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Biomedical subjects

L Gonzalez

Publications and source records attributed to L Gonzalez.

At least 55 records · Page 3Linked to original sources

Expression of the skin-homing receptor in peripheral blood lymphocytes from subjects with nonimmediate cutaneous allergic drug reactions.

BACKGROUND: In nonimmediate cutaneous reactions to drugs, the skin is the organ most frequently involved, and T cells may play a relevant role. T cells related to skin immune responses express the cutaneous lymphocyte-associated antigen (CLA), the skin-homing receptor. METHODS: We studied the expression of the CLA in peripheral blood T cells from nine subjects with exanthematous reactions induced by beta-lactams (4), phenytoin (2), propyphenazone (1), spiramycin plus metronidazol (1), and captopril plus tiazide (1). The cutaneous symptoms appeared at least 6 h after drug intake. CLA expression was evaluated by flow cytometry at the time of the reaction (T1) and 1 month later (T2). HLA-DR activation marker expression was also evaluated at T1. In four patients, it was necessary to readminister the culprit drug to establish a causal relationship, and sequential estimation of the markers was performed. Two control groups were included: healthy controls and subjects exposed to the culprit drugs with good tolerance. Values were compared by nonparametric statistics. RESULTS: The expression of circulating CLA + T cells at T1 was increased compared to healthy controls (median = 20.4 vs 9.4) (P < 0.001), and the patients also expressed increased levels of HLA-DR (median = 3.8) (P < 0.005). Comparison between T1 and T2 (median = 11.2) also showed differences in levels of CLA+ T cells (P < 0.01). The patients re-exposed to the culprit drug showed an increase followed by a decrease of circulating CLA+ T cells (P < 0.05) and CLA+ HLA-DR+ (P < 0.05) paralleling the symptoms. CONCLUSIONS: These data support the immunologic nature of delayed skin reactions to drugs, and suggest that these CLA+ T cells parallel the disease evolution and may participate in the pathophysiologic mechanisms.

Adult↗

Role of persistent amenorrhea in bone mineral metabolism of young hemodialyzed women.

BACKGROUND: Chronic renal failure in women is frequently associated with endocrine disturbances leading to menstrual disorders. However, most studies on renal osteodystrophy have not taken into account the possible role of these hormonal disturbances on the pathogenesis of bone alterations seen in these patients. In the present study, we evaluated bone mineral metabolism in a group of young hemodialyzed women with persistent amenorrhea and compared them with similar women with regular menstruation. METHODS: We studied 74 women who were further subdivided into 43 women with regular menstrual periods and 31 women with persistent amenorrhea, defined as the absence of menstrual bleeding for more than six months. In all patients, we performed a bone mineral density (BMD) analysis and simultaneously evaluated different biochemical parameters, intact parathyroid hormone (iPTH), sexual hormone determinations that included total estradiol, follicle-stimulating (FSH), and luteinizing hormone and markers of bone resorption such as the procollagen type 1 cross-linked carboxy-terminal telopeptide (ICTP). RESULTS: Serum calcium, phosphorus, and iPTH were similar in both groups. Serum alkaline phosphatase was higher in amenorrheic women. Although the total serum estradiol concentration was normal in the amenorrheic women when compared with nonuremic women, the values were significantly lower than those in regularly menstruating women. Serum FSH and ICTP values were significantly higher in the amenorrheic women. Trabecular BMD in the lumbar spine was also significantly lower in the amenorrheic women compared with regularly menstruating dialysis patients. Lumbar spine BMD and total estradiol levels correlated significantly in the amenorrheic group. CONCLUSIONS: These studies show that persistent amenorrheic young women on dialysis have lower trabecular BMD and evidence of increased bone resorption when compared with normal menstruating women on dialysis. The possible impact of these results in the natural history of the uremic osteodystrophy remains to be determined.

Adult↗

Salivary gland ultrastructural alterations in mice inoculated with Tityus discrepans (Buthidae) venom.

In this work we have studied the possible relationships between clinical manifestations such as sialorrhea, appearing in response to the toxic aggression by Tityus discrepans venom, and the alterations or changes at cellular or subcellular levels in sub-maxillary salivary glands in the murine model. To evaluate salivary gland subcellular response to Tityus discrepans venom, male C57/Bl adult mice were randomised into two groups: a group of mice were intraperitoneally injected with Tityus discrepans venom at a dose of 5 mg/Kg of weight and controls received saline solution. In the salivary glands from the envenomed animals sub-cellular changes such as hyperchromatic nucleus, swollen rough endoplasmic reticulum, granules of different electron density, some of them practically transparent, nucleolus of low density and big size and electron-transparent cisterns were observed. Capillary wall was augmented in certain areas and thin in others. Endothelial cell infolding to the lumen was seen. The distribution of the vesicles and its density varied. Macrophages and plasmocytes were observed next to the damaged capillaries. Different electron density of cytoplasm was noticed. In conclusion, we suggest that sialorrhea is determined by salivary gland damage produced by toxins present in this venom.

Animals↗

Solvent-dependent conformational behaviour of lipochitoligosaccharides related to Nod factors.

The solution conformation of two lipooligosaccharides related to Nod factors or lipochitoligosaccharides have been analysed by 1D and 2D 1H and 13C NMR spectroscopy, molecular mechanics and dynamics calculations. The obtained data indicate that the glycosidic torsion angles have restricted fluctuations, but may adopt a variety of shapes. Remarkably, the relative orientation of the fatty acid chain towards the oligosaccharide backbone is solvent dependent. In water solution, the acyl residue and the oligosaccharide adopt a quasi-parallel orientation for a significant amount of time.

Carbohydrate Conformation↗

SNARE interactions are not selective. Implications for membrane fusion specificity.

The SNARE hypothesis proposes that membrane trafficking specificity is mediated by preferential high affinity interactions between particular v (vesicle membrane)- and t (target membrane)-SNARE combinations. The specificity of interactions among a diverse set of SNAREs, however, is unknown. We have tested the SNARE hypothesis by analyzing potential SNARE complexes between five proteins of the vesicle-associated membrane protein (VAMP) family, three members of the synaptosome-associated protein-25 (SNAP-25) family and three members of the syntaxin family. All of the 21 combinations of SNAREs tested formed stable complexes. Sixteen were resistant to SDS denaturation, and most complexes thermally denatured between 70 and 90 degreesC. These results suggest that the specificity of membrane fusion is not encoded by the interactions between SNAREs.

Cell Membrane↗

Complete sequence of enzootic nasal tumor virus, a retrovirus associated with transmissible intranasal tumors of sheep.

The sequence of the complete genome of ovine enzootic nasal tumor virus, an exogenous retrovirus associated exclusively with contagious intranasal tumors of sheep, was determined. The genome is 7,434 nucleotides long and exhibits a genetic organization characteristic of type B and D oncoviruses. Enzootic nasal tumor virus is closely related to the Jaagsiekte sheep retrovirus and to sheep endogenous retroviruses.

Amino Acid Sequence↗

Jaagsiekte retrovirus is widely distributed both in T and B lymphocytes and in mononuclear phagocytes of sheep with naturally and experimentally acquired pulmonary adenomatosis.

Jaagsiekte sheep retrovirus (JSRV) is a type D retrovirus specifically associated with a contagious lung tumor of sheep, sheep pulmonary adenomatosis (SPA). JSRV replicates actively in the transformed epithelial cells of the lung, and JSRV DNA and RNA have been detected in lymphoid tissues of naturally affected animals. To determine the lymphoid target cells of JSRV, CD4(+) T cells, CD8(+) T cells, B lymphocytes, and adherent cell (macrophage/monocyte) populations were isolated from the mediastinal lymph nodes of naturally affected sheep and lambs inoculated with JSRV. Cells were enriched to high purity and then analyzed for JSRV proviral DNA by heminested PCR, and the proviral burden was quantitated by limiting dilution analysis. JSRV proviral DNA was found in all subsets examined but not in appropriate negative controls. In sheep naturally affected with SPA, JSRV proviral burden was greatest in the adherent cell population. In the nonadherent lymphocyte population, surface immunoglobulin-positive B cells contained the greatest proviral burden, while CD4(+) and CD8(+) T cells contained the lowest levels of JSRV proviral DNA. In most of the cases (5 of 8), provirus also could be detected in the peripheral blood mononuclear cell (PBMC) population. A kinetic study of JSRV infection in the mediastinal lymphocyte population of newborn lambs inoculated with JSRV found that JSRV proviral DNA could be detected as early as 7 days postinoculation before the onset of pulmonary adenomatosis, although the proviral burden was greatly reduced compared to adult natural cases. This was reflected in the levels found in PBMC since proviral DNA was detected in 2 of 13 animals. At the early time points studied (7 to 28 days postinoculation) no one subset was preferentially infected. These data indicate that JSRV can infect lymphoid and phagocytic mononuclear cells of sheep and that dissemination precedes tumor formation. Infection of lymphoid tissue, therefore, may play an important role in the pathogenesis of SPA.

Animals↗

Gonadal and age-related influences on NMDA-induced growth hormone secretion in male rats.

Activation of N-methyl-D,L-aspartic acid (NMDA) receptors stimulates growth hormone (GH) secretion. The mechanisms involved in this action are still a matter of debate. Present experiments were carried out to assess specifically: (1) the age-related changes in NMDA effects; (2) the physiological role of NMDA in pulsatile GH secretion; (3) the hypothalamic and/or pituitary actions of NMDA, and (4) the influence of gonadal function on NMDA-induced GH release. NMDA (15 mg/kg i.p.) stimulated GH secretion in neonatal, prepubertal and adult males, this effect being blocked by MK-801, a selective antagonist of NMDA receptors. In adult males, pulsatile GH secretion was abolished after administration of MK-801 and AP-5, antagonists of NMDA receptors. The stimulatory effect of NMDA on GH release was exerted at the hypothalamic level, since in vitro GH secretion was slightly inhibited in the presence of NMDA (0.5 mM). The increase in GH release after NMDA treatment cannot be explained through an increase in GHRH release, as the NMDA effect persisted in animals pretreated with GHRH antiserum and in those neonatally injected with mono- sodium glutamate, a drug that destroys GHRH neurons. In addition, NMDA-induced GH secretion was independent of testicular function since it remained after orchidectomy, testosterone replacement as well as after permanent damage of testicular function by neonatal administration of estrogens (500 microg on day 1 of life). We conclude that NMDA receptors play a physiological role stimulating GH secretion through a hypothalamic mechanism that is, at least partially, not GHRH-dependent, and is not modulated by testicular secretion.

2-Amino-5-phosphonovalerate↗

Regulation of serum leptin levels by gonadal function in rats.

The aim of this study was to investigate the regulation of serum leptin levels by gender and gonadal steroid milieu. Thus, we measured serum leptin levels by radioimmunoassay in (a) intact male and female rats, (b) female rats at different stages of the estrous cycle and (c) ovariectomized or orchidectomized rats. Gonadectomized groups were or were not implanted with silastic capsules (10 or 30 mm in length, 1.519mm internal diameter; 3.06 mm external diameter) containing estradiol or testosterone and decapitated two weeks later. We found (i) intact female rats weighing 50 g, 250 g and 300 g exhibited higher serum leptin concentrations than intact male rats of similar body weight; (ii) leptin concentrations were not affected by the phase of the estrous cycle; (iii) two weeks after gonadectomy serum leptin concentrations increased in both male (from 4.47+/-1.87 to 8.76+/-1.24 ng/ml) and female (from 1.97+/-0.46 to 5.29+/-0.51 ng/ml) rats. The ovariectomy-induced increase in serum leptin levels was not dependent, at least completely, on changes in body weight since it could be observed when comparisons were made between ovariectomized rats and intact rats in estrus matched for body weight. In contrast the effect of orchidectomy on serum leptin levels appears to be dependent on changes in body weight since it was no longer observed when comparisons were made with a group of intact male rats matched for body weight. In conclusion, these results suggest that serum leptin concentrations are controlled by gonadal function either directly or as a consequence of changes in body weight.

Animals↗

Pancreas ultrastructural alterations in mice inoculated with Tityus discrepans (Buthidae) venom.

The symptoms of scorpionic envenomation in mice appear almost immediately after intraperitoneal injection and are manifested by great agitation, hair bristling, accelerated respiration, salivation and lacrimation, vomits and diarrhoea. In this work we intend to correlate those clinical manifestations appearing in response to the toxic aggression by Tityus discrepans venom, to the cellular or subcellular alterations produced in the mouse pancreas, probably similar to those damages found in envenomed humans. To evaluate pancreas subcellular response to Tityus discrepans venom, male C57/Bl adult mice were randomised into two groups: envenomed were intraperitoneally injected (hypochondrial left region) at a dose of 5 mg/Kg weight and controls received saline solution. Samples after preparation were studied in a Hitachi-300 transmission electron microscope. The most relevant ultrastructural changes in pancreatic tissues were an increase in the nuclear heterochromatin, with a corresponding decrease of euchromatin. In the cytoplasm, rough endoplasmic reticulum exhibited zones of oedema, losing its organised aspect. The secretion granules presented smaller electron density and variability in dimensions. At higher magnification a nucleus with picnotic appearance, with indentation of its perinuclear cistern was observed. There was a mitochondrial degeneration, with destruction of the mitochondrial matrix and autophagic vacuoles in its interior. At 48 h the lesions became intensified, with an evident increase in the intercellular spaces.

Animals↗

Mechanical complications in chronic peritoneal dialysis.

BACKGROUND: A significant number of complications and catheter failures in CAPD are due to mechanical problems. METHODS: We reviewed 105 consecutive peritoneal dialysis catheters, generally implanted by blind insertion technique, in 80 patients over an 11-year period. 137 mechanical problems were collected and classified according to their etiologies into the following: those related to the insertion procedure (n = 21; 15.3%), those related to the presence of dialysate in peritoneum (n = 33; 24%), catheter-related malfunction (n = 28; 20.4%), secondaries to abdominal events (n = 3; 0.2%), catheter accidents (n = 37; 26.2%) and others (n = 15; 11%). RESULTS: Removal of the catheter was performed in 86 of 105 catheters: mechanical complications accounted for 19 of them (21.8%) and 9 patients were definitively transferred to hemodialysis due to this problem. The most frequent complications were catheter accidents, although only a few of them required catheter removal. CONCLUSION: The majority of the catheter removals were due to catheter displacement (31.5%), this problem being more frequent in straight than in Swan Neck catheters.

Accidents↗

Survey, analysis and genetic organization of genes encoding eukaryotic-like signaling proteins on a cyanobacterial genome.

Bacteria usually use two-component systems for signal transduction, while eukaryotic organisms employ Ser/Thr and Tyr kinases and phosphatases for the same purpose. Many prokaryotes turn out to harbor Ser/Thr and Tyr kinases, Ser/Thr and Tyr phosphatases, and their accessory components as well. The sequence determination of the genome of the cyanobacterium Synechocystis sp. strain PCC 6803 offers the possibility to survey the extent of such molecules in a prokaryotic organism. This cyanobacterium possesses seven Ser/Thr kinases, seven Ser/Thr and Tyr phosphatases, one protein kinase interacting protein, one protein kinase regulatory subunit and several WD40-repeat-containing proteins. The majority of the protein phosphatases presented in this study were previously reported as hypothetical proteins. We analyze here the structure and genetic organization of these ORFs in the hope of providing a guidance for their functional analysis. Unlike their eukaryotic counterparts, many of these genes are clustered on the chromosome, and this genetic organization offers the opportunity to study their possible interaction. In several cases, genes of two-component transducers are found within the same cluster as those encoding a Ser/Thr kinase or a Ser/Thr phosphatase; the implication for signal transduction mechanism will be discussed.

Amino Acid Sequence↗

Lack of a specific immune response against a recombinant capsid protein of Jaagsiekte sheep retrovirus in sheep and goats naturally affected by enzootic nasal tumour or sheep pulmonary adenomatosis.

Enzootic nasal tumour (ENT) and sheep pulmonary adenomatosis (SPA) are two contagious adenocarcinomas of the respiratory tract of sheep and goats. Both diseases are associated with related, but distinct, type-D-retroviruses (ENTV and JSRV respectively). No evidence of circulating antibodies has been described in animals affected by either ENT or SPA using antigens from natural sources. We evaluated the usefulness of a recombinant JSRV capsid protein (JSRV-CA) as antigen to study the antibody responses of animals naturally affected by ENT or SPA, using immunoblotting. Positive reactions were detected in the sera of both affected and unaffected sheep and goats. The reactivity was abolished completely by absorption with the GST fusion partner but not by JSRV-CA, suggesting that it was not specific. The results support prior observations indicating that sheep and goats infected by JSRV and ENTV do not develop specific humoral responses to these retroviruses.

Animals↗

Trough to peak ratio of once-daily lisinopril and twice-daily captopril in patients with essential hypertension.

The objective of this study was to assess the antihypertensive effect and the trough to peak (T:P) ratio of lisinopril and captopril, in patients with essential hypertension. After 2 weeks of placebo, 69 of 115 eligible patients had office diastolic blood pressure (DBP) between 90 and 114 mm Hg and daytime average DBP above 85 mm Hg during a 25-h ambulatory BP monitoring (ABPM) and were randomised to receive lisinopril (20 mg once daily) or captopril (50 mg twice daily) for 4 weeks. Office and ambulatory BP were then repeated. Indices of 24-h BP and T:P ratios were calculated and compared. Both drugs significantly reduced both office and ambulatory BP. The final BP obtained with lisinopril was less than with captopril. On office measurement, 75% of the patients treated with lisinopril and 44% on captopril were controlled (P < 0.001), but responses by ABPM were not significantly different. T:P ratios calculated in all patients were 0.75 and 0.66 for lisinopril and captopril respectively, but in patients who responded to each drug the corresponding ratios were 0.78 and 0.73. In conclusion both 20 mg once-daily lisinopril and 50 mg captopril twice-daily achieve a favourable T:P ratio in patients with essential hypertension.

Adult↗

Alterations in colonic anatomy induced by chronic stimulant laxatives: the cathartic colon revisited.

Cathartic colon is a historic term for the anatomic alteration of the colon secondary to chronic stimulant laxative use. Because some have questioned whether this is a real entity, we investigated changes occurring on barium enema in patients ingesting stimulant laxatives. Our study consisted of two parts. In part 1, a retrospective review of consecutive barium enemas performed on two groups of patients with chronic constipation (group 1, stimulant laxative use [n=29]; group 2, no stimulant laxative use [n=26]) was presented to a radiologist who was blinded to the patient group. A data sheet containing classic descriptions of cathartic colon was completed for each study. Chronic stimulant laxative use was defined as stimulant laxative ingestion more than three times per week for 1 year or longer. To confirm the findings of the retrospective study, 18 consecutive patients who were chronic stimulant laxative users underwent barium enema examination, and data sheets for cathartic colon were completed by another radiologist (part 2). Colonic redundancy (group 1, 34.5%; group 2, 19.2%) and dilatation (group 1, 44.8%; group 2, 23.1%) were frequent radiographic findings in both patient groups and were not significantly different in the two groups. Loss of haustral folds, however, was a common finding in group 1 (27.6%) but was not seen in group 2 (p < 0.005). Loss of haustral markings occurred in 15 (40.5%) of the total stimulant laxative users in the two parts of the study and was seen in the left colon of 6 (40%) patients, in the right colon of 2 (13.3%) patients, in the transverse colon of 5 (33.3%) patients, and in the entire colon of 2 (13.3%) patients. Loss of haustra was seen in patients chronically ingesting bisacodyl, phenolpthalein, senna, and casanthranol. We conclude that long-term stimulant laxative use results in anatomic changes in the colon characterized by loss of haustral folds, a finding that suggests neuronal injury or damage to colonic longitudinal musculature caused by these agents.

Aged↗

Intra-umbilical vein injection and retained placenta: evidence from a collaborative large randomised controlled trial. Grupo Argentino de Estudio de Placenta Retenida.

OBJECTIVE: To determine whether intra-umbilical vein injection with saline solution, with or without oxytocin, reduces the need for manual removal of placenta compared with expectant management. DESIGN: Multicenter, randomised controlled trial. SETTING: Eleven hospitals in four cities of Argentina: Buenos Aires, Corrientes, Rosario, and Salta. PARTICIPANTS: Two hundred and ninety-one women showing no evidence of placental separation thirty minutes after vaginal delivery. INTERVENTIONS: Three different management strategies: 1. intra-umbilical vein injection of saline solution plus oxytocin; 2. intra-umbilical vein injection of saline solution alone; and 3. expectant management. MAIN OUTCOME MEASURES: Primary: manual removal of the placenta. Secondary: blood loss after trial entry, haemoglobin level at 24 to 48 hours and at 40 to 45 days after delivery, blood transfusion, curettage, infection, and days of hospital stay. RESULTS: Rates of subsequent manual removal were similar: intra-umbilical vein injection of saline solution plus oxytocin (58%; RR 0.92; 95% CI 0.73-1.15), or saline alone (63%; RR 1.00; 95% CI 0.80-1.24), compared with expectant management (63%). There were also no detectable effects of the active managements on any of the secondary measures of outcome. CONCLUSIONS: Based on evidence available from randomised controlled trials, including this trial, it is unlikely that intra-umbilical injection with or without oxytocin, is clinically useful. We recommend that this intervention should not be used in third stage management of labour.

Female↗