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Biomedical subjects

R Johnson

Publications and source records attributed to R Johnson.

At least 343 records · Page 19Linked to original sources

P300 in patients with unilateral temporal lobectomies: the effects of reduced stimulus quality.

The effects of stimulus quality on the amplitude, peak latency, onset latency, and duration of the P300 component of the event-related brain potential were studied in patients with either a left or a right anterior temporal lobectomy and in normal controls. Stimulus quality was reduced by adding "noise" letters to words which signalled either a left or a right hand button press. Consistent with an interpretation that stimulus quality affects the subject's degree of equivocation, P300 peak latency, reaction time, and errors were all inversely related to stimulus quality, whereas P300 amplitude was directly related to stimulus quality. There were no significant differences between normal controls and either patient group for any of the ERP parameters or reaction time. Right temporal lobectomy patients made, however, significantly more errors, particularly on the catch trials, which suggests that they did not process the stimuli as thoroughly and accurately as the subjects in the other two groups. The absence of significant group differences in either the lateral symmetry or overall P300 amplitude extends the evidence against the idea that anterior temporal lobe structures make any substantial contribution to the scalp P300 in a visual discrimination paradigm. Because of observed delays in the onset of P300 in the low-quality stimulus condition, procedures were developed to quantify both P300 onset latency and P300 duration. Reduced stimulus quality significantly increased P300 onset latency whereas P300 duration remained unaffected, indicating that stimulus categorization must occur prior to, and not during, P300.

Adult↗

Complexities related to cognitive slow wave experiments: a reply to Rösler and Heil.

Rösler and Heil (1991) were unable to replicate one of the results of our previous study of slow wave activity and mental arithmetic (Ruchkin, Johnson, Mahaffey, & Sutton, 1988). Thorough examination of the error rates indicates that the greater complexity of their response selection procedure caused crucial differences between how the task was performed in the two studies. Thus Rösler and Heil's study emphasizes the need to avoid using a response that is so complex that it produces a superfluous task that obscures the results.

Attention↗

L-3,4-dihydroxyphenylalanine synthesis by genetically modified Schwann cells.

We have investigated whether Schwann cells can be modified by gene transfer to synthesize L-3,4-dihydroxyphenylalanine (L-DOPA), the immediate precursor in the formation of dopamine. By using a retrovirus containing a rat tyrosine hydroxylase (TH) cDNA, we established an immortalized rodent Schwann cell line that stably expressed high levels of TH and secreted L-DOPA in vitro when supplied with tyrosine and the essential cofactor biopterin. We also infected primary Schwann cells and demonstrated that cells expressing TH secreted L-DOPA while maintaining their capacity to myelinate neurons in vitro. This study indicate that it may be feasible to utilize autotransplantation of genetically modified Schwann cells to alleviate the movement disorders in Parkinson's disease.

Animals↗

Signs of cognitive change in HIV disease: an event-related brain potential study.

We recorded event-related brain potentials (ERPs) from 2 groups of human immunodeficiency virus (HIV)-positive men with no physical illness or neurologic involvement: 9 asymptomatic (AS+) and 9 classified as having either acquired immunodeficiency syndrome (AIDS; 7) or AIDS-related complex (ARC; 2). In separate choice reaction time tasks, the subjects pressed buttons to randomly presented auditory or visual stimuli at probabilities of either 20/80 or 50/50. There were no group differences on any of the neuropsychological tests commonly used in screening batteries for HIV patients. In contrast, reduced P300 amplitudes and increased P300 latencies occurred in ARC/AIDS patients in response to both auditory and visual stimuli, while in AS+ patients such alterations occurred only in the visual modality. Significant delays in P2 latency were found only in the auditory modality and then only in ARC/AIDS patients. ARC/AIDS patients alone showed delayed response times, and only in the auditory modality. The P300 results demonstrate alterations in stimulus evaluation and processing speed in the earliest stages of HIV disease, even before cognitive deficits can be detected by more traditional measures.

AIDS-Related Complex↗

Progressive supranuclear palsy: altered sensory processing leads to degraded cognition.

We studied the latencies, amplitudes, and scalp distributions of the early and late components of the event-related brain potential (ERP) in patients with progressive supranuclear palsy (PSP) and matched normal controls. In separate choice reaction time (RT) tasks, the subjects pressed buttons to visual stimuli presented randomly at probabilities of either 20/80 or 50/50. Compared with normal controls, PSP patients had significantly reduced amplitudes and increased latencies for both the visual P2 and P300 components at all levels of probability. RTs and percent errors were significantly greater in the patients compared with controls. Neither the amplitude nor latency of the visual N1 component was significantly altered in these patients. There were no significant group differences in the distribution of electrical activity over the scalp for any of these ERP components, a finding which suggests that the neural structures responsible for generating these potentials were intact in these patients. The decreased ERP component amplitudes and increased ERP component latencies, combined with intact scalp distributions and increased RTs and error rates, present a pattern of results suggesting that the stimulus identification or categorization processes in these patients are significantly degraded.

Analysis of Variance↗

Optical mark reader technology and data base development in anesthesiology and critical care medicine at the Johns Hopkins Medical Institutions.

The Department of Anesthesiology and Critical Care Medicine (DACCM) has substantially upgraded its computer resources within the past two years by installing a local area network (LAN) and replacing low-end PC's with PC's utilizing Intel 80286 or 80386 microprocessor technology. Data base development has now become a priority. Data bases are being developed for both clinical and administrative purposes. We are replacing the traditional method of "keypunching" with optical card scanners which results in faster and more accurate data entry directly into the data bases. Previously, such card scanners have been confined to large organizations. We describe a method of data capture and data base development with wide applicability in medicine.

Anesthesiology↗

The effectiveness of a layered baseplate training aid in the preclinical instruction of second-year dental students.

The effectiveness of the Cavidrill baseplate in the training of second-year dental students in cavity preparations in primary ivorine teeth was assessed. The preclinical class of 112 students was divided into four groups: Cavidrill-only group, two groups combining Cavidrill training with traditional typodont training, and a typodont-only group. The Cavidrill baseplate was found not to improve the students' performance in cavity preparation when assessed on midterm and final examinations.

Dental Cavity Preparation↗

Buspirone in the treatment of posttraumatic stress disorder.

Three patients with a DSM-III-R diagnosis of posttraumatic stress disorder were successfully treated with buspirone in final maximum dosages ranging from 35-60 mg daily. The onset of clinical efficacy ranged from 5-29 days. Symptoms that improved included anxiety, insomnia, flashbacks, and depressed mood. Patients experienced no side effects. Serotonin partial agonist effects are a possible mechanism underlying buspirone's efficacy.

Aged↗

A flow interruption device for measurement of airway resistance.

Unlike conventional methods, the interrupter method for measuring airway resistance is non-invasive and requires minimal patient co-operation. It can therefore be applied in critically ill patients, acute asthmatics, neonates, pre-school children, geriatric patients and unconscious patients. The method is based on transient interruption of airflow at the mouth for a brief period during which alveolar pressure equilibrates with mouth pressure. Measurement of mouth pressure is used to estimate alveolar pressure prior to interruption and the ratio of this to flow prior to interruption gives airway resistance. Using the interrupter method we have developed a portable device for measuring airway resistance which is simple to use and gives a direct instantaneous reading. Measurements of airway resistance obtained using the new device were compared with those obtained using conventional body plethysmograph methods in 43 adult patients. A close correlation was seen (r = 0.86). The two methods appear equally sensitive in detecting changes in airway resistance following bronchodilator therapy. The device has been used successfully in pre-school children unable to co-operate with conventional methods.

Adult↗

Fructosamine Test-Plus, a modified fructosamine assay evaluated.

We have evaluated Fructosamine Test-Plus, a commercial fructosamine assay based on the reduction of nitro-blue tetrazolium dye in alkaline buffer (Clin Chem 1985;31:1550-4), modified by including a detergent and uricase in the reagent, by changing the concentrations of buffer and dye, and by changing the approach to primary calibration. Specimens were from 2321 participants in a health screening survey in a local workforce. Compared with the original fructosamine method, the Fructosamine Test-Plus method was less affected by protein concentration in the sample and less subject to interference from hyperlipidemia. The changes have also extended the linearity of the assay in the pathological range. However, as a screening method for diabetes mellitus in a population with a disease prevalence of 2.28%, the performance of Fructosamine Test-Plus was similar to the original assay.

Adult↗

Expression of the BNLF-1 oncogene of Epstein-Barr virus in the skin of transgenic mice induces hyperplasia and aberrant expression of keratin 6.

The BNLF-1 gene of Epstein-Barr virus (EBV) encodes the latent membrane protein (LMP), one of the putative oncogene products of the virus. This gene has been expressed from two different enhancer-promoter constructs in transgenic mice, to determine its biological activity and possible contribution to oncogenesis. While transgenic mice expressing LMP in many tissues demonstrated poor viability, expression of LMP specifically in the epidermis induces a phenotype of hyperplastic dermatosis. Concomitant with the expression of LMP in this tissue (and in the esophagus) is an induction of the expression of a hyperproliferative keratin, K6, at aberrant locations within the epidermis. The epithelial hyperplastic phenotype caused by the LMP-encoding transgenes implies that the LMP plays a role in the acanthotic condition of the tongue epithelium in the human EBV- and HIV-associated syndrome oral hairy leukoplakia, as well as possibly predisposing the nasopharyngeal epithelium to carcinogenesis.

Animals↗

Auditory sensory gating in hippocampal neurons: a model system in the rat.

Diminished evoked response to repeated auditory stimuli, an example of sensory gating normally present in human subjects, is often absent in schizophrenics. To examine the mechanism of the normal response and to delineate possible sites of its abnormality in psychosis, it would be desirable to reproduce the phenomenon in laboratory animals. In this study, we show that the pattern of diminished response to the second of paired auditory stimuli is found in activity recorded from the CA3 region of the hippocampus of anesthetized rats. The evoked potential recorded from this area is predominantly an N40 wave, at identical latency to the prominent negative wave recorded from the skull surface of unanesthetized rats. Similar responses were not found in other areas, including the auditory neocortex and the medial geniculate nucleus. Amphetamine, which diminished sensory gating in both animals and humans, diminished the gating of the evoked potential recorded in the hippocampus. The effect of amphetamine was reversed by haloperidol. The rat hippocampus may therefore contain neurons that can be used to study the neurobiology of sensory gating.

Action Potentials↗

Relationship between clinical efficacy and laboratory correlates of inflammatory and immunologic activity in rheumatoid arthritis patients treated with nonsteroidal antiinflammatory drugs.

Eighteen rheumatoid arthritis (RA) patients, who had been treated with nonsteroidal antiinflammatory drugs (NSAIDs) only, were enrolled in a 12-week, open-label, randomized protocol to determine whether clinical responses might be associated with improvement in laboratory measures of inflammation and immunologic activity in RA patients treated with NSAIDs. Following a 2-week drug washout period, patients were given either long-acting ibuprofen (2,400 mg/day) or flurbiprofen (200 mg/day); clinical, laboratory, and immunologic assessments were done biweekly for 10 weeks. A clinical efficacy index, utilizing a combination of measures of disease activity, identified 7 "responders" and 10 "nonresponders" (1 patient discontinued therapy because of a rash). Flow cytometric analysis revealed no abnormalities in the numbers of circulating CD3+, CD4+, or CD8+ lymphocytes in the 17 patients. The density of these T cell markers at enrollment was similar in patients and control subjects. However, following the 2-week drug washout, significant worsening of morning stiffness, erythrocyte sedimentation rate (ESR), and C-reactive protein (CRP) was accompanied by a significant decrease (P less than or equal to 0.05) in the density of these T cell surface determinants, as is characteristic of activated T cells. After 10 weeks of NSAID therapy, increased density of CD3, CD4, and CD8 was observed in 47%, 73%, and 50% of the patients, respectively. However, in only the responders was the density of these T cell surface markers increased significantly (P less than or equal to 0.04). The responders, but not the nonresponders, also demonstrated significant reductions in the ESR, CRP level, serum IgM rheumatoid factor (RF) titer, and spontaneous synthesis of RF by lymphocytes in vitro (P less than or equal to 0.05). There were significant correlations between improvements in the clinical parameters (50-foot walk time, joint score, and global assessment) and reductions in the ESR, CRP level, and serum RF titer (P less than or equal to 0.05). These findings demonstrate that clinical improvement in RA patients treated with NSAIDs may be associated with the disappearance of phenotypically activated circulating T cells and functionally activated B cells, as well as with reductions in acute-phase reactants and serum RF titers.

Anti-Inflammatory Agents, Non-Steroidal↗

Wound-inducible potato inhibitor II genes: enhancement of expression by sucrose.

Expression of a chimeric potato Inhibitor II-CAT gene in transgenic tobacco plants was enhanced 50-fold when leaf tissue was floated on solutions containing 1% sucrose. The expression of the chimeric gene was also enhanced when leaf sections were floated on solutions of glucose, fructose, and maltose, but not when floated on solutions of mannitol. The increased expression due to sucrose was found to be correlated with an increase in CAT mRNA. Thus, the carbohydrates or their metabolic products may control Inhibitor II gene expression by regulating transcription. Levels of potato Inhibitor II proteins in leaf sections from young potato plants floated on 3% sucrose solutions increased 3-fold compared to leaf sections floated on water, supporting the possibility that sucrose may have a role in regulating or enhancing the expression of wound-inducible proteinase inhibitor genes in potato tissues. It is suggested that the Inhibitor II gene and perhaps other genes regulated by sucrose may contain a specific 'sucrose enhancer' that strongly increases transcription of genes already active at low levels.

Carbohydrates↗

Regulation of expression of a wound-inducible tomato inhibitor I gene in transgenic nightshade plants.

A wound-inducible proteinase Inhibitor I gene from tomato containing 725 bp of the 5' region and 2.5 kbp of the 3' region was stably incorporated into the genome of black nightshade plants (Solanum nigrum) using an Agrobacterium Ti plasmid-derived vector. Transgenic nightshade plants were selected that expressed the tomato Inhibitor I protein in leaf tissue. The leaves of the plants contained constitutive levels of the inhibitor protein of up to 60 micrograms/g tissue. These levels increased by a factor of about two in response to severe wounding. Only leaves and petioles exhibited the presence of the inhibitor, indicating that the gene exhibited the same tissue specificity of expression found in situ in wounded tomato leaves. Inhibitor I was extracted from leaves of wounded transformed nightshade plants and was partially purified by affinity chromatography on a chymotrypsin-Sepharose column. The affinity-purified protein was identical to the native tomato Inhibitor I in its immunological reactivity and in its inhibitory activity against chymotrypsin. The protein exhibited the same Mr of 8 kDa as the native tomato Inhibitor I and its N-terminal amino acid sequence was identical to that of the native tomato inhibitor I, indicating that the protein was properly processed in nightshade plants. These experiments are the first report of the expression of a member of the wound-inducible tomato Inhibitor I gene family in transgenic plants. The results demonstrate that the gene contains elements that can be regulated in a wound-inducible, tissue-specific manner in nightshade plants.

Amino Acid Sequence↗