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Biomedical subjects

K L Johnson

Publications and source records attributed to K L Johnson.

At least 91 records · Page 5Linked to original sources
PubMed1994

Human dermatophyte-responsive T-cell lines recognize cross-reactive antigens associated with mannose-rich glycoproteins.

Resistance to dermatophyte infections has been shown to be mediated in part by T lymphocytes. The dermatophyte antigens recognized by human T lymphocytes and their degree of cross-reactivity were analyzed. Dermatophyte-responsive T-cell lines were generated by in vitro sensitization to crude fungal extracts obtained from Trichophyton rubrum, Trichophyton tonsurans, Microsporum canis and Epidermophyton floccosum. Proliferation was measured by incorporation of 3H-thymidine. The human T-cell lines responded to fungal extracts derived from these various dermatophyte species, demonstrating the recognition of cross-reactive antigens by human T cells. However, the T cells were dermatophyte-specific as they did not respond to herpes antigen, nor did herpes-specific T cells derived from the same donors respond to dermatophyte antigens. The mannose-rich glycoprotein fraction (mannan) isolated from T. rubrum was able to induce proliferation of T-cell lines generated by stimulation with various fungal extracts. Furthermore, a T-cell line generated by stimulation with mannan derived from T. rubrum proliferated in response to extracts from various fungal species, indicating that a major cross-reactive dermatophyte T-cell antigen was present in the mannose-rich glycoprotein fraction.

Adult↗
PubMed1993

Investigation of the metabolic fate of the neuroleptic drug haloperidol by capillary electrophoresis-electrospray ionization mass spectrometry.

Combined capillary electrophoresis-mass spectrometry (CE-MS) is a powerful analytical tool for the characterization of components of complex mixtures. Furthermore, when interfaced with an electrospray ionization (ESI) source, skimmer induced fragmentation can yield structural information that aids compound identification. We show that these techniques can be used to probe the metabolic fate of drugs by investigation of the phase I metabolism of the widely used neuroleptic drug haloperidol. In addition, we demonstrate differences of in vitro metabolism of haloperidol by mouse and guinea pig hepatic microsomes.

Animals↗
PubMed1993

Blood pressure changes during daytime sleep and comparison of daytime and nighttime sleep-related blood pressure changes in patients with chronic renal failure.

Blood pressure has a diurnal pattern primarily related to activity and sleep. Chronic renal failure patients may lack the normal nocturnal decline in blood pressure during sleep. In 33 subjects (14 with normal renal function and 19 with renal dysfunction), the relationship between depth of daytime sleep, as determined by electroencephalographic sleep phase, and change in mean arterial blood pressure (MAP) and heart rate measured oscillometrically, was correlated. In 15 chronic renal failure patients, the effect of daytime and nighttime sleep on MAP and heart rate was compared. The percent change in night asleep versus day awake MAP and heart rate was measured (with Space Labs ambulatory blood pressure monitors) and compared with the percent change in daytime sleep-related MAP and heart rate measured during a daytime sleep electroencephalographic study. During daytime sleep, MAP changes are not significantly different in the normal versus renal dysfunction groups. In the 33 study subjects, MAP declines progressively from the upright position to Phase 3/4 sleep (118 +/- 3.6 to 106 +/- 3.6 mm Hg). The largest decline occurs between the upright to recumbent position, before sleep. Heart rate declines moving from the upright to recumbent position, 76 +/- 2.3 to 70 +/- 2.1 beats/min, but does not decline further with sleep. In 15 chronic renal failure patients, heart rate (10.8 +/- 2.8%; P < 0.05), but not MAP, declines during nighttime sleep. Both MAP (7.7 +/- 3.3%) and heart rate (5.4 +/- 1.9%) decline significantly during daytime sleep. The responses of MAP and heart rate to daytime and nighttime sleep were in opposite directions in 3 of 15 subjects.(ABSTRACT TRUNCATED AT 250 WORDS)

Blood Pressure↗
PubMed1993

Use of transdermal clonidine in chronic hemodialysis patients.

Large fluctuations of blood pressure are commonly experienced by hypertensive, chronic hemodialysis patients. Many patients hold anti-hypertensive medication immediately prior to dialysis to prevent intradialytic hypotension. Weekly dosing of continuously released antihypertensive agents may result in better blood pressure control than conventional daily dosing. To evaluate the effect of weekly transdermal clonidine on this problem, we compared intra- and interdialytic blood pressure control and side effects during six weeks of transdermal clonidine monotherapy and six weeks of conventional oral antihypertensive treatment in nine stable chronic hemodialysis patients. Since transdermal clonidine is recommended for mild to moderately severe hypertension and since clonidine is excreted by the kidneys and removed by hemodialysis, we also evaluated blood pressure control and clonidine levels while utilizing high-dose transdermal clonidine, up to 0.12 mg per week. Intradialytic blood pressure was monitored twice weekly during the weeks 3-6 of transdermal clonidine and conventional therapy. Twenty-four hour blood pressure was monitored weeks 3 and 6 of each study phase. Plasma clonidine levels were measured by HPLC in 11 patients. Transdermal clonidine monotherapy failed to adequately control blood pressure in 6 of 21 chronic dialysis patients with moderate to severe hypertension. No significant difference in intra- or interdialytic blood pressure control or side effects (including dry mouth or thirst) was found comparing conventional to transdermal clonidine therapy. While not statistically different, heart rate was lower during transdermal clonidine therapy compared to conventional therapy, especially at very high doses. Despite a mean hemodialysis clearance of clonidine of 59.2 +/- 7.8 ml/min, clonidine levels remained therapeutic beyond one week.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Cutaneous↗
PubMed1992

Alopecia areata. Autoreactive T cells are variably enriched in scalp lesions relative to peripheral blood.

BACKGROUND AND DESIGN: Alopecia areata is a condition characterized by hair loss in association with perifollicular infiltration of T cells and antigen-presenting cells. Autoreactive T cells are postulated to amplify this abnormality by interacting with DR+ follicular epithelium. These cells may recognize either autologous major histocompatibility complex class II antigen or an autoantigen restricted by major histocompatibility complex class II. Limiting dilution analysis was used to determine the frequency of autoreactive lymphocytes in scalp biopsy specimens and peripheral blood from seven adult patients with alopecia areata. Autoreactive T cells are defined for this study as those that proliferate in response to autologous irradiated peripheral blood mononuclear cells. RESULTS: Autoreactive lymphocytes were enriched in scalp biopsy specimens relative to peripheral blood in five of seven patients. This enrichment was statistically significant in four of five patients. Five autoreactive T-cell clones derived from lesional scalp were characterized. Four of these clones were CD3+CD4+CD8- and one clone was CD3+CD4-CD8+. CONCLUSIONS: Enrichment of autoreactive cells in lesions of alopecia areata supports a role for these cells in the pathogenesis of this condition. Enrichment of autoreactive lymphocytes is also found in allergic contact dermatitis. Thus, these autoreactive lymphocytes may have a general role in inflammation.

Adult↗
PubMed1992

Oral ketamine preanesthetic medication in children.

The authors sought to define a dose of oral ketamine that would facilitate induction of anesthesia without causing significant side effects. Forty-five children (ASA Physical Status 1 and 2; aged 1-7 yr) were assigned randomly in a prospective, double-blind fashion to three separate groups that received either 3 mg/kg, 6 mg/kg, or no ketamine mixed in 0.2 ml/kg cola-flavored soft drink. They also were evaluated preoperatively and postoperatively for acceptance of oral ketamine as a premedicant, reaction to separation from parents, emotional state, and emergence phenomena. The authors detected no episodes of respiratory depression, tachycardia, or arterial hemoglobin desaturation before, during, or after surgery. The 6 mg/kg dose was well accepted; provided uniform, predictable sedation within 20-25 min; and allowed calm separation from parents and good induction conditions. The 3 mg/kg dose did not always cause sedation and calm separation from parents. Neither dose of ketamine increased the incidence of laryngospasm, prolonged recovery times, or caused emergence phenomena. The authors conclude that an oral dose of 6 mg/kg ketamine is easily administered and well accepted in young children and provides predictable, satisfactory premedication without significant side effects.

Administration, Oral↗
PubMed1992

Accuracy of the Denver-II in developmental screening.

One of the oldest and best known developmental screening tests was recently restandardized and revised as the Denver-II. Because it was published without evidence of its accuracy, the present study was undertaken with 104 children between 3 and 72 months of age attending one of five day-care centers. To determine the presence of developmental problems, children were administered individual measures of intelligence, speech-language, achievement, and adaptive behavior. A second psychological examiner, blind to the outcome of the diagnostic battery, administered the Denver-II. Developmental problems including language impairments, learning disabilities, mild mental retardation, and/or functional developmental delay were found in 17% of the children. The Denver-II identified correctly 83% and thus had high rates of sensitivity. However, more than half the children with normal development also received abnormal, questionable, or untestable Denver-II scores. Thus the test had limited specificity (43%) and a high overreferral rate. The alternative scoring method, categorizing questionable/untestable scores as normal, caused sensitivity to drop to 56% although specificity rose to 80%. Since neither scoring method produced acceptable levels of accuracy, an effort was made to locate the sources of accuracy and inaccuracy within the test. Only items in the language domain were modestly helpful in discriminating children with and without difficulties. The findings suggest that the authors of the Denver-II need to engage in further development of the instrument including revising scoring criteria and item placement in relation to children's ages. In the interim, test users should employ screening tests which are more accurate such as the Minnesota Inventories or the Battelle Developmental Inventory Screening Test.

Child, Preschool↗
PubMed1991

Three poliovirus 2B mutants exhibit noncomplementable defects in viral RNA amplification and display dosage-dependent dominance over wild-type poliovirus.

Many functions of the poliovirus genome in virally infected cells have been elucidated. However, the role of 2B (and of its precursor polypeptide, 2BC), encoded by the P2 region in the poliovirus genome, remains unknown. We have employed a genetic approach to examine the role of 2B in poliovirus-infected cells. We report here the phenotype of one previously isolated mutant in the 2B coding region, 2B201. In addition, we have constructed one additional mutation in the 2B coding region of an infectious poliovirus cDNA clone. Upon transfection into monkey Vero cells we could recover two 2B mutant polioviruses, 2B204 and 2B205. All three mutants exhibited small-plaque phenotypes on monkey Vero and human HeLa cells and displayed primary defects in viral RNA synthesis. None of the 2B mutants could be complemented by wild-type virus. Instead, the mutants exhibited a dosage-dependent dominance over wild-type poliovirus. Thus, the phenotypes of these 2B mutants implicate 2B and possibly its precursor, 2BC, in viral RNA amplification in poliovirus-infected cells, and the dominance of the 2B mutants suggests a structural role for 2B in viral replication complexes.

Animals↗
PubMed1990

Enrichment and function of urushiol (poison ivy)-specific T lymphocytes in lesions of allergic contact dermatitis to urushiol.

The frequencies of urushiol (poison ivy)-specific T cells were determined in the lesional skin and peripheral blood of patients with allergic contact dermatitis to urushiol. Lesions of urushiol dermatitis were biopsied and the T cells retrieved. Frequencies of Ag-specific cells were determined by limiting dilution assay. Enrichment of urushiol specific T cells was detected in lesional skin or blister fluid of five of five of these donors as well as seven of seven donors with urushiol patch tests. There was also enrichment relative to tetanus toxoid specific T cells in blood and skin of six of seven donors. The frequency of lesional T cells specific for urushiol was less than 1/100 and generally less than 1/1000. Furthermore, the frequency of urushiol specific T cells was often less than 1/10,000 in the peripheral blood during an acute eruption. Autoreactive T cells that proliferated to autologous irradiated PBMC were also enriched in skin lesions relative to blood in 5/5 urushiol patch tests. These autoreactive T cells were expanded and found to be CD4+. It has been proposed that such autoreactive T cells recognize autologous DR and may have a role in immunoregulation. Urushiol-specific T cells were expanded from limiting dilution wells of two donors and characterized. The majority of the urushiol-specific cells were CD8+, and 13/43 lines were suppressive for PWM-induced IgG synthesis.

Antigens, Differentiation, T-Lymphocyte↗
PubMed1987

Anaesthesia for children with junctional epidermolysis bullosa (letalis).

The anaesthetic management of two children with junctional epidermolysis bullosa, formerly called the letalis form, is described. Anaesthesia for children with this disease has not been described previously. Special precautions were taken to avoid mucosal injury and some customary monitoring devices were omitted. The previous anaesthetic literature, which discusses related but distinct forms of bullous skin diseases, is reviewed. The special concerns which relate to airway management in this disease are discussed.

Anesthesia, General↗
PubMed1985

Use of 111In-labeled autologous leukocytes to image an abdominal abscess in a horse.

Indium 111-labeled autologous leukocytes were used to image an abdominal abscess in a horse with a palpable abdominal mass and history of Streptococcus equi infection. A focal area of radioactivity was identified in the location corresponding to the abscess. Imaging of this focal uptake was optimal 48 hours after injection. Similar scans obtained in 2 clinically normal horses revealed no evidence of focal radioactivity in this region. The cell labeling procedure gave acceptable labeling efficiency (87.5%) but an excessive number of damaged WBC, resulting in persistent lung radioactivity on all images. No adverse effects were noted. Radiation measured in the horse and its excreta were well within acceptable limits.

Abdomen↗
PubMed1985

Rapid accurate absolute granulocyte count determination during severe leukopenia using the flow cytometer.

The absolute granulocyte count (AGC) in 125 blood samples from patients with total white blood cell counts of less than 1,000/microliter was estimated using three different methods, which were then compared for efficiency and accuracy. The three methods were 25 cell differential counts using Wright's-stained blood smears, granulocyte percentage estimates from WBC counting chambers, and combined narrow- and wide-angle light-scatter characteristics determined on a flow cytometer. A survey of clinical laboratories at University Hospital Cancer Centers revealed that the smear differential was the most-often-used method in those laboratories even when less than 25 cells could be counted. Consequently the data obtained from the counting chamber and flow cytometer methods were compared to the smear differential "standard" using linear regression, and outliers were identified. There was good correlation between AGC determined by smear differential and WBC counting chamber (correlation coefficient .911) and excellent correlation between the AGC determined by smear differential and the flow cytometer method (correlation coefficient .970). The flow cytometer method used in this investigation required minimal specimen preparation, and test results were available at a rate of 60 seconds/sample. The ease of sample preparation, speed, and statistical reliability of test results makes the flow cytometer an attractive alternate method of determining granulocyte counts on leukopenic patients as compared to the stained blood smear differential.

Flow Cytometry↗
PubMed1984

Selenite-induced protection of bromobenzene hepatotoxicity in male rats.

Acute treatment with sodium selenite effectively reduces bromobenzene hepatotoxicity in male, Sprague-Dawley rats. Hepatocellular damage was ameliorated as shown by marked decreases in plasma alanine and aspartate aminotransferase (ALT and AST) activities. A single dose of selenite (12.5 or 30 mumol Se/kg, ip) was administered to rats at 4, 24, 48, or 72 hr before injection of bromobenzene (7.5 mmol/kg, ip). Plasma ALT and AST activities and hepatic glutathione (GSH) content were measured 24 hr after bromobenzene treatment. As the length of time of selenite pretreatment increased, the extent of reduction of bromobenzene-induced elevation in plasma enzyme activities by selenite was enhanced, and generally, in a dose-related manner with optimal protection occurring in rats pretreated 72 hr prior with selenite. However, depletion of liver GSH by bromobenzene was not affected by selenite treatment. Hepatic GSH levels and GSH detoxication enzyme activities were measured at various intervals in rats treated with selenite alone. Selenite increased hepatic GSH content 20 to 25% at both 24 and 48 hr after injection, with a return to GSH control levels at 72 hr. Selenite treatment produced slight decreases in GSH peroxidase activity but did not alter GSH S-transferase activity. These studies suggest that the reduction of bromobenzene hepatotoxicity by selenite does not involve alterations in the activity of hepatic GSH detoxication enzymes; however, the data suggest that factors in addition to selenite-induced changes in hepatic glutathione levels are also involved.

Alanine Transaminase↗