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Biomedical subjects

S A Johnson

Publications and source records attributed to S A Johnson.

At least 73 records · Page 4Linked to original sources
PubMed1997

Heterogeneity of clonal lymphocytes with regard to bcl-2 protein concentration and cell size.

The existence of subpopulations of clonal lymphocytes in patients with low grade lymphoproliferative disorders, with regard to both cell size and bcl-2 protein concentration is reported. Flow cytometric analysis showed that the lymphocytes with higher levels of bcl-2 corresponded to a subset of larger lymphocytes. Statistical analysis suggested that the increased concentration of bcl-2 was not accounted for by the increase in cell size and it is possible that these cells form a functionally distinct component of the clonal proliferation. One patient, analysed in greater detail during treatment with a purine analogue, showed the subpopulations to exhibit a differential sensitivity to chemotherapy.

Antigens, CD19↗
PubMed1997

A population-based analysis of qualitative features of the neuropsychological test performance of individuals with dementia of the Alzheimer type: implications for individuals with questionable dementia.

Qualitative features of the neuropsychological test performance of individuals with dementia of the Alzheimer type (DAT) were examined in a population-based study. Qualitative error scores were derived from measures of verbal and figural memory, verbal fluency and confrontation naming for 38 patients with clinically diagnosed DAT, 236 normal elderly (NE) individuals, and 72 others who were questionably demented and at risk (AR) for DAT. Persons with DAT made a greater proportion of intrusion and perseverative errors, and more lexical and semantic naming errors, than the NE participants. These measures provided fair specificity but poor sensitivity for the diagnosis of DAT, and a logistic model based on these measures correctly classified 98% of the NE participants, but only 29% of the DAT participants. The AR participants demonstrated a pattern of errors that was highly similar to that of the DAT patients, and when their scores were subjected to the logistic model, 90% were classified as NE and 10% as DAT. These results indicate that specific error types that have been associated with DAT in self-referred or clinic-based samples also occur in the general population to a greater degree in individuals with DAT or questionable dementia than in NE individuals. Furthermore, these qualitative features may have some diagnostic usefulness in that their presence provides reasonable specificity for DAT or questionable dementia.

Aged↗
PubMed1996

Distribution and coverage of beta cells in the cat retina.

We have reexamined the retinal distribution and dendritic field dimensions of beta cells in the cat retina. Beta cells were labeled by retrograde transport from the A-layers of the lateral geniculate nucleus and distinguished from alpha cells on the basis of soma size. Dendritic fields of beta cells were visualized by intracellular staining in vitro. The fraction of cat ganglion cells that were beta cells varied with retinal location. Except near the area centralis, beta cells represented about half of all ganglion cells in the nasal hemiretina. They contributed as heavily as the other major ganglion cell classes to the nasal visual streak. In and near the area centralis and in the temporal retina, beta cells represented about two-thirds of all ganglion cells. The areas of beta cell dendritic fields were reciprocally related to beta cell density. For example, they were 3-fold smaller within the visual streak than at matched eccentricities outside it. For many cells, we could estimate both local beta cell density and dendritic field area. Coverage factor (dendritic field area x local density) remained constant at about 4 despite 100-fold variations in beta cell density, and was independent of eccentricity, nasotemporal location, or position relative to the visual streak. Analysis in terms of sampling theory suggests that the beta cell array is matched to X-cell spatial resolution so as to optimize acuity. The beta cell distribution and its systematic reflection in dendritic architecture predict acuity levels that apparently correlate well with actual visual performance across the cat's visual field.

Animals↗
PubMed1996

The free radical site in pea seedling copper amine oxidase probed by resonance Raman spectroscopy and generated by photolysis of caged substrate.

Resonance Raman spectra were obtained of the free radical site in substrate reduced anaerobic samples of pea seedling copper amine oxidase (PSAO). The spectra differ significantly from those reported previously for E. coli copper amine oxidase [Moenne-Loccoz et al. (1995) Biochemistry 34, 7020]. The spectra were found to be independent of substrate (benzylamine, spermidine or methylamine) used to reduce the TOPA quinone cofactor, however, several of the peaks in the Raman spectrum displayed small shifts on using [15N]benzylamine, proving incorporation of the substrate nitrogen atom onto the cofactor radical. Changes in the spectrum were also observed when measured in D2O solution indicating a strongly bound proton in the radical. The spectra were independent of pH values between 5 and 9 and are interpreted as showing that the radical exists as a semiiminoquinone radical monoanion. Benzylamine and phenethylamine have been caged with 2-nitrobenzaldehyde and shown by laser flash photolysis to uncage on a sub-millisecond timescale. Preliminary experiments have shown the formation of the enzyme radical intermediate on laser flash photolysis of 2-nitrobenzyl-caged benzylamine in the presence of enzyme. This should permit time-resolved resonance Raman spectral investigations of the catalytic cycle of copper amine oxidases.

Amine Oxidase (Copper-Containing)↗
PubMed1996

Quenching of reactive oxidative species by probucol and comparison with other antioxidants.

One-electron oxidation of the antiatherogenic and antiatherosclerotic drug probucol has been studied in relation to its activity as an antioxidant. Oxidation by triplet excited states of duroquinone and benzophenone, and by the inorganic radicals Br2.- and N3., lead to the formation of a transient absorption at 500 nm. This was identified by time-resolved resonance Raman spectroscopy as the phenoxyl radical from probucol, formed by hydrogen atom or electron plus proton loss from one of the phenolic groups of probucol. The reactivity of probucol with triplet duroquinone and triplet benzophenone, and as a quencher of singlet oxygen, was compared with the reactivities of other antioxidants (alpha-tocopherol, palmitoyl ascorbic acid, dihydrolipoic acid and N-acetyl cysteine). In quenching of the triplet states the reactivity of probucol was comparable with that of alpha-tocopherol, whereas as a quencher of singlet oxygen probucol (k < 10(6) M-1 s-1) was less effective than alpha-tocopherol (k = 2.0 x 10(8) M-1 s-1) by more than two orders of magnitude. This difference in reactivity may allow the contribution of singlet oxygen towards oxidative stress to be quantified separately.

Acetylcysteine↗
PubMed1996

Purine analogues in the management of lymphoproliferative diseases.

Three analogues of the purine 2-deoxyadenosine are available for the treatment of low grade lymphoproliferative disorders: pentostatin, cladribine and fludarabine. They have some common features in their mode of action, but differ both in their detailed pharmacology and the extent to which they have activity against specific lymphoid malignancies. Studies defining the scope of these drugs as single agents are now being followed by plans to exploit their potential synergy with other agents and clinically to define useful combination therapies.

Antineoplastic Agents↗
PubMed1996

Cloning, expression and characterization of a blood group B active recombinant alpha-D-galactosidase from soybean (Glycine max).

A cDNA encoding soybean alpha-D-galactosidase [E.C. 3.2.1.22] was obtained by screening a soybean library with Phaseolus alpha-D-galactosidase cDNA. The Glycine max alpha-D-galactosidase cDNA is 1.75 kb long and contains untranslated 5' and 3' sequences. The deduced amino acid sequence of the soybean gene has a high degree of homology with other eucaryotic alpha-D-galactosidases. Recombinant alpha-D-galactosidase (rGal) was expressed in Pichia pastoris and purified by affinity chromatography. Purified rGal was homogeneous as judged by SDS-PAGE analysis with the relative molecular mass under reducing conditions of 39.8, and under nonreducing conditions 38.0 kDa. The expressed protein contained the sequence NGLGHTPPMG at the N-terminus, corresponding to the deduced amino acid sequence of the soybean gene. The relative native molecular mass by Sephacryl S-200 chromatography was determined to be 33.1 kDa. The specific activity was 295.6 mumoles of PNP-alpha-D-galactopyranoside hydrolyzed per mg pure rGal per min. rGal was highly specific for alpha-D-galactosyl residues. No detectable hemagglutinin or protease activity was present in the preparations. Furthermore, rGal was active against the blood group B antigen in native human erythrocyte cell suspension assays. The only detectable erythrocyte phenotypic change was loss of the B and P1 epitopes. Consequently, recombinant Glycine max alpha-D-galactosidase may have useful biotechnical applications in the potential mass production of universally transfusable type O erythrocytes by enzymatic conversion.

ABO Blood-Group System↗
PubMed1996

Unilateral nasal infection of cotton rats with respiratory syncytial virus allows assessment of local and systemic immunity.

An in vivo model for the study of local and systemic effectors of immunity to respiratory syncytial virus (RSV) is described. Cotton rats (Sigmodon fulviventer) inoculated in one nostril with a small volume (2 microliters) of virus suspension contracted a unilateral nasal infection which did not extend to the contralateral nasal turbinates, nor to the lungs. Immunity to subsequent RSV challenge could be induced by small priming doses ( < 10 p.f.u. per animal), but was dependent upon viral replication, as virus inactivated by UV light was not immunogenic. Immunity occurred in the absence of detectable neutralizing serum antibody. The onset of resistance to viral challenge occurred simultaneously in ipsilateral nasal, contralateral nasal and pulmonary tissues. However, low levels of transient viral replication occurred in contralateral nasal turbinates and in lungs following virus challenge, thus indicating that local components of immunity acting at the ipsilateral site of infection were more effective than systemic components acting at the other sites. Further evidence is provided to suggest that three types of immunological effectors - local, persistent, systemic and transient systemic - participate in the immune response to RSV infection.

Animals↗
PubMed1996

Repetitive behavior and repetition avoidance: the role of the right hemisphere.

Based on clinical observations of patients suffering from brain damage, a recent model assumes a right hemisphere dominance for the suppression of repetitive behavior. This study set out to test whether or not the well-known effect of repetition avoidance in sequential response production is likewise mediated by the right hemisphere. It was found that, in 40 healthy subjects, avoidance of repetitions in a random number-generation task correlated positively with a relative superiority for design as compared to letter fluency. Since design fluency is predominantly mediated by the right frontal lobe and letter fluency by the left, this finding supports the notion of a right hemisphere dominance for the avoidance of repetitive responses. This study illustrates the usefulness of a neurobehavioral approach to repetition behavior in the randomization of response. In particular, it demonstrates that the phenomenon of repetition avoidance may be better accounted for in terms of a control mechanism preventing perservation than by referring to human subjects' "generally biased concept of randomness."

Adult↗
PubMed1996

Altered epidermal cell growth control in vivo by inducible expression of transforming growth factor beta 1 in the skin of transgenic mice.

An inducible bovine KIV* keratin gene promoter was used to target expression of latent or activated transforming growth factor beta 1 (TGF beta 1) to keratinocytes in transgenic mice. This short (2.2-kb) keratin 6 (K6) promoter element was generally silent in untreated animals but was induced in keratinocytes when placed in culture or, in vivo, in response to hyperplasia that follows topical application of the tumor promoter, 12-O-tetradecanoylphorbol-13-acetate. All of the K6-TGF beta 1 transgenic lines studied showed attenuation of the basal keratinocyte proliferative response to 12-O-tetradecanoylphorbol-13-acetate as a consequence of inducible TGF beta 1 gene expression. One of the six lines studied showed constitutive transgene expression at low levels in the skin, and this line had a 2- to 3-fold increase in epidermal DNA labeling index over control mice. Although in vitro TGF beta 1 is known to be a potent negative regulator of epithelial cell proliferation, in vivo TGF beta 1 has complex biological activities and can act as either a positive or negative regulator of keratinocyte proliferation.

Animals↗
PubMed1996

Thoracic duct function in fetal, newborn, and adult sheep.

We measured thoracic duct lymph flow rate versus outflow pressure in 7 chronically catheterized adult sheep and in 6 newborn lambs and compared our results to data previously obtained from 10 fetal sheep. In fetal sheep the thoracic duct lymph flow rate was 34.5 +/- 17.2 ml/hr or 11.7 +/- 6.0 ml/kg/hr. Fetal thoracic duct lymph flow deviated from baseline between 8 and 12 torr outflow pressure and lymph stopped at 18 +/- 2.5 torr. In newborn lambs the thoracic duct lymph flow rate was 49.5 +/- 22.0 ml/hr or 7.4 +/- 2.5 ml/kg/hr. The range of outflow pressures over which newborn lymph flow deviated from baseline was between 15 and 18 torr and lymph flow stopped at 26.2 +/- 6.4 torr. Adult sheep thoracic duct lymph flow rate was 130 +/- 74 ml/hr or 2.3 +/- 1.3 ml/kg/hr. Adult lymph flow deviated from baseline between 25 and 35 torr and stopped at an outflow pressure of 41.7 +/- 6.7 torr. The ability of the thoracic duct to return lymph against an outflow pressure improves with maturation. However, lymph flow rate corrected for body weight is greatest in immature animals. The higher corrected lymph flow rate in conjunction with the decreased ability to pump against an outflow pressure may help account for immature animals predisposition for edema.

Animals↗
PubMed1995

The Rab protein family: genetic mapping of six Rab genes in the mouse.

Rab proteins constitute a family of GTP-binding proteins that are located in distinct intracellular compartments and play a role in the regulation of vesicular trafficking. Yeast mutations in Rab gene homologs cause defects in vesicular transport similar to those observed in beige (bg) mice. To investigate Rab genes as candidates for mouse mutations characterized by defects in vesicular trafficking, we utilized an inter-subspecific backcross [C57BL/6J-bgJ x (C57BL/6J-bgJ x CAST/Ei)F1] segregating for the bg locus. Restriction fragment length polymorphisms (RFLPs) were obtained through Southern hybridization of F1 and C57BL/6J chromosomal DNA with the coding sequences of Rab genes. These RFLPs and 12 polymorphic microsatellites were used to determine the segregation of the Rab genes in 93 backcross mice. Rab4a, Rab4b, Rab7, Rab10, Rab22, and Rab24 were localized on mouse chromosomes 8, 7, 9, 12, 2, and 13, respectively. Although the results exclude these loci as candidates for bg, they demonstrate a wide dispersion of Rab genes throughout the mouse genome and reveal that Rab4b and Rab24 are possible candidates for the mouse mutations reduced pigmentation (rp) and purkinje cell degeneration (pcd), respectively.

Animals↗
PubMed1995

Role of the Syk autophosphorylation site and SH2 domains in B cell antigen receptor signaling.

To explore the mechanism(s) by which the Syk protein tyrosine kinase participates in B cell antigen receptor (BCR) signaling, we have studied the function of various Syk mutants in B cells made Syk deficient by homologous recombination knockout. Both Syk SH2 domains were required for BCR-mediated Syk and phospholipase C (PLC)-gamma 2 phosphorylation, inositol 1,4,5-triphosphate release, and Ca2+ mobilization. A possible explanation for this requirement was provided by findings that recruitment of Syk to tyrosine-phosphorylated immunoglobulin (Ig) alpha and Ig beta requires both Syk SH2 domains. A Syk mutant in which the putative autophosphorylation site (Y518/Y519) of Syk was changed to phenylalanine was also defective in signal transduction; however, this mutation did not affect recruitment to the phosphorylated immunoreceptor family tyrosine-based activation motifs (ITAMs). These findings not only confirm that both SH2 domains are necessary for Syk binding to tyrosine-phosphorylated Ig alpha and Ig beta but indicate that this binding is necessary for Syk (Y518/519) phosphorylation after BCR ligation. This sequence of events is apparently required for coupling the BCR to most cellular protein tyrosine phosphorylation, to the phosphorylation and activation of PLC-gamma 2, and to Ca2+ mobilization.

Amino Acid Sequence↗
PubMed1995

Phosphorylated immunoreceptor signaling motifs (ITAMs) exhibit unique abilities to bind and activate Lyn and Syk tyrosine kinases.

Signal transduction by T and B cell Ag receptors and certain receptors for Ig Fc regions (Fc gamma RI, hFc gamma RIIA, Fc gamma RIII, Fc alpha R, and Fc epsilon RI) involves a conserved sequence motif, termed an immunoreceptor tyrosine-based activation motif (ITAM) and found in multiple receptor chains. Phosphorylation of the two ITAM tyrosines is a critical event in signal transduction. To address the function of this phosphorylation, we assessed the ability of nonphosphorylated and biphosphorylated ((p)2ITAM) ITAM peptides to bind and modify the activity of src and syk family kinases in vivo and in vitro. All (p)2ITAMs, but not their nonphosphorylated counterparts, induced extensive protein tyrosine phosphorylation in permeabilized cells. However, the patterns of proteins phosphorylated differed among (p)2ITAMs. This phosphorylation was found to reflect activation of the src family kinase Lyn, but not Syk. In vitro studies using purified Lyn showed that src family kinase activation resulted from a direct interaction with (p)2ITAM. Binding studies demonstrated clear differences in binding specificity of (p)2ITAMs. Most strikingly, Ig alpha (p)2ITAM and TCR-zeta c and CD3 epsilon (p)2ITAMs exhibit inverse binding preferences for src and syk family kinases. Taken together, these findings demonstrate a novel mechanism by which src family tyrosine kinases are activated, and are consistent with the possibility that different ITAMs may preferentially activate distinct signaling pathways as a consequence of distinct effector Src homology 2 domain (SH2) binding preference.

Amino Acid Sequence↗