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Biomedical subjects

S Garcia

Publications and source records attributed to S Garcia.

At least 55 records · Page 3Linked to original sources

[Hemorrhagic mandibular metastasis of renal origin: usefulness of therapeutic embolization].

BACKGROUND: Vascular metastatic tumors of the mandible are unusual and management of bleeding may be difficult. CASE REPORT: An 83-year-old woman with a mandibular metastasis from a renal-cell carcinoma developed oral pain and episodes of bleeding of 2-weeks duration. Embolization was successful in stopping blood loss which occurred during surgical biopsy. Eight months after embolization, the patient is pain free and no bleeding has recurred. DISCUSSION: Embolization during arteriography procedures for tumor exploration can be useful in acute situations to improve survival and patient comfort. The aim may be palliative care or preparation for curative excision.

Aged↗

DNA vaccination: transfection and activation of dendritic cells as key events for immunity.

The mechanisms underlying initiation and maintenance of CD4 T cell responses after DNA vaccination were studied using a construct coding for nonsecreted fifth component of complement (C5) protein, thus restricting the availability of antigen. The only cell types to express C5 were keratinocytes at the site of DNA application and a small number of dendritic cells present in the draining lymph nodes. Antigen expression persisted for up to 12 wk in keratinocytes, but dendritic cells did not express C5 beyond 2 wk after vaccination. Cross-priming of dendritic cells by C5 expressed in keratinocytes did not occur unless keratinocyte death was induced by irradiation in vitro. CD4 T cells were activated in the draining lymph nodes only and subsequently migrated to the spleen, where memory T cells persisted for longer than 40 wk despite the absence of a source of persistent antigen. While DNA vaccination resulted in transfection of a small proportion of dendritic cells only, it led to general activation of all dendritic cells, thus providing optimal conditions for effective T cell activation and maintenance of memory.

Animals↗

Cystic fibrosis patients with the 3272-26A-->G mutation have mild disease, leaky alternative mRNA splicing, and CFTR protein at the cell membrane.

We characterized the 3272-26A-->G mutation in the cystic fibrosis transmembrane conductance regulator (CFTR) gene, creating an alternative acceptor splice site in intron 17a, that competes with the normal one, although we predict from consensus values, with lower efficiency. We analyzed five Cystic Fibrosis (CF) Portuguese patients with the 3272-26A-->G/F508del genotype. Besides clinical and haplotype characterization of those patients, we report here results from CFTR transcript analysis in nasal brushings from all five patients. RT-PCR analysis supports alternative splicing in all patients and carriers, but not in controls. By sequencing, we determined that the alternative transcript includes 25 nucleotides from intron 17a, which predictively cause frameshift and a premature stop codon. The use of this alternative splice site causes a reduction in the levels of normal transcripts from the allele with this mutation and, most probably, of normal protein as well. By immunocytochemistry of both epithelial primary cell cultures and slices from CF polyps, CFTR protein is detected at the cell membrane, with three different antibodies. Ussing chamber analysis of one nasal polyp shows a high sodium absorption, characteristic of CF. Altogether, the results suggest that the main defect caused by the 3272-26A-->G mutation is a reduction in normal CFTR transcripts and protein and therefore this mutation should be included in class V, according to Zielenski and Tsui.

Adolescent↗

[Hepatocellular carcinoma in a non-cirrhotic liver. Presentation of series of 77 operated patients].

OBJECTIVE: To present epidemiologic profile of this supposedly rare condition, its diagnostic management and the results of surgical treatment in a population of the mediterranean border. PATIENTS AND METHODS: Between 1987 and 1999, the records of patients operated on for hepatocellular carcinoma and in whom cirrhosis was not present on pathological examination of liver parenchyma were collected. Data were collected prospectively. RESULTS: Mean age was 57.6 years. There were 61 men (79%) and 16 women but sex ratio was 1/1 for patients under 50. Hepatitis B and/or C serology was positive in 22 patients (29%). At presentation, 56 patients (73%) suffered of symptoms and there was evidence of tumor at clinical examination in 30 (39%). Sensitivity of alpha-fetoprotein measurement was 55%, and 58% for preoperative percutaneous biopsy. Twelve had exploratory laparotomy only, 61 underwent partial liver resection and 4 were transplanted. Resection was presumed curative in 56 cases (73%). There was one single tumor mass in 41 cases (53%) and its mean size was 10.3 cm. Liver fibrosis was present in 24 cases (29%). After curative resection, 5-year survival rate was 46%, and favorable prognostic factors were: alpha-fetoprotein within normal range, single tumor mass or tumor size less than 10 cm. CONCLUSION: Hepatocellular carcinoma arising on noncirrhotic liver is not a rare occurrence. It is usually encountered at an advanced stage of the disease. Nonetheless, it remains extirpable in many cases with low postoperative mortality and long term results are better than those of resections for hepatocellular carcinoma on cirrhotic liver.

Actuarial Analysis↗

Following the development of a CD4 T cell response in vivo: from activation to memory formation.

The in vivo differentiation of CD4 T cells from naive to memory cells was followed after their adoptive transfer together with syngeneic dendritic cells into MHC mismatched adoptive hosts lacking lymphocytes and NK cells. Functional and molecular changes were measured as the antigenic stimulus, provided by the cotransferred dendritic cells, disappeared. Memory cells as opposed to effector cells show an inversion in the relative expression of Bcl-2 family members in favor of antiapoptotic molecules, and compared with naive cells they have an increased ratio of bcl-xL to bcl-2. They differ qualitatively from naive T cells, suggesting that accelerated CD4 memory responses can occur without the need for increased frequencies of specific T cells.

Adoptive Transfer↗

Plasma-electrolytes in natives to hypoxia after marathon races at different altitudes.

PURPOSE: It is well known that altitude natives differ from sea level natives in aspects of fluid and electrolyte homeostasis. METHODS: To evaluate exercise and environmental influences on the electrolyte and water status in hypoxia adapted subjects, we investigated 11 well-trained marathon runners (33.7 +/- 0.7 yr, 60.5 +/- 1.9 kg), native to an altitude above 2600 m, before and after two marathon races. One competition was held at moderate altitude (AM, 2650 m, 14 degrees C, 55% RH, running time 3 h 6 min +/- 22 min) and another under tropical conditions (HM, 470 m, 28 degrees C, 70% RH, running time 2 h 54 min +/- 30 min). Blood samples were taken 3 d before, immediately after, 1 h after, and 24 h after the races. RESULTS: The loss in body fluid was calculated to be 2.15 L during AM and 5.05 L during HM, respectively. It was compensated mostly by ingested fluids without electrolyte content and by metabolically produced water, which led to hyponatremia during AM (plasma [Na+] from 144.3 +/- 0.7 to 131.7 +/- 2.1 mmol x L(-1)). Severe dehydration without significant changes in plasma [Na+] could be detected after HM. Serum antidiuretic hormone concentrations and serum aldosterone concentrations significantly increased during both races and remained at a high level for at least 1h after both competitions. Serum atrial natriuretic peptide (ANP) concentrations were at a high level at rest, increasing during HM, and decreasing during AM. CONCLUSION: Under tropical conditions, we found a severe state of dehydration characterized by an extended ANP-response, which was not prevented by water intake during the race. Under hypoxic conditions, however, we found that hyponatremia had developed. This can be partly explained by pure water intake and metabolically produced water, and also, possibly, by a special hypoxia-induced effect.

Adult↗

E-cadherin and beta-catenin expression in breast medullary carcinomas.

The initial step of cancer invasion and metastasis is the escape of tumour cells from the primary site, involving disruption of normal cell-cell adhesion and E-cadherin (E-cad) and beta-catenin (beta-cat) down-regulation, as shown in various types of human malignancies including breast carcinomas. Medullary carcinomas are high grade and poorly differentiated tumours with syncytial typical pattern, and prognosis unexpectedly better than that in high grade breast carcinomas. In a series of 55 breast typical medullary carcinomas diagnosed according to the strict use of Ridolfi et al (Cancer 40: 1365-1385, 1977) criteria, E-cad and beta-cat were investigated using quantitative (SAMBA 2005 system) immunocytochemical assays on frozen sections. Results were compared to that obtained on paraffin sections and in a series (n=55) of grade 3 ductal carcinomas. It was shown that medullary carcinomas significantly (p<0.001) expressed more E-cad and beta-cat than grade 3 ductal carcinomas. E-cad and beta-cat correlated with high expression of P53, of c-erbB, and of Ki-67 antigens, and with lack of hormone receptors antigenic sites (p<0.001). It was concluded that favourable prognosis and syncytial pattern of typical breast medullary carcinomas likely results, at least partly, from a particular expression of cell-cell adhesion molecules, significantly limiting tumour growth and efficiently mastering the tumour cell dissemination, opposing to high proliferative activity (grade 3).

Adult↗

[Urinary lithotripsy in children. Multicenter study of the Pediatric Urology Study Group].

The authors present the results of a survey conducted among French paediatric urologists belonging to the Groupe d'Etudes en Urologie Pédiatrique (GEUP) (Paediatric Urology Study Group). This study, based on 122 cases observed in 13 centres, is not exhaustive, but is nevertheless statistically significant. The preoperative assessment confirms the usual findings of urinary stones in children: pyelonephritis, haematuria and abdominal pain, the usual presenting complaint, concomitant malformative uropathy (10% of cases) and a predominance of calcium stones. More than 200 stones were treated, larger than 10 millimeters in diameter in one-third of cases. Renal stones, mainly caliceal (more than 50%), included 11 staghorn calculi. This study also included 22 ureteric stones, mainly in the pelvic ureter, and 2 bladder stones. Lithotripsy was ultrasound-guided in 2/3 of cases and required general anaesthesia in about 3/4 of cases. Ureteric catheterization was required in 19 infants preoperatively, but in only 2 infants (stein strasse) postoperatively. One or two lithotripsy sessions were sufficient in most cases, but 4 sessions were necessary in 5 patients, to the same kidney in 1 case. The mean hospital stay was 2 to 3 days, but the procedure was performed on an outpatient basis in 15 cases. The immediate postoperative course was uneventful and asymptomatic. This survey revealed about 10% of complete failures, corresponding to solitary caliceal stones in 2/3 of cases; 29 partial failures were essentially due to lower caliceal stones and staghorn calculi; 84 successes (stone-free), mainly pelvic or simple caliceal stones. Scintigraphy did not reveal any immediate postoperative impairment of renal function. This study reported a success rate of about 70%, regardless of the type of apparatus used. Assessment of the results of ESWL requires sufficient follow-up both concerning the outcome of fragmented stones and evaluation of possible functional repercussions. This survey defines the main indications: although ESWL can be applied to most stones, some stones constitute poor indications (cystine stones, stenotic malformative uropathy) or dubious indications: small lower caliceal stones, densely calcified staghorn calculi in older children. This study confirmed the efficacy and low morbidity of ESWL in children. A prospective study needs to be conducted according to a rigorous protocol in order to refine the technique and indications while reducing the possible long-term risks.

Abdominal Pain↗

Smoking, acculturation and family cohesion in Mexican-American women.

OBJECTIVE: To compare the characteristics of smokers and non-smokers in a setting that includes predominately Mexican-American women, with particular attention to acculturation, nativity and family cohesion. DESIGN: Cross-sectional survey in a public hospital women's clinic. METHODS: A self-administered survey was completed by gynecologic patients. It assessed: demographics, acculturation, birthplace and family cohesion. Comparisons of ever/never smokers and current/non-smokers were made using chi-square tests. Stratified analysis was used to assess for confounding. RESULTS: Smoking was very common in the white non-Hispanic group (ever smoking 86%, current smoking 70%). High rates were also seen among certain subgroups of Mexican-American women: US-born (ever smoking 65%, current smoking 44%), high acculturation (ever smoking 57%, current smoking 40%) and those with less cohesive families (ever smoking 67%, current smoking 67%). Stratified analysis revealed that place of birth and family cohesion, controlling one for the other, had adjusted prevalence ratios for current smoking of 3.7 (95% CI 1.5, 9.0) and 3.2 (95% CI 1.3, 8.1) respectively. CONCLUSION: Very high rates of smoking were observed among white non-Hispanic patients and certain subgroups of Latino subjects in this population. In Latinos, being US-born and having membership in a less cohesive family unit were independently associated with smoking.

Acculturation↗

Neurotensin is an antagonist of the human neurotensin NT2 receptor expressed in Chinese hamster ovary cells.

The human levocabastine-sensitive neurotensin NT2 receptor was cloned from a cortex cDNA library and stably expressed in Chinese hamster ovary (CHO) cells in order to study its binding and signalling characteristics. The receptor binds neurotensin as well as several other ligands already described for neurotensin NT1 receptor. It also binds levocabastine, a histamine H1 receptor antagonist that is not recognised by neurotensin NT1 receptor. Neurotensin binding to recombinant neurotensin NT2 receptor expressed in CHO cells does not elicit a biological response as determined by second messenger measurements. Levocabastine, and the peptides neuromedin N and xenin were also ineffective on neurotensin NT2 receptor activation. Experiments with the neurotensin NT1 receptor antagonists SR48692 and SR142948A, resulted in the unanticipated discovery that both molecules are potent agonists on neurotensin NT2 receptor. Both compounds, following binding to neurotensin NT2 receptor, enhance inositol phosphates (IP) formation with a subsequent [Ca2+]i mobilisation; induce arachidonic acid release; and stimulate mitogen-activated protein kinase (MAPK) activity. Interestingly, these activities are antagonised by neurotensin and levocabastine in a concentration-dependent manner. These activities suggest that the human neurotensin NT2 receptor may be of physiological importance and that a natural agonist for the receptor may exist.

Amino Acid Sequence↗

The role of bradykinin in the regulation of blood flow to hindlimb muscle groups of the anaesthetized cat.

1. Male cats were anaesthetized with alphaxalone-alphadolone and breathed spontaneously following tracheotomy, Using coloured microspheres, muscle blood flow was measured at rest and during two periods of contraction elicited by simultaneous stimulation of the left sciatic and femoral nerves at 3 Hz for 10 min. In one group, the hindlimb blood flow was allowed to increase during muscle contraction and in another group the perfusion of the hindlimb was limited by a stenosis on the left external iliac artery. 2. In the absence of flow restriction, soleus muscle blood flow increased from 18.9 +/- 3.8 to 30.4 +/- 3.3 ml min-1 (100 g tissue)-1 (n = 6; P < 0.02) and gastrocnemius muscle blood flow increased from 24.8 +/- 5.9 to 61.6 +/- 12.8 ml min-1 (100 g tissue)-1 (n = 6; P < 0.01) during contraction. The bradykinin (BK) antagonists HOE 140 (1 mg kg-1, i.v.) did not affect the response in either the soleus (37.7 +/- 7.3 ml min-1 (100 g tissue)-1; n = 6; n.s.) or the gastrocnemius (62.9 +/- 7.9 ml min-1 (100 g tissue)-1; n = 6; n.s.) muscles. 3. In the stenosis group, soleus muscle blood flow increased from 9.8 +/- 2.3 to 22.9 +/- 4.9 ml min-1 (100 g tissue)-1 (n = 6; P < 0.01) and gastrocnemius muscle blood flow increased from 15.8 +/ 3.4 to 36.4 +/- 5.5 ml min-1 (100 g tissue)-1 (n = 6; P < 0.01) during contraction. Following administration of HOE 140, functional hyperaemia in the soleus muscle was unaffected (blood flow, 17.8 +/- 2.2 ml min-1 (100 g tissue)-1, n = 6; n.s.) white blood flow in the gastrocnemius muscle was reduced to 21.8 +/- 6.0 ml min-1 (100 g tissue)-1 (n = 6; P < 0.05). 4. The results show that BK does not contribute ot functional hyperaemia associated with twitch contraction at 3 Hz when blood flow is unrestricted, but may contribute up to 40% of the vasodilation of predominantly glycolytic muscle groups such as the gastrocnemius when flow is restricted. BK plays no role in hyperaemia associated with twitch contraction of oxidative muscle groups such as the soleus.

Anesthesia↗

Differential susceptibility to activation-induced apoptosis among peripheral Th1 subsets: correlation with Bcl-2 expression and consequences for AIDS pathogenesis.

It has been proposed that HIV infection is associated with an imbalance in Th1 and Th2 subsets. Recent reports indicate that Th1 and Th2 effectors differ in their susceptibility to activation-induced apoptosis. To determine whether increased T cell apoptosis in HIV-infected patients contributes to alterations in cytokine synthesis, we performed single-cell analysis of type 1 and type 2 cytokine production by CD4 and CD8 T cells, simultaneously with detection of apoptosis. We demonstrate that a differential alteration in representation of Th1 subsets, rather than commitment of T cells to secrete Th2 cytokines, occurs throughout HIV infection. A significant decrease in the number of IL-2- or TNF-alpha-producing T cells was observed, whereas those producing IFN-gamma remained preserved. Furthermore, there is a gradient of susceptibility to activation-induced apoptosis (IL-2 < IFN-gamma < TNF-alpha) among the different Th1 subsets. This gradient was detected in both CD4 and CD8 subsets, as well as in control donors and HIV-infected patients, in whom the susceptibility to apoptosis of IL-2 and IFN-gamma producers was increased compared with controls. This differential intrinsic apoptosis susceptibility of Th1 effectors was found to be tightly regulated by Bcl-2 expression. In HIV-infected persons, disappearance of IL-2-producing T cells was a good indicator of disease progression and was correlated with the progressive shrinkage of the CD4+ CD45RA+ T cell compartment and a gradual increased susceptibility to activation-induced apoptosis of the IL-2-producing subset. This close relationship between the CD45RA/CD45R0 ratio, the level of type 1 cytokine production, and susceptibility to apoptosis should be considered in HIV-infected patients under antiviral or immune-based therapies.

Acquired Immunodeficiency Syndrome↗

Prognostic significance of Nm23/NDPK expression in breast carcinoma, assessed on 10-year follow-up by automated and quantitative immunocytochemical assays.

The Nm23 gene has been described as an antimetastatic gene; in some studies, disease progression in patients with solid tumours is related to Nm23 protein expression, which can be detected by immunohistochemical procedures. Detection of Nm23-H1 protein in breast cancer may be relevant for the monitoring of patient therapy, provided that the technical procedures are reliable and cost-effective. The aim of the present study was to determine the prognostic significance of Nm23, assessed by quantitative immunocytochemical assays (Nm23 ICAs), under optimal technical conditions. Nm23-H1 ICAs were performed on frozen sections, using an automated immunoperoxidase technique (Ventana) and computer-assisted analysis of digitized colour microscopic images (SAMBA), in a series of 168 breast carcinomas. The results of automated quantitative ICAs were correlated with patients' follow-up (129 months). Nm23-H1 immunocytochemical expression in histological sections of tumours in which more than 3 per cent of the surface area was positively stained was significantly (0.012) correlated with longer metastasis-free survival in both node-positive and node-negative groups of patients (P = 0.032 and P = 0.036, respectively) (Kaplan-Meier log-rank test, NCSS 6.0.1 software). Nm23 expression (cut-point 3 per cent) did not, however, correlate with overall survival, or with the recurrence-free survival. In multivariate analysis (proportional hazards regression, Cox model), the prognostic significance of Nm23 in terms of metastasis-free survival was independent of tumour size and grade, and of histological grade, in the entire cohort of patients. It is concluded that Nm23 immunodetection is only of limited practical clinical relevance in breast carcinoma, even when assessed under optimal technical conditions.

Adult↗

Nutritional status and physical fitness of elderly sportsmen.

The nutritional status of elderly sportsmen has not been reported on, neither has the nutritional balance nor the precise relationship between nutritional status and physical fitness been detailed for this population. Thus, group of 18 sportsmen [age 63 (SD 4.5) years] was monitored by weighing their food during a 6-day period. Macro nutrient, mineral and vitamin content was derived from tables. Daily energy expenditure (DEE) and sport activity (DSA) were quantified over a 7-day period using a questionnaire. Physical fitness was assessed by maximal oxygen uptake (VO2max) measurements. The DEE was 11429 (SD 1890) kJ x day(-1). The DSA corresponded to 38% of DEE and VO2max to 35.9 (SD 6.1) ml x min(-1) x kg(-1). When compared with French recommended dietary allowances (RDA) intakes were higher for energy (+ 24%), macro nutrients, and most minerals and vitamins. Despite high energy intakes, some subjects had mineral and vitamin deficits. Energy intakes were significantly related to intakes of magnesium, phosphorus, iron, vitamins B2, B6, C and to VO2max, but not to age. Stepwise regressions indicated that vitamin C intake was the only determinant to have a relationship with VO2max. Thus, most elderly sportsmen had higher nutritional status than RDA, although some had mineral and vitamin deficits. It is therefore suggested that elderly sportsmen should be encouraged to consume food with higher mineral and vitamin contents.

Aged↗

VCAM (IGSF) adhesion molecule expression in breast carcinomas detected by automated and quantitative immunocytochemical assays.

Expression of vascular cell adhesion molecules (VCAM) in tumors is associated with endothelial cell activation and may facilitate adherence of carcinomatous cells to the vessel wall, promoting bloodborne metastases. Expression of VCAM was investigated in 202 breast carcinomas using automated (Ventana System) and quantitative (SAMBA image analyzer) immunoperoxidase staining of frozen sections. Positive VCAM immunoreactivity was observed in 83 tumors (41%) (mean immunostained surface, 12.4%; SD, 10.5). The mean area of immunostaining was correlated with clinical and pathologic prognostic indicators and with the immunohistochemical expression in tissue sections of various indicators of cell proliferation, metastatic potential, and drug resistance or sensitivity, evaluated according to the same method. There was no correlation of VCAM immunoreactivity with tumor size, type, or grade or with nodal status. Also, no significant correlation was observed between VCAM and MIB1/Ki67, p53, Bcl-2, E cadherin, CD44v, cathepsin D, CD31, P-gp, ER, PR, or pS2. However, VCAM immunoreactivity was significantly correlated with ELAM and VLA2 (P = .001) and VLAs (P = .008) expression. The results suggest that VCAM expression in breast carcinoma tissue sections is likely not a prognostic indicator. Its practical clinical relevance, if any, must be established by correlation with patients' outcomes and tumor sensitivity to drugs.

Adult↗