine alone (20 mg) and in combination with adrenaline (400 micrograms) was studied on capsaicin-induced cough in 10 healthy subjects. Cough was significantly reduced between five and 25 minutes by lignocaine. Adrenaline alone had no inhibitory effect and it neither augmented nor prolonged the antitussive effect of lignocaine. The subjective anaesthesia by lignocaine was short lasting (less than 15 minutes) and not altered by adrenaline, suggesting different sensory mechanisms for anaesthesia and cough suppression. Plasma concentrations of lignocaine were low (< 30 ng/ml), not altered by adrenaline, and did not correlate with the local anaesthetic or the antitussive effect. Lignocaine acts locally in the oropharynx and airways and adrenaline does not alter the effect or absorption of nebulised lignocaine on the human respiratory mucosa.

Impact of familial amyloid associated polyneuropathy on duodenal endocrine cells.

Duodenal endocrine cells in 11 patients with familial amyloid associated polyneuropathy (FAP) were compared with those in 12 healthy volunteers by means of immunohistochemistry and morphometry. The total endocrine cell content, determined by the argyrophilic reaction and chromogranin A immunoreactivity, was significantly reduced in FAP patients compared with controls. There was a significant reduction in the serotonin, cholecystokinin/gastrin, and secretin immunoreactive cell content. A decreased cell content was also noted for somatostatin and gastric inhibitory polypeptide immunoreactive cells but this was not statistically significant. Amyloid deposits were noted in seven of the 11 biopsy specimens from FAP patients, but otherwise the duodenum was histologically normal in both groups. The reduction in endocrine cell content was not correlated with the degree of amyloid deposit in the duodenum. These findings indicate that patients with FAP have reduced intestinal endocrine cells. This does not seem to be related to amyloid deposits in the mucosa or to villous or crypt abnormalities. The observed changes in endocrine cells may contribute to the development of intestinal motility dysfunction and maldigestion in these patients.

Cellular Composition of the Pancreatic Islets in Mongolian gerbils (Meriones unguiculatus)

In Mongolian gerbil, morphological changes with age in the content of endocrine cells in the pancreatic islets were analyzed and their relation evaluated by an oral glucose tolerance test. The glucose level 2 hours after glucose administration was 125 +/- 5 mg./d1 in the young group and 103 +/- 4 mg./d1 in the old group. In the dorsal portion, B cells were mainly observed in the central area of the islets, surrounded by circular layers of A cells in the peripheral area. Between the A cells and B cells, D cells were scattered or present in layers. A few PP cells were present in the peripheral area of the islets. In the ventral portion, only a few A cells were observed in the peripheral area of the islets, and B cells were surrounded by PP cells. Secretory granules of A cells generally had an electron-dense spherical core in the limiting membrane. The halo between the limiting membrane and core in A cells was narrower than that in B cells. Secretory granules of B cells were larger than those in A cells, and the core was less electron-dense, and the halo was wider. Secretory granules of D cells were similar in size to those of A cells; the core showed low electron density, and the halo was very narrow. Granules of PP cells resembled those of A cells, but the electron density of the core was slightly lower. The gerbils showed changes in glucose tolerance, the size of the pancreatic islets, the percentage of B cells, and of A cells in the dorsal portion with age.(ABSTRACT TRUNCATED AT 250 WORDS)