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Biomedical subjects

J Alvarez

Publications and source records attributed to J Alvarez.

At least 91 records · Page 5Linked to original sources
PubMed1999

Collagenase 3 is a target of Cbfa1, a transcription factor of the runt gene family involved in bone formation.

Collagenase 3 (MMP-13) is a recently identified member of the matrix metalloproteinase (MMP) gene family that is expressed at high levels in diverse human carcinomas and in articular cartilage from arthritic patients. In addition to its expression in pathological conditions, collagenase 3 has been detected in osteoblasts and hypertrophic chondrocytes during fetal ossification. In this work, we have evaluated the possibility that Cbfa1 (core binding factor 1), a transcription factor playing a major role in the expression of osteoblastic specific genes, is involved in the expression of collagenase 3 during bone formation. We have functionally characterized a Cbfa motif present in the promoter region of collagenase 3 gene and demonstrated, by cotransfection experiments and gel mobility shift assays, that this element is involved in the inducibility of the collagenase 3 promoter by Cbfa1 in osteoblastic and chondrocytic cells. Furthermore, overexpression of Cbfa1 in osteoblastic cells unable to produce collagenase 3 leads to the expression of this gene after stimulation with transforming growth factor beta. Finally, we show that mutant mice deficient in Cbfa1, lacking mature osteoblasts but containing hypertrophic chondrocytes which are also a major source of collagenase 3, do not express this protease during fetal development. These results provide in vivo evidence that collagenase 3 is a target of the transcriptional activator Cbfa1 in these cells. On the basis of these transcriptional regulation studies, together with the potent proteolytic activity of collagenase 3 on diverse collagenous and noncollagenous bone and cartilage components, we proposed that this enzyme may play a key role in the process of bone formation and remodeling.

3T3 Cells↗
PubMed1999

Antiglomerular basement membrane antibody-mediated glomerulonephritis after intranasal cocaine use.

We report a case of rapidly progressive glomerulonephritis due to antiglomerular basement membrane (anti-GBM) antibodies that progressed to end-stage renal disease in a 35-year-old man who used intranasal cocaine on an occasional basis. In contrast to many prior reports of acute renal failure occurring with cocaine-associated rhabdomyolysis, this patient did not have any evidence of acute muscle damage and myoglobin release. Circulating anti-GBM antibodies and renal biopsy with linear IgG and C3 deposits confirmed the diagnosis of anti-GBM disease. The possibility of anti-GBM must be considered in the differential diagnosis of acute renal failure in cocaine addicts. This unusual combination raises complex questions regarding the pathogenesis of this type of renal injury.

Acute Kidney Injury↗
PubMed1999

CRABS CLAW and SPATULA, two Arabidopsis genes that control carpel development in parallel with AGAMOUS.

To help understand the process of carpel morphogenesis, the roles of three carpel development genes have been partitioned genetically. Mutants of CRABS CLAW cause the gynoecium to develop into a wider but shorter structure, and the two carpels are unfused at the apex. Mutants of a second gene, SPATULA, show reduced growth of the style, stigma, and septum, and the transmitting tract is absent. Double mutants of crabs claw and spatula with homeotic mutants that develop ectopic carpels demonstrate that CRABS CLAW and SPATULA are necessary for, and inseparable from, carpel development, and that their action is negatively regulated by A and B organ identity genes. The third carpel gene studied, AGAMOUS, encodes C function that has been proposed to fully specify carpel identity. When AGAMOUS function is removed together with the A class gene APETALA2, however, the organs retain many carpelloid properties, suggesting that other genes are also involved. We show here that further mutant disruption of both CRABS CLAW and SPATULA function removes remaining carpelloid properties, revealing that the three genes together are necessary to generate the mature gynoecium. In particular, AGAMOUS is required to specify the identity of the carpel wall and to promote the stylar outgrowth at the apex, CRABS CLAW suppresses radial growth of the developing gynoecium but promotes its longitudinal growth, and SPATULA supports development of the carpel margins and tissues derived from them. The three genes mostly act independently, although there is genetic evidence that CRABS CLAW enhances AGAMOUS and SPATULA function.

AGAMOUS Protein, Arabidopsis↗
PubMed1999

Growth plate cartilage formation and resorption are differentially depressed in growth retarded uremic rats.

To characterize the modifications of growth plate in individuals with growth impairment secondary to chronic renal failure, young rats were made uremic by subtotal nephrectomy (NX) and, after 14 d, their tibial growth plates were studied and compared with those of sham-operated rats fed ad libitum (SAL) or pair-fed with NX (SPF). NX rats were growth retarded and severely uremic. Growth plate height (mean +/- SD) was much greater (P<0.05) in NX (868.4+/-85.4 microm) than SAL (570.1+/-93.5 microm) and SPF (551.9+/-99.7 microm) rats as a result of a higher (P<0.05) hypertrophic zone (661.0+/-89.7 versus 362.8+/-71.6 and 353.0+/-93.9 microm, respectively). The increased size of the growth plate was associated with a greater number of chondrocytes and modifications in their structure, particularly in the hypertrophic zone adjacent to bone. In this zone, chondrocytes of NX animals were significantly (P<0.05) smaller (12080.4+/-1158.3 microm3) and shorter (34.1+/-2.5 microm) than those of SAL (16302.8+/-1483.4 microm3 and 37.8+/-2.0 microm) and SPF (14465.8+/-1521.0 microm3 and 36.3+/-1.8 microm). The interface between the growth plate cartilage and the metaphyseal bone appeared markedly irregular in NX rats. Kinetics of chondrocytes was also modified (P<0.05) in the NX rats, which had lower cell turnover per column per day (5.4+/-0.9), longer duration of hypertrophic phase (89.0+/-15.2 h), and reduced cellular advance velocity (7.4+/-2.2 microm/h) compared with SAL (8.0+/-1.6, 32.1+/-6.7 h, and 11.3+/-2.7 microm/h) and SPF (7.2+/-1.1, 34.8+/-5.1 h, and 10.1+/-2.5 microm/h). Cell proliferation was no different among the three groups. Because the growth plates of SPF and SAL rats were substantially not different, modifications observed in the NX rats cannot be attributed to the nutritional deficit associated with renal failure. These findings indicate that chronic renal failure depresses both the activity of the growth plate cartilage by altering chondrocyte hypertrophy and the replacement of cartilage by bone at the metaphyseal end. The two processes are differentially depressed since cartilage resorption is more severely lowered than cartilage enlargement and this leads to an accumulation of cartilage at the hypertrophic zone.

Animals↗
PubMed1999

[Obstetric anesthesia/analgesia in Spain. Study notes on its historical evolution during the 1st half of this century].

This historical review of obstetric analgesia-anesthesia in Spain covers the first half of the twentieth century. Following usual practice for researching medical history, we have performed an exhaustive review of Spanish medical literature published during the study period, followed by classification, study and critical analysis. We found that the first half of the century saw considerable change in the application of analgesic-anesthetic techniques for childbirth and obstetric procedures, indicating that practitioners were far from apathetic as had been obstetricians of the second half of the nineteenth century, who generally rejected any type of analgesia for use during labor and birth. The numerous techniques in vogue during that period under study are described, although analgesia-anesthesia by inhaled ether and chloroform was undoubtedly the most widely used by obstetricians until well into the 1950's.

Analgesia, Obstetrical↗
PubMed1998

Peripheral axons of Wlds mice, which regenerate after a delay of several weeks, do so readily when transcription is inhibited in the distal stump.

We have raised the hypothesis that differentiated Schwann cells repress regrowth of axons but become permissive upon dedifferentiation. WId(S) mouse is a strain in which severed peripheral nerves do not degenerate for several weeks, and axonal regeneration does not occur either [5,11]. In this strain, we studied the role of resident cells upon axonal regeneration by inhibiting transcription. Regeneration was assessed with the pinch test, electron microscopy and Dil (a fluorescent lipid soluble dye). After a crush, WId(S) axons did not regenerate but they did so when the crush was made through a nerve segment treated with actinomycin D (ActD), an inhibitor of transcription. In contrast, when the crush was made distal to the treated segment no regeneration ensued. Our results support the notion that normal resident cells of peripheral nerves repress axonal growth.

Animals↗
PubMed1998

Regenerating axons of the rat require a local source of proteins.

Regenerating axons need proteins to grow and we explored whether a local supply is necessary. Crushed peroneal nerves were entubulated with silicone sleeves, plain or loaded with cycloheximide (CHX); some nerves were frozen to kill resident cells. When a plain sleeve was placed distal to the crush, axons regrew 5.0 mm in 3 days (pinch test), and 4.6 mm when the sleeve was placed around a frozen nerve (n.s). CHX administered distal to the crush reduced the elongation by approximately 58% (P < 0.01) in unfrozen or frozen nerves whilst its administration central to the crush was ineffectual. Immunostaining of nerves with GAP-43 gave similar values. Under the electron microscope, axonal sprouts were less frequent when CHX was used irrespective of the cellular or acellular condition of the nerve. Therefore, an inhibitor of protein synthesis reduces axonal regrowth, an effect mediated neither by parent neurones nor by resident cells. We propose that axons synthesize proteins.

Animals↗
PubMed1998

Cerebrospinal fluid of HTLV-1 associated myelopathy patients induces axonal sproutings and Schwann cell proliferation in the rat sciatic nerve.

HTLV-1 (human T-cell leukemia virus type I) associated myelopathy (HAM) is a demyelinating disease. We showed that the CSF of patients and heated CSF of normal subjects induce a segmentary demyelination in rat nerves, and potentiate trypsin in vitro. Here we further characterize the neuropathy induced by the CSF of patients. Peroneal nerves injected 5-8 days before with native or heated CSF of patients, besides extensive demyelination, presented proliferation of myelinating and nonmyelinating Schwann cells, axonal sprouting, fine fibres with a few turns of myelin, disarray of nonmedullated bundles, desmosome-like junctions, and coated pits and vesicles in Schwann cells and axons. The normal CSF was innocuous to the nerve in its native form, but after heating, it induced a neuropathy in all, similar to that elicited by the CSF of patients. Our findings indicate that the CSF of HAM patients contains a thermostable pathogen for nerves of the rat; a thermostable pathogen also occurs in the normal CSF although its activity is checked by endogenous thermolabile factors. We suggest that the pathogen present in the CSF of HAM patients participates in the disease.

Animals↗
PubMed1998

Early complete recanalization in internal carotid artery embolism treated with high-dose t-PA: a sequential angiographic study in a novel model of embolism in rats.

Complete early recanalization rate of human internal carotid artery embolic occlusion treated with thrombolytic drugs is low. To study factors related with this difficulty to recanalize we have developed a novel model of rat ica embolism using a fragment of human embolus. In 50 male Wistar rats the ica was embolized through the external carotid artery with a fragment of an embolus obtained from a human embolectomy passed through a catheter of 0.8 mm diameter. Recanalization was assessed by sequential angiograms from 15 to 120 min after embolization. Reperfusion was classified according to TIMI grades. Emboli of either 1 (group 1) or 2 mm (group 2) in length were cut. In group 1, four groups of nine animals each were treated, 15 min after embolization, with i.v. t-PA at doses of 1 mg/kg, 10 mg/kg and 20 mg/kg or saline. In group 2 there was one control group of seven animals treated with saline and another of seven animals treated with 10 mg/kg t-PA. Complete recanalization (TIMI grade 3) within the first 30 min was present in two animals treated with 10 and 20 mg/kg. Complete recanalization within the first 60 min was present in 0% of controls and animals treated with 1 mg/kg and in 44% of the 10 and 20 mg/kg groups (P<0.05 in chi-square test). Incomplete recanalization (TIMI grades 0, 1 and 2) occurred in 33%. In group 2 total recanalization occurred in 1/7 controls and in 3/7 animals receiving 10 mg/kg of t-PA. Early (60 min) complete i.v. t-PA induced internal carotid artery embolic recanalization is low with standard doses and increases moderately when high doses are used. Further increases in the dose do not improve recanalization rate, which is not clearly influenced by embolus size. Complete recanalization within 30 min, the period after which infarction develops in the rat, is uncommon in our model.

Angiography↗
PubMed1998

Collagenase-3 (MMP-13) expression in chondrosarcoma cells and its regulation by basic fibroblast growth factor.

Human collagenase-3 (MMP-13) is a member of the matrix metalloproteinase family of enzymes that was originally identified in breast carcinomas and subsequently detected during fetal ossification and in arthritic processes. In this work, we have found that collagenase-3 is produced by HCS-2/8 human chondrosarcoma cells. An analysis of the ability of different cytokines and growth factors to induce the expression of collagenase-3 in these cells revealed that basic fibroblast growth factor (bFGF or FGF-2) strongly up-regulated the expression of this gene. By contrast, other factors, including interleukin-1beta and transforming growth factor-beta, previously found to induce collagenase-3 expression in other cell types, did not exhibit any effect on the expression of this gene in chondrosarcoma cells. Further analysis of the bFGF-induced expression of collagenase-3 in human chondrosarcoma cells revealed that its effect was time and dose dependent, but independent of the de novo synthesis of proteins. Western blot analysis revealed that the up-regulatory effect of bFGF on collagenase-3 was also reflected at the protein level as demonstrated by the increase of immunoreactive protein in the conditioned medium of HCS-2/8 cells treated with bFGF. Immunohistochemical analysis of the presence of collagenase-3 in a series of 8 benign and 16 malignant cartilage-forming neoplasms revealed that all analyzed malignant chondrosarcomas stained positively for collagenase-3, whereas only 2 of 8 benign lesions produced this protease. In addition, the finding that bFGF was detected in all analyzed chondrosarcomas, together with the above in vitro studies on HCS-2/8 cells, suggest that this growth factor may be an in vivo modulator of collagenase-3 expression in these malignant tumors. These results extend the pattern of tumor types with ability to produce this matrix metalloproteinase and suggest that collagenase-3 upregulation may contribute to the progression of human chondrosarcomas.

Adolescent↗
PubMed1998

Functional measurements of [Ca2+] in the endoplasmic reticulum using a herpes virus to deliver targeted aequorin.

Changes in the free calcium concentration of the endoplasmic reticulum ([Ca2+]er) play a central role controlling cellular functions like contraction, secretion or neuronal signaling. We recently reported that recombinant aequorin targeted to the endoplasmic reticulum (ER) [Montero M., Brini M., Marsault R. et al. Monitoring dynamic changes in free Ca2+ concentration in the endoplasmic reticulum of intact cells. EMBO J 1995; 14: 5467-5475, Montero M., Barrero M.J., Alvarez J. [Ca2+] microdomains control agonist-induced Ca2+ release in intact cells. FASEB J 1997; 11: 881-886] can be used to monitor selectively [Ca2+]er in intact HeLa cells. Here we have used a herpes simplex virus type 1 (HSV-1) based system to deliver targeted aequorin into a number of different cell types including both postmitotic primary cells (anterior pituitary cells, chromaffin cells and cerebellar neurons) and cell lines (HeLa, NIH3T3, GH3 and PC12 cells). Functional studies showed that the steady state lumenal [Ca2+]er ranged from around 300 microM in granule cells to 800 microM in GH3 cells. InsP3-coupled receptor stimulation with agonists like histamine (in HeLa, NIH3T3 and chromaffin cells), UTP and bradykinin (in PC12 cells) or thyrotropin-releasing hormone (TRH, in GH3 cells) produced a very rapid decrease in lumenal [Ca2+]er. Caffeine caused a rapid Ca2+ depletion of the ER in chromaffin cells, but not in the other cell types. Depolarization by high K+ produced an immediate and reversible increase of [Ca2+]er in all the excitable cells (anterior pituitary, GH3, chromaffin cells and granule neurons). We conclude that delivery of recombinant aequorin to the ER using HSV amplicon provides the first direct quantitative and dynamic measurements of [Ca2+]er in several primary non-dividing cells.

Aequorin↗
PubMed1998

[Pheochromocytoma and cardiac insufficiency].

Catecholamine-induced cardiomyopathy is a rare complication of pheochromocytoma. We present a case of pheochromocytoma that developed preoperative heart failure. Left ventricular dilation and severe hypokinesia were demonstrated by echocardiography. Heart failure was successfully treated with digitalis, diuretics and captopril. There were no surgical complications and the follow up showed and improvement on the systolic function evaluated by echocardiography and isotope ventriculography, 3 and 6 months after surgery. We review the pathophysiology and evolution of catecholamine induced cardiomyopathy. Preload reserve can be one of the adaptive mechanisms of the ventricle in catecholamine-induced cardiomyopathy. Conventional therapy of hypertension and heart failure can be effective to correct the symptoms of cardiac dysfunction.

Adrenal Gland Neoplasms↗
PubMed1998

[Transesophageal echocardiography follow-up of patients operated on using the Bono-Bentall technique in aneurysms or dissection of the ascending aorta].

INTRODUCTION: Increasingly patients are surviving after reconstructive surgery of the ascending aorta. These patients require follow-up to detect postoperative prognostic markers, such as persistence of the flow in a false lumen, intimal rupture, or graft complications. We conducted a study with transthoracic and transesophageal echocardiography in order to detect residual abnormalities and establish the usefulness of this technique in a group of patients after Bono-Bentall surgery for ascending aorta pathology. PATIENTS AND METHODS: Twelve patients were studied with transthoracic and transesophageal echocardiography, four after surgery for annulo-aortic ectasia with severe aortic insufficiency and eight for type A aortic dissection. The Bono-Bentall surgical procedure was used in all the patients with Cabrol's modification being added in three. RESULTS: Seven of the eight (87%) patients with aortic dissection had residual abnormalities: five persistence of the distal dissection, one pseudo-aneurysm, and one peritubular haematoma. A residual lesion (pseudo-aneurysm) was found in just one of the four patients (25%) who underwent surgery for annulo-aortic ectasia. The ejection fraction was normal in those patients who had been operated on for aortic dissection and depressed in those who had annulo-aortic ectasia (60 +/- 9 vs 40 +/- 10; p = 0.005). CONCLUSIONS: In patients undergoing surgery with the Bono-Bentall procedure there is a high incidence of residual aortic abnormalities, especially when the operation is for aortic dissection. Transesophageal echocardiography is an ideal diagnostic method for the detection and follow up of residual abnormalities after ascending aorta surgery. We believe this technique should be included in the periodic follow up of these patients.

Adult↗
PubMed1998

[Dehiscence of a composite aortic graft (Bono and Bentall technique) secondary to Acinetobacter endocarditis].

Acinetobacter sp. are gram-negative bacteria and usually resistant to multiple antibiotics. They are a customary cause of nosocomial infections, but are uncommon etiologic agents of endocarditis. We present a case of endocarditis caused by Acinetobacter iwoffi in a composite aortic graft with a St. Jude prosthetic valve, using the Bono and Bentall procedure, complicated with multiple graft dehiscenses causing first a peritube pseudoaneurysm and finally severe paraprosthetic valve regurgitation to the left ventricle which required emergency surgery.

Acinetobacter Infections↗
PubMed1998

[Angina caused by subclavian-coronary steal in patients revascularized with internal mammary artery].

After coronary bypass surgery in the left internal mammary artery, occlusive atherosclerosis in the proximal subclavian artery can produce reverse flow in the mammary artery and myocardial ischemia (coronary-subclavian steal syndrome). This is a rare cause of recurrent myocardial ischemia. We present two patients with postoperative complete obstruction in the proximal subclavian artery and inverse flow in the mammary artery producing severe ischemia in the left anterior descending artery territory. Both patients were treated with subclavian-subclavian bypass, which in one patient was ineffective in producing an adequate anterograde flow in the left internal mammary artery. We review clinical management, diagnostic methods and therapeutic options used in the coronary-subclavian steal syndrome.

Aged↗