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Biomedical subjects

John Morris

Publications and source records attributed to John Morris.

At least 19 recordsLinked to original sources
PubMed2024

X-chromosome-wide association study for Alzheimer's disease.

Due to methodological reasons, the X-chromosome has not been featured in the major genome-wide association studies on Alzheimer's Disease (AD). To address this and better characterize the genetic landscape of AD, we performed an in-depth X-Chromosome-Wide Association Study (XWAS) in 115,841 AD cases or AD proxy cases, including 52,214 clinically-diagnosed AD cases, and 613,671 controls. We considered three approaches to account for the different X-chromosome inactivation (XCI) states in females, i.e. random XCI, skewed XCI, and escape XCI. We did not detect any genome-wide significant signals (P ≤ 5 × 10-8) but identified seven X-chromosome-wide significant loci (P ≤ 1.6 × 10-6). The index variants were common for the Xp22.32, FRMPD4, DMD and Xq25 loci, and rare for the WNK3, PJA1, and DACH2 loci. Overall, this well-powered XWAS found no genetic risk factors for AD on the non-pseudoautosomal region of the X-chromosome, but it identified suggestive signals warranting further investigations.

Humans↗
PubMed2006

Annexin 1, glucocorticoids, and the neuroendocrine-immune interface.

Annexin 1 (ANXA1) was originally identified as a mediator of the anti-inflammatory actions of glucocorticoids (GCs) in the host defense system. Subsequent work confirmed and extended these findings and also showed that the protein fulfills a wider brief and serves as a signaling intermediate in a number of systems. ANXA1 thus contributes to the regulation of processes as diverse as cell migration, cell growth and differentiation, apoptosis, vesicle fusion, lipid metabolism, and cytokine expression. Here we consider the role of ANXA1 in the neuroendocrine system, particularly the hypothalamo-pituitary-adrenocortical (HPA) axis. Evidence is presented that ANXA1 plays a critical role in effecting the negative feedback effects of GCs on the release of corticotrophin (ACTH) and its hypothalamic-releasing hormones and that it is particularly pertinent to the early-onset actions of the steroids that are mediated via a nongenomic mechanism. The paracrine/juxtacrine mode of ANXA1 action is discussed in detail, with particular reference to the significance of the secondary processing of ANXA1, the processes that control the intracellular and transmembrane trafficking of the protein of the molecule and the mechanism of ANXA1 action on its target cells. In addition, the role of ANXA1 in the perinatal programming of the HPA axis is discussed.

Animals↗
PubMed2005

Distance learning and toxicology: new horizons for Paracelsus.

Distance learning offers many advantages to students and teachers of almost any scientific discipline. Toxicology is no exception. For example, should Paracelsus be interested in learning more about toxicology at Drexel University, he would have the opportunity to take two courses in this subject utilizing the content management software, WebCT. The two courses would offer a website from which he could view and/or download his notes for each class. He could correspond with the instructor as well as fellow students, participate in discussions about timely topics, and make presentations to the class, all via electronic communication. Moreover, his examinations would also be computerized. Although he might have the option of attending traditional "face-to-face" lectures with other students in the class, he could also access these lectures at any time from a remote location by using the archive of taped lectures on the class website. Overall, Paracelsus would have access to many tools to enhance his understanding of toxicology, and he probably would never have to worry about parking before class (!). The two WebCT modules in toxicology that we have developed at Drexel represent the successful migration of two courses from a traditional "face-to-face" model of classroom instruction to hybrid models that combine "face-to-face" interaction with online instruction. Student and faculty evaluations of these courses have been very positive. Future plans include linking the two modules together so that students in the advanced class can do "review" or "remedial" work in the basic module. Furthermore, a library of video clips is also planned in which researchers will be discussing their work on various toxicologic topics. Students will be able to access these clips as resources from which to write research papers.

Education, Distance↗
PubMed2005

Pallidal stimulation reduces treatment-induced dyskinesias in "minimal-change" multiple system atrophy.

Deep brain stimulation therapy is increasingly gaining acceptance in the management of levodopa-induced dyskinesia and fluctuations in idiopathic Parkinson's disease. It is generally not recommended for the other forms of parkinsonism such as progressive supranuclear palsy or multiple system atrophy where the response to levodopa is usually poor and disease progression more rapid, making any benefit short-lived. Here, we present an autopsy-confirmed case of "minimal-change" multiple system atrophy in whom pallidal stimulation surgery was effective in abolishing severe levodopa-induced dyskinesia.

Deep Brain Stimulation↗
PubMed2005

Seasonal allergic rhinitic and normal subjects respond differentially to nasal provocation with acetic acid vapor.

Individuals with seasonal allergic rhinitis (SAR) show a more marked nasal obstructive response (increases in nasal airways resistance or NAR) after provocation with chlorine gas (Cl2) than do nonrhinitic (NR) controls. We were interested in learning whether similar differential responsiveness was apparent after provocation with acetic acid vapor. Sixteen nonsmoking, nonasthmatic subjects, aged 21-63 yr, equally divided by gender and nasal allergy status, were enrolled in a single-blinded crossover study involving exposure to acetic acid (AA) vapor (15 ppm) or air for 15 min on separate days 1 wk apart. NAR was measured in triplicate before, immediately post-, and 15 min postexposure, was normalized to baseline on a given exposure day, and was expressed as Net [NAR/baseline] after acetic acid versus control (air) exposure. After log transformation to achieve normality, the mean loge of Net [NAR/baseline] was 0.22 for SAR subjects and -0.11 for NR subjects immediately postexposure (p<.05); the corresponding values were 0.24 and -0.08, respectively, at 15 min postexposure (p<.05). Inhalation of acetic acid at the (NIOSH-recommended) short-term exposure limit of 15 ppm for 15 min produces differential nasal airflow obstruction among SAR versus NR subjects, with the former showing greater physiologic reactivity to this stimulus. This differential responsiveness is consistent with our previous findings with Cl2, indicating that there may be a generalized susceptibility factor associated with allergic rhinitis. The response occurs with slight subjective nasal irritation.

Acetic Acid↗
PubMed2004

In situ generation of pseudotyped retroviral progeny by adenovirus-mediated transduction of tumor cells enhances the killing effect of HSV-tk suicide gene therapy in vitro and in vivo.

BACKGROUND: Hybrid adeno-retroviral vector systems utilize the high efficiency of adenovirus transduction to direct the in situ production of retroviral progeny. In this study, we show that a single-step transduction of glioma cells with trans-complementing hybrid adeno-retroviral vectors effectively turns these cells into retrovirus vector-producing cells, which in turn facilitates the transduction of adjacent cells. METHODS: We have adapted the adeno-retroviral hybrid viral vector system to enhance the ganciclovir (GCV) killing of glioma cells following transfer of the herpes simplex virus thymidine kinase (HSV-tk) gene. To assess the effect of the in situ production of retroviral vectors on the transduction efficiency of glioma cells, 9L cells were transduced with adeno-retroviral hybrid vectors that separately express a retroviral genome (AVC2.GCEGFP or AVC2.GCTK) and retroviral packaging proteins (AxTetGP and AxTetVSVG). The generation of an integrated HSV-tk provirus by trans-complementation of the adeno-retroviral vectors was verified by analysis of the flanking retroviral LTR sequences. Tumors established on nu/nu mice were injected with the viruses followed by intraperitoneal injections of either PBS or GCV. We also estimated the copy numbers of the HSV-tk transgene present in the tumors of the treated mice. To determine the expression pattern of the HSV-tk transcripts within a tumor, in situ hybridization analysis was performed using an RNA probe specific for HSV-tk. RESULTS: The co-transduction of rat 9L glioma cells with AVC2.GCEGFP together with vectors expressing packaging proteins of retroviruses increased the transduction efficiency. Transduction with AVC2.GCTK together with packaging vectors increased the in vitro sensitivity of cells to the pro-drug GCV by one log compared with control cells that were incapable of generating retrovirus. In vivo, the injection of established subcutaneous 9L tumors on athymic mice with a combination of AVC2.GCTK and packaging vectors followed by GCV treatment resulted in complete tumor regression in 50% of tumors at day 22, while no tumor regression was observed in control animals. Retroviral sequences diagnostic of 3' LTR reduplication in vivo were detected in genomic DNA extracted from the transduced tumors, indicating pro-viral integration of the retroviral genome derived from the adeno-retroviral hybrid vector. Furthermore, the relative copy number of the HSV-tk gene in tumors treated with the adeno-retroviral vectors was up to approximately 250-fold higher than in control tumors. In situ hybridization suggested dispersion of the HSV-tk product across a wider area of the tumor than in control tumors, which indicates the spread of the in situ generated retroviruses. CONCLUSIONS: Although the efficacy of this system has to be evaluated in orthotopic models, our observations suggest that this hybrid adeno-retroviral vector system could improve the suicide gene therapy of tumors.

Adenoviridae↗
PubMed2004

Progress on new vaccine strategies against chronic viral infections.

Among the most cost-effective strategies for preventing viral infections, vaccines have proven effective primarily against viruses causing acute, self-limited infections. For these it has been sufficient for the vaccine to mimic the natural virus. However, viruses causing chronic infection do not elicit an immune response sufficient to clear the infection and, as a result, vaccines for these viruses must elicit more effective responses--quantitative and qualitative--than does the natural virus. Here we examine the immunologic and virologic basis for vaccines against three such viruses, HIV, hepatitis C virus, and human papillomavirus, and review progress in clinical trials to date. We also explore novel strategies for increasing the immunogenicity and efficacy of vaccines.

AIDS Vaccines↗
PubMed2003

Inter-rater reliability of nursing home quality indicators in the U.S.

BACKGROUND: In the US, Quality Indicators (QI's) profiling and comparing the performance of hospitals, health plans, nursing homes and physicians are routinely published for consumer review. We report the results of the largest study of inter-rater reliability done on nursing home assessments which generate the data used to derive publicly reported nursing home quality indicators. METHODS: We sampled nursing homes in 6 states, selecting up to 30 residents per facility who were observed and assessed by research nurses on 100 clinical assessment elements contained in the Minimum Data Set (MDS) and compared these with the most recent assessment in the record done by facility nurses. Kappa statistics were generated for all data items and derived for 22 QI's over the entire sample and for each facility. Finally, facilities with many QI's with poor Kappa levels were compared to those with many QI's with excellent Kappa levels on selected characteristics. RESULTS: A total of 462 facilities in 6 states were approached and 219 agreed to participate, yielding a response rate of 47.4%. A total of 5758 residents were included in the inter-rater reliability analyses, around 27.5 per facility. Patients resembled the traditional nursing home resident, only 43.9% were continent of urine and only 25.2% were rated as likely to be discharged within the next 30 days. Results of resident level comparative analyses reveal high inter-rater reliability levels (most items >.75). Using the research nurses as the "gold standard", we compared composite quality indicators based on their ratings with those based on facility nurses. All but two QI's have adequate Kappa levels and 4 QI's have average Kappa values in excess of.80. We found that 16% of participating facilities performed poorly (Kappa <.4) on more than 6 of the 22 QI's while 18% of facilities performed well (Kappa >.75) on 12 or more QI's. No facility characteristics were related to reliability of the data on which Qis are based. CONCLUSION: While a few QI's being used for public reporting have limited reliability as measured in US nursing homes today, the vast majority of QI's are measured reliably across the majority of nursing facilities. Although information about the average facility is reliable, how the public can identify those facilities whose data can be trusted and whose cannot remains a challenge.

Aged↗
PubMed2003

Identifying the pattern of olfactory deficits in Parkinson disease using the brief smell identification test.

BACKGROUND: Selective olfactory deficits occur in 70% to 90% of patients with Parkinson disease, independent of disease severity and duration. Olfactory testing may be a useful diagnostic aid for Parkinson disease, but the types of odors most commonly affected need to be identified. OBJECTIVE: To determine the pattern and types of odors affected in Parkinson disease by means of the University of Pennsylvania 12-item Brief Smell Identification Test (B-SIT; Sensonics, Inc, Haddon Heights, NJ). DESIGN: Testing patients with Parkinson disease and control subjects in 5 movement disorder clinics. PARTICIPANTS: Forty-nine nondemented patients with Parkinson disease and 52 age- and sex-matched controls. MAIN OUTCOME MEASURES: Normal or abnormal olfactory function was determined in each subject according to predetermined age and sex norms. Predictive statistics and discriminant function analyses were performed to determine the pattern and types of odors best discriminating patients from controls. RESULTS: Abnormal olfactory function was present in 40 (82%) of patients compared with 12 (23%) of controls. The B-SIT score was unaffected by smoking behavior, disease duration, or severity. The sensitivity of the B-SIT for Parkinson disease was 0.82, with a specificity and predictive value of 0.82 and 0.77, respectively. Only 5 of the 12 B-SIT odors (gasoline, banana, pineapple, smoke, and cinnamon) were required to adequately discriminate patients with Parkinson disease from controls. CONCLUSIONS: With the use of the B-SIT, 5 specific odors appear primarily affected in patients with Parkinson disease. Significantly, the ability of patients to detect some odors was unimpaired compared with that of controls. Better diagnostic aids could be developed on the basis of the selective pattern of hyposmia observed in Parkinson disease.

Adult↗
PubMed2003

Annexin 1: a paracrine/juxtacrine mediator of glucorticoid action in the neuroendocrine system.

Glucocorticoids (GCs) play an essential role in the maintenance of homeostasis. In normal circumstances their secretion is tightly regulated by a complex servo mechanism through which the steroids suppress the synthesis and release of ACTH and its hypothalamic releasing factors (CRH and AVP) and thereby reduce the positive drive to the adrenal cortex. The feedback actions of GCs on hormone release develop rapidly (within minutes), well before any changes in hormone synthesis are apparent. By using immunoneutralization, gene targeting and pharmacological strategies in in vivo and in vitro models, we have identified annexin 1, a Ca(2+)- and phospholipid-binding protein, as a key mediator of the early inhibitory actions of GCs on peptide release. This brief review outlines this work and describes molecular and cellular studies which have provided insight into the mechanism of annexin 1-dependent GC signalling in the neuroendocrine system.

Adrenocorticotropic Hormone↗
PubMed2003

The quality of quality measurement in U.S. nursing homes.

PURPOSE: This article examines various technical challenges inherent in the design, implementation, and dissemination of health care quality performance measures. DESIGN AND METHODS: Using national and state-specific Minimum Data Set data from 1999, we examined sample size, measure stability, creation of ordinal ranks, and risk adjustment as applied to aggregated facility quality indicators. RESULTS: Nursing home Quality Indicators now in use are multidimensional and quarterly estimates of incidence-based measures can be relatively unstable, suggesting the need for some averaging of measures over time. IMPLICATIONS: Current public reports benchmarking nursing homes' performances may require additional technical modifications to avoid compromising the fairness of comparisons.

Nursing Homes↗
PubMed2003

The amygdala and development of the social brain.

The amygdala comprises part of an extended network of neural circuits that are critically involved in the processing of socially salient stimuli. Such stimuli may be explicitly social, such as facial expressions, or they may be only tangentially social, such as abstract shapes moving with apparent intention relative to one another. The coordinated interplay between neural activity in the amygdala and other brain regions, especially the medial prefrontal cortex, the occipitofrontal cortex, the fusiform gyrus, and the superior temporal sulcus, allows us to develop social responses and to engage in social behaviors appropriate to our species. The harmonious functioning of this integrated social cognitive network may be disrupted by congenital or acquired lesions, by genetic anomalies, and by exceptional early experiences. Each form of disruption is associated with a slightly different outcome, dependent on the timing of the experience, the location of the lesion, or the nature of the genetic anomaly. Studies in both humans and primates concur; the dysregulation of basic emotions, especially the processing of fear and anger, is an almost invariable consequence of such disruption. These, in turn, have direct or indirect consequences for social behavior.

Amygdala↗
PubMed2003

The oral health of a group of prison inmates.

The oral health of prison inmates in England has come under increased scrutiny with the arrival of joint responsibility between the Home Office and the NHS for prison healthcare. This brief study indicates very high levels of oral disease amongst a group of prisoners attending for treatment in an English prison. Further study of the oral health of prisoners seems timely, as does the exploration of effective oral health promotion for this group of people.

Adolescent↗
PubMed2002

A pilot test of WebOSCE: a system for assessing trainees' clinical skills via teleconference.

WebOSCE is a computer-based system that allows a student at an affiliate site to participate in a 10-station standardized patient-based exam using a videoconference interface, while nine other students take the exam on-site. We pilot-tested this system during a required year-end objective structured clinical exam. We compared performance data between the 26 distance students taking the exam via WebOSCE with 221 on-site students. We also compared both student groups' responses on a post-exam questionnaire, and conducted a post-exam structured interview to elicit the Pittsburgh students' perspectives on the WebOSCE experience. Students taking the exam via WebOSCE scored significantly lower in most categories except for physical exam and information-giving skills, on which the groups did not differ. There were no differences between groups in students' overall evaluation of the exam experiences. In general, Pittsburgh students rated WebOSCE highly and offered many helpful comments to improve the technology and the experience.

Clinical Clerkship↗
PubMed2002

Risk of respiratory complications and wound infection in patients undergoing ambulatory surgery: smokers versus nonsmokers.

BACKGROUND: Smoking is considered to be a risk factor for patients undergoing surgery and anesthesia, but it is unclear whether this is applicable to patients undergoing ambulatory surgery. The aim of this study was to determine the risk of respiratory complications and wound infection among smokers. METHODS: The authors studied a random selection of 489 adult patients undergoing ambulatory surgery. Smoking status was determined by self-report and confirmed with end-expired carbon monoxide analysis. The risk of respiratory complications (i.e., desaturation, cough, laryngospasm, bronchospasm, breath-holding, or apnea) and wound infection (i.e., wound redness or discharge +/- positive microbial culture, requiring antibiotic therapy) in smokers nonsmokers was ascertained. Odds ratios were estimated from multivariable logistic regression and adjusted for age, gender, body mass index, partner's smoking status, domiciliary smoking exposure, and extent and duration of surgery. RESULTS: Most smokers continued to smoke up until the day of surgery. Smokers had a higher rate of respiratory complications (32.8% vs. 25.9%; adjusted odds ratio, 1.71; 95% confidence interval, 1.03-2.84; = 0.038) and wound infection (3.6% vs. 0.6%; odds ratio, 16.3; 95% confidence interval, 1.58-175; = 0.019). Odds ratios comparing current plus ex-smokers with nonsmokers were of similar magnitude for most of these complications. CONCLUSIONS: Smoking was associated with an increased risk of respiratory complications and postoperative wound infection in ambulatory surgery patients. These findings warrant increased efforts at promoting smoking avoidance and cessation.

Adult↗
PubMed2002

Associating the onset of motor impairments with disability progression in nursing home residents.

OBJECTIVES: To evaluate the association between the onset of movement impairments and disability progression in nursing home residents. DESIGN: Retrospective cohort analysis of data from the State of New York Minimal Data Set, version 2.0, between November 1998 and October 1999. Participants were nursing home residents (n = 84,346) in the State of New York. Items defined as "functional limitation in range of motion" and "lack of voluntary movement" served as measures of movement impairments. Scores on the activities of daily living summary scale served as a measure of disability. Age, sex, measures of cognition, depression, and measures of medical stability served as adjustment variables. RESULTS: After adjusting for age, sex, cognition, depression, and measures of medical stability, the onset of either singular or combined movement impairments in voluntary movement or range of motion was associated with a concurrent step-wise loss in activities of daily living (P < 0.001). The progression in activities of daily living loss occurred regardless of location or limb type. CONCLUSION: This study directly links the onset of movement impairments with disability progression. These findings have important implications for physiatrists and other practitioners of geriatric rehabilitation.

Activities of Daily Living↗