Slipped capital femoral epiphysis associated with radiation therapy

We reviewed 32 children with 41 radiation-therapy associated slipped capital femoral epiphyses (RTASCFE). Ten were from the authors' institutions and 22 from the literature. Gender distribution was equal. The age at diagnosis of the malignancy was 4.3 +/- 3.1 years; the amount of radiation was 4,240 +/- 1,445 rads. Children with RTASCFE presented younger (10.4 +/- 3.2 years) than a routine SCFE. The average symptom duration was 5 +/- 6 months. Children with RTASCFE are usually thin (median weight, 10th percentile) in contrast to children with typical SCFE, who are usually obese (<95th percentile). The majority (82%) of the slips were mild, compared to routine SCFEs (approximately 50%); 28% were bilateral. There was a positive linear relationship between the age at presentation of the SCFE and the age at diagnosis of the malignancy; there was a negative linear relationship between the age at presentation of the SCFE and the amount of radiation therapy.     

The effects of instructional match and content overlap on generalized reading performance

This study examined the effects of instructional match and content overlap on students' ability to generalize from passage reading instruction. Four students with mild disabilities served as participants. Using a multielement design, students were instructed with passages at two levels of text difficulty (instructionally matched vs. instructionally mismatched), and generalization was assessed with passages at two levels of similarity to those instructed (low vs. high content overlap). Results indicated that students' oral reading accuracy and fluency showed the greatest degree of generalization when instructional materials were matched to the students' skill level and assessment materials were similar to those used during instruction. Moreover, these results were maintained at 1-month follow-up. The implications of these findings for classroom reading instruction and the assessment of students' reading skills are discussed.     

Presence of immunocytes and sulfidopeptide leukotrienes in the inflamed guinea pig distal colon

This study examined whether the immunocyte recruitment associated with a mild inflammatory state induced by acetic acid would produce detectable sulfidopeptide leukotriene (LT) levels from colonic tissues or in dialysates. Histological examination and measurements of peroxidase activities of inflamed tissues indicated edema, hyperplasia and neutrophil infiltration. Significant elevated LTB4 and prostaglandin E2(PGE2) levels were found but only slight elevations in sulfidopeptide LTs occurred. A slight elevation in eosinophil peroxidase indicated that eosinophil infiltration also occurred. The increase in sulfidopeptide LT levels appeared insufficient by itself to alter secretory responses in the distal colon. However, combined with other immunocyte products such as PGs, the sulfidopeptide LTs may influence the symptomology of inflammatory bowel disease.     

Biomagnetic neurosensors. 2. Magnetically stimulated sensors

We report the generation of action potentials in crayfish neurons by magnetic pulses for analytical purposes. A copper wire toroid, containing a ferrite core, was placed around the nerve bundle, and square wave current pulses were sent through the wire to generate a magnetic field. The magnetic field generated an action potential in the neuron that was detected downfield by a pickup microelectrode. The biosensor was used to detect local anesthetics by monitoring the time necessary for complete blockage of the action potential. Techniques for improving the efficiency and lifetimes of neural biosensors are discussed.     

FOLD: integrated analysis and display of protein secondary structure

FOLD, a computer program for the definition and analysis of protein secondary structure, is described. Algorithms implemented in the software are reviewed. These include methods for the identification of simple features such as hydrogen bonds, alpha helices, beta strands, beta bulges, and beta and psi turns. Techniques are also described for the definition and analysis of higher-order structures, such as beta hairpins, beta sheets and their topology, and beta barrels. In addition to considerable textual output the program supports visualization of protein secondary structure in either an atom-based display style or one reproducing the characteristics of a so-called ribbon drawing.     

Hydrophilic peptides derived from the transframe region of Gag-Pol inhibit the HIV-1 protease

The HIV-1 transframe region (TFR) is between the structural and functional domains of the Gag-Pol polyprotein, flanked by the nucleocapsid and the protease domains at its N and C termini, respectively. Transframe octapeptide (TFP) Phe-Leu-Arg-Glu-Asp-Leu-Ala-Phe, the N terminus of TFR, and its analogues are competitive inhibitors of the action of the mature HIV-1 protease. The smallest, most potent analogues are tripeptides: Glu-Asp-Leu and Glu-Asp-Phe with Ki values of approximately 50 and approximately 20 microM, respectively. Substitution of the acidic amino acids in the TFP by neutral amino acids and d or retro-d configurations of Glu-Asp-Leu results in an >40-fold increase in Ki. Protease inhibition by Glu-Asp-Leu is dependent on a protonated form of a group with a pKa of 3.8; unlike other inhibitors of HIV-1 protease which are highly hydrophobic, Glu-Asp-Leu is extremely soluble in water, and its binding affinity decreases with increasing NaCl concentration. However, Glu-Asp-Leu is a poor inhibitor (Ki approximately 7.5 mM) of the mammalian aspartic acid protease pepsin. X-ray crystallographic studies at pH 4.2 show that the interactions of Glu at P2 and Leu at P1 of Glu-Asp-Leu with residues of the active site of HIV-1 protease are similar to those of other product-enzyme complexes. It was not feasible to understand the interaction of intact TFP with HIV-1 protease under conditions of crystal growth due to its hydrolysis giving rise to two products. The sequence-specific, selective inhibition of the HIV-1 protease by the viral TFP suggests a role for TFP in regulating protease function during HIV-1 replication.     

Plasma membrane cholesterol is a key molecule in shear stress-dependent activation of extracellular signal-regulated kinase

Shear stress, the dragging force generated by fluid flow, differentially activates extracellular signal-regulated kinase (ERK) and c-Jun NH2-terminal kinase (JNK) in bovine aortic endothelial cells (BAEC) (Jo, H., Sipos, K., Go, Y. M., Law, R., Rong, J., and McDonald, J. M. (1997) J. Biol. Chem. 272, 1395-1401). Here, we examine whether cholesterol-enriched compartments in the plasma membrane are responsible for such differential regulation. Pretreatment of BAEC with a cholesterol-binding antibiotic, filipin, did not inhibit shear-dependent activation of JNK. In contrast, filipin and other membrane-permeable cholesterol-binding agents (digitonin and nystatin), but not the lipid-binding agent xylazine, inhibited shear-dependent activation of ERK. The effect of cholesterol-binding drugs did not appear to be due to membrane permeabilization, since treatment of BAEC with a detergent, Triton X-100 which also permeabilizes membranes, did not inhibit shear-dependent activation of ERK. Furthermore, shear-dependent activation of ERK, but not JNK, was inhibited by cyclodextrin, a membrane-impermeable cholesterol-binding agent, which removes cell-surface cholesterol. Moreover, the effects of cyclodextrin were prevented by adding cholesterol during the incubation. These results indicate that cholesterol or cholesterol-sensitive compartments in the plasma membrane play a selective and essential role in activation of ERK, but not JNK, by shear stress. Although exposure to shear stress (1 h) increased the number of caveolae by 3-fold, treatment with filipin had no effect in either control or shear-exposed cells suggesting that caveolae density per se is not a crucial determinant in shear-dependent ERK activation. In summary, the current study suggests that cholesterol-sensitive microdomains in the plasma membrane, such as caveolae-like domains, play a critical role in differential activation of ERK and JNK by shear stress.