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Biomedical subjects

N R Brown

Publications and source records attributed to N R Brown.

At least 37 records · Page 2Linked to original sources
PubMed1991

Subjective organization of U.S. presidents.

College students appear to subjectively organize U.S. presidents into three groups and to use this organization to help them learn new information. Results of a paired comparison task in Experiment 1 suggested that subjects organized the presidents into Founding Fathers (Washington through John Quincy Adams), post-World War II presidents (Truman through Reagan), and noncontemporary presidents (Jackson through Franklin Roosevelt). This hypothesized organization was tested in Experiment 2 by presenting subjects with several lists with alternative organizations of the presidents. Difficulty of learning classifications of particular presidents within each list was predicted on the basis of the relation between that president's classification in the list and in the hypothesized preexisting organization. Instances where the preexisting and new classifications were consistent both for the particular president and for all other members of the group were easiest to learn. Instances where the particular president's classification was consistent but where some other presidents in the group were classified differently were of intermediate difficulty. Instances where neither the individual president's classification nor that of the entire group were consistent were most difficult. The results provided converging evidence for the hypothesized subjective organization of the presidents and also demonstrated the usefulness of a method that may be applicable to testing subjective organizations in a wide variety of other areas.

Adolescent↗
PubMed1990

Investigation of the structural basis of the interaction of calpain II with phospholipid and with carbohydrate.

Two forms of pig kidney calpain II were isolated, both of which appeared to contain an intact 80 kDa large subunit, but which showed specific proteolytic degradation at the N-terminal end of the 30 kDa small subunit. The structure of each of these molecules was investigated by amino acid sequence analysis. The forms corresponded to molecules with small subunits starting at residue 38 (degraded calpain A) and at residue 62 (degraded calpain B) of the complete sequence. These molecules were tested for their ability to interact with phosphatidylinositol and with carbohydrate (agarose gel-filtration media). Calpain and degraded calpain A, but not degraded calpain B, would interact with phosphatidylinositol. Thus the sequence (G)17TAMRILG (residues 38-61) is essential for the interaction. Neither calpain nor the degraded forms of the enzyme showed specific interaction with carbohydrate.

Amino Acid Sequence↗
PubMed1988

A soluble CD4 protein selectively inhibits HIV replication and syncytium formation.

The CD4 (T4) molecule is expressed on a subset of T lymphocytes involved in class II MHC recognition, and is probably the physiological receptor for one or more monomorphic regions of class II MHC (refs 1-3). CD4 also functions as a receptor for the human immunodeficiency virus (HIV) exterior envelope glycoprotein (gp120) (refs 4-9), being essential for virus entry into the host cell and for membrane fusion, which contributes to cell-to-cell transmission of the virus and to its cytopathic effects. We have used a baculovirus expression system to generate mg quantities of a hydrophilic extracellular segment of CD4. Concentrations of soluble CD4 in the nanomolar range, like certain anti-CD4 monoclonal antibodies, inhibit syncytium formation and HIV infection by binding gp120-expressing cells. Perhaps more importantly, class II specific T-cell interactions are uninhibited by soluble CD4 protein, whereas they are virtually abrogated by equivalent amounts of anti-T4 antibody. This may reflect substantial differences in CD4 affinity for gp120 and class II MHC.

Animals↗
PubMed1988

Molecular cloning of the common acute lymphoblastic leukemia antigen (CALLA) identifies a type II integral membrane protein.

Common acute lymphoblastic leukemia antigen (CALLA) is a 100-kDa cell-surface glycoprotein expressed on most acute lymphoblastic leukemias and certain other immature lymphoid malignancies and on normal lymphoid progenitors. The latter are either uncommitted to B- or T-cell lineage or committed to only the earliest stages of B- or T-lymphocyte maturation. To elucidate to homogeneity, obtained the NH2-terminal sequence from both the intact protein and derived tryptic and V8 protease peptides and isolated CALLA cDNAs from a Nalm-6 cell line lambda gt10 library using redundant oligonucleotide probes. The CALLA cDNA sequence predicts a 750-amino acid integral membrane protein with a single 24-amino acid hydrophobic segment that could function as both a transmembrane region and a signal peptide. The COOH-terminal 700 amino acids, including six potential N-linked glycosylation sites compose the extracellular protein segment, whereas the 25 NH2-terminal amino acids remaining after cleavage of the initiation methionine form the cytoplasmic tail. CALLA+ cells contain CALLA transcripts of 2.7 to 5.7 kilobases with the major 5.7- and 3.7-kilobase mRNAs being preferentially expressed in specific cell types.

Amino Acid Sequence↗
PubMed1988

Adhesion domain of human T11 (CD2) is encoded by a single exon.

The 50-kDa T11 (CD2) T-lymphocyte surface glycoprotein facilitates physical adhesion between T-lineage cells and their cognate cellular counterparts (cytotoxic T-lymphocytes-target cells, helper T lymphocytes-antigen-presenting cells, or thymocytes-thymic epithelium) as well as signaling through the antigen-specific T3-Ti receptor complex. To examine the relationship between the structure and function of the T11 molecule, we have utilized a baculoviral expression system to produce milligram quantities of the hydrophilic extracellular T11 segment. Enzyme cleavage, microsequencing, and HPLC analyses of the expressed protein in conjunction with genomic cloning information show that the domain involved in cellular adhesion is encoded by a single 321-base-pair exon.

Amino Acid Sequence↗
PubMed1988

Binding site for human immunodeficiency virus coat protein gp120 is located in the NH2-terminal region of T4 (CD4) and requires the intact variable-region-like domain.

The external segment of the T4 (CD4) glycoprotein functions as the T-cell surface receptor for human immunodeficiency virus by binding the major viral coat protein (gp120) with relatively high affinity. To more precisely define the region of T4 involved in gp120 interaction, we used purified, soluble forms of T4 anchor-minus polypeptides (produced in a baculovirus system) in conjunction with proteolytic fragmentation, microsequencing, and a specific T4-gp120 binding assay. The results indicate that the NH2-terminal region of T4 including the immunoglobulin variable-region-like domain is required for gp120 interaction. In contrast, the COOH-terminal half of the molecule, containing the two potential N-linked glycosylation sites, is not necessary. Furthermore, reduction of intrachain disulfide bonds in the T4 molecular abrogates gp120 binding, thereby strongly implying that the binding site for gp120 is dependent on the stabilized domain structure of the active binding region.

Amino Acid Sequence↗
PubMed1987

Molecular cloning and expression of T11 cDNAs reveal a receptor-like structure on human T lymphocytes.

The T11 (CD2) sheep-erythrocyte-binding protein is a T-cell surface molecule involved in activation of T lymphocytes and thymocytes, including those lacking the T3-Ti antigen-receptor complex. The primary structure of T11 was deduced from protein microsequencing and cDNA cloning. The mature human protein appears to be divided into three domains: a hydrophilic 185 amino acid external domain bearing only limited homology to the T-cell surface protein T4 and the immunoglobulin kappa light chain variable region, a 25 amino acid hydrophobic transmembrane segment, and a 126 amino acid cytoplasmic domain rich in prolines and basic residues. Transfection of cDNAs encoding either the 1.7- or the 1.3-kilobase T11 mRNA into COS-1 cells resulted in expression of surface T11 epitopes as well as sheep-erythrocyte-binding capacity. The predicted structure is consistent with the possibility that T11 functions in signal transduction.

Amino Acid Sequence↗
PubMed1987

DNA sequence analysis of two bovine immunoglobulin CH gamma pseudogenes.

A bovine calf liver DNA library in lambda 2001 bacteriophage has been screened with a human Ig gamma 4 heavy-chain constant-region gene probe. Four hybridizing clones have been identified, and the DNA sequences in two of these, which have high homology with CH gamma genes, are reported here. Within the bovine sequences, four separate exons can be identified, corresponding to the three CH domains and the hinge of gamma heavy-chain genes. Both of these genes contain atypical sequences around one or more of their exon/intron boundaries with consequent loss of splice sites, indicating that these are probably gamma pseudogenes. One sequence codes for a C-terminal peptide which matches the 18-mer C-terminal heavy-chain peptide of bovine serum IgG2, the other encodes a C-terminal peptide unknown in the bovine. These results suggest that evolutionary duplication of CH gamma genes has occurred in the bovine.

Amino Acid Sequence↗
PubMed1981

Sodium and rubidium uptake in cells transformed by Rous sarcoma virus.

Rates of uptake and intracellular concentrations of monovalent cations were measured in virus-transformed and nontransformed chick embryo (CE) cells. Uptake of 22Na+ into cells transformed by the BH strain of Rous sarcoma virus (RSV-BH) (CE-BH) was about double the rate of uptake into CE cells, or cells transformed by the Schmidt-Ruppin strain (RSV-SR): CE-SR. Likewise, the rate of efflux of 22Na+ was greater in CE-BH cells than in CE or CE-SR cells. The greater permeability of CE-BH cells to Na+ was apparent in higher intracellular Na+ concentrations. Experiments with cells exhibiting temperature-dependent transformation showed that new RNA and protein synthesis was a requirement for the acquisition of increased Na+ permeability, suggesting that the change is an indirect effect of the virus-coded transformation-inducing protein. Rates of 86Rb+ uptake, used as a measure of K+ influx, were indistinguishable in CE, CE-BH, and CE-SR cells. Also, equilibrium intracellular levels of 86Rb+ were similar in transformed and nontransformed cells, as were observed concentrations of K+. Also, no differences in ATPase activity, as indicated by ouabain binding or temperature sensitivity, were observed. We conclude that monovalent cations play no direct role in RSV-induced transformation, although the higher levels of Na+ in CE-BH cells may be responsible for other distinguishing biochemical features of these cells.

Animals↗
PubMed1981

Increased glucose uptake capacity of Rous-transformed cells and the relevance of deprivation derepression.

The increased rate of glucose uptake found in cells transformed by Rous sarcoma virus was shown to be enhanced relative to the changes in uptake induced in nontransformed cells by deprivation of glucose (deprivation derepression). Glucose-specific uptake sites were distinguished from glucose-galactose sites in nontransformed cells, and the capacities for glucose uptake and for galactose uptake were increased to about the same extent by the exclusion of glucose from the cell culture medium. Deprivation derepression occurred without a requirement for new RNA or protein synthesis, suggesting that preexisting inactivate uptake sites were activated. Deprivation derepression could be mimicked by the treatment of cells with adenosine triphosphatase activators, and adenosine triphosphate levels were reduced in glucose-deprived cells and in cells treated with adenosine triphosphatase activators. Cells transformed by the Bryan strain of Rous sarcoma virus were unresponsive to addition of high concentrations of glucose, to glucose starvation, or to treatment with adenosine triphosphatase activators, and the relative capacity for glucose uptake in these transformed cells was enhanced much more than the capacity of galactose uptake. It was concluded that cells infected by the Bryan strain of rous sarcoma virus in the process of transformation selectively synthesize more sites specific for glucose uptake. Lower levels of adenosine triphosphate found in transformed cells possibly contribute to a chronic derepression of uptake sites.

Adenosine Triphosphate↗
PubMed1978

Sodium concentrations affect metabolite uptake and cellular metabolism.

Rates of uptake of glucose (measured with 3H-2-deoxy-d-glucose), galactose, and leucine after exposure of chick embryo cells to increasing concentrations of Na+ over the range 100 to 200 mM. Uptake of nucleosides was unaffected by [Na+] over this range. Prior exposure of cells was required for the [Na+] effect on uptake. Changes were measureable within two hours after changing [Na+], and although the capacity for deoxyglucose uptake remained constant thereafter, the capacity for leucine uptake continued to change during the next few hours. Inhibition of protein synthesis by cycloheximide, or of RNA synthesis by Actinomycin D, failed to prevent these uptake changes. Analysis of the kinetics of uptake showed that only the Km for uptake of deoxyglucose or leucine was affected by [Na+]; the maximum V for each compound remained the same. Effects of [Na+]; could be distinguished from the increased capacity for glucose uptake induced by glucose starvation. Incorporation of both radioactive uridine into RNA, and radioactive thymidine into DNA, were affected by [Na+[, but the differences were not correlated with uptake of other metoblites. No differences in countable mitoses were apparent, although the growth of chick embryo cells in increased slightly with increasing [Na+]. Changes in uptake due to differing [Na+] also were observed in mammalian (rat NRK) cells. However, no effects of [Na+] on rates of cell growth or saturation density were observed with these cells.

Animals↗
PubMed1978

Cytoplasmic vacuoles of Rous virus transformed cells are organelles involved in cation uptake.

Cytoplasmic vacuoles induced during transformation of cells by Bryan strain Rous sarcoma virus (RSV-BH) have been studied using the cationic dye, neutral red(NR). Both the rate of uptake and the accumulation of NR are greater in RSV-BH transformed cells than non-transformed cells however, uptake was greater in vacuolated than in non-vacuolated cells, whether or not they were transformed. The NR was incorporated into pre-existing vacuoles in the absence of cytoplasmic staining, suggesting the existence of direct channels from the cell surface to the vacuoles. Other low mol. wt. cationic dyes could also be incorporated into vacuoles, although those with branched structures or cationic weights greater than 330 were excluded. No anionic dyes were incorporated. Infection of cells with a virus mutant, RSV-BH-Ta, induces temperature-dependent vacuolization. After a shift to the vacuole-permissive temperature, vacuoles developed at different rates and with morphological variations with different cations. Vacuoles which had formed in the presence of several cations, (K+, Rb+, tris+, choline+) failed to disappear when cells were incubated at a temperature sufficient to revert vacuoles formed in Na+-containing medium. No short-term effects of Cl-replacements (Br-, I-, or SO2-4) on vacuolization or reversal were observed. The results suggest that these vacuoles are organelles involved in cation uptake. A possible function for these organelles in RSV-BH induced malignancy is discussed.

Animals↗