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T S Johnson

Publications and source records attributed to T S Johnson.

At least 19 recordsLinked to original sources
PubMed1990

HLA class II-restricted binding of muramyl peptides to B lymphocytes of normal and narcoleptic subjects.

The propensity for narcolepsy, a clinical sleep disorder of unknown etiology, is virtually totally included within the HLA-DR2,DQw1 (DRw15,DQw6) phenotype. The disorder is characterized by decreased sleep latency, early onset of rapid eye movement sleep, and a paucity of nocturnal slow-wave sleep. Muramyl peptides, naturally occurring bacterial cell wall peptidoglycans, potently enhance the duration and amplitude of slow-wave sleep in animals, bind to murine mononuclear cells, and exhibit a major histocompatibility complex-restricted immunoadjuvant effect in mice. We examined the binding of muramyl peptides to peripheral blood mononuclear leukocytes of HLA-typed normal (n = 13) and narcoleptic (n = 10) subjects. Muramyl peptides bound specifically and with high affinity to normal B- but not T-lymphocyte-enriched preparations. There was no significant specific binding to B-cell-enriched preparations from narcoleptic patients. Furthermore, B-lymphocyte-enriched preparations of normal individuals who had the HLA-DR2,DQw1 phenotype (n = 8) exhibited a lower level of specific binding than those of normals who did not have this phenotype (n = 5, p less than 0.001). These observations are an additional indication of the relevance of muramyl peptides to slow-wave sleep and provide a basis for a better understanding of the relation between narcolepsy and the MHC at the biochemical level.

Acetylmuramyl-Alanyl-Isoglutamine↗
PubMed1989

Dexamethasone as prophylaxis for acute mountain sickness. Effect of dose level.

Rapid exposure of unacclimatized persons to high altitude causes the syndrome acute mountain sickness (AMS). Prophylactic treatment with frequent high doses of dexamethasone has been shown to prevent AMS. To determine whether lower, less frequent doses were effective in preventing AMS, 28 men between the ages of 18 and 32 were exposed to a simulated altitude of 4,570 m for 45 h in a hypobaric chamber on two occasions while taking one of three doses of dexamethasone (4 mg, 1 mg, or .25 mg every 12 h) or a placebo in a double-blind, crossover design. The 4-mg dose of dexamethasone reduced the incidence of AMS symptoms compared with placebo and the other dose levels. Dexamethasone did not alter fluid balance or plasma volume changes, but treatment with 1 mg and 4 mg suppressed cortisol secretion. There was no evidence of adrenal cortical suppression after treatment with dexamethasone or placebo 48 h after discontinuing altitude exposure and drug treatment. The results indicate that 4 mg of dexamethasone twice daily is an effective prophylactic treatment for AMS, while lower doses are relatively ineffective.

Adolescent↗
PubMed1988

Relief of sleep apnea by revision of the adult upper airway. A review of clinical experience.

Surgical revision of the upper airway for obstructive sleep apnea has repeatedly improved subjective more than objective laboratory outcome measures. To examine this disparity, we obtained subjective sleepiness questionnaire scores, Continuous Performance test, and polysomnography (PSG) in 40 patients with mild to moderate obstructive sleep apnea (mean apnea index, 33.9; mean minimum oxygen saturation during sleep, 75.4%). Continuous Performance test confirmed abnormal daytime sleepiness and correlated with minimum oxygen saturation and number of transitions between stages. Postoperatively, questionnaire scores fell a mean of 62%, indicating a marked improvement in subjective sleepiness. Changes in questionnaire score correlated with changes in minimum oxygen saturation. Mean PSG indexes showed no change. Individual patients without PSG improvement reported long-term improvement in daytime functioning, as confirmed by family members. These results suggest that measures in addition to PSG, including patient subjective response, would more fully characterize the outcome of revision of the upper airway for sleep apnea.

Adult↗
PubMed1988

Flow cytometric applications in cytopathology.

Flow cytometric (FCM) methodology represents a powerful analytical tool for screening and detecting abnormal and malignant cells, for subclassifying malignancies beyond conventional morphologic type and grade and for transcending light microscopic features by providing more biologically meaningful information. This paper reviews the historical background leading to the development of the FCM methodology and instrumentation that is presently being used for cytopathologic (and histopathologic) diagnosis, tumor subclassification and identification of aggressive cancers. Emphasis is placed on human carcinomas, with reference to hematologic malignancies when appropriate. Examples of FCM DNA content and cytokinetic techniques are described for the various cytologic sampling methods. The advantages, limitations and future prospects for the application of flow cytometric techniques in cytopathology are discussed.

Biopsy↗
PubMed1988

Hemodynamic and sympathoadrenal responses to altitude in humans: effect of dexamethasone.

Altitude exposure alters hemodynamics and sympathoadrenal function and elicits acute mountain sickness (AMS). Since dexamethasone prevents AMS and influences responsiveness to catecholamines, we studied hemodynamic and sympathoadrenal responses to 4,570 m simulated altitude in 8 subjects treated with dexamethasone or placebo. Mean pulse rates were less at altitude with dexamethasone (96.1 for placebo and 84.1 for dexamethasone; treatment-altitude interaction, p = 0.0045). Altitude led to a postural decline in mean arterial pressure (posture-altitude interaction, p = 0.0026), but this was not affected by dexamethasone. Dexamethasone reduced urinary epinephrine to a greater extent during altitude exposure (from 9.41 ng.mg-1 creatinine with placebo to 4.16 with dexamethasone) when compared with sea level (from 3.24 to 3.08). Urinary excretion of norepinephrine was unchanged at altitude. We conclude that acute altitude exposure is associated with stimulation of the adrenal medulla and not the sympathetic nervous system. Dexamethasone blocks the adrenal medullary response and blunts the pulse rate increase at altitude.

Adrenal Medulla↗
PubMed1987

Cervical carcinoma DNA content, S-fraction, and malignancy grading. I. Interrelationships.

The flow cytometric measured DNA content (i.e., DNA index), S-fractions, and histopathologic malignancy grades were studied for ninety uterine cervical squamous cell carcinomas using tissue biopsies taken prior to radiotherapy. The DNA aneuploidy frequency for low S-phase tumors (%S less than 14) was only 9/29 (31%) compared to 22/30 (73%) for intermediate (%S 15-23) and 30/31 (97%) for high (%S greater than 24) tumors. An overall mean %S of 20 +/- 7 (range 2-45%) was observed for these cervical cancers, with the S-fraction significantly increasing (P = less than 0.01) from 12 +/- 5, to 18 +/- 8, and 26 +/- 7 for diploid/near diploid, low-degree DNA aneuploidy, and high-degree DNA aneuploidy tumors, respectively. Broad heterogeneity was observed for the microscopic scored malignancy grades within DNA index and the cell-cycle S-fraction subgroups. Generally, multifactorial histopathology scoring was not significantly correlated with either the tumor DNA index or %S variables. Based on statistical analysis, the malignancy grades more closely reflected the tumor proliferative activity than the DNA index, with nuclear polymorphism, mitotic frequency, and the invasion pattern showing the lowest P values (which were not significant at P = 0.05). High tumor S-fraction was associated with high malignancy grade, as evidenced by 19/25 (75%) of high S-fraction, high degree DNA aneuploidy tumors having greater than average malignancy grade compared to only 2/14 (14%) low to moderate S-fraction tumors having similar DNA index. The results indicate that more reliable identification of biologically different cervical cancers can be achieved by evaluating the tumor DNA index in relationship to the cell-cycle %S and malignancy grading.

Biopsy↗
PubMed1987

Cervical carcinoma DNA content, S-fraction, and malignancy grading. II. Comparison with clinical staging.

In an attempt to achieve more biologically meaningful subclassification of squamous cell cervical cancers and ultimately more reliable prediction of tumor behavior, we have studied the tumor pretreatment DNA content (i.e., DNA index), cell-cycle S-fraction, and histomorphologic malignancy grading properties for tumors having similar and different clinical staging. The tumor DNA index, %S-phase cells, and average malignancy grades were statistically tested against known clinical predictive variables for 90 primary squamous cell carcinomas of the uterine cervix studied prior to radiotherapy. We observed that the biological and morphological tumor properties of cervical cancers broadly overlapped between different stages of disease and for other clinical criteria including the gross morphology, lymph node status, and intravenous positivity. No significant differences were detected in the DNA indices, %S, or malignancy grades between the stages of disease or the other clinical criteria. It was concluded that: the gross clinical staging criteria inadequately reflected the tumor biological properties; and that the possibility exists for refining prognosis by use of the biological and morphological noncodependent tumor parameters to supplement staging criteria; and the use of cell-cycle cytokinetic and malignancy grading criteria in addition to tumor DNA index is superior to DNA index (or DNA content) alone for identifying biologically different cervical cancers.

Carcinoma, Squamous Cell↗
PubMed1987

Effect of dexamethasone on symptoms of acute mountain sickness at Pikes Peak, Colorado (4,300 m).

In a previous controlled study, dexamethasone (DEX) was shown to prevent acute mountain sickness (AMS) during exposure to simulated high altitude. To determine the effect of DEX during actual altitude exposure, 16 young men were treated with either DEX (4 mg every 6 h) or placebo for 48 h prior to and 48 h after being rapidly transported from sea level to the summit of Pikes Peak, CO (4,300 m). Symptoms of AMS were evaluated twice daily at Pikes Peak using the Environmental Symptoms Questionnaire and a clinical assessment. During treatment the mean symptom scores were higher for subjects taking placebo in 18 out of 20 comparisons. On an individual basis, 60% of the subjects receiving placebo met the criteria for being "sick" compared to 31% of subjects receiving DEX. Beginning 24 h after cessation of treatment, DEX subjects experienced a progressive increase in symptom scores which lasted through the end of the altitude sojourn (day 6). The results indicate that DEX is an effective prophylactic treatment for AMS in an actual mountain environment, but that AMS symptoms can occur if the drug is stopped abruptly.

Acute Disease↗
PubMed1986

Isolation and biochemical studies of enriched populations of spermatogonia and early primary spermatocytes from rat testes.

A method to obtain several highly enriched populations of testis cell types from rats of a single age is described. Single cell suspensions from immature rat testes were prepared after enzymatic removal of interstitial cells. Cells were separated on the basis of size into four fractions (bulk preparations) or eight fractions (analytical preparations) by centrifugal elutriation. These elutriator fractions were further separated by equilibrium density centrifugation in Percoll gradients. In this manner, populations of 2 X 10(7) type A spermatogonia (51% purity), 3 X 10(7) type B spermatogonia (76% purity), 5 X 10(7) zygotene/early pachytene spermatocytes (56% purity), 3 X 10(7) midpachytene spermatocytes (70% purity), and 4 X 10(7) Sertoli cells (89% purity) could be obtained from 50 immature rats within 6 h after killing. Purities, determined by examination of cytologic smears, were verified by Coulter volume and flow cytometric DNA determinations. These separation methods were used to obtain cell populations for characterization of levels and synthesis of high mobility group proteins in the early stages of spermatogenesis.

Animals↗
PubMed1985

Flow cytometric analysis of head and neck carcinoma DNA index and S-fraction from paraffin-embedded sections: comparison with malignancy grading.

Archival, paraffin-embedded, pathology specimens representing pretreatment tissue biopsies from 73 patients with epidermoid carcinoma of the head and neck were analyzed for DNA Index and %S-phase cells by flow cytometry and were scored for quantitative histomorphology. The DNA fluorescence/light scatter size patterns derived from paraffin-embedded specimens were shown to be essentially the same as those from mechanically disaggregated, ethanol-fixed cells obtained from the same tissue specimen. Patterns ranged from lymphocyte-like to highly abnormal DNA Index cytokinetic patterns. The DNA Index values ranged from 0.70 to 3.50 (median 1.42), with an aneuploidy frequency of 63/73 (86%). DNA distribution %S ranged from 4% to 45% (mean 19), with the microscopic malignancy grading showing broad heterogeneity (mean 2.1, range 1.0-3.0, where 1.0-1.7 = well differentiated, 1.8-2.3 = moderately differentiated, 2.4-3.0 = poorly differentiated). Cross-comparison of these data showed that (1) the tumor %S was dependent on DNA Index (higher %S at higher ploidy), (2) low to high malignancy tumors were randomly distributed between diploid/near diploid tumors and high-degree DNA abnormality tumors, and (3) proliferative activity values broadly overlapped between low to high malignancy scored tumors. However, those carcinomas characterized by high DNA Index (greater than or equal to 1.50) and high %S-phase fractions (greater than or equal to 20) had a five fold higher incidence of high-degree malignancy, invasive tumors than diploid/near diploid (%S less than or equal to 19) tumors.

Biopsy↗
PubMed1985

Diagnosis of narcolepsy using the multiple sleep latency test: analysis of current laboratory criteria.

Multiple sleep latency tests (MSLT) performed on 144 patients with excessive daytime somnolence were examined for the diagnostic reliability of a short sleep latency (SL less than 5 min) and the presence of sleep-onset REM periods (SOREMPs). Based on clinical criteria, 61 patients (42%) were diagnosed as having narcolepsy. Thirty-five narcoleptic patients and five nonnarcoleptic patients exhibited a mean SL less than 5 min, yielding a sensitivity of 57% and a specificity of 94% for this criterion for pathological drowsiness. The occurrence of two or more SOREMPs was found in 52 narcoleptic patients but in only one nonnarcoleptic patient (sensitivity of 84% and specificity of 99%). Those narcoleptic patients with cataplexy demonstrated a shorter SL and more frequent SOREMPs than their noncataplectic counterparts. It was concluded that the MSLT is a highly reliable laboratory tool for the confirmation of the diagnosis of narcolepsy based on the SOREMP criterion. The criterion value for SL in pathological drowsiness may depend on laboratory conditions as well as the patient population selected.

Adolescent↗
PubMed1985

Comparison of cytologic and acridine-orange flow-cytometric detection of malignant cells in human body cavity fluids.

Flow cytometrically (FCM) derived DNA and RNA profiles were studied in acridine orange (AO)-stained body cavity fluid (BCF) specimens obtained from 78 patients with various solid tissue and hematologic malignancies. The ploidy (DNA index), RNA content (RNA index), proliferative activity (% S + G2M) and DNA and RNA scattergram patterns were tested "double-blind" against the cytologic scoring of specimens as malignant, benign or reactive. It was determined that expression of an "abnormal" RNA index (greater than or equal to 2.8) and an elevated proliferative activity (% S + G2M greater than or equal to 7.4) was dependent on the presence of malignancy; 21 of 22 specimens having those abnormal indices had DNA aneuploidy and were cytologically scored as positive. The AO FCM sensitivity and specificity for detecting malignant cells (when measured against cytology scoring) were 61% and 90%, respectively, using the "abnormal" RNA index and % S + G2M cut-offs together with the cellular DNA aneuploidy marker. By supplementing the cytologic scoring with AO FCM DNA and RNA features, the sensitivity for detecting malignant cells was 94%, as compared to 72% for cytology alone. Two specimens gave false-positive FCM results: a tuberculous effusion with a tetraploid subpopulation and a reactive mesothelial proliferation that was diploid and negative cytologically. Scoring for malignancy based on the visual pattern of the DNA and RNA FCM scattergrams, while showing good correlation for aneuploid specimens, in some cases failed to identify diploid disease. The results demonstrate the usefulness of FCM DNA and RNA analysis for supplementing cytologic examination of BCF specimens for the purpose of detecting malignant cells.(ABSTRACT TRUNCATED AT 250 WORDS)

Acridine Orange↗
PubMed1979

A closed lung system study of inert gas absorption.

The demonstration that the rate of rise of the alveolar fraction of nitrous oxide is enhanced when the inspired N2O concentration is high is termed the "concentration effect." A similar effect on a second gas has been termed the "second gas effect". These effects have been observed in open systems and attributed to differential changes between inspired and expired ventilation. The purpose of this investigation is to study these effects in a closed system. A breath-holding maneuver was utilized with a high and a low N2O concentration in argon and oxygen. The results indicate that breath holding with a high N2O concentration "concentrates" both the alveolar fraction of N2O and argon. These results are attributable to alveolar volume shrinkage as a consequence of the large absorption of N2O by the pulmonary blood. A mathematical model verifies this interpretation and suggests that volume shrinkage can be important in breath-holding maneuvers designed for noninvasive measurement of cardiac output and lung tissue volume.

Argon↗