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Biomedical subjects

M Arellano

Publications and source records attributed to M Arellano.

At least 19 recordsLinked to original sources

Previous cognitive impairment and failure to thrive syndrome in patients who died in a geriatric convalescence hospitalization unit.

Cognitive impairment and depression are commonly associated with poor outcomes in geriatric patients. Both are part of the "failure to thrive syndrome" (FTS), that is a combined group of symptoms as a result from progressive functional, mental and nutritional impairment status in older patients. This paper was aimed at evaluating the presence of FTS in the patients who died in a geriatric convalescence unit (GCU) (intermediate care facility) and comparing the characteristics of patients with primary FTS (not associated with an evident identifiable disease) and secondary FTS (associated with an evident identifiable disease). Finally, we wanted to analyze if the presence of cognitive impairment before admission was associated with the type of FTS. We analyzed 78 patients retrospectively. The presence of the next three conditions was necessary to define the FTS: (i) Impaired functional status and malnutrition. (ii) Cognitive impairment and/or depression. (iii) Absence of improvement, after a specific geriatric intervention program during the hospitalization. Functional status for basic and instrumental activities of daily living (ADL and IADL) and the presence of symptoms cognitive impairment before admission were evaluated. Of the 78 analyzed patients, there were 30 (38.4%) with symptoms of FTS. Seventeen of them (56.6%) had a secondary FTS and 13 (43.3%) a primary one. This last group of patients had a significantly higher mean age (84.7 +/- 5.8 vs. 78.6 +/- 7.2; p < 0.02) and before admission they were significantly more dependent for ADL: 10 patients (76.9%) vs. 7 (41.0%) chi2 = 3.833, p < 0.05. A higher proportion of subjects with cognitive impairment before admission was found in the group of patients with primary FTS, than in those secondary FTS, although this difference did not reach statistical significance. Patients with primary FTS seem to be older and more dependent for ADL before admission, than those with secondary FTS.

Aged↗

Clinical impact of different scores of the mini nutritional assessment (MNA) in the diagnosis of malnutrition in patients with cognitive impairment.

It was aimed at evaluating the clinical usefulness of the mini nutritional assessment (MNA) to identify malnutrition in elderly patients with cognitive impairment, admitted to a geriatric convalescence unit (intermediate care facility). Sixty-three patients with cognitive impairment were studied. Cognitive impairment was considered when mini mental state examination (MMSE) scores were below 21. MNA and a nutritional evaluation according to the sequential model of the American Institute of Nutrition (AIN) were performed at admission. According to the AIN criteria, malnutrition was considered, if there were abnormalities in at least one of the following parameters: albumin, cholesterol, body mass index (BMI), and branchial circumference. Based on these criteria, 27 patients (42.8%) proved to be undernourished at admission, whereas if taking the original MNA scores, 39 patients (61.9%) were undernourished, 23 (36.5%) were at risk of malnutrition, and 1 (1.5%) was normal. The analyzed population was divided in four categories (quartiles) of the MNA scores: very low (</= 13.5), low (> 13.5 and </= 16), intermediate (> 16 and </= 18.5) and high (> 18.5). Likelihood ratios of each MNA quartile were obtained by dividing the percentage of patients in a given MNA category who were undernourished (according to AIN) by the percentage of patients in the same MNA category who were not undernourished. In the very low MNA quartile, this likelihood ratio was 2.79 and for the low MNA quartile it was 0.49. For intermediate and high MNA categories, likelihood ratios were 1.0 and 0.07 respectively. In the present study, MNA identified undernourished patients with a high clinical diagnostic impact value only, when very low scores (</= 13) are obtained.

Aged↗

Validation of a modified version of the Gijon's social-familial evaluation scale (SFES): the "Barcelona SFES Version", for patients with cognitive impairment.

The aim was to validate an abbreviated version of the Gijon's social-familial evaluation scale (SFES) (Barcelona-SFES version), on patients with cognitive impairment. A group of 34 patients with cognitive impairment, admitted to an intermediate-long-term-care facility, were analyzed. Mean age was 80.2 +/- 7.4 years. Gijón's SFES was abbreviated and only the first three item groups corresponding to family conditions, social contacts and assistance from the social network were selected. Barcelona-SFES version had a range score between 3 to 15 points, in which low scores identify older patients who live with their family, have good contacts, and participate in community activities. In contrast, high scores identify older persons who live alone and have poor social support and little participation with community activities. Three social risk categories were established according to the Barcelona-SFES score: low social risk (>/= 7 points), intermediate social risk (8-9 points) and high social points). Validation criteria used in the present study were: predictive value of Barcelona-SFES score of post-discharge destination (home or institution), and patient's (or family's) request for a definitive institutionalization in a nursing home. There were 9 patients with low social risk (26.4 %), 8 with intermediate social risk (23.5 %) and 17 with high social risk (50 %). A significant relationship between Barcelona-SFES scores and post-discharge destination was found. Eighty percent of patients discharged to an institution(nursing and residential homes), they had high social risk SFES scores (>/= 10) Also, a significant correlation was found between the number of patients for which a definitive institutionalization request was performed and the Barcelona-SFES scores. Fifteen (88.2 %) of the 18 patients for whom the request was done, were in the high social risk group. The lowest scores from SFES were predictive of home discharge, while the highest scores were predictive of a definitive institutionalization.

Aged↗

Observational scale and geriatric depression scale of Yesavage to identify depressive symptoms in older patients.

The diagnosis of depression by clinical interview may be difficult in the patients with communication problems (aphasia, severe cognitive impairment or severe deafness). In these cases, depressive symptoms may be observed by others (nurses and caregivers). The aim of this study was to evaluate the clinical usefulness of an observational scale to identify depression in older patients. Seventy-six institutionalized patients in an intermediate-long-term care center were evaluated. Of them, 39 were excluded because they were unable to perform a clinical interview, needed to diagnose depression. Of the excluded patients, 18 had aphasia, 7 showed severe cognitive impairment: their mini mental state examination (MMSE) score < 14, and 14 collaborated very poorly. Thus 37 patients were analyzed, mean age was 83 +/- 0.86 years (30 women and 7 men). Diagnostic categories were: neurological 16 patients (43.2%), fractures/orthopedics 6 (16.2%), pulmonary/cardiology 5 (13.5%) and others 10 (27.1%). The mean Barthel index was 57.0 +/- 31.6 and mean MMSE score was 21.1 +/- 4.3. The observational scale (OS) designed with six items, was applied to all patients. Each item was scored as never (0 points), sometimes (1 point) and always (2 points). Thus total OS score ranged from 0 to 12. Two observers, who knew the patients (nurses), applied the OS. A trained geriatrician, using the 15-item geriatric depression scale (GDS) performed detection of depressive symptoms. There were 15 patients (40.5 %) with depression on the GDS. OS scale score with a cutoff point of 5 or more was present in 13 patients; nine of them had depression (69.2 %). In the remaining 24 patients with an OS score < 5, depression was present only in 6 cases (25%) (chi2 = 6.844; p < 0.01). The OS >/= 5, in the present study, obtained a sensitivity of 60 %, a specificity of 81 %, a positive predictive value of 69 %, and a negative predictive value of 75 %.We concluded that (i) the OS has been useful for identifying depressive symptoms with an acceptable sensitivity and specificity, and (ii) the OS may be an alternative to detect depression in patients who are unable to perform a clinical interview.

Aged↗

Prevalence of delirium in a geriatric convalescence hospitalization unit: patient's clinical characteristics and risk precipitating factor analysis.

The aim was to evaluate the prevalence of delirium among patients discharged from an acute care hospital and admitted to a geriatric convalescence unit (GCU), and to analyze patient's characteristics and risk precipitating factors. Sixty-eight patients were analyzed during a 2-week period. The confusion assessment method (CAM) was used to detect delirium. The precipitating factors evaluated were: major surgery-intensive care unit(ICU) stay, pulmonary and heart failure, acute infections, metabolic disorders/anemia,psychoactive medications, other drugs, severe pain, changing environmental influences and others. According to CAM, fifteen patients presented delirium (22%), and in 14 of them(93.3 %) the delirium was developed before admission at GCU. The precipitating factors in the studied population were the following: changing environmental influences in 66 patients(97%) (15 with delirium and 51 without delirium); other drugs 56 (82.3 %) (11 vs. 45);others 56 (82.3%) (9 vs. 24); psychoactive medications 50 (73.5%) (12 vs. 38); acute infections 48 (70.5 %) (13 vs. 35); metabolic disorders/anemia 40 (58.8 %) (9 vs. 31); major surgery-ICU stay 28 (41 .1%) (8 vs. 20); severe pain 26 (38.2%) (6 vs. 20); pulmonary and heart failure 22 (32.3%) (5 vs. 17). The univariant analysis showed that, none of the precipitating factors studied was significantly related to delirium. Seventy-two patients (91.1%) had simultaneously >3 precipitating factors. There were 16 patients with >6 precipitating factors, 7 of 15 with delirium and 9 of the 53 without delirium (46.6 % vs 16.9 %) (p < 0.05). The prevalence of delirium has been 22 %. Most of the patients had developed delirium before the admission at GCU. A high proportion of patients had >3 precipitating factors. In the study the presence of > 6 precipitating factors simultaneously has been significantly related to delirium.

Aged↗

Routine analysis of short-chain fatty acids for anaerobic bacteria identification using capillary electrophoresis and indirect ultraviolet detection.

The diagnosis of anaerobes can be difficult to perform, using classical biochemical tests. Characterization of metabolic end-products such as short-chain fatty acids (SCFA) was often used because of their reproducible biosynthesis. Despite this, SCFA are difficult to study using gas chromatography, due to their high volatility. Furthermore, the treatment of the samples are long and fastidious. Capillary electrophoresis and indirect UV detection (CE-indirect UV) is a well-known analytical method to study inorganic or organic anions. In this work, we validate the analysis of SCFA using CE-indirect UV detection. To do this, we studied the culture media of 98 anaerobic strains for the detection and quantitation of the following acids: succinic, pyruvic, acetic, lactic, propionic, 2-hydroxybutyric, butyric, 2-hydroxyvaleric, isovaleric, isocaproic, and 3-phenylpropionic. We verified that the CE-indirect UV detection analysis of SCFA for taxonomical data can be used as a mean for rapid identification for the study of anaerobes.

Bacteria, Anaerobic↗

Proper ascospore maturation requires the chs1+ chitin synthase gene in Schizosaccharomyces pombe.

We have cloned chs1+, a Schizosaccharomyces pombe gene with similarity to class II chitin synthases, and have shown that it is responsible for chitin synthase activity present in cell extracts from this organism. Analysis of this activity reveals that it behaves like chitin synthases from other fungi, although with specific biochemical characteristics. Deletion or overexpression of this gene does not lead to any apparent defect during vegetative growth. In contrast, chs1+ expression increases significantly during sporulation, and this is accompanied by an increase in chitin synthase activity. In addition, spore formation is severely affected when both parental strains carry a chs1 deletion, as a result of a defect in the synthesis of the ascospore cell wall. Finally, we show that wild-type, but not chs1-/chs1-, ascospore cell walls bind wheatgerm agglutinin. Our results clearly suggest the existence of a relationship between chs1+, chitin synthesis and ascospore maturation in S. pombe.

Base Sequence↗

Schizosaccharomyces pombe rho2p GTPase regulates cell wall alpha-glucan biosynthesis through the protein kinase pck2p.

Schizosaccharomyces pombe rho1(+) and rho2(+) genes are involved in the control of cell morphogenesis, cell integrity, and polarization of the actin cytoskeleton. Although both GTPases interact with each of the two S. pombe protein kinase C homologues, Pck1p and Pck2p, their functions are distinct from each other. It is known that Rho1p regulates (1,3)beta-D-glucan synthesis both directly and through Pck2p. In this paper, we have investigated Rho2p signaling and show that pck2 delta and rho2 delta strains display similar defects with regard to cell wall integrity, indicating that they might be in the same signaling pathway. We also show that Rho2 GTPase regulates the synthesis of alpha-D-glucan, the other main structural polymer of the S. pombe cell wall, primarily through Pck2p. Although overexpression of rho2(+) in wild-type or pck1 delta cells is lethal and causes morphological alterations, actin depolarization, and an increase in alpha-D-glucan biosynthesis, all of these effects are suppressed in a pck2 delta strain. In addition, genetic interactions suggest that Rho2p and Pck2p are important for the regulation of Mok1p, the major (1-3)alpha-D-glucan synthase. Thus, a rho2 delta mutation, like pck2 delta, is synthetically lethal with mok1-664, and the mutant partially fails to localize Mok1p to the growing areas. Moreover, overexpression of mok1(+) in rho2 delta cells causes a lethal phenotype that is completely different from that of mok1(+) overexpression in wild-type cells, and the increase in alpha-glucan is considerably lower. Taken together, all of these results indicate the presence of a signaling pathway regulating alpha-glucan biosynthesis in which the Rho2p GTPase activates Pck2p, and this kinase in turn controls Mok1p.

Cell Wall↗

Fusobacterium nucleatum involvement in adult periodontitis and possible modification of strain classification.

BACKGROUND: This investigation was designed to evaluate the involvement of Fusobacterium nucleatum clinical strains in adult periodontitis by subspecies and expression of hemagglutination activity. METHODS: Forty-nine Fusobacterium strains were isolated from 40 sites in 40 subjects presenting with adult periodontitis. F. nucleatum subspecies identification was based on the electrophoretic migration of glutamate dehydrogenase and 2-oxoglutarate reductase. Hemagglutination activity and inhibition by galactose were tested on sheep erythrocytes. RESULTS: The 49 isolates belonged to the F. nucleatum species with a predominance of the nucleatum (34.7%) followed by the vincentii (26.5%) subspecies. In parallel, 71% of the strains belonging to the nucleatum subspecies were preferentially associated with Porphyromonas gingivalis. Prevotella intermedia/nigrescens detection was essentially correlated with identification of Fusobacterium nucleatum subspecies vincentii. No correlation was established between any particular subspecies and the pathogenicity factors tested (hemagglutination and production of short-chain fatty acids). On the other hand, significant predominance (65%, P= 0.017) of strongly hemagglutinating strains (titre > or =8 U) was observed in the sites where Porphyromonas gingivalis, Prevotella intermedia/nigrescens and/or Campylobacter rectus were not detected. These strains also showed higher butyric acid production. CONCLUSION: The importance of the adherence factors for Fusobacterium nucleatum strains and their multimodal aspect may indicate a higher pathogenicity or a higher involvement of certain strains and could lead to a classification of these strains, which is more closely related to their implication in the development of periodontal disease.

Adult↗

RHO GTPases in the control of cell morphology, cell polarity, and actin localization in fission yeast.

The fission yeast Schizosaccharomyces pombe undergoes morphogenetic changes during both vegetative and sexual cell cycles that require asymmetric cell growth and actin cytoskeleton reorganisations. Different complex signal transduction pathways participate in S. pombe morphogenesis. The Rho family of GTPases are present in all eukaryotic cells, from yeast to mammals, and their role as key regulators in the signalling pathways that control actin organisation and morphogenetic processes is well known. In this review, we will briefly summarize the role of the Rho GTPases in the establishment and maintenance of cell polarity and growth of S. pombe. As in other fungi, S. pombe morphogenesis is closely related to cell wall biosynthesis, and Rho GTPases are critical modulators of this process. They provide the coordinated regulation of cell wall biosynthetic enzymes and actin organisation required to maintain cell integrity and polarised growth.

Actins↗

Determination of tartaric acid in solid wine residues by capillary electrophoresis and indirect UV detection.

Tartaric acid, used in pharmaceuticals and industrial food preparation, is an important by-product of wine preparation. It is produced by wine factories in large quantities and cannot be rejected into the environment. Wineries precipitate tartaric acid using calcium hydroxide and then evaporate the mixture. The raw compact powder obtained, which contains calcium tartarate and a lot of other constituents (sugars, tannins, etc.) is sold to factories which purify tartaric acid. The different analytical methodologies which are used to determine the tartaric acid concentration in the solid wine residues are long and tedious (Goldenberg method, 14 samples per day). They also suffer from poor reproducibility. Some other methods use ion chromatography or solid Fourier transform IR, which are not currently used for such topics. We propose a capillary electrophoresis method, which not only is very quick (2 min of analysis) but also highly reproducible. Finally it provides very simple electropherograms. The intra-day and inter-day repeatability, the inter-person reproducibility and recovery were estimated. They demonstrate the ruggedness of this new method.

Benzoates↗

Fission yeast alpha-glucan synthase Mok1 requires the actin cytoskeleton to localize the sites of growth and plays an essential role in cell morphogenesis downstream of protein kinase C function.

In fission yeast protein kinase C homologues (Pck1 and Pck2) are essential for cell morphogenesis. We have isolated mok1(+) in a genetic screen to identify downstream effectors for Pck1/2. mok1(+) is essential for viability and encodes a protein that has several membrane-spanning domains and regions homologous to glucan metabolic enzymes. mok1 mutant shows abnormal cell shape, randomization of F-actin and weak cell wall. Biochemical analysis shows that Mok1 appears to have alpha-glucan synthase activity. Mok1 localization undergoes dramatic alteration during the cell cycle. It localizes to the growing tips in interphase, the medial ring upon mitosis, a double ring before and dense dot during cytokinesis. Double immunofluorescence staining shows that Mok1 exists in close proximity to actin. The subcellular localization of Mok1 is dependent upon the integrity of the F-actin cytoskeleton. Conversely, overexpression of mok1(+) blocks the translocation of cortical actin from one end of the cell to the other. pck2 mutant is synthetically lethal with mok1 mutant, delocalizes Mok1 and shows a lower level of alpha-glucan. These results indicate that Mok1 plays a crucial role in cell morphogenesis interdependently of the actin cytoskeleton and works as one of downstream effectors for Pck1/2.

Actins↗

Schizosaccharomyces pombe protein kinase C homologues, pck1p and pck2p, are targets of rho1p and rho2p and differentially regulate cell integrity.

Schizosaccharomyces pombe rho1(+) is required for maintenance of cell integrity and polarization of the actin cytoskeleton. However, no other effector besides the (1,3)beta-D-glucan synthase enzyme has been identified in S. pombe. We have further investigated if rho1(+ )signalling could be also mediated by the two protein kinase C homologues, pck1p and pck2p. We show in this study that both kinases interact with rho1p and rho2p only when bound to GTP, as most GTPase effectors do. Interestingly, the interaction was mapped in a different part of the proteins than in Saccharomyces cerevisiae Pkc1p. Thus, active rho1p binds to the amino-terminal region of the pcks where two HR1 motifs are located, and binding to the GTPase dramatically stabilizes the kinases. Detailed biochemical analysis suggests that pck2p is more important in the regulation of the enzyme (1-3)beta-D-glucan synthase. Thus, overexpression of pck2(+), but not pck1(+), caused a general increase in cell wall biosynthesis, mainly in beta-glucan, and (1-3)beta-D-glucan synthase activity was considerably augmented. When this activity was separated into soluble and membrane fractions and reconstituted, the increase caused by pck2(+) overexpression was exclusively detected in the membrane component. We also show that both protein kinase C homologues are required for the maintenance of cell integrity. pck1delta and pck2delta strains present a number of defects related to the cell wall, indicating that this structure might be co-ordinately regulated by both kinases. In addition, pck2p, but not pck1p, seems to be involved in keeping cell polarity. Genetic evidence indicates that both pck1(+) and pck2(+) interact with cps1(+) and gls2(+), two genes similar to S. cerevisiae FKS1 and FKS2 that encode membrane subunits of the (1-3)beta-D-glucan synthase. pck1(+ )also showed a genetic interaction with ras1(+) and ral1(+) suggesting the existence of a functional link between both signalling pathways.

Amino Acid Sequence↗

The anti-cancer drug 5-fluorouracil is metabolized by the isolated perfused rat liver and in rats into highly toxic fluoroacetate.

We report the first demonstration of the biotransformation of the anti-cancer drug 5-fluorouracil (FU) into two new metabolites, alpha-fluoro-beta-hydroxypropionic acid (FHPA) and fluoroacetate (FAC), in the isolated perfused rat liver (IPRL) and in the rat in vivo. IPRL was perfused with solutions of pure FU at two doses, 15 or 45 mg kg(-1) body weight, and rats were injected i.p. with 180 mg of FU kg(-1) body weight. Fluorine-19 NMR analysis of perfusates from IPRL and rat urine showed the presence of the normal metabolites of FU and low amounts of FHPA (0.4% or 0.1% of injected FU in perfusates from IPRL treated with 15 or 45 mg of FU kg(-1) body weight, respectively; 0.08% of the injected FU in rat urine) and FAC (0.1% or 0.03% of injected FU in perfusates from IPRL treated with 15 or 45 mg of FU kg(-1) body weight, respectively; 0.003% of the injected FU in rat urine). IPRL was also perfused with a solution of alpha-fluoro-beta-alanine (FBAL) hydrochloride at 16.6 mg kg(-1) body weight dose equivalent to 15 mg of FU kg(-1) body weight. Low amounts of FHPA (0.2% of injected FBAL) and FAC (0.07%) were detected in perfusates, thus demonstrating that FHPA and FAC arise from FBAL catabolism. As FAC is a well-known cardiotoxic poison, and FHPA is also cardiotoxic at high doses, the cardiotoxicity of FU might stem from at least two sources. The first one, established in previous papers (Lemaire et al, 1992, 1994), is the presence in commercial solutions of FU of degradation products of FU that are metabolized into FHPA and FAC; these are formed over time in the basic medium necessary to dissolve the drug. The second, demonstrated in the present study, is the metabolism of FU itself into the same compounds.

Animals↗

Characterization of the geranylgeranyl transferase type I from Schizosaccharomyces pombe.

The Schizosaccharomyces pombe cwg2+ gene encodes the beta-subunit of geranylgeranyl transferase I (GGTase I), which participates in the post-translational C-terminal modification of several small GTPases, allowing their targeting to the membrane. Using the two-hybrid system, we have identified the cwp1+ gene that encodes the alpha-subunit of the GGTase I. cwp1p interaction with cwg2p was mapped to amino acids 1-244 or 137-294 but was not restricted to amino acids 137-244. The genomic cwp1+ was isolated and sequenced. It has two putative open reading frames of 677 and 218 bp, separated by a 51 bp intron. The predicted amino acid sequence shows significant similarity to GGTase I alpha-subunits from different species. However, complementation of Saccharomyces cerevisiae ram2-1 mutant by overexpressing the cwp1+ gene was not possible. Expression of both cwg2+ and cwp1+ in Escherichia coli allowed 'in vitro' reconstitution of the GGTase I activity. S. pombe cells expressing the mutant enzyme containing the cwg2-1 mutation do not grow at 37 degrees C, but the growth defect can be suppressed by the addition of sorbitol. Actin immunostaining of the cwg2-1 mutant strain grown at 37 degrees C showed an abnormal distribution of actin patches. The cwg2-1 mutation was identified as a guanine to adenine substitution at nucleotide 604 of the coding region, originating the change A202T in the cwg2p. Deletion of the cwg2 gene is lethal; delta cwg2 spores can divide two or three times before losing viability. Most cells have aberrant morphology and septation defects. Overexpression of the rho1G15VC199R double-mutant allele in S. pombe caused loss of polarity but was not lethal and did not render the (1-3)beta-D-glucan synthase activity independent of GTP. Therefore, geranylgeranylation of rho1p is required for the appropriate function of this GTPase.

Actins↗

The Cdk inhibitors p25rum1 and p40SIC1 are functional homologues that play similar roles in the regulation of the cell cycle in fission and budding yeast.

p25rum1 and p40SIC1 are specific inhibitors of p34(cdc2/CDC28) kinase complexes with B-type cyclins that play a central role in the regulation of the G1 phase of the cell cycle. We show here that low levels of expression of SIC1 in Schizosaccharomyces pombe rescues all the phenotypes of cells lacking the rum1+ gene. In addition, high level expression of SIC1 in S. pombe induces extra rounds of DNA replication without mitosis, a phenotype very similar to the overexpression of rum1+. Transient expression of rum1+ in S. cerevisiae restores the G1 arrest phenotype of cdc4 sic1Delta double mutants. Overproduction of rum1+ in Saccharomyces cerevisiae causes a cell cycle block in G1 with a phenotype similar to inactivation of all the Clb cyclins. Finally, we have mapped the cyclin interacting domain and Cdk inhibitory domain to a region of about 80 amino acids in p25rum1 that has significant homology to the C-terminal domain of p40SIC1. All these observations suggest that fission yeast p25rum1 and budding yeast p40SIC1 define a family of Cdk inhibitors that specifically down regulate cyclin B/Cdk1 during the G1 phase of the cell cycle.

Cell Cycle↗