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Biomedical subjects

L Alvarez

Publications and source records attributed to L Alvarez.

At least 109 records · Page 6Linked to original sources
PubMed1998

The subthalamic nucleus and tremor in Parkinson's disease.

The role of the subthalamic nucleus (STN) in the origin of parkinsonian tremor is discussed. Previous studies in monkeys made parkinsonian by MPTP (1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine) administration suggested a direct participation of the STN in the pathophysiology of tremor. We recorded tremor-related activity in the STN in 12 patients with Parkinson's disease (PD) and found that microstimulation of the sensorimotor region of the nucleus, where these neurons are present, stopped the tremor with a very short latency. Long-term treatment by means of bilateral deep-brain stimulation (DBS) in the same 12 patients led to a significant reduction of tremor as well as other cardinal features of PD. This effect was blindly assessed at 3 months after implantation. In another group of seven patients, a unilateral lesion of the STN was performed. Both postural and resting tremor were significantly improved on the limbs contralateral to the lesion side. In three patients, tremor disappeared completely after 12 months of follow up. The electrophysiologic data and therapeutic effect of inactivating the STN strongly indicated that this structure is directly involved in the origin of parkinsonian tremor, as suggested by the MPTP model.

Adult↗
PubMed1998

Electrophysiologic assessment of calcium channel blockers in transplanted hearts: an experimental study.

The effects of calcium channel blockers on automaticity, conduction, and refractoriness were studied in a model of heterotopic heart transplantation in dogs, which combined an innervated heart (recipient) and a denervated one (donor). Following the surgical procedure, 0.2 mg/kg verapamil (n = 10), 0.15 mg/kg diltiazem (n = 10), or 5 microg/kg + 30 microg/kg/h nifedipine (n = 10) was administered intravenously. In basal situation and after drug administration, each heart was assessed for AV interval, cycle length, sinoatrial conduction time, atrioventricular node antegrade block point, and atrioventricular node and ventricular refractory periods; electrocardiographic PR and QT intervals and QRS complexes; systemic arterial, pulmonary artery, central venous, and pulmonary capillary wedge pressures; and cardiac output. The depressor effects of these calcium channel blockers on automaticity, refractoriness, and conduction were more intense in the transplanted hearts, very possibly because of the absence of adrenergic reflexes mediated by the autonomic nervous system; in particular, verapamil produced a great depression of sinus automaticity in a large number of cases.

Animals↗
PubMed1998

Characterization of a new human embryonal rhabdomyosarcoma cell line, RMS-GR.

A human tumor cell line designated RMS-GR was established from an embryonal rhabdomyosarcoma. The monolayer cells were polygonal, round or spindle-shaped. The RMS-GR cell line became stable with a doubling time of 42 h. Tumorigenicity of the cells was confirmed by heterotransplantion into nude mice. Electron microscopic images showed typical cytoplasmic inclusion of aggregated intermediate filaments and myofibril-like thin filaments. The expression of desmin, vimentin, actin and human myoglobin was recognized by cytofluorometric analyses, and a large fraction of CK-MM and small fractions of CK-BB and MCK-1 isoenzymes were found. Chromosomal analysis showed that the modal chromosome number was consistently near triploid with structural abnormalities mostly involving chromosomes 1, 3 and 8, and additional unidentified markers. No alteration of chromosome 2 was observed. The RMS-GR cell line may provide a system to identify genes which are involved in the pathogenic mechanism of rhabdomyosarcomas, and to investigate the modulation of myogenic differentiation.

Actins↗
PubMed1998

Epilepsy surgery in the first three years of life.

PURPOSE: Partial seizures in early postnatal life may be catastrophic and associated with poor long-term outcome. Epilepsy surgery can alleviate partial seizures in older children and adults, but there is little experience with surgical therapy in infancy apart from hemispheric epilepsy syndromes. METHODS: We analyzed the results of cortical resection to treat medically refractory partial epilepsy in 31 children (16 boys, 15 girls) aged <3 years (mean, 18.3 months). Subjects were included only if seizure relief was the primary indication for surgery. RESULTS: Follow-up of at least 1 year (mean, 4.6 years) in 26 patients revealed that 16 were seizure-free, 4 had >90% seizure reduction, and 6 had <90% reduction. There was no significant difference in seizure outcome between hemispherectomy/multilobar resections and lobar resections or temporal versus extratemporal resection. Seizure outcome was independent of the amount of cortex removed in nonlesional patients. Only the presence of a discrete lesion on preoperative neuroimaging correlated with a favorable outcome. Family perceptions of accelerated development in seizure-free patients were not confirmed on developmental assessment. CONCLUSIONS: We conclude that cortical resection often benefits very young children with catastrophic partial seizures, but does not guarantee enhanced neurological development. The location and extent of the excised cortex may not be critical as long as the entire epileptogenic region and lesion are removed.

Adult↗
PubMed1998

Collagen-related markers of bone turnover reflect the severity of liver fibrosis in patients with primary biliary cirrhosis.

The influence of a nonskeletal disease with increased connective tissue synthesis or degradation in the collagen-related markers of bone turnover has been evaluated in 34 women with primary biliary cirrhosis (PBC; age range 41-81 years), a disease with increased hepatic fibrosis, often associated with osteoporosis. Serum osteocalcin (BGP), and carboxy-terminal (PICP) and amino-terminal (PINP) propeptides of type I collagen were assessed as indexes of bone formation, whereas serum tartrate-resistant acid phosphatase (TRAP), and cross-linked carboxy-terminal telopeptide of type I collagen (ICTP), and urinary hydroxyproline (HYP), pyridinoline (PYR), deoxypyridinoline (DPYR), and type I collagen cross-linked N- (NTX) and C-telopeptide (CTX) were measured as markers of bone resorption. The histologic stage of the disease and serum amino-terminal propeptide of type III collagen (PIIINP) as an index of liver fibrogenesis were also evaluated. BGP levels were significantly lower, whereas PICP and PINP levels were higher in patients than in controls. Among the bone resorption markers, serum ICTP and urinary PYR, DPYR, HYP, NTX, and CTX levels were significantly higher in patients than in controls. Serum PIIINP levels were also increased in PBC patients. BGP did not correlate with PICP and PINP, but these markers of bone formation as well as ICTP, PYR, DPYR, and NTX correlated with serum PIIINP levels. Serum TRAP did not correlate with collagen-related markers of bone resorption. Moreover, patients with PIIINP and bilirubin above normal levels had higher PICP, PINP, ICTP PYR, DPYR, CTX, and NTX. These markers correlated with the histologic stage of the disease, but not with osteopenia measured by densitometric procedures in 22 patients. In conclusion, collagen-related markers of bone turnover do not reflect bone remodeling in PBC. The close association of these markers with PIIINP and the clinical and histologic stage of the liver disease suggests that they are influenced by liver collagen metabolism.

Acid Phosphatase↗
PubMed1998

Cape Town solution in prolonged myocardial preservation: structural and ultrastructural study.

This study deals with myocardial preservation after 24 hours of continuous, hypothermic and oxygenated perfusion with Cape Town (CT) solution, focusing on the morphological changes produced by preservation and reperfusion, and their possible relationship to the composition of the solution and the immediate hemodynamic findings after orthotopic heart transplantation in dogs. After preservation, aside from mild or moderate mitochondrial changes, the most relevant lesions included edema and vasoconstriction. Reperfusion was followed by the development of areas of necrosis forming contraction bands and an increment in the mitochondrial damage; the intercalated disks conserved their normal structure; edema became more prominent and was invariably accompanied by hemorrhage; vasoconstriction was very pronounced and was accompanied on occasion by evidence of capillary rupture; and inflammatory cells were observed in the interstitium. These results indicate that colloid must be added to Cape Town solution and that reperfusion probably requires selective approaches to deal with vasoconstriction and inflammation.

Animals↗
PubMed1998

[Coronary revascularization surgery with arterial grafts].

Coronary artery revascularization surgery is well established procedure throughout the world. The benefits are based on the blood perfusion through the implanted grafts distal to the coronary occlusions and continue as long as the grafts remains patent. The immediate success of this procedure is related to the surgical technique and the anatomical characteristics of the grafted coronary arteries. However, the long term results are mainly dependent on the type of grafts used. The modern era of myocardial revascularization started in the sixties with the use of saphenous vein grafts by Johnson and Favaloro. Alternative vascular conduits to the saphenous vein have been tried, and the internal mammary artery has become the first choice. In recent years, various publications have demonstrated the supremacy of the internal mammary artery over the saphenous vein when used as a single, bilateral, sequential of free graft. In order to obtain full myocardial revascularization, the use of alternatives to the internal mammary artery is required. The gastroepiploic artery, the inferior epigastric artery and the radial artery have been used as alternatives to the saphenous vein with the hope of obtaining long term results similar to the internal mammary artery.

Arteries↗
PubMed1998

Optimization of the tyrosinase mRNA probe to detect circulating melanocytes with reverse transcription and polymerase chain reaction.

It was recently suggested that reverse transcription polymerase chain reaction (RT-PCR)-based detection of tyrosinase messenger RNA (mRNA) in peripheral blood is useful in the early detection of circulating tumor cells, since tyrosinase is thought to be a melanocyte-specific marker. However, the sensitivity of detection of these cells in circulation is controversial, some authors reporting 0% effectiveness, others obtaining 100% efficacy. We developed a modification of a technique to process blood samples to detect tyrosinase mRNA, and tested the method with 50 samples from as many patients with histologically confirmed malignant melanoma in different stages. Whole blood was processed by discarding the plasma and extracting RNA from density gradient-isolated peripheral blood lymphocytes. The RNA samples were tested with a sensitive nested primer RT-PCR assay. Sensitivity was tested using RNA extracted from SK-mel-1 human melanoma cells diluted serially with peripheral blood obtained from healthy control subjects. A lymph node from a patient with confirmed disseminated melanoma served as the positive control. Our technique was able to detect tyrosinase mRNA in samples from the 37 patients with progressive metastatic melanoma. The test detected tyrosinase mRNA from both the melanoma cell line and the positive lymph node. Our method to extract RNA from whole blood improves the specificity and sensitivity of tyrosinase mRNA detection by RT-PCR. The test should be of use in determining the prognosis of patients with melanoma, and in deciding when to initiate early treatment in patients with malignant melanoma.

Humans↗
PubMed1997

Characterization of rat liver-specific methionine adenosyltransferase gene promoter. Role of distal upstream cis-acting elements in the regulation of the transcriptional activity.

Methionine adenosyltransferase is a ubiquitous enzyme that catalyzes the only known route of biosynthesis of S-adenosylmethionine, the major methyl group donor in cell metabolism. In mammals, two different methionine adenosyltransferases exist: one is confined to the liver, and the other one is distributed in extrahepatic tissues. In the present study, we report the cloning of the 5'-flanking region of liver-specific methionine adenosyltransferase gene from rat. Two closely spaced sites for transcriptional initiation were identified by primer extension analysis. The major transcription start site was determined to be 29 nucleotides downstream from the putative TATA box. Transient transfection assays of constructs containing sequentially deleted 5'-flanking sequences fused to the luciferase gene showed that rat hepatic methionine adenosyltransferase promoter was able to efficiently drive reporter expression not only in liver-type cells (rat hepatoma H35 cells and human hepatoblastoma HepG2 cells) but also in Chinese hamster ovary cells. Two regions spanning nucleotides -1251 to -958 and -197 to +65 were found to be crucial for the promoter efficiency. The distal upstream region contains elements that positively regulate promoter activity in H35 and HepG2 cells but are ineffective in Chinese hamster ovary cells. Eight protein binding sites were characterized in both regions by DNase I footprinting analysis. Two of these elements, sites A and B, located in the distal region, were found to be essential for the regulation of promoter activity. Electrophoretic mobility shift assays and competition experiments showed that site A is recognized by an NF1 protein. Site B was able to interact with a member of HNF-3 family when nuclear extracts from rat liver and H35 cells were used in the in vitro assay, but an additional binding activity to an NHF1-like protein was obtained with the hepatoma cell extracts. It is suggested that this differential binding can contribute to the cell specificity of promoter function.

Animals↗
PubMed1997

Stimulation of DNA synthesis by natural ceramide 1-phosphate.

We found that natural (long-chain) ceramide 1-phosphate can be dispersed into aqueous solution when dissolved in an appropriate mixture of methanol/dodecane (49:1, v/v). This solvent mixture facilitates the interaction of this phosphosphingolipid with cells. Under these conditions, incubation of EGFR T17 fibroblasts with natural ceramide 1-phosphate caused a potent stimulation of DNA synthesis. This effect was accompanied by an increase in the levels of proliferating-cell nuclear antigen. Concentrations of natural ceramide 1-phosphate that stimulated the synthesis of DNA did not inhibit adenylate cyclase activity, nor did they stimulate phospholipase D. Natural ceramide 1-phosphate did not alter the cellular phosphorylation state of tyrosine residues or of mitogen-activated protein kinase. Furthermore, natural ceramide 1-phosphate failed to induce the expression of the proto-oncogenes c-myc and c-fos. Both the stimulation of DNA synthesis and the induction of proliferating-cell nuclear antigen by natural ceramide 1-phosphate were inhibited by natural ceramides. This work suggests that the use of methanol and dodecane to deliver natural ceramide 1-phosphate to cells may be useful for elucidation of the biological function(s) and mechanism(s) of action of ceramide 1-phosphate.

3T3 Cells↗
PubMed1997

Relationship between biochemical markers of bone turnover and bone scintigraphic indices in assessment of Paget's disease activity.

OBJECTIVE: To evaluate the relationship between biochemical markers of bone turnover and bone scan indices of disease activity, as well as to analyze their variations based on skeletal involvement, in Paget's disease. METHODS: Serum samples were obtained from 51 patients with Paget's disease to determine the levels of total alkaline phosphatase (total AP), bone alkaline phosphatase (bone AP), propeptide carboxyterminal of type I procollagen (PICP), propeptide aminoterminal of type I procollagen (PINP), osteocalcin, tartrate-resistant acid phosphatase, and telopeptide carboxyterminal of type I collagen. Urine samples were analyzed for levels of hydroxyproline (HYP), pyridinoline (PYR), deoxypyridinoline (DPYR), C-terminal telopeptide of type I collagen (CTx), and N-terminal telopeptide of type I collagen (NTx). In addition, 2 semiquantitative scintigraphic indices, disease activity (AI) and disease extent (EI), were obtained. Pagetic skeletal locations were evaluated individually, with special attention to skull involvement. RESULTS: All biochemical markers correlated with the AI and the EI. Serum PINP, bone AP, and total AP showed the highest proportions of increased values among the bone formation markers (94%, 82%, and 76%, respectively). Among the bone resorption markers, urinary NTx showed the highest proportion of increased values in patients with Paget's disease (96%), compared with PYR (69%), DPYR (71%), CTx (65%), and HYP (64%). In patients with mild disease activity, serum PINP was the marker with the highest proportion of increased values (71%). In contrast, serum PICP and urinary CTx were the most discriminative markers for skull involvement. Except for higher values for most of the biochemical markers of bone turnover in flat bones, no major differences in other skeletal locations were observed. CONCLUSION: The determination of serum PINP as a marker of bone formation and urinary NTx as a marker of bone resorption provided the best biochemical profile to ascertain the extent and activity of Paget's disease. In patients with skull involvement, serum PICP and urinary CTx were shown to be the most discriminative markers.

Acid Phosphatase↗
PubMed1997

Biochemical markers of bone turnover in Camurati-Engelmann disease: a report on four cases in one family.

Moderate increases in "classical" biochemical markers of bone turnover have been described only in some patients with Camurati-Engelmann disease. However, the determination of the following "new" markers has not been previously performed: serum osteocalcin (BGP), bone alkaline phosphatase (BAP), carboxyterminal propeptide of type I procollagen (PICP), aminoterminal propeptide of type I procollagen (PINP), tartrate-resistant acid phosphatase (TRAP), telopeptide carboxyterminal of type I collagen (ICTP), urinary pyridinoline (PYR), crosslinked N-telopeptides of type I collagen (NTX), and Crosslaps (CL). Such a determination may improve the evaluation of the disease activity. To evaluate the usefulness of biochemical markers of bone turnover reflecting Camurati-Engelmann disease activity we measured the levels of all these markers in four affected patients. The results were compared with bone scintigraphic indices of disease activity. Except for PICP and TRAP, bone formation and resorption markers were abnormal in all patients and were related to bone scan indices of disease activity. Among the markers of bone formation PINP, BAP, and BGP showed the highest values, whereas NTX and CL were the most sensitive markers of bone resorption. These results suggest that the determination of NTX or CL, and PINP or either BAP and BGP, associated with bone scan evaluation, provides the best assessment of Camurati-Engelmann disease activity.

Acid Phosphatase↗
PubMed1997

Etidronate versus fluoride for treatment of osteopenia in primary biliary cirrhosis: preliminary results after 2 years.

BACKGROUND & AIMS: Because osteopenia increases morbidity of primary biliary cirrhosis (PBC), the effects of cyclical etidronate vs. sodium fluoride on bone mass were compared in patients with PBC. METHODS: Thirty-two women with PBC were randomly assigned to receive etidronate (400 mg/day during 14 days every 3 months) or fluoride (50 mg/day, enteric-coated tablets). Bone mineral density of the lumbar spine and proximal femur were measured initially and every 6 months. Bone fractures were also evaluated. RESULTS: Sixteen patients were allocated into each group, which were comparable with respect to the severity of PBC and osteopenia. Thirteen patients with etidronate and 10 patients with fluoride completed 2 years in the study. In the etidronate group, bone mineral density increased in the lumbar spine (P = 0.02) and did not change in the proximal femur. In the fluoride group, lumbar bone mineral density did not change but femoral bone mass decreased, particularly in the Ward's triangle. Two patients in the fluoride and none in the etidronate group developed new vertebral fractures, and the number of new nonvertebral fractures was similar in both groups. Neither treatment impaired liver function or cholestasis. CONCLUSIONS: Cyclical etidronate is more effective and better tolerated than sodium fluoride in preventing bone loss in PBC.

Absorptiometry, Photon↗
PubMed1997

Actinomycin D treatment leads to differentiation and inhibits proliferation in rhabdomyosarcoma cells.

Human embryonal cell line RD is derived from rhabdomyosarcoma, a tumor of childhood that arises from rhabdomyoblasts probably arrested somewhere along their pathway to maturation. Because actinomycin D is a drug of choice in the treatment of rhabdomyosarcomas, and because it has been used to induce differentiation as an alternative therapy for myeloproliferative syndromes, we treated RD cells with different concentrations of actinomycin D and evaluated the effects on growth and differentiation. Actinomycin D treatment in vitro caused time- and dose-dependent growth inhibition. Interestingly, RD cells treated with low doses (2.85 and 5.7 nmol/L) of actinomycin D for 6 days showed morphologic and phenotypic differentiation, with increased expression of desmin, alpha-actinin, and tropomyosin. However, treatment with 11.4 nmol/L actinomycin D strongly inhibited growth and had cytotoxic effects that prevented the cells from attaining myogenic differentiation. We conclude that exposure of this human embryonal rhabdomyosarcoma cell line to low concentrations of actinomycin D released the neoplastic cells from their blockade, allowing them to recover normal myogenic development. We suggest a potential role for differentiation therapy in the treatment of rhabdomyosarcomas.

Antibiotics, Antineoplastic↗
PubMed1997

S-adenosylmethionine synthesis: molecular mechanisms and clinical implications.

Methionine adenosyltransferase (MAT) is an ubiquitous enzyme that catalyzes the synthesis of S-adenosylmethionine from methionine and ATP. In mammals, there are two genes coding for MAT, one expressed exclusively in the liver and a second enzyme present in all tissues. Molecular studies indicate that liver MAT exists in two forms: as a homodimer and as a homotetramer of the same oligomeric subunit. The liver-specific isoenzymes are inhibited in human liver cirrhosis, and this is the cause of the abnormal metabolism of methionine in these subjects.

Animals↗
PubMed1997

Recombinant rat liver S-adenosyl-L-methionine synthetase tetramers and dimers are in equilibrium.

Rat liver S-adenosyl-L-methionine synthetase is present in two oligomeric forms, tetramers and dimers, with different substrate kinetics and regulation. In vivo the relative amounts of both forms may change in some instances. The basis of this regulatory mechanism is not known. When rat liver cDNA was used to express the protein in Escherichia coli the two oligomeric forms were found. Gel filtration chromatography of the purified recombinant enzyme suggested that these two isoforms might be in equilibrium. This was confirmed by kinetic experiments which showed that the specific activity of the enzyme was dependent on the protein concentration. From these experiments, apparent equilibrium constants of (5.6 +/- 0.4) x 10(5) M-1 and (3.5 +/- 0.9) x 10(5) M-1 were obtained at 2mM and 60 microM methionine concentrations, respectively. Using hydrophobic chromatography on phenyl-Sepharose to separate the tetrameric and dimeric forms, an equilibrium constant of (4.9 +/- 0.7) x 10(5) M-1 was calculated. A rate constant for the dissociation of the tetramer of k-1 = (8.1 +/- 0.4) x 10(-4) s-1 at 4 degrees C was also calculated using the same approach. In summary, we have shown that the rat liver S-adenosyl-L-methionine synthetase produced in bacterial cells is present in two oligomeric forms, tetramers and dimers, which are in equilibrium. This system might be useful for studying the dynamics and the regulation of the distribution of oligomeric forms in the mammalian liver.

Animals↗
PubMed1997

Comparative plasma disposition kinetics of ivermectin, moxidectin and doramectin in cattle.

The persistence of the broad-spectrum antiparasitic activity of endectocide compounds relies on their disposition kinetics and pattern of plasma/tissues exchange in the host. This study evaluates the comparative plasma disposition kinetics of ivermectin (IVM), moxidectin (MXD) and doramectin (DRM) in cattle treated with commercially available injectable formulations. Twelve (12) parasite-free male Hereford calves (180-210 kg) grazing on pasture were allocated into three groups of four animals each. Animals in each group received either IVM (Ivomec 1%, MSD AGVET, Rahway, NJ, USA), MXD (Cydectin 1%. American Cyanamid, Wayne, NJ, USA) or DRM (Dectomax 1%, Pfizer Inc., New York, NY, USA) by subcutaneous injection at a dose of 200 micrograms/kg. Jugular blood samples were collected from 1 h up to 80 days post-treatment, and plasma extracted, derivatized and analysed by high performance liquid chromatography (HPLC) using fluorescence detection. The parent molecules were detected in plasma between 1 h and either 70 (DRM) or 80 (IVM and MXD) days post-treatment. The absorption of MXD from the site of injection was significantly faster (absorption half-life (t1/2ab) = 1.32 h) than those of IVM (t1/2ab = 39.2 h) and DRM (t1/2ab = 56.4 h). MXD peak plasma concentration (Cmax) was reached significantly earlier (8.00 h) compared to those of IVM and DRM (4-6 days post-treatment). There were no differences on Cmax values: the area under the concentration-time curve (AUC) was higher for IVM (459 ng.d/mL) and DRM (627 ng.d/mL) compared to that of MXD (217 ng.d/mL). The mean plasma residence time was longer for MXD (14.6 d) compared to IVM (7.35 d) and DRM (9.09 d). Unidentified metabolites were detected in plasma: they accounted for 5.75% (DRM), 8.50% (IVM) and 13.8% (MXD) of the total amount of their respective parent drugs recovered in plasma. The comparative plasma disposition kinetics of IVM, MXD and DRM in cattle, characterized over 80 days post-treatment under standardized experimental conditions, is reported for the first time.

Animals↗