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Biomedical subjects

J Perez

Publications and source records attributed to J Perez.

At least 55 records · Page 3Linked to original sources

Is obsessive-compulsive disorder caused by a second-messenger imbalance?

Although the precise etiologic nature of obsessive-compulsive disorder (OCD), one of the most common psychiatric conditions, is unknown, several findings indicate involvement of the serotonin (5-HT) transporter. Apart from the specific effects of selective 5-HT reuptake inhibitors, other studies show decreased functionality of the platelet 5-HT transporter in OCD. In this report, the authors combine data from two independent studies of patients with OCD, showing both an increased activity of protein kinase type C (PKC) and a decreased activity of protein kinase type A (PKA). The authors propose a unifying hypothesis that OCD might be determined by an imbalance between PKC and PKA, with a prevalence of the former and, more generally, of the phosphoinositide over the cyclic adenosine monophosophate (cAMP) pathway. Should this hypothesis prove correct, the path would be open for new therapeutic interventions in the treatment of OCD.

Journal Article↗

Implications of the cAMP signaling pathway in psychiatric disorders: a systematic review of the evidence.

The last decade has seen a shift in the theoretical framework addressing the pathophysiology of psychiatric disorders. During this period, research endeavors have been directed toward investigating the biochemical mechanisms involved in the transduction of information from the cell surface to the cell interior. The emerging picture, supported by growing evidence, is that in addition to neurotransmitters and their receptors, various signal transduction pathways may be linked to the pathophysiology of major psychiatric disorders. In this review, the role of one such pathway--the cyclic adenosine monophosphate (cAMP) signaling pathway--will be highlighted. We review data suggesting the involvement of the upstream and downstream components of this system in the pathophysiology of psychiatric disorders.

Journal Article↗

Protein kinase A and Rap1 levels in platelets of untreated patients with major depression.

We have recently reported altered levels of protein kinase A and Rap1 in patients with bipolar disorder. The purpose of the current investigation was to assess the levels of these proteins in platelets from untreated euthymic and depressed patients with major unipolar depression. Platelets were collected from 45 drug-free unipolar patients (13 euthymic and 32 depressed) and 45 healthy subjects. The levels of protein kinase A and Rap1 were assessed by Western blot analysis, immunostaining and computer-assisted imaging. The immunolabeling of the regulatory subunit type II of protein kinase A and that of Rap1 was significantly lower in untreated depressed patients compared with untreated euthymic patients and healthy subjects. No significant differences were found in the immunolabeling of both the regulatory type I and the catalytic subunits of protein kinase A among groups. Levels of the regulatory subunit type II of protein kinase A and Rap1 are altered in platelets of unipolar depressive patients. These findings may provide new insight about the relationship between components of cAMP signaling and affective disorders.

Adult↗

Key interactions in the immunoglobulin-like structure of apo-neocarzinostatin: evidence from nuclear magnetic resonance relaxation data and molecular dynamics simulations.

The three-dimensional structure of apo-neocarzinostatin (apo-NCS, MW: ca.11000, antitumoral chromophore carrier protein) is based on a seven-stranded antiparallel beta-sandwich, very similar to the immunoglobulin folding domain. We investigated the backbone dynamics of apo-NCS by (13)C-NMR relaxation measurements and molecular dynamics simulation. Model-free parameters determined from the experimental data are compared with a 1.5-nsec molecular simulation of apo-NCS in aqueous solution. This comparison provides an accurate description of both local and collective movements within the protein. This analysis enabled us to correlate dynamic processes with key interactions of this beta-protein. Local motions that could be relevant for the intermolecular association with the ligand are also described.

Antibiotics, Antineoplastic↗

Integrating the methadone patient in the traditional addiction inpatient rehabilitation program--problems and solutions.

Physicians have reported alcoholism and opioid addiction as co-morbid conditions since the 19th century. From the inception of methadone maintenance treatment, heroin addicts with serious alcohol conditions have enrolled in methadone maintenance programs. Programs that treat alcoholism, including the traditional addiction inpatient rehabilitation programs of the Addiction Treatment Centers (ATCs) operated by New York State, have based their treatment regimen on 12-step abstinence models. Methadone maintenance was considered antithetical to this philosophy. It was regarded as simply substituting one drug for another and not a legitimate treatment for opiate dependence. Therefore, methadone patients were often not accepted into alcohol treatment programs, since they were perceived as active addicts taking a mood-altering drug. Alcohol-related conditions among methadone patients are major causes of liver disease and death, and behavior problems associated with excessive drinking are major reasons for discharging patients. To address these issues and the lack of treatment facilities, the administration of the New York State Office of Alcoholism and Substance Abuse Services (OASAS), which licenses both methadone programs and the ATCs in New York State, realized that many of the methadone patients with alcohol problems are in need of the services provided at the ATCs. They instituted, therefore, a rigorous educational effort for the medical and counseling staffs of the ATCs, designed to integrate methadone treatment into the ATC treatment framework. Eighty percent of the 220 methadone patients who entered the ATCs in a demonstration project during the 1997/1998 state fiscal year have been compliant with the treatment regimen. These results have led to acceptance of methadone patients into the ATCs.

Alcoholism↗

Two-year study of the protective efficacy of the oral whole cell plus recombinant B subunit cholera vaccine in Peru.

The protective efficacy of an oral inactivated whole cell Vibrio cholerae plus recombinant B subunit cholera vaccine was determined against El Tor cholera among Peruvian children and adults (2-65 years old) in a randomized, double-blind manner. Study subjects received 2 doses of vaccine or placebo 2 weeks apart, followed by a booster dose 10 months later. Surveillance for cholera was performed actively, with 2 visits per week to each household, and passively, at a local hospital. Stool samples were collected during diarrhea episodes and were cultured for V. cholerae. A total of 17,799 persons received 2 doses of vaccine or placebo, and 14,997 of these persons received the booster dose. After 2 doses (first surveillance period), V. cholerae biotype O1 was isolated from 17 vaccinees and 16 placebo recipients, demonstrating vaccine efficacy (VE) of -4%. After 3 doses (second surveillance period), V. cholerae O1 was isolated from 13 vaccinees and 32 placebo recipients, demonstrating VE of 61% (95% confidence interval ¿CI, 28%-79%). In the second surveillance period, the VE for illness requiring hospitalization was 82% (95% CI, 27%-96%). VE was also higher for persons >15 years old (VE, 72%; 95% CI, 28%-89%).

Administration, Oral↗

Emergency department presentations of typhoid fever.

Typhoid fever, a systemic infectious disease caused by Salmonella typhi, is classically characterized by fever, paradoxical bradycardia, abdominal pain, and a rose colored rash. This was a retrospective review of 21 confirmed cases over a 5-year period. Mean age was 32.6 years (range 2-60 years), and Mexico (7/21) and El Salvador (3/21) represented the most common countries of origin. Recent travel to an endemic area was noted in 14 patients. The most common complaints were fever (15/21), headache (10/21), abdominal pain (9/21), and diarrhea (6/21). Average duration of symptoms before presentation to the Emergency Department (ED) was 7.9 days. High fever associated with bradycardia was noted in 12 patients. Leukopenia was present in 7 patients. Blood culture was the most sensitive confirmatory test while the Widal test was positive in 7 out of 11 cases. Fever of unknown origin (12/21), followed by presumed typhoid fever (3/21) were the most common ED diagnoses. It is important to recognize that patients with typhoid fever may present to EDs in the US and this disease should be included in the differential diagnosis of febrile patients from Latin America or those with a history of recent travel to endemic countries.

Abdominal Pain↗

Abnormal levels of cAMP-dependent protein kinase regulatory subunits in platelets from schizophrenic patients.

Abnormalities in the cAMP-dependent protein kinase (PKA), a central component of cAMP signaling, have been reported in several psychiatric disorders. Previous studies showed cAMP signaling alterations in schizophrenic patients but less is known about the involvement of PKA in such disorder. Therefore, we investigated the PKA subunits by Western blot analysis in platelets from 12 patients with schizophrenia and 13 controls. The results showed that the immunolabeling of the PKA regulatory subunits type I (RI) and type II (RII) was significantly reduced in patients compared with controls whereas no differences were observed in the catalytic (C) subunit of the enzyme. These preliminary data suggest that schizophrenic patients have altered PKA levels, thus supporting that dysfunctions in the components of cAMP signaling may contribute to the pathophysiology of schizophrenia.

Actins↗

Abnormalities of cAMP signaling in affective disorders: implication for pathophysiology and treatment.

OBJECTIVE: During the last decade, much attention has been given to the role of signal transduction pathways in affective disorders. This review describes the possible role of the cAMP signaling in such disorders. METHODS: Among the components of cAMP signaling, this review focuses on the cAMP-dependent phosphorylation system. We analyzed the basic components of the cAMP-dependent phosphorylation system and the preclinical evidence supporting their involvement in the biochemical action of antidepressants and mood stabilizers. The clinical data available until now, concerning the possible link between the cAMP-dependent phosphorylation system and the pathophysiology of affective disorders, are also reviewed. RESULTS: The studies herein presented demonstrated that the levels and the activity of cAMP-dependent protein kinase are altered by antidepressants and mood stabilizers. Furthermore. these medications are able to modify the phosphorylation state, as well as the levels of some of the cAMP-dependent protein kinase substrates. More recently, clinical studies have reported abnormalities in the cAMP-dependent phosphorylation system in both peripheral cells and the postmortem brain of patients with affective disorders. CONCLUSIONS: Overall, these studies support an involvement of cAMP signaling in affective disorders. The precise knowledge of the findings has the potential to improve the understanding of pharmacotherapy and to provide directions for the development of novel biochemical and genetic research strategies on the pathogenesis of affective disorders.

Antidepressive Agents↗

Multiple paternity increases effective size of southern Atlantic salmon populations.

Genetic analyses were performed on the progeny of Atlantic salmon (Salmo salar L.) sampled in natural redds of three rivers flowing into the Bay of Biscay, the Nivelle, the Mandeo and the Sella. These rivers are at the southern limit of the European distribution of the species and their populations are small and endangered by human activities. Nine variable number of tandem repeat (VNTR) loci (five minisatellites and four microsatellites) were used for parentage analysis. Multiple male participation was recognized in the fertilization of eggs. A large proportion was fertilized by precociously mature parr. We demonstrate that multiple paternity derived from mature parr is crucial for the conservation of genetic variability in small populations of Atlantic salmon.

Animals↗

Second messenger-regulated protein kinases in the brain: their functional role and the action of antidepressant drugs.

Depression has been treated pharmacologically for over three decades, but the views regarding the mechanism of action of antidepressant drugs have registered recently a major change. It was increasingly appreciated that adaptive changes in postreceptor signaling pathways, rather than primary action of drugs on monoamine transporters, metabolic enzymes, and receptors, are connected to therapeutic effect. For some of the various signaling pathways affected by antidepressant treatment, it was shown that protein phosphorylation, which represents an obligate step for most pathways, is markedly affected by long-term treatment. Changes were reported to be induced in the function of protein kinase C, cyclic AMP-dependent protein kinase, and calcium/calmodulin-dependent protein kinase. For two of these kinases (cyclic AMP- and calcium/calmodulin-dependent), the changes have been studied in isolated neuronal compartments (microtubules and presynaptic terminals). Antidepressant treatment activates the two kinases and increases the endogenous phosphorylation of selected substrates (microtubule-associated protein 2 and synaptotagmin). These modifications may be partly responsible for the changes induced by antidepressants in neurotransmission. The changes in protein phosphorylation induced by long-term antidepressant treatment may contribute to explain the therapeutic action of antidepressants and suggest new strategies of pharmacological intervention.

Animals↗

Isolation, characterization, and chromosomal location of the tRNA(Met) genes in Atlantic salmon (Salmo salar) and brown trout (Salmo trutta).

This work describes the isolation, characterization, and physical location of the methionine tRNA in the genome of Atlantic salmon (Salmo salar L.) and brown trout (Salmo trutta L.). An Atlantic salmon genomic library was screened using a tRNA(Met) probe from Xenopus laevis. Two cosmid clones containing the Atlantic salmon tRNA(Met) gene were isolated, subcloned and sequenced. The tRNA(Met) was mapped to metaphase chromosomes by fluorescence in situ hybridization (FISH). Chromosomal data indicated that the tDNA of methionine is tandemly repeated in a single locus in both species. Analysis of genomic DNA by Southern hybridization confirmed the tandem organization of this gene.

Animals↗

Normal values of regional left ventricular endocardial motion: multicenter color kinesis study.

Our goal was to establish normal values for quantitative color kinesis indexes of left ventricular (LV) wall motion over a wide range of ages, which are required for objective diagnosis of regional systolic and diastolic dysfunction. Color-encoded images were obtained in 194 normal subjects (95 males, 99 females, age 2 mo to 79 yr) in four standard views. Quantitative indexes of magnitude and timing of systolic and diastolic function were studied for age- and gender-related differences. Normal limits of all ejection and filling indexes were in a narrow range (< or =25% of the mean), with no major gender-related differences. Despite invariable ejection fractions, both peak filling and ejection rates decreased with age (30 and 20%, correspondingly) with a concomitant increase in mean filling and ejection times, resulting in five- and twofold increases in the late to early filling and ejection ratios, correspondingly. Diastolic asynchrony increased with age (from 4.7 +/- 2.0 to 6.4 +/- 3.2 from the 2nd to 7th decade). The normal values of color kinesis indexes should allow objective detection of regional LV systolic and diastolic dysfunction.

Adolescent↗

Altered cAMP-dependent protein kinase A in platelets of patients with obsessive-compulsive disorder.

OBJECTIVE: The purpose of this study was to assess cAMP-dependent protein kinase A in patients with obsessive-compulsive disorder (OCD). METHOD: The levels and the activity of protein kinase A were evaluated in whole platelets obtained from 12 unmedicated patients with OCD and 15 healthy comparison subjects. RESULTS: The immunolabeling of protein kinase A regulatory subunits type I and II were significantly greater but that of the catalytic subunit significantly lower in patients with OCD than in healthy subjects. The cAMP-stimulated activity in patients with OCD was significantly lower than that in healthy subjects. CONCLUSIONS: These data suggest a possible role of protein kinase A in the pathophysiology of OCD.

Actins↗

Venlafaxine versus fluvoxamine in the treatment of delusional depression: a pilot double-blind controlled study.

BACKGROUND: Previous studies have reported the efficacy of selective serotonin reuptake inhibitors as monotherapy in the treatment of delusional depression. The clinical efficacy of venlafaxine, a serotonin-norepinephrine reuptake blocker, has been demonstrated in the treatment of patients with moderate-to-severe depression, but, to date, no evidence is available about its use in depressed patients with psychotic features. METHOD: Under double-blind conditions, 28 hospitalized patients who met DSM-IV criteria for major depression, severe with psychotic features, were randomly assigned to receive fluvoxamine or venlafaxine, 300 mg/day, for 6 weeks. Severity was evaluated using the Hamilton Rating Scale for Depression (HAM-D) and the Dimensions of Delusional Experience Rating Scale (DDERS) administered at baseline and every week thereafter. Side effects were also recorded. Clinical response was defined as a reduction of the scores in the 21-item HAM-D to 8 or below and in the DDERS to 0. RESULTS: At study completion, the response rates were 78.6% (N = 11) and 58.3% (N = 7) for fluvoxamine and venlafaxine, respectively. No significant difference was found between drugs (Fisher exact test, p = .40). Analysis of covariance on HAM-D scores did not reveal a significantly different decrease of depressive symptomatology between the 2 treatment groups (p = .14). Treatment response appeared to be unrelated to the demographic and clinical characteristics recorded. The overall safety profile of both fluvoxamine and venlafaxine was favorable. CONCLUSION: The results of this pilot double-blind trial show that fluvoxamine is useful in the treatment of delusional depression and suggest that venlafaxine may also be an effective compound in the treatment of this disorder. The latter finding, although promising, warrants further replication in a larger sample of patients.

Adult↗

Laser hair removal.

We are in a state of evolution in long-term hair removal. Safe and effective technology is now available. Lasers will always become smaller, faster, and perhaps more effective. For those interested in offering this procedure, evidence indicates that we are beyond the experimental phase. The treating physician should carefully review current available technology and receive proper training specific to that system.

Humans↗

An open standard platform for interoperability of medical devices.

Patient care in Intensive Care Units and Operating Rooms requires sophisticated instrumentation for monitoring, treatment and control. A major technical problem is the communication between devices, since the connection of medical devices from different manufacturers has similar problems to the communication between people from different countries who do not share a common language. Several proprietary solutions have been developed by initiatives from well-known international companies. These proprietary, non-open solutions have not gained general acceptability and have failed to draw upon the immense resources for instrumentation development which are available in the industry. Consequently, a set of open European standards for Medical Device Intercommunication has recently been created (ratified 1999) to provide the ability to connect devices to each other freely and to exchange data between them. The development of such standards has lead to the design and implementation of a network platform over which those standards could be tested and validated. At the same time guidelines have been defined for the development and deployment of open solutions for any kind of medical device, including existing legacy devices. The design and testing of this open standards implementation is described in this paper.

Computer Communication Networks↗