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Biomedical subjects

D Johnson

Publications and source records attributed to D Johnson.

At least 235 records · Page 13Linked to original sources

Evaluation of an AIDS training program for traditional healers in the Central African Republic.

Training designed to improve AIDS knowledge, attitude, and practice was delivered to 96 traditional healers in the Central African Republic. The training (17 to 36 hours) was conducted by traditional healers with the assistance of staff from the Ministry of Health. Training included the following topics: prevention of HIV transmission during traditional practice; diagnosis, treatment, and prevention of sexually transmitted diseases; condom promotion; AIDS education at the community level; psychosocial support for people with AIDS; and promotion of a positive image for traditional healers. The evaluation of the training consisted of a prospective assessment of knowledge and attitude immediately prior to and after training. These assessments were conducted using structured interviews. Improvement in knowledge and/or attitudes was observed in all areas assessed except for prevention of HIV transmission during traditional practice. We concluded that AIDS training can be successfully delivered to traditional healers.

Acquired Immunodeficiency Syndrome↗

Detection of medulloblastoma and astrocytoma-associated ganglioside GD3 in cerebrospinal fluid.

Shedding of gangliosides by tumor cells may enhance tumor development. We recently showed that cells of the human brain tumor, medulloblastoma, shed gangliosides in vitro and have therefore examined ganglioside shedding by pediatric brain tumors into the cerebrospinal fluid (CSF). GD3, a major ganglioside in medulloblastoma and astrocytoma, was the target for detection in the CSF by immunostaining using the monoclonal antibody R24 and enhanced chemiluminescence detection. Mean CSF GD3 levels in patients with medulloblastomas (n = 9) and astrocytomas (n = 10) were significantly higher than those of controls (mean +/- SD 44.7 +/- 8.4 versus 18.2 +/- 1.9 pmol/ml, n = 20, P < 0.0002). Mass spectrometric analysis showed that tumor-derived ganglioside GD3 contained heterogeneous ceramide structures and, interestingly, the ceramide subspecies with shorter fatty acyl chains were selectively shed. The elevated CSF GD3 concentrations in patients with medulloblastoma and astrocytoma support the concept that ganglioside shedding, which may have significant biological consequences, is characteristic of human brain tumors.

Astrocytoma↗

Proteinase-mediated insect resistance to Bacillus thuringiensis toxins.

Two Bacillus thuringiensis (Bt)-resistant strains of the Indianmeal moth, Plodia interpunctella, lack a major gut proteinase that activates Bt protoxins. The absence of this enzyme is genetically linked to larval survival on Bt-treated diets. When considered with previous data supporting the existence of receptor-mediated insect resistance to Bt, these results provide evidence that insect adaptation to these toxins occurs through multiple physiological mechanisms, which complicate efforts to prevent or manage resistance to Bt toxins in insect control programs.

Animals↗

Identification of the regions on the M110 subunit of protein phosphatase 1M that interact with the M21 subunit and with myosin.

We have previously isolated a form of protein phosphatase-1 (PP1M) from avian smooth muscle myofibrils that is composed of the catalytic subunit of PP1 (PP1C) bound to an M-complex consisting of 110-kDa (M110) and 21-kDa (M21) subunits. The interaction of PP1C with an N-terminal region of the M110 subunit enhances the dephosphorylation of myosin and suppresses the dephosphorylation of other substrates [Alessi, D. R., MacDougall, L. K., Sola, M. M., Ikebe, M. & Cohen, P. (1992) Eur. J. Biochem. 210, 1023-1035; Chen, Y. H., Chen, M. X., Alessi, D. R., Campbell, D. G., Shanahan, C., Cohen, P. & Cohen, P. T. W. (1994) FEBS Lett. 356, 51-56; Johnson, D. F., Moorhead, G., Caudwell, F. B., Cohen, P., Chen, Y. H., Chen, M. X. & Cohen, P. T. W. (1996) Eur. J. Biochem. 239, 317-325]. In this paper, we establish that PP1M accounts for nearly all the myosin phosphatase activity in myofibrils, that the M110 and M21 subunits are present at similar concentrations in the myofibrillar fraction, and that these subunits are entirely bound to PP1. We demonstrate that the M21 subunit does not interact with PP1C, but with the C-terminal 72 residues of the M110 subunit, a region which is 43% identical to residues 87-161 of the M21 subunit. A fragment of the M21 subunit, M21-(M1-L146), which lacks the C-terminal leucine zipper, also bound to the M110 subunit, but two other fragments M21-(M1-E110) and M21-(E110-K186) did not. The M110 and M21 subunits were both found to be myosin-binding proteins. The C-terminal 291 residues of the M110 subunit, but not the C-terminal 72 residues, bound to myosin, but the N-terminal fragments M110-(M1-E309) and M110-(M1-S477) did not. Thus, the region of the M110 subunit that stimulates the dephosphorylation of myosin by PP1C is distinct from the region that targets PP1M to myosin. Remarkably, each myosin dimer was capable of binding about 20 mol M21 subunit and many of the M21-binding sites were located in the myosin rod domain. The potential significance of this observation is discussed.

Amino Acid Sequence↗

A pilot study of protracted low dose cisplatin and etoposide with concurrent thoracic radiotherapy in unresectable stage III nonsmall cell lung cancer.

PURPOSE: A Phase II study to evaluate the response rate and toxicity of daily protracted cisplatin and etoposide with concurrent chest irradiation in patients with locally advanced, unresectable nonsmall cell lung cancer (NSCLC). METHODS AND MATERIALS: Twenty-one patients with histologically confirmed locally advanced inoperable NSCLC (Stage IIIA or IIIB) were entered on study. Radiotherapy consisted of 50.4 Gy in 1.8 Gy fractions followed by a 10 Gy boost in 2 Gy fractions. Chemotherapy included the following: Cisplatin was given at 5 mg/m2 i.v. Monday-Friday before RT weeks 1-6. Etoposide was given at 25 mg/m2 i.v. M-F weeks 1, 2, 5, and 6, with 50 mg/m2 p.o. daily on the same weekends. Because of severe myelosuppression in the first two patients, etoposide only was subsequently changed to 20 mg/m2 i.v. M-F weeks 1, 2, 5, and 6. RESULTS: Twenty patients were eligible and evaluable. The overall response rate was 65% (95% confidence interval 41-85%). The median progression-free survival was 43 weeks. The median overall survival was 50.2 weeks with a 1-year survival rate of 45%. Five patients (25%) developed severe radiation pneumonitis, leading to early closure of the study. CONCLUSIONS: Combining daily protracted cisplatin and etoposide with concurrent thoracic irradiation in patients with locally advanced unresectable NSCLC yields a high overall response rate and a median survival that is at least comparable to other combined modality trials. However, future studies using protracted radiosensitizing chemotherapy should be approached cautiously in light of the high incidence of severe radiation pneumonitis encountered in this trial.

Aged↗

Ultrastructural changes in the trabecular meshwork of human eyes treated with corticosteroids.

OBJECTIVES: To study the ultrastructure of the trabecular meshwork in human eyes with corticosteroid-induced glaucoma and to determine whether the changes noted also occur in the eyes of patients with primary open-angle glaucoma (POAG) who have been treated with corticosteroids. METHODS: The trabecular meshwork from 5 patients in whom corticosteroid-induced glaucoma was diagnosed and from 6 patients with POAG who had been treated with systemic or topical corticosteroids for months to years was investigated with light and electron microscopy. None of the eyes with POAG were considered to have corticosteroid-induced elevation of the intraocular pressure. RESULTS: Eyes with corticosteroid-induced glaucoma had the accumulation of extracellular material distinct from the sheath-derived plaques typical of POAG. A finger-printlike arranged material resembling basement membranes (FBM material), considered characteristic of corticosteroid-induced glaucoma, was found in all eyes with corticosteroid-induced glaucoma. In addition, an abnormal accumulation of densely packed, fine fibrils immediately beneath the inner wall endothelium of Schlemm's canal was present. The findings were similar among patients receiving topical or systemic treatment and among patients of different ages. In the eyes from donors with POAG who had been treated with corticosteroids, the fine fibrillar material and FBM material were present in small amounts in 3 of 6 donors and were not found in the other 3 donors. CONCLUSIONS: The extracellular material that accumulates in eyes with corticosteroid-induced glaucoma differs from that seen in eyes with POAG. Eyes with POAG exposed to long-term corticosteroid treatment did not all respond with the formation of the abnormal extracellular materials characteristic of those found in eyes with corticosteroid-induced glaucoma.

Adolescent↗

Three-dimensional ultrasound: display modalities in obstetrics.

Three-dimensional ultrasound (3DUS) has recently been introduced into clinical practice. Various techniques are available for display of the volume data. We review the importance of selecting the proper display option and rendering mode depending on the specific diagnostic question. Current display options include (1) arbitrary planar images similar to conventional two-dimensional US images, (2) surface rendering with emphasis on soft tissues or skeletal detail, (3) stereo viewing using liquid crystal glasses or red/blue glasses, and (4) cine review of gated studies. Rotation of volume data also is important in understanding/comprehending patient anatomy. The range of rotation angles varies depending on the clinical setting. Also data storage requirements increase as the number of views increases.

Echocardiography, Doppler, Color↗

Hospitalization patterns in severe acute asthma in children.

We set out to determine associations between hospitalization and disease severity before and 2 hours after initiation of asthma therapy in the Emergency Department, and to describe the outcome of patients admitted and discharged. This is a retrospective review of data and charts from a randomized, double blind, placebo-controlled trial (R.C.T.) of 120 asthmatics 5-17 years of age with baseline forced expiratory volume in 1 second (FEV1) < 50% predicted, treated with 3 or 1 or 0 doses of nebulized ipratropium added to three albuterol nebulizations administered over 1 hour. None of the clinical parameters measured at baseline were associated with hospitalization. However, by 2 hours after initiation of therapy, both the FEV1 percent of predicted values (% pred.) and the total asthma score were associated with likelihood of hospital admission. Baseline O2 saturation < 92% indicated a longer hospital stay (75.3 +/- 51 hours vs. 43.0 +/- 24.4 hours, P = 0.015) and a later onset of infrequent nebulizations (46.7 +/- 35.1 vs. 26.6 +/- 17.4 hours, P = 0.006). By 2 hours, those with a post-treatment FEV1 % pred < or = 30% and an asthma score > or = 6 of 9 had a high likelihood of hospitalization (86 and 80%, respectively, combined probability 100%), whereas FEV1 % pred > or = 60% and total asthma score < 3 were associated with successful discharge (probability of 92 and 83%, respectively). We conclude that pre-treatment assessments were not associated with hospitalization, while patients with post-treatment FEV1 % pred < or = 30% and a score > or = 6 had high likelihood of hospitalization.

Administration, Inhalation↗

Pentoxifylline prevents endothelial damage due to ischemia and reperfusion injury.

BACKGROUND: Endothelial injury after ischemia and reperfusion is characterized by an increase in permeability, cellular edema, and loss of acetylcholine-mediated vasorelaxation. Three hours of ischemia followed by 2 hr of reperfusion in the New Zealand white rabbit hindlimb has been shown to result in loss of acetylcholine-induced superficial femoral artery vasorelaxation. The purpose of this study was to evaluate the effect of intraarterial pentoxyfylline (PTX) on this endothelial injury. METHODS: New Zealand white rabbits underwent 3 hr of complete hindlimb ischemia followed by 2 hr of reperfusion. Twenty milliliters of either 100 microM PTX or normal saline was infused over 20 min via the circumflex iliac artery at initiation of reperfusion. Superficial femoral artery rings were then evaluated in vitro for endothelial cell-mediated relaxation. Rings were exposed to standardized incremental doses of acetylcholine after norepinephrine-induced contraction and percentage relaxation was measured. Sections of arteries were also sent for hematoxylin and eosin staining. RESULTS: Similar contraction responses following NE stimulation were observed between control and PTX-treated rings. Control rings relaxed a mean of 14.97 +/- 3.64, 23.17 +/- 5.61, and 31.84 +/- 8.43% in response to acetylcholine doses of 6 x 10(-8), 1 x 10(-7), and 1.5 x 10(-7) M, respectively. In contrast, PTX-treated segments relaxed a mean of 47.52 +/- 8.88, 62.32 +/- 6.83, and 76.73 +/- 4.91% to the same doses of acetylcholine. Differences in relaxation between control and PTX-treated vessels were significantly different at each dose (P < 0.05, Student's t test). Histologic examination of the PTX-treated and control arteries revealed an intact endothelium without morphologic differences between the two groups. CONCLUSION: In this model of rabbit hindlimb ischemia, endothelial cell-mediated vasorelaxation was preserved with the administration of intraarterial PTX during reperfusion compared to controls. The different relaxation responses could not be attributed to altered arterial contractility in response to norepinephrine, or explained by histologic changes in the arterial wall. These studies demonstrate a potential modality for therapeutic intervention to reduce reperfusion injury after acute limb ischemia.

Acetylcholine↗

Factors that influence effect size in 15O PET studies: a meta-analytic review.

The PET literature is growing exponentially, creating a need and an opportunity to perform a meta-analytic review consolidating the published information. This study describes the use of effect size as an index in PET studies and discusses how this measure can be used for comparing findings across studies, laboratories, and paradigms. In comparing studies across laboratories it is essential to know how the methods employed affect the results and conclusions drawn. This study also compared effect size for two different methods of tracer delivery in 15O PET studies ([15O]H2O bolus injection versus inhalation of [15O]CO2), whether averaged versus single-scan conditions were used, and the data analytic strategy employed. The effect sizes observed across studies were consistently large with a median effect size of 8.55, indicating that the phenomena investigated in 15O PET studies are strong. The largest peak activation reported in a study was found to be affected by variability in sample size, data analytic strategy, and repeat versus single-scan conditions. However, the impact of these factors was not examined on smaller or less intense peaks. Minimal standards for reporting statistical results are discussed.

Data Interpretation, Statistical↗

Depletion of activated neutrophils by a filter during cardiac valve surgery.

PURPOSE: To determine whether inclusion of a neutrophil-specific filter into the extracorporeal circuit during open heart valve surgery alters postoperative outcomes. METHODS: Convenience sampling of 24 patients undergoing elective open heart valve surgery between July 1993 and June 1994. Patients were randomized to a neutrophil-specific filter (n = 11) or to a standard blood filter (n = 13) during cardiopulmonary bypass. RESULTS: Neutrophil-specific filter diminished (P < 0.02) the expression of CD18, a neutrophil surface adhesion molecule, at I (84.5 +/- 4.2 vs 94.8 +/- 3.8%), 4 (80.0 +/- 4.2 vs 95.1 +/- 3.9%) and 24 hr (75.2 +/- 4.2 vs 98.2 +/- 3.9%) post-operatively compared with standard filter. Total white blood cell count, neutrophil count, and pro-inflammatory cytokines (IL-6, IL-8) were similar between groups at all times. Measured outcomes including: PaO2 cardiac index, ejection fraction, haemodynamic variables, use of inotropes, spirometry (FEV1, FVC), and hospitalization duration were similar between groups. CONCLUSIONS: Inclusion of the neutrophil filter during open heart valve surgery selectively depletes activated neutrophils. There were no other detectable differences between the two groups and the use of a neutrophil-specific filter in routine clinical practice for patients undergoing open heart valve surgery is not supported.

Adult↗

Cardiovascular responses to dynamic submaximal exercise in children previously treated with anthracycline.

This study assessed the long-term (5-year) outcome of pediatric low-dose anthracycline therapy on the circulatory response to moderate exercise. Thirteen patients (13 +/- 4 years old) and 15 age-matched control subjects completed a maximal cycle ergometer protocol as well as two 5-minute cycling tests at 33% and 66% maximal oxygen uptake (V(O2)max) for determination of cardiac index (carbon dioxide rebreathing). V(O2)max was lower in patients than in control subjects (1.3 +/- 0.5 L/min vs 2.3 +/- 0.6 L/min) (p< 0.05). Smaller relative increases in cardiac index for similar increases in relative exercise intensities were found in patients (33% V(O2)max, 73% vs 116%; 66% V(O2)max, 115% vs 192%), as a result of smaller increases in stroke index from rest (33% V(O2)max, 33% vs 54%; 66% V(O2)max, 33% vs 69%; p< 0.05). Similarly, despite normal resting systolic function, patients exhibited a lower stroke index and higher heart rate for any given value of oxygen uptake (milliliters per minute per square meter). Children who had survived cancer exhibited stroke index impairment during exercise similar in intensity to that of recreational activities or play, attesting to a limited inotropic reserve.

Adolescent↗

Combined exposure to cigarette smoke and hypercholesterolemia decreases vasorelaxation of the aorta.

PURPOSE: The purpose of this study was to determine the physiologic effects of cigarette smoke exposure and dietary cholesterol on the availability of nitric oxide in aortic vascular rings. METHODS: Four groups of New Zealand White rabbits were placed in an air flow chamber for 3 hours per day for 8 weeks. Two of these groups were exposed to smoke from 600 cigarettes per day 5 days a week added to the chamber inflow by a robotic smoke generator. One of these groups was made hypercholesterolemic by being fed a 0.3% cholesterol diet. Two groups of rabbits were similarly placed in the air flow chamber but without smoke exposure, of which one group was also made hypercholesterolemic. After an 8-week period, the rabbits were killed and the infrarenal aortas were excised. The vessels were cut into 3 mm rings and suspended from tension transducers. The rings were contracted with potassium chloride to determine vessel integrity. Then one ring from each aorta was maximally contracted with norepinephrine, and the experimental ring was contracted to 50% of maximum. Relaxation of the rings in response to incremental doses of acetylcholine was measured. RESULTS: No significant differences were seen in contraction to potassium chloride or norepinephrine in any group. A significant decrease in acetylcholine-mediated relaxation was seen only in the smoke-exposed, cholesterol-fed group. CONCLUSIONS: Endothelial damage, as measured by acetylcholine-mediated vasorelaxation, occurs in the infrarenal aorta in rabbits that are exposed to both cigarette smoke and elevated dietary cholesterol. Cigarette smoke exposure alone or hypercholesterolemia alone in this model did not result in significant alteration in acetylcholine-mediated vasorelaxation.

Acetylcholine↗

Respiratory outcomes with early extubation after coronary artery bypass surgery.

OBJECTIVE: Aortocoronary bypass surgery has undergone recent changes, promoting the concept of "fast tracking," in which patients are extubated and discharged postoperatively at an accelerated pace compared with previous historic patterns. Postoperative respiratory function and complications have not been previously studied in patients selected for "fast tracking." DESIGN: Matched retrospective cohort study. SETTING: Referral university teaching hospital. PATIENTS: Thirty-one patients who were compared with a retrospective matched cohort of 112 patients. Matching was based on forced vital capacity, age, and gender. INTERVENTIONS: Respiratory physiological outcomes defined as pneumonia, postoperative pulmonary spirometry, chest x-ray atelectasis or lobar collapse, and gas exchange were compared. MAIN RESULTS: The increase in atelectasis score compared with preoperative (0 = no atelectasis, 4 = lobar collapse) was higher (p < 0.01) on the day of extubation in the late extubation group (4.1 +/- 1.4) compared with the early extubation group (2.6 +/- 1.3). These chest radiographic findings were not related to pain (0 to 10 visual analog scalei, which were equivalent between groups (4.0 +/- 2.3 v 4.2 +/- 1.6). The decreases in spirometry on postoperative day 5 (FVC 1.15 +/- 0.42 v 0.86 +/- 0.54 liters; FEV1 0.92 +/- 0.38 v 0.59 +/- 0.50 liters) were greater (p < 0.001) in the late extubation group. A significantly (p < 0.001) greater decrease in FEV1/FVC ratio in the late extubation group (3.25 +/- 0.87 v -1.6 +/- 1.11%) was indicative of greater airway obstruction. Fluid balance until extubation was greater in the late extubation group (4.0 +/- 2.1 v 1.4 +/- 1.2 liters). CONCLUSIONS: Differences in chest radiographs in the late extubation group at the time of extubation may be related to greater use of fluids or increased airway obstruction. The rationale of early extubation is based on cost minimization to decrease hospital duration. This article suggests that respiratory physiological outcomes are not worsened in patients who are extubated and discharged early after elective aortocoronary bypass surgery.

Airway Obstruction↗

Measurement of the power output during the acceleration phase of all-out arm cranking exercise.

The purpose of this study was to develop an original friction loaded ergometer allowing measurement of the resisting torque (Mb) and the angular velocity (omega) by means of a force transducer and an optical pick-up during all-out arm cranking exercises. Taking into account the kinetic energy variations of the flywheel, the peak power developed at the crank (P(c)peak) and the peak angular velocity (omegapeak) were determined in 6 male and 6 female able-bodied subjects during 6-8 bouts of 3 s duration, performed at maximal velocity, with Mb varying from 0.07 to 0.87 Nm x kg(-1). In each subject, the Mb increase was related to a decrease of omegapeak. This relationship was expressed through a negative linear regression (0.92 < R2 < 0.99) for omegapeak between 13 and 28 rad x s(-1) for the males and 10 and 24 rad x s(-1) for the females. The relationship between P(c)peak and Mb did not fit well for all subjects (0.01 < R2 < 0.93) with a parabolic equation, indicating that for upper limb testing, the maximal power should be defined as the highest power measured during several bouts performed with appropriate resisting torque. The present study also demonstrated the importance of taking into account the inertia of the moving flywheel during the acceleration phase of an all-out arm crank exercise, when determining the peak power output.

Acceleration↗