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Biomedical subjects

R Madrid

Publications and source records attributed to R Madrid.

At least 19 recordsLinked to original sources
PubMed2001

Polarized trafficking and surface expression of the AQP4 water channel are coordinated by serial and regulated interactions with different clathrin-adaptor complexes.

Aquaporin 4 (AQP4) is the predominant water channel in the brain. It is targeted to specific membrane domains of astrocytes and plays a crucial role in cerebral water balance in response to brain edema formation. AQP4 is also specifically expressed in the basolateral membranes of epithelial cells. However, the molecular mechanisms involved in its polarized targeting and membrane trafficking remain largely unknown. Here, we show that two independent C-terminal signals determine AQP4 basolateral membrane targeting in epithelial MDCK cells. One signal involves a tyrosine-based motif; the other is encoded by a di-leucine-like motif. We found that the tyrosine-based basolateral sorting signal also determines AQP4 clathrin-dependent endocytosis through direct interaction with the mu subunit of AP2 adaptor complex. Once endocytosed, a regulated switch in mu subunit interaction changes AP2 adaptor association to AP3. We found that the stress-induced kinase casein kinase (CK)II phosphorylates the Ser276 immediately preceding the tyrosine motif, increasing AQP4-mu 3A interaction and enhancing AQP4-lysosomal targeting and degradation. AQP4 phosphorylation by CKII may thus provide a mechanism that regulates AQP4 cell surface expression.

Amino Acid Sequence↗
PubMed2000

Individual functions of the HAK and TRK potassium transporters of Schwanniomyces occidentalis.

We have cloned the gene encoding the TRK transporter of the soil yeast Schwanniomyces occidentalis and obtained the HAK1 trk1 delta and the hak1 delta TRK1 mutant strains. Analyses of the transport capacities of these mutants have shown that (i) the HAK1 and the TRK1 potassium transporters are the only transporters operating at low and medium K+ concentrations (< 1 mM); (ii) the HAK1 transporter is functional at low pH but fails at high pH; and (iii) the TRK1 transporter functions at neutral and high pH and fails at low pH. At neutral pH, both transporters are functional, but HAK1 is not expressed, except at very low K+ concentrations (< 50 microM) where HAK1 is very effective. TRK1 is also involved in the control of the membrane potential.

Amino Acid Sequence↗
PubMed1998

Ectopic potassium uptake in trk1 trk2 mutants of Saccharomyces cerevisiae correlates with a highly hyperpolarized membrane potential.

Null trk1 trk2 mutants of Saccharomyces cerevisiae exhibit a low-affinity uptake of K+ and Rb+. We show that this low-affinity Rb+ uptake is mediated by several independent transporters, and that trk1Delta cells and especially trk1Delta trk2Delta cells are highly hyperpolarized. Differences in the membrane potentials were assessed for sensitivity to hygromycin B and by flow cytometric analyses of cellular DiOC6(3) fluorescence. On the basis of the latter analyses, it is proposed that Trk1p and Trk2p are involved in the control of the membrane potential, preventing excessive hyperpolarizations. K+ starvation and nitrogen starvation hyperpolarize both TRK1 TRK2 and trk1Delta trk2Delta cells, thus suggesting that other proteins, in addition to Trk1p and Trk2p, participate in the control of the membrane potential. The HAK1 K+ transporter from Schwanniomyces occidentalis suppresses the K+-defective transport of trk1Delta trk2Delta cells but not the high hyperpolarization, and the HKT1 K+ transporter from wheat suppresses both defects, in the presence of Na+. We discuss the mechanism involved in the control of the membrane potential by Trk1p and Trk2p and the causal relationship between the high membrane potential (negative inside) of trk1Delta trk2Delta cells and its ectopic transport of alkali cations.

Biological Transport↗
PubMed1997

Calcium mediates the activation of the inhibitory current induced by odorants in toad olfactory receptor neurons.

In toad olfactory neurons, a putrid odorant mixture inducing inhibitory responses increases Ca2+-activated K+ conductance, developing a hyperpolarizing receptor potential. Removal of extracellular Ca2+ or exposure to nifedipine reversibly reduced the inhibitory response, suggesting that odorants induce a Ca2+ influx. We show evidence for an odorant-induced Ca2+ current. Using confocal microscopy, it is shown that odorants induce a nifedipine-sensitive elevation of Ca2+ in the apical end of the cell. These results suggest an inhibitory mechanism in which an apical Ca2+ influx causes an increase in internal Ca2+, opening Ca2+-activated K2+ channels that lead to membrane hyperpolarization.

Animals↗
PubMed1997

Acceleration of the maturation of oligodendroblasts into oligodendrocytes and enhancement of their myelinogenic properties by a chemically defined medium.

Because of the importance of oligodendrocytes (OL) in forming and maintaining myelin in the CNS and the fact that the remyelination in the CNS is very limited in contrast to the peripheral nervous system, we investigated the effect of a chemically defined medium OLDEM, previously characterized by the maintenance of mature myelinating OL, on oligodendroblasts (or OL progenitors) in culture. The effect of each component of this medium as well as different combinations of them were also examined. Cultures were examined at different developmental stages immunocytochemically for developmental markers, such as transferrin, sulfatides, myelin basic protein and proteolipid protein. OLDEM accelerated the appearance of developmental markers and concomitant morphological changes. Furthermore, myelin-specific enzymes such as glycerophosphorylcholine phosphodiesterase; p-nitro-phenolphosphocholine phosphodiesterase; 2'3'-cyclic nucleotide 3'-phosphodiesterase and UDP galactose: ceramide galactosyltransferase had enzymatic activities similar to values found in pure myelin, indicating that OLDEM allows the optimal expression of myelin-related genes. The effect of each OLDEM constituent was evaluated by immunocytochemistry and by measurement of enzymatic activities. With each single additive or multiple combinations, oligodendrocytes displayed different degrees of maturation. Deletion of selenium, glucose, and galactose severely affected cell survival as well as enzymes expression in young cultures. However, older cultures were more resistant to these deletions. Putrescine and insulin did not cause such effects on survival, but their absence affected cell maturation. None of the OLDEM additives individually supported survival and/or maturation. Enzyme assays performed on isolated myelin-like membranes or the cells soma revealed a redistribution of the activity between these fractions as the cell matured. The biological role of each of these constituents on the maturation of the oligodendroglial cells is discussed. These observations indicate that OLDEM constituents have a powerful effect on OL progenitor maturation, and membrane formation. This medium will be used for investigating the remyelination potential of adult OL progenitors.

Animals↗
PubMed1996

Coronary fistula associated with double mitral valve disease. A case report.

The authors report a case of a 54-year-old white male with a coronary fistula associated with double mitral valve disease. The patient was studied by invasive and non-invasive cardiac methods including coronary angiogram in order to reach the correct diagnosis and to define the successful surgical treatment that included the closure of the fistula, partial resection of the left atrium and insertion of a mechanical mitral valve prosthesis. It is concluded that this case represents a very rare association between coronary fistula and double mitral valve disease.

Atrial Fibrillation↗
PubMed1995

Physiological changes in antioxidant defences in fetal and neonatal rat liver.

This study describes the physiological changes in the activities of the hepatic antioxidant enzymes superoxide dismutase isoenzymes (Cu/Zn-and Mn-superoxide dismutase) and catalase, in the glutathione content and in the lipid peroxidation levels in fetal (20 and 21 days of gestation) and neonatal rat liver (Days 1, 8, 15, and 22 post partum). The catalase and superoxide dismutase activities decreased before birth and increased after birth. The oxidized:reduced glutathione (GSSG:GSH) ratio declined before birth, but it increased between Days 1 and 15 post partum and then remained stable. Finally, newborn rat liver from the 1st day of life shows the highest susceptibility to lipid peroxidation. These results suggest that the changes in antioxidant defences could be related mainly to the beginning of diet intake after birth, which entails a higher hepatic metabolism rate, as well as a higher oxygen consumption.

Animals↗
PubMed1995

Silent giant left atrium. A case report.

A sixty-two-year-old white woman with a 14.5 cm (145 mm) silent giant left atrial enlargement secondary probably to rheumatic heart disease is presented. Aside from mild progressive shortness of breath during the past year, the patient had been asymptomatic all her life. Her clinical picture was manifested for the first time by syncope secondary to slow atrial fibrillation, for which a permanent pacemaker was required. The correct diagnosis of the enlarged chamber was not possible through the routine chest roentgenogram. In this case, the echocardiogram, nuclear angiogram, and computed tomography were the pertinent studies needed to reach the diagnosis.

Cardiomegaly↗
PubMed1991

False aneurysm of the left ventricle due to a penetrating chest wound.

A 24-year-old white man had a knife chest wound, and four months after this event, manifested progressive dyspnea. A false aneurysm of the left ventricle was diagnosed by 2D echocardiogram. Surgical resection of the aneurysmal sac with closure of the orifice of the lateral wall of the left ventricle was performed successfully.

Echocardiography↗
PubMed1984

Rapid identification of Trypanosoma cruzi isolates by 'dot-spot' hybridization.

The presence of isolate-specific Trypanosoma cruzi minicircles has been shown in the kinetoplast DNA of this parasite. This led to the rapid identification of isolates and clones of trypanosomes by means of 'dot-spot' hybridizations with molecularly cloned minicircle probes. Unexpectedly, whole kDNAs were also suitable as probes for this purpose, provided that filters were washed under stringent conditions. This was attributed to the presence of the above-mentioned isolate-specific minicircle sequences. The fact that parasites could be directly spotted onto nitrocellulose filters simplified the rapid routine screening of a large number of samples.

Animals↗
PubMed1978

The peroneal muscular atrophy syndrome: clinical, genetic, electrophysiological and nerve biopsy studies. I. Clinical, genetic and electrophysiological findings and classification.

1. A clinical, genetic, electrophysiological and nerve biopsy study of 49 index cases with peroneal muscular atrophy is reported. 2. In dominantly inherited cases, motor conduction velocities of the upper limbs within kinships indicated segregation into five groups which we have termed: a) hypertrophic neuropathy (less than 25 m/sec); b) intermediate group (25-45 m/sec); c) neuronal sensorimotor neuropathy (greater than 45 m/sec); d) neuronal motor neuropathy (greater than 45 m/sec); e) neuronal motor neuropathy with upper motor neurone involvement (greater than 45 m/sec). 3. The intermediate group is distinguished from the hypertrophic neuropathy group by the absence of clinically observed nerve hypertrophy and by the presence of a number of clinical features, including a more rapidly progressive disease. It is concluded to be genetically separate. This group is similarly quite distinct from the neuronal groups. Nerve biopsy studies support this view (Madrid et al., 1977; Bradley et al., 1977). 4. There was a relationship between severity of the disease and the conduction velocity which was most evident in the intermediate group. 5. There appeared to be an increase in motor conduction velocity with age in the hypertrophic neuropathy group, while the velocity fell in older patients in the intermediate group. 6. Sensory conduction velocity generally paralleled motor velocity but showed relatively less reduction. 7. Upper motor neurone features were not uncommon, appearing particularly in the intermediate group. Their presence may not therefore be a reliable basis for the classification of cases of peroneal muscular atrophy. 8. Tremor was observed in the hypertrophic, intermediate and neuronal motor neuropathy groups of patients, and does not provide a useful criterion for the classification of peroneal muscular atrophy. 9. There was occasional evidence to suggest poor or abnormal expression of the gene in dominantly inherited cases. Until more specific markers are available sporadic cases should be classified on the basis of the dominant forms, though they show a greater variability.

England↗
PubMed1977

The peroneal muscular atrophy syndrome. Clinical, genetic, electrophysiological and nerve biopsy studies. Part 2. Observations on pathological changes in sural nerve biopsies.

The light-and electron-microscopic, single teased nerve and morphometric studies of a series of 17 sural nerve biopsies from patients with personeal muscular atrophy are presented. The cases are divided into the following groups according to the criteria of Davis, Bradley and Madrid (1977): Hypertrophic Neuropathy Group; Intermediate Group; Neuronal Sensorimotor Group; Neuronal Motor Group. The Hypertrophic Neuropathy Group had nerve hypertrophy and marked segmental demyelination and onion bulb formation. The Intermediate Group also had segmental demyelilination and onion bulb formation, but nerve hypertrophy was not seen, and axonal degeneration and regeneration were prominent. The Neuronal Sensorimotor Group cases were all sporadic, and showed some onion bulbs, paranodal demyelination and evidence of axonal degeneration and regeneration. The sensory nerve biopsy in the Neuronal Motor Group showed no major abnormality apart from some cluster formation indicating axonal regeneration. The data tend to support the classification of peroneal muscular atrophy proposed by Davis et al. (1977), though there was overlap between the groups in individual pathological parameters.

Adolescent↗
PubMed1977

The peroneal muscular atrophy syndrome. Clinical genetic, electrophysiological and nerve biopsy studies. Part 3. Clinical, electrophysiological and pathological correlations.

This report analyses correlations between clinical, electrophysiological and pathological data derived from a series of families with peroneal muscular atrophy. It was found that the observed differences between families in median nerve forearm motor conduction velocity were unlikely to be due to differences in the age or severity of the cases. Similarly it it was unlikely that the pathological differences between cases were due to age or severity of the case. The conduction velocity in the Hypertrophic Neuropathy Group tended to increase slightly with age, while that in other cases tended to fall slightly. The conduction velocity and total myelinated fibre counts were inversely related to the degree of segmental demyelination. The Hypertrophic Neuropathy Group and the Intermediate Group of cases were found to behave differently in a number of correlative analyses, thus supporting the suggestion that they represent different disease entities.

Adolescent↗
PubMed1975

Recurrent brachial plexus neuropathy.

The clinical, electrophysiological and pathological changes in 3 patients with recurrent attacks of non-traumatic brachial plexus neuropathy have been described. Two had recurrent attacks and a dominant family history of similar attacks, together with evidence of lesser degrees of nerve involvement outside the brachial plexus. In one patient the attacks were moderately painful, while in the other there was little or no pain. Only one showed undue slowing of motor nerve conduction during ischaemia, but in both cases the sural nerves had the changes of tomaculous neuropathy, with many sausage-shaped swellings of the myelin sheaths, and extensive segmental demyelination and remyelination. The third patient had two attacks of acute brachial plexus neuropathy which were both extremely painful. The clinical features were compatible with a diagnosis of neuralgic amuotrophy. In the second attack, there was vagus nerve involvement and the sural nerve showed evidence of healed extensive segmental demyelination. The various syndromes presenting with acute non-traumatic brachial plexus neuropathy are reviewed, and a tentative nonsological classification advanced. Most patients fall into the category of acute, painful paralysis with amyotrophy, with no family history and no evidence of lesions outside the brachial plexus. It is suggested that the term "neuralgic amyotrophy" be restricted to this group. Patients with features outside this clinical picture probably suffer from other disease entities presenting with brachial plexus neuropathy. The familial cases constitute one or more aetioliogical subgroups, differing from neuralgic amyotrophy in the frequency of recurrences, the relative freedom from pain in the attacks, the frequency of nerve lesions outside the brachial plexus, and of hypotelorism. Individual attacks of acute brachial plexus neuropathy, however, may be identical in patients with the different diseases, and further pathological and biochemical studies are awaited to aid in nosology.

Acute Disease↗