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Biomedical subjects

C Morales

Publications and source records attributed to C Morales.

At least 181 records · Page 10Linked to original sources

Effects of propranolol, clonidine and hydrochlorothiazide treatment and abrupt discontinuation on central and peripheral noradrenergic activity in essential hypertension.

This study was undertaken to investigate further the CNS actions of commonly employed antihypertensive drugs. Measurements of cerebrospinal fluid (CSF) and plasma catecholamines (CA) were made in an attempt to estimate the activity of central and peripheral noradrenergic neurons during treatment with or after abrupt discontinuation of treatment with clonidine (CLO), propranolol (PRO), hydrochlorothiazide (HCTZ) or placebo, in patients with essential hypertension. A randomized, parallel, placebo-controlled, single-blind design was employed. BP reductions equal to or greater than 10 mmHg were observed with CLO (0.36 +/- 0.07 mg daily), PRO (160 mg +/- 0 mg daily) or HCTZ (70 +/- 12 mg daily). CLO reduced plasma norepinephrine (NE) by 64% and PRO increased it by 25%. Neither HCTZ nor placebo modified plasma NE. Plasma renin activity (PRA) was reduced by PRO (51%, P less than 0.01) and CLO (35%, P less than 0.05). CSF-NE levels (pg/ml) were significantly lower in the CLO group (CLO: 175 +/- 23; PRO: 278 +/- 35; HCTZ: 255 +/- 34; placebo: 203 +/- 7).

Adrenergic Fibers↗

Intracellular pathways of endocytosed transferrin and non-specific tracers in epithelial cells lining the rete testis of the rat.

The uptake and pathway of different markers and ligands for fluid-phase, adsorptive and receptor mediated endocytosis were analyzed in the epithelial cells lining the rete testis after their infusion into the lumen of these anastomotic channels. At 2 min after injection, diferric transferrin bound to colloidal gold was seen attached to the apical plasma membrane and to the membrane of endocytic coated and uncoated pits and vesicles. The injection of transferrin-gold in the presence of a 100-fold excess of unconjugated diferric transferrin revealed no binding or internalization of transferrin-gold. Similarly, apotransferrin-gold was neither bound to the apical plasma membrane nor internalized by these cells. These results thus indicate the presence of specific binding sites for diferric transferrin. At 5 min, internalized diferric transferrin-gold reached endosomes. At 15 and 30 min, the endosomes were still labeled but at these time intervals the transferrin-gold also appeared in tubular elements connected to or associated with these bodies or seen in close proximity to the apical plasma membrane. At 60 and 90 min, most of the transferrin-gold was no longer present in these organelles and was seen only exceptionally in secondary lysosomes. These results thus suggest that the tubular elements may be involved in the recycling of transferrin back to the lumen of the rete testis. The coinjection of transferrin-gold and the fluid-phase marker native ferritin revealed that both proteins were often internalized in the same endocytic pit and vesicle and shared the same endosome.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Cyclic endocytic activity and kinetics of lysosomes in Sertoli cells of the rat: a morphometric analysis.

Native ferritin was injected into the rete testis of rats, and seminiferous tubules infused with the tracer were collected 6 h later and prepared for electron microscopic analysis. As a result of internalization of the tracer by Sertoli cells, label was found within 12-66% of the secondary lysosomes, depending on the stage of the cycle of the seminiferous epithelium. The Zeiss MOP-3 instrument was used on selected electron microscope photographs to measure a number of morphometric parameters. Applying appropriate formulae and a computerized program, it was possible to determine the absolute numbers of labeled and unlabeled secondary lysosomes per Sertoli cell for each one of the 14 stages of the cycle. Knowing the duration of these stages, it was also possible to evaluate the turnover kinetics and life span of lysosomes for each stage of the cycle. The percentage of ferritin-labeled lysosomes, regarded as an index of the endocytic activity of Sertoli cells, remained low in stages II to VIII, increased abruptly during stage IX, stayed high during stages X to XIV, and decreased to a low level during stage I of the following cycle. Correspondingly, the turnover of secondary lysosomes was relatively slow and their life span relatively long during stages II through VIII, while the turnover of lysosomes was faster and their life span shorter during stages X through XIV-I of the cycle. During stage IX, there was a sharp drop in the number of lysosomes per Sertoli cell associated with a fast rate of disappearance and a remarkably short life span of less than 4 h for the lysosomes. These features, characteristic of stage IX, are explained by the rapid fusion of lysosomes with residual bodies, which are phagocytosed by Sertoli cells at this particular stage of the cycle. The accelerated endocytosis taking place during stages IX through XIV of the cycle may explain the reduction of the surface area of the adluminal plasma membrane of Sertoli cells as well as the reduction in volume of the tubular lumen observed during these stages. Thus, the demonstrated cyclic endocytic activity of Sertoli cells and several other cyclical events taking place within seminiferous tubules correlate well.

Animals↗

Receptor-mediated endocytosis of transferrin by Sertoli cells of the rat.

Binding of 125I-transferrin (125I-Tf) to the plasma membrane of Sertoli cells and its endocytosis were analyzed by means of light- and electron-microscope quantitative radioautography. Five minutes after 125I-Tf was injected into the interstitial space of the testis, a strong labeling of the basal aspect of the seminiferous epithelium was observed in light-microscope radioautographs. Injection of the same dose of 125I-Tf plus a 200-fold excess of cold transferrin resulted in a marked diminution of the radioautographic reaction, indicating that the initial strong labeling with radiolabeled transferrin was specific. These results were consistent with the localization of immunoreactive fluorescence of transferrin receptor at the base of the seminiferous epithelium. In electron-microscope radioautographs of tubules collected at 5 min after injection, the membrane of Sertoli cells facing the basement membrane was well labeled with 125I-Tf. At 15 and 30 min, the plasma membrane was less intensely labeled, but the silver grains were then seen overlying multivesicular bodies with an electron-lucent matrix, identified as endosomes. This population of endosomes was always seen at a short distance from the basal membrane of Sertoli cells. At 90 min, no more labeling of the plasma membrane, endosomes, or any other cytoplasmic component was observed. Isolated seminiferous tubules and Sertoli cells labeled with 125I-Tf at 4 degrees C were rinsed and reincubated in a label-free medium at 37 degrees C for various periods of time from 5 to 90 min. A radioactive protein precipitated by trichloroacetic acid, presumably intact transferrin, was released from the tubules into the incubating medium; when measured, it was found to increase rapidly from 5 to 45 min and stabilize thereafter. These results suggest that transferrin was internalized by receptor-mediated endocytosis, reached endosomes, and then was released to the extratubular space. When native ferritin (NF), a tracer for fluid-phase endocytosis, was infused within the lumen of seminiferous tubules and 125I-Tf was simultaneously injected into the interstitial space, both markers rapidly reached different populations of endosomes. Endosomes labeled with NF, scattered throughout the cytoplasm, evolved with time into dense multivesicular bodies and secondary lysosomes, whereas radiolabeled transferrin reached only the endosomes located in the basal cytoplasm of Sertoli cells. The latter thus appeared to be principally involved in the uptake and recycling of transferrin.

Animals↗

Fluid-phase and adsorptive endocytosis in ciliated epithelial cells of the rat ductuli efferentes.

Ciliated cells of the ductuli efferentes show at their apex a discrete endocytic apparatus composed of small vesicles connected to or subjacent to the apical plasma membrane, small apical membranous tubules, and pale multivesicular bodies. Deeper in the cytoplasm, there are acid phosphatase-positive denser, multivesicular bodies and secondary lysosomes showing an electron-dense cortex and a crystalline, paler stained core. Cationic ferritin and concanavalin A-ferritin used to demonstrate adsorptive endocytosis, when injected into the rete testis, rapidly reached the lumen of the ductuli efferentes. At 1 min after injection, these tracers were seen bound to the apical plasma membrane of ciliated cells and within small endocytic vesicles and by 5 min in narrow apical tubules. At 15 and 30 min after injection, the tracers appeared in pale multivesicular bodies while at 1 hr they were found within dense multivesicular bodies. At 2 hr and longer time intervals these tracers accumulated within secondary lysosomes. Native ferritin, concanavalin A-ferritin in the presence of alpha-methyl-D-mannoside, and horseradish peroxidase or albumin-colloidal gold complexes were used to analyze fluid-phase endocytosis. At various intervals following their injection into the rete testis, these tracers presented a distribution identical in all respects to that described for cationic ferritin and concanavalin A-ferritin. In the present work, none of the above tracers were transported to the abluminal aspect of the ciliated cells. These cells, like the nonciliated epithelial cells of the ductuli efferentes are thus involved in adsorptive as well as in fluid-phase endocytosis.

Adsorption↗

Endocytosis in nonciliated epithelial cells of the ductuli efferentes in the rat.

The nonciliated cells lining the ductuli efferentes presented three distinct cytoplasmic regions. The apical region contained, in addition to cisternae of endoplasmic reticulum and mitochondria, two distinct membranous elements. The tubulovesicular system consisted of dilated tubules connected to the apical plasma membrane and subjacent distended vesicular profiles. The apical tubules, not connected to the cell surface, consisted of numerous densely stained tubules of small size which contain a compact, finely granulated material. The supranuclear region, in addition to a Golgi apparatus and ER cisternae, contained dilated vacuoles, pale and dense multivesicular bodies, as well as numerous dense granules identified cytochemically as lysosomes. The basal region contained the nucleus and many lipid droplets. The endocytic activity of these cells was investigated using cationic ferritin (CF) and concanavalin-A-ferritin (Con-A-ferritin) as markers of adsorptive endocytosis; and native ferritin (NF), concanavalin-A-ferritin in the presence of alpha-methyl mannoside, and horseradish peroxidase or albumin bound to colloidal gold for demonstrating fluid-phase endocytosis. These tracers were injected separately into the rete testis, and animals were sacrificed at various time intervals after injection. At 1 min, CF or Con-A-ferritin were seen bound to the apical plasma membrane, to the membrane of microvilli, and to the membrane delimiting elements of the tubulovesicular system. Between 2 and 5 min, these tracers accumulated in the densely stained apical tubules and at 15 min in the dilated vacuoles. Between 30 min and 1 hr, the tracers appeared in multivesicular bodies of progressively increasing density, whereas at 2 hr and later time intervals, many dense lysosomal elements became labeled. The tracers for fluid-phase endocytosis showed a distribution similar to that for CF or Con-A-ferritin except that they did not bind to the apical plasma membrane, microvilli, or membrane delimiting the tubulovesicular system. At no time interval were any of the tracers observed in the abluminal spaces. Thus, the nonciliated epithelial cells of the ductuli efferentes are actively involved in fluid-phase and adsorptive endocytosis, both of which result in the sequestration of endocytosed material within the lysosomal apparatus of the cell.

Animals↗

Endocytosis in epithelial cells lining the rete testis of the rat.

The endocytic activity of the low cuboidal cells lining the rete testis was analyzed by electron microscopy following injection of various tracers into the lumen of these anastomotic channels. At 1 and 5 minutes after injection, cationic ferritin (CF) and concanavalin A-ferritin (Con A) were seen bound to the apical plasma membrane and to the membrane of subjacent vesicles or invaginations connected to this apical membrane. At 30 and 60 minutes, these tracers were found in intracytoplasmic vesicles and in vesicles connected to the lateral or basal plasma membrane as well as in the lateral intercellular space and in the lamina lucida of basal lamina. At 30 minutes, CF and Con A also appeared in the matrix of pale multivesicular bodies while at 1 hour dense multivesicular bodies were labeled. At 2 hours and later time intervals, the tracers accumulated in dense granules identified as lysosomes. Native ferritin (NF), concanavalin A-ferritin in presence of alpha-methyl-D-mannoside, and horseradish peroxidase or albumin bound to colloidal gold were all to be incorporated by the lysosomal system of these epithelial cells, as just described for CF and Con A, but these various tracers were not bound to the apical plasma membrane or to the membrane of cytoplasmic vesicles, nor were they found in the intercellular spaces or the lamina lucida at the base of the cells. Thus, the epithelial cells of the rete testis do not appear to be only involved in the uptake of substances from the lumen and their disposal by the lysosomal system, but also appear to contribute to the transport of certain macromolecules from the lumen to the laterobasal surfaces of the cells. These cells may thus play a role in determining the composition of the rete testis fluid.

Albumins↗

Demonstration of fluid-phase endocytosis in epithelial cells of the male reproductive system by means of horseradish peroxidase-colloidal gold complex.

The occurrence of fluid-phase endocytosis in Sertoli cells as well as epithelial cells of the rete testis and ductuli efferentes was demonstrated by use of horseradish peroxidase combined with colloidal gold (HRP-G) as a tracer. The characteristic electron dense spherical colloidal gold particles facilitate the localization of the HRP-G complex in pinocytotic vesicles, multivesicular bodies, and lysosomes of these epithelial cells. With this method, which does not require the use of diaminobenzidine, a clear distinction can be made between peroxidases from endogenous and exogenous origins.

Animals↗

Childhood choroid plexus neoplasms. A study of 14 cases less than 2 years old.

Fourteen children less than 2 years old with choroid plexus papilloma (CPP) were studied. Of these patients nine had the tumor in the lateral ventricles (LV), three in the fourth ventricle (4th V), one in the third ventricle (3rd V) and one in the third and left lateral ventricle (LLV). Ten cases showed benign CPP, three cases malignant CPP, and one case had a venous malformation of the choroid plexus (VMCP). Computed tomography (CT) was the best method for neuroradiological study, although a very small CPP in the 3rd V was not detected in an early study. Malignant and benign CPP can be differentiated with CT, especially if the study is performed with contrast media. Pneumoencephalography must be rejected because it is very dangerous and may be the cause of death in some cases. The follow-up of patients with CPP showed a poor prognosis, even after correctly removing the tumor and inserting a shunt.

Cerebral Ventricle Neoplasms↗

Evolution of Sertoli cell processes invading the cytoplasm of rat spermatids.

Sertoli cell processes invaginating the cytoplasm of rat spermatids were investigated in thin or thick sections stained respectively with ferrocyanide-reduced osmium (Karnovsky, 1971) and the Ur-Pb-Cu metallic impregnation method (Thiéry and Rambourg, 1976). Two types of Sertoli cell processes were observed: Some, seen in steps 11-15 of spermiogenesis, were associated with a tight network of ER cisternae located within the spermatid cytoplasm subjacent to the plasma membrane facing the Seertoli cell process; others, seen from step 11 until the end of spermiogenesis, were not associated with such a spermatid subsurface ER network. Following their formation, the ER-associated Sertoli cell processes were cleaved into double-walled vesicles. Concomitantly, the enclosed Sertoli cell cytoplasm underwent autolysis followed by the dissolution of the Sertoli cell plasma membrane leaving within the spermatid cytoplasm many empty-looking vacuoles delimited only by the plasma membrane of the spermatid. Thereafter, i.e., in steps 15 and 16 of spermiogenesis, these vacuoles clustered, and with the collapse of the vacuoles they gave rise to a single compact mass of interlaced ER cisternae and small vacuoles. With the dissolution of ER cisternae, in step 18, this mass was finally dispersed. These observations suggested that the ER-associated Sertoli cell processes may constitute a pathway for the delivery of material from the Sertoli cells into spermatids. In contrast, the Sertoli cell processes not associated with a network of ER cisternae did not show cleavage or autolysis and appear to be involved mainly in holding the cytoplasm of the spermatid in place.

Acrosome↗

[Seckel's syndrome: a form of chondrodysplasia? (author's transl)].

The true entity of Seckel's (bird headed dwarfism) has been hardly questioned due to the variety of malformations reported in these patients. However all cases reported have in common: dwarfism, bird head, microcephaly, mental retardation and malformations of different kinds. All these features must be present for the correct diagnosis. In two cases of Seckel's syndrome, full diagnostic features and post-mortem findings are reported. Special emphasis is made on the neuropathologic lesions. For the first time in the literature, changes in the epiphyseal tibial cartilage (with histochemical and EM studies) are described and correlated to dwarfism. Based on morphological data the authors propose Seckel syndrome as a condrodysplasia.

Abnormalities, Multiple↗

Cryptic arteriovenous malformation of the choroid plexus of the third ventricle.

A patient with a history of subarachnoid hemorrhage is reported. CT scan evidenced a high-density, round lesion in the anterior part of the third ventricle. A full angiographic study demonstrated no vascular malformation. After removal of a circumscribed hematoma in the anterior part of the third ventricle, an arteriovenous malformation of the choroid plexus was excised.

Adult↗