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Biomedical subjects

A Goldstein

Publications and source records attributed to A Goldstein.

At least 73 records · Page 4Linked to original sources
PubMed1994

Primary structure and functional expression of a guinea pig kappa opioid (dynorphin) receptor.

A full-length cDNA encoding the guinea pig kappa opioid (dynorphin) receptor has been isolated. The deduced protein contains 380 aa and seven hydrophobic alpha-helices characteristic of the G protein-coupled receptors. This receptor is 90% identical to the mouse and rat kappa receptors, with the greatest level of divergence in the N-terminal region. When expressed in COS-7 cells, the receptor displays high affinity and stereospecificity toward dynorphin peptides and other kappa-selective opioid ligands such as U50, 488. It does not bind the mu- and delta-selective opioid ligands. The expressed receptor is functionally coupled to G protein(s) to inhibit adenylyl cyclase and Ca2+ channels. The guinea pig kappa receptor mRNA is expressed in many brain areas, including the cerebellum, a pattern that agrees well with autoradiographic maps of classical guinea pig kappa binding sites. Species differences in the pharmacology and mRNA distribution between the cloned guinea pig and rat kappa receptors may be worthy of further examination.

Amino Acid Sequence↗
PubMed1994

Romanticism and self-esteem among pregnant adolescents, adolescent mothers, and nonpregnant, nonparenting teens.

Feelings of romanticism and self-esteem among pregnant adolescents, adolescent mothers, and a control group of nonpregnant, nonparenting adolescents were investigated. The Bachman Self-Esteem Scale (Bachman, O'Malley, & Johnston, 1978) and the Dean Romanticism Scale (Dean, 1961) were distributed to 649 U.S. female adolescents--255 pregnant adolescents, 121 adolescent mothers, and 273 teenagers in the control group. For romanticism, the results indicated a significant main effect for group (pregnant teens, teen mothers, and a control group consisting of nonpregnant, nonparenting teenagers) and ethnicity (White, Hispanic, African American, and Asian) but not for age (13 to 15 years and 16 to 19 years). The pregnant teens and teen mothers thus had a higher degree of romanticism than the control group did. For self-esteem, there was a significant main effect for race, but not for group or for age. This main effect was qualified by a significant interaction between ethnicity and age.

Adolescent↗
PubMed1994

Detection of rectal antibodies to HIV-1 by a sensitive chemiluminescent western blot immunodetection method.

Western blot with a time-dependent enhanced chemiluminescence immunodetection method (ECL-WB) was shown to be 100-fold more sensitive than standard commercial colorimetric Western blots (WB) for detecting serum IgG to human immunodeficiency virus type 1 (HIV-1). ECL-WB was then used to test rectal secretions from 15 HIV-1 infected subjects (HIV+) and 7 uninfected subjects (HIV-) to document local IgG, IgA, and secretory component-associated immunoglobulin (SC-Ig) to HIV-1 proteins. Fourteen of 15 HIV+ subjects had rectal IgA to at least 1 HIV-1 protein, most often to gp41 (80%) or p24 (60%) and 14 (93%) had IgG to gp160, gp120, or gp41. Of seven HIV- subjects, none had detectable bands to HIV-1 proteins. SC-Ig to HIV-1 proteins was detected in all five rectal samples tested. However, the antibody profiles differed from those of rectal IgA, suggesting more than one source of rectal IgA to HIV. ECL-WB requires individual optimization and interpretation for each specimen as well as expensive reagents and is, therefore, not currently applicable to screening assays. However, the method offers promise as a sensitive method to characterize low-level immune responses (IgG, IgA, and SC-Ig) to HIV-1 proteins at local sites such as rectal mucosae.

Blotting, Western↗
PubMed1993

Cloning and pharmacological characterization of a rat kappa opioid receptor.

A full-length cDNA was isolated from a rat striatal library by using low-stringency screening with two PCR fragments, one spanning transmembrane domains 3-6 of the mouse delta opioid receptor and the other unidentified but homologous to the mouse delta receptor from rat brain. The novel cDNA had a long open reading frame encoding a protein of 380 residues with 59% identity to the mouse delta receptor and topography consistent with a seven-helix guanine nucleotide-binding protein-coupled receptor. COS-1 cells transfected with the coding region of this clone showed high-affinity binding to kappa opioid receptor-selective ligands such as dynorphin A and U-50,488 and also nonselective opioid ligands such as bremazocine, ethylketocyclazocine, and naloxone. Not bound at all (or bound with low affinity) were dynorphin A-(2-13), enantiomers of naloxone and levophanol [i.e., (+)-naloxone and dextrorphan], and selective mu and delta opioid receptor ligands. Activation of the expressed receptor by kappa receptor agonists led to inhibition of cAMP. Finally, in situ hybridization revealed a mRNA distribution in rat brain that corresponded well to the distribution of binding sites labeled with kappa-selective ligands. These observations indicate that we have cloned a cDNA encoding a rat kappa receptor of the kappa 1 subtype.

3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cycloh↗
PubMed1993

Amino acid residues essential for biological activity of a peptide derived from a major histocompatibility complex class I antigen.

The stimulatory activity of peptides from the alpha 1 domain of the major histocompatibility complex (MHC) class I antigen on adipose cell glucose transport was previously shown to require a preformed, ordered conformation of the peptide. The two peptides studied previously were Dk-(61-85) (ERETQIAKGNEQSFRVDLRTLLRYY) and Dk-(69-85). We now show that systematic alanine substitution in Dk-(69-85) identifies residues that are essential for biological activity. Ordered structure of the peptides, estimated by circular dichroism, was found in all peptides with activity, but with a complex variety of spectra. Inactive peptides were in either a random coil or an ordered structure. Ordered structure, therefore, is not sufficient for activity. The peptides self-interact in the absence of cells and form aggregates that precipitate upon centrifugation. The tendency to aggregate is correlated with biological potency. Only MHC class I molecules have significant homology to the peptides studied here. The peptide self-interaction suggests that the biological effects in cells, which result from inhibition of receptor and transporter internalization, may be due to the binding (tantamount to self-interaction) of the peptide to the homologous sequences in the alpha 1 domain of the MHC class I molecule.

Adipose Tissue↗
PubMed1993

Cancer associated haemolytic uraemic syndrome developing prior to treatment with cytotoxic agents.

The haemolytic uraemic syndrome has been reported in children and adults with neoplasias treated with mitomycin C and occasionally in adults prior to chemotherapeutic treatment, but it has not been reported in a child prior to the use of cytotoxic drugs. This case report concerns the development of the haemolytic uraemic syndrome in a 7-year-old male child with a metastatic hepatocellular carcinoma. The child had persisting haemolysis and renal impairment, and died three weeks after presentation. Though our experience with similar tumours suggested the outlook would be poor, we had hoped to provide palliative chemotherapy. This proved impossible as optimal chemotherapy could not be used because of the renal impairment.

Anemia, Hemolytic↗
PubMed1993

Chronic granulomatous disease presenting in childhood with Pseudomonas cepacia septicaemia.

Two children who presented with fever, enlarged liver and spleen and ascites were found to have Pseudomonas cepacia septicaemia which proved fatal despite appropriate antibiotics and maximum supportive care. Chronic granulomatous disease of childhood (CGD) was subsequently diagnosed in both children. The possibility of CGD needs to be considered in any child with unexplained P. cepacia infection.

Anti-Bacterial Agents↗
PubMed1993

Overview of the physics of US.

In ultrasonography (US), high-frequency sound waves are transmitted through the body by a transducer. When a transmitted ultrasound pulse encounters a tissue target, some of its energy is deflected back to the transducer. The time of flight of this ultrasound echo is used to calculate depth of the target in the transducer beam. The pulse-echo parameters used in the formation of images include echo amplitude, target spatial position, and frequency shift between the transmitted pulse and the received echo. The first two are displayed in gray-scale images and all three in color flow images. In gray-scale US, echo amplitude is encoded into shades of gray, with the lighter shades representing higher amplitude echoes. In color flow US, velocity of moving blood is usually presented in blue for motion toward the transducer and in red for motion away from it. A Doppler spectrum depicts changing blood velocity as a function of time. US has become more clinically valuable due to its ability to demonstrate soft-tissue structures, real-time imaging capability, relative safety, portability, and cost-effectiveness.

Biophysical Phenomena↗
PubMed1993

Instrumentation of digital gray-scale US.

Modern, high-resolution, gray-scale, ultrasound (US) imaging equipment is computer based, with all hardware signal processing functions under software control. This systems architecture permits maximum flexibility in function, rapid upgrades, and reliable performance. With modern US equipment, the spatial dimensions of the analog image are transformed into a digital matrix of picture elements (pixels). The volume of tissue, or voxel, that contributes to the echo amplitudes received from each pixel depends crucially on the section (ie, "slice") thickness at the voxel depth. Partial volume effects are more likely to occur in a longer voxel located at a depth outside the section thickness focal zone. The echo signal voltage, or amplitude, is acquired by an analog-to-digital converter simultaneously with the pixel location of the image echo origin. The most accurate echo amplitudes (with least partial volume averaging) occur at the highest image magnification when the voxel dimensions are the smallest in and out of the scan plane. With computer-based imaging, postprocessing procedures, such as fill-in algorithms and digital calipers (measurements of distances in images), can be used to aid in diagnosis.

Analog-Digital Conversion↗
PubMed1993

Primary care physicians' views on access and health care reform: the situation in North Carolina.

BACKGROUND: This cross-sectional study assessed physicians' satisfaction with the current insurance-based reimbursement system and preferences for the two most frequently discussed health care reform proposals, and estimated the association between demographic and practice characteristics and attitudes toward health policy issues and reform plans. METHODS: A random sample of 300 physicians was drawn from state licensure files of general practitioners, family physicians, and pediatricians practicing in North Carolina. All sample physicians were sent a schematic outline of the two major health reform alternatives and a 1-page self-administered questionnaire to determine their attitudes toward the current health care system and their preferences for health reform alternatives. RESULTS: Sixty-nine percent of physicians responded to the survey. The responses indicated dissatisfaction with the current system and strong beliefs that access to care is inadequate in this diverse state with a large poor and rural population. Nearly one third of the physicians reported having insufficient information to choose between plans. Among physicians expressing a preference, 37% preferred managed competition, 38% preferred continuing the current system, and 25% preferred a single-payer system. CONCLUSIONS: A uniform opinion about health care policy is a thing of the past for American medicine. Because terms used in the health reform debate (especially "managed competition") are ambiguous and set in the context of an increasingly diverse medical profession, no single direction of health reform (much less a specific plan) secures widespread understanding or support from a large proportion of physicians. None of the plans will please all of the doctors all of the time.

Adult↗
PubMed1993

Correlation between insulin receptor occupancy and tyrosine kinase activity at low insulin concentrations and effect of major histocompatibility complex class I-derived peptide.

In rat adipocytes, insulin dose-response curves were determined for the following effects in the same cells under the same conditions: glucose uptake, binding to insulin receptors (IR), IR autophosphorylation in vivo and in vitro, IR tyrosine kinase activity and insulin-stimulated phosphatidylinositol (PI) kinase. All the EC50 values were essentially the same (mean +/- S.E.M. was 7 +/- 1 nM), except for glucose uptake, which was 170 pM. Using an improved method, we were able to measure PI kinase activity at picomolar concentrations of insulin (> 30 pM) corresponding to the EC50 for glucose uptake. These experiments showed that insulin-stimulated increase in glucose uptake was associated with an increase in antiphosphotyrosine antibody precipitable PI kinase activity, consistent with the view that IR tyrosine kinase activity may be involved in insulin-mediated signaling of glucose uptake. Small peptides (17-25 residues long) derived from major histocompatibility complex class I have previously been shown to inhibit IR internalization without any effect on the affinity of insulin to the receptor. It is now shown that the peptide-mediated inhibition of internalization, which doubles the number of insulin-occupied receptors at an insulin concentration of 70 pM, also results in a corresponding enhancement of PI kinase activity and glucose uptake. Thus, the receptors arrested on the cell surface by the peptide are biologically active.

1-Phosphatidylinositol 4-Kinase↗
PubMed1993

Variables related to romanticism and self-esteem in pregnant teenagers.

In this study, the Dean Romanticism Scale and the Bachman Self-esteem Scale were administered to 121 teenagers between the ages of 12 and 19 in Southern California to investigate their degree of romanticism and self-esteem. The study also explored whether there was any relationship between the dependent variables of romanticism and self-esteem and ten independent variables--age, race, place of residence during pregnancy, age when first sexual intercourse occurred, age when pregnancy occurred, incidence of sexual abuse, incidence of abortion, adoption considerations, whether the subject was currently sexually active, and whether the teenager planned to have a child with the father of the baby. The results indicated that two variables were significantly related to feelings of romanticism--adoption considerations and whether the adolescent planned to have a child with the baby's father. In addition, two variables were significantly related to self-esteem--the incidence of sexual abuse and the incidence of abortion.

Abortion, Induced↗
PubMed1992

Expression cloning of cDNA encoding a seven-helix receptor from human placenta with affinity for opioid ligands.

Here we report the expression cloning of cDNA encoding a putative opioid receptor from a human placenta cDNA library. Placental opioid receptors are of the kappa type. As the dynorphin opioid peptides are kappa-selective, a dynorphin ligand was used in an affinity-enrichment (panning) procedure to select transiently transfected COS-7 cells expressing kappa receptor binding sites. The cloned cDNA encodes a 440-residue protein of the seven-helix guanine nucleotide-binding protein (G-protein)-coupled receptor family. Ligand binding reveals a stereospecific site with typical opioid properties, which binds peptide and nonpeptide opioids with moderate affinity (Kd approximately 100 nM) and which lacks the expected kappa selectivity. The deduced transmembrane domain is 93% identical to the homologous region of the human neuromedin K (neurokinin B) receptor, but the N-terminal and C-terminal sequences have many dissimilarities. The expressed receptor binds opioid ligands but not tachykinins; and under the same conditions, a cloned rat neuromedin K receptor binds tachykinins but not opioids.

Amino Acid Sequence↗