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Biomedical subjects

C Blanco

Publications and source records attributed to C Blanco.

At least 37 records · Page 2Linked to original sources

Pathological gambling: addiction or compulsion?

There is considerable debate about the appropriate conceptualization of pathological gambling and its place in psychiatric nosology. The authors examined the existing research on different areas of pathological gambling to find evidence for a particular model of this disorder. There are 2 dominant models of pathological gambling: as a nonpharmacologic addiction and as an obsessive-compulsive spectrum disorder. The data available from different areas seem to converge in suggesting that pathological gambling has characteristics that are similar to those of substance abuse, and less close to those of obsessive-compulsive disorder, although those conceptualizations are not mutually exclusive. An alternative model of pathological gambling is that it constitutes a heterogeneous disorder with some subtypes resembling obsessive-compulsive disorder, and other subtypes being closer to substance abuse disorders. Improved understanding of the conceptualization of this disorder may help improve the quality of the treatments available.

Gambling↗

Psychopathology and the binding problem.

Normal cerebral activity is based on the rapid and flexible alternation of an enormous quantity of spatial-temporal patterns of neuronal firing. There is still much to learn about the mechanism that keeps neurons on functionally closed assemblies firing in synchronization. The explanation of this mechanism is the so called 'binding problem', one of the cornerstones of the generation of perceptions, cognitions, emotions and behaviours by the brain, and therefore of great interest to psychiatry. We explore the possibility that a 'binding dysfunction' could be a relevant aspect of the pathophysiology of mental disorders, and apply it to schizophrenia, in an attempt to integrate some neurobiological findings in this disorder, including a few preliminary data obtained with transcranial magnetic stimulation (TMS).

Brain↗

Psychiatric comorbidity in pathological gamblers seeking treatment.

OBJECTIVE: The authors' goal was to determine the frequency of psychiatric comorbidity among treatment-seeking pathological gamblers, compare the severity of gambling and psychological problems in gamblers with and without comorbid disorders, and investigate differences between gamblers with and without comorbid disorders in the dopamine D(2) receptor gene (DRD(2)). METHOD: Sixty-nine pathological gamblers who consecutively applied to a specialized outpatient treatment program were evaluated with structured interviews, self-report questionnaires, and psychological scales and were genotyped for a DRD(2) polymorphism. RESULTS: A comorbid psychiatric disorder was present in 43 (62.3%) of the gamblers. The most frequent diagnoses were personality disorders (N=29 [42.0%]), alcohol abuse or dependence (N=23 [33.3%]), and adjustment disorders (N=12 [17.4%]). Gamblers with comorbid psychiatric disorders had gambling scores and psychological scale scores indicating greater severity of gambling and psychopathology. Significant differences in DRD(2) allele distribution were found in gamblers with and without comorbid disorders. CONCLUSIONS: Psychiatric comorbidity is common among pathological gamblers and is associated with greater severity of clinical problems. The DRD(2) gene could be a liability genetic factor for psychiatric comorbidity in pathological gambling.

Comorbidity↗

Comorbidity, impairment, and suicidality in subthreshold PTSD.

OBJECTIVE: Reliance on the categorical model of psychiatric disorders has led to neglected study of posttraumatic sequelae that fall short of full criteria for posttraumatic stress disorder (PTSD). Substantial disability and suicidal risk is associated with subthreshold PTSD, but this association has not been well studied. In addition, no studies have examined the role of comorbidity in explaining disability and impairment in subthreshold PTSD. METHOD: On National Anxiety Disorders Screening Day 1997, 2,608 out of 9,358 individuals screened for affective and anxiety disorders at 1,521 sites across the United States reported at least one PTSD symptom of at least 1 month's duration. Impairment, comorbid anxiety disorders, major depressive disorder, and rates of suicidality were determined and compared for individuals with no, one, two, three, or four (full PTSD) symptoms on a screening questionnaire. Regression analyses examined the relative contribution of subthreshold PTSD and comorbid disorders to impairment and suicidal ideation. RESULTS: Impairment, number of comorbid disorders, rates of comorbid major depressive disorder, and current suicidal ideation increased linearly and significantly with each increasing number of subthreshold PTSD symptoms. Individuals with subthreshold PTSD were at greater risk for suicidal ideation even after the authors controlled for the presence of comorbid major depressive disorder. CONCLUSIONS: Higher numbers of subthreshold PTSD symptoms were associated with greater impairment, comorbidity, and suicidal ideation. Disability and impairment found in previous studies of subthreshold PTSD symptoms may be related in part to the presence of comorbid disorders. However, the presence of subthreshold PTSD symptoms significantly raised the risk for suicidal ideation even after the authors controlled for major depressive disorder. Given the broad public health implications of these findings, more efforts are needed to identify subthreshold PTSD symptoms in clinical populations, epidemiologic surveys, and treatment studies.

Adolescent↗

Prescription of psychotropic medications to youths in office-based practice.

OBJECTIVE: This study sought to determine sociodemographic characteristics of treatment of children and adolescents for whom psychotropic medications are prescribed and to describe the clinical management approaches associated with the prescription of each major class of psychotropic medication in office-based medical practices in the United States. METHODS: Data for a four-year period (1992-1996) were drawn from the National Ambulatory Medical Care Survey, a nationally representative survey of office-based medical practices, to determine prescribing patterns, patients' sociodemographic characteristics, and clinical management approaches associated with visits during which psychotropic medications were prescribed to patients aged 19 years or under. RESULTS: Psychotropic medications were prescribed during 2.2 percent of all visits. A majority of the prescriptions for psychotropic medications (84.8 percent) were provided by general practitioners or pediatricians. For the visits during which a psychotropic medication was prescribed, stimulants were the most commonly prescribed (53.9 percent of such visits), but prescription of other classes of medications was not uncommon: antidepressants (30 percent), anxiolytics (7.2 percent), antipsychotics (7.2 percent), and mood stabilizers (12.7 percent). Significant differences were observed in the prescription of each class of medication by sex, race, and payment source. CONCLUSIONS: General practitioners and pediatricians have a role in the office-based treatment of youths with psychotropic medications.

Adolescent↗

System for cleavable Fc fusion proteins using tobacco etch virus (TEV) protease.

We describe a novel Fc fusion protein system that can be cleaved by tobacco etch virus (TEV) protease. This system is desirable because it takes advantage of the high specificity of TEV protease and its activity at 4 degrees C. We produced two TEV-Fc fusion proteins that contain the first three Ig domains and all six Ig domains of the cell adhesion molecule L1. Both proteins were efficiently cleaved by TEV protease at 4 degrees C. Functional analysis of the cleavage products in neurite outgrowth assays showed they had similar activities to their parental Fc fusion proteins. Therefore, TEV-Fc fusion proteins may increase the utility and flexibility of the Fc fusion protein system.

Animals↗

Translocation of jellyfish green fluorescent protein via the Tat system of Escherichia coli and change of its periplasmic localization in response to osmotic up-shock.

The bacterial twin arginine translocation (Tat) pathway is capable of exporting cofactor-containing enzymes into the periplasm. To assess the capacity of the Tat pathway to export heterologous proteins and to gain information about the property of the periplasm, we fused the twin arginine signal peptide of the trimethylamine N-oxide reductase to the jellyfish green fluorescent protein (GFP). Unlike the Sec pathway, the Tat system successfully exported correctly folded GFP into the periplasm of Escherichia coli. Interestingly, GFP appeared as a halo in most cells and occasionally showed a polar localization in wild type strains. When subjected to a mild osmotic up-shock, GFP relocalized very quickly at the two poles of the cells. The conversion from the halo structure to a periplasmic gathering at particular locations was also observed with spherical cells of the DeltarodA-pbpA mutant or of the wild type strain treated with lysozyme. Therefore, the periplasm is not a uniform compartment and the polarization of GFP is unlikely to be caused by simple invagination of the cytoplasmic membrane at the poles. Moreover, the polar gathering of GFP is reversible; the reversion was accelerated by glucose and inhibited by azide and carbonyl cyanide m-chlorophenylhydrazone, indicating an active adaptation of the bacteria to the osmolarity in the medium. These results strongly suggest a relocalization of periplasmic substances in response to environmental changes. The polar area might be the preferential zone where bacteria sense the change in the environment.

Animals↗

Is the accumulation of osmoprotectant the unique mechanism involved in bacterial osmoprotection?

Sucrose, trehalose, maltose, cellobiose, gentiobiose, turanose and palatinose are very unusual osmoprotectants for Sinorhizobium meliloti, because these compounds, unlike other bacterial osmoprotectants, do not accumulate as cytosolic osmolytes in salt-stressed S. meliloti cells. Rather, these compounds were catabolized during early exponential growth, and contributed to enhance the cytosolic levels of the two endogenously-synthesized osmolytes: glutamate and the dipeptide N-acetylglutaminylglutamine amide (NAGGN). Furthermore, all of the disaccharides that acted as powerful osmoprotectants shared the same uptake routes in S. meliloti. Here, we show that these disaccharides, in fact, belong to a new family of non-accumulated sinorhizobial osmoprotectants and that two mechanisms of osmoprotection coexist in S. meliloti.

Bacteria↗

Glycine betaine-assisted protein folding in a lysA mutant of Escherichia coli.

Osmoprotectants exogenously supplied to a hyperosmotic culture medium are efficiently imported and amassed by stressed cells of Escherichia coli. In addition to their evident role in the recovery and maintenance of osmotic balance, these solutes should play an important role on the behavior of cellular macromolecules, for example in the process of protein folding. Using a random chemical mutagenesis approach, a conditional lysine auxotrophic mutant was obtained. The growth of this mutant was restored by addition of either lysine or osmoprotectants including glycine betaine (GB) in the minimal medium. The growth rate increased proportionally with the augmentation of the intracellular GB concentration. The mutation was located in the lysA gene and resulted in the substitution of the Ser at position 384 by Phe of the diaminopimelate decarboxylase (DAPDC), which catalyzes the conversion of meso-diaminopimelate to L-lysine. We purified both the wild type DAPDC and the mutated DAPDC-sf and demonstrated that GB was capable of activating DAPDC-sf in vitro, thus confirming the in vivo results. Most importantly, we showed that the activation was correlated with a conformational change of DAPDC-sf. Taken together, these results show, for the first time, that GB may actively assist in vivo protein folding in a chaperone-like manner.

Bacterial Proteins↗

Oral iron cutaneous adverse reaction and successful desensitization.

BACKGROUND: The oral administering of iron preparations sometimes produces adverse gastrointestinal effects. In contrast, cutaneous reactions are extremely rare. OBJECTIVE: We report a patient with several episodes of generalized pruritus and erythematous maculopapular eruption after receiving oral compounds of iron and on whom desensitization with oral iron was attempted. METHODS: We studied a female with microcytic anemia due to gynecologic blood loss who presented several episodes of cutaneous eruption after receiving oral compounds of iron. Skin prick-test and two simple-blind, placebo-controlled oral challenges were performed with various iron compounds, and finally desensitization with oral iron was carried out. RESULTS: Skin prick-test and patch-test with iron preparations were negative. Two simple-blind, placebo-controlled oral challenges were performed and the patient began experiencing similar cutaneous symptoms. We started a slow desensitization protocol using increasing doses until the target amount of the drug was tolerated without adverse effects. The chronic administration of oral iron therapy once a day for 9 months sustained the desensitized state and the anemia disappeared. CONCLUSION: We present methods to effectively manage iron supply for a microcytic anemia patient with cutaneous reactions due to oral iron compounds, to avoid repeated transfusions, slow desensitization with oral iron was successfully attempted.

Administration, Oral↗

Pocket 4 in the HLA-DRB1 antigen-binding groove: an association with atopy.

BACKGROUND: Many studies have attempted to identify an association between HLA genes and atopy, given the role of HLA molecules in the regulation of the immune response. In the case of house-dust mites, it is difficult to find an association with a particular HLA allele, due to the complexity of the allergen. The objective was to investigate whether HLA-DRB1 functional groups are better correlated with the atopic disease in our population than DRB1 alleles. METHODS: The method was reanalysis of the HLA-DRB1 data of a previous case/ control study. RESULTS: The "Dr" group was found to be associated with the atopic disease in our population. CONCLUSIONS: Grouping HLA-DRB1 alleles into functional categories may assist in the search for predictive factors in relation to atopic disease.

Adult↗

Pathological gambling and DNA polymorphic markers at MAO-A and MAO-B genes.

This study was conducted to detect a possible association of MAOA and/or MAOB genes with pathological gambling (PG). DNA polymorphisms in MAOA and MAOB genes were screened by molecular analysis in 68 individuals (47 males and 21 females) meeting ICD-10 and DSM-IV criteria for pathological gambling and 68 healthy comparison controls matched for age and sex. There were no significant differences between pathological gamblers and healthy volunteers in overall allele distribution at the MAOA gene polymorphism. However there was a significant association between allele distribution and the subgroup of severe male gamblers (n = 31) compared to the males in the group of healthy volunteers (chi2 = 5246; df = 1; P < 0.05 [Bonferroni corrected]). No association was found between the MAOB polymorphic marker and PG. Allele variants at the MAOA, but not the MAOB gene may be a genetic liability factor in PG, at least in severe male gamblers. Molecular Psychiatry(2000) 5, 105-109.

Adult↗

Solitary intestinal fibromatosis as a cause of bile vomiting in a neonate.

The authors describe a 3-day-old newborn admitted with signs of intestinal obstruction caused by solitary intestinal fibromatosis (SIF). This is a very rare lesion, which has an excellent prognosis. The differential diagnosis of bilious vomiting in a neonate caused by other than tumorous processes in the neonatal intestine is extensive. Probably this kind of lesion is more frequent in the neonatal period than thought until now but underdiagnosed because of the difficulty of diagnosis. Therapy of choice is wide local excision, and prognosis is excellent.

Bile↗

Class I chitinases, the panallergens responsible for the latex-fruit syndrome, are induced by ethylene treatment and inactivated by heating.

BACKGROUND: Class I chitinases have been identified as the major panallergens in fruits associated with the latex-fruit syndrome, such as avocado, banana, and chestnut. However, other plant foods containing these enzymes have not been related to this syndrome. OBJECTIVE: We sought out class I chitinases in the green bean, a legume that is known to express chitinases but is not associated with latex allergy, and examined whether the content or allergenic activity of chitinases can be modified by physical or chemical treatments. METHODS: IgE-binding proteins in untreated bean samples, as well as in ethylene- and heat-treated samples, were detected by using a pool of sera from patients with latex-fruit allergy. Putative allergens were purified by cation-exchange chromatography and characterized by N-terminal sequencing, enzymatic activity assays, immunodetection with sera and antichitinase antibodies, and immunoblot inhibition tests. Skin prick tests with untreated and heated purified allergens were also carried out. RESULTS: An IgE-binding protein of 32 kd that was also recognized by antichitinase antibodies was detected in green bean extracts. This reactive component was strongly induced by ethylene treatment. The protein, designated PvChI, was identified as a class I chitinase closely related to the major avocado allergen Prs a 1. Immunoblot inhibition assays demonstrated cross-reactivity between both allergens. Purified PvChI induced positive skin prick test responses in 7 of 8 patients with latex-fruit allergy. Heat treatment of both Prs a 1 and PvChI produced a full loss of their allergenic capacities both in vitro and in vivo. No IgE-binding component was detected in the white mature bean in which the main isolated 32-kd protein corresponded to a nonreactive phytohemagglutinin. CONCLUSIONS: Ethylene treatment induces the expression of plant class I chitinases. The allergenic activity of plant class I chitinases seems to be lost by heating. This fact could explain why plant foods containing these putative allergens that are consumed after cooking are not usually associated with the latex-fruit syndrome.

Amino Acid Sequence↗

Glycine betaine, carnitine, and choline enhance salinity tolerance and prevent the accumulation of sodium to a level inhibiting growth of Tetragenococcus halophila.

Natural-abundance (13)C-nuclear magnetic resonance was used to probe the intracellular organic solute content of the moderately halophilic bacterium Tetragenococcus halophila. When grown in complex growth media supplemented or not with NaCl, T. halophila accumulates glycine betaine and carnitine. Unlike other moderate halophiles, T. halophila was not able to produce potent osmoprotectants (such as ectoines and glycine betaine) through de novo synthesis when cultured in defined medium under hyperosmotic constraint. Addition of 2 mM carnitine, glycine betaine, or choline to defined medium improved growth parameters, not only at high salinity (up to 2.5 M NaCl) but also in media lacking NaCl. These compounds were taken up when available in the surrounding medium. The transport activity occurred at low and high salinities and seems to be constitutive. Glycine betaine and carnitine were accumulated by T. halophila in an unmodified form, while exogenously provided choline led to an intracellular accumulation of glycine betaine. This is the first evidence of the existence of a choline-glycine betaine pathway in a lactic acid bacterium. An assay showed that the compatible solutes strikingly repressed the accumulation of glutamate and slightly increased the intracellular potassium level only at high salinity. Interestingly, osmoprotectant-treated cells were able to maintain the intracellular sodium concentration at a relatively constant level (200 to 300 nmol/mg [dry weight]), independent of the NaCl concentration of the medium. In contrast, in the absence of osmoprotectant, the intracellular sodium content increased sharply from 200 to 2,060 nmol/mg (dry weight) when the salinity of the medium was raised from 1 to 2 M. Indeed, the imported compatible solutes play an actual role in regulating the intracellular Na(+) content and confer a much higher salt tolerance to T. halophila.

Adaptation, Physiological↗

Osmoprotection by pipecolic acid in Sinorhizobium meliloti: specific effects of D and L isomers.

DL-Pipecolic acid (DL-PIP) promotes growth restoration of Sinorhizobium meliloti cells facing inhibitory hyperosmolarity. Surprisingly, D and L isomers of this imino acid supplied separately were not effective. The uptake of L-PIP was significantly favored in the presence of the D isomer and by a hyperosmotic stress. Chromatographic analysis of the intracellular solutes showed that stressed cells did not accumulate radiolabeled L-PIP. Rather, it participates in the synthesis of the main endogenous osmolytes (glutamate and the dipeptide N-acetylglutaminylglutamine amide) during the lag phase, thus providing a means for the stressed cells to recover the osmotic balance. (13)C nuclear magnetic resonance analysis was used to determine the fate of D-PIP taken into the cells. In the absence of L-PIP, the imported D isomer was readily degraded. Supplied together with its L isomer, D-PIP was accumulated temporarily and thus might contribute together with the endogenous osmolytes to enhance the internal osmotic strength. Furthermore, it started to disappear from the cytosol when the L isomer was no longer available in the culture medium (during the late exponential phase of growth). Together, these results show an uncommon mechanism of protection of osmotically stressed cells of S. meliloti. It was proved, for the first time, that the presence of the two isomers of the same molecule is necessary for it to manifest an osmoprotective activity. Indeed, D-PIP seems to play a major role in cellular osmoadaptation through both its own accumulation and improvement of the utilization of the L isomer as an immediate precursor of endogenous osmolytes.

Magnetic Resonance Spectroscopy↗