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Biomedical subjects

P G Johnson

Publications and source records attributed to P G Johnson.

At least 19 recordsLinked to original sources
PubMed1999

Developmental, cognitive, and behavioral sequelae of child abuse.

There is growing interest in the neurologic, behavioral, and cognitive effects of child abuse and neglect. This article explores the literature on the short and long term sequelae of physically and sexually abused and neglected children, along with controversies generated by the studies themselves. Recommendations are made for swift and ongoing intervention in cases of child abuse to protect young victims from potentially devastating effects.

Age Factors↗
PubMed1999

Increased DNA synthesis in INIT/10T1/2 cells after exposure to a 60 Hz magnetic field: a magnetic-field or a thermal effect?

This study was designed to test the hypothesis that a 0.1-0.8-mT 60 Hz magnetic field may act as a promoter of carcinogenesis. C3H 10T1/2 mouse fibroblasts initiated with the carcinogen methylcholanthrene (INIT/10T1/2 cells) were used; in these cells, expression of the carcinogenic phenotype is suppressed indefinitely by the presence of retinyl acetate in the culture medium. After withdrawal of retinyl acetate, expression of the carcinogenic phenotype may be observed as the loss of contact inhibition. Cells grown without retinyl acetate were exposed to 0.1-0.8-mT (rms) 60 Hz magnetic fields or to sham fields. Eight days after exposure, magnetic-field and sham-exposed cells showed the same levels of incorporation of [3H]thymidine, and both had counts significantly higher than those of unexposed cells. The rate of incorporation of [3H]thymidine was very sensitive to small (0.1-0.8 degrees C) and transient (60 min) increases in incubation temperature during the first few days of withdrawal of retinyl acetate. Exposure of Jurkat (human acute T-cell lymphoma) and GH3 (rat pituitary tumor) cells to magnetic fields and sham conditions yielded similar results. INIT/10T1/2 cells cultured in the presence of retinyl acetate showed no effect of exposure conditions. Both magnetic-field and sham exposures caused a slight increase in temperature within the exposure zone in the incubator. Thus the differences between rates of incorporation of [3H]thymidine in magnetic field-exposed, sham-exposed and unexposed cells seem to be attributable at least in part to a slight elevation in temperature during exposure. Since some cells appear to be extremely sensitive to small increases in temperature, measurements of magnetic-field effects must be made and interpreted with caution.

Animals↗
PubMed1998

Absence of 60-Hz, 0.1-mT magnetic field-induced changes in oncogene transcription rates or levels in CEM-CM3 cells.

Our objective was to assess the reproducibility of the 60-Hz magnetic field-induced, time-dependent transcription changes of c-fos, c-jun and c-myc oncogenes in CEM-CM3 cells reported by Phillips et al. (Biochim. Biophys. Acta, 1132 (1992) 140-144). Cells were exposed to a 60-Hz magnetic field (MF) at 0.1 mT (rms), generated by a pair of Helmholtz coils energized in a reinforcing (MF) mode, or to a null magnetic field when the coils were energized in a bucking (sham) mode. After MF or sham exposure for 15, 30, 60 or 120 min, nuclei and cytoplasmic RNA were extracted. Transcription rates were measured by a nuclear run-on assay, and values were normalized against either their zero-time exposure values, or against those of the c-G3PDH (housekeeping) gene at the same time points. There was no significant difference, at P=0.05, detected between MF and either sham-exposed or control cells at any time point. Transcript levels of the oncogenes were measured by Northern analysis and normalized as above. No significant difference (P=0.05) in transcript levels between MF and either sham-exposed or control cells was detected.

Electromagnetic Fields↗
PubMed1998

Electrorheological modeling of the permeabilization of the stratum corneum: theory and experiment.

Experimentally observed changes in the conductivity of skin under the influence of a pulsing electric field were theoretically analyzed on the basis of a proposed electrorheological model of the stratum corneum (SC). The dependence of relative changes in conductivity on the amplitude of electric field and timelike parameters of applied pulses or pulse trains have been mathematically described. Statistical characteristics of phenomena of transient and long-term electroporation of SC were taken into consideration. The time-dependent decreases of skin resistance depicted by the models were fitted to experimental data for transient and long-term skin permeabilization by electric pulses. The results show two characteristic times and two spectra of characteristic energies for transient and long-term permeabilizations. The rheological parameters derived from the fittings agreed with those reported elsewhere for biological membranes.

Animals↗
PubMed1998

The effect of tacrolimus (FK506) on intestinal barrier function and cellular energy production in humans.

BACKGROUND & AIMS: The maintenance of the intestinal mucosal barrier may be energy dependent. Tacrolimus is a potent immunosuppressive drug that decreases mitochondrial adenosine triphosphate production and increases intestinal permeability in animals. METHODS: Twelve liver graft recipients receiving tacrolimus, 9 healthy volunteers, and 5 liver graft recipients not receiving immunosuppression underwent a combined absorption-permeability-mitochondrial function test using 5 g lactulose, 1 g L-rhamnose, 0.5 g D-xylose, 0.2 g 3-O-methyl-D-glucose, 1 mg/kg 2-keto[1-13C]isocaproic acid ([13C]KICA), and 20 mg/kg L-leucine. The respiratory quotient and resting energy expenditure were measured by indirect calorimetry. Tacrolimus pharmacokinetic profiles and levels of endotoxin and IgM and IgG endotoxin core antibodies were determined. RESULTS: Tacrolimus inhibited the decarboxylation of [13C]KICA, the resting energy expenditure, and the respiratory quotient in an exposure-dependent manner, suggesting an inhibition of mitochondrial respiration. Tacrolimus inhibited intestinal absorptive capacity in an exposure-dependent manner. Tacrolimus-treated patients had an increased intestinal permeability and significantly higher endotoxin levels compared with healthy volunteers. CONCLUSIONS: Tacrolimus inhibits cellular energy production in humans at clinically relevant doses. This is associated with an increased intestinal permeability, endotoxemia, and an impaired intestinal absorptive capacity.

Adolescent↗
PubMed1998

A pulsed electric field enhances cutaneous delivery of methylene blue in excised full-thickness porcine skin.

We used electric pulses to permeabilize porcine stratum corneum and demonstrate enhanced epidermal transport of methylene blue, a water-soluble cationic dye. Electrodes were placed on the outer surface of excised full-thickness porcine skin, and methylene blue was applied to the skin beneath the positive electrode; 1 ms pulses of up to 240 V were delivered at frequencies of 20-100 Hz for up to 30 min. The amount of dye in a skin sample was determined from absorbance spectra of dissolved punch biopsy sections. Penetration depth and concentration of the dye were measured with light and fluorescence microscopy of cryosections. At an electric exposure dose VT (applied voltage x frequency x pulse width x treatment duration) of about 4700 Vs, there is a threshold for efficient drug delivery. Increasing the applied voltage or field application time resulted in increased dye penetration. Transport induced by electric pulses was more than an order of magnitude greater than that seen following iontophoresis. We believe that the enhanced cutaneous delivery of methylene blue is due to a combination of de novo permeabilization of the stratum corneum by electric pulses, passive diffusion through the permeabilization sites, and electrophoretic and electroosmotic transport by the electric pulses. Pulsed electric fields may have important applications for drug delivery in a variety of fields where topical drug delivery is a goal.

Administration, Cutaneous↗
PubMed1997

Characterization of electric-pulse-induced permeabilization of porcine skin using surface electrodes.

We measured the transient and long-term changes of permeability of full-thickness porcine skin after the application of a single or a train of electric pulses, as the basis for optimization of the electrical parameters for enhancing transdermal drug or gene delivery by electroporation. Two electrodes were attached to the stratum corneum of excised skin for transdermal electric pulse delivery and impedance measurement. Both transient and long-term permeabilization were found to be dependent on the electrical exposure dose, i.e., the product of pulse voltage and cumulative pulsing (exposure) time. Skin resistance dropped to about 20% of its prepulsing value when pulsed beyond a critical dosage of 0.4 V-s (with 20-40 V across each skin path), but recovered rapidly within seconds after the pulse. Long-term permeabilization of the skin required repeated pulsing with a minimum potential of 160 V (80 V across each skin path). The maximum long-term resistance drop, to 35% of the initial value, required a dose greater than 200 V-s, recovering slowly and seldom completely in tens of minutes to hours. The decrease and recovery of the resistance were dependent on the frequency and pulse length only for low-dose electrical exposure.

Administration, Cutaneous↗
PubMed1995

Photosensitization of murine tumor, vasculature and skin by 5-aminolevulinic acid-induced porphyrin.

The effects of topical and systemic administration of 5-aminolevulinic acid (ALA) were examined in several murine tumor systems with regard to porphyrin accumulation kinetics in tumor, skin and blood, vascular and tumor cell photosensitization and tumor response after light exposure. Marked, transient increases in porphyrin levels were observed in tumor and skin after systemic and topical ALA. Rapid, transient, dose-dependent porphyrin increases were also observed in blood; these were pronounced after systemic ALA injection and mild after topical application. They were highest within 1 h after ALA injection, thereafter declining rapidly. This matched the clearing kinetics of injected exogenous protoporphyrin IX (PpIX). Initially, vascular photosensitivity changed inversely to blood porphyrin levels, increasing gradually up to 5 h post-ALA, as porphyrin was clearing from the bloodstream. This pattern was again matched by injected, exogenous PpIX. After therapeutic tumor treatment vascular disruption of the tumor bed, while observed, was incomplete, especially at the tumor base. Minimal direct tumor cell kill was found at low photodynamic therapy (PDT) doses (250 mg/kg ALA, 135 J/cm2 light). Significant, but limited (< 1 log) direct photodynamic tumor cell kill was obtained when the PDT dose was raised to 500 mg/kg systemic ALA, followed 3 h later by 270 J/cm2, a dose that was however toxic to the animals. The further reduction of clonogenic tumor cells over 24 h following treatment was moderate and probably limited by the incomplete disruption of the vasculature. Tumor responses were highest when light treatment was carried out at the time of highest tumor porphyrin content rather than at the time of highest vascular photosensitivity. Tumor destruction did not reach the tumor base, regardless of treatment conditions.

Administration, Topical↗
PubMed1994

Damage induced in episomal EBV DNA in Raji cells by antitumor drugs as measured by pulsed field gel electrophoresis.

The studies described below were carried out to analyze the damage induced by DNA active drugs to episomal (Epstein-Barr virus, EBV) DNA in the Raji Burkitt's lymphoma cell line. This work: (i) applies pulsed-field gel electrophoresis (PFGE) techniques to quantify DNA damage on a large (approximately 180 kbp), circular target, (ii) investigates the DNA strand-scission behavior of different classes of drugs on the EBV episome, and (iii) compares EBV episomal damage to that generated in genomic DNA in the Raji cell line. Cells were treated with ionizing radiation to induce random strand scission, and the migration of topological forms of EBV was measured using PFGE. DNA damage induced in the episome by DNA active drugs was then assayed. Three drugs, acting by different types of DNA interactive mechanisms, were used: bleomycin, an intercalative DNA strand-scission agent; and amsacrine (mAMSA) and teniposide (VM26), intercalative and nonintercalative topoisomerase II active drugs, respectively. Rad equivalency of damage was determined by comparing the drug-induced change in percentage of Forms I and III to that generated by ionizing radiation. Additionally, single- and double-strand scission induced in genomic (total cellular) DNA by X-rays, bleomycin, amsacrine, and teniposide were assayed by high-sensitivity alkaline and neutral filter elution techniques. We demonstrate that pulsed-field gel electrophoresis is a useful technique for measuring form conversion in large episomal DNA. While all three drugs effect both episomal and genomic DNA strand scission, bleomycin appears to preferentially damage the EBV episome. The topoisomerase II active drugs mAMSA and VM26 show no evidence of episome-directed damage in this system and, in fact, damage genomic DNA at somewhat higher rates.

Amsacrine↗
PubMed1994

Measurements of 2H and 18O in body water: analytical considerations and physiological implications.

Measurement of energy expenditure with doubly-labelled water and of body composition and breast milk output with 2H or 18O requires accurate and precise techniques for measuring isotopic enrichments. The possibility of an inaccuracy in measurements of 2H and 18O isotopic enrichment arising from the matrix in biological fluids was investigated (1) by simulating a dilution experiment in both water and urine samples and (2) by reconstituting urine samples, ranging from 10 to 60 g/kg in solid concentration, from freeze-dried urinary solids mixed with either natural abundance or doubly-labelled water. Current techniques involved in measuring 2H and 18O isotopic enrichments were used (reduction of the samples to H2 gas with either Zn or U, and CO2/H2O equilibration or direct measurement of mass 20:18 ratios on water vapour for 18O analysis). All four methods accurately measured serial dilutions in both urine and water. Dilution space calculated from isotopic enrichments, compared with the water content of urine (determined by freeze-drying and accounting for exchangeable isotopes) was overestimated by about 2.4% by the Zn technique whereas other methods were accurate. The urinary solids content of a water solution was related to that inaccuracy. The use of the Zn technique with biological samples is likely to create biases in 2H distribution space. Examination of recent literature supports this view. Caution should therefore be used when physiological conclusions have to be made from the relative size of 2H and 18O distribution spaces.

Body Water↗
PubMed1994

The use of cannulated screws in musculoskeletal trauma. A review of surgical techniques.

The use of minimally invasive techniques for the treatment of articular and periarticular fractures is becoming more popular, especially when formal open reduction and internal fixation is contraindicated because of associated soft-tissue compromise and swelling. Cannulated screws are frequently effective in these situations and can be inserted by way of limited open or percutaneous techniques in many cases. Accurate fracture reduction can be attained through insertion of cannulated screws over a guide pin, resulting in provisional stability of the fracture. In most instances, such methods of fracture reduction are adjunctive and require the addition of external fixation, limited internal fixation, and cast bracing or orthotic considerations. Applications of cannulated screw fixation in specific trauma injuries are discussed as are indications, contraindications, advantages, and disadvantages of such methods.

Adult↗
PubMed1993

Angle measurements of the distal radius: a cadaver study.

The quality of reduction of distal radius fractures is assessed mainly by degree of restoration of radial angle and palmar tilt. This cadaver study investigates the effects of forearm rotation of these measurements. A 5 degree rotational change produces a 1.6 degree change in palmar tilt on the conventional lateral view and a 1.0 degree change on the 15 degree lateral view. Lateral radiographs could be rotated 15 degrees-30 degrees and still be considered acceptable. Therefore, rotation may produce up to a 4.0 degree (15 degrees lateral view) or 6.4 degree (conventional lateral view) change in measured palmar tilt. To provide clearer measuring landmarks and minimize error due to rotation, we recommend obtaining the 15 degree lateral view routinely in fractures with significant dorsal angulation. We also studied the interobserver variability of different surgeons assessing radial angle and palmar tilt. The mean standard deviation between surgeons was 3.2 degrees for radial angle, 3.6 degrees for conventional lateral palmar tilt, and 2.1 degrees for 15 degrees lateral palmar tilt.

Forearm↗
PubMed1992

Dependence of weight loss during very-low-calorie diets on total energy expenditure rather than on resting metabolic rate, which is associated with fat-free mass.

The assumption that total energy expended is related to resting metabolic rate (RMR) has not been validated. Intuitively, weight lost should be determined by the difference between the total energy consumed and the total energy expended. The ratio of actual daily energy usage to RMR by subjects dieting for 11 wk on a 1695-kJ (405-kcal) very-low-calorie diet (VLCD) was variable 1.9 +/- 0.3 (range 1.47-2.36). Weight loss correlated with total energy expenditure measured by 2H2 18O and not RMR, body mass index or body composition. Although RMR may be a reliable indicator of fat-free mass, there is little evidence that subjects with similar RMR will lose comparable weight or have comparable difficulty in weight maintenance.

Adult↗
PubMed1989

The etiology and repair of rotary ankle instability.

The ankle and subtalar joints form a coupling which acts like a universal joint. When the anterior talofibular ligament is disrupted, rotation of the talus about the long axis of the leg is permitted. This abnormal rotation in the transverse plane is the distinguishing feature of rotary ankle instability. The pathomechanics of rotary ankle instability are described. A simple and direct approach to repairing and reinforcing the anterior talofibular ligament and the results of 37 consecutive delayed reconstructions by this method are reported. Advantages of this procedure are felt to be a restoration of the original anatomy, preservation of the peroneal tendons, maintenance of the integrity of the subtalar joint and excellent postoperative results. Disadvantages include a lack of objective diagnostic criteria.

Adolescent↗