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Biomedical subjects

J Johnson

Publications and source records attributed to J Johnson.

At least 253 records · Page 14Linked to original sources

African American children and adolescents exposure to community violence: a pilot study.

Children and adolescents living in communities with frequent episodes of violence are an at-risk population. Chronic exposure to community violence can compromise children and adolescents' health, cognitive functioning, and development. This interdisciplinary pilot study was conducted in an urban community to ascertain a description of children and adolescents' exposure to the type and frequency of violence. Children were found to witness more community violence, while adolescents both witness and experience more community and individual-level violence. Reduction of violence and creation of healthy and safe communities are critical to the well-being and productivity of all residents.

Adolescent↗

Transforming p21ras mutants and c-Ets-2 activate the cyclin D1 promoter through distinguishable regions.

Several different oncogenes and growth factors promote G1 phase progression. Cyclin D1, the regulatory subunit of several cyclin-dependent kinases, is required for, and capable of shortening, the G1 phase of the cell cycle. The present study demonstrates that transforming mutants of p21ras (Ras Val-12, Ras Leu-61) induce the cyclin D1 promoter in human trophoblasts (JEG-3), mink lung epithelial (Mv1.Lu), and in Chinese hamster ovary fibroblast cell lines. Site-directed mutagenesis of AP-1-like sequences at -954 abolished p21ras-dependent activation of cyclin D1 expression. The AP-1-like sequences were also required for activation of the cyclin D1 promoter by c-Jun. In electrophoretic mobility shift assays using nuclear extracts from cultured cells and primary tissues, several AP-1 proteins (c-Jun, JunB, JunD, and c-Fos) bound the cyclin D1 -954 region. Cyclin D1 promoter activity was stimulated by overexpression of mitogen-activated protein kinase (p41MAPK) or c-Ets-2 through the proximal 22 base pairs. Expression of plasmids encoding either dominant negative MAPK (p41MAPKi) or dominant negatives of ETS activation (Ets-LacZ), antagonized MAPK-dependent induction of cyclin D1 promoter activity. Epidermal growth factor induction of cyclin D1 transcription, through the proximal promoter region, was antagonized by either p41MAPKi or Ets-LacZ, suggesting that ETS functions downstream of epidermal growth factor and MAPK in the context of the cyclin D1 promoter. The activation of cyclin D1 transcription by p21ras provides evidence for cross-talk between the p21ras and cell cycle regulatory pathways.

Animals↗

Synthesis and evaluation of some 10-mono- and 2',10-diesters of 10-deacetylpaclitaxel.

10-Deacetylpaclitaxel, isolated from the bark of Taxus brevifolia, was converted into paclitaxel in one composite step (trimethylsilylation, acetylation, and desilylation) and in an overall yield of 80-85%. A series of 10-monoesters of 10-deacetylpaclitaxel are prepared by protection of the 2'- and 7-hydroxyls with a chloroacetyl group, acylation, and deprotection. Depending on the reaction conditions, the 10-monoesters, either exclusively or accompanied by the 2',10-diesters, are formed. The mono- and diesters were evaluated using the L-1210 cell culture assay. The 10-monoesters were comparable to paclitaxel and more active than the corresponding 2',10-diesters. The 10-[(4-methoxyphenyl)acetyl], 10-(2-nitrobenzoyl), and 10-(phenylacetyl) esters were found to be somewhat more active than paclitaxel.

Animals↗

Epidermal growth factor and c-Jun act via a common DNA regulatory element to stimulate transcription of the ovine P-450 cholesterol side chain cleavage (CYP11A1) promoter.

The P-450 side chain cleavage (CYP11A1) gene encodes the enzyme that catalyzes the initial step in steroid biosynthesis, resulting in the conversion of cholesterol to pregnenolone. Expression of the CYP11A1 gene is increased by hormones, such as adrenocorticotropin and luteinizing hormone, as well as by a number of growth factors, suggesting that its promoter may contain regulatory elements that respond to multiple signal transduction pathways. Using transient expression assays of the ovine CYP11A1 promoter in JEG-3 placental cells, distinct regulatory elements were found to mediate transcriptional stimulation by cAMP and epidermal growth factor (EGF). The cAMP response was mediated through a GC-rich sequence localized between -117 and -92. In contrast, EGF induced CYP11A1 transcription through an adjacent but distinct sequence (-92 to -77 base pairs) that was shown previously to bind nuclear proteins in DNase I footprinting reactions. This EGF-responsive element (EGF-RE) resembles an activator protein-1 (AP-1) site and was also required for transactivation by co-transfected c-Jun. A point mutation within the EGF-RE impaired stimulation by both EGF and c-Jun, suggesting that these pathways converge on a common regulatory element. Transfer of single or multiple copies of the EGF-RE upstream of an heterologous promotor conferrd EGF and c-Jun responses, providing further evidence that this element is sufficient for both responses. Transfection studies employing mutant c-Jun proteins confirmed a requirement for its DNA binding, leucine zipper and amino-terminal domains, each of which are required for activation of a classical AP-1 reporter. Gel shift studies demonstrated that protein binding to the CYP11A1 EGF-RE was competed specifically by a canonical AP-1 site, and the addition of an anti-JUN antibody confirmed the presence of AP-1 proteins. Consistent with the possibility that EGF may act in part via c-Jun, EGF stimulated the activity of a chimeric GAL4 c-Jun protein, indicating that JUN can serve as a potential target of EGF in JEG-3 cells. EGF also induced mitogen-activated protein kinase activity, and a dominant negative mutant of mitogen-activated protein kinase partially blocked EGF stimulation of GAL4 c-Jun activity. We conclude that EGF stimulates the CYP11A1 promoter through an AP-1 like element and that c-Jun is one of the targets of EGF action.

Animals↗

INR reporting in Canadian medical laboratories. Thrombosis Interest Group of Canada.

A written survey of all licensed medical laboratories in Canada performing coagulation testing was performed to investigate the level of knowledge and overall usage of the INR system for reporting prothrombin time results in medical laboratories. There was an overall response rate of 857 of 1,228 laboratories surveyed. Fifty-seven percent of responding laboratories utilized some format of INR reporting. The ISI of the individual thromboplastin utilized was known by 89% of laboratories. The ISI of the thromboplastin utilized was known to be specific for the particular reagent/instrument combination in 44% of cases. Fifty-five percent of client physicians preferred PT results to be reported in seconds while 42% desired an INR format. The situation in Canada is similar to the United States in that further education regarding the INR system for PT reporting is required by both medical laboratories and physicians.

Administration, Oral↗

Self-efficacy, pain, and physical activity among fibromyalgia subjects.

PURPOSE: The purpose of this study was to examine the effects of self-efficacy on self-report pain and physical activities among subjects with fibromyalgia (FM). In addition, descriptive statistics of the Arthritis Impact Measurement Scale (AIMS), a measure developed for use with arthritis patients, were reported. METHODS: Seventy-nine subjects with FM, as classified by the American College of Rheumatology (ACR) criteria, completed the Visual Analogue Scale for Pain, the AIMS, and the Arthritis Self-Efficacy Scale. A myalgic score was obtained during a tender point evaluation. Hierarchical multiple regression analyses were used to assess the effect of self-efficacy on self-report pain and physical activities measures after controlling for demographic variables (age, education, and symptom duration), disease severity (myalgic scores), and psychological distress (negative affect from the AIMS). RESULTS: Higher self-efficacy was associated with less pain and less impairment on the physical activities measure after controlling for demographic and disease severity measures. CONCLUSIONS: This study underscores the unique importance of self-efficacy in understanding pain and physical activities impairment.

Activities of Daily Living↗

The significance of the phi rhythm.

We reviewed two series of patients with the phi rhythm (posterior rhythmic slow waves occurring after eye closure) to determine its characteristics and clinical significance. Phi rhythm was defined as a minimum of three consecutive monomorphic posterior delta waves occurring within 2 sec of eye closure on at least two occasions during electroencephalography. Group 1 consisted of 30 patients (16 male and 14 female) with a mean age of 11.6 +/- 8.4 years (range, 3 to 46 years) who were evaluated between 1978 and 1993. Phi rhythm most commonly occurred when the patient was alert and after concentrated visual attention, such as reading or picture or pattern scanning. Seventeen of these patients had epilepsy (11 generalized, 3 focal, 1 both, and 2 unclassified). The frequency of epilepsy was not significantly different from that of a control group of 60 patients matched for age and sex; however, generalized epilepsies were more common in the phi group (P = 0.008). Group 2 consisted of a previously unreported series of 121 patients evaluated between 1960 and 1962. A diverse range of underlying clinical diagnoses was evident in both groups. The mechanism of the phi rhythm is unknown, but the findings suggest that the origin is subcortical and that the presence of this activity should not be considered diagnostic of a seizure disorder.

Adolescent↗

Combined antenatal vitamin K and phenobarbital therapy for preventing intracranial hemorrhage in newborns less than 34 weeks' gestation.

UNLABELLED: ōk--q----_xD-xD whether maternal antenatal therapy with vitamin K and phenobarbital prevents intracranial hemorrhage in premature newborns. METHODS: Women at high risk for spontaneous or indicated premature delivery before 34 weeks' gestation were randomly assigned to receive either placebo or vitamin K and phenobarbital. All patients received betamethasone and antibiotics and were managed uniformly by a single perinatal group in one hospital. All newborns were managed uniformly in the same nursery by one neonatal group. Two independent interpretations of neonatal head ultrasound examinations were obtained. RESULTS: The duration of gestation at study entry and at delivery were similar in the placebo (181 mothers) and treatment (191) groups. With the hospital radiology group (the primary interpreter), the incidence rates of severe intracranial hemorrhage (8 versus 7%) and mild intracranial hemorrhage (38 versus 32%) were similar for both groups. With the secondary interpreter (a single pediatric radiologist), the incidence rates of severe intracranial hemorrhage (9 versus 7%) and mild intracranial hemorrhage (27 versus 26%) were also similar. Neonatal mortality was equivalent in both the placebo and treatment groups (8 versus 10%). CONCLUSION: Combined antenatal therapy with vitamin K and phenobarbital does not reduce the frequency or severity of intracranial hemorrhage in premature newborns.

Adolescent↗

Metal ion binding to apo, holo, and reconstituted horse spleen ferritin.

The binding of Cd2+, Zn2+, Cu2+, Ni2+, Co2+, Mn2+, and Mg2+ to apo, holo, reconstituted horse spleen ferritin (HoSF), and native holo HoSF with phosphate removed was measured by gel-exclusion chromatography. Three classes of strong binding interactions (Kd < 10(-7) M) with apo HoSF at pH 7.5 were found for the various M2+ studied: high stoichiometric binding (30-54 M2+/HoSF) for Cd2+, Zn2+, Cu2+, with two protons released per metal bound; intermediate binding (16 M2+/HoSF) for Ni2+ and Co2+, with one proton released per metal bound; and low levels of binding (2-12 M2+/HoSF) for Mn2+, Mg2+, and Fe2+, with < 0.5 protons released per metal bound. M2+ binding to apo HoSF was nearly abolished at pH 5.5, except for Fe2+ and Cu2+, which remained unaffected by pH alteration. Holo HoSF bound much higher levels of M2+, a result directly attributable to the presence of phosphate binding sites. This conclusion was confirmed by decreased binding of M2+ to HoSF reconstituted in the absence of phosphate and by native holo HoSF with phosphate chemically removed. The binding of Cd2+ to apo HoSF was 54 per HoSF, but in the presence of developing core, the amount bound decreased to about 30 Cd2+/HoSF. This result indicated that Cd2+ and developing core were competing for the same sites on the HoSF interior, suggesting that 24 of the Cd2+ were bound to the inside surface. No other M2+ studied bound to the interior of HoSF by this criterion. Several of the M2+ appeared to bind strongly to the phosphate-free mineral core surface in reconstituted HoSF.

Animals↗

A preliminary study of the neuropsychological heterogeneity of familial schizophrenia.

This exploratory study describes the heterogeneity of the neuropsychological deficits that characterize familial schizophrenia. Forty-six familial schizophrenics showed significantly more variability in abstraction and problem-solving and motor control than 39 non-familial schizophrenics. Cluster analyses of these two neuropsychological parameters indicate that while the non-familial schizophrenics fall into one homogeneous cluster, the familial schizophrenics fall into three relatively distinct clusters which differ significantly in their morbid risk for schizophrenic-spectrum disorder. These preliminary data suggest that frontal lobe deficits are associated with an increased familial risk for schizophrenia.

Adolescent↗

V/Q defects and deep venous thrombosis following total hip replacement.

Seventy-two patients undergoing elective total hip replacement were studied with bilateral venography, pre-operative and post-operative lung scans. Twelve belonged to a control group that received placebo injections and 60 patients to treatment groups that received low molecular weight heparin. The incidence of deep venous thrombosis was 11 (92%) of 12 patients in the control group and 18 (30%) of 60 patients in the treatment group (X2: P < 0.001). The incidence of pulmonary embolism (new unmatched perfusion defects) was five (42%) of the 12 patients in the control group and five (8.3%) of the 60 patients in the treatment groups (X2: P < 0.002). The incidence of pulmonary embolism (new unmatched perfusion defects) was eight (27.5%) of 29 patients with deep venous thrombosis and two (4.6%) of 43 without deep venous thrombosis (X2: P < 0.02). Of the ten patients who had pulmonary embolism according to this study's criteria (one or more new defect on perfusion, unmatched on the ventilation scan), eight would have been classified as high probability by the Biello criteria, and only five by the PIOPED criteria, if the pre-operative scans were not available. We conclude that having a pre-operative lung scan improves ability to interpret the postoperative lung scans in high risk patients.

Elective Surgical Procedures↗

Assessment of two protocols for the human lymphocyte cytokinesis-blocked micronucleus assay.

This study indicated that by adding cytochalasin B (6 micrograms/ml) at 24 h, the lymphocyte culture time for micronucleus (MN) assay could be shortened to 64 h. In both unirradiated and ex-vivo irradiated (2 Gy) lymphocytes from three populations, we found that the differences in MN yield obtained by our modified cytokinesis-blocked time frame and that recommended by Fenech and Morley (1985) were insignificant (P = 0.66-0.87). We believe that the shorter assay time may enhance the applicability of MN assay for the rapid assessment of ionizing radiation overexposures.

Analysis of Variance↗

Serial casting of the lower extremity to correct contractures during the acute phase of burn care.

Severe contractures that develop early following a burn may not improve with splinting and exercise treatment. An alternative treatment is serial casting, which has been used to promote increased range of motion, to facilitate patient compliance with positioning, and to prevent the patient from scratching the burned area. This case report describes the use of serial casting for resolution of ankle plantar-flexion contractures that occurred in the acute phase of burn injury. The child described in this case report sustained a 49% total body surface area scald burn and developed contractures within 1 week after injury. The contractures, which were not corrected with thermoplastic splints, improved with casting from 45 degrees of plantar flexion to neutral dorsiflexion over 2 months with biweekly cast changes. The patient had multiple skin grafts and progressed in functional activities. Serial casting is a conservative and effective modality in correcting contractures resulting from burns. Further documentation of the efficacy of this treatment approach is necessary to support its use in burn care throughout various stages of healing.

Acute Disease↗

Utility of Tc-99m mebrofenin scintigraphy in the assessment of infantile jaundice.

Technetium-99m mebrofenin hepatobillary excretory patterns were assessed in 36 infants with hyperbilirubinemia. Phenobarbital was administered to 22 patients before imaging. Final diagnoses included: intrahepatic cholestasis (14 patients), neonatal hepatitis (nine patients), biliary atresia (eight patients), alpha-1-antitrypsin deficiency (two patients), Alagille's syndrome (two patients), and cystic fibrosis (one patient). No patient with biliary atresia showed bowel activity by 24 hours. Of the 28 infants without biliary atresia, 23 (82%) had bowel activity visualized by 6-8 hours and 26 (90%) had bowel activity by 24 hours. Two had no bowel activity at 24 hours: one had cystic fibrosis and one had neonatal hepatitis. Of the 26 patients with bowel visualization, the time to visualize bowel did not differ between patient groups with and without phenobarbital induction. All of the patients with hepatitis, including those with marked dysfunction, showed good hepatic uptake. Mebrofenin scintigraphy is an important imaging technique in the diagnostic evaluation of infants with hyperbilrubinemia. In addition to biliary atresia, intrahepatic cholestasis due to cystic fibrosis and severe neonatal hepatitis may also cause bowel nonvisualization up to 24 hours. The results of this study suggest phenobarbital induction may not be needed when Tc-99m mebrofenin scintigraphy is used for the assessment of infantile jaundice.

Aniline Compounds↗

Identification of pioneer viridans streptococci in the oral cavity of human neonates.

Three hundred and sixty-seven strains of pioneer streptococci isolated from the mouths of 40 healthy, full-term infants during the first month of life were examined by two taxonomic schemes that incorporated biochemical and physiological characteristics, IgA1 protease production and glycosidase activities. Streptococcus mitis biovar 1 and S. oralis comprised 55.0% of the pioneer streptococci isolated from neonates. S. salivarius constituted 25.3% of the isolates, while S. anginosus, S. mitis biovar 2, S. sanguis and S. gordonii accounted collectively for 11.4%. Difficulties in identifying streptococci were encountered and 8.4% of the 367 isolates could not be assigned to a recognised species.

Bacterial Proteins↗

Achievable standards, benchmarks for reporting and criteria for evaluating cervical cytopathology.

The cervical smear test, like all screening tests, is not 100% effective in detecting abnormality. In order to prevent 80-90% of invasive cancers, cervical screening requires cervical smears to be taken competently at regular intervals and correctly interpreted. With laboratories following the guidelines in this report, the NHSCSP should be able to meet the Health of the Nation target to reduce the incidence of invasive cervical cancer to less than 12 cases per 100 000 women in the UK by the year 2000.

Biomarkers, Tumor↗