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D Johnson

Publications and source records attributed to D Johnson.

At least 55 records · Page 3Linked to original sources
PubMed2001

Are keloids really "gli-loids"?: High-level expression of gli-1 oncogene in keloids.

BACKGROUND: Keloids are a common lesion arising from sites of previous trauma and are a considerable source of morbidity because of continued growth of lesions, pruritus, and physical appearance. They consist of mesenchymal cells embedded in a stroma of disordered collagen matrix. Clinically, keloids are distinguished from scars in that keloids demonstrate continued growth over the borders of the original injury. Keloids appear with increased frequency in patients of African and Asian descent. Currently, no entirely satisfactory method of treatment exists for these lesions. Recently, a patient who was enrolled in a clinical trial of topical tacrolimus for atopic dermatitis applied this drug to a keloid and noted clearing. OBJECTIVE: Based on this clinical observation and the observation that rapamycin, a chemically similar compound to tacrolimus, is known to inhibit signaling from the gli-1 oncogene, we examined keloids and scars for expression of Gli-1 protein. METHODS: Skin sections from keloids and scars were examined by immunohistochemical staining for gli-1. To further confirm the presence of gli-1 expression in keloids, reverse transcriptase-polymerase chain reaction was carried out. RESULTS: Expression of gli-1 was strongly elevated in keloids compared with scars. CONCLUSION: These results provide a rationale for the treatment of keloids with topical rapamycin analogs, including tacrolimus. Clinical trials of topical tacrolimus are warranted.

DNA↗
PubMed2001

Induction chemoradiation and surgical resection for non-small cell lung carcinomas of the superior sulcus: Initial results of Southwest Oncology Group Trial 9416 (Intergroup Trial 0160).

OBJECTIVE: The rate of complete resection (50%) and the 5-year survival (30%) for non-small cell lung carcinomas of the superior sulcus have not changed for 40 years. Recently, combined modality therapy has improved outcome in other subsets of locally advanced non-small cell lung carcinoma. This trial tested the feasibility of induction chemoradiation and surgical resection in non-small cell lung carcinoma of the superior sulcus with the ultimate aim of improving resectability and survival. METHODS: Patients with mediastinoscopy-negative T3-4 N0-1 superior sulcus non-small cell lung carcinoma received 2 cycles of cisplatin and etoposide chemotherapy concurrent with 45 Gy of radiation. Patients with stable or responding disease underwent thoracotomy 3 to 5 weeks later. All patients received 2 more cycles of chemotherapy and were followed up by serial radiographs and scans. Survival was calculated by the Kaplan-Meier method and prognostic factors were assessed for significance by Cox regression analysis. RESULTS: From April 1995 to September 1999, 111 eligible patients (77 men, 34 women) were entered in the study, including 80 (72.1%) with T3 and 31 with T4 tumors. Induction therapy was completed as planned in 102 (92%) patients. There were 3 treatment-related deaths (2.7%). Cytopenia was the main grade 3 to 4 toxicity. Of 95 patients eligible for surgery, 83 underwent thoracotomy, 2 (2.4%) died postoperatively, and 76 (92%) had a complete resection. Fifty-four (65%) thoracotomy specimens showed either a pathologic complete response or minimal microscopic disease. The 2-year survival was 55% for all eligible patients and 70% for patients who had a complete resection. To date, survival is not significantly influenced by patient sex, T status, or pathologic response. CONCLUSIONS: (1) This combined modality treatment is feasible in a multi-institutional setting; (2) the pathologic complete response rates were high; and (3) resectability and overall survival were improved compared with historical experience, especially for T4 tumors, which usually have a grim prognosis.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed2001

Cardiac surgery increases the activity of matrix metalloproteinases and nitric oxide synthase in human hearts.

OBJECTIVES: Heart function is variably impaired after cardiopulmonary bypass. We hypothesized that, similar to other myocardial injury states, cardiopulmonary bypass leads to enhanced activity of nitric oxide synthase and matrix metalloproteinases. METHODS: We obtained right atrial biopsy specimens and plasma samples at the onset and termination of cardiopulmonary bypass in 10 patients. Biopsy specimens were analyzed for nitric oxide synthase activity by using a citrulline assay, whereas plasma and tissue were analyzed for matrix metalloproteinase-9 and matrix metalloproteinase-2 activity by using zymography. Tissue inhibitor of metalloproteinase-4 was analyzed by means of Western blotting. The cellular expression of inducible nitric oxide, endothelial nitric oxide synthase, matrix metalloproteinase-2, and matrix metalloproteinase-9 was determined in right atrial biopsy samples from 3 additional patients by using the appropriate conjugated antibodies. RESULTS: Nitric oxide synthase activity increased from the beginning to the end of bypass (4.46 +/- 1.07 vs 16.77 +/- 4.86 pmol citrulline/mg of protein per minute, respectively; P =.018). Pro-matrix metalloproteinase-9 activity increased in hearts (199 +/- 41 vs 660 +/- 177 density units/mg protein; P =.008) and plasma (14.1 +/- 4.6 vs 52.2 +/- 5.9 density units/mg protein; P =.008). Pro-matrix metalloproteinase-2 activity increased in the heart (201 +/- 23 vs 310 +/- 35 density units/mg protein, P <.05) but not in plasma. Tissue inhibitor of metalloproteinase-4 expression in the heart decreased (1574 +/- 280 vs 864 +/- 153 density units, P =.014). CONCLUSIONS: Cardiopulmonary bypass activates enzymes mediating acute inflammation and organ injury (ie, nitric oxide synthase, matrix metalloproteinase-9, and matrix metalloproteinase-2). Decreased tissue inhibitor of metalloproteinase-4 expression allows relatively unopposed increases in matrix metalloproteinase tissue activity. We postulate that these changes play a role in the pathogenesis of heart dysfunction after bypass surgery.

Aged↗
PubMed2001

Increased prostatic lysophosphatidylcholine acyltransferase activity in human prostate cancer: a marker for malignancy.

PURPOSE: Phospholipase A2 and lysophosphatidylcholine acyltransferase (LAT) constitute a deacylation-reacylation cycle that incorporates arachidonic acid into the lipid membrane. In a preliminary report we found increased LAT activity in malignant prostate tissue. We measured LAT activity in prostate tissue from a large number of patients undergoing prostatectomy. MATERIALS AND METHODS: Prostate tissue from 93 patients undergoing radical prostatectomy for prostate carcinoma, 14 undergoing cystoprostatectomy for bladder cancer, 55 undergoing transurethral resection for benign prostatic hyperplasia and 11 with prostate cancer undergoing transurethral resection for relief of obstructive symptoms was analyzed for LAT activity. RESULTS: In radical prostatectomy specimens using oleoyl coenzyme A as substrate mean increase in LAT activity between malignant and benign portions of the same specimen was 0.68 +/- 0.12 nmol./mg. protein per minute (p <0.00001). In all radical prostatectomy specimens analyzed LAT activity was 43% higher in the malignant than benign portions (2.25 +/- 0.15 versus 1.57 +/- 0.11 nmol./mg. protein per minute, p <0.001). In the 10 benign prostate specimens obtained from cystoprostatectomy mean LAT activity was 1.12 +/- 0.18 nmol./mg. protein per minute, which was significantly lower than that of benign portions of radical prostatectomy (p <0.05). LAT activity in benign cystoprostatectomy specimens was significantly higher than that in the 50 benign transurethral resection specimens (0.54 +/- 0.05, p <0.01), possibly due to heat damage in transurethral resection specimens during collection. However, LAT activity in transurethral resection specimens from patients with known prostate cancer was similarly increased. Similar results were obtained using arachidonoyl coenzyme A. CONCLUSIONS: We demonstrated increased LAT activity in malignant tissue from patients with prostate cancer. Thus, the deacylation-acylation remodeling cycle may be enhanced to provide more arachidonic acid to meet the demand for prostaglandin E2 synthesis in malignant tissue.

1-Acylglycerophosphocholine O-Acyltransferase↗
PubMed2001

Baclofen overdose in two siblings.

Baclofen is a muscle relaxant used in both adults and children with neuromuscular disorders to control spasticity. In children, relatively few cases of overdose have been previously reported. We report two cases of baclofen overdose occurring in two siblings. One sibling with cerebral palsy was being treated with baclofen at the time of overdose. Both cases presented with severe respiratory depression requiring mechanical ventilation. Serum baclofen concentrations from both children were significantly elevated. We also review the published literature on baclofen overdose in children and adolescents. These cases emphasize the importance of warning parents about the potential toxicity of baclofen when prescribing the drug to a family member.

Baclofen↗
PubMed2001

Prevalence and mechanisms of macrolide resistance in Streptococcus pyogenes in Santiago, Chile.

Thirty-two macrolide-resistant Streptococcus pyogenes isolates were found among 594 clinical isolates collected from 1990 to 1998 in Santiago, Chile, for an overall prevalence of 7.2%. Among the 32 resistant isolates, 28 (87.5%) presented the M phenotype and 4 (12. 5%) presented the MLS(B) phenotype. Serotyping and pulsed-field gel electrophoresis analysis showed genetic diversity among the resistant isolates.

Anti-Bacterial Agents↗
PubMed2001

Resetting of the cardiopulmonary baroreflex 10 years after surgical repair of coarctation of the aorta.

OBJECTIVE: To characterise cardiopulmonary baroreflex responses and examine the effects of a 45 minute cycling bout late after successful repair of coarctation of the aorta. SUBJECTS: 10 young adults (mean (SEM) age 18.1 (2.6 years)) operated on for coarctation of the aorta 12.7 (3.5) years earlier, and 10 healthy controls. DESIGN: Forearm blood flow (venous occlusion plethysmography) and vascular resistance, left ventricular internal diastolic diameter, and central venous pressure estimated from an antecubital vein were measured in the supine position at baseline and during five minute applications of lower body negative pressure (LBNP) at -15 mm Hg (LBNP(-15)) and -40 mm Hg (LBNP(-40)). Venous samples were obtained at baseline and during LBNP(-40) for noradrenaline (norepinephrine), adrenaline (epinephrine), renin activity, and aldosterone. The tests were repeated after 45 minutes of moderate exercise. RESULTS: Baseline heart rate (78 (9) v 64 (6) beats/min), echocardiographic cardiac output (6.9 (1.1) v 5.0 (0.2) l/min), shortening fraction (41.7 (1.8)% v 33.3 (1.3)%), and forearm blood flow (3.4 (0.4) v 2.3 (0.3) ml/100 g/min) were higher in the coarctation group than in the controls (p < 0.05). Changes in forearm blood flow and forearm vascular resistance from baseline to LBNP(-40) were similar in both groups, but the relation between forearm vascular resistance and estimated central venous pressure or left ventricular internal diastolic diameter was shifted downward in the coarctation group. Plasma adrenaline was increased in the coarctation group (baseline: 3.2 (0.6) v 2.4 (0.3) pmol/l in controls; LBNP(-40): 687 (151) v 332 (42) pmol/l) (p < 0.05). Both groups showed a similar downward displacement of forearm vascular resistance (p < 0.05) after exercise. CONCLUSIONS: There appears to be resetting of the cardiopulmonary baroreflex to a lower forearm vascular resistance in young adults operated on for coarctation of the aorta, associated with hyperdynamic left ventricular function. Raised circulating adrenaline could contribute to the lower forearm vascular resistance.

Adolescent↗
PubMed2001

Gender differences in temperature and vascular characteristics during exercise recovery.

Temperature and vascular responses during exercise recovery were examined in men and women of similar age and fitness status (VO2max: 76 +/- 5 vs 73 +/- 5 mL O2 / kg Fat Free Mass x min). Forearm blood flow (venous occlusion plethysmography; FBF), rectal (Trectal) and forearm skin (Tskin) temperatures (degree C) were measured before and every 15 min up to 105 min (t105) during recovery from a 45-min run at 75% of VO2max. Results indicate Trectal decreased to pre-exercise levels within 25 min in men but reached and remained at values lower than baseline between 60 and 105 min of recovery in women. From 90 to 105 min of recovery, Tskin was lower in women than men (t105 : 29.0 +/- 1.3 vs 30.7 +/- 1.5; p <.05). Recovery FBF (mL/100mL x min) was higher in men than women from the start (6.2 +/- 1.9 vs 4.9 +/- 1.9) to the end of recovery (t105 = 1.7 +/- 0.6 vs 2.6 +/- 1.1) (p <.05). Heat flux calculated at the forearm was higher in women and increased throughout the last hour of recovery (p <.05). Further investigations are needed to examine mechanisms underlying failure of post-exercise core and skin temperatures in women to stabilize at pre-exercise levels.

Adult↗
PubMed2001

Direct evidence for tonic sympathetic support of resting metabolic rate in healthy adult humans.

The sympathetic nervous system (SNS) plays an important role in the regulation of energy expenditure. However, whether tonic SNS activity contributes to resting metabolic rate (RMR) in healthy adult humans is controversial, with the majority of studies showing no effect. We hypothesized that an intravenous propranolol infusion designed to achieve complete beta-adrenergic blockade would result in a significant acute decrease in RMR in healthy adults. RMR (ventilated hood, indirect calorimetry) was measured in 29 healthy adults (15 males, 14 females) before and during complete beta-adrenergic blockade documented by plasma propranolol concentrations > or =100 ng/ml, lack of heart rate response to isoproterenol, and a plateau in RMR with increased doses of propranolol. Propranolol infusion evoked an acute decrease in RMR (-71 +/- 11 kcal/day; -5 +/- 0.7%, P < 0.0001), whereas RMR was unchanged from baseline levels during a saline control infusion (P > 0.05). The response to propranolol differed from the response to saline control (P < 0.01). The absolute and percent decreases in RMR with propranolol were modestly related to baseline plasma concentration of norepinephrine (r = 0.38, P = 0.05; r = 0.44, P = 0.02, respectively). These findings provide direct evidence for the concept of tonic sympathetic beta-adrenergic support of RMR in healthy nonobese adults.

Adrenergic beta-Antagonists↗
PubMed2001

Prevalence and causes of low bone density and fractures in kidney transplant patients.

Osteoporosis is known to occur in patients with kidney transplants, but limited information is available about the prevalence and causes of this complication. We asked all 330 patients with kidney transplants in our unit to participate in this study of whom 165 (50%) agreed to do so. The characteristics of the participating patients were similar to the remaining 165 nonparticipants. Seventy of 165 (42%) of the participants were women of whom 40 were postmenopausal in contrast to the men of whom only one was hypogonadal. Bone mineral density (BMD) was significantly reduced at the radius (Z score, -1.5) and femoral neck (Z score, -0.7), but the lumbar spine was normal. BMD was lower in women than men at all skeletal sites. Osteoporosis was found in 10-44% and osteopenia was found in 35-50% of women depending on the site. BMD was related inversely to time since transplantation and cumulative prednisolone dose. Twenty-seven of the 165 (16%) patients had either vertebral deformities or a history of a low trauma fracture after transplantation. This fracture group consisted of 10/27 (37%) men and 17/27 (63%) women, of whom 14 were postmenopausal. Fracture patients tended to be older and have a longer duration of renal failure, dialysis, transplantation, greater cumulative steroid dose, and higher bone resorption markers than the nonfracture group. No differences were found for cumulative doses of cyclosporin or tacrolimus. Logistic regression showed that only duration of dialysis and time since transplantation significantly increased fracture risk, with odds ratio (OR) for each year of dialysis or transplantation being 1.21 (CI, 1.00-1.48) and 1.14 (CI, 1.05-1.23), respectively. These data show that low bone density and fractures are common in patients with kidney transplant and are determined by both pre- and posttransplant variables. Fracture risk was greatest in women, particularly if they were postmenopausal and we recommend that this subgroup is targeted for assessment and treatment.

Adolescent↗
PubMed2001

Identification of novel genes differentially expressed in omental fat of obese subjects and obese type 2 diabetic patients.

Obesity is associated with an increased risk for developing type 2 diabetes, insulin resistance, hypertension, dyslipidemia, cardiovascular disease, respiratory dysfunction, and certain forms of cancer. Insulin resistance in many type 2 diabetic patients is the result of increased visceral adiposity. To identify novel genes implicated in type 2 diabetes and/or obesity and to elucidate the molecular mechanisms underlying both diseases, we analyzed gene expression in omental fat from lean and obese nondiabetic subjects and obese type 2 diabetic patients using mRNA differential display and subtracted library techniques. After screening over 13,800 subtracted cDNA clones and 6,912 cDNA amplification products, we identified 2,078 cDNAs that showed potential differential expression in the omental fat of lean versus obese nondiabetic subjects versus obese type 2 diabetic patients. Data analysis showed that 70.7% of these clones corresponded to unknown genes (26.7% matched express sequence tags [ESTs]) and 29.3% corresponded to known genes. Reverse Northern and classic Northern analyses further confirmed that the expression of five of these cDNA clones was elevated in obese nondiabetic subjects and obese type 2 diabetic patients. Four candidate genes were further evaluated for tissue distribution, which showed expression primarily in adipose and skeletal muscle tissue, and chromosomal localization. We concluded that both mRNA differential display and subtracted cDNA libraries are powerful tools for identifying novel genes implicated in the pathogenesis of obesity and type 2 diabetes.

Adipose Tissue↗
PubMed2001

Music as a therapeutic intervention for anxiety in patients receiving radiation therapy.

PURPOSE/OBJECTIVES: To determine whether music moderates the level of anxiety that patients experience during radiation therapy. DESIGN: Experimental, longitudinal, random assignment to music or no music therapy. SETTING: Urban radiation oncology center in a Department of Veterans Affairs hospital in the southeastern United States. SAMPLE: Forty-two men (19 in the experimental group, 23 in the control group) aged 39-80 years (74% white, 12% African American, 12% Hispanic, and 2% other) receiving definitive external beam radiation therapy for pelvic or abdominal malignancies. METHODS: Patients in the experimental group listened to music of their choice provided via audiotapes and headphones before and during their simulation and daily treatments for the duration of the planned course of therapy. The control group received standard care. The State-Trait Anxiety Inventory was administered initially to participants in both groups at the time of evaluation (time 1), post-simulation (time 2), at the end of the first week (time 3), at the end of the third week (time 4), and at the end of the fifth week or end of radiation therapy (time 5). MAIN RESEARCH VARIABLE: State anxiety. FINDINGS: No significant difference existed between the two groups to suggest that music moderated the level of anxiety during radiotherapy. However, post-hoc analyses identified changes and trends in state anxiety scores, suggesting a possible benefit of music therapy during radiotherapy. CONCLUSIONS: Despite a lack of group differences, early intervention with music therapy for patients with high levels of anxiety may be beneficial. IMPLICATIONS FOR NURSING PRACTICE: Nurses and other clinicians may administer state anxiety scales at the initial visit or prior to pretreatment radiation planning (simulation). Individuals who have high state anxiety scores may receive nursing interventions tailored to reduce anxiety during simulation and the early part of radiotherapy.

Adult↗
PubMed2000

Sequence and analysis of chromosome 5 of the plant Arabidopsis thaliana.

The genome of the model plant Arabidopsis thaliana has been sequenced by an international collaboration, The Arabidopsis Genome Initiative. Here we report the complete sequence of chromosome 5. This chromosome is 26 megabases long; it is the second largest Arabidopsis chromosome and represents 21% of the sequenced regions of the genome. The sequence of chromosomes 2 and 4 have been reported previously and that of chromosomes 1 and 3, together with an analysis of the complete genome sequence, are reported in this issue. Analysis of the sequence of chromosome 5 yields further insights into centromere structure and the sequence determinants of heterochromatin condensation. The 5,874 genes encoded on chromosome 5 reveal several new functions in plants, and the patterns of gene organization provide insights into the mechanisms and extent of genome evolution in plants.

Animals↗
PubMed2000

A novel ATPase on mouse chromosome 7 is a candidate gene for increased body fat.

A region of mouse chromosome 7, just distal to the pink-eyed (p) dilution locus, contains a gene or genes, which we have named p-locus-associated obesity (plo1), affecting body fat. Mice heterozygous for the most distally extending chromosomal deletions of this region have nearly double the body fat of mice when the deletion is inherited maternally as when it is inherited paternally. We have physically mapped the 1-Mb critical region, which lies between the Gabrb3 and Ube3a/Ipw genes, and DNA sequencing has localized a new member of the third subfamily of P-type ATPases to the minimal region specifying the trait. This gene, which we have called p-locus fat-associated ATPase (pfatp) is differentially expressed in human and mouse tissues with predominant expression in the testis and lower levels of expression in adipose tissue and other organs. We propose this ATPase as the prime candidate for the gene at the plo1 locus modulating body fat content in the mouse. The unusual inheritance pattern of this phenotype suggests either genomic imprinting, known to occur in other local genes (Ube3a, Ipw), or an effect of maternal haploinsufficiency during pregnancy or lactation on body fat in the progeny.

Adenosine Triphosphatases↗
PubMed2000

High-risk behaviors during incarceration in African-American men treated for HIV at three Los Angeles public medical centers.

OBJECTIVES: This paper describes research that examined the association between high-risk sexual and drug-using behaviors during incarceration and HIV infection for African-American men receiving HIV care at three public medical centers in Los Angeles County (LAC), California. METHODS: A case-control study was conducted in which 305 HIV-infected African-American men and 305 neighborhood controls, ages 20 to 49, were frequency-matched by age. RESULTS: After controlling for anal sex while not incarcerated, we found no association between anal sex during incarceration and HIV (odds ratio [OR], 1.1; 95% confidence interval [CI], 0.6-2.2). Among men with a history of incarceration (n = 332), the percentage reporting anal sex with men outside of incarceration (45%) was greater than those reporting anal sex while incarcerated (16%). Injection drug use (IDU) during incarceration was also not associated with HIV when controlling for IDU outside of incarceration (OR, 1.6; 95% CI, 0.5- 4.9). Increased time in jail or prison was associated with less HIV infection (p =.001). CONCLUSIONS: Although high-risk behaviors are more common in the community than in the incarcerated setting for this study group, incarcerated populations represent a high-risk group for whom access to prevention messages is limited. Periods of incarceration represent a unique opportunity to convey prevention messages that focus on high-risk behaviors outside the incarcerated setting.

Adult↗