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Biomedical subjects

C Johnson

Publications and source records attributed to C Johnson.

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

Seasonal variation in bone lead contribution to blood lead during pregnancy.

Population blood lead level (PbB) often shows seasonal variation, frequently being higher in summer and lower in winter. As vitamin D metabolites also show seasonal variability, and the metabolites are associated with bone metabolism, some authors have posited a role for bone lead release in seasonal PbB changes. We made third trimester and postdelivery PbB measurements on 414 immigrant women (98% Latina) in Los Angeles. We measured in vivo tibia and calcaneus (heel) lead concentration postdelivery via K-shell X-ray fluorescence. We saw evidence of seasonal variation in prenatal PbB, but not postnatal PbB. PbB was highest in spring and lowest in autumn. Tibia lead concentration was associated with prenatal PbB, as reported before. The contribution of tibia lead to prenatal PbB varied seasonally, with the greatest contribution occurring in the winter quarter and the least in the summer quarter. The temporal pattern of bone lead contribution to PbB follows the seasonal alteration of insolation. There was no seasonal component in prenatal PbB associated with calcaneus lead, nor were there seasonal variations in either calcaneus or tibia lead contributions to postnatal PbB. Bone turnover in the third trimester of pregnancy may be higher in winter months than in summer months, resulting in greater fetal lead exposure in spring than at other times of the year.

Bone and Bones↗
PubMed2001

Evidence for the involvement of the NADPH oxidase enzyme complex in the optimal accumulation of Platelet-activating factor in the human cell line PLB-985.

Platelet-activating factor (PAF) is an early product of the inflammatory environment, influencing development and resolution of inflammation. Its production is greater in neutrophils and macrophages, which predominantly synthesize 1-alkyl sn-2 acetyl glycerophosphocholine (GPC) than in nongranulocytes (B cells and endothelial cells), which lack a respiratory burst and synthesize 1-acyl sn-2 acetyl GPC as their major PAF species. This study investigated whether the respiratory burst was responsible for the quantitative and qualitative differences in sn-2 acetyl GPC species generation by neutrophils and macrophages versus those cells lacking the NADPH oxidase complex. The myeloid cell line PLB-985 (capable of differentiation into neutrophils) was used to test this hypothesis, since these cells had previously been generated with a non-functional respiratory burst (X-CGD PLB-985). Differentiated PLB-985 cells underwent a large respiratory burst in response to PMA (phorbol ester), and smaller respiratory bursts in response to A23187 (calcium ionophore), and the bacterial polypeptide fMLP (receptor mediated activation). Concurrently, treated cells were assessed for production of 1-hexadecyl and 1-palmitoyl sn-2 acetyl GPC species by gas chromatography/mass spectrometry. Neither cell type generated these lipid species in response to PMA, but both cell types generated equal levels of sn-2 acetyl GPC in response to A23187, with five times more 1-hexadecyl than 1-palmitoyl species. Upon fMLP activation, X-CGD PLB-985 cells produced significantly less 1-hexadecyl and 1-palmitoyl sn-2 acetyl GPC in comparison to the wild-type PLB-985 cells. These findings suggest phagocytic oxidant production by NADPH oxidase is not essential for sn-2 acetyl GPC generation, but appears important for optimal production of PAF in response to some stimuli.

Calcimycin↗
PubMed2001

Clinical isolates of Streptococcus pneumoniae resistant to levofloxacin contain mutations in both gyrA and parC genes.

Thirty Streptococcus pneumoniae clinical isolates resistant to levofloxacin were analyzed for the quinolone resistance-determining DNA sequences to identify point mutations and were tested for in vitro susceptibility to multiple drug classes. Of these isolates, 29 had mutations in both gyrA and parC genes of DNA gyrase and topoisomerase IV, respectively. In GyrA, an amino acid change from Ser-81-->Phe was detected in 27 isolates and a Glu-85-->Lys change was found in the remaining three. Of the 29 isolates for which ParC data were available, Ser-79-->Tyr or Phe were the predominant mutations observed. MICs for levofloxacin were 4-16 mg/l, whereas those for moxifloxacin were 1-2 mg/l. Twenty-four (80%) isolates were susceptible to erythromycin, 25 (83%) to azithromycin, 26 (87%) to clarithromycin, 27 (90%) to clindamycin, 20 (67%) to penicillin, 21 (70%) to ceftriaxone and 30 (100%) to amoxycillin/clavulanate. These results confirm the presence of double mutations among clinical isolates of S. pneumoniae from diverse geographical regions of North America and also suggest that quinolone resistance may develop independently of resistance to other drug classes.

Amino Acid Substitution↗
PubMed2001

Activation peptide of carboxypeptidase B and anionic trypsinogen as early predictors of the severity of acute pancreatitis.

BACKGROUND: Early prediction of severity is important in the management of patients with acute pancreatitis. The presence of activation peptides and certain pancreatic proenzymes in plasma and urine has been shown to correlate with severity. This study was designed to assess the value of measuring levels of the activation peptide of carboxypeptidase B (CAPAP) and of anionic trypsinogen. METHODS: Concentrations of CAPAP and anionic trypsinogen were measured in the urine and serum in 60 patients with acute pancreatitis. Preset cut-off levels were used to analyse the accuracy of the tests. Severity was classified retrospectively according to the Atlanta classification. RESULTS: Concentrations of CAPAP in urine and serum and of anionic trypsinogen in urine correlated with the severity of the pancreatitis. CAPAP in urine showed the highest accuracy. The overall accuracy was 90 per cent, with a positive predictive value of 69 per cent and a negative predictive value of 98 per cent. CONCLUSION: In this study, measurement of CAPAP in urine was an accurate way to predict the severity of acute pancreatitis, and was superior to assay of anionic trypsinogen in urine and serum. Measurement of CAPAP in urine may be of value in the management of individual patients with pancreatitis and in the selection of patients for therapeutic trials.

Acute Disease↗
PubMed2001

Chloroplast lysates support directed mutagenesis via modified DNA and chimeric RNA/DNA oligonucleotides.

Chimeric RNA/DNA and modified DNA oligonucleotides have been shown to direct gene-conversion events in vitro through a process involving proteins from several DNA-repair pathways. Recent experiments have extended the utility of these molecules to plants, and we previously demonstrated that plant cell-free extracts are competent to support oligonucleotide-directed genetic repair. Using this system, we are studying Arabidopsis DNA-repair mutants and the role of plant proteins in the DNA-repair process. Here we describe a method for investigating mechanisms of plastid DNA-repair pathways. Using a genetic readout system in bacteria and chimeric or modified DNA oligonucleotides designed to direct the conversion of mutations in antibiotic resistance genes, we have developed an assay for genetic repair of mutations in a spinach chloroplast lysate system. We report genetic repair of point and frameshift mutations directed by both types of modified oligonucleotides. This system enables the mechanistic study of plastid gene repair and facilitates the direct comparison between plant nuclear and organelle DNA-repair pathways.

Arabidopsis↗
PubMed2001

In vivo target promoter-binding activities of a xenobiotic stress-activated TGA factor.

Xenobiotic chemicals induce the expression of nuclear detoxification genes. A full understanding of this protective response will require characterization of its transcriptional regulatory machinery. We describe here the use of a recently developed plant chromatin immunoprecipitation (ChIP) assay to define nuclear promoter targets of TGA1a, a tobacco basic/leucine zipper transcription factor whose activity is potentiated by herbicide-induced xenobiotic stress. TGA1a selectively binds as-1-type cis-elements, which regulate transcription of putative detoxification and defense genes. With ChIP, we show that endogenous TGA1a binds as-1-containing promoter sequences of two tobacco glutathione S-transferase genes, GNT1 and GNT35. This binding activity is strongly enhanced by xenobiotic stress, as is expression of these genes. In contrast, TGA1a apparently does not bind in vivo to functional as-1 elements in promoters of PR-1a and PG13, genes whose expression is insensitive to this stimulus. The findings here thus discriminate between a number of possible functional promoter binding sites for a trans-regulatory factor, within the context of a signal response pathway.

Antibodies↗
PubMed2001

Strontium-89 treatment for prostate cancer bone metastases: does a prostate-specific antigen response predict for improved survival?

A review of 50 patients treated with strontium-89 for prostate cancer bone metastases from January 1993-1997 at the Wellington Cancer Centre was undertaken to determine if there was any correlation between changes in prostate-specific antigen (PSA) following treatment and subsequent survival. Thirty cases were evaluable for PSA response. Of these, 14 had a fall in PSA following strontium-89 treatment, and their mean survival was 641 days. The remaining 16 patients did not demonstrate a post-treatment fall in PSA and their mean survival was 275 days. A difference between these two groups in the time to development of new bone symptoms following treatment was also observed. No significant correlation between pretreatment PSA and PSA response was observed. In conclusion, a PSA response following strontium-89 treatment appears to predict for improved survival in patients with bone metastases from carcinoma of the prostate. Further prospective studies are indicated.

Aged↗
PubMed2001

Static scapholunate dissociation: a new reconstruction technique using a volar and dorsal approach in a cadaver model.

We used 4 fresh-frozen cadaver arms to assess a method of reconstruction we designed for static scapholunate dissociation. The dorsal scapholunate ligament, scapholunate interosseous ligament, radioscapholunate, and radioscaphocapitate ligaments were sectioned. Radiographs were taken before sectioning, after sectioning, and after reconstruction. Passive motion was also measured before sectioning and after the repair. The dorsal scapholunate ligament was repaired directly; the palmar radioscapholunate and radioscaphocapitate ligaments were reconstructed using a free flexor carpi radialis tendon autograft and Mitek mini suture anchors (1.8-mm diameter and 5.4-mm length; Mitek Products, Norwood, MA) for anatomic fixation. An independent board-certified hand surgeon analyzed the radiographs of the wrists taken before and after sectioning and after reconstruction. Assessment of the unsectioned wrists revealed an average scapholunate angle of 45 degrees. After scapholunate dissociation was created the average scapholunate angle was 71 degrees. Repair of the dorsal scapholunate ligament alone did not improve the scapholunate angle. Average scapholunate angle after repair of the dorsal scapholunate ligament and reconstruction of the palmar ligaments was 43 degrees. Average range of motion on flexion, extension, and radial and ulnar deviation before ligament sectioning and after reconstruction was unchanged at 54 degrees, 59 degrees, 19 degrees, and 40 degrees respectively. This technique shows an improvement in scapholunate angle on lateral radiographs, and passive motion remained relatively unchanged.

Cadaver↗
PubMed2001

Symptom frequency and severity in patients with metastatic or locally recurrent lung cancer: a prospective study using the Lung Cancer Symptom Scale in a community hospital.

PURPOSE: To define symptoms and therapeutic requirements for patients with metastatic or locally recurrent lung cancer. METHODS AND MATERIALS: Data were collected from 69 consecutive patients with locally advanced lung cancer seen in consultation at a radiation oncology facility serving a community hospital in Virginia. The Lung Cancer Symptom Scale, a validated quality of life instrument, measured the incidence of symptoms in this group. RESULTS: Average survival for the entire group was 7 months. Fifty-seven patients received 81 courses of radiation therapy, 33 directed at thoracic disease and 48 delivered to sites of metastasis. Thirty-three percent of those who received radiation therapy required treatment to more than one anatomic site. Every patient was symptomatic at the time of consultation, with the number (p = 0.001) and severity (p = 0.001) of symptoms they suffered worse in the patient group seen 0 to 3 months prior to death rather than 4 to 6 months prior to death. With the exception of cough, symptoms were marked in their severity. CONCLUSIONS: Patients with advanced lung cancer suffer frequent and severe symptoms that worsen in the final months of life. The appropriate timing and combination of radiotherapy and chemotherapy are yet to be resolved. Future studies will require use of validated quality of life instruments to better catalogue palliation and treatment toxicity.

Aged↗
PubMed2001

Bacteriologic and clinical efficacy of high dose amoxicillin/clavulanate in children with acute otitis media.

OBJECTIVES: To determine the bacteriologic and clinical efficacy of high dose amoxicillin/clavulanate (90/6.4 mg/kg/day) against common bacterial pathogens causing acute otitis media (AOM), including penicillin-resistant Streptococcus pneumoniae (PRSP). METHODS: In this open label multicenter study, 521 infants and children with AOM [mean age, 18.6 months; age < 24 months, n = 375 (72%)] were treated with amoxicillin/clavulanate 90/6.4 mg/kg/day in two divided doses for 10 days. Bilateral otitis media, previous episodes of AOM, antibiotic treatment within 3 months and day-care attendance were recorded in 60.1, 35.7, 50.2 and 38.2% of the children, respectively. Tympanocentesis was performed before the first dose and repeated on Days 4 to 6 for all children with S. pneumoniae at 22 centers and for all children with any pathogen at 3 centers. Clinical response was assessed at end of therapy. RESULTS: Pathogens were isolated from 355 (68%) of 521 enrolled children; 180 children underwent repeat tympanocentesis and were bacteriologically evaluable. Baseline pathogens were S. pneumoniae (n = 122 enrolled/93 bacteriologically evaluable), Haemophilus influenzae (n = 160/51), both (n = 37/32) and others (n = 36/4). Pathogens were eradicated from 172 (96%) of 180 bacteriologically evaluable children. Overall 122 (98%) of 125 isolates of S. pneumoniae were eradicated, including 31 (91%) of 34 PRSP isolates (penicillin MICs 2 to 4 micrograms/ml). Seventy-eight (94%) of 83 isolates of H. influenzae were eradicated. Symptoms and otoscopic signs of acute inflammation were completely resolved or improved on Days 12 to 15 in 263 (89%) of 295 clinically evaluable children with bacteriologically documented AOM. CONCLUSIONS: On the basis of bacteriologic outcome on Days 4 to 6 and clinical outcome on Days 12 to 15, we found that high dose amoxicillin/clavulanate (90/6.4 mg/kg/day) was highly efficacious in children with AOM, including those most likely to fail treatment, namely children < 24 months of age and those with infectious caused by PRSP.

Acute Disease↗
PubMed2001

Reinforcement of occupational history taking: a success story.

BACKGROUND: This article describes the results of a retrospective study of 3 classes of medical students who participated in a targeted occupational and environmental health curriculum at the University of Connecticut School of Medicine. PURPOSE: We wanted to determine if targeted focused curricular interventions which integrated occupational and environmental health principles into routine history taking would result in increased scores on the number of questions posed during the Clinical Skills Assessment Program in the 4th year. METHODS: We analyzed Clinical Skills Assessment Program questions for 3 graduating medical school classes from 1997 to 1999. RESULTS: It appears that intense, focused training may increase the occupational and environmental questions which students ask. By revisiting the components of the history during the 3rd year, the final assessment of 4th-year students substantially and significantly increased. CONCLUSIONS: Those who wish to stem the decline in history-taking skills as students enter their clinical years should consider reinforcing these skills using structured programs and practice in areas of the history that are traditionally neglected but recognized as essential in gathering comprehensive data on patients.

Analysis of Variance↗
PubMed2001

Oncology thinking cap: scaffolded use of a simulation to learn clinical trial design.

BACKGROUND: Physicians often are called on to participate in and interpret clinical trials, but their training in this area may not provide them with the inquiry skills that are needed. Simulations have the potential to be a promising tool for helping medical students learn the skills involved in clinical trial design. However, simulations may be complex and require additional scaffolding to support learning. DESCRIPTION: The goal of this study was to teach aspects of cancer clinical trial design through the scaffolded use of a simulation, the Oncology Thinking Cap. The software-based scaffolding provided guidance in designing the trial. Subsequently, the simulation allowed students to run the designed trial, which produces detailed patient histories. This feedback then could be used to redesign the trial. EVALUATION: Twenty-four 4th-year medical students were asked to design a clinical trial in advance, on paper, to test a new anticancer drug. Student groups then designed and simulated running the clinical trial assisted by the software environment. Instructional effectiveness was measured using a pretest-posttest design that included having students (a) write a group research proposal and (b) individually critique a flawed proposal. At the group level (N = 6 groups), students demonstrated a 34% increase in the number of elements of a clinical trial that they included in their research proposals. At the individual level (N = 24), students improved by 48% in their critiques of flawed proposals. CONCLUSIONS: Scaffolding embedded in the simulator is a promising approach to helping students learn about clinical trial design.

Antineoplastic Agents↗
PubMed2001

The affective and memorial components of distinctiveness-based illusory correlations.

Two studies were conducted to test a model of the distinctiveness-based illusory correlation (IC) phenomenon that suggests there are two components operating with ICs: cognitive memorial, and affective. In Expt 1 (N = 118), two stimulus arrays were developed that were equivalent in regards to valence (good or bad extremity) but differed in regards to the affect dimension (high or low emotional intensity). Consistent with predictions drawn from the proposed model, the magnitude of the IC effect was higher in the high emotional intensity than in the low emotional intensity condition, but only significantly so on the measures (estimation and general evaluation) that have been hypothesized to be most sensitive to the affective component. In Expt 2 (N = 52), the affective qualities were matched and the valence properties varied in two stimulus arrays. As predicted, the IC effect differed significantly between conditions only on the measure (assignment) thought to be most sensitive to the memorial component. The results are discussed in terms of the implications of the findings for the proposed mechanisms of illusory correlation.

Adult↗