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Biomedical subjects

B Johnson

Publications and source records attributed to B Johnson.

At least 163 records · Page 9Linked to original sources

Expression of the MAGE-1 tumor antigen is up-regulated by the demethylating agent 5-aza-2'-deoxycytidine.

MAGE-1 is a gene that encodes an antigen on a melanoma cell line that is recognized by cytolytic T-cells. We have used a reverse transcription-polymerase chain reaction assay to analyze expression of the MAGE-1 gene by cell lines from different types of tumors, melanomas from different stages of disease progression, normal diploid cell lines, and melanocyte and nevus tissue from which malignant melanomas are derived. MAGE-1 is expressed by melanoma tissue from all stages of disease, but not melanocytes, nevus tissue, or any normal diploid cell line tested. A fraction of tumor lines derived from various epithelial and neuroectodermal malignancies expressed MAGE-1 but not peripheral blood cells from patients with melanoma. 5-Aza-2'-deoxycytidine (DAC), a demethylating agent, was capable of inducing MAGE-1 expression by a MAGE-1-negative melanoma cell line 888-mel as well as by a number of other melanoma cell lines. At an optimum concentration of 1 microM DAC, MAGE-1 expression was detectable by 24 h, plateaued by 72 h, but remained high for two weeks after removal of DAC from treated 888-mel cells, consistent with induction by demethylation. With the exception of tumor-infiltrating leukocytes, no normal diploid cell line could be induced with DAC to upregulate MAGE-1 expression. DAC-treated 888-mel cells were lysed by a MAGE-1-specific major histocompatibility complex restricted cytolytic T-cell clone, whereas control untreated cells were not, suggesting that production of the antigen encoded by the MAGE-1 gene was induced by DAC and that it was presented in association with major histocompatibility complex class I molecules at the cell surface for T-cell recognition.

Antigens, Neoplasm↗

Practice guidelines and reminders to reduce duration of hospital stay for patients with chest pain. An interventional trial.

OBJECTIVE: The acceptability, safety, and efficacy of practice guidelines have rarely been evaluated. Moreover, despite the recent development of guidelines and decision aids for patients admitted to coronary care and intermediate care units, few have been tested in clinical practice. DESIGN: A prospective, controlled clinical trial with an alternate-month design. SETTING: A large teaching community hospital. PATIENTS: Patients admitted to coronary care and intermediate care units with chest pain who were considered at low risk for complications according to a practice guideline (n = 375). INTERVENTION: Physicians caring for patients with chest pain who were at low risk for complications received concurrent, personalized written and verbal reminders regarding a guideline that recommended a 2-day hospital stay. RESULTS: Use of the practice guideline recommendation with concurrent reminders was associated with a 50% to 69% increase in guideline compliance (P < 0.001) and a decrease in length of stay from 3.54 +/- 4.1 to 2.63 +/- 3.0 days (0.91-day reduction, 95% CI, 0.18 to 1.63; P = 0.02) for all patients with chest pain considered at low risk for complications. The intervention was associated with a total (direct and indirect) cost reduction of $1397 per patient (CI, $176 to $2618; P = 0.03). No significant difference was found in the hospital complication rate between patients admitted to the hospital during control and intervention periods, and no significant difference was noted in complications, patient health status, or patient satisfaction when measured 1 month after hospital discharge. CONCLUSION: These results suggest that implementation of this practice guideline through concurrent reminders reduced hospital costs for patients with chest pain considered at low risk for complications. Further study of the guideline is warranted.

Aged↗

Cutaneous polyarteritis nodosa. Reports of two cases in children and review of the literature.

BACKGROUND: Polyarteritis nodosa (PAN) is a necrotizing vasculitis of small- and medium-sized arteries that most often affects the kidneys, heart, and liver but can affect any organ system. A cutaneous form of PAN without visceral involvement, which follows a benign but often chronic course, has also been described. Both forms are rare in children. OBSERVATIONS: We describe two children with cutaneous PAN who were admitted to The Johns Hopkins Children's Center, Baltimore, Md, within a 1-week period. Both girls, aged 2 and 6 years old, presented with multiple, red, painful, edematous nodules on the extremities, face, and trunk. Dermatologic findings were accompanied by fever, arthralgias, and arthritis, but neither child had evidence of severe systemic disease. Skin biopsy specimens revealed necrotic small- and medium-sized muscular arteries with neutrophilic and eosinophilic infiltrate and fibrin thrombi. Both patients responded to treatment with prednisone. CONCLUSIONS: In children with cutaneous PAN, systemic symptoms may be present, but the lack of life-threatening complications distinguishes this relatively benign disease from systemic PAN.

Biopsy↗

Stage- and region-dependent chondrogenesis and growth of chick wing-bud mesenchyme in serum-containing and defined tissue culture media.

During development, limb-bud mesenchymal cells carry out complex spatiotemporal-patterns of growth and differentiation. Tissue and organ culture facilitate analysis of environmental influences on these cell behaviors, allowing their partial dissection into exogenous and endogenous components. Two factors that complicate such in vitro analyses are the heterogeneity of the cultured cells and imprecise knowledge of culture medium composition. Limb mesenchyme comprises a heterogenous cell population with important regional differences in cell type. Dividing the limb into subregions helps limit the cellular heterogeneity and using chemically defined, serum-free medium alloys concerns about medium composition. In the present study, mesenchyme from different regions along the anteroposterior and proximodistal axes of stage 21-22 and stage 23-24 chick wing buds was grown in high-density microtiter cultures in chemically defined and in serum-containing medium. Four-day cultures of the various regions were compared in terms of culture morphology and the accumulation of Alcian blue-positive cartilage matrix and DNA. The results demonstrate stage- and region-dependent differences in the in vitro growth, differentiation, and responsiveness of these cells. For example, mesenchyme from the distal anterior region of the wing bud exhibited lower intrinsic chondrogenic capacity and greater responsiveness to serum than other regions. Patterns of in vitro chondrogenesis also suggest that, at the stages examined, distal wing-bud mesenchyme may be less homogeneous than has been believed. A case is made for the suitability of serum-free medium for future in vitro studies of chick limb-bud mesenchyme. The results are considered in relation to the process of limb development and regional expression of pattern-related genes.

Animals↗

Stage- and region-dependent responses of chick wing-bud mesenchymal cells to retinoic acid in serum-free microcultures.

Retinoic acid (RA) has been shown to affect skeletal patterning in vivo in both developing and regenerating limbs. Regional differences in RA concentrations alone cannot account for the region-specific cell behaviors involved in limb-skeletal morphogenesis. The present study explores a role for regional differences in signal interpretation in RA's effects along the anteroposterior and proximodistal axes of stage 21-22 and 23-24 chick wing-buds. Mesenchymal cells isolated from specific limb regions were grown in chemically defined medium and exposed to 5 or 50 ng/ml of RA for 4 days in high-density microtiter cultures. Previous studies showed that RA's effects on chondrogenesis and growth in such cultures differed depending on the position along the limb's proximodistal axis from which the cells were isolated. The present study is the first to show that such differences in RA-responsiveness also exist along the limb's anteroposterior axis, especially in the distal subridge mesenchyme. The region-dependent relationships between RA's effects on growth and chondrogenesis suggest that RA affects these two behaviors through different mechanisms. The regional differences in the responsiveness of these cells to exogenous RA are discussed with respect to their correspondence to the in vivo patterns of expression of RA-binding proteins, RA-receptors, and other patterning-related genes.

Animals↗

Relationship of episiotomy to perineal trauma and morbidity, sexual dysfunction, and pelvic floor relaxation.

OBJECTIVE: Our purpose was to compare consequences for women of receiving versus not receiving median episiotomy early and 3 months post partum on the outcomes perineal pain, urinary and pelvic floor functioning by electromyography, and sexual functioning and to analyze the relationship between episiotomy and third- and fourth-degree tears. STUDY DESIGN: A secondary cohort analysis was performed of participants within a randomized clinical trial, analyzed by type of perineal trauma and pain, pelvic floor, and sexual consequences of such trauma, while controlling for trial arm. The study was conducted in three university or community hospitals; 356 primiparous and 341 multiparous women were studied. RESULTS: Early and 3-month-postpartum perineal pain was least for women who gave birth with an intact perineum. Spontaneous perineal tears were less painful than episiotomy. Sexual functioning was best for women with an intact perineum or perineal tears. Postpartum urinary and pelvic floor symptoms were similar in all perineal groups. At 3 months post partum those delivered with an intact perineum had the strongest pelvic floor musculature, those with episiotomy the weakest. Among primiparous women third- and fourth-degree tears were associated with median episiotomy (46/47). After forceps births were removed and 21 other variables potentially associated within such tears were controlled for, episiotomy was strongly associated with third- and fourth-degree tears (odds ratio +22.08, 95% confidence interval 2.84 to 171.53). Physicians using episiotomy at high rates also used other procedures, including cesarean section, more frequently. CONCLUSION: Perineal and pelvic floor morbidity was greatest among women receiving median episiotomy versus those remaining intact or sustaining spontaneous perineal tears. Median episiotomy was causally related to third- and fourth-degree tears. Those using episiotomy at the highest rates were more likely use other interventions as well. Episiotomy use should be restricted to specified fetal-maternal indications.

Adolescent↗

In vivo binding of 1-nitropyrene to albumin in the rat.

Human risk assessment from exposure to nitropolynuclear aromatic hydrocarbons (NO2-PAH) has not been clearly defined, despite the widespread occurrence of such agents in the environment and their possible involvement in the etiology of some human cancers. This study was conducted since methods to determine exposure to and uptake of metabolically activated NO2-PAH are lacking. 1-Nitropyrene (1-NP), the most abundant and most extensively studied NO2-PAH, was found to bind to rat albumin at a level of 0.04 +/- 0.01% (mean +/- SD, n = 3) of the dose administered by gavage; the binding was linear over five orders of magnitude (P < 0.01). The adducts cleared at a rate (half-life = 60 h) similar to that of the unmodified rat albumin. Chromatographic analysis revealed that albumin adducts could be resolved further into a major and a minor component. Mild acid hydrolysis of the major 1-NP-albumin adduct yielded phenolic derivatives that, when subjected to acetylation, produced a material with a mass spectrum similar to that of a synthetically prepared mixture, consisting of more than one isomer, 1-acetylamino-X,Y-diacetoxypyrenes (chromatographic separation of the individual isomers was not achieved). Thus, this phenolic material that is released upon the acid treatment of albumin adducts may be a suitable indicator(s) for monitoring exposure to and metabolic activation of 1-NP.

Animals↗

Loss of heterozygosity of the human cytosolic glutathione peroxidase I gene in lung cancer.

The consistent deletion of 3p21 in lung cancer has led to intensive efforts to identify a lung tumor suppressor gene at this locus. We recently mapped the gene for the selenium-dependent drug-detoxifying enzyme glutathione peroxidase 1 (GPX1) to this location by in situ hybridization. We developed a polymerase chain reaction-based assay which demonstrated the existence of three GPX1 alleles characterized by the number of alanines in a polyalanine coding sequence in exon 1. These three alleles produced a heterozygote frequency of 70% in two separate populations: normal tissue DNA taken from Centre d'Etude du Polmorphisme Humain (CEPH) parents and normal tissue taken from cancer patients. In contrast, 10 heterozygote tumors were detected out of 64 lung cancer specimens. Linkage analysis of GPX1 to Genethon 3p markers in CEPH pedigrees demonstrated that GPX1 was located between the two microsatellite markers believed to flank the lung cancer deletion site. Nucleotide sequence analysis of GPX1 alleles did not reveal any mutations of this gene in lung tumors. However, sequence analysis did reveal that the three GPX1 alleles were characterized by three nucleotide substitutions in addition to the polyalanine polymorphism, including a substitution at codon 198 which results in either a proline or leucine at that position. Therefore, the different GPX1 alleles encode structurally different hGPx1 subunits. In addition, analysis of allele frequency suggests that the GPX1*ALA7 allele may occur less frequently in tumors with 3p21 deletions.

Alleles↗

Reducing lengths of stay in the coronary care unit with a practice guideline for patients with congestive heart failure. Insights from a controlled clinical trial.

Although more than 1,000 medical practice guidelines have been developed, there have been few evaluations of their use in clinical practice or information to judge whether practice guidelines can be used to reduce health care costs. For this reason, the authors conducted a prospective controlled clinical trial with an alternating-month design at a large teaching community hospital to study the use of a practice guideline to promote early transfer of patients admitted to a hospital with congestive heart failure (CHF) from the coronary care unit (CCU) and intermediate care unit to unmonitored beds. The practice guideline was supported by locally derived risk information and recommended consideration of early "step-down" transfer of low-risk patients with CHF 24 hours after hospital admission. Physicians caring for patients identified as "low risk" received concurrent personalized written and verbal reminders concerning the guideline recommendation. Study subjects were patients admitted to a hospital CCU and intermediate care unit between November 1, 1991 and April 30, 1993 with a diagnosis of CHF or pulmonary edema. Ninety patients with CHF were identified as low risk according to the guideline during the study period. Feedback of the practice guideline recommendation was not associated with a significant increase in physician adoption of the guideline or shorter lengths of stay in the CCU or intermediate care unit. Physicians may have compensated for statistically insignificant reductions in monitored lengths of stay by increasing the length of stay in unmonitored beds (1.80 +/- 2.32 to 4.02 +/- 4.09 days, P = .002) and the total length of stay (4.73 +/- 2.43 to 6.71 +/- 5.44 days, P = .03). Quality of patient care, patient outcomes, and patient satisfaction were not affected by the guideline. Our study results suggest that implementation of a locally derived practice guideline for patients with CHF did not result in adoption of the guideline by physicians. The complexity of implementing the guideline, changes in physician practice before the study, and the failure of the guideline to address the continuum of patient care across monitored and unmonitored beds may have accounted for rejection of the guideline. Our experience demonstrates that practice guidelines, whenever possible, should be evaluated in prospective trials before they should be disseminated for widespread use.

Adult↗

Cellular sensitivity to oxidative stress in the photosensitivity dermatitis/actinic reticuloid syndrome.

Skin fibroblasts from certain patients with the photosensitivity dermatitis/actinic reticuloid syndrome show enhanced sensitivity to ultraviolet radiation compared to normal fibroblasts. To probe further the link between oxidative damage and this disease, we have obtained a more extensive set of cell lines from patients with a severe form of the disease and examined their sensitivity towards oxidative stress by measuring cell survival following UVA radiation (330-450 nm) or hydrogen peroxide treatment (0.1-2.4 mM). The activation of the stress gene, heme oxygenase, has also been assessed by measuring the accumulation of mRNA after hydrogen peroxide treatment. Our studies have confirmed that a slight ultraviolet sensitivity is a characteristic of photosensitivity dermatitis/actinic reticuloid syndrome cell strains and we further demonstrate that these cell lines are particularly sensitive to hydrogen peroxide with up to a three- to fourfold increased sensitivity as compared to normal controls. We also show that certain ataxia telangiectasia strains that are especially sensitive to hydrogen peroxide are also slightly sensitive to ultraviolet radiation. Hydrogen peroxide induces accumulation of mRNA for the oxidant-inducible stress protein, heme oxygenase, with similar kinetics (maximum mRNA accumulation 2-4 h following treatment) and with a similar range of magnitudes in both normal (6.6-20.6 times mRNA increase over basal levels) and photosensitivity dermatitis/actinic reticuloid (2.9-12.8 times) skin cells. Because cells from photosensitivity dermatitis/actinic reticuloid patients show increased sensitivity towards oxidative stress but show no significant change in oxidant activation of the heme oxygenase gene, we propose that the defect involves a late stage of processing of oxidative damage rather than a compromised free radical scavenging system.

Adolescent↗

Interleukin-3 administration enhances human monocyte function in vivo.

In addition to its haemopoietic effects, interleukin-3 (IL-3) enhances leucocyte function in vitro. In this study we examined the effects on haematological variables and monocyte function of a single IL-3 infusion in five haematologically normal individuals. There was a rapid fall in circulating monocyte (to 24 +/- 6% of pre-infusion value) and eosinophil numbers (to 3 +/- 2%) with a nadir at 30 min and gradual return to baseline over 6 h. No significant changes in monocyte expression of the adhesion molecules CD11b or L-selectin or of monocyte respiratory burst activity were detected. There was a significant increase in monocyte phagocytosis and killing of Candida after IL-3 infusion: the percentage of monocytes which had ingested Candida increased from 39 +/- 10% to 62 +/- 12% and the total number of Candida killed per 100 monocytes increased from 63 +/- 34 to 210 +/- 59 (P < 0.05 and P < 0.01 respectively). There was no inhibition of neutrophil migration into a 'skin window' site and monocyte migration was moderately enhanced (peak increase of 260 +/- 47%). These results show that IL-3 has significant effects on monocyte function in vivo and could be of use in augmenting host defence mechanisms in immunocompromised patients.

CD11 Antigens↗

Siblings and eating disorders: a phenomenological perspective.

The purpose of this study was to develop an increased awareness of the sibling experience in families where one child has an eating disorder. Using a phenomenological approach, five female adolescents whose sisters had been diagnosed with anorexia nervosa each participated in two open-ended, unstructured interviews, which were coded and analysed using methods consistent with phenomenological research. Two overarching constructs evolved, which subsumed five major themes. All siblings (1) described intense and conflicted emotions, and (2) experienced their sisters' illness as a pervasive phenomenon in their lives. In this context, perspective of the illness, disruption of intra- and extrafamilial relationships, role strain, special status awarded the anorectic sister, and coping with the illness were significant themes which emerged for participants. Findings support the need for nurses to be involved in family-focused health care practice, and to be cognizant of the impact on siblings in families where one member's illness is a factor.

Adaptation, Psychological↗

Temperature may be an appropriate sensor for chronotropically incompetent patients with postural syncope.

Chronotropically incompetent patients benefit most from sensor driven rate response during exercise. Postural syncope may occur despite the chronotropic response because of the failure of currently available sensors to respond physiologically to postural changes. Seven chronotropically incompetent patients with postural syncope who had a dual chamber rate adaptive pacemaker (Circadia) that modulates heart rate in response to temperature change were studied with respect to: (1) response to exercise; and (2) head-up tilt (HUT). During exercise, continuous-wave Doppler of aortic velocities and two-dimensional echocardiographic derived measurements of left ventricular systolic function were used to assess cardiac function. Patients exercised longer (by an average of 168 sec) in the DDDR compared to the DDI mode (P = 0.013). Increase in exercise duration was due mostly to the sensor driven increase during DDDR pacing. During DDDR pacing, heart rate increased from 71 +/- 6 to 121 +/- 17 ppm compared to 70 +/- 1 to 103 +/- 21 ppm for the DDI pacing (P = 0.038). Stroke volume as assessed by Doppler derived stroke distance (SD) contributed more significantly to the cardiac output increase during exercise in the DDI mode (SD increased from 13.4 +/- 4 to 18 +/- 7 cm in DDI compared to 13 +/- 4 to 14 +/- 2 cm in DDDR mode), although these mechanisms were insufficient to fully compensate for failure of appropriate chronotropic response. In response to the HUT, right ventricular temperature increased from 36.78 degrees C +/- 0.29 degrees C to 36.89 degrees +/- 0.28 degrees C (P = 0.0002), and heart rate increased from 54 +/- 3 to 71 +/- 8 ppm (P = 0.0003) in the DDDR mode. No significant change in heart rate occurred in the DDI mode in response to the HUT. Strong positive correlation of temperature and heart rate was noted in all patients in response to HUT (P = 0.001, R2 = 0.755-0.976). We conclude that temperature sensor responds physiologically to exercise and HUT. Therefore, temperature sensing rate adaptive dual chamber pacing may be appropriate for chronotropically incompetent patients with posture related syncope.

Aged↗

Efficacy of Selected Respiratory Protective Equipment Challenged with Bacillus subtilis subsp. niger.

The efficacy of powered air-purifying respirators, surgical masks, dust/mist respirators, and high-efficiency respirators were tested with a biological aerosol under simulated breathing conditions. Protective ability ranged from 67 to 99.95%. The majority of penetration in negative-pressure respirators occurred at the face-mask interface rather than through the filter material.

Journal Article↗

Effect of treatment on titer, function, and antigen recognition of serum antibodies to Actinobacillus actinomycetemcomitans in patients with rapidly progressive periodontitis.

Although periodontal treatment by scaling and root planing (SCRP) is known to induce bacteremia, the effect of this procedure on the host immune response is not known. We have determined pre- and post-SCRP immunoglobulin G antibody titers to antigens of Actinobacillus actinomycetemcomitans in the sera of 22 patients with rapidly progressive periodontitis. We also assessed the ability of these sera to enhance phagocytosis and killing of A. actinomycetemcomitans by human polymorphonuclear leukocytes by using a polymorphonuclear leukocyte chemiluminescence (CL) assay. Specific anti-A. actinomycetemcomitans antibody titers were significantly increased at 6 and 12 months after beginning treatment, and CL values were significantly increased at 12 months, whereas mean interproximal pocket depths were significantly decreased at 12 months after beginning treatment. When patients were classified as either seropositive (twice the median titer of control subjects; n = 10) or seronegative (n = 12), both median titers and CL values were significantly increased for the seronegative group at 6 and 12 months after treatment. In the seropositive group, only the median titer was significantly increased at 12 months. Western blot (immunoblot) patterns for six seronegative and six seropositive patients differed remarkably at the baseline. Before treatment, all of the seropositive patients recognized high-molecular-mass lipopolysaccharide (LPS) and a large number of protein components. Patterns were virtually unaffected by therapy. Before treatment, only one of the seronegative patients recognized the LPS smear and none reacted strongly with protein components. Following treatment, slight LPS staining was observed for five of six seronegative patients and detection of protein bands was enhanced in all cases. We conclude that treatment by SCRP induces a humoral immune response, especially in seronegative patients, and that response may play a role in the observed beneficial effects of periodontal treatment.

Adult↗

Experimental Brucella abortus strain 19 arthritis in young cattle.

Several reports have shown an association between lameness in cattle and vaccination with Brucella abortus strain 19. Affected joints are culture negative for Brucella, but the synovial fluid is positive for B. abortus antibodies. The joints contain cloudy fluid, with villous proliferation of the synovium. Brucella abortus antigens are often found in the synovium with fluorescent antibody staining. This report describes the experimental reproduction of a chronic synovitis in 6 young Angus steers using intra-articular injections of B. abortus strain 19. The carpal and tibial joints were injected with 5 x 10(9) colony-forming units/ml of B. abortus strain 19 and regularly biopsied over a 28-day period. Steers started becoming serologically positive for B. abortus on post-inoculation day (PID) 5 and were all positive by PID 7. Joints were cultured and examined by fluorescent antibody staining, immunohistochemical methods, and light and transmission electron microscopy. Lesions typical of the field cases were present by PID 21. Brucella abortus was cultured more often during PID 1-5 (6 of 9 joints) than during PID 7-28 (3 of 15 joints). Brucella abortus was only found on PID 1 and 5 by fluorescent antibody staining and in only 2 joints immunohistochemically on PID 5 and 7. The reproduction of lesions typical of field cases but the inability to locate B. abortus antigens in the synovium raises the question of whether in field cases the synovium is continually or intermittently seeded with bacteria or if factors other than just the bacterium are needed to perpetuate the lesion.

Animals↗

Development of methods to monitor exposure to 1-nitropyrene.

On the basis of 32P-postlabeling analysis, treatment of rats with 1-nitropyrene (1-NP) resulted in the formation of multiple DNA adducts in the liver, mammary glands, and peripheral lymphocytes. The one adduct resulting from nitroreduction, N-(deoxyguanosin-8-yl)-1-aminopyrene, constitutes only a minor component among the adducts. In the present study, incubation of calf thymus DNA with mutagenic ring-oxidized metabolites of 1-NP in vitro in the presence and absence of xanthine oxidase also resulted in the formation of multiple adducts. On the basis of their chromatographic behavior, it appears that DNA adducts derived from such metabolites may have been formed in vivo; however, this needs to be confirmed. [3H]1-NP was given to male and female F344 rats and Sprague-Dawley rats by gavage at five dose levels in the range of 0.1 to 1000 micrograms/kg bw. This led to stable hemoglobin adducts accounting for 0.08 +/- 0.05% of the dose (n = 3 rats). The radioactivity associated with hemoglobin following administration of [3H]1-NP was cleared with a half-life of about 14 days, which is faster than that of unmodified erythrocytes in the rat (t1/2 = 30 days). Treatment of the hemoglobin with 1% HCl in acetone, to precipitate the globin, released the radioactivity; it was all bound to the heme moiety. The structures of the heme adducts have not been elucidated; yet, because of their stability, they may be useful as dosimeters for human exposure to 1-NP.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Oral↗