Showing papers by "University of California, San Francisco published in 1985"
TL;DR: In this article, six monoclonal antibodies have been isolated from mice immunized with synthetic peptide immunogens whose sequences are derived from that of the human c-myc gene product.
Abstract: Six monoclonal antibodies have been isolated from mice immunized with synthetic peptide immunogens whose sequences are derived from that of the human c-myc gene product. Five of these antibodies precipitate p62c-myc from human cells, and three of these five also recognize the mouse c-myc gene product. None of the antibodies sees the chicken p110gag-myc protein. All six antibodies recognize immunoblotted p62c-myc. These reagents also provide the basis for an immunoblotting assay by which to quantitate p62c-myc in cells.
2,520 citations
TL;DR: The entire 1,370-amino-acid sequence of the human insulin receptor precursor is deduced from a single complementary DNA clone, finding sequence homologies to human epidermal growth factor receptor and the members of the src family of oncogene products.
Abstract: We have deduced the entire 1,370-amino-acid sequence of the human insulin receptor precursor from a single complementary DNA clone. The precursor starts with a 27-amino-acid signal sequence, followed by the receptor α-subunit, a precursor processing enzyme cleavage site, then the β-subunit containing a single 23-amino-acid transmembrane sequence. There are sequence homologies to human epidermal growth factor receptor and the members of the src family of oncogene products.
2,140 citations
TL;DR: Identification of complementary DNAs encoding the human glucocorticoid receptor predicts two protein forms, of 777 (α) and 742 (β) amino acids, which differ at their carboxy termini, which may define the DNA-binding domain.
Abstract: Identification of complementary DNAs encoding the human glucocorticoid receptor predicts two protein forms, of 777 (alpha) and 742 (beta) amino acids, which differ at their carboxy termini. The proteins contain a cysteine/lysine/arginine-rich region which may define the DNA-binding domain. Pure radiolabelled glucocorticoid receptor, synthesized in vitro, is immunoreactive and possesses intrinsic steroid-binding activity characteristic of the native glucocorticoid receptor.
1,854 citations
TL;DR: A clone encoding PrP 27-30, the major protein in purified preparations of scrapie agent, was selected from a scrapie-infected hamster brain cDNA library by oligonucleotide probes corresponding to the N terminus of the protein.
1,514 citations
TL;DR: A cloned approximately 5 kb cDNA (human placenta) contains the coding sequences for the insulin receptor; the nucleotide sequence predicts a 1382 amino acid precursor and the overall structure is reminiscent of the EGF receptor.
1,418 citations
TL;DR: In this article, a comparative study of mtDNA and nuclear DNA variability is presented, with emphasis on mtDNA's uniparental and apparently haploid mode of inheritance, which makes mtDNA a superb tool for building trees and time scales relating molecular lineages at and below the species level.
Abstract: This essay reviews comparative studies of animal mitochondrial DNA (mtDNA), with emphasis on findings made and ideas developed at Berkeley. It argues that such studies are bringing together two previous paths of progress in evolutionary biology. One path is that of those who worked far above the species level and were concerned with genealogical trees, time scales and the accumulation of new mutations on surviving molecular lineages. The other path is that of those who worked at and below the species level and were concerned mainly with population structure, migration and the frequencies of alleles that existed in an ancestral population. This fusion of paths is made possible by the high rate at which mutations accumulate on mtDNA lineages and by this molecule's uniparental and apparently haploid mode of inheritance. These properties make mtDNA a superb tool for building trees and time scales relating molecular lineages at and below the species level. In addition, owing to its mode of inheritance, mtDNA is more sensitive to bottlenecks in population size and to population subdivision than are nuclear genes. Joint comparative studies of both mtDNA and nuclear DNA variability give us valuable insights into how effective population size has varied through time. Such studies also give insight into the conditions under which mtDNA from one species can colonize another species.
1,208 citations
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01 Jan 1985TL;DR: Ekman et al. as discussed by the authors described how lies vary in form and can differ from other types of misinformation, as well as how a person's body language, voice, and facial expressions can give away a lie but still escape detection.
Abstract: From breaking the law to breaking a promise, how do people lie and how can they be caught? Ekman study describes how lies vary in form and can differ from other types of misinformation, as well as how a person's body language, voice, and facial expressions can give away a lie but still escape detection.
1,096 citations
TL;DR: Transfection of DNA encoding foreign secretory proteins into regulated secretory cells has provided insight into the specificity of sorting into secretory vesicles.
Abstract: Protein secretion from cells can take several forms. Secretion is constitutive if proteins are secreted as fast as they are synthesized. In regulated secretion newly synthesized proteins destined for secretion are stored at high concentration in secretory vesicles until the cell receives an appropriate stimulus. When both constitutive and regulated protein secretion can take place in the same cell a mechanism must exist for sorting the correct secretory protein into the correct secretory vesicle. The secretory vesicle must then be delivered to the appropriate region of plasma membrane. Transfection of DNA encoding foreign secretory proteins into regulated secretory cells has provided insight into the specificity of sorting into secretory vesicles.
1,020 citations
TL;DR: The nucleotide sequence of molecular clones of DNA from a retrovirus, ARV-2, associated with the acquired immune deficiency syndrome (AIDS), was determined and the cloned gag and env genes of ARv-2 were shown to express viral proteins.
Abstract: The nucleotide sequence of molecular clones of DNA from a retrovirus, ARV-2, associated with the acquired immune deficiency syndrome (AIDS) was determined. Proviral DNA of ARV-2 (9737 base pairs) has long terminal repeat structures (636 base pairs) and long open reading frames encoding gag (506 codons), pol (1003 codons), and env (863 codons) genes. Two additional open reading frames were identified. Significant amino acid homology with several other retroviruses was noted in the predicted product of gag and pol, but ARV-2 was as closely related to murine and avian retroviruses as it was to human T-cell leukemia viruses (HTLV-I and HTLV-II). By means of an SV-40 vector in transfected simian cells, the cloned gag and env genes of ARV-2 were shown to express viral proteins.
723 citations
TL;DR: Analysis of this region by replacement of specific portions with nondiscriminatory control elements from viral systems shows that a transcriptional enhancer is located in the distal portion of the 5' flanking DNA; its position has been mapped by deletion analysis.
Abstract: The 59 flanking DNA of the rat insulin I gene contains sequences controlling cell-specific expression. Analysis of this region by replacement of specific portions with nondiscriminatory control elements from viral systems shows that a transcriptional enhancer is located in the distal portion of the 59 flanking DNA; its position has been mapped by deletion analysis. Additional experiments suggest that another distinct regulatory element is located more proximal to the transcription start site. The activity of both elements is restricted to pancreatic B cells. The combinatorial effect of multiple control elements could explain the cell-specific expression of insulin genes.
676 citations
TL;DR: An in vitro transcription system derived from uninfected HeLa cells that accurately initiates RNA synthesis at the herpes virus thymidine kinase (TK) promoter is characterized and three distinctive protein binding sites are identified.
TL;DR: The sequence of cloned rat liver PDI complementary DNA is described which predicts a protein with two distinct regions homologous with Escherichia coli thioredoxin, a known cofactor in oxidation–reduction reactions, suggesting that PDI, similar in action to thiOREDoxin, catalyses disulphide bond interchange via an internal disulPHide–sulphydryl interchange.
Abstract: The formation of disulphide bonds is essential to the structure and function of proteins. These bonds rapidly form either cotranslationally or immediately post-translationally in the lumen of the endoplasmic reticulum. Native disulphide pairing for such proteins has been achieved in vitro; however, the rates of reassembly are slow and the conditions non-physiological. To account for these observations, Anfinsen et al. proposed that a 'disulphide interchange protein' was the in vivo catalyst of disulphide bond rearrangement. Other groups discovered an activity with similar characteristics that catalysed the reductive cleavage of insulin and may be associated with insulin degradation, although this result has been disputed. The enzyme involved, protein disulphide isomerase (PDI; EC 5.3.4.1), may be the in vivo catalyst of disulphide bond formation. Here we describe the sequence of cloned rat liver PDI complementary DNA which predicts a protein with two distinct regions homologous with Escherichia coli thioredoxin, a known cofactor in oxidation-reduction reactions. Each of these regions contains the presumed active site sequence Trp-Cys-Gly-His-Cys-Lys, suggesting that PDI, similar in action to thioredoxin, catalyses disulphide bond interchange via an internal disulphide-sulphydryl interchange. The cDNA predicts a signal peptide consistent with the view that PDI is a luminal endoplasmic reticulum protein. PDI messenger RNA, although ubiquitous, is more highly concentrated in secretory cells.
TL;DR: It is shown that a neighboring gene has a large region with strong homology to engrailed, and that it also contains a homeo box, which is located near the 3' end of a 1700 bp open reading frame.
TL;DR: In this article, problems of managing chronic illness at home are addressed in terms of the concept of work: what types and subtypes of work, entailing what tasks, who does them, how, where, the consequences, the problems involved.
Abstract: Problems of managing chronic illness at home are addressed in terms of the concept of “work:” what types and subtypes of work, entailing what tasks, who does them, how, where, the consequences, the problems involved. Three types of work and consequences of their interplay are discussed: illness work, everyday life work, and biographical work. Theoretical concerns of the sociology of work are addressed as well as the substantive issues of managing chronic illness.
TL;DR: In this article, the authors conceptualize the division of labor in terms of work, and make a necessary distinction between work and workers, and its implications, including actor, accountability, division of rights versus division of labour, work patterns and interactional styles.
Abstract: The paper is an attempt to conceptualize the division of labor in terms of work. This perspective leads to a necessary distinction between work and workers, and its implications. Among the main considerations discussed are actor, accountability, division of rights versus division of labor, work patterns and interactional styles, rapidly changing organizations and industries in relation to their divisions of labor, and reciprocal macro and micro impacts. Some research implications are also discussed.
TL;DR: The relative amount of apolipoprotein (apo-) E mRNA in 12 different tissues of the rat and marmoset was examined by dot blot hybridization using cloned cDNA probes as discussed by the authors.
Abstract: The relative amount of apolipoprotein (apo-) E mRNA in 12 different tissues of the rat and marmoset was examined by dot blot hybridization using cloned cDNA probes. As expected, it was found to be most abundant in the liver. However, substantial amounts of apo-E mRNA were found in the brain and adrenals at relative levels about one-third of that found in the liver. Significant quantities of apo-E mRNA were detected in all of the other peripheral tissues as well. The apo-E mRNA levels in these tissues were 2-10% of that found in the liver of the rat and 10-30% of that found in the liver of the marmoset. Apo-E mRNA was also abundant in human brain and in each species examined; it was distributed throughout all major areas of this organ. In contrast, apo-A-I mRNA was detected in abundant amounts only in the small intestine and in the liver. Extrahepatic apo-E mRNA appears to be functional, generating a translation product similar or identical to that generated by the liver. During fetal and neonatal development, apo-E mRNA is rapidly induced from low levels to approximately equal to 60% of adult levels in liver at parturition. The fetal yolk sac contains more apo-E mRNA than the fetal liver, suggesting a significant role for the yolk sac as a source of apo-E during gestation.
TL;DR: Patients with severely impaired exercise tolerance had significantly higher rest pulmonary capillary wedge and right atrial pressures than those with a VO2max of 10 to 18 ml/min/kg; however, overlap among individual patients was considerable, and only pulmonaryCapillary wedge pressure at rest correlated significantly withVO2max.
Abstract: Previous studies have shown poor correlations between exercise tolerance and measurements of left ventricular (LV) function during rest in patients with congestive heart failure (CHF). To further evaluate the determinants of exercise tolerance and their relation to prognosis, we performed rest and exercise hemodynamic measurements and blood pool scintigraphy in 27 patients with CHF. All patients were treated with digitalis and diuretic drugs, but not vasodilator drugs. Exercise capacity was assessed by maximal oxygen consumption (VO2max) during upright bicycle ergometry. Both right ventricular (RV) and LV ejection fractions were measured by radionuclide techniques, and arterial, right atrial and pulmonary artery pressures, cardiac output, and derived hemodynamic indexes were determined. As a group, patients with severely impaired exercise tolerance (group 1, VO2max less than 10 ml/min/kg) had significantly higher rest pulmonary capillary wedge and right atrial pressures (30 +/- 4 vs 23 +/- 6 and 12 +/- 4 vs 7 +/- 2 mm Hg, respectively) than those with a VO2max of 10 to 18 ml/min/kg (group 2). They also had lower LV and RV ejection fractions (16 +/- 4% vs 21 +/- 4% and 19 +/- 12% vs 27 +/- 7%, respectively). However, overlap among individual patients was considerable, and only pulmonary capillary wedge pressure at rest correlated significantly (r = 0.69, p less than 0.001) with VO2max.(ABSTRACT TRUNCATED AT 250 WORDS)
TL;DR: Ribosomal frameshifting may affect production of other proteins in higher eukaryotes, including proteins encoded by several retroviruses and transposable elements.
Abstract: The pol gene of Rous sarcoma virus is positioned downstream of the gag gene in a different, briefly overlapping reading frame; nevertheless, the primary translation product of pol is a gag-pol fusion protein. Two mechanisms, ribosomal frameshifting and RNA splicing, have been considered to explain this phenomenon. The frameshifting model is supported by synthesis of both gag protein and gag-pol fusion protein in a cell-free mammalian translation system programmed by a single RNA species that was synthesized from cloned viral DNA with a bacteriophage RNA polymerase. Under these conditions, the ratio of the gag protein to the fusion protein (about 20 to 1) is similar to that previously observed in infected cells, the frameshifting is specific for the gag-pol junction, and it is unaffected by large deletions in gag. In addition, synthesis of the fusion protein is ten times less efficient in an Escherichia coli cell-free translation system and cannot be explained by transcriptional errors or in vitro modification of the RNA. Ribosomal frameshifting may affect production of other proteins in higher eukaryotes, including proteins encoded by several retroviruses and transposable elements.
TL;DR: Results indicate that there is a retrograde bead translocator which is pharmacologically and immunologically distinct from kinesin, a direction that corresponds to anterograde transport in the axon.
TL;DR: A set of small vectors based on the tumor‐inducing (Ti) plasmid of Agrobacterium tumefaciens which allow the transfer of exogenous DNA into plant chromosomes are constructed and it is shown that only the right border of the T‐DNA is necessary for DNA transformation.
Abstract: We have constructed a set of small vectors based on the tumor-inducing (Ti) plasmid of Agrobacterium tumefaciens which allow the transfer of exogenous DNA into plant chromosomes. These vectors contain: (i) a chimeric gene containing the transcriptional control signals from the nopaline synthase gene and the coding sequence for neomycin phosphotransferase; (ii) the ColE1 replicon; (iii) the cos site of bacteriophage λ; (iv) the border sequences from the ends of the T-DNA region of the Ti plasmid; and (v) a wide host range replicon. Due to the small size of these cosmid vectors, DNA fragments up to 35 kbp can be inserted by an in vitro packaging method in Escherichia coli. The ability of these vectors to be stably replicated in both E. coli and A. tumefaciens allows their subsequent transfer to and maintenance in Agrobacterium without intermediate genetic manipulations. We demonstrate that DNA cloned into these vectors in A. tumefaciens can efficiently transform plants when in trans with a wild-type Ti plasmid which donates the functions necessary for DNA transfer and integration. We also show that only the right border of the T-DNA is necessary for DNA transformation.
TL;DR: The RNA-dependent DNA polymerase of the AIDS-associated retrovirus (ARV) gives highest activity with the synthetic template, poly(rA)oligo(dT) and prefers Mg2+ over Mn2+ as a divalent cation.
TL;DR: It is demonstrated that developmental compartments subdivide the embryonic insect segments and that in the compartments of the later developmental stages the engrailed locus is expressed in the posterior but not the anterior compartments.
TL;DR: Under the retrospective reimbursement system in place at the time, hospitals in more competitive environments exhibited significantly higher costs of production than did those in less competitive environments.
TL;DR: Fiberoptic bronchoscopy is extremely accurate for the detection of pathogens in patients with the acquired immunodeficiency syndrome, especially when bronchoalveolar lavage and transbronchial biopsy are combined.
Abstract: The efficacy of bronchoalveolar lavage and transbronchial biopsy in diagnosing lung infection was determined in 276 fiberoptic bronchoscopic examinations done on 171 patients with known or suspected acquired immunodeficiency syndrome. Of 173 pathogens (Pneumocystis carinii, cytomegalovirus, Mycobacterium avium-intracellulare, Cryptococcus neoformans, M. tuberculosis, Coccidioides immitis, and Histoplasma capsulatum) identified during the initial evaluation or in the subsequent month, the initial bronchoscopic examination detected 166 (96%). Bronchoalveolar lavage and transbronchial biopsy had sensitivities of 86% and 87%, respectively. When bronchoscopy included both bronchoalveolar lavage and transbronchial biopsy, the yield for all pathogens was 98% and the sensitivity for P. carinii infections was 100%. Follow-up for at least 3 weeks after examination failed to detect any additional false-negative results. Fiberoptic bronchoscopy is extremely accurate for the detection of pathogens in patients with the acquired immunodeficiency syndrome, especially when bronchoalveolar lavage and transbronchial biopsy are combined. In patients at high risk of complications from transbronchial biopsy, bronchoalveolar lavage is sufficiently accurate to be used alone.
TL;DR: Vertebral compression fractures or wedging was generally absent in patients with vertebral mineral values above 110 mg cm-3, whereas almost all patients with values below 65 mgcm-3 had fractures.
TL;DR: The cloning of the human PSAP gene and complementary DNA is described and features of the unusual encoded protein are discussed, which lowers surface tension by spreading to create a thin interfacial film.
Abstract: Pulmonary surfactant is a phospholipid-protein complex which serves to lower the surface tension at the air-liquid interface in the alveoli of the mammalian lung and is essential for normal respiration. Inadequate levels of surfactant at birth, a frequent situation in premature infants, results in respiratory failure. In all species examined, surfactant is composed primarily of dipalmitoylphosphatidylcholine and two major protein species of relative molecular mass (Mr) 32,000 (32K) and 10K (refs 2-5). Reconstitution in vitro of purified 32K pulmonary surfactant apoprotein (PSAP) with synthetic lipids forms a lipoprotein complex that lowers surface tension by spreading to create a thin interfacial film. Here we describe the cloning of the human PSAP gene and complementary DNA, and discuss features of the unusual encoded protein.
TL;DR: The complex final form of the head and terminalia derive from earlier simple subdivision of these areas into developmental fields by engrailed, suggesting that engrailing may be responding to pair-rule segmentation gene products.
TL;DR: The onset of lichen planus could not be associated with any evident factors, such as family history, Candida albicans, glucose intolerance, and smoking.
TL;DR: In 19 patients, reduction in tumor size was evident by 6 weeks, but in the other 8, such reduction was not noted until the 6 month evaluation, and a reduction in PRL levels always preceded any detectable change intumor size.
Abstract: To assess the effectiveness of bromocriptine in reducing the size of PRL-secreting macroadenomas with extrasellar extension, we conducted a prospective multicenter trial in patients without prior radiotherapy, applying a standard protocol of treatment and tumor size evaluation. Basal serum PRL levels [1441 +/- 417 (+/- SEM) ng/ml for women; 3451 +/- 1111 ng/ml for men] fell in all patients and to 11% or less of basal values in all patients but 1. Normal PRL levels were reached in 18 of the 27 patients. In 13 patients (46%), tumor size was reduced by greater than 50%, in 5 patients (18%) by about 50%, and in 9 patients (36%) by approximately 10-25%. The extent of tumor size reduction did not correlate with basal PRL, nadir PRL, percent fall in PRL, or whether PRL levels reached normal. However, a reduction in PRL levels always preceded any detectable change in tumor size. In 19 patients, reduction in tumor size was evident by 6 weeks, but in the other 8, such reduction was not noted until the 6 month evaluation. In the 4 patients in whom bromocriptine was discontinued at the end of 1 yr, tumor reexpansion occurred in 3. Visual fields improved in 9 of the 10 patients in whom they were abnormal. Because of the excellent results found in most of the patients in this series, we suggest that therapy with bromocriptine should be considered as initial management for patients with PRL-secreting macroadenomas.
TL;DR: It is concluded that the more potent S(+) isomer of ketamine was associated with a more rapid recovery of psychomotor skills than the currently used racemic mixture.
Abstract: The clinical and electroencephalographic (EEG) effects of the individual ketamine isomers were compared with the racemic mixture in five volunteers who received each drug on a separate occasion. Racemic ketamine 275 ± 25 mg, s(+) ketamine 140 ± 21 mg or R(−) ketamine 429 ± 37 mg produced an anaesthetic state lasting 6 ± 2 min (mean ± SD). However, the EEG evaluation of the R(−) isomer revealed less overall slowing, and an absence of the large slow wave complexes produced by the s(+) isomer and the racemic mixture. The pharmacokinetic profiles for the individual isomers of ketamine did not differ significantly from the racemic mixture. Even though the apparent anaesthetic state produced in these healthy volunteers did not differ qualitatively between the three drug groups, recovery times (assessed using a standardized battery of psychometric tests) were consistently shorter following the individual isomers compared with the racemic mixture. The serum ketamine concentrations associated with regaining consciousness and orientation were consistent with an s(+):R(−) isomer potency ratio of 4:1. In terms of their ability to impair psychomotor function, the s(+):R(−) potency ratio varied from 3:1 to 5:1. After comparable degrees of CNS depression, we conclude that the more potent s(+) isomer of ketamine was associated with a more rapid recovery of psychomotor skills than the currently used racemic mixture.