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Biomedical subjects

J del Valle

Publications and source records attributed to J del Valle.

17 recordsLinked to original sources

[Low sensitivity of IGF-I, IGFBP-3 and urinary GH in the diagnosis of growth hormone insufficiency in slowly-growing short-statured boys. Grupo Español de Estudio de la Talla Baja].

BACKGROUND: The usefulness of IGF-I, IGFBP-3, and the urinary GH excretion in the diagnostic evaluation of growth retardation in boys with short stature was studied. SUBJECTS AND METHOD: Serum samples from two GH-stimulation tests and two 24-h urine samples were sent to a Central Laboratory to measure serum and urinary GH, serum IGF-I, IGFBP-3 and GHBP, both in absolute and standardized values (Z-score). Short children were classified as growth hormone deficient (GHD) (n = 25), and idiopathic short statured (ISS) (n = 54), on the basis of the peak stimulated GH concentration of < 7.5 microg/l or > or = 7.5 microg/l respectively. A group of 15 normally growing children and adolescents was also included. RESULTS: Height-velocity standard deviation score (HV)-SDS was lower and body mass index higher in GHD than ISS. Standardized IGF-I differed significantly by ANOVA among the three groups (p = 0.001). Multiple stepwise linear regression analysis with HV-SDS as dependent variable showed IGF-I SDS as the best predictor followed by peak GH clonidine response and uGH excretion. ROC curves showed optimum cut-off level for IGF-I SDS as 2.05 (sensitivity: 32%, specificity: 90%) and 1.14 for IGFBP-3 SDS sensitivity: 28%, specificity: 94%). CONCLUSIONS: Standardized IGF-I and IGFBP-3 measurements were highly efficient only in diagnosis of severe GHD, but they show low sensitivity for the diagnosis of isolated idiopathic GHD as defined according to the low GH response to stimulation tests.

Adolescent↗

The human histamine H(2) receptor regulates c-jun and c-fos in a differential manner.

Previously, we demonstrated that activation of the human H(2) receptor (hH(2)R) leads to an increase in c-fos transcription and cell proliferation. The purpose of these studies was to examine whether hH(2)R regulates c-jun expression and, if so, explore the mechanisms by which it does so. Histamine induced an increase in c-jun mRNA in human embryonic kidney cells stably transfected with the hH(2)R (maximal effect: 554.6 +/- 86.8% of control). The protein kinase C (PKC) inhibitors staurosporine (10(-6) M) and GF-109203X (10(-6) M) significantly inhibited histamine-stimulated c-fos mRNA while not altering c-jun expression. The protein kinase A (PKA) pathway inhibitors Rp-cAMP and protein kinase inhibitor did not affect the action of histamine on c-jun or c-fos mRNA. Histamine (10(-4) M) stimulated extracellularly regulated kinase 2 tyrosine phosphorylation. The specific inhibitor of the mitogen-activated protein (MAP) kinase pathway, PD-98059 (5 x 10(-5) M), significantly inhibited histamine-induced c-fos and c-jun mRNA. Of interest, the p70 S6 kinase inhibitor rapamycin (10(-6) M) but not wortmannin decreased histamine-stimulated c-jun mRNA by 58.5 +/- 12% (mean +/- SE, n = 4) while not significantly altering c-fos message. Histamine (10(-4) M) also led to an approximately 4.5-fold increase in Jun NH(2)-terminal kinase activity in a PKC-, PKA-, and MAP kinase-independent but rapamycin-sensitive manner. Our findings suggest that histamine stimulates both c-fos and c-jun mRNA in a differential manner. PKC is involved in histamine-mediated c-fos activation, whereas p70 S6 kinase is important for linkage of this receptor to c-jun.

Androstadienes↗

Regulation and function of p38 protein kinase in isolated canine gastric parietal cells.

We examined the regulation and functional role of p38 kinase in gastric acid secretion. p38 kinase was immunoprecipitated from cell lysates of highly purified gastric parietal cells in primary culture, and its activity was quantitated by in vitro kinase assay. Carbachol effects were dose- and time-dependent, with a maximal 10-fold stimulatory effect detected after 30 min of incubation. SB-203580, a highly selective inhibitor of p38 kinase, blocked carbachol induction of p38 kinase activity, with maximal inhibition at 10 microM. Stimulation by carbachol was unaffected by preincubation of parietal cells with the intracellular Ca(2+) chelator BAPTA-AM, but incubation of cells in Ca(2+)-free medium led to a 50% inhibition of carbachol induction of p38 kinase activity. Because some of the effects of carbachol are mediated by the small GTP-binding protein Rho, we examined the role of Rho in carbachol induction of p38 kinase activity. We tested the effect of exoenzyme C3 from Clostridium botulinum (C3), a toxin known to ADP-ribosylate and specifically inactivate Rho. C3 led to complete ADP-ribosylation of Rho, and it inhibited carbachol induction of p38 kinase by 50%. We then tested the effect of SB-203580 and C3 on carbachol-stimulated uptake of [(14)C]aminopyrine (AP). Inhibition of p38 kinase by SB-203580 led to a dose-dependent increase in AP uptake induced by carbachol, with maximal (threefold) effect at 10 microM SB-203580. Similarly, preincubation of parietal cells with C3 led to a twofold increase in AP uptake induced by carbachol. Thus carbachol induces a cascade of events in parietal cells that results in activation of p38 kinase through signaling pathways that are at least in part dependent on Rho activation and on the presence of extracellular Ca(2+). p38 kinase appears to inhibit gastric acid secretion.

ADP Ribose Transferases↗

Gastrin induces c-fos gene transcription via multiple signaling pathways.

We previously observed that the trophic actions of gastrin (G17) on the AR42J rat acinar cell line are mediated by mitogen-activated protein kinase (MAPK)-induced c-fos gene transcription via protein kinase C (PKC)-dependent and -independent pathways. In this study, we further investigated the signaling pathways that target c-fos in response to G17. G17 led to a sixfold induction in luciferase activity in cells transfected with plasmids containing the -356+109 sequence of the murine c-fos promoter, which includes the Sis-inducible element (SIE), serum response element (SRE), and the Ca2+/cAMP response element (CRE) regulatory elements. Addition of either the selective PKC inhibitor GF-109203X or the MAPK/extracellular signal-regulated kinase inhibitor PD-98059 resulted in an 80% reduction in luciferase activity. G17 induced the transcriptional activity of both Elk-1 and Sap-1a, transcription factors that bind to the E26 transformation specific (Ets) DNA sequence of the SRE, and this effect was inhibited by both GF-109203X and PD-98059. Point mutations in the Ets sequence led to a 4-fold induction of c-fos transcription stimulated by G17 and to a 1.3-fold induction in response to epidermal growth factor (EGF). In contrast, mutations in the CA rich G (CArG) sequence of the SRE prevented transcriptional activation by both G17 and EGF. G17 induction of the Ets mutant construct was unaffected by either GF-109203X or PD-98059. Because activation of the SRE involves the small GTP-binding protein Rho A, we examined the role of Rho A in G17 induction of c-fos transcription. Inactivation of Rho A by either the specific inhibitor C3 or by expression of a dominant negative Rho A gene inhibited G17 induction of both the wild-type and the Ets mutant constructs by 60%. C3 also inhibited G17-stimulated AR42J cell proliferation. Thus G17 targets the c-fos promoter CArG sequence via Rho A-dependent pathways, and Rho A appears to play an important role in the regulation of the trophic action of G17.

Animals↗

Cell type-specific requirement of the MAPK pathway for the growth factor action of gastrin.

Gastrin (G17) has a CCKB receptor-mediated growth-promoting effect on the AR42J rat acinar cell line that is linked to induction of both mitogen-activated protein kinase (MAPK) and c-fos gene expression. We investigated the mechanisms that regulate the growth factor action of G17 on the rat pituitary adenoma cell line GH3. Both AR42J and GH3 cells displayed equal levels of CCKB receptor expression and similar binding kinetics of 125I-labeled G17. G17 stimulation of cell proliferation was identical in both cell lines. G17 stimulation of GH3 cell proliferation was completely blocked by the CCKB receptor antagonist D2 but not by the MEK inhibitor PD-98059 or the protein kinase C inhibitor GF-109203X, which completely inhibited G17 induction of AR42J cell proliferation. G17 induced a c-fos SRE-luciferase reporter gene plasmid more than fourfold in the AR42J cells, whereas it had no effect in the GH3 cells. In contrast to what we observed in the AR42J cells, G17 failed to stimulate MAPK activation and Shc tyrosyl phosphorylation and association with the adapter protein Grb2. Epidermal growth factor induced the MAPK pathway in the GH3 cells, demonstrating the integrity of this signaling system. G17 induced Ca2+ mobilization in both the GH3 and AR42J cells. The calmodulin inhibitor N-(6-aminohexyl)-5-chloro-1-naphthalenesulfonamide inhibited AR42J cell proliferation by 20%, whereas it completely blocked G17 induction of GH3 cell growth. The Ca2+ ionophore ionomycin stimulated GH3 cell proliferation to a level similar to that observed in response to G17, but it had no effect on AR42J cell proliferation. Thus there are cell type specific differences in the requirement of the MAPK pathway for the growth factor action of G17. Whereas in the AR42J cells G17 stimulates cell growth through activation of MAPK and c-fos gene expression, in the GH3 cells, G17 fails to activate MAPK, and it induces cell proliferation through Ca2+-dependent signaling pathways. Furthermore, induction of Ca2+ mobilization in the AR42J cells appears not to be sufficient to sustain cell proliferation.

Adaptor Proteins, Signal Transducing↗

Clonal descent and microevolution of Neisseria meningitidis during 30 years of epidemic spread.

Serogroup A meningococci of subgroups III, IV-1 and IV-2 are probably descended from a common ancestor that existed in the nineteenth century. The 10.5kb sequences spanning five distinct chromosomal loci, encoding cell-surface antigens, a secreted protease or housekeeping genes and intergenic regions, were almost identical in strains of those subgroups isolated in 1966, 1966 and 1917 respectively. During the subsequent two to three decades, all of these loci varied as a result of mutation, translocation or import of DNA from unrelated neisseriae. Thus, microevolution occurs frequently in naturally transformable bacteria. Many variants were isolated only once or within a single geographical location and disappeared thereafter. Other variants achieved genetic fixation within months or a few years. The speed with which sequence variation is either eliminated or fixed may reflect sequential bottlenecks associated with epidemic spread and contrasts with the results of phylogenetic analyses from bacteria that do not cause epidemics.

Alleles↗

Our experience in combining mechanics.

The use of more than one orthodontic technique in an orthodontic practice can significantly increase treatment capability. Being able to carry out the efficient and effective use of multiple techniques, however, requires that the appliance and the force systems are designed to do both tipping and translation in an optimal manner, either individually or in a variable combination. The application of this philosophy of combining treatment mechanics has been very favorable in our practice. The case reports and mechanics described were selected from our practice to show the diversity and potential that is possible with combination anchorage treatment mechanics. The key to success in a multiattachment straight wire system is to have the ability to use light tipping movements in combination with rigid translation and to be able to vary the location of either, at any time the need arises during treatment.

Child↗

Immunogenicity and evolutionary variability of epitopes within IgA1 protease from serogroup A Neisseria meningitidis.

Five murine epitopes were defined and mapped within IgA1 protease produced by Neisseria meningitidis. Epitopes 1 and 2 were present in IgA1 protease from all strains, and from Neisseria gonorrhoeae. Epitopes 3 through to 5 varied between subgroups of serogroup A meningococci, but have remained constant over decades within the subgroups, except for epitope 4, which changed between 1983 and 1987 during the spread of subgroup III meningococci from Asia to Africa. Binding of monoclonal antibodies to epitopes 1, 4 and 5 neutralized enzymatic function. Human sera containing antibodies to IgA1 protease as a result of natural infection inhibited binding of monoclonal antibodies to epitope 4 but not to the other epitopes.

Animals↗

Bradykinin (Bk) increases cytosolic calcium in cultured rat myenteric neurons via Bk-2 type receptors coupled to mobilization of extracellular and intracellular sources of calcium: evidence that calcium influx is prostaglandin dependent.

We examined the effect of bradykinin (Bk) on cytosolic calcium ([Ca++]i) in cultured rat ileal myenteric neurons. The receptor subtype(s) and calcium pool(s), e.g., extracellular and/or intracellular calcium that mediate Bk's effect on [Ca++]i in myenteric neurons, have not been reported. Superfusion with Bk (10 nM) increased [Ca++]i by 96 +/- 10 nM over basal levels in approximately 80% of the neurons tested that were not affected by a Bk-1 receptor antagonist but were inhibited 72% by a Bk-2 receptor antagonist. The Bk-generated increase in [Ca++]i was reduced by 45% and 52% of control response in calcium-free buffer and indomethacin, respectively, supporting involvement of extracellular and intracellular pools of calcium and mediation, in part, by a prostaglandin-dependent pathway. Bk increased [Ca2++]i by 54 +/- 6 nM in calcium-free buffer that was indomethacin insensitive, suggesting that Bk stimulation of extracellular calcium influx was mediated by a prostaglandin-dependent pathway. Bk (1 microM) increased tissue prostaglandin E2 (PGE2) production by 62% over basal levels in isolated rat ileal myenteric ganglia. Finally, superfusion with PGE2 (10 microM) increased [Ca++]i by 105 +/- 16 nM over basal levels that were blocked in calcium-free buffer. In summary, our studies suggest that cultured rat ileal myenteric neurons express the Bk-2 receptor subtype that is coupled to mobilization of extracellular and intracellular pools of calcium. Bk stimulates influx of extracellular calcium via a prostaglandin-dependent pathway.

Animals↗

Human monoclonal antibodies against an epitope on the class 5c outer membrane protein common to many pathogenic strains of Neisseria meningitidis.

Neisseria meningitidis is a causative agent of meningitis. Despite vaccination programs, it still causes a large number of deaths in young children. Early diagnosis followed by passive immunization with human monoclonal antibodies could be an approach to effective therapy. Peripheral blood lymphocytes from normal, healthy blood donors and from vaccinated individuals were immunized in vitro, using outer membrane proteins purified from N. meningitidis B:4:P1.15. The immunized human B cells were Epstein-Barr virus transformed and fused to a heteromyeloma. Several stable human hybridoma cell lines were established and two, secreting antibodies against the 31-kDa class 5c outer membrane protein, were characterized further. The human antibodies were of IgG1 and IgG3 isotypes, with kappa light chains. The recognized epitope was commonly found among pathogenic strains of N. meningitidis; thus, these human monoclonal antibodies may be important in the evaluation of N. meningitidis infections.

Animals↗

Immunoglobulin V regions of a bactericidal anti-Neisseria meningitidis outer membrane protein monoclonal antibody.

C6 is a potentially therapeutic murine monoclonal antibody that recognizes the class 1 outer membrane protein of Neisseria meningitidis. C6 specifically immunoblots this antigen and augments in vitro killing of N. meningitidis bacteria. We describe a general method of obtaining the heavy and light chain variable-region sequence from immunoglobulin-secreting cells. The method uses mixed polymerase chain reaction (PCR) primers designed from the 5' end of the framework 1 (FR1) sequences of the heavy and light chains, and 3'-end primers for constant-region conserved sequences. The method has been applied to the cloning and sequencing of the variable region of C6 to construct a humanized monoclonal antibody. Rapid amplification and sequencing of variable regions by this general method have multiple applications in the study of the immune response to infectious diseases.

Amino Acid Sequence↗

Effect of antipyretics on the length of hospital stay of pediatric patients with bacterial infections.

Antipyretic use in pediatric patients with uncomplicated bacterial infections was characterized, and the effect of such therapy on the length of hospital stay of these patients was studied. Study patients were divided into six groups of 30 patients. Patients with pneumococcal pneumonia, staphylococcal cellulitis, or H. influenzae meningitis receiving at least two antipyretic doses were compared with their counterparts receiving one or no antipyretic doses. Of the total 299 antipyretic doses administered, 284 were acetaminophen. Patients with H. influenzae meningitis received a mean of 4.57 doses per patient, which was significantly greater than the other study groups (p less than 0.05). In contrast, patients with staphylococcal cellulitis received the highest mean dose of 12.51 mg/kg of acetaminophen. There appeared to be a relationship between the admitting temperature and the mean length of hospital stay; higher admitting temperatures were correlated with increased length of stay. Analysis of covariance for the different study groups indicated no significant difference in length of hospital stay (p greater than 0.05).

Anti-Inflammatory Agents, Non-Steroidal↗

[Barcelona Bipolar Eating Disorder Scale (BEDS): a self-administered scale for eating disturbances in bipolar patients].

INTRODUCTION: The presence of eating disorders in bipolar population is not rare, with rates over 10 %, according to the few available epidemiologic studies, however the literature on this issue is still scarce. An even higher percentage of bipolar individuals suffer from serious problems related to eating behavior without fulfilling criteria for DSM-IV eating disorder. METHODS: The Bipolar Eating Disorders Scale (BEDS) was designed on the basis of the existing eating scales, adjusted to the characteristics of bipolar disorders from the complaints of our sample of patients (n=350). Subsequently, a group of experts made the selection of the most representative and independent items in order to obtain a short, 10-item scale, aimed at assessing the intensity and frequency of eating dysfunctions in the bipolar population and not at diagnosis. We administered the scale to a healthy control group (n=55) to evaluate feasibility and to determine the cut-off score. RESULTS: The BEDS is a 10-item simple, self-administered scale. Average time of completing this scale is about 1.13 min (1 min, 21 seconds) +/-26 seconds. Median score was 6 and the mean score was 6.6 with a standard deviation of 3.7, this being the reason why the cut-off point was found to be around 13 points. Patients receiving scores over 13 may require an individualized intervention to evaluate which were the main difficulties and to propose treatment. CONCLUSIONS: The BEDS allows for a rapid and effective evaluation of both the intensity and the frequency of eating dysfunctions in bipolar patients in order to perform an adequate intervention for the specific needs of each one of the patients.

Bipolar Disorder↗

[Conjunctival ophthalmomyiasis caused by Oestrus ovis].

BACKGROUND: Microbiologic diagnosis of conjunctival ophthalmomyiasis. MATERIAL AND METHODS: Material extracted from three patients' conjunctiva who complained of sudden presence of foreign body and were diagnosed as conjunctival ophthalmomyiasis has been studied. Patients were recruited over two months from the Emergency Department. Diagnosis was performed through observation using the light microscope. RESULTS: Oestrus ovis first-instance larvas were observed in all the samples studied. CONCLUSIONS: This observation of similar cases in a short period of time and the low frequency of diseased people who lived in a urban environment makes necessary to think in this agent as cause of ophthalmomyiasis in our area and therefore perform an adequate differential diagnosis.

Adolescent↗