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Biomedical subjects

A Dominguez

Publications and source records attributed to A Dominguez.

At least 37 records · Page 2Linked to original sources
PubMed2000

Hereditary nonpolyposis colorectal cancer (Lynch syndrome II) in Uruguay.

PURPOSE: We updated an Uruguayan family with hereditary nonpolyposis colorectal cancer first described in 1977, incorporating knowledge of how the hMLH1 germline mutation has been established and shown to segregate in accord with the expected autosomal dominant mode of genetic transmission. METHODS: DNA-based molecular genetic testing was performed in conjunction with genetic counseling. Individuals were provided with their genetic test results, so that at-risk family members would be able to benefit from targeted management programs. RESULTS: We counseled 19 members of this kindred, 13 of whom were positive for the hMLH1 germline mutation. Specific recommendations for surveillance and management were provided. We were able to describe follow-up, including anecdotal cancer survival and pathology findings extending from the initial 1977 report of this family to the present. A remarkable sibship within this kindred was comprised of eight siblings, six of whom underwent resections for colorectal carcinoma between 1963 and 1971. Colon carcinomas before 1977 in this sibship were treated with classic hemicolectomies. Of those who had hemicolectomies for their first primary colorectal cancers, two had a second colon cancer primary, and two had a third colon cancer primary. CONCLUSIONS: Attention given to this extended family with hereditary nonpolyposis colorectal cancer has had a positive impact on the physician community in Uruguay, leading to the identification of additional families with hereditary nonpolyposis colorectal cancer.

Adaptor Proteins, Signal Transducing↗
PubMed2000

Molecular typing of methicillin-resistant Staphylococcus aureus by pulsed-field gel electrophoresis: comparison of results obtained in a multilaboratory effort using identical protocols and MRSA strains.

Pulsed-field gel electrophoresis (PFGE) has become the gold standard of molecular methods in epidemiological investigations. In spite of its high resolving power, use of the method has been hampered by inadequate laboratory-to-laboratory reproducibility. In the project described here we have addressed this problem by organizing a multilaboratory effort in which the same bacterial strains (subtype variants of the Iberian and Brazilian methicillin-resistant Staphylococcus aureus--MRSA--clones) were analyzed by twenty investigators in thirteen different laboratories according to an indentical protocol, which is reproduced here in detail. PFGE patterns obtained were analyzed at a central laboratory in order to identify specific technical problems that produced substandard macrorestriction patterns. The results including the specific technical problems and their most likely causes are described in this communication. Also listed are seven major epidemic clones of MRSA which have been characterized by molecular fingerprinting techniques and the prototypes of which have been deposited at the American Type Culture Collection, from where they will be available for interested investigators for the purpose of typing MRSA isolates. It is hoped that this communication will contribute to the improvement of the reproducibility and technical/aesthetic quality of PFGE analysis.

Bacterial Typing Techniques↗
PubMed2000

Transport and metabolism of serotonin in the human placenta from normal and severely pre-eclamptic pregnancies.

We have attempted to elucidate the possible participation of serotonin as an etiological factor in pre-eclampsia. The transport of serotonin into vesicles from the maternal-facing brush border membrane was measured, as well as the metabolism induced by monoamine oxidase (MAO) in placental homogenate obtained from normal-term and severely pre-eclamptic placentas. Kinetic analysis of serotonin uptake by the placental brush border membrane of the syncytiotrophoblast between normally pregnant and severely pre-eclamptic subjects showed no significant difference (similar Vmax and Km values). However, the metabolism of serotonin was significantly higher in placental homogenate from normal pregnancies than in placentas from severely pre-eclamptic pregnancies. These findings suggest that the higher plasma-free serotonin levels observed in severe pre-eclampsia are mainly due to a reduction in MAO-A activity and not limited by the rate of serotonin uptake into the cells.

Adult↗
PubMed1999

Sequence analysis of SLA2 of the dimorphic yeasts Candida albicans and Yarrowia lipolytica.

We report the complete nucleotide sequence of SLA2 of the dimorphic yeasts Candida albicans and Yarrowia lipolytica. In Saccharomyces cerevisiae, SLA2 codes for an actin binding protein. The deduced amino acid (aa) sequences of C. albicans CaSla2p and Y. lipolytica YlSla2p consist of 1063 and 1054 aa, respectively. The alignment of the deduced proteins of Saccharomyces cerevisiae, Y. lipolytica and C. albicans shows regions of identity in the N-terminal part of the proteins, which are essential for growth at 37 degrees C, endocytosis and actin organization in S. cerevisiae. The Sla2p proteins have also several conserved regions in the C-terminal moiety, the I/LWEQ boxes, displaying homology to the talin protein of mouse, Dictyostelium discoideum, Caenorhabditis elegans and to human huntingtin interacting protein (Hip 1p). The sequence data of C. albicans SLA2 are registered in the EMBL database (AJ009556), and for the Y. lipolytica gene in GenBank (U65409).

Amino Acid Sequence↗
PubMed1999

Control of filament formation in Candida albicans by polyamine levels.

Candida albicans, the most common fungal pathogen, regulates its cellular morphology in response to environmental conditions. The ODC gene, which encodes ornithine decarboxylase, a key enzyme in polyamine biosynthesis, was isolated and disrupted. Homozygous null Candida mutants behaved as polyamine auxotrophs and grew exclusively in the yeast form at low polyamine levels (0.01 mM putrescine) under all conditions tested. An increase in the polyamine concentration (10 mM putrescine) restored the capacity to switch from the yeast to the filamentous form. The strain with a deletion mutation also showed increased sensitivity to salts and calcofluor white. This Candida odc/odc mutant was virulent in a mouse model. The results suggest a model in which polyamine levels exert a pleiotrophic effect on transcriptional activity.

Alleles↗
PubMed1998

Analysis of the ntp1+ gene, encoding neutral trehalase in the fission yeast Schizosaccharomyces pombe.

We have cloned and sequenced the ntp1+ gene that codes for neutral trehalase in the fission yeast Schizosaccharomyces pombe. The ntp1+ gene product (Ntp1p) showed a 45-55% identity with neutral trehalases from other yeasts at the amino acid sequence level. However, in clear contrast to other neutral yeast trehalases so far characterized (which show two cAMP phospho-sites), only one consensus site for cAMP-dependent protein phosphorylation was found in Ntp1p. Northern blot hybridization experiments demonstrated that the Wis-Phh1/Sty1 MAP kinase cascade regulates ntp1+ expression during osmostress.

Amino Acid Sequence↗
PubMed1996

Cloning and sequencing of the LYS1 gene encoding homocitrate synthase in the yeast Yarrowia lipolytica.

The alpha-aminoadipate pathway for the biosynthesis of lysine is present only in fungi and euglena. The first step in the pathway is the condensation of acetyl-CoA and alpha-ketoglutarate into homocitrate, and this step is carried out by the enzyme homocitrate synthase (EC 4.1.3.21). In spite of extensive genetic analysis, no mutation affecting this step has been isolated until now in model organisms such as Saccharomyces cerevisiae or Neurospora crassa, although identification of mutations affecting the structural gene (LYS1) for homocitrate synthase was reported in the yeast Yarrowia lipolytica several years ago. Here we used these mutants for the cloning and sequencing of the Yarrowia LYS1 gene. The LYS1 gene encodes a predicted 446 amino acid polypeptide, with a molecular mass of 48442 Da. The Lys1p sequence displays two regions, one near the N-terminal section and the other in the central region, that contain conserved signatures found in prokaryotic homocitrate synthases (nifV genes of Azotobacter vinelandii and Klebsiella pneumoniae), as well as in all alpha-isopropyl malate synthases so far described. A putative mitochondrial targeting signal of 41-45 amino acids is predicted at the N-terminus. The Lys1p sequence shows 84% identity at the amino acid level with the putative product of open reading frame D1298 of S. cerevisiae. Northern blot hybridizations revealed a LYS1 transcript of approximately 1.7 kb in Y. lipolytica. Deletion of the LYS1 gene resulted in a Lys- phenotype. Our results indicate that we cloned the structural gene for homocitrate synthase in Y. lipolytica, and that the enzyme is encoded by a single gene in this yeast.

Amino Acid Sequence↗
PubMed1996

Comparison of fungal ornithine decarboxylases.

We designed PCR primers by comparison of the deduced amino acid sequences of several ornithine decarboxylase (ODC) genes. They were used to amplify fragments homologous to these genes from several dimorphic fungi. These were sequenced and the deduced amino acid sequences were compared with the corresponding regions of ODCs from different sources. Fungal ODCs fell into a compact group, well separated from the ODCs of other taxa. Sequence homology among fungal enzymes corresponded to their taxonomic position. Interesting patterns of amino acid conservation in ODCs from fungi, distinct from other organisms, were detected.

Amino Acid Sequence↗
PubMed1996

Effects of HOE 140 on some renal functions in type I diabetic mice.

To investigate in mice the mechanisms underlying renal functions in a type I diabetes model, we have suppressed B2 kinin receptors local activities by their specific antagonist D-Arg [Hyp3-Thi5-D-Tic7-Oic8]BK (HOE 140). Mice made diabetic with low consecutive doses of streptozotocin (STZ) (45 mg/k BW during 5 days) were injected with HOE 140 (15 micrograms/twice a day) for 15 days. This drug did not modify glycemia of STZ treated animals but a significantly reduction of urinary proteins, nitrites and kallikrein was observed. These results indicate that kinin B2-receptors activation is implicated in the alterations of renal function in this model of type I diabetes in mice.

Analysis of Variance↗
PubMed1996

Distinctive control of metabolic pathways by Chlorella autotrophica in semicontinuous culture.

The marine microalga Chlorella autotrophica was cultured semicontinuously under light-dark synchronizing conditions at two nutrient concentrations (2 and 4 mmol N.L-1) and five rates of daily renewal (from 10 to 50% of culture volume). Under such conditions, the biochemical composition of C. autotrophica was strongly influenced by the renewal rate, but unlike other marine microalgae, the nutrient concentration had no effect on the biochemical composition of the organic fraction of the microalga at a given growth rate. Results suggest that this species exerts a strong control over metabolic pathways, independent of the nutrient concentration in the medium.

Carbohydrates↗
PubMed1996

Evaluation of lead levels in children living near a Los Angeles county battery recycling facility.

This cross-sectional study examined the association between environmental lead measurements surrounding a Los Angeles County battery recycling facility and the blood lead levels of the children living nearby. Environmental lead measurements and blood lead levels of young children living in a community adjacent to a stationary lead source were compared to those living in a community without a stationary lead source. Predictors of blood lead level were identified. The blood lead levels of the children living near the secondary lead smelter were within the normal range (< 5 micrograms/dl). The absence of ground cover was associated with slightly increased blood lead levels; however, this increase was not of biological significance. Lead levels in surface soil near the stationary lead source were elevated compared to the control community; however, the soil affected community, which may be due in part to controls recently installed at the stationary lead source.

California↗
PubMed1995

Utility of the gallium-67 citrate scan for the early diagnosis of tuberculosis in patients infected with the human immunodeficiency virus.

Diagnosis of tuberculosis in patients infected with the human immunodeficiency virus (HIV) is sometimes difficult because of atypical clinical and radiographic findings. The aim of this retrospective study was to determine the utility of a gallium-67 citrate scan (67Ga scan) of the chest for the early diagnosis of tuberculosis in patients infected with HIV. We selected 174 67Ga scans performed as a part of the clinical evaluation of 145 HIV-infected patients with normal pulmonary parenchyma (seen on chest radiographs) and fever of unknown origin. Scans were evaluated as to whether there was uptake in lymphoid regions (a positive 67Ga scan) or not (a negative scan). Tuberculosis was the most common condition associated with a positive 67Ga scan (48[72.7%] of 66 positive 67Ga scans). Nodal uptake had a 72.7% positive predictive value and a 92.6% negative predictive value for tuberculosis. In our experience, 67Ga scanning is a useful tool for the clinical evaluation of HIV-infected patients with unexplained fever. In areas with a high prevalence of tuberculous infection, a 67Ga scan of an HIV-infected patients that shows nodal uptake allows the clinician to initiate prompt empirical antituberculous therapy while waiting for culture results. Conversely, a 67Ga scan that does not show nodal uptake makes the diagnosis of tuberculosis unlikely.

AIDS-Related Opportunistic Infections↗
PubMed1994

Streptozotocin-induced hyperglycemia is decreased by nitric oxide inhibition.

1. Diabetes mellitus type I was induced in 3-month old male C57 BL/KS-mdb mice (N = 24) by ip injection of streptozotocin (STZ, 45 mg/kg body weight) for 5 days. 2. To determine the possible protective effects of nitric oxide inhibition against hyperglycemia, the STZ-diabetic rats received two doses of NG-nitro-L-arginine- methyl ester (L-NAME) (10 mg/kg body weight and 10 mg/mouse) dissolved in PBS for 45 consecutive days. Another group of STZ-treated rats was similarly treated with L-arginine (5 mg/mouse). 3. Blood glucose levels were 118 +/- 37 mg/dl after 8 days of L-NAME administration (10 mg/kg body weight, N = 12) and 186 +/- 22 mg/dl (N = 12) after 5 days of L-NAME administration at the 5 mg/mouse dose. Treatment with L-arginine (5 mg/mouse, N = 12) caused a significant increase in blood glucose level to 151 +/- 17.5 mg/dl, showing the relevance of nitric oxide formation in this type of diabetes. 4. In STZ-diabetic mice treated with L-NAME (N = 12), diuresis was reduced by approximately 58% compared to STZ animals, whereas in L-arginine-treated animals (N = 12) diuresis returned to STZ levels. Urinary protein excretion, which was significantly affected by STZ (123% compared to control) was significantly reduced by 66% after treatment with L-NAME for 45 days, whereas treatment with L-arginine caused a return to STZ values. 5. Urinary kallikrein excretion, which was reduced by 80% in STZ mice compared to control, returned to control levels after L-NAME treatment. 6. The present results suggest a relationship between nitric oxide levels and the reduction of diabetic state and improved renal function by L-NAME.

Animals↗
PubMed1993

Kinetic behaviour of a repressible acid phosphatase from the yeast Yarrowia lipolytica: a comparative study between the solubilized enzyme, the enzyme bound to cell-wall fragments and the enzyme bound to intact cells.

(1) The substrate specificities and types of inhibitors of a repressible acid phosphatase from the yeast Yarrowia lipolytica as solubilized enzyme, enzyme bound to cell-wall fragments and enzyme bound to the intact cell were found to be essentially the same. (2) A similar pattern for the activation of the enzymatic activity by ionic strength was found for solubilized enzyme, the enzyme in cell-wall fragments and the enzyme in intact cells. (3) v[S] studies with all three locations of the enzyme revealed non-linear Eadie-Hofstee plots with concave-up curves of the negative cooperativity type; these were correctly fitted with a rate equation of 2:2 degree polynomial quotient. In all cases, the same behaviour was obtained and no new kinetic properties were observed when the enzyme was bound to the cell-wall matrix with respect to the solubilized enzyme. (4) Inhibition by phosphate was characterized for the three locations of the enzyme by v[I] and v[S] studies. The same pattern of partial inhibition and non-Michaelian inhibition of 'non-competitive' nature was observed for all three forms. (5) The above results are interpreted in terms of the hypothesis that the cell wall of Y. lipolytica has a slight negative charge but behaves as a permeable matrix that does not lead to novel characteristics regarding the catalytic and regulatory properties shown by the enzyme molecule in free solution.

Acid Phosphatase↗
PubMed1993

Prehepatic portal hypertension in rats modifies norepinephrine metabolism in hypothalamus, medulla oblongata and portal vein.

The present experiments investigated the possible relationship between portal hypertension and norepinephrine metabolism in the central nervous system (hypothalamus and medulla oblongata) and the portal vein in the rat. Group I (72), portal hypertensive, and group II (70) sham-operated animals, were sacrificed day 14, and endogenous norepinephrine content, uptake and release from hypothalamus, medulla oblongata, and portal vein were investigated. In group I our results showed increases in norepinephrine storage (69%; 8.3%) and release (19.7%; 43.8%) and a diminished uptake (42.3%; 27.5%) in the hypothalamus and medulla oblongata, respectively. Portal veins showed a decreased content and uptake (62.5% and 43.5%, respectively) and increased release (25%) compared to group II rats. These results suggest a close relationship between the central nervous system and rat portal hypertension, perhaps related to modifications of central sympathetic activity.

Animals↗
PubMed1992

Giant ovarian cyst: case report.

We present the case of a woman 22 years old with an ovarian cyst of 6 years' duration. The total weight of the tumor was 154 pounds (70 kg). She was treated surgically with good results.

Adult↗
PubMed1991

Theophylline produces an adverse effect on myocardial lactate metabolism at a therapeutic serum concentration: an effect blocked by verapamil.

To assess the actions of theophylline on coronary blood flow and myocardial energetics, 1 mg/kg/min of this methylxanthine was infused i.v. in the dog for 15 min, producing an average concentration of 18 +/- 3 micrograms/ml. Heart rate increased by 20 +/- 7 min-1, P less than .05, but left ventricular (LV) systolic and end-diastolic pressures, cardiac output and LV peak dp/dt did not change. Although coronary vascular resistance decreased by 0.26 +/- 0.08 mm Hg/ml/min, P less than .05, coronary flow and myocardial oxygen consumption and extraction did not change. Myocardial lactate extraction decreased, from 22 +/- 2 to 1 +/- 5%, P less than .05. The decrement in lactate extraction was not related to heart rate, but to the change in LV peak dp/dt, r = 0.74, P less than .05. Furthermore, with verapamil, 0.2 mg/kg, pretreatment, and 0.2 mg/kg, during the theophylline infusion, reduction in lactate extraction was blocked and LV peak dp/dt increased by 843 +/- 311 mm Hg/sec, P less than .05. Thus, at therapeutic concentrations, theophylline reduces myocardial lactate extraction, an effect that is associated with the absence of the expected inotropic actions of theophylline. However, when verapamil is administered with theophylline, a reduction of myocardial extraction does not occur and myocardial inotropy is enhanced.

Animals↗