Learning disabilities, low achievement, and mild mental retardation: more alike than different?

Children identified with learning disabilities (LD), low achievement (LA), or mild mental retardation (MMR) were contrasted on 41 measures of ability, academic achievement, social skills, problem behavior, academic engaged time, perceptual-motor skills, and school history. Both multivariate, univariate, and meta-analytic comparisons among the three groups showed relatively large differences on measures of aptitude and achievement, with the LD group scoring higher on measures of cognitive ability than the LA and MMR groups and the LA group showing higher tested academic achievement than the LD and MMR groups. Teacher ratings of academic competence showed similar levels of functioning for the LD and LA groups. No differences among the groups were found on measures of social skills, problem behaviors, or academic engaged time, or on most indices reflecting school history. Results were interpreted in light of studies contrasting LD and LA groups. Comparisons with earlier studies were difficult in light of demographic differences in samples and the lower cognitive and academic functioning of children in the present study. The current study showed that 61% of the LD group could be differentiated from the LA group, with LD-MMR and LA-MMR differentiation levels being 68.5% and 67.5%, respectively.     

Two isozymes of P450nor of Cylindrocarpon tonkinense: molecular cloning of the cDNAs and genes, expressions in the yeast, and the putative NAD(P)H-binding site

The cDNAs and genes for two isozymes of cytochrome P450nor of the fungus Cylindrocarpon tonkinense, P450nor1 and P450nor2, were cloned and sequenced. Their deduced amino acid sequences respectively showed 83 and 70% identity to that of P450nor of Fusarium oxysporum, and 69% identity to each other. The genes for P450nor1 and P450nor2 were termed, respectively, CYP 55A2 and CYP 55A3. The cDNA for P450nor1 contained a targeting-like presequence upstream the N-terminus of mature protein whereas that for P450nor2 did not, suggesting their different intracellular localisations. We also succeeded in expressing these P450nor isoforms in the host-vector system of the yeast Saccharomyces cerevisiae. We purified one of the recombinant proteins, P450nor of F oxysporum. Little difference could be observed between the native and recombinant proteins in catalytic and spectroscopic properties. We constructed chimeric proteins of P450nor of F oxysporum and P450nor2 which are different in their specificity against the electron donors: reduced pyridine nucleotides. The specificity of chimeric proteins against NADH/NADPH showed that the specificity is determined by the N-terminal half of protein. We found a consensus amino acid sequence between three isoforms of P450nor, A-X-G-X-X-A, similar to the NAD-binding motif G-X-G-X-X-G/A in the region that corresponds to the B'-helix in P450cam.     

Expression of CYP71B7, a cytochrome P450 expressed sequence Tag from Arabidopsis thaliana

c-Yes was purified 322-fold from a rat liver plasma membrane fraction to a single 60-kDa band on SDS-PAGE. The purified protein contained essentially no phosphotyrosine residues and was autophosphorylated with Mg2+. ATP exclusively at tyrosine residues with a concomitant increase in the protein-tyrosine kinase activity. The autophosphorylated c-Yes was extensively digested by trypsin and the resultant two major phosphopeptides, peptides I and II, were purified by HPLC on a reversed-phase C-18 column. The amino acid sequence of peptide I was determined to be LIEDNEYTAR, which is identical with the sequence from Leu-418 through Arg-427 of mouse c-Yes, indicating that one of the autophosphorylation sites corresponds to Tyr-424 of the mouse c-Yes. After partial determination of the N-terminal sequence of 10 amino acid residues of peptide II, the 230 bp sequence of rat cDNA that encodes the N-terminal 76 amino acid residues of c-Yes covering peptide II, was determined. From the predicted amino acid sequence, the sequence of peptide II was assumed to be from Tyr-16 through Lys-46, YTPENPTEPVNTSAGHYGVEHATAATTSSTK. The purified c-Yes phosphorylated the tyrosine residue of synthetic peptides covering Tyr-32 and its surrounding sequence but did not phosphorylate peptides covering Tyr-16 and its surrounding sequence, suggesting that the other autophosphorylation site is Tyr-32.     

Recombinant expression and characterization of the major beta-lactamase of Mycobacterium tuberculosis

New antibiotic regimens are needed for the treatment of multidrug-resistant tuberculosis. Mycobacterium tuberculosis has a thick peptidoglycan layer, and the penicillin-binding proteins involved in its biosynthesis are inhibited by clinically relevant concentrations of beta-lactam antibiotics. beta-Lactamase production appears to be the major mechanism by which M. tuberculosis expresses beta-lactam resistance. beta-Lactamases from the broth supernatant of 3- to 4-week-old cultures of M. tuberculosis H37Ra were partially purified by sequential gel filtration chromatography and chromatofocusing. Three peaks of beta-lactamase activity with pI values of 5.1, 4.9, and 4.5, respectively, and which accounted for 10, 78, and 12% of the total postchromatofocusing beta-lactamase activity, respectively, were identified. The beta-lactamases with pI values of 5.1 and 4.9 were kinetically indistinguishable and exhibited predominant penicillinase activity. In contrast, the beta-lactamase with a pI value of 4.5 showed relatively greater cephalosporinase activity. An open reading frame in cosmid Y49 of the DNA library of M. tuberculosis H37Rv with homology to known class A beta-lactamases was amplified from chromosomal DNA of M. tuberculosis H37Ra by PCR and was overexpressed in Escherichia coli. The recombinant enzyme was kinetically similar to the pI 5.1 and 4.9 enzymes purified directly from M. tuberculosis. It exhibited predominant penicillinase activity and was especially active against azlocillin. It was inhibited by clavulanic acid and m-aminophenylboronic acid but not by EDTA. We conclude that the major beta-lactamase of M. tuberculosis is a class A beta-lactamase with predominant penicillinase activity. A second, minor beta-lactamase with relatively greater cephalosporinase activity is also present.     

Clinical evaluation of bioactive glass in the treatment of periodontal osseous defects in humans

The purpose of this study was to compare the use of bioactive glass to demineralized freeze-dried bone allograft (DFDBA) in the treatment of human periodontal osseous defects. Fifteen systemically healthy patients (6 males and 9 females, aged 30 to 63) with moderate to advanced adult periodontitis were selected for the study. All patients underwent initial therapy, which included scaling and root planing, oral hygiene instruction, and an occlusal adjustment when indicated, followed by re-evaluation 4 to 6 weeks later. Paired osseous defects in each subject were randomly selected to receive grafts of bioactive glass or DFDBA. Both soft and hard tissue measurements were taken the day of surgery (baseline) and at the 6-month re-entry surgery. The clinical examiner was calibrated and blinded to the surgical procedures, while the surgeon was masked to the clinical measurements. Statistical analysis was performed by using the paired Student's t test. The results indicated that probing depths were reduced by 3.07 +/- 0.80 mm with the bioactive glass and 2.60 +/- 1.40 mm with DFDBA. Sites grafted with bioactive glass resulted in 2.27 +/- 0.88 mm attachment level gain, while sites grafted with DFDBA had a 1.93 +/- 1.33 mm gain in attachment. Bioactive glass sites displayed 0.53 +/- 0.64 mm of crestal resorption and 2.73 mm bone fill. DFDBA-grafted sites experienced 0.80 +/- 0.56 mm of crestal resorption and 2.80 mm defect fill. The use of bioactive glass resulted in 61.8% bone fill and 73.33% defect resolution. DFDBA-grafted defects showed similar results, with 62.5% bone fill and 80.87% defect resolution. Both treatments provided soft and hard tissue improvements when compared to baseline (P < or = 0.0001). No statistical difference was found when comparing bioactive glass to DFDBA; however, studies with larger sample sizes may reveal true differences between the materials. This study suggests that bioactive glass is capable of producing results in the short term (6 months) similar to that of DFDBA when used in moderate to deep intrabony periodontal defects.     

Coupling of skeletal muscle to a prosthesis for circulatory support

A durable bond between the end of skeletal muscles and prosthetic structures could, with appropriate linkage, allow circulatory support power by synchronous and/or sequential contraction of several in situ conditioned muscles. Potential advantages relative to a myoplasty wrap involve 1) less traumatic dissection, 2) efficient linear force development, 3) selectable contraction rate, 4) greater stroke work, 5) independent control of muscle pre-load and end diastolic pressure, and 6) independent control of duration of muscle tension and ejection time. However, no existing means of tissue-prosthetic bonding appears adequate. Practicality would demand that full tension bearing capacity by the bond take no longer than muscle conditioning. A prosthesis was developed to achieve those goals. As scaled for this study, it is made of 7,200-7,800 unspun, unplaited, 22 to 26 microns diameter polyester fibers swaged into four taper needles for weaving through distal muscle. The other end is formed into a polyurethane sheathed kernmantel cord for distal fixation. Devices were implanted in six 3 to 4 kg rabbits (unilateral posterior tibial tendon replacement, random side selection with contralateral dissection/closure controls), and their tensile strength was tested at 30 days. All healed well; leg movements were normal after 1 week. Limbs were frozen at -70 degrees C between death and testing. Control failure occurred at 243 +/- 94 N and experimental at 163 +/- 44 N (p = 0.065, t-test); highest estimated requirement was 17.2 N. Interface strength was adequate by 30 days. Continued investigations, addressing other questions, are warranted.     

Altered inotropic response of endothelin-1 in cardiomyocytes from rats with isoproterenol-induced cardiomyopathy

Retrograde transport from the Golgi to the ER is an essential process. Resident ER proteins that escape the ER and proteins that cycle between the Golgi and the ER must be retrieved. The interdependence of anterograde and retrograde vesicle trafficking makes the dissection of both processes difficult in vivo. We have developed an in vitro system that measures the retrieval of a soluble reporter protein, the precursor of the yeast pheromone alpha-factor fused to a retrieval signal (HDEL) at its COOH terminus (Dean, N., and H.R.B Pelham. 1990. J. Cell Biol. 111:369-377). Retrieval depends on the HDEL sequence; the alpha-factor precursor, naturally lacking this sequence, is not retrieved. A full cycle of anterograde and retrograde transport requires a simple set of purified cytosolic proteins, including Sec18p, the Lma1p complex, Uso1p, coatomer, and Arf1p. Among the membrane-bound v-SNAP receptor (v-SNARE) proteins, Bos1p is required only for forward transport, Sec22p only for retrograde trafficking, and Bet1p is implicated in both avenues of transport. Putative retrograde carriers (COPI vesicles) generated from Golgi-enriched membranes contain v-SNAREs as well as Emp47p as cargo.