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At least 991 records · Page 55Linked to original sources
PubMed2004

Immortalization of human osteoblasts by transferring human telomerase reverse transcriptase gene.

In the current study, in order to establish an immortalized osteoblast cell line, human mesenchymal stem cells (hMSCs) had been inducted into osteoblasts directionally by an osteo-inductive conditioned medium, then the osteoblasts were steadily transduced by a retroviral vector containing human telomerase reverse transcriptase (hTERT) gene. The expression of hTERT, the telomerase activity, the telomere lengths, the tumorigenesis and the osteogenesis characteristics of transduced cells at different population doublings (PDs) and the primary normal human osteoblast (hOB) were identified. The results demonstrated that hTERT gene had been transferred into human osteoblasts successfully; the transduced cell line-clone5 expressed telomerase activity and divided vigorously and now have undergone more than 120 PDs; The telomere length of clone5 elongated and was stable; Different eras of clone5 (PD 40 and PD 88) both expressed bone-specific markers, such as alkaline phosphatase (ALP), collagen type I, and osteopontin. And the quantitative assay of ALP activity showed that there were no significant differences among untransduced cells, PD 40 and PD 88 clone5 cells. Furthermore, the immortalized cell line was benign in nude mice tumor formation and soft agar colony formation assay.

Adenoviridae↗
PubMed2004

Computational models of epileptiform activity in single neurons.

A series of original computational models written in NEURON of increasing physiological and morphological complexity were developed to determine the dominant causes of epileptiform behavior. Current injections to a model hippocampal pyramidal neuron consisting of three compartments produced the sustained depolarizations (SD) and simple paroxysmal depolarizing shifts (PDS) characteristic of ictal and interictal behavior in a cell, respectively. Our results indicate that SDs are the result of the semi-saturation of Na+, Ca2+ and K+ active channels, particularly the CaN, with regular Na+/K+ spikes riding atop a saturated depolarization; PDS rides on a similar semi-saturated depolarization whose shape depends more heavily on interactions between low-threshold voltage-gated Ca2+ channels (CaT) and Ca(2+)-dependent K+ channels. Our results reflect and predict recent physiological data, and we report here a cellular basis of epilepsy whose mechanisms reside mainly in the membrane channels, and not in specific morphology or network interactions, advancing a possible resolution to the cellular/network debate over the etiology of epileptiform activity.

Action Potentials↗
PubMedDate not supplied

Patterns of axis II comorbidity in early-onset versus late-onset panic disorder in Japan.

Early onset of psychiatric disorders has been reported to be associated with increased familial risk or more severe clinical symptoms. In this study, we specifically examine the association between clinical severity and early versus late onset in panic disorder. We hypothesize the existence of differences in rates of axis II disorders in these two groups that will relate to clinical severity. Subjects were a consecutive clinical case series of 105 panic disorder patients (age, 18.3 to 70.9 years). Thirty-one panic disorder patients were classified as early onset (age of onset < or = 25 years) and 74 as late onset (age of onset >25). We compared symptomatology and rates of comorbid axis II disorders (diagnosed by structured clinical interview) between the early- and the late-onset groups. We found a statistically significant increase in the number of suicide attempts and likelihood of comorbid axis II disorders in the early-onset group compared to the late-onset group. In logistic regression analyses, cluster B personality disorders (PDs), especially borderline and histrionic, were statistically significantly associated with the presence of suicide attempts. The following limitations are present: first, we have not taken into consideration comorbidity of other axis I disorders, especially major depression. Second, there is imprecision associated with efforts to date the onset of panic disorder retrospectively. We conclude that comorbid axis II disorders are more likely to occur in early-onset panic disorder patients. Cluster B PDs, especially borderline or histrionic, may be associated with a high frequency of suicide attempts in this group. In clinical practice, efforts to aggressively detect and treat axis II disorders in early-onset panic disorder patients are warranted.

Adolescent↗
PubMed2006

The interrater reliability of the Structured Interview for DSM-IV Personality.

We examined the joint interview interrater reliability of the Structured Interview for Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Personality Disorders (SIDP-IV) in 433 non-treatment-seeking military recruits. Reliability was computed for the diagnosis of a specific personality disorder (PD) and for the number of PD criteria present, and computed using a dimensional score. Reliability increased when PDs were computed using dimensional scores rather than categorical scores. Avoidant and dependent PDs demonstrated the highest interrater reliability, whereas schizoid and schizotypal showed the lowest. This large sample allowed us to perform item-level analyses of the SIDP-IV. Interrater reliability for each of the PD criteria was generally more than 0.70, with the notable exception of criteria scored through observation only. Overall, the SIDP-IV demonstrated good reliability in a non-treatment-seeking population.

Diagnostic and Statistical Manual of Mental Disord↗
PubMed2003

UV-induced de novo protein synthesis enhances nucleotide excision repair efficiency in a transcription-dependent manner in S. cerevisiae.

DNA damage results in the up-regulation of several genes involved in different cellular physiological processes, such as the nucleotide excision repair (NER) mechanism that copes with a broad range of DNA alterations, including the carcinogenic ultraviolet (UV) light-induced pyrimidine dimers (PDs). There are two NER sub-pathways: transcription coupled repair (TCR) that is specific for the transcribed strands (TS) of active genes and global genomic repair (GGR) that repairs non-transcribed DNA sequences (NTD) and the non-transcribed strands (NTS) of expressed genes. To elucidate the role of UV-dependent de novo protein synthesis in nucleotide excision repair in the budding yeast, we investigated the effect of the protein synthesis inhibitor, cycloheximide, on the removal of PDs. Log phase as well as G(1)-synchronized cells were treated with the drug shortly before UV irradiation and immediately thereafter, and the repair of damaged DNA was assessed with the high resolution primer extension technique. The results show that in both cellular conditions, the inhibition of UV-dependent de novo protein synthesis by cycloheximide impairs the excision repair of the transcriptionally active GAL10 and URA3 genes, with a greater effect on the non-transcribed strands. This indicates that UV-mediated de novo protein synthesis is required for efficient nucleotide excision repair, but not for the preferential repair of the TSs. On the other hand, cycloheximide did not affect the repair of either strand of the repressed GAL10 gene or the non-transcribed promoter region of the URA3 gene, showing that UV-induced de novo protein synthesis is not required for PD removal from transcriptionally inactive DNA sequences. Together, these data show that despite the fact that NTD and NTSs are normally repaired by the GGR sub-pathway, their requirement for UV-dependent de novo protein synthesis is different, which may suggest a difference in the processing of UV lesions in these non-transcribed sequences of the genome.

Cycloheximide↗
PubMed2005

Do personality disorders predict negative treatment outcome in obsessive-compulsive disorders? A prospective 6-month follow-up study.

BACKGROUND: Comorbid personality disorders (PDs) are discussed as risk factors for a negative treatment outcome in obsessive-compulsive disorder (OCD). However, studies published so far have produced conflicting results. The present study examined whether PDs affect treatment outcome in patients with OCD. METHOD: The treatment sample consisted of 55 patients with OCD who were consecutively referred to a Behaviour Therapy Unit for an in-patient or day-clinic treatment. Treatment consisted of an individualised and multimodal cognitive behaviour therapy (CBT, with or without antidepressive medication). Measurements were taken prior and after treatment and 6-month after admission. RESULTS: A large percentage of patients benefited from treatment irrespective of the presence of a PD and were able to maintain their improvement at follow-up. Duration of treatment was not prolonged in OCD patients with concomitant Axis II disorders. However, some specific personality traits (schizotypal, passive-aggressive) were baseline determinants for later treatment failure at trend level. CONCLUSIONS: Results are encouraging for therapists working with patients co-diagnosed with Axis II disorders since these patients are not necessarily non-responders. The results stress the importance of a specifically tailored treatment approach based on an individual case formulation in OCD patients with complex symptomatology and comorbid Axis II disorders.

Adolescent↗
PubMed2004

Age related microsatellite instability in T cells from healthy individuals.

Many immune functions decline with age and may jeopardize the elderly, as illustrated, for example by the significantly higher mortality rate from influenza in old age. Although innate and humoral immunity are affected by aging, it is the T cell compartment, which manifests most alterations. The mechanisms behind these alterations are still unclear, and several explanations have been offered including thymic involution and Telomere attrition leading to cell senescence. Age related accumulation of mutations has been documented and could serve as an additional mechanism of T cell dysfunction. One effective repair mechanism capable of rectifying errors in DNA replications is the mismatch repair (MMR) system. We previously reported a comparative examination of individual DNA samples from blood cells obtained at 10 year intervals from young and old subjects. We showed significantly higher rates of microsatellite instability (MSI), an indicator of MMR dysfunction in older subjects, compared to young. In the present study we confirm this result, using direct automated sequencing and in addition, we demonstrate that as CD8 lymphocytes from aged individuals, undergo repeated population doublings (PDs) in culture, they develop MSI. CD4 clones that also undergo repeated PDs in culture develop significant MSI as well. Elucidation of this previously unexplored facet of lymphocyte dynamics in relation to aging may help identify novel mechanisms of immunosenescence and pathways that could serve as targets for interventions to restore immune function.

Adult↗
PubMed2006

Pancreaticoduodenectomy in the very elderly.

It is estimated that by 2050, there will be a 300% increase in the elderly population (> or =65 years) and a corresponding increase in elderly patients presenting for surgical evaluation. Surgical decision-making in this population can be difficult because outcomes in the elderly are poorly defined. We reviewed 2698 consecutive pancreaticoduodenectomies (PDs) at our institution over a 35-year period (April 1970 through March 2005), with the last 1000 resections being done in the last 4 years. Data collected included surgical indication, mortality (defined as 30-day or in-hospital mortality), complications, and survival. Patients were divided by age into three groups (<80, 80-89, and > or =90 years) and evaluated using multiple logistic regression. Two hundred seven patients > or =80 years old underwent a PD (7.7% of 2698). Patients 80-89 years of age had a mortality rate of 4.1% (8 of 197) and a complication rate of 52.8% (99 of 197), whereas patients < or =79 years of age had a mortality of 1.7% and a complication rate of 41.6% (P < 0.05). There were no perioperative deaths among the 10 patients > or =90 years of age, and their complication rate was 50% (5 of 10). One-year survival for patients 80-89 years of age was 59.1%, and that for patients > or =90 years was 60%. Age was not an independent risk factor for perioperative mortality and morbidity following PD after adjusting for preoperative comorbidities. We demonstrate that PD can be safely performed in patients over 80 years of age and conclude that age alone should not be a contraindication to pancreatic resection. The advent of improved surgical outcomes and an aging population will likely result in a significant increase in the number of PDs performed in the next few decades.

Age Factors↗
PubMedDate not supplied

Personality characteristics among cardiothoracic transplant recipients.

Personality characteristics are clinically believed to predict posttransplant adherence and outcome; however, data, as to the prevalence and type of personality disorders (PDs) and distribution of personality traits among transplant (txp) populations, are sparse and inconclusive. This paper reports on the prevalence and type of PD and range of personality traits, according to the Five-Factor model, among 73 adult cardiothoracic txp recipients. It represents the first systematic assessment of PDs and traits in a sample of txp recipients. Personality disorders were assessed with a semistructured diagnostic interview; personality traits were assessed with a self-report instrument. Thirty-three percent of the sample met diagnostic criteria for a PD, approximately three times higher than prevalence of PD previously reported among nonpsychiatric populations. Mean values of personality traits for the sample were in the normative range but with wide variability; extreme values on four of the five traits were scored by subjects with a PD. This unexpectedly high prevalence of PD and the wide variability in traits among heart and lung recipients alert clinicians to consider personality characteristics when planning interventions to increase compliance and maximize quality of life after cardiothoracic transplantation.

Adult↗
PubMed2006

A new hydrogel for the extended and complete prednisolone release in the GI tract.

The issue of incomplete release of poorly soluble drugs from sustained-release oral formulations is addressed using prednisolone (PDS) as the model drug and a novel highly swelling hydrogel as the rate-controlling material. The hydrogel was formed by heating N-carboxymethylchitosan (CMC) to 80 degrees C for 24 h. Swelling, alkalimetry, FTIR, DSC, and solid-state NMR studies showed that the treatment produced physical crosslinking, i.e., polymer chain entanglement. A controlled-release system was prepared by coating an inert compacted support of ethylcellulose (50 mg; diameter, 6 mm) with a CMC layer containing dispersed PDS powder (10-50 microm). The system was heated to crosslink the CMC coating, then drug release to simulated GI fluids was studied in vitro. The drug release pattern and term were modulated via the layer mass (LM) (10 or 14 mg cm(-2)) and/or the drug-polymer wt ratio (D/P) (1:5 or 2:5). The rate parameter, K, and the time exponent, n, of the Peppas equation were: K=26.6+/-0.3 h(-n), n = 0.78+/-0.02 (LM, 10 mg cm(-2); D/P, 1:5); K = 24.7+/-0.7 h(-n), n = 0.56+/-0.02 (LM, 14 mg cm(-2); D/P, 1:5); K = 20.7+/-0.3 h(-n), n = 0.76+/-0.01 (LM, 10 mg cm(-2); D/P, 2:5). Hydrogel swelling was faster than drug release. This was controlled, in a first stage, by drug dissolution-diffusion in the swollen gel, and subsequently, by diffusion. The drug release rate was unaffected by the GI pH variations, and slightly affected by the environmental hydrodynamics. The system promises an extended and complete release of poorly soluble drugs in the GI tract.

Chitosan↗
PubMed2006

Adolescent axis I and personality disorders predict quality of life during young adulthood.

PURPOSE: To investigate and compare the prospective association of adolescent Axis I mental disorder and personality disorder (PD) with young adult quality of life (QOL) in the general population. METHODS: Seven hundred fifty mothers and youths participating in a prospective longitudinal community-based study were interviewed. Mental disorders were measured at a mean age 16 years. QOL as the outcome indicators were assessed at a mean age 22. RESULTS: Adolescent Axis I disorder predicted elevated negative affect and higher levels of stress some 6 years later. Adolescent PD predicted elevated negative affect and higher levels of stress, and also problems in social support and relationships, and poorer residential, mobility, and financial and health resources in adulthood. Youths with both Axis I disorder and one or more PDs had the worst outcomes with regard to health problems, stressful occupational or educational settings, and resources, net of the effects of adolescent health problems. Nevertheless, some aspects of adult QOL were not significantly related to adolescent disorder, including a positive perspective on the future, own morale in a chosen occupation or educational setting, or the amount of autonomy experienced in that setting. CONCLUSIONS: Among adolescents in the community, PDs during adolescence may have a more adverse impact on young adult QOL than do Axis I disorders. A combination of Axis I and PD may represent a particular risk for new physical health problems and resource inadequacy, including poor access to health care.

Adolescent↗
PubMed2006

Physician perspectives to inform a new recommendation for meningococcal conjugate vaccine (MCV4).

PURPOSE: In January 2005, the U.S. Food and Drug Administration licensed a new tetravalent meningococcal conjugate vaccine (MCV4). Before any policy decisions by the U.S. Advisory Committee on Immunization Practices (ACIP) related to MCV4, the Centers for Disease Control and Prevention requested a study to explore the perspective of primary care physicians regarding different recommendation scenarios for use of MCV4. METHODS: Cross-sectional mail survey of a national random sample of pediatricians (PDs) and family physicians (FPs), conducted January 2005. Respondents chose from four MCV4 recommendation scenarios in terms of ability to implement, perceived patient/parent preferences, scientific evidence, and overall best fit. RESULTS: Response rate to the single-mailing survey was 57%. In terms of ability to implement, respondents generally preferred an MCV4 recommendation targeted to middle-school entry (11-12 years old) or with the Td booster at any age, but on the basis of scientific evidence they favored MCV4 at high school completion. For "overall best fit," relatively equal proportions of respondents favored a recommendation at middle school entry and one linked to Td booster administration (whenever it occurred); there were no significant differences between PDs and FPs. Major influences on willingness to recommend MCV4 were vaccine safety/side effects and insurance coverage/reimbursement. CONCLUSIONS: Support for an MCV4 recommendation at middle school entry is common but not universal among primary care providers. Data suggest that respondents appreciate the potential discrepancy between practical aspects of vaccine delivery and the need to protect those adolescents at greatest risk of disease. Respondents' preferences for the overall best fit appear to prioritize ease of implementation over epidemiologic patterns.

Adolescent↗
PubMed2005

The relationship between obsessive-compulsive and posttraumatic stress symptoms in clinical and non-clinical samples.

Although case reports suggest the existence of a unique relationship between obsessive-compulsive disorder (OCD) and posttraumatic stress disorder (PTSD), results from large-scale epidemiological and clinical studies have been more equivocal. Furthermore, symptom overlap may artificially inflate the significance of the relationship between OCD and PTSD. Utilizing the Obsessive-Compulsive Inventory [OCI; Psychol. Assess. 10 (1998) 206] and the Posttraumatic Diagnostic Scale [PDS; Psychol. Assess. 9 (1997) 445], this study examined the relationship between OCD and PTSD symptoms in 128 patients diagnosed with OCD, 109 patients diagnosed with PTSD, 63 patients diagnosed with another anxiety disorder, and 40 college students. Experts in OCD and PTSD independently rated items on the OCI and PDS for the degree of overlap across the disorders. On the basis of these ratings, we created a scale from each measure that included only non-overlapping items. Results revealed that overall symptoms of OCD and PTSD were related in all samples. However, after controlling for depression and overlapping symptoms simultaneously, this relationship was no longer significant in the OCD and PTSD samples, although it remained significant in the anxious and college student comparison groups. These results support the presence of a relationship between symptoms of OCD and PTSD that may be largely accounted for by a combination of symptom overlap and depression.

Adult↗
PubMed2004

Horizontal versus vertical dark-adapted pupil diameters in normal individuals.

PURPOSE: To determine the distribution of the difference between the horizontal and vertical dark-adapted entrance pupil diameters (PDs) in normal individuals. SETTING: Texas Tech University Health Sciences Center, Lubbock, Texas, USA. METHODS: In this observational cohort study, high-magnification infrared pupil photography was performed of the right eye of 26 normal volunteers from 20 to 47 years of age. The horizontal and vertical PDs were measured using commercially available digital-image software, taking into account the effect of photographic parallax. RESULTS: In 24 subjects (85%), the vertical PD was larger than the horizontal PD; in 8 subjects (31%), it was 0.30 mm to 0.50 mm larger. In 2 subjects, the horizontal diameter was slightly larger but the difference was <0.10 mm. The mean horizontal to vertical PD ratio was 0.97. CONCLUSIONS: In this study population, the vertical PD was larger than the horizontal PD in most subjects. Although the difference was a fraction of the total PD, it may be important for laser refractive surgery planning and preoperative risk counseling of some patients.

Adult↗
PubMed2006

The mechanomyography of persons after stroke during isometric voluntary contractions.

This study was to investigate the properties of mechanomyography (MMG), or muscle sound, of the paretic muscle in the affected side of hemiplegic subjects after stroke during isometric voluntary contractions, in comparison with those from the muscle in the unaffected side of the hemiplegic subjects and from the healthy muscle of unimpaired subjects. MMG and electromyography (EMG) signals were recorded simultaneously from the biceps brachii muscles of the dominant arm of unimpaired subjects (n=5) and the unaffected and affected arms of subjects after stroke (n=8), when performing a fatiguing maximal voluntary contraction (MVC) associated with the decrease in elbow flexion torque, and then submaximal elbow flexions at 20%, 40%, 60% and 80% MVCs. The root mean squared (RMS) values, the mean power frequencies (MPF, in the power density spectrum, PDS) of the EMG and MMG, and the high frequency rate (HF-rate, the ratio of the power above 15Hz in the MMG PDS) were used for the analysis. The MMG RMS decreased more slowly during the MVC in the affected muscle compared to the healthy and unaffected muscles. A transient increase could be observed in the MMG MPFs from the unaffected and healthy muscles during the MVC, associated with the decrease in their simultaneous EMG MPFs due to the muscular fatigue. No significant variation could be seen in the EMG and MMG MPFs in the affected muscles during the MVC. The values in the MPF and HF-rate of MMG from the affected muscles were significantly lower than those from the healthy and unaffected muscles (P<0.05) at the high contraction level (80% MVC). Both the MMG and EMG RMS values in the healthy and unaffected groups were found to be significantly higher than the affected group (P<0.05) at 60% and 80% MVCs. These observations were related to an atrophy of the fast-twitch fibers and a reduction of the neural input in the affected muscles of the hemiplegic subjects. The results in this study suggested MMG could be used as a complementary to EMG for the analysis on muscular characteristics in subjects after stroke.

Adult↗
PubMed2006

Transfer of NIR calibrations for pharmaceutical formulations between different instruments.

In order to evaluate how well existing techniques for transferring NIR calibrations perform for solid pharmaceutical formulations, a study on four assays of active ingredients was undertaken. The study included two configurations of dispersive NIR instruments and one Fourier transform (FT) instrument. Three methods for calibration transfer: slope/bias correction, local centring and piecewise direct standardisation (PDS), were tested and evaluated. Our conclusions are that the calibration transfer methods tested can perform equally well. It was shown that it is possible to transfer calibrations between instruments of different configurations or even of different types, without loosing the prediction ability of the calibration. To achieve a good calibration transfer, a larger variation in the content of the active ingredient in the samples and more samples are needed for the slope and bias correction method compared to the local centring method. For PDS to be a successful calibration transfer method, an optimisation of the number of transfer samples and how they are selected together with various factors specific for this method is needed. Local centring is the preferred transfer method as its performance is excellent yet it is simple to perform, no optimisation is needed, only a few transfer samples are required and the transfer samples do not have to vary in their content of the active ingredient.

Calibration↗
PubMed2005

Continuous growth of telomerase-immortalised fibroblasts: how long do cells remain normal?

Previously, we reported successful immortalisation following hTERT introduction in primary human fibroblasts, strain VH25. Since one subclone in that study developed some abnormalities, we decided to study eight additional independent immortalised clones to get an indication of the frequency and type of abnormalities that develop after hTERT-mediated immortalisation. We show that although some cell lines can maintain a normal phenotype for 500 population doublings (PDs), in four clones after 150-300PDs changes developed in basal and radiation-induced p53 and p21(WAF-1,CIP-1) levels. Our experiments demonstrate that, after prolonged culture, cells with abnormalities in cell cycle control parameters can take over the population. This calls for caution when working with hTERT-immortalised cells in vitro as well as in vivo.

Cell Cycle↗
PubMedDate not supplied

Modality-specific impairments in response habituation following postnatal binge ethanol.

The rate of habituation of the heart rate orienting response (OR) to both olfactory and auditory cues was examined in subjects neonatally exposed to ethanol. Subjects were administered 5.25 g/kg/day ethanol in a binge-like manner on either postnatal days (PDs) 4-9 or 10-15. Controls were given sham intubations. Ethanol exposure had no effect on the form or magnitude of the heart rate OR; all subjects exhibited a monophasic bradycardia to the olfactory and auditory cues. However, ethanol treatment severely affected the rate of response habituation to an olfactory cue, regardless of the timing of that exposure. Ethanol treatment on either PDs 4-9 or 10-15 resulted in a failure of animals to show complete heart rate response habituation. For the auditory cue, rate of response habituation was unaffected by ethanol treatment. These results indicate that response habituation deficits in a postnatal model of human fetal-alcohol exposure are modality specific. The response habituation paradigm may be useful for studying mechanisms of short-term recognition memory deficits following early alcohol exposure, although modality of the test stimulus needs to be taken into account. The results suggest that central nervous system structures affected by ethanol may be specific to those involved in olfactory processing, such as the olfactory bulb or hippocampus.

Acoustic Stimulation↗