Hypersecretory Activity Research Articles

Skin Cancer Microenvironment: What We Can Learn from Skin Aging?

Aging is a natural intrinsic process associated with the loss of fibrous tissue, a slower cell turnover, and a reduction in immune system competence. In the skin, the continuous exposition of environmental factors superimposes extrinsic damage, mainly due to ultraviolet radiation causing photoaging. Although not usually considered a pathogenic event, photoaging affects cutaneous biology, increasing the risk of skin carcinogenesis. At the cellular level, aging is typified by the rise of senescence cells a condition characterized by reduced or absent capacity to proliferate and aberrant hyper-secretory activity. Senescence has a double-edged sword in cancer biology given that senescence prevents the uncontrolled proliferation of damaged cells and favors their clearance by paracrine secretion. Nevertheless, the cumulative insults and the poor clearance of injured cells in the elderly increase cancer incidence. However, there are not conclusive data proving that aged skin represents a permissive milieu for tumor onset. On the other hand, tumor cells are capable of activating resident fibroblasts onto a pro-tumorigenic phenotype resembling those of senescent fibroblasts suggesting that aged fibroblasts might facilitate cancer progression. This review discusses changes that occur during aging that can prime neoplasm or increase the aggressiveness of melanoma and non-melanoma skin cancer.

Dysfunction of calcium-regulated exocytosis at a single-cell level causes catecholamine hypersecretion in patients with pheochromocytoma

Neuroendocrine tumors constitute a heterogeneous group of tumors arising from hormone-secreting cells and are generally associated with a dysfunction of secretion. Pheochromocytoma (Pheo) is a neuroendocrine tumor that develops from chromaffin cells of the adrenal medulla, and is responsible for an excess of catecholamine secretion leading to severe clinical symptoms such as hypertension, elevated stroke risk and various cardiovascular complications. Surprisingly, while the hypersecretory activity of Pheo is well known to pathologists and clinicians, it has never been carefully explored at the cellular and molecular levels. In the present study, we have combined catecholamine secretion measurement by carbon fiber amperometry on human tumor cells directly cultured from freshly resected Pheos, with the analysis by mass spectrometry of the exocytotic proteins differentially expressed between the tumor and the matched adjacent non-tumor tissue. In most patients, catecholamine secretion recordings from single Pheo cells revealed a higher number of exocytic events per cell associated with faster kinetic parameters. Accordingly, we unravel significant tumor-associated modifications in the expression of key proteins involved in different steps of the calcium-regulated exocytic pathway. Altogether, our findings indicate that dysfunction of the calcium-regulated exocytosis at the level of individual Pheo cell is a cause of the tumor-associated hypersecretion of catecholamines.

<p>Pathological studies on <em>Pteris cretica</em> (L.) fern-Bovine Papilloma Virus infection in Syrian Golden Hamsters (<em>Mesocricetus auratus</em>)</p>

Pteris cretica (L.) commonly known as Cretan brake is widely distributed in nature and considered as potential environmental carcinogen. However, only limited literature is available on this fern commonly taken by cattle while grazing. It is known that in cattle Bovine papilloma virus (BPV) induced benign tumours are converted into malignant with interaction of ptaquiloside (Pta) present in ferns. In the present investigation, we evaluated the pathological effects of P. cretica (PC)-BPV infection in laboratory model hamster. Though toxic principle Pta was detected in fern samples but quercetin could not be found. Tumours were successfully induced in hamsters by cutaneous wart suspension and histopathologically diagnosed as fibroma and lipofibroma. Histopathologically, hamsters showed mild to moderate vascular changes in vital organs, multiple cysts, degenerative changes, bile duct hyperplasia and necrosis in liver, haemorrhages and haemosiderosis in spleen, hypersecretory activity and prominent Peyer’s patches in ileum, degenerative changes and presence of eosinophilic casts in renal tubules. Ultrastructural study revealed apoptosis in hepatocytes, abundance of variable shaped mitochondria in renal tubular lining epithelial cells and enterocytes showed abundance of mitochondria and cytoplasmolysis in the fern fed groups. Almost all the hamsters from BPV, fern and virus infection (PC+BPV) groups developed similar type of tumorous growths. The visible growths in the hamsters of these groups were either single or double large sized except multiple tumorous growths in one hamster from PC+BPV group. However, multiple palpable subcutaneous nodules were developed at the site of scarification in all the hamsters of BPV and PC+BPV groups. Our findings suggest that the Pta containing P. cretica feeding induced hepatotoxic and nephrotoxic lesions in hamsters, but effects of P. cretica -BPV infection were found negligible.

Effects of Carbaryl and γ-BHC on the Histology of Midgut and Digestive Enzyme Profiles in the Third Instar Larvae of Fruit-sucking Moth, Othreis materna (Linn.) (Lepidoptera: Noctuidae)

The effects of LC50 dose of carbaryl and gamma benzene hexachloride (γ-BHC) on midgut histopathology and midgut enzyme activities in the third instar larvae of fruit-sucking moth, Othreis materna (L.) were studied. The sub-lethal doses of carbaryl and \gamma-BHC caused initially hypersecretory activity in the midgut epithelial cells leading to deposition of numerous secretory vesicles in the extraperitrophic space, clumping of chromatin matter, and regression and vacuolization of the columnar cells, but later on they were recovered within 24 h. Activities of the midgut digestive enzymes (amylase, invertase, lipase, and protease) were significantly affected. Carbaryl enhanced (P < 0.05) the amylase, invertase, lipase, and protease activities initially up to 4 h and 6 h of treatment, but after 24 h of treatment, amylase and invertase activities resumed while an inhibitory effect was observed on lipase and protease activities. \gamma-BHC did not affect the amylase and protease activities up to 4 h but later on it significantly (P < 0.05) enhanced their activities up to 6 h and 12 h, respectively. Thereafter it fell without showing any sign of recovery. \gamma-BHC enhanced (P < 0.05) invertase and lipase activities but they fell after 4 h treatment.

Rab18 Is Reduced in Pituitary Tumors Causing Acromegaly and Its Overexpression Reverts Growth Hormone Hypersecretion

Rab proteins regulate the sequential steps of intracellular membrane transport. Alterations of these GTPases and their associated proteins are emerging as the underlying cause for several human diseases involving dysregulated secretory activities. Herein we investigated the role of Rab18, which negatively regulates hormone secretion by interacting with secretory granules, in relation to the altered functioning of tumoral pituitary somatotropes causing acromegaly. A total of 18 patients diagnosed with pituitary tumors causing acromegaly (nine patients) or nonfunctioning adenomas (nine patients) underwent endoscopic transsphenoidal surgery. Adenomas were subsequently processed to evaluate Rab18 production in relation to GH secretion. We found that somatotropinoma cells are characterized by a high secretory activity concomitantly with a remarkably reduced Rab18 expression (15%) and protein content levels (30%), as compared with cells from nonfunctioning pituitary adenomas derived from patients with normal or reduced GH plasma levels (100%). Furthermore, immunoelectron microscopy revealed that Rab18 association with the surface of GH-containing secretory granules was significantly lower in somatotropes from acromegalies than nonfunctioning pituitary adenomas. Finally, we provide evidence that modulation of Rab18 gene expression can revert substantially the hypersecretory activity of cells because Rab18 overexpression reduced by 40% the capacity of cells from acromegalies to respond to GHRH stimulation. These results suggest that molecular alterations affecting individual components of the secretory granule traffic machinery can contribute to maintain a high level of GH in plasma. Accordingly, Rab18 constitutes a valuable target as a diagnostic, prognostic, and/or therapeutic tool for human acromegaly.

Molecular mechanisms of the antiproliferative activity of somatostatin receptors (SSTRs) in neuroendocrine tumors

The current treatment of neuroendocrine tumors include the use of somatostatin (SST) agonists. These compounds are able to control most of the symptoms caused by the hypersecretory activity of the tumor cells, and for this reason, they provide a significant improvement in the well-being of the patients. Although, several reports also showed a possible direct antiproliferative activity of SST agonists in different neuroendocrine tumors, the therapeutic potential of an in vivo antiproliferative activity mediated by SST receptors is still debated. In recent years, there has been great insights on understanding the molecular basis of the antitumoral activity of SST that appears to be exerted via both direct and indirect mechanisms. Direct mechanisms require the activation of SST receptors in tumor cells and the induction of cell cycle arrest or apoptosis, mainly through the regulation of phosphotyrosine phosphatase (PTP) and MAP kinase activities. The indirect mechanisms involve the inhibition of tumor angiogenesis and the inhibition of the secretion of factors which are required for tumor growth. Here, we will review the molecular mechanisms which are implicated in the antiproliferative activity of SST. Such an understanding is necessary for improving the antitumoral efficacy of SSTR agonists as well as for the development of novel therapeutic strategies.

Hypersensitivity of the adrenal cortex to trophic and secretory effects of angiotensin II in Lyon genetically-hypertensive rats.

In Lyon hypertensive (LH) rats, a model of low-renin genetic hypertension, we investigated adrenal sensitivity to angiotensin II in terms of angiotensin II receptor (AT1 and AT2 receptors) regulation, morphological changes, and aldosterone and corticosterone secretion. Twelve-week-old LH rats, compared with normotensive LN and LL rats, were either untreated or treated for 4 weeks with AT1 receptor antagonist irbesartan (50 mg/kg/d), angiotensin-converting enzyme inhibitor perindopril (3 mg/kg/d), or perindopril (3 mg/kg/d) plus angiotensin II infusion (200 ng/kg/min). At 16 weeks, untreated LH rats had high systolic blood pressure (P<0.05), low aldosterone (P<0.05), and increased corticosterone (P<0.05) plasma levels. AT1-receptor binding density in the zona glomerulosa was similar in the three strains. In LH rats, angiotensin II infusion increased the relative adrenal weight from 10.5+/-0.3 to 16.7+/-0.7 mg/100g (P<0.05), whereas this change was very modest in normotensive rats. Zona glomerulosa enlarged and plasma aldosterone increased after angiotensin II infusion in the 3 strains, but more markedly in LH versus normotensive rats (2.4- versus 1.3- and 1.6-fold, respectively; 20- versus 10-fold in normotensive rats, P<0.05). Surprisingly, after angiotensin II infusion, despite the absence of angiotensin II receptors in the three strains, the zona fasciculata-reticularis enlarged 1.5-fold and plasma corticosterone increased 1.7-fold only in LH rats (P<0.05), suggesting an indirect control of this compartment by angiotensin II. The hypertrophy and hypersecretory activity of both zona glomerulosa and zona fasciculata-reticularis in LH rats in response to angiotensin II point to the adrenal cortex as a pivotal tissue in the pathophysiology of hypertension in LH rats.

Castration-induced hyperactivity of seminal vesicle in the catfish Clarias batrachus: a case of paradox and blockade by antiandrogen (cyproterone acetate) treatment.

Castration of the catfish Clarias batrachus in late preparatory-early prespawning phase (April-May) caused time-dependent stimulatory effect on morphology, weight, and in the concentrations of biochemical correlates, such as total proteins, fructose, hexosamines and sialic acid in the seminal vesicle (SV). The peak changes were noticed on week 4 of castration. The hyperactivity was related to augmented production of testosterone by the SV of castrates with the levels significantly high from week 3 onwards. As a result, serum testosterone level fluctuated with a significant decrease in the first and fifth weeks, a significant increase in the third week, and no significant difference in the second and fourth weeks. Serum E2 level decreased significantly throughout. Cyproterone acetate treatment (CA; 1 mg/fish daily for 21 days) from the second day of castration decreased the size and weight of the SV and the concentrations of total proteins, hexosamines, fructose and sialic acid. The antiandrogen treatment did not alter serum testosterone level but the E2 level was significantly decreased. It is concluded that the hypersecretory activity of the SV in castrates is a sequel to local synthesis and action of testosterone and the effect could be prevented by CA by blocking androgen actions.

Neurally maintained hypersecretion in undernourished rat intestine activated by E. coli STa enterotoxin and cyclic nucleotides in vitro.

1. The electrogenic secretory responses of stripped jejuna and ilea from chronically undernourished rats (50% control diet for 21 days) to the bacterial enterotoxin Escherichia coli STa, measured as the short-circuit current in vitro, show an enhanced maximum secretion (ISC, max) with a prolonged duration compared with fed intestine. 2. The ISC, max is unaffected by pretreatment of the intestine in vitro with hexamethonium, atropine, procaine or indomethacin, or by desensitization to 5-hydroxytryptamine (5-HT), while the prolonged duration is unaffected by atropine, indomethacin or 5-HT desensitization but is reduced by hexamethonium and procaine. 3. Both 8-bromo-cyclic GMP and dibutyryl cyclic AMP added serosally activate the enhanced ISC, max and its maintenance. Pretreatment with tetrodotoxin had no effect on the initial ISC, max but prevented its maintenance. 4. Bethanechol, dimethyl phenyl piperazinium, vasoactive intestinal polypeptide, 5-HT and luminal propionate all induced the characteristic hypersecretory activity in the undernourished intestine compared with the fed state, but none could activate the maintenance circuit to prolong their transient responses. 5. Maintenance of the induced hypersecretory activity is the first example of induction of the neural control of intestinal secretion by the dietary intake level and illustrates the plasticity of the enteric nervous system.

Synthesis-secretion coupling of insulin: effect of pregnancy and lactation.

Synthesis-secretion coupling of insulin was determined using perfused pancreata taken from either control, pregnant, or lactating female Sprague-Dawley rats. The pancreata were stimulated for 3 h with one of the two glucose concentrations used: either 150 or 300 mg/dl. In the case of pregnancy, the pancreata exhibited a twofold hypersecretory activity in response to the physiological glucose level of 150 mg/dl. Net insulinogenesis did not occur in response to the normoglycemic glucose concentration, and, as with the controls, there was an overall depletion of insulin stores. There was no insulin hypersecretion at the hyperglycemic level of 300 mg/dl, but net insulinogenesis did occur; however, it matched that of the controls. Therefore, the hypersecretion of insulin ascribed to pregnancy appears to be a function of the secretory process only, to be most demonstrable under normoglycemic conditions, and not to be due to enhanced synthesis-secretion coupling. In the case of pancreata from lactating rats, just the converse was observed. Compared with controls, there was no substantial difference in insulin secretion by pancreata from lactating rats at either glucose level or of insulinogenesis under normoglycemia conditions. However, when glucose was at a hyperglycemic load in the lactating group, not only was there no net insulinogenesis, but this condition actually resulted in a depletion of intracellular insulin stores (as opposed to both the control and the pregnant groups). This suggests that the hypoinsulinemia noted during lactation may be related to a reduced capacity of those beta-cells to synthesize insulin the face of prolonged hyperglycemic stimulation.

Mutations in the Alpha Subunit of the Stimulatory Regulatory Protein of Adenylyl Cyclase (Gs) in Human GH-Secreting Pituitary Adenomas: Biochemical, Clinical, and Morphological Aspects

Very recently a subset of human GH-secreting pituitary adenomas carrying a somatic mutation in the alpha subunit of the stimulatory regulatory protein of adenylyl cyclase (Gs) was identified. In all these tumors (Group 2; about 30% of all the GH secreting tumors studied) the alpha s cDNAs contained mutations; in 8 tumors mutations replaced Arginine 201 with either Cystein or Histidine while in the remaining tumors Glutamine 227 was replaced by either Arginine or Leucine. No mutations were observed in the remaining adenomas (Group 1). The two mutations caused a constitutive activation of adenylyl cyclase and a turn on of cAMP synthesis by inhibiting GTPase activity. The transformed phenotype was reflected in adenomatous cells with high rate of cAMP production and in vitro GH secretion. No difference in age, sex, clinical features, duration of the disease and cure rate were observed between the patients without (Group 1) or with alpha s mutation (Group 2), while higher serum GH levels and smaller tumor size were present in Group 2 patients. Moreover, hypersecretory activity in Group 2 tumors was also apparent at electron microscopy; cells of Group 2 tumors were densely granulated and showed prominent rough endoplasmic reticulum and Golgi complex. With respect to Group 1, Group 2 patients were less responsive to GH-releasing hormone (GHRH), while they were more sensitive to somastostatin. The former finding is in agreement with the hypothesis that the oncogenic proteins mimic the effects of extracellular growth factors, so removing the requirement for GHRH; the latter might explain the low rate of tumor growth as due to the counteracting role of endogenous inhibitory factors.

Clinical, Biochemical, and Morphological Correlates in Patients Bearing Growth Hormone-Secreting Pituitary Tumors with or without Constitutively Active Adenylyl Cyclase

Somatic mutations in the alpha-chain (alpha s) of the stimulatory regulatory protein of adenylyl cyclase (Gs) causing constitutive activation of the enzyme have been identified in a subset of human GH-secreting pituitary adenomas. This study reports on the differences between acromegalic patients bearing tumors without (group 1; n = 51) or with (group 2; n = 29) this alteration. No difference in age, sex, clinical features, duration of the disease, or cure rate was observed between the two groups. By contrast, group 2 patients had higher basal GH levels than group 1. Moreover, a significant difference in sellar morphology was found; group 2 patients more frequently showed sellas of normal size (grade I) than group 1. Hypersecretory activity of group 2 tumors was also apparent at electron microscopy; contrary to those of group 1, cells of group 2 tumors were densely granulated and showed prominent rough endoplasmic reticulum and Golgi complex. With respect to group 1, group 2 patients were less responsive to GH-releasing hormone, while they were more sensitive to somatostatin- and dopamine-induced GH inhibition. These results suggest that patients with constitutively active adenylyl cyclase have hyperactive tumors; the sensitivity of these tumors to inhibitory agents (somatostatin and dopamine), possibly counteracting the expression of activating mutations, might explain the low rate of tumor growth.

Histoautoradiographic study of rRNA and mRNA transcription activity related to secretory function in lizard epididymis.

The lizard epididymis is an androgen-dependent organ whose epithelial cells undergo marked changes in structure and secretory activity during the annual cycle. These changes are connected to fluctuations of testosterone levels. During the breeding season, the epididymis produces a major protein secretion, the L-proteins. In the present work we studied the fluctuations of RNA synthesis and accumulation during the annual cycle by means of histoautoradiographic methods. Total RNA synthesis was determined by uridine incorporation; accumulation of rRNAs and L-protein mRNAs were determined by in situ hybridization. Total RNA synthesis began during reorganization (Phase I), then increased gradually during differentiation and growth (Phase II). The synthesis peaked during maturation (Phase III), but stopped abruptly during hypersecretory activity (Phase IV). The rRNAs were very abundant from Phase II to Phase IV, which is related to the presence of many ribosomes as revealed by electron microscopy. The mRNAs of L-proteins were detected only during Phases III and IV in all epithelial cells. For every phase of the sexual cycle there exists a strong correspondence between the changes in transcriptional activity (rRNA and specific mRNA) of the epithelial cells and changes in the testosterone levels.

Acetaminophen: Macula densa hypersecretory activity by induced hepatotoxicity

Introduction. Experimental induction of altered histology by chemical toxins is of particular importance if its outcome resembles histopathological phenomena. Hepatotoxic drugs and chemicals are agents that can be converted by the liver into various metabolites which consequently evoke toxic responses. Very often, these drugs are intentionally administered to resolve an illness unrelated to liver function. Because of hepatic detoxification, the resulting metabolites are suggested to be integrated into the macromolecular processes of liver function and cause an array of cellular and tissue alterations, such as increased cytoplasmic lysis, centrilobular and localized necroses, chronic inflammation and “foam cell” proliferation of the hepatic sinusoids (1-4).Most experimentally drug-induced toxicity studies have concentrated primarily on the hepatic response, frequently overlooking other physiological phenomena which are directly related to liver function. Categorically, many studies have been short-term effect investigations which seldom have followed up the complications to other tissues and organs when the liver has failed to function normally.

Ultrastructural and developmental alterations induced by Periconia circinata toxin in the root tip of sorghum

Cytological and developmental effects induced by Periconia circinata toxin were examined to better understand the mechanism of action for this toxin. Roots of sorghum seedlings susceptible and resistant to P. circinata were incubated in 500 ng toxin/mL (treated) or water (controls). Root cap cells of resistant seedlings treated with the toxin were cytologically similar to those of controls, although the toxin caused a transient inhibition of mitosis in cells of the primary root tip. In outer root cap cells of susceptible seedlings treated for 0.25 h, hypersecretory activity was lost, secretory vesicles were fewer, and secretory product accumulated between the plasma membrane and cell wall. Also, inner root cap cells showed increased vacuolation. Longer treatments caused increased vacuolation, loss of starch, increased numbers of lipid bodies, pleomorphic amyloplasts, regularly stacked endoplasmic reticulum, apparent changes in the amounts of cytomembranes, dispersion of heterochromatin, and autolysis. Mitochondrial morphology was normal, but lesions in the tonoplast occurred before autolysis. The toxin also inhibited expansion and sloughing off of root cap cells and mitotic activity in the root tip. Stacked endoplasmic reticulum, nonhypersecretory dictyosomes, fewer secretory vesicles, increased vacuolation, reorganization of heterochromatin, and increased secretory product outside the protoplast were induced by P. circinata toxin and by cyanide. These data suggested that a cyanogenic compound is biologically active in cells treated with P. circinata toxin. Our results suggest that the toxin transiently affects resistant seedlings and in susceptible seedlings alters vacuolar expansion, secretory activity, and endomembrane flow, although other processes may also be affected.

Inhibition of histamine biosynthesis and gastric function in the rat: effect on pentagastrin-induced gastric acid secretion.

A very simple and rapid method to measure gastric acid secretion in the conscious unoperated fasted rat is reported. Antisecretory activity of cimetidine and hypersecretory activity of pentagastrin are detected by this procedure. Pentagastrin induces gastric acid secretion and causes an increase by 2-fold in histidine decarboxylase activity. There is a delay between the increase of gastric acid output and the appearance of histidine decarboxylase activity. Co-administration of monofluoromethyl histidine, a specific irreversible inhibitor of histidine decarboxylase, does not modify the peak response to pentagastrin but shortens the duration of stimulation. We suggest from this data that histamine biosynthesis is needed for maintenance of elevated gastric acid secretion.

Ultrastructure of the toad pars intermedia after the extirpation of the pars distalis

The ultrastructure of the toad pars intermedia (PI) was studied 1, 2, 4, and 12 weeks after the extirpation of the pars distalis. Three regions were distinguished in the PI of pars distalisectomized toads. Region I, close to the neural lobe; the ventrocaudal area, which in the normal animal faces the pars distalis, was regarded as region III; region II was the medial third located between regions I and III. One and two weeks after the operation the secretory cells of the PI, especially those of region I, presented all the ultrastructural features associated with hypersecretory activity. One month after pars distalisectomy changes were found in the three regions. Colloid secreting cells were hypertrophied and widely distributed in the gland. Region II was mostly occupied by hypertrophied “MSH cells.” These cells frequently formed syncytial structures. In region II but especially in region III cells appeared which were characterized by a hypertrophied RER, an atrophic Golgi apparatus, and in most cases abundant secretory granules whose size and inner structure differ from those of MSH granules. The most typical feature was the presence within the RER cisternae of numerous and regularly spaced microtubular structures. Two other cell types were found in region III, especially in the vicinity of blood vessels. One of them was characterized by hypertrophied Golgi complexes and RER and the presence of small secretory granules (170 nm). Few of the RER cisternae had microtubular structures. The other cell type had large secretory granules (1000 nm) filling the cytoplasm. Degenerating nerve fibers were neither found in the PI, nor in the neural lobe, nor in the median eminence.

Studies on the functional morphology ofOdontopus nigricornisStål (Heteroptera: Pyrrhocoridae)

Summary The male internal organs of reproduction in Odontopus nigricornis are similar to those of other Heteroptera described earlier except that this species has a very peculiarly developed unpaired ectadene gland and that the paired mesadene glands are multi-lobed. The mesadene glands secrete two types of secretion. The outer wall of the antero-dorsal lobe of the tri-lobed ectadene gland exhibits hypersecretory activity and the secretion is different from that of the rest of the gland. The strong circular muscles of the median dorsal groove of the bulbus ejaculatorius exercise a significant role in sucking the sperm bundles from the common ducts of vesiculum seminis and mesadene gland of each side into the bulbus, dissociating them and mixing them with the ectadene secretion and pumping the spermatozoa out through the ductus ejaculatorius.

On the fine structure of differentiating mucilage papillae of Marchantia

In Marchantia, the mucilage papillae are initiated by differential divisions occurring in marginal cells of scales at early stages of their development. Establishment of a new polarity axis was observed in mucilage papilla mother cells as well as in their daughter cells, which were destined to develop into mucilage papillae. During polarization the marginal cells synthesize cytoplasm and free ribosomes; subsequently, the cells grow outwards. Concomitantly, organelles migrate to the apical region, where some rough endoplasmic reticulum (ER) membranes and dictyosomes are polarly placed. The subplasmalemmal microtubules become reoriented during polarization.The spindle-shaped preprophase and prophase nucleus of the mucilage papilla mother cell is surrounded by two distinct microtubular systems: the preprophase band of microtubules and an extranuclear sheath of microtubules; the latter is aligned along the spindle axis, close to the nuclear membrane and convergent at polar areas which contain ER membranes.Among the first structural signs of mucilage papillae differentiation are the following: increase of cytoplasm, free ribosomes, rough ER membranes, and dictyosomes; preferential association of plastids with ER membranes and mitochondria, as well as the transverse orientation of subplasmalemmal microtubules. As differentiation ensues the cells acquire more cytoplasm and their organelles proliferate markedly, while new specific organelle relationships become evident.The increase of rough ER membranes predominates and keeps pace with dictyosome proliferation. Among the organelles the ER membranes display a key role in diverse mucilage papilla differentiation and an intermediary one in their secretory activity.The particularly active secretory phase of mucilage papillae is marked by an hypersecretory activity of dictyosomes which produce abundant vesicles. Histochemical staining revealed polysaccharides in the larger vesicles, the space between plasmalemma and cell wall, and within the wall.Ultimately, the mucilage papillae either undergo a partial degradation of protoplasm or even degenerate. In the former case they undergo an intense vacuolation and finally appear structurally similar to other cells of scales.

The thymus of spontaneously hypertensive rats: light-and electron-microscopic studies.

1. The present investigation was undertaken to study the possibility that hypertensive vascular disease could be associated with changes in the morphology of the thymus. 2. Using light- and electron-microscopic techniques, the thymus of spontaneously hypertensive rats (SHR) with (1 year of age) and without (10 weeks of age) severe vascular lesions were compared with appropriate controls. 3. The thymus of SHR with severe hypertensive vascular disease showed: (a) marked hyperplasia and hypertrophy of the epithelial cells, with ultrastructural features of hypersecretory activity, and (b) in contrast to the paucity of plasma cells in the thymus of the control animals, the SHR had numerous plasma cells. 4. These observations may suggest the involvement of an autoimmunological mechanism in the development of the vascular lesions in SHR.