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Biomedical subjects

M Martín

Publications and source records attributed to M Martín.

At least 55 records · Page 3Linked to original sources
PubMed2001

Impaired type-1 activity and increased NK cells in Gleich's syndrome.

BACKGROUND: An altered production of cytokines has been described in Gleich's syndrome. Our aim was to study the cytokine production at the single-cell level in a patient with Gleich's syndrome and to determine whether it changed during a flare episode. METHODS: Blood samples were obtained from a 30-year-old woman diagnosed with Gleich's syndrome before and during the subsequent flare of edema of trunk and arms and weight gain. The major lymphoid subsets (CD4+, CD8+, and CD19+) and natural killer (NK) cells were measured by flow cytometry. Cytokine-producing T cells (IL-2, IFN-gamma, and IL-4) were quantified in whole blood by intracellular staining with specific monoclonal antibodies and flow cytometry analysis after polyclonal stimulation with phorbol 12-myristate 13-acetate and ionomycin. RESULTS: Increased numbers of immature CD4+CD8+ T cells and NK cells were observed in peripheral blood during the asymptomatic period. The latter population significantly decreased during the flare. Type-1 cells were decreased in both asymptomatic and, more markedly, during the attack with respect to healthy subjects. CONCLUSIONS: The decreased type-1 response demonstrated in this patient might be the basis of the hypereosinophilia of Gleich's syndrome. Besides, the NK cells might play a role in the pathogenesis of these inflammatory episodes.

Adult↗
PubMed2001

Melatonin, mitochondria, and cellular bioenergetics.

Aerobic cells use oxygen for the production of 90-95% of the total amount of ATP that they use. This amounts to about 40 kg ATP/day in an adult human. The synthesis of ATP via the mitochondrial respiratory chain is the result of electron transport across the electron transport chain coupled to oxidative phosphorylation. Although ideally all the oxygen should be reduced to water by a four-electron reduction reaction driven by the cytochrome oxidase, under normal conditions a small percentage of oxygen may be reduced by one, two, or three electrons only, yielding superoxide anion, hydrogen peroxide, and the hydroxyl radical, respectively. The main radical produced by mitochondria is superoxide anion and the intramitochondrial antioxidant systems should scavenge this radical to avoid oxidative damage, which leads to impaired ATP production. During aging and some neurodegenerative diseases, oxidatively damaged mitochondria are unable to maintain the energy demands of the cell leading to an increased production of free radicals. Both processes, i.e., defective ATP production and increased oxygen radicals, may induce mitochondrial-dependent apoptotic cell death. Melatonin has been reported to exert neuroprotective effects in several experimental and clinical situations involving neurotoxicity and/or excitotoxicity. Additionally, in a series of pathologies in which high production of free radicals is the primary cause of the disease, melatonin is also protective. A common feature in these diseases is the existence of mitochondrial damage due to oxidative stress. The discoveries of new actions of melatonin in mitochondria support a novel mechanism, which explains some of the protective effects of the indoleamine on cell survival.

Adenosine Triphosphate↗
PubMed2001

Circadian urinary 6-sulphatoxymelatonin, cortisol excretion and locomotor activity in airline pilots during transmeridian flights.

Airline pilots divided into two groups of age (over and under 50 years) were studied before, during and after westbound (Madrid-Mexico City-Madrid, n = 12) and eastbound (Madrid-Tokyo-Madrid, n = 21) flights. A group of 10 age-matched people staying in Madrid were submitted to the same tests and served as a control group. Changes in urinary 6-sulphatoxymelatonin (6-aMTs) and free cortisol excretion (determined in 6-hr intervals) were measured by radioimmunoassay. Using wrist actigraphy, the circadian locomotor activity rhythm (LAR) was also monitored. Maximal baseline excretion of 6-aMTs occurred between 00:00 and 12:00 hr and maximal excretion of cortisol took place between 6:00 and 12:00 hr in the control group. Analysed globally, older pilots exhibited significantly lower values of 6-aMTs than younger ones. In both flight directions, pilots maintained the pattern of excretion of 6-aMTs, corresponding to baseline. The return flight to Madrid from Mexico and Tokyo coincided with a maximum in 6-aMTs excretion. Pilots kept the cortisol pattern found in the control group, with those over 50 years of age exhibiting significantly lower cortisol values than the younger ones. A 7-hr delay in acrophase of LAR after 2 days in Mexico City was found after cosinor analysis, and similar pre-flight values were found after returning to Madrid. An 8-9-hr acrophase advance of LAR was observed after arriving in Tokyo, with acrophase on the post-return flight day still being advanced 3 4 hr as compared to pre-flight values. Decreases in the amplitude of LAR in older pilots were found at Mexico City, as well as at Tokyo stopover and on post-flight day. Data confirm the occurrence of internal desynchronization in airline crewmembers after transmeridian flights.

Adult↗
PubMed2001

Calcium-dependent effects of melatonin inhibition of glutamatergic response in rat striatum.

The effects of melatonin, amlodipine, diltiazem (L-type Ca2+ channel blockers) and omega-conotoxin (N-type Ca2+ channel blocker) on the glutamate-dependent excitatory response of striatal neurones to sensory-motor cortex stimulation was studied in a total of 111 neurones. Iontophoresis of melatonin produced a significant attenuation of the excitatory response in 85.2% of the neurones with a latency period of 2 min. Iontophoresis of either L- or N-type Ca2+ channel blocker also produced a significant attenuation of the excitatory response in more than 50% of the recorded neurones without significant latency. The simultaneous iontophoresis of melatonin + amlodipine or melatonin + diltiazem did not increase the attenuation produced by melatonin alone. However, the attenuation of the excitatory response was significantly higher after ejecting melatonin + omega-conotoxin than after ejecting melatonin alone. The melatonin-Ca2+ relationship was further supported by iontophoresis of the Ca2+ ionophore A-23187, which suppressed the inhibitory effect of either melatonin or Ca2+ antagonists. In addition, in synaptosomes prepared from rat striatum, melatonin produced a decrease in the Ca2+ influx measured by Fura-2AM fluorescence. Binding experiments with [3H]MK-801 in membrane preparations from rat striatum showed that melatonin did not compete with the MK-801 binding sites themselves although, in the presence of Mg2+, melatonin increased the affinity of MK-801. The results suggest that decreased Ca2+ influx is involved in the inhibitory effects of melatonin on the glutamatergic activity of rat striatum.

Amlodipine↗
PubMed2001

Protein intake, control of serum phosphorus, and relatively low levels of parathyroid hormone in elderly hemodialysis patients.

In maintenance hemodialysis (MHD) patients, advanced age is a factor associated with relative hypoparathyroidism and an adynamic bone. However, the underlying mechanism remains elusive. The aim of the present study was to analyze whether the observed spontaneous decrease in protein intake in the elderly favors a better control of serum phosphorus (P) and parathyroid hormone (PTH) levels. A cross-sectional study including 207 MHD patients (mean age, 60 +/- 14; 59% males; time on dialysis, 61 +/- 55 months) dialyzed 3.5 to 4.5 hours 3 times a week using bicarbonate hemodialysis from 6 Spanish hemodialysis centers was performed. In 95 patients, the nutrient intake was recorded over a 5-day period, and average daily ingestion of nutrients was calculated using a computerized diet analysis system. One-way analysis of variance showed that serum phosphorus and intact PTH decreased with age. In addition, patients with serum phosphorus lower than 4 mg/dL as compared with those with serum phosphorus greater than 4 mg/dL were older (68 +/- 9 v 58 +/- 15 years, P < 0.001), had a lower protein (0.86 +/- 0.3 v 1.05 +/- 0.4 g/kg body weight, P < 0.01) and caloric intake (21.9 +/- 7.4 v 25.7 +/- 8.3 kcal/Kg body weight, P < 0.01), and had lower PTH levels (102 +/- 155 v 290 +/- 345 pg/mL, P < 0.001). An inverse and significant correlation was observed between age and protein intake (r = -0.48; P < 0.01), caloric intake (r = -0.37, P < 0.01), serum phosphorus concentration (r = -0.40; P < 0.01), and PTH levels (r = -0.26; P < 0.01). Additionally, a significant positive correlation was found between serum phosphorus and PTH levels (r = 0.40; P < 0.01). The results obtained in the present study suggest that a lower serum phosphorus level due to spontaneous reduction of protein intake might contribute to the relative low PTH levels observed in elderly hemodialysis patients.

Age Factors↗
PubMed2001

Arabidopsis thaliana ecotype Cvi shows an increased tolerance to photo-oxidative stress and contains a new chloroplastic copper/zinc superoxide dismutase isoenzyme.

A new chloroplastic Cu/Zn-superoxide dismutase (SOD) isoenzyme was identified in Arabidopsis thaliana ecotype Cvi. Genetic analyses indicated that the new isoenzyme was encoded by a Cvi-specific allele of Csd2 that was named Csd2-2. Paraquat treatments of A. thaliana ecotypes Ler and Cvi resulted in higher levels of chloroplastic Cu/Zn-SOD activity in Cvi, suggesting that the Cvi isoenzyme has a higher stability and/or turnover rate than the Ler variant under photo-oxidative conditions. In addition, Cvi showed a higher tolerance to paraquat treatments. Hybrid plant populations expressing Csd2-2 also exhibited an increased tolerance, suggesting that the Cvi isoenzyme is one of the factors that contribute to a better fitness in photo-oxidative stress conditions.

Arabidopsis↗
PubMed2001

Hydrogen peroxide mediates the induction of chloroplastic Ndh complex under photooxidative stress in barley.

Chloroplast-encoded NDH polypeptides (components of the plastid Ndh complex) and the NADH dehydrogenase activity of the Ndh complex (NADH-DH) increased under photooxidative stress. The possible involvement of H2O2-mediated signaling in the photooxidative induction of chloroplastic ndh genes was thoroughly studied. We have analyzed the changes in the NADH-DH and steady-state levels of NDH-F polypeptide and ndhB and ndhF transcripts in barley (Hordeum vulgare cv Hassan) leaves. Subapical leaf segments were incubated in growing light (GL), photooxidative light (PhL), GL and H2O2 (GL + H2O2), or PhL and 50 nM paraquat in the incubation medium. Treatments with H2O2 under GL mimicked the photooxidative stimulus, causing a dose-dependent increase of NADH-DH and NDH-F polypeptide. The kinetic of Ndh complex induction was further studied in leaves pre-incubated with or without the H2O2-scavenger dimethyltiourea. NADH-DH and NDH-F polypeptide rapidly increased up to 16 h in PhL, GL+ H2O2, and, at higher rate, in PhL and paraquat. The observed increases of NADH-DH and NDH-F after 4 h in PhL and GL + H2O2 were not accompanied by significant changes in ndhB and ndhF transcripts. However, at 16-h incubations NADH-DH and NDH-F changes closely correlated with higher ndhB and ndhF transcript levels. All these effects were prevented by dimethylthiourea. It is proposed that the induction of chloroplastic ndh genes under photooxidative stress is mediated by H2O2 through mechanisms that involve a rapid translation of pre-existing transcripts and the increase of the ndh transcript levels.

Base Sequence↗
PubMed2001

Platinum compounds in the treatment of advanced breast cancer.

Interest in platinum compounds for the treatment of breast cancer has been reawakened because of preclinical studies indicating synergy of platinum salts with the monoclonal antibody trastuzumab in human breast cancer cell lines that overexpress HER2/neu. Cisplatin, carboplatin, and iproplatin are not very active as single agents in patients with previously treated metastatic breast cancer (MBC). The activity of oxaliplatin has not been adequately tested in refractory MBC. On the other hand, cisplatin is very active as first-line chemotherapy, with response rates (RR) of 50%; carboplatin appears to be moderately active in patients without prior chemotherapy (RR around 30%). The clinical effectiveness of the other platinum compounds (iproplatin, oxaliplatin, and others) has not yet been fully tested as first-line chemotherapy. Platinum compounds have been extensively tested in combination with other antitumoral agents. Cisplatin combinations have been employed as neoadjuvant chemotherapy in women with locally advanced breast cancer. These combinations are very active, although the precise contribution of cisplatin to the overall activity is not known. Combinations with cisplatin have been investigated, essentially, as salvage therapy for patients with previously treated MBC. The combinations of cisplatin with older pharmacological agents (5-fluorouracil, etoposide) have moderate activity, while the combinations of cisplatin with the newer agents (vinorelbine, paclitaxel, docetaxel, gemcitabine) appear to be more active. The combinations of carboplatin with the classical agents (5-fluorouracil, etoposide) are poorly active in previously treated MBC; however, the combination of carboplatin with the taxanes (docetaxel, paclitaxel) is more active. Of greatest interest is the synergy between the platinum derivatives and the monoclonal antibody trastuzumab demonstrated in vitro in breast cancer cell lines overexpressing HER2/neu. Currently, several combinations of platinum compounds (either cisplatin or carboplatin) with docetaxel and trastuzumab are under clinical testing in patients with MBC who overexpress HER2/neu. The preliminary results are very promising, and these combinations will soon be tested in the adjuvant setting. Cisplatin, carboplatin, and perhaps, oxaliplatin appear to have some antitumor activity in MBC and can be combined safely with other agents that are active in this disease. However, the precise role that platinum compounds play in the treatment of breast cancer remains to be defined.

Antimetabolites, Antineoplastic↗
PubMed2001

Primary transcripts of ndhD of Liliaceae and Aloaceae require editing of the start and 20th codons.

About 350 nucleotide sequences around the start codon of the plastid ndhD gene were determined in six species to investigate the requirement of C to U editing of the cryptic start codons. The comparison with other sequences in databanks showed that, in contrast to grasses and similarly to dicots, Liliaceae and Aloaceae require editing of the primary transcript to generate the AUG start codon. Primary transcripts of Liliaceae and Aloaceae also show a new editing site at the 59th nucleotide, which has not been described in other plants. In some cases, transcripts showed partial editing which suggests that the synthesis of the protein may be controlled at the level of transcript processing.

Amino Acid Sequence↗
PubMed2001

Evaluation of handicap and socio-economic status in patients with multiple sclerosis--data from a population-based survey in the sanitary area of Calatayud, northern Spain.

There are a few reports about handicap and socio-economic status in patients with multiple sclerosis (MS) based on epidemiological studies. The objective of our work is to evaluate handicap in patients with multiple sclerosis in the sanitary area of Calatayud, northern Spain, as well as the socio-economic situation--in comparison with patients from other parts off the world. In this study we included 34 patients with clinically definite MS found in a long-term and prospective population-based survey. For assessing the handicap degree and socio-economic status we used the Environmental Status Scale (ESS) recommended by the International Federation of MS. We compared the results with those found in 1116 patients from 7 different international series. The global mean score in ESS was 9.9 (sd 9.3, range 0-31). The mean score for the item "actual work status" was 3.3 (sd 2.3, range 0-5), for the item "financial/economic status" was 1 (sd 1.7, range 0-5), for the item "personal residence/home" was 0.8 (sd 1, range 0-4), for the item "personal assistance" was 1.2 (sd 1.7, range 0-5), for the item "transportation" was 1.5 (sd 1.7, range 0-5), for the item "community health services" was 0.7 (sd 1.3, range 0-5) and for "social activity" was 1.3 (sd 1.5, range 0-4). In the comparative assessment we found that our patients were better in all items, but in the item "actual work status" where our patients yielded higher scores than those obtained in other series. Socio-economic status measured with ESS correlates well with the degree of impairment measured with EDSS and it is more favourable than previously recognized, except for "actual work status" item. The high rate of labour incapacity in our series could be due to the considerable restrictions handicapped people have to cope with in order to find employment in rural areas.

Activities of Daily Living↗
PubMed2000

The 18q21 region in colorectal and pancreatic cancer: independent loss of DCC and DPC4 expression.

UNLABELLED: The 18q21 region is frequently altered in gastrointestinal tumors. Three candidate tumor suppressor genes have been identified in it: DCC, Smad4/DPC4 and Smad2; the mechanisms involving their inactivation have not been completely elucidated. In this study, genetic losses at 18q21 and expression of DCC and DPC4 in colorectal (n=12) and pancreatic (n=16) cell lines and in colorectal tissues (n=10) were analyzed. The status of the 18q21 region was assessed using microsatellite analysis and duplex PCR of exonic sequences; expression was analyzed by RT-PCR; mutational analysis of DPC4 cDNA was performed in selected cases. Homozygous losses of microsatellite markers at 18q21 were not observed in colon or pancreas lines; however, a higher proportion of apparent homozygosity than expected was found. DCC and DPC4 transcripts were detected in 11/12 and 12/12 colorectal cancer lines, respectively. In tumors, homozygous losses at 18q21 were detected in three cases, without affecting DCC. All tumors retained DCC and DPC4 mRNA expression. In pancreatic lines, DPC4 was inactivated through homozygous deletion (n=5), intragenic mutation (n=3), and lack of protein (n=2). IN CONCLUSION: (1) microsatellite analysis does not provide adequate information regarding homozygous losses at 18q21; (2) approximately 65% of pancreas cancer lines show inactivation of DPC4; and (3) loss of DCC and DPC4 occur independently.

Aged↗
PubMed2000

Transcripts of the ndhH-D operon of barley plastids: possible role of unedited site III in splicing of the ndhA intron.

The plastid ndhH-D operon produces several transcripts containing ndhA sequence with and without its group II intron. After sequencing an 8125 bp fragment of barley plastid DNA including the ndhH-D operon, we investigated the editing-splicing status of transcripts in the range 1.0-7.8 kb. Reverse transcription and sequencing of RNA bands separated by electrophoresis were used to determine C-->U editing sites. Sites I, II and IV of ndhA and site V of ndhD were edited in all transcripts analysed and, probably, were edited before any splicing had taken place. In contrast, site III of ndhA (13 bp from the 5'-end base of the second exon) was not edited in transcripts containing the intron (including the 1.7 kb intermediary transcript consisting of the intron and the second exon) but was edited in all transcripts lacking the ndhA intron. Comparison of the secondary structures of the ndhA intron and intron-second exon intermediate suggests that G pairing prevents editing of site III in transcripts containing the intron and maintains the secondary structure required for splicing. Splicing of the ndhA intron releases the site III C from pairing and, probably, brings it close to cis-acting elements for editing upstream in the first exon.

Base Sequence↗
PubMed2000

Chlororespiration and poising of cyclic electron transport. Plastoquinone as electron transporter between thylakoid NADH dehydrogenase and peroxidase.

Polypeptides encoded by plastid ndh genes form a complex (Ndh) which could reduce plastoquinone with NADH. Through a terminal oxidase, reduced plastoquinone would be oxidized in chlororespiration. However, isolated Ndh complex has low activity with plastoquinone and no terminal oxidase has been found in chloroplasts, thus the function of Ndh complex is unknown. Alternatively, thylakoid hydroquinone peroxidase could oxidize reduced plastoquinone with H(2)O(2). By immunoaffinity chromatography, we have purified the plastid Ndh complex of barley (Hordeum vulgare L.) to investigate the electron donor and acceptor specificity. A detergent-containing system was reconstructed with thylakoid Ndh complex and peroxidase which oxidized NADH with H(2)O(2) in a plastoquinone-dependent process. This system and the increases of thylakoid Ndh complex and peroxidase activities under photooxidative stress suggest that the chlororespiratory process consists of the sequence of reactions catalyzed by Ndh complex, peroxidase (acting on reduced plastoquinone), superoxide dismutase, and the non-enzymic one-electron transfer from reduced iron-sulfur protein (FeSP) to O(2). When FeSP is a component of cytochrome b(6).f complex or of the same Ndh complex, O(2) may be reduced with NADH, without requirement of light. Chlororespiration consumes reactive species of oxygen and, eventually, may decrease their production by lowering O(2) concentration in chloroplasts. The common plastoquinone pool with photosynthetic electron transport suggests that chlororespiratory reactions may poise reduced and oxidized forms of the intermediates of cyclic electron transport under highly fluctuating light intensities.

Ascorbate Peroxidases↗
PubMed2000

Mechanisms of CD26/dipeptidyl peptidase IV cytokine-dependent regulation on human activated lymphocytes.

Among the cellular pathways activated by IL-12, we had previously found that both the percentage and intensity of CD26(+)cells in the PHA-stimulated T cells increased when IL-12 was present (independently of its CD4 or CD8 phenotype). Now, we examined the molecular mechanisms of this IL-12-mediated effect. The IL-12 regulation pathway is dependent of de novo protein synthesis and independent of cytokine secretion. Our results show two transcripts for CD26 in PBMC for the first time and no regulation by ILs at this level. Furthermore, secretion of the serum forms of CD26/DPPIV were not affected by IL-12. Interestingly, assays with neutralizing mAbs against TNF-alpha suggest that this cytokine negatively modulates CD26 expression. The fact that translation and probably translocation of CD26 toward the cell surface can be regulated by IL-12 and TNF-alpha reveals new aspects about the control of this T(H1)marker.

Cells, Cultured↗
PubMed2000

4-Hydroxybenzoate uptake in an isolated soil Acinetobacter sp.

The isolated soil bacteria Acinetobacter strain BEM2 is able to utilize some xenobiotic aromatic compounds as a carbon source. In this study the metabolism of 4-hydroxybenzoate (4-HBA) by strain BEM2 was characterized. Degradation involved a meta-cleavage pathway yielding 3,4-dihydroxybenzoate (3,4-DHBA) as an intermediate and CO(2) as the principal product from the C atoms in the aromatic ring. 4-HBA uptake was studied, and the kinetic parameters were determined. The uptake was shown to be directly coupled to ATP hydrolysis and its synthesis, according to the Mitchell chemiosmotic hypothesis.

Acinetobacter↗
PubMed2000

Different scalp topography of brain potentials related to expression and identity matching of faces.

Event-related potentials (ERPs) and behavioral data were recorded while subjects performed two tasks on the same set of faces (presented in pairs). One task was identity matching and the other expression matching. Two groups of subjects participated, one familiar and the other unfamiliar with the faces. Subjects were less accurate in matching expressions than identity. Familiarity facilitated identity but not expression matching. ERPs to mismatches in both tasks elicited a negativity around 400 ms, which was similar in latency and amplitude in the two tasks, but differed in scalp topography. Whereas the mismatch negativity had the same landscape over the left hemisphere for both tasks, the component related to expression had larger amplitudes over the right-temporal regions. Familiarity had no effect on these negativities, although it affected a late positivity (LP). These results support the idea of distinct neural systems subserving face processing, and agree with a role of the right hemisphere for the processing of emotional expressions.

Adult↗