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Biomedical subjects

C Garcia

Publications and source records attributed to C Garcia.

At least 55 records · Page 3Linked to original sources

Cardiac involvement in autosomal-dominant polycystic kidney disease: a hypertensive heart disease.

BACKGROUND: There is little information regarding the occurrence and distribution of cardiovascular abnormalities during the course of autosomal-dominant polycystic kidney disease (ADPKD). We conducted a cross-sectional study in three different groups of ADPKD patients to determine the profile and prevalence of cardiac involvement in this population. METHODS: Doppler color echocardiography was performed in 130 ADPKD patients. Patients were divided into normotensive (Group I, n=60), hypertensive (Group II, n=32) and those undergoing hemodialysis (Group III, n=38). RESULTS: There was a progressive increase in left ventricular mass (LVM) index (88.6+/-19.7, 127.6+/-40.4 and 150.5+/-56.5 g/m2, p < 0.0001) and in the prevalence of left ventricular hypertrophy (LVH) (3%, 43%, 62%, p < 0.0001) in Groups I, II and III, respectively. E/A ratio < 1 was found in 2% of normotensives, 46% of hypertensives and 62% of hemodialysis patients (p < 0.0001). Prevalence ofmitral valve prolapse and aortic and/or mitral regurgitation was 4.3% and 8.6%, respectively, in non-dialysis patients. The majority of valvular abnormalities occurred in dialysis patients, and were generally related to annular mitral calcification (28%) or aortic valve calcification (38%). Age, sex, systolic blood pressure (BP) and hemoglobin were independent predictors of LVM index in the entire population, systolic BP and creatinine in non-dialysis patients and systolic BP in dialysis patients. Age, heart rate and diastolic BP in the entire group, and age, heart rate and LVM index in non-dialysis patients remained as independent predictors of abnormal diastolic function. CONCLUSIONS: Cardiac involvement in ADPKD patients is a continuous process that evolves during the course of this disease. It is characterized by a low prevalence of specific valvular abnormalities, a progressive increase in LVM, LVH, and diastolic dysfunction, which are greatest in the latter stages of the disease. This study confirms the major influence of BP on cardiovascular abnormalities of ADPKD patients.

Adult↗

[Anti-endothelial cell antibodies in chronic leg ulcer: prevalence and significance].

BACKGROUND: Anti-endothelial cell antibodies are detected in auto-immune vasculitis and connective tissue diseases such as scleroderma, with possible pathogenic involvement. We looked for these antibodies in patients presenting chronic ulcers. PATIENTS AND METHODS: Eighty patients were tested: 35 presented vascular ulcers (27 of venous origin and 8 arterial). A control group of 14 patients with connective tissue disease and vasculitis was formed, and a third group included 31 patients without vascular or immune disease. Their sera were tested by ELISA technique on EAhy 926 cell (obtained from hybridization of human endothelial and line A 549/8 cells). RESULTS: Blood tests were positive in 37.5 p. 100 of patients. Antibodies were present in 48.5 p. 100 of patients with leg ulcers (of which 59 p. 100 (16/27) venous ulcers). Fifty-seven per cent of the autoimmune group and 12 p. 100 of the third group were positive. Association with anti-phospholipid antibodies was observed twice in leg ulcers. The level of antibodies was higher in patients with leg ulcers. COMMENTS: The presence of high levels of anti-endothelial cells antibodies in 48.5 p. 100 of patients presenting leg ulcers shows that these antibodies are not specific to autoimmune diseases. Since they are involved in coagulation, inflammation (enhancing of adhesion molecules and tissue lysis) and apoptosis of endothelial cells, their significance in chronic ulcers, both as a consequence and/or possible cofactor merits discussion.

Adolescent↗

A subset of NKT cells that lacks the NK1.1 marker, expresses CD1d molecules, and autopresents the alpha-galactosylceramide antigen.

In the present report, we characterize a novel T cell subset that shares with the NKT cell lineage both CD1d-restriction and high reactivity in vivo and in vitro to the alpha-galactosylceramide (alpha-GalCer) glycolipid. These cells preferentially use the canonical Valpha14-Jalpha281 TCR-alpha-chain and Vbeta8 TCR-beta segments, and are stimulated by alpha-GalCer in a CD1d-dependent fashion. However, in contrast to classical NKT cells, they lack the NK1.1 marker and express high surface levels of CD1d molecules. In addition, this NK1.1(-) CD1d(high) T subset, further referred to as CD1d(high) NKT cells, can be distinguished by its unique functional features. Although NK1.1(+) NKT cells require exogenous CD1d-presenting cells to make them responsive to alpha-GalCer, CD1d(high) NKT cells can engage their own surface CD1d in an autocrine and/or paracrine manner. Furthermore, in response to alpha-GalCer, CD1d(high) NKT cells produce high amounts of IL-4 and moderate amounts of IFN-gamma, a cytokine profile more consistent with a Th2-like phenotype rather than the Th0-like phenotype typical of NK1.1(+) NKT cells. Our work reveals a far greater level of complexity within the NKT cell population than previously recognized and provides the first evidence for T cells that can be activated upon TCR ligation by CD1d-restricted recognition of their ligand in the absence of conventional APCs.

Animals↗

Standardization of experimental infection with Flavobacterium psychrophilum, the agent of rainbow trout Oncorhynchus mykiss fry syndrome.

Rainbow trout fry syndrome (RTFS) is a septicaemic infection of young rainbow trout Oncorhynchus mykiss occurring at low temperatures and responsible for severe economic losses in European fish farming. The causative agent, Flavobacterium psychrophilum, is a gliding bacterium, and difficulties in culturing it have long been an impediment to investigations on pathogenesis and immunity. Successful attempts at experimentally inducing the disease have been reported, but no experimental model resulting in well-controlled and quantitatively reproducible effects has been described. Recent improvements in F. psychrophilum cultivation made it possible to produce bacterial suspensions with nearly constant viability and to complete challenge injections in rainbow trout fingerlings, using accurately adjusted infective doses. Parenteral injection resulted in significant mortality, which was higher when administered intramuscularly (IM) than intraperitoneally (IP). Lethal doses 50 % lower than 10(3) colony forming units were consistently obtained in trout weighing 3 to 5 g, and the regular shape of the cumulative mortality curves appeared to lend itself to quantitative analyses. Bath experiments produced milder effects, although mortality ranging between 45 and 60 % was obtained in 6 g trout when skin lesions or stressors were induced along with bacterial exposure. Temperature, salinity and the process of preserving isolates (at least over short periods of time) did not seem to be associated with the severity of infection. Nevertheless, infection trials performed at 2 different locations differing both in water quality and in the system of fish maintenance resulted in different mortalities. These findings notwithstanding, the proposed IM model appears easy to apply under standardized experimental conditions and should contribute to effective advances in the study of the disease.

Animals↗

Changes in the apomyoglobin folding pathway caused by mutation of the distal histidine residue.

Factors governing the folding pathways and the stability of apomyoglobin have been examined by replacing the distal histidine at position 64 with phenylalanine (H64F). Acid and urea-induced unfolding experiments using CD and fluorescence techniques reveal that the mutant H64F apoprotein is significantly more stable than wild-type apoMb. Kinetic refolding studies of this variant also show a significant difference from wild-type apoMb. The amplitude of the burst phase ellipticity in stopped-flow CD measurements is increased over that of wild-type, an indication that the secondary structure content of the earliest kinetic intermediate is greater in the mutant than in the wild-type protein. In addition, the overall rate of folding is markedly increased. Hydrogen exchange pulse labeling was used to establish the structure of the initial intermediate formed during the burst phase of the H64F mutant. NMR analysis of the samples obtained at different refolding times indicates that the burst phase intermediate contains a stabilized E helix as well as the A, G, and H helices previously found in the wild-type kinetic intermediate. Replacement of the polar distal histidine residue with a nonpolar residue of similar size and shape appears to stabilize the E helix in the early stages of folding due to improved hydrophobic packing. The presence of a hydrophilic histidine at position 64 thus exacts a price in the stability and folding efficiency of the apoprotein, but this residue is nevertheless highly conserved among myoglobins due to its importance in function.

Amino Acid Substitution↗

Synthesis of novel push-pull unsymmetrically substituted alkynyl phthalocyanines

Two families of "push-pull" phthalocyanines 1-3 having an unusually strong dipole moment have been prepared. The syntheses of unsymmetrically substituted phthalocyanines 1a,b and 2 bearing one or two electron-withdrawing 4-nitrophenylethynyl moieties, respectively, and six alkoxy substituents were performed by combination of a zinc or nickel templated cyclotetramerization and cross-coupling palladium mediated methodologies. In a similar way, the "push-pull" compounds 3a,b having a reversal substitution pattern, characterized by the presence of one electron-donor 4-(dimethylamino)phenylethynyl unit and six strong acceptor alkylsulfonyl substituents were prepared. The compounds show very large second-order nonlinear optical responses.

Journal Article↗

In situ examination of tyrosine hydroxylase activity in the rat locus coeruleus using (3',5')-[(3)H(2)]-alpha-fluoromethyl-tyrosine as substrate of the enzyme.

Tyrosine hydroxylase (TH) activity can be modified by changes in the specific activity of the enzyme (SA(TH)) or in the levels of active enzyme. We developed a methodology making it possible to measure with excellent anatomical resolution TH enzymatic activity and TH protein quantity by quantitative autoradiography and immunoautoradiography, respectively, from adjacent sections taken at serial intervals along the longitudinal extent of a same brain. SA(TH) was estimated by the slope of linear regressions established between TH activity and TH quantity measured at each anatomical plane. To evaluate TH activity, we used (3',5')-[(3)H(2)]-(D, L)-alpha-fluoromethyl-tyrosine [(3)H(2)]-MFMT, which is transformed by TH to [(3)H]-MFM-dopa, a potent and irreversible substrate for aromatic amino acid decarboxylase. We found that the SA(TH) in the cell body area of the LC (PKA) was 48% lower than that evaluated in the surrounding pericoerulean neuropil (PCN). In the PCN, 22% only of TH level exhibited a level of enzymatic activity above threshold. We also examined how SA(TH) was distributed in the LC 15 min and 3 days after RU 24722 treatment, a potent phasic and tonic activator of TH enzyme in noradrenergic neurons. Two distinct mechanisms have been observed: the short-term effect was due to an increase in the SA(TH) in the PKA only, while the long-term effect was mainly caused by an increase in the number of active TH proteins in the PCN. These results suggest that the fine regulation of TH activity which occurs in the different compartments of LC neurons may be critical in the functions involving the LC.

Animals↗

Selective involvement of the Fas (CD95)/Fas ligand pathway in bone marrow B cell progenitors.

B lymphocyte generation in bone marrow (BM) compensates for cell loses. The Fas / Fas ligand (FasL) pathway has been implicated in apoptosis of various cell types. Abnormalities of the Fas receptor or of FasL expression are associated with excessive T cell proliferation and autoimmunity. To examine the role of the Fas / FasL system in B cell differentiation, we created double-chimeric mice by transferring both C57BL / 6 (B6)-Fas(+) and lpr-FasL(+) BM cells into RAG-2(- / -) hosts. Equal numbers of stem cells were co-injected into sublethally irradiated recipients, and their progeny were studied by using antibodies directed against the B6-Ly5. 1(+)5.2(+) and lpr-Ly5.1(-)5.2(+) populations. A longitudinal study lasting for up to 6 months revealed that cells of the lpr phenotype dominated the B6 phenotype in the BM, as a result of their active proliferation. Analysis of the B cell compartment showed more lpr than B6 cells among immature HSA(hi)B220(lo) populations. In contrast, the lpr and B6 phenotypes were equally represented among mature B cells. BM transfer to second hosts indicated that B6-derived B cell progenitors were absent from the first host. These data suggest that activation of the Fas / FasL pathway disturbs the early steps of B cell development and might therefore contribute to the onset of autoimmune disorders.

Animals↗

Fine-needle aspiration diagnosis of Kaposi's sarcoma in a developing country.

Fine-needle aspiration (FNA) cytology was performed on 15 patients with peripheral lymphadenopathy and/or skin lesions referred to the Department of Pathology of the Hospital Central of Maputo, Maputo, Mozambique. Epitrochlear lymph nodes were the most frequently aspirated site. All aspirates allowed diagnoses of Kaposi's sarcoma (KS). Smears contained loosely cohesive clusters of bland spindle cells, with a radial arrangement and nuclear crush artifacts. These diagnostic clues have not been described in other spindle-cell intranodal lesions that should be considered in differential diagnoses. Taking into consideration the high prevalence of AIDS and limited resources for diagnosis in Africa, FNA cytology appears to be a useful method for the diagnosis of KS in developing countries, reducing the necessity for surgical lymph node excision.

AIDS-Related Opportunistic Infections↗

Binding properties of a selective tritiated vasopressin V2 receptor antagonist, [H]-SR 121463.

BACKGROUND: [3H]-SR 121463 is the first radiolabeled selective nonpeptide vasopressin V2 receptor antagonist ligand that has been reported to date. In the present work, we studied the binding properties of [3H]-SR 121463 for renal V2 receptors from animal and human origins. METHODS: Binding studies were performed with [3H]-SR 121463 in Chinese hamster ovary (CHO) cells transfected with the human V2 receptor and in various kidney preparations expressing the native V2 receptors (rat, rabbit, dog, pig, monkey, and human). Autoradiographies were performed in rat and human kidney sections. RESULTS: [3H]-SR 121463 binding to CHO cells stably transfected with the cloned human renal V2 receptor was specific, highly stable, time dependent, saturable, and reversible. A single population of high-affinity binding sites was identified (Kd = 0.94 +/- 0.34 nmol/L, Bmax = 9876 +/- 317 fmol/mg protein). Of note, [3H]-SR 121463 revealed a higher number (about 40%) of V2 sites than [3H]-AVP in the same preparation. Displacement of [3H]-SR 121463 binding by reference peptide and nonpeptide vasopressin/oxytocin compounds exhibited a typical AVP V2 profile. [3H]-SR 121463 also displayed a high affinity for native V2 receptors in several kidney preparations from rat, pig, dog, rabbit, bovine, monkey, and human. The autoradiographic experiments using rat and human kidney sections showed intense labeling in the medullopapillary region and lower intensity in the cortex, consistent with a main localization of V2 receptors on collecting tubules. CONCLUSION: [3H]-SR 121463 is a useful ligand for the specific labeling of animal and human V2 receptors and could be a suitable probe for the search and in situ localization of V2 sites.

Animals↗

Alexandrite laser hair removal is safe for Fitzpatrick skin types IV-VI.

BACKGROUND: Various lasers have been developed for epilation of unwanted hair. Most studies, however, have been done in white patients with minimal reference to dark-skinned individuals. OBJECTIVE: To determine the safety profile of a long-pulsed alexandrite laser for hair removal in patients with Fitzpatrick skin types IV-VI exclusively. METHODS: Prospective clinical evaluation conducted from June 1998 to April 1999 at a referral private clinic. Prelaser skin testing was performed starting at 16 J/cm2 and energy fluence selected according to response. Complications were recorded at each visit. RESULTS: One hundred and fifty patients are reported (18 men and 132 women) ranging in age from 15 to 50 years, for a total of 550 treatment sites. Complications occurred in only 2% of cases. CONCLUSION: The long-pulsed alexandrite laser is safe for hair removal in darker skin tones. Prelaser skin testing was not helpful in this study, as there was no relationship between skin reaction and the incidence of complications.

Adolescent↗

Touch-Sensitive NADH Oxidase Activity of Pea and Cucumber Tendrils and Soybean Hypocotyl Sections.

The cell surface reduced nicotinamide adenine dinucleotide (NADH) oxidase activity of soybean stems and of pea and cucumber tendrils responded to touch with a several-fold increase in activity. The increase in NADH oxidase persisted for 20 min or longer, and further touch stimulation during this period did not alter activity. With soybean sections, the specific activities in response to touch approximated those achieved maximally by auxin. Where the NADH oxidase was fully stimulated by 2,4-d, the NADH oxidase failed to respond further to touch. The findings indicate that the NADH oxidase of the plant cell surface is involved in the growth response to touch and in tendril coiling.

Journal Article↗

Effects of lorazepam on emotional reactivity, performance, and vigilance in subjects with high or low anxiety.

This study examined the hypothesis that low doses of lorazepam modify emotional response. In accord with the results of prior studies that suggest a differential effect of benzodiazepines according to the subjects' anxiety level, the authors tested the effect of lorazepam (0.5 mg twice daily) on 2 groups of 32 subjects: those with high anxiety (HA) and those with low anxiety (LA). These groups were formed a priori on the basis of their scores on the Cattell Anxiety Scale and the Hamilton Rating Scale for Anxiety. The two groups were evaluated for psychomotor function and vigilance (visual analog scales [VAS], digit-symbol substitution test [DSST], and choice reaction time [CRT]), as well as emotional reactivity. Six emotions (fear, anger, disgust, sadness, joy, and neutral state) were induced by the presentation of six movie excerpts, and subjects' emotional responses were measured using the Differential Emotions Scale. The results suggest that at the doses studied, lorazepam led to an increase in negative emotions and a decrease in positive emotions, compared with placebo. This shift of emotional reactivity toward more negative emotions was slightly stronger with the HA than with the LA subjects. However, no reliable differences in the levels of performance and vigilance (CRT, DSST, and VAS) were observed as a function of either treatment or subject group. These findings suggest a possible relationship between benzodiazepine effects and subjects' anxiety level.

Adult↗

Low-cost improvements in prehospital trauma care in a Latin American city.

OBJECTIVE: Prehospital care is a critical component of efforts to lower trauma mortality. In less-developed countries, scarce resources dictate that any improvements in prehospital care must be low in cost. In one Latin American city, recent efforts to improve prehospital care have included an increase in the number of sites of ambulance dispatch from two to four and introduction of the Prehospital Trauma Life Support (PHTLS) course. METHODS: The effect of increased dispatch sites was evaluated by comparing response times before and after completion of the change. The effect of PHTLS was evaluated by comparing prehospital treatment for the 3 months before initiation of the course (n = 361 trauma patients) and the 6 months after (n = 505). RESULTS: Response time decreased from a mean of 15.5 +/- 5.1 minutes, when there were two sites of dispatch, to 9.5 +/- 2.7 minutes, when there were four sites. Prehospital trauma care improved after initiation of the PHTLS course. For all trauma patients, use of cervical immobilization increased from 39 to 67%. For patients in respiratory distress, there were increases in the use of oropharyngeal airways (16-39%), in the use of suction (10-38%), and in the administration of oxygen (64-87%). For hypotensive patients, there was an increase in use of large-bore intravenous lines from 26 to 58%. The improved prehospital treatment did not increase the mean scene time (5.7 +/- 4.4 minutes before vs. 5.9 +/- 6.8 minutes after). The percent of patients transported who died in route decreased from 8.2% before the course to 4.7% after. These improvements required a minimal increase (16%) in the ambulance service budget. CONCLUSION: Increase in sites of dispatch and increased training in the form of the PHTLS course improved the process of pre-hospital care in this Latin American city and resulted in a decrease in prehospital deaths. These improvements were low cost and should be considered for use in other less developed countries.

Adult↗

Hypertonic saline and pentoxifylline prevent lung injury and bacterial translocation after hemorrhagic shock.

Previous reports have shown beneficial effects of pentoxifylline (PTX) and hypertonic saline (HS) in the treatment of hemorrhagic shock. We compared the effects of these solutions to those of conventional lactated Ringer's (LR) treatment on bacterial translocation (BT), lung injury and total and differential cell count in the bronchoalveolar lavage fluid (BAL) after hemorrhagic shock. Rats (280-330 g) were bled to a MAP of 35 mmHg for 1 h and then randomized into 4 groups: LR (3x shed blood); HS (7,5% NaCl, 4 mL/kg); LR+PTX (25 mg/kg) and SHAM (no shock, no treatment). Additionally, total shed blood was reinfused. At 24 h lung injury was analyzed by a pathologist blinded to the groups, and a score was calculated. BT was determined by microbiological cultures of mesenteric lymph node complex. BAL was performed on a separate set of animals that received the same treatments. Lung score was significantly higher in LR group (11.5+/-1.4) as compared to HS (6.8+/-0.9), and PTX treated animals (7.2+/-0.9). The percentage of neutrophils in the BAL of LR animals (15.8%) was also significantly higher as compared with HS (5.25%) and PTX groups (9.72%). BT was noted in 50% of rats for LR group, 30% for PTX, 10% for HS and 0% for sham group. HS and PTX reduced BT and lung injury after hemorrhage. Attenuation of lung injury could be the result of less neutrophil infiltration into the lungs of HS and PTX treated animals. LR resuscitation caused pronounced lung injury and BT.

Animals↗

Differences in genotypes of Helicobacter pylori from different human populations.

DNA motifs at several informative loci in more than 500 strains of Helicobacter pylori from five continents were studied by PCR and sequencing to gain insights into the evolution of this gastric pathogen. Five types of deletion, insertion, and substitution motifs were found at the right end of the H. pylori cag pathogenicity island. Of the three most common motifs, type I predominated in Spaniards, native Peruvians, and Guatemalan Ladinos (mixed Amerindian-European ancestry) and also in native Africans and U.S. residents; type II predominated among Japanese and Chinese; and type III predominated in Indians from Calcutta. Sequences in the cagA gene and in vacAm1 type alleles of the vacuolating cytotoxin gene (vacA) of strains from native Peruvians were also more like those from Spaniards than those from Asians. These indications of relatedness of Latin American and Spanish strains, despite the closer genetic relatedness of Amerindian and Asian people themselves, lead us to suggest that H. pylori may have been brought to the New World by European conquerors and colonists about 500 years ago. This thinking, in turn, suggests that H. pylori infection might have become widespread in people quite recently in human evolution.

Amino Acid Isomerases↗

In vitro activity of cefepime and cefotaxime compared to six other agents against 350 penicillin-susceptible and penicillin-resistant Streptococcus pneumoniae.

From January 1996 to December 1997, we evaluated the in vitro activity of 8 antimicrobials (penicillin, amoxycillin, amoxycillin/clavulanate, cefuroxime, ceftazidime, cefepime, cefotaxime, and imipenem) against 350 Streptococcus pneumoniae clinical isolates collected from two hospitals. Imipenem, cefepime and cefotaxime were the most active antibiotics against penicillin-intermediate (PI) and highly penicillin-resistant (PR) S. pneumoniae with MICs 2- to 8-fold lower than penicillin. Against PI and PR pneumococci amoxycillin and amoxycillin/clavulanate were 2-times less active than cefepime and cefotaxime, while cefuroxime was 4-8-times less active. The majority of strains of serotypes 6B, 23F, 14, 9 and 19 were penicillin-resistant, both intermediate (68%) and highly resistant (32%).

Anti-Bacterial Agents↗