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Biomedical subjects

J Pardo

Publications and source records attributed to J Pardo.

At least 19 recordsLinked to original sources

Infrastructure of radiotherapy in Spain: a minimal standard of radiotherapy resources.

PURPOSE: To assess the state of our specialty, the Spanish Society of Radiotherapy and Oncology ordered a survey of all Spanish services of radiation oncology. METHODS AND MATERIALS: In June 1999, the Society ordered an analysis of the state of radiation oncology. It created a survey that was sent to all radiotherapy units in Spain. A database was created in which 230 variables were analyzed. RESULTS: Eighty-four centers were analyzed, and 157 external beam irradiation, megavoltage units were counted, of which 67 were cobalt units and 90 were linear accelerators. The cobalt units worked an average of 11.4 h daily and the linear accelerators 11.6 h. The number of patients/unit/y was 472 for the cobalt units and 442 for the linear accelerators. The number of patients by physician and year was 179. Each center received a mean of 958 new patients annually. The average between the reception and start of treatment was 25.52 days (maximum 60), and it was estimated that only 38.1% of cancers were irradiated. The number of radiation oncologists working was 392. Spain has a deficit of 297 radiation oncologists. CONCLUSION: There is a need for 44 MV units and for the replacement of 67 cobalt units. The present lack of units has had an impact on palliative treatment, which has resulted in pharmacy costs. As long as these instrumental deficiencies are not solved, waiting lists will continue to be inherent to the system. There are also important staff deficiencies, in that about 297 radiation oncologists would be needed to cover the needs.

Health Services Needs and Demand↗

Cervical length evaluation by transvaginal sonography in nongravid women with a history of preterm delivery.

OBJECTIVE: To evaluate cervical length in the nongravid period in women with a past history of preterm delivery. METHODS: The study population comprised 54 women who had delivered spontaneously before 34 weeks of gestation. Etiology of preterm delivery was suspected to be related to cervical incompetence, defined as a painless and progressive dilatation of the cervix in the absence of other causes. Patients with pre-eclampsia, intrauterine growth restriction, uterine anomalies, fetal anomalies, multiple gestation and similar complications were excluded. Shortening of the cervix was recorded during pregnancy in all study patients. One hundred and four women matched for age, parity and body mass index who had given birth at term served as the control group. Cervical length was evaluated in all women at least 12 weeks after delivery by transvaginal sonography in the mid-sagittal plane. RESULTS: The mean gestational age at delivery was 30.8 +/- 1.2 weeks in the study group and 38.8 +/- 2.1 weeks in the control group (P = 0.03). The mean cervical length in the two groups was 36 +/- 6 and 38 +/- 4 mm, respectively. This difference was not statistically significant (P = 0.9). CONCLUSIONS: In nongravid women with unexplained preterm delivery there is no difference in cervical length compared to patients who deliver at term. Shortening of the cervix is most probably a reversible phenomenon that occurs during pregnancy and represents a failure of the competence mechanism to adapt to pregnancy.

Adult↗

Anapsos (Polypodium leucotomos) modulates lymphoid cells and the expression of adhesion molecules.

Anapsos is a medical prescription registered in the Health Ministry of Spain, that is obtained from the rhizomes of the fern Polypodium leucotomos. An immunomodulating effect of Anapsos on certain lymphocyte subsets and cytokines has already been described in the literature. The current study extends and supports part of the aforementioned results of the product on the immune system, showing the ability of Anapsos to stimulate proliferation and activation of T and natural killer lymphocytes, as well as an important down-regulating effect on CD11, CD18 and CD62-L adhesion molecules, both on peripheral blood mononuclear cells and on U-937 and HL-60 cell lines.

Adjuvants, Immunologic↗

Functional cloning of Src-like adapter protein-2 (SLAP-2), a novel inhibitor of antigen receptor signaling.

In an effort to identify novel therapeutic targets for autoimmunity and transplant rejection, we developed and performed a large-scale retroviral-based functional screen to select for proteins that inhibit antigen receptor-mediated activation of lymphocytes. In addition to known regulators of antigen receptor signaling, we identified a novel adaptor protein, SLAP-2 which shares 36% sequence similarity with the known Src-like adaptor protein, SLAP. Similar to SLAP, SLAP-2 is predominantly expressed in hematopoietic cells. Overexpression of SLAP-2 in B and T cell lines specifically impaired antigen receptor-mediated signaling events, including CD69 surface marker upregulation, nuclear factor of activated T cells (NFAT) promoter activation and calcium influx. Signaling induced by phorbol myristate acetate (PMA) and ionomycin was not significantly reduced, suggesting SLAP-2 functions proximally in the antigen receptor signaling cascade. The SLAP-2 protein contains an NH2-terminal myristoylation consensus sequence and SH3 and SH2 Src homology domains, but lacks a tyrosine kinase domain. In antigen receptor-stimulated cells, SLAP-2 associated with several tyrosine phosphorylated proteins, including the ubiquitin ligase Cbl. Deletion of the COOH terminus of SLAP-2 blocked function and abrogated its association with Cbl. Mutation of the putative myristoylation site of SLAP-2 compromised its inhibitory activity and impaired its localization to the membrane compartment. Our identification of the negative regulator SLAP-2 demonstrates that a retroviral-based screening strategy may be an efficient way to identify and characterize the function of key components of many signal transduction systems.

Adaptor Proteins, Signal Transducing↗

A role of the mitochondrial apoptosis-inducing factor in granulysin-induced apoptosis.

Granulysin is a cytolytic molecule released by CTL via granule-mediated exocytosis. In a previous study we showed that granulysin induced apoptosis using both caspase- and ceramide-dependent and -independent pathways. In the present study we further characterize the biochemical mechanism for granulysin-induced apoptosis of tumor cells. Granulysin-induced death is significantly inhibited by Bcl-2 overexpression and is associated with a rapid (1-5 h) loss of mitochondrial membrane potential, which is not mediated by ceramide generation and is not inhibited by the general caspase inhibitor benzyloxycarbonyl-Val-Ala-Asp-fluoromethylketone. Ceramide generation induced by granulysin is a slow event, only observable at longer incubation times (12 h). Apoptosis induced by exogenous natural (C(18)) ceramide is truly associated with mitochondrial membrane potential loss, but contrary to granulysin, this event is inhibited by benzyloxycarbonyl-Val-Ala-Asp-fluoromethylketone. Ceramide-induced apoptosis is also completely prevented by Bcl-2 overexpression. The nuclear morphology of cells dying after granulysin treatment in the presence of caspase inhibitors suggested the involvement of mitochondrial apoptosis-inducing factor (AIF) in granulysin-induced cell death. We demonstrate using confocal microscopy that AIF is translocated from mitochondria to the nucleus during granulysin-induced apoptosis. The majority of Bcl-2 transfectants are protected from granulysin-induced cell death, mitochondrial membrane potential loss, and AIF translocation, while a small percentage are not protected. In this small percentage the typical nuclear apoptotic morphology is delayed, being of the AIF type at 5 h time, while at longer times (12 h) the normal apoptotic morphology is predominant. These and previous results support a key role for the mitochondrial pathway of apoptosis, and especially for AIF, during granulysin-induced tumoral cell death.

Antigens, Differentiation, T-Lymphocyte↗

Guillain-Barré syndrome in Spain, 1985-1997: epidemiological and public health views.

Retrospective demographic information and hospital record data were collected for 337 patients resident in Spain who had validated Guillain-Barré syndrome (GBS) diagnoses and clinical onset during the period 1985-1997 and had been admitted to 11 centres, covering a population of 3.9 million. The European age-adjusted GBS incidence per 100,000 for 1985-1997 among the population aged 20 and over was 0.85, with a breakdown of 1.14 in men and 0.58 in women. Incidence increased with age and time, with occasional rises that mimicked outbreaks and occurred at irregular 2- to 4-year intervals, mainly in winter. Spatial variation was modest. Respiratory and gastrointestinal infections respectively constituted 49.3 and 19.3% of recorded preceding events. The 97.5% intercentile limit, obtained from the 1985-1997 monthly incidences using predictions from a Poisson model, was proposed as the threshold value for pilot epidemiological surveillance of GBS in 1998-1999.

Adult↗

Ewing tumor: tumor biology and clinical applications.

The Ewing tumor family includes classical Ewing's sarcoma of bone and soft tissues, peripheral primitive neuroectodermal tumors (pPNET), Askin tumor, and other less frequent variants. This group of tumors is defined by the consistent presence of chromosomal translocations resulting in gene fusions between EWS gene and a member of the ETS family of transcription factors, mainly FLI1 and ERG. Analogous fusions are seen in other solid developmental tumors, like desmoplastic small round cell tumor. These fusions, which are consistently present and tumor-specific, control transcription of several target genes, largely unknown but critical to cell proliferation and differentiation. Therefore, gene fusions are useful to diagnose and classify small round cell tumors, have prognostic significance, are probably useful to detect micrometastasis and monitor minimal residual disease, and are potential therapeutic targets. Secondary molecular alterations, which include mutations of cell cycle regulatory genes, are not tumor-specific but are related to progression and may have prognostic value. The Ewing tumor family represents a paradigm of the application of the knowledge of biology of neoplasia to the clinical management of patients.

Artificial Gene Fusion↗

Inflammatory myofibroblastic tumour of larynx.

Inflammatory myofibroblastic tumour (IMT) is a benign pseudoneoplastic proliferation, mainly developing in the lung and extremely rare in the larynx. A patient with a two-month history of dysphonia and a polypoid left true vocal fold tumour is presented. Histological and clinical knowledge of this lesion is important to exclude a misdiagnosis (e.g. malignant epithelial or mesenchymal tumours) and an inappropriate treatment.

Aged↗

Effects of endurance training on the breathing pattern of professional cyclists.

The aim of this longitudinal study was to clarify the changes induced by endurance training on the breathing pattern of 13 professional cyclists (age+/-SD: 24+/-2 years; VO(2 max) approximately 75 ml x kg(-1) x min(-1)) during the three periods (rest, precompetition, and competition) of a sports season. Both the volume and the intensity of training were quantified during these periods. In each session (corresponding to each of the three periods) all subjects performed (1) a pulmonary function test (to measure forced vital capacity [FVC], peak expiratory flow [PEF], and maximal voluntary ventilation [MVV]), and (2) a ramp test until exhaustion on a cycle ergometer (workload increases of 25 W x min(-1)). The following variables were recorded every 100 W until the end of the tests: pulmonary ventilation (VE, in l x min(-1) BTPS), tidal volume (VT, inl BTPS), breathing frequency (f(b), in breaths x min(-1)), ventilatory equivalents for oxygen (VE x VO(2)(-1)) and carbon dioxide (VE x VCO(2)(-1)), inspiratory (TI) and expiratory (TE) times (s), ratio of TI to total respiratory duration or inspiratory "duty cycle" (TI/TTOT, and mean inspiratory flow rate (VT)/TI), in l x s(-1)). The results showed no changes in any of these variables (p>0.05) between the three periods of study, despite significant changes in training loads (i.e., increases in the volume and/or intensity of training throughout the season). These findings suggest that endurance conditioning does not alter the breathing pattern of professional cyclists during an incremental exercise test.

Adult↗

The adhesive protein of Choromytilus chorus (Molina, 1782) and Aulacomya ater (Molina, 1782): a proline-rich and a glycine-rich polyphenolic protein.

The adhesive polyphenolic proteins from Aulacomya ater and Choromytilus chorus with apparent molecular masses of 135000 and 105000, respectively, were digested with trypsin and the peptides produced resolved by reversed phase liquid chromatography. About 5 and 12 major peptides were obtained from the protein of A. ater and C. chorus, respectively. The major peptides were purified by reverse-phase chromatography and the amino acid sequence indicates that both polyphenolic proteins consisted of repeated sequence motifs in their primary structure. The major peptides of A. ater contain seven amino acids corresponding to the consensus sequence AGYGGXK, whereas the tyrosine was always found as 3, 4-dihydroxyphenylalanine (Dopa), the X residue in position 6 was either valine, leucine or isoleucine, and the carboxy terminal was either lysine or hydroxylysine. On the other hand, the major peptides of C. chorus ranged in size from 6 to 21 amino acids and the majority correspond to the consensus sequence AKPSKYPTGYKPPVK. Both proteins differ markedly in the sequence of their tryptic peptides, but they share the common characteristics of other adhesive proteins in having a tandem sequence repeat in their primary structure.

Amino Acid Sequence↗

Spontaneous intracranial hypotension: use of unenhanced MRI.

We report a case of spontaneous intracranial hypotension diagnosed with unenhanced cranial MRI, showing laminar subdural fluid and engorgement of the hypophysis and perisellar sinuses. Cerebrospinal fluid pressure was low. MRI was normal after resolution of symptoms. Prior reports emphasise the enhancing pachymeninges seen in this syndrome. We maintain that, when subdural collections and perisellar engorgement are detected on unenhanced MRI in the proper clinical setting, contrast enhancement may not be necessary for the diagnosis.

Adult↗

Mast cells in chronic rejection of human renal allografts.

An increased number of mast cells (MCs) is found in renal specimens of patients with diseases associated with persistent chronic inflammation. MCs proliferation is partly dependent on the presence of T lymphocytes. Both chronic inflammation and T-lymphocytes are essential in the development of chronic rejection (CR), and probably for the infiltration of MCs. MC-derived products such as heparin, histamine, and serine proteases may be responsible for endothelial proliferation and excess collagen production by fibroblasts. In this study, a quantitative evaluation of the MCs infiltration in kidney allografts with CR is performed. The extent of renal fibrosis was analysed in samples stained with Masson's trichrome. To evaluate the potential relationship between MCs and fibrosis in CR we analysed 30 kidneys with CR (25 from nephrectomies and 5 from autopsies). Ten transplanted kidneys obtained from patients died by causes not related with rejection were used as controls. CR was graded according to the Banff schema, which assesses the degree of vasculopathy, tubular atrophy, interstitial fibrosis and transplantation glomerulopathy. Giemsa-stained sections and immunohistochemistry using anti-MC tryptase and c-kit monoclonal antibodies were used to detect MCs. The mean number of MCs per 20 high-power fields (HPF) in the transplanted kidney with CR was 101.8+/-15.3 in the renal cortex and 46.60+/-6.52 in the medulla. MCs were significantly more numerous in CR with respect to normal kidneys, both in the cortex (P<0.01; Mann-Whitney U test) and in the medulla (P<0.01; Mann-Whitney U test). There was a positive correlation between the number of MCs and extent of fibrosis (P<0.01; Kruskal-Wallis one-way anova test) and tubular atrophy (P<0.01). These results suggest that MCs may play a role in the process of development of interstitial fibrosis in CR.

Adolescent↗

In vitro polymerization of mussel polyphenolic proteins catalyzed by mushroom tyrosinase.

The in vitro enzymatic polymerization of the polyphenolic protein purified from the mussels Aulacomya ater, Mytilus edulis chilensis and Choromytilus chorus was studied. Mushroom tyrosinase was used to oxidize the dopa residues present in these proteins, and polymerization was monitored by acid-urea polyacrylamide gel electrophoresis. The protein from A. ater polymerized at a faster rate than the other two. Amino acid analysis of the crosslinked protein showed a notable decrease in the content of dopa, but no significant change of other amino acids. This suggests that crosslink formation may be limited to the oxidized dopa derivatives of the protein molecules.

Agaricales↗

Evaluation of low serum vitamin B(12) in the non-anaemic pregnant patient.

Low serum vitamin B(12) concentrations in pregnancy may not indicate true megaloblastic anaemia. In the present study we compared biochemical indices of vitamin B(12) deficiency (serum homocysteine and urine methylmalonic acid) in non-anaemic pregnant women with and without low serum vitamin B(12) concentrations. The groups were matched for age, parity and gestational age. No differences were found, and all values were within normal range. These results suggest that the measurement of low serum B(12) concentrations in pregnant women should be followed by analysis at the biochemical level before vitamin B(12) injections are started.

Adult↗

Metabolic and neuromuscular adaptations to endurance training in professional cyclists: a longitudinal study.

The aim of this longitudinal study was to analyze the changes in several metabolic and neuromuscular variables in response to endurance training during three defined periods of a full sports season (rest, precompetition and competition). The study population was formed by thirteen professional cyclists (age +/- SEM: 24+/-1 years; mean V(O2 max) approximately 74 ml kg(-1) min(-1)). In each testing session, subjects performed a ramp test until exhaustion on a cycle ergometer (workload increases of 25 W min(-1)). The following variables were recorded every 100 W until the tests: oxygen consumption (V(O2) in l min(-1)), respiratory exchange ratio (RER in V(CO2) V(O2)(-1)) and blood lactate, pH and bicarbonate concentration [HCO3(-)]. Surface electromyography (EMG) recordings were also obtained from the vastus lateralis to determine the variables: root mean square voltage (rms-EMG) and mean power frequency (MPF). RER and lactate values both showed a decrease (p<0.05) throughout the season at exercise intensities corresponding to submaximal workloads. In contrast, no significant differences were found in mean pH or [HCO(3-)]. Finally, rms-EMG tended to increase during the season, with significant differences (p<0.05) observed mainly between the competition and rest periods at most workloads. In contrast, precompetition MPF values increased (p<0.05) with respect to resting values at most submaximal workloads but fell (p<0.05) during the competition period. Our findings suggest that endurance conditioning induces the following general adaptations in elite athletes: (1) lower circulating lactate and increased reliance on aerobic metabolism at a given submaximal intensity, and possibly (2) an enhanced recruitment of motor units in active muscles, as suggested by rms-EMG data.

Adaptation, Physiological↗