Intermediate Cells of the Pancreas

1972 ◽  
Vol 11 (2) ◽  
pp. 449-475 ◽  
Author(s):  
R. N. MELMED ◽  
CAROL J. BENITEZ ◽  
S. J. HOLT

The normal existence of cells in the pancreas with a structure intermediate between those of exocrine and endocrine cell types has long been a matter of dispute. The present study shows that, based upon morphological criteria, such intermediate cells are present in both the endocrine and exocrine tissues of the normal pancreas of the rat, guinea-pig, rhesus monkey, goat, chicken and frog. There is a tendency for intermediate cells to occur most frequently in the frog, where exocrine and endocrine cells are intermingled, and least frequently in higher species such as the rat, guinea-pig, monkey and goat where the endocrine cells are localized in discrete islets. Their occurrence in the chick appears to lie between these 2 extremes. The existence of intermediate cell types has been attributed to a ‘transformation’ of one form of specialized cell in the pancreas into another in response to a metabolic demand. However, the widespread occurrence of intermediate cells in the normal pancreas suggests that they represent, ab initio, a distinct category of cell, the existence of which poses interesting questions concerning the genetic control of their specialized functions and of developmental processes in the pancreas. Moreover, intermediate cells, such as acinar cells containing endocrine β-granules might serve as a source of insulin additional or alternative to that provided by cells that are wholly endocrine in character.

Development ◽  
1994 ◽  
Vol 120 (7) ◽  
pp. 1873-1881 ◽  
Author(s):  
D. Gu ◽  
M.S. Lee ◽  
T. Krahl ◽  
N. Sarvetnick

We examined the spectrum of intermediate cell types in the regenerating pancreas as duct epithelial cells progressed through their differentiation pathway to become mature endocrine cells. The model used was transgenic mice in which the pancreatic islets continue to grow during adulthood, unlike normal mice whose islet cell formation ceases early in life. Because the intermediate cells migrated into islet-like clusters at specific locations, we propose a specific pathway for islet development. Endocrine cells are derived from duct cells co-expressing a duct cell antigen, carbonic anhydrase II (CA II) and an exocrine enzyme, amylase. The CA II/amylase cells become amylase/endocrine intermediate cells as they exited from their lumenal location. The abluminal amylase/endocrine cells continue to differentiate to multihormone-bearing young endocrine cells, which migrated to form clusters with other differentiating endocrine cells.


2021 ◽  
Author(s):  
Ying Ying Liu ◽  
Jian Guo ◽  
Ji Chen ◽  
Hai Xia Li ◽  
Zeng Tao Wang ◽  
...  

Abstract Background: Tracheal mucoepidermoid carcinoma is a rare form of non-small cell lung carcinoma and is defined as a tumor characterized by a combination of squamous, mucus-secreting, and intermediate cell types. This carcinoma is usually located in the lobar or segmental bronchus. Currently, surgery is the preferred treatment for this disease, which includes pneumonectomy, lobectomy, and sleeve lobectomy. Case presentation: A 50-year-old Chinese male presented with cough, shortness of breath and hemoptysis, and the effect of antibiotic therapy was not good. Subsequently, the airway occupied lesion was found by chest CT, and he was transferred to our hospital for surgical resection. Histologically, the tumor contained squamous epidermal cells, mucoepidermoid cells and intermediate cells. Immunohistochemistrically, the tumor cells were positive for p63, CK5/6, CK7 and Ki67. However, the tumor is generally negative for TTF-1 and neuroendocrine markers. The patient had no recurrence 15 months after the surgery.Conclusions: We report a rare case of mucoepidermoid carcinoma in the distal trachea in which the surgery was difficult and could not be performed like a traditional pulmonary resection. We first provide a comprehensive description of airway management and anesthesia intubation. After surgery, we reviewed the literature and found that PD-1/PD-L1 detection had never been reported in tracheal mucoepidermoid carcinoma. Therefore, we studied the PD-1/PD-L1 pathway in this patient, and the results were negative, which may indicate that potential adjuvant therapy with immune checkpoint inhibitors (ICIs) is not useful in this case.


Author(s):  

Background: Tracheal mucoepidermoid carcinoma is a rare form of non-small cell lung carcinoma and is defined as a tumor characterized by a combination of squamous, mucus-secreting, and intermediate cell types. This carcinoma is usually located in the lobar or segmental bronchus. Currently, surgery is the preferred treatment for this disease, which includes pneumonectomy, lobectomy, and sleeve lobectomy. Case presentation: A 50-year-old Chinese male presented with cough, shortness of breath and hemoptysis, and the effect of antibiotic therapy was not good. Subsequently, the airway occupied lesion was found by chest CT, and he was transferred to our hospital for surgical resection. Histologically, the tumor contained squamous epidermal cells, mucoepidermoid cells and intermediate cells. Immunohistochemistrically, the tumor cells were positive for p63, CK5/6, CK7 and Ki67. However, the tumor is generally negative for TTF-1 and neuroendocrine markers. The patient had no recurrence 15 months after the surgery. Conclusions: We report a rare case of mucoepidermoid carcinoma in the distal trachea in which the surgery was difficult and could not be performed like a traditional pulmonary resection. We first provide a comprehensive description of airway management and anesthesia intubation. After surgery, we reviewed the literature and found that PD-1/PD-L1 detection had never been reported in tracheal mucoepidermoid carcinoma. Therefore, we studied the PD-1/PD-L1 pathway in this patient, and the results were negative, which may indicate that potential adjuvant therapy with immune checkpoint inhibitors (ICIs) is not useful in this case.


1998 ◽  
Vol 111 (23) ◽  
pp. 3529-3539 ◽  
Author(s):  
T.L. Woodward ◽  
M.A. Sia ◽  
O.W. Blaschuk ◽  
J.D. Turner ◽  
D.W. Laird

Epithelial, fibroblast and intermediate cell lines were employed to examine the mechanism(s) essential for heterocellular gap junction intercellular communication in vitro. These cell lines were characterized extensively for cell type based on morphology, intermediate cytoskeletal proteins, cell adhesion molecules and their associated proteins, tight junction proteins as well as functional differentiation. All cell types expressed connexin43 and were dye-coupled in homocellular culture. Epithelial and intermediate cells or fibroblasts and intermediate cells readily assembled heterocellular connexin43-positive gap junction plaques when co-cultured, while gap junction plaques in mixed cultures of epithelial cells and fibroblasts were rare. Dye microinjection studies were used to show that there was little gap junction intercellular communication between epithelial cells and fibroblasts. However, intermediate cells were able to communicate with epithelial cells and, to a lesser extent, fibroblasts and could transfer dye to both epithelial cells and fibroblasts when all three cell types were cultured together. Fibroblasts that were stably transfected with a cDNA encoding E-cadherin had a greater tendency to aggregate and exhibited a more epithelial-like phenotype but heterocellular gap junction intercellular communication with epithelial cells, which endogenously express E-cadherin, was not enhanced. These results suggest that mutual expression of E-cadherin is insufficient to stimulate gap junction formation between epithelial cells and fibroblasts. Moreover, our results also demonstrate that communication gaps between epithelial cells and fibroblasts can be bridged by intermediate cells, a process that may be important in mammary gland development, growth, differentiation and cancer.


Blood ◽  
1982 ◽  
Vol 60 (5) ◽  
pp. 1122-1131 ◽  
Author(s):  
RF Levine ◽  
KC Hazzard ◽  
JD Lamberg

Normal guinea pig and human megakaryocytes in suspension were measured with an optical micrometer. The range of megakaryocyte diameters in both species was from 10 to about 65 micrometer. Approximately 20%-25% of megakaryocytes were smaLler than 20 micrometer in diameter and were mostly missed in past studies. However, virtually the entire population of megakaryocytes was larger than all but a very small percent of the other marrow cells. This size range and the existence of a visual threshold size between the megakaryocytes and nonmegakaryocytes were confirmed by flow cytometric analysis of fresh unfixed cells. On human bone marrow smears there was some flattening of all cell types, but the megakaryocytes were consistently at least minimally greater in size than almost all the nonmegakaryocytes. Normal marrow cells greater than 20 micrometer in diameter were always megakaryocytes. Cells 14–20 micrometer were still noticeably larger than the general marrow population; thus easily found, they could be examined for specific morphological criteria. Size, therefore, is a useful first criterion for the identification of megakaryocytes. The larger sizes of megakaryocytes were related to their greater DNA content per cell (polyploidy) compared to nonmegakaryocytes. The relationship between megakaryocyte size, ploidy, and maturation was examined by the simultaneous measurement for the first time of each of these parameters in the same cell. Maturation was quantitated by the new scheme based on the progressive changes in megakaryocytes nuclear configuration. Within each maturation stage the mean cell volume of guinea pig megakaryocytes doubled with each ploidy doubling. Within each ploidy group, the sizes of megakaryocytes increased with maturation stage. However, maturation and polyploidization appear to be linked; the data showed that 80% of the low ploidy (4N-8N) megakaryocytes were immature and that 95% of the platelet-shedding megakaryocytes were 16N-32N.


Function ◽  
2021 ◽  
Author(s):  
Adrienne Assmus ◽  
Linda Mullins ◽  
Mairi Ward ◽  
Ross Dobie ◽  
Robert Hunter ◽  
...  

Abstract The kidney cortical collecting duct (CCD) comprises of principal cells (PC), intercalated cells (IC) and the recently discovered intermediate cell type. Kidney pathology in a mouse model of the syndrome of apparent aldosterone excess (SAME) revealed plasticity of the cortical collecting duct (CCD), with altered principal cell (PC): intermediate cell: intercalated cell (IC) ratio. The self-immortalized mouse CCD cell line, mCCDcl1, shows functional characteristics of PCs but displays a range of cell types, including intermediate cells, making it ideal to study plasticity. We knocked out Adam10, a key component of the Notch pathway, in mCCDcl1 cells, using CRISPR-Cas9 technology, and isolated independent clones, which exhibited severely affected sodium transport capacity and loss of aldosterone response. Single-cell RNA sequencing revealed significantly reduced expression of major PC-specific markers, such as Scnn1g (γ-ENaC) and Hsd11b2 (11ßHSD2), but no significant changes in transcription of components of the Notch pathway were observed. Immunostaining in the knockout clone confirmed the decrease in expression of γ-ENaC and importantly, showed an altered, diffuse distribution of PC and IC markers, suggesting altered trafficking in the Adam10 knockout clone as an explanation for the loss of polarisation.


Blood ◽  
1982 ◽  
Vol 60 (5) ◽  
pp. 1122-1131 ◽  
Author(s):  
RF Levine ◽  
KC Hazzard ◽  
JD Lamberg

Abstract Normal guinea pig and human megakaryocytes in suspension were measured with an optical micrometer. The range of megakaryocyte diameters in both species was from 10 to about 65 micrometer. Approximately 20%-25% of megakaryocytes were smaLler than 20 micrometer in diameter and were mostly missed in past studies. However, virtually the entire population of megakaryocytes was larger than all but a very small percent of the other marrow cells. This size range and the existence of a visual threshold size between the megakaryocytes and nonmegakaryocytes were confirmed by flow cytometric analysis of fresh unfixed cells. On human bone marrow smears there was some flattening of all cell types, but the megakaryocytes were consistently at least minimally greater in size than almost all the nonmegakaryocytes. Normal marrow cells greater than 20 micrometer in diameter were always megakaryocytes. Cells 14–20 micrometer were still noticeably larger than the general marrow population; thus easily found, they could be examined for specific morphological criteria. Size, therefore, is a useful first criterion for the identification of megakaryocytes. The larger sizes of megakaryocytes were related to their greater DNA content per cell (polyploidy) compared to nonmegakaryocytes. The relationship between megakaryocyte size, ploidy, and maturation was examined by the simultaneous measurement for the first time of each of these parameters in the same cell. Maturation was quantitated by the new scheme based on the progressive changes in megakaryocytes nuclear configuration. Within each maturation stage the mean cell volume of guinea pig megakaryocytes doubled with each ploidy doubling. Within each ploidy group, the sizes of megakaryocytes increased with maturation stage. However, maturation and polyploidization appear to be linked; the data showed that 80% of the low ploidy (4N-8N) megakaryocytes were immature and that 95% of the platelet-shedding megakaryocytes were 16N-32N.


Author(s):  
Juan Mora-Galindo ◽  
Jorge Arauz-Contreras

The zinc iodide-osmium tetroxide (ZIO) technique is presently employed to study both, neural and non neural tissues. Precipitates depends on cell types and possibly cell metabol ism as well.Guinea pig cecal mucosa, already known to be composed of epithelium with cells at different maturation stages and lamina propria which i s formed by morphologically and functionally heterogeneous cell population, was studied to determine the pat tern of ZIO impregnation. For this, adult Guinea pg cecal mucosa was fixed with buffered 1.2 5% g 1 utara 1 dehyde before incubation with ZIO for 16 hours, a t 4°C in the dark. Further steps involved a quick sample dehydration in graded ethanols, embedding in Epon 812 and sectioning to observe the unstained material under a phase contrast light microscope (LM) and a transmission electron microscope (TEM).


1989 ◽  
Vol 262 (1) ◽  
pp. 83-89 ◽  
Author(s):  
K J Föhr ◽  
J Scott ◽  
G Ahnert-Hilger ◽  
M Gratzl

The inositol 1,4,5-trisphosphate (IP3)-sensitive Ca2+ compartment of endocrine cells was studied with alpha-toxin- and digitonin-permeabilized rat insulinoma (RINA2) and rat pheochromocytoma (PC12) cells. The Ca2+ uptake was ATP-dependent, and submicromolar concentrations of IP3 specifically released the stored Ca2+. Half-maximal Ca2+ release was observed with 0.25-0.5 mumol of IP3/l, and the amount of Ca2+ released due to IP3 could be enhanced by additional loading of the Ca2+ compartment. Consecutive additions of the same concentration of IP3 for 1-2 h always released the same amount of Ca2+ without desensitization, providing an ideal basis to further characterize the IP3-induced Ca2+ release. Here we describe for the first time a reversible inhibitory effect of decavanadate on the IP3-induced Ca2+ release. Among the vanadium species tested (decavanadate, oligovanadate and monovanadate), only decavanadate was inhibitory, with a half-maximal effect at 5 mumol/l in both cell types. The effect of decavanadate could be overcome by increasing the amount of sequestered Ca2+ or added IP3. Decavanadate did not affect the ATP-driven Ca2+ uptake but oligovanadate was inhibitory on Ca2+ uptake. p-Hydroxymercuribenzoate (pHMB) at concentrations between 10 and 30 mumol/l also inhibited the Ca2+ release due to IP3. Thiol compounds such as dithiothreitol (DTT; 1 mmol/l) added before pHMB removed all its inhibitory effect on the IP3-induced Ca2+ release, whereas the inhibition caused by decavanadate was unaffected by DTT. Thus, the decavanadate-dependent inhibition functions by a distinctly different mechanism than pHMB and could serve as a specific tool to analyse various aspects of the IP3-induced Ca2+ release within endocrine cells.


Development ◽  
1987 ◽  
Vol 100 (4) ◽  
pp. 661-671 ◽  
Author(s):  
B. Kramer ◽  
A. Andrew ◽  
B.B. Rawdon ◽  
P. Becker

To determine whether mesenchyme plays a part in the differentiation of gut endocrine cells, proventricular endoderm from 4- to 5-day chick or quail embryos was associated with mesenchyme from the dorsal pancreatic bud of chick embryos of the same age. The combinations were grown on the chorioallantoic membranes of host chick embryos until they reached a total incubation age of 21 days. Proventricular or pancreatic endoderm of the appropriate age and species reassociated with its own mesenchyme provided the controls. Morphogenesis in the experimental grafts corresponded closely to that in proventricular controls, i.e. the pancreatic mesenchyme supported the development of proventricular glands from proventricular endoderm. Insulin, glucagon and somatostatin cells and cells with pancreatic polypeptide-like immunoreactivity differentiated in the pancreatic controls. The latter three endocrine cell types, together with neurotensin and bombesin/gastrin-releasing polypeptide (GRP) cells, developed in proventricular controls and experimental grafts. The proportions of the major types common to proventriculus and pancreas (somatostatin and glucagon cells) were in general similar when experimental grafts were compared with proventricular controls but different when experimental and pancreatic control grafts were compared. Hence pancreatic mesenchyme did not materially affect the proportions of these three cell types in experimental grafts, induced no specific pancreatic (insulin) cell type and allowed the differentiation of the characteristic proventricular endocrine cell types, neurotensin and bombesin/GRP cells. However, an important finding was a significant reduction in the proportion of bombesin/GRP cells, attributable in part to a decrease in their number and in part to an increase in the numbers of endocrine cells of the other types. This indicates that mesenchyme may well play a part in determining the regional specificity of populations of gut endocrine cells.


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