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Biomedical subjects

G Johnson

Publications and source records attributed to G Johnson.

At least 721 records · Page 40Linked to original sources
PubMedDate not supplied

Localization of a novel adhesion-promoting site on acetylcholinesterase using catalytic antiacetylcholinesterase antibodies displaying cholinesterase-like activity.

A monoclonal antibody (MAb) raised against human acetylcholinesterase was found to have catalytic activity. A similar phenomenon was observed in a polyclonal antibody raised against the same antigen. The antibodies were demonstrated to be pure, and no contamination with either acetylcholinesterase or butyrylcholinesterase was found. Both antibodies hydrolyzed acetylthiocholine, an acetylcholinesterase substrate, and the MAb followed Michaelis-Menten kinetics. Six other MAbs and one other polyclonal antibody showed no evidence of catalytic activity. Acetylcholinesterase is a key component in the transmission of the nerve impulse, and is also expressed nonsynaptically during embryonic development, and abnormalities in expression are seen in neural tumors and degenerative disorders. This unusual expression is believed to be associated with a novel function of the enzyme related to differentiation and cell adhesion. Autoantibodies to acetylcholinesterase have been observed in a variety of neurologic, muscular, and autoimmune disorders. In an investigation of the possible role of acetylcholinesterase in cell adhesion, we showed that the enzyme promoted neurite outgrowth in neuroblastoma cell lines, and conversely, that certain antiacetylcolinesterase antibodies abrogated cell-substrate adhesion. Interestingly, the antibodies most effective in this regard were catalytic. Preliminary epitope analysis indicated a conformational epitope in the N-terminal domain. This domain contains the active site within a deep gorge and the peripheral anionic site at the rim of the gorge. Peripheral-site inhibitors, but not active-site inhibitors, also interfered with adhesion, and competed with the catalytic monoclonal binding to acetylcholinesterase, indicating that the epitope recognized is associated with the peripheral anionic site. The inhibitor data also support the supposition that catalysis in these antibodies may have arisen from stable complexation of acetylcholinesterase with an inhibitor. We conclude that the catalytic antiacetylcholinesterase antibody interacts with structures associated with the peripheral anionic site, thus defining a novel site on the molecule involved in cell adhesion. This finding has implications for our understanding of the potential importance of this peripheral site in a variety of congenital, neoplastic, and degenerative conditions.

Acetylcholinesterase↗
PubMedDate not supplied

Growing up and growing old: the politics of age exclusion.

The young and the old are inherently vulnerable to the workings of power in a society dominated by the middle-aged. This situation is an outcome of the gradual exclusion of the two ends of the life cycle from productive roles, despite their increasing biological capacities. Consequences of age-based exclusion include economic discrimination, age stereo-typing, and territorial segregation.

Adolescent↗
PubMedDate not supplied

Mosquito surveillance and polymerase chain reaction detection of West Nile virus, New York State.

West Nile (WN) virus was detected in the metropolitan New York City (NYC) area during the summer and fall of 1999. Sixty-two human cases, 7 fatal, were documented. The New York State Department of Health initiated a departmental effort to implement a statewide mosquito and virus surveillance system. During the 2000 arbovirus surveillance season, we collected 317,676 mosquitoes, submitted 9,952 pools for virus testing, and detected 363 WN virus-positive pools by polymerase chain reaction (PCR). Eight species of mosquitoes were found infected. Our mosquito surveillance system complemented other surveillance systems in the state to identify relative risk for human exposure to WN virus. PCR WN virus-positive mosquitoes were detected in NYC and six counties in the lower Hudson River Valley and metropolitan NYC area. Collective surveillance activities suggest that WN virus can disperse throughout the state and may impact local health jurisdictions in the state in future years.

Animals↗
PubMedDate not supplied

Dynamic contrast-enhanced T2*-weighted MR imaging of tumefactive demyelinating lesions.

PURPOSE: Dynamic contrast-enhanced T2*-weighted MR imaging has been helpful in characterizing intracranial mass lesions by providing information on vascularity. Tumefactive demyelinating lesions (TDLs) can mimic intracranial neoplasms on conventional MR images, can be difficult to diagnose, and often result in surgical biopsy for suspected tumor. The purpose of this study was to determine whether dynamic contrast-enhanced T2*-weighted MR imaging can be used to distinguish between TDLs and intracranial neoplasms that share common features on conventional MR images. METHODS: We retrospectively reviewed the conventional and dynamic contrast-enhanced T2*-weighted MR images and medical records of 10 patients with tumefactive demyelinating disease that was diagnosed by either biopsy or strong clinical suspicion supported by laboratory evaluation that included CSF analysis and evoked potential tests. Twelve TDLs in 10 patients and 11 brain tumors that appeared similar on conventional MR images were studied. Relative cerebral blood volume (rCBV) was calculated from dynamic MR data and was expressed as a ratio to contralateral normal white matter. rCBV values from 11 patients with intracranial neoplasms with very similar conventional MR imaging features were used for comparison. RESULTS: The rCBV values of TDLs ranged from 0.22 to 1.79 (n = 12), with a mean of 0.88 +/- 0.46 (SD). The rCBV values of intracranial neoplasms ranged from 1.55 to 19.20 (n = 11), with a mean of 6.47 +/- 6.52. The difference in rCBV values between the two groups was statistically significant (P =.009). The difference in rCBV values between TDLs and primary cerebral lymphomas (n = 4) was less pronounced but was statistically significant (P =.005). CONCLUSION: Dynamic contrast-enhanced T2*-weighted MR imaging is a useful diagnostic tool in differentiating TDLs from intracranial neoplasms and may therefore obviate unnecessary surgical biopsy.

Adolescent↗
PubMedDate not supplied

[Minimizing the risks associated with QTc prolongation in people with schizophrenia. A consensus statement by the Cardiac Safety in Schizophrenia Group].

Schizophrenia is one of the most debilitating mental illnesses, complicated by an increased incidence of suicide amongst patients compared with the general population. A recent report has also demonstrated a 33% increase in -relative risk of death associated with circulatory disease, indicating that the latter may be a more critical factor than either suicide or accidental death in this population. Indeed, the average life expectancy of a person with schizophrenia is currently approximately a decade less than that of the general population. Additionally, it has been shown that in over 50% of people with schizophrenia, there is a reduction in their chance of reaching psychosocial goals. Since the arrival of the first antipsychotic drugs in the middle of the last century, the outlook for patients with schizophrenia has improved markedly. In particular, the introduction of the new generation (atypical) class of antipsychotic agents in the 1980s and 90s has resulted in a significant reduction in the incidence of violent and aggressive episodes in treated patients. A better side-effect profile of these drugs, especially reduced extra pyramidal symptoms (EPS), has resulted in improved patient outcomes and the possibility of good long-term control of the disorder. However, while the introduction of antipsychotic agents has undoubtedly revolutionised the prognosis for patients with schizophrenia, these medications are not without their own problems. One of the concerns to emerge over the last fifteen years is unpredictable, sudden and unexplained death in patients taking antipsychotic drugs. The cause of sudden death in this population is controversial and the role of drugs is not clear. People with schizophrenia also appear to be at higher risk of cardiovascular disease compared with the general population. Many factors may play a role in this including a higher prevalence of smoking, poorer diet, more sedentary lifestyle and a greater likelihood of alcoholism and substance abuse. However, it is possible that the impact of adverse effects on the cardiovascular system related to certain antipsychotic drug use may well increase the prevalence of mortality and morbidity due to cardiovascular events and may also play a significant role in the reduced life expectancy of the patient with schizophrenia. The range of mechanisms whereby antipsychotic drugs can influence cardiovascular function is very broad and includes: receptor blockade; conduction disturbance (eg bundle branch block); delayed ventricular repolarisation (prolonged QTc interval); left ventricular dysfunction; sinus node abnormalities; myocarditis; postural hypotension; polydipsia-hyponatremia syndrome; weight gain; glucose intolerance. Of these, QTc interval prolongation, with the risk of progression to the potentially fatal ventricular tachyarrhythmia Torsades de Pointes (TdP), is of particular concern as this arrhythmia is unpredictable and difficult to manage. Coupled with these clinical concerns are regulatory issues regarding several compounds that have received warnings or been withdrawn from the market. Recently, there has been no clear guidance for psychiatrists regarding QTc interval prolongation and TdP. This document seeks: 1) to explore drug-induced ventricular arrhythmias with particular emphasis on QTc interval prolongation as a warning of increased vulnerability, 2) to provide guidelines on the therapeutic management of the patient with schizophrenia to minimize the risk of iatrogenic cardiotoxicity. Several guidance documents have previously been published in this area including the report published by the UK Working Group of the Royal College of Psychiatrists' Psychopharmacology Sub-Group in 1997, and the policy document on the potential for QTc prolongation and proarrhythmia by non-antiarrhythmic drugs published in June 1999 under the auspices of the European Society of Cardiology. This document seeks to supplement currently published guidelines.

Antipsychotic Agents↗
PubMedDate not supplied

Spinal cord concussion in pediatric athletes.

Children with a narrowed canal secondary to spinal stenosis or congenital malformation may be predisposed to spinal cord concussion when the canal is further narrowed in hyperflexion or hyperextension. Review of the medical records of the Winnipeg and Ottawa Children's Hospitals disclosed 12 children who had been treated for transient sensory or motor loss after a spinal injury. Measurements of the spinal canal were compared with standard normal measurements, and the spinal canal width was expressed as a percentage of the vertebral width (the Torg ratio). This study shows that narrowing of the spinal canal is an inconsistent predisposing factor to spinal cord concussion in children. A poor correlation between the Torg ratio and comparison with a series of normal control canal widths was noted.

Adolescent↗
PubMedDate not supplied

Diffusion tensor imaging in multiple sclerosis: assessment of regional differences in the axial plane within normal-appearing cervical spinal cord.

BACKGROUND AND PURPOSE: Evaluation of the spinal cord is important in the diagnosis and follow-up of patients with multiple sclerosis. Our purpose was to investigate diffusion tensor imaging (DTI) changes in different regions of normal-appearing spinal cord (NASC) in relapsing-remitting multiple sclerosis (RRMS). METHODS: Axial DTI of the cervical spinal cord was performed in 24 patients with RRMS and 24 age- and sex-matched control subjects. Fractional anisotropy (FA) and mean diffusivity (MD) were calculated in separate regions of interest (ROIs) in the anterior, lateral, and posterior spinal cord, bilaterally, and the central spinal cord, at the C2-C3 level. Patients and control subjects were compared with respect to FA and MD with the use of an exact Mann-Whitney test. Logistic regression and receiver operating characteristic (ROC) curve analysis assessed the utility of each measure for the diagnosis of RRMS. RESULTS: DTI metrics in areas of NASC in MS were significantly different in patients compared with control subjects; FA was lower in the lateral (mean +/- SD of 0.56 +/- 0.10 versus 0.69 +/- 0.09 in control subjects, P < .0001), posterior (0.52 +/- 0.11 versus 0.63 +/- 0.10, P < .0001), and central (0.53 +/- 0.10 versus 0.58 +/- 0.10, P = .049) NASC ROIs. Assessing DTI metrics in the diagnosis of MS, a sensitivity of 87.0% (95% confidence interval [CI], 66.4 to 97.1) and a specificity of 91.7% (95% CI, 73.0 to 98.7) were demonstrated. CONCLUSION: The NASC in RRMS demonstrates DTI changes. This may prove useful in detecting occult spinal cord pathology, predicting clinical course, and monitoring disease progression and therapeutic effect in MS.

Adult↗
PubMedDate not supplied

Whole-brain N-acetylaspartate spectroscopy and diffusion tensor imaging in patients with newly diagnosed gliomas: a preliminary study.

BACKGROUND AND PURPOSE: Glial cancer cells can be found well beyond the MR imaging T2 signal-intensity hyperintensity. To quantify the extent of the diffuse microstructural tissue damage possibly due to the presence of these satellite tumor cells, we investigated the relationships between global metabolic and microstructural abnormalities in the normal-appearing brain regions of patients with newly diagnosed glioma. MATERIAL AND METHODS: Ten patients (6 men, 4 women) with radiologically suspected untreated supratentorial glial tumors and 9 healthy controls (5 men, 4 women) were studied with T1- and T2-weighted MR imaging, diffusion-weighted echo-planar MR imaging, and whole-brain N-acetylaspartate (WBNAA) proton MR spectroscopy. The relationship between the WBNAA concentration, the mean diffusivity (MD), and fractional anisotropy (FA) values in a large contralateral normal-appearing white matter (NAWM) brain region was investigated with the Spearman rank correlation test. RESULTS: WBNAA values were significantly lower (P < .001) in patients (9.7 +/- 1.7 mmol/L) than controls (13.1 +/- 1.1 mmol/L). MD values were higher (P = .0001) in patients (0.95 +/- 0.07 mm(2)s(-1)) than in controls (0.61 +/- 0.04 mm(2)s(-1)). FA values did not differ between patients (0.42 +/- 0.08) and controls (0.43 +/- 0.041). A strong inverse correlation between WBNAA and MD (r = -0.88, P = .0008) was found in the patients but not in controls (r = 0.012, P = .975). CONCLUSION: The correlation between the WBNAA and MD in the contralateral NAWM suggests that the microstructural damage possibly related to the presence of infiltrative tumor cells contributes to WBNAA decline in these patients.

Adult↗
PubMedDate not supplied

Major stump trauma following below-knee amputation. Outcome and recommendations for therapy.

Injury to the stump of a below-knee amputation (BKA) may require revision to a higher level of amputation. We undertook a retrospective review of BKAs performed during a 14-year period. Twenty-three patients suffered trauma to their stumps. Most (80%) trauma resulted from a fall. The severity of the trauma was graded on a three-part scale. Operative reclosure was attempted in 8 cases with 2 successes. Closure by secondary intent was successful in 7 of the 12 attempts. A total of 11 patients had revision to above-knee amputation (AKA) as the final outcome. The severity of trauma correlated inversely with the likelihood of eventual stump salvage. We conclude that primary reclosure or closure by secondary intent should be considered, since in 53% of attempts this results in knee preservation. Analysis of noninvasive vascular testing prior to the BKA was not helpful in predicting successful salvage of traumatized stumps.

Accidental Falls↗