Immigrant incorporation in the garment industry of Los Angeles.
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Americas↗
Biomedical subjects
R Kim
Publications and source records attributed to R Kim.
Structure-based assignment of the biochemical function of a hypothetical protein: a test case of structural genomics.
Many small bacterial, archaebacterial, and eukaryotic genomes have been sequenced, and the larger eukaryotic genomes are predicted to be completely sequenced within the next decade. In all genomes sequenced to date, a large portion of these organisms' predicted protein coding regions encode polypeptides of unknown biochemical, biophysical, and/or cellular functions. Three-dimensional structures of these proteins may suggest biochemical or biophysical functions. Here we report the crystal structure of one such protein, MJ0577, from a hyperthermophile, Methanococcus jannaschii, at 1.7-A resolution. The structure contains a bound ATP, suggesting MJ0577 is an ATPase or an ATP-mediated molecular switch, which we confirm by biochemical experiments. Furthermore, the structure reveals different ATP binding motifs that are shared among many homologous hypothetical proteins in this family. This result indicates that structure-based assignment of molecular function is a viable approach for the large-scale biochemical assignment of proteins and for discovering new motifs, a basic premise of structural genomics.
Adenosine Triphosphatases↗
Crystal structures of eukaryotic translation initiation factor 5A from Methanococcus jannaschii at 1.8 A resolution.
Eukaryotic translation initiation factor 5A (eIF-5A) is a ubiquitous protein found in all eukaryotic cells. The protein is closely associated with cell proliferation in the G1-S stage of the cell cycle. Recent findings show that the eIF-5A proteins are highly expressed in tumor cells and act as a cofactor of the Rev protein in HIV-1-infected cells. The mature eIF is the only protein known to have the unusual amino acid hypusine, a post-translationally modified lysine. The crystal structure of eIF-5A from Methanococcus jannaschii (MJ eIF-5A) has been determined at 1.9 A and 1.8 A resolution in two crystal forms by using the multiple isomorphous replacement method and the multiwavelength anomalous diffraction method for the first crystal form and the molecular replacement method for the second crystal form. The structure consists of two folding domains, one of which is similar to the oligonucleotide-binding domain found in the prokaryotic cold shock protein and the translation initiation factor IF1 despite the absence of any significant sequence similarities. The 12 highly conserved amino acid residues found among eIF-5As include the hypusine site and form a long protruding loop at one end of the elongated molecule.
Amino Acid Sequence↗
Purification, crystallization and preliminary X-ray crystallographic analysis of Pyrococcus furiosus DNA polymerase.
DNA polymerase gene from the hyperthermophilic Archaeon Pyrococcus furiosus has been cloned and the protein overexpressed in Escherichia coli to produce an active enzyme. The purified protein was crystallized from 0.08 M ammonium sulfate, 0.05 M Na-cacodylate, pH 6.5, 0.15%(v/v) NP40, 0.05%(v/v) Tween 20 and 4.5%(w/v) polyethylene glycol 6000 by the vapour-diffusion method. The orthorhombic crystals had unit-cell dimensions of a = 92.5, b = 125.4, c = 192.1 A; alpha = beta = gamma = 90 degrees. The crystals diffracted beyond 4 A on a 1.08 A synchrotron radiation source.
Cloning, Molecular↗
Crystal structure of a small heat-shock protein.
The principal heat-shock proteins that have chaperone activity (that is, they protect newly made proteins from misfolding) belong to five conserved classes: HSP100, HSP90, HSP70, HSP60 and the small heat-shock proteins (sHSPs). The sHSPs can form large multimeric structures and have a wide range of cellular functions, including endowing cells with thermotolerance in vivo and being able to act as molecular chaperones in vitro; sHSPs do this by forming stable complexes with folding intermediates of their protein substrates. However, there is little information available about these structures or the mechanism by which substrates are protected from thermal denaturation by sHSPs. Here we report the crystal structure of a small heat-shock protein from Methanococcus jannaschii, a hyperthermophilic archaeon. The monomeric folding unit is a composite beta-sandwich in which one of the beta-strands comes from a neighbouring molecule. Twenty-four monomers form a hollow spherical complex of octahedral symmetry, with eight trigonal and six square 'windows'. The sphere has an outer diameter of 120 A and an inner diameter of 65 A.
Amino Acid Sequence↗
Small heat shock protein of Methanococcus jannaschii, a hyperthermophile.
Small heat shock proteins (sHSPs) belong to a family of 12- to 43-kDa proteins that are ubiquitous and are conserved in amino acid sequence among all organisms. A sHSP homologue of Methanococcus jannaschii, a hyperthermophilic Archaeon, forms a homogeneous multimer comprised of 24 monomers with a molecular mass of 400 kDa in contrast to other sHSPs that show heterogeneous oligomeric complexes. Electron microscopy analysis revealed a spherically shaped oligomeric structure approximately 15-20 nm in diameter. The protein confers thermal protection of other proteins in vitro as found in other sHSPs. Escherichia coli cell extracts containing the protein were protected from heat-denatured precipitation when heated up to 100 degreesC, whereas extracts from cells not expressing the protein were heat-sensitive at 60 degreesC. Similar results were obtained when purified sHSP protein was added to an E. coli cell lysate. The protein also prevented the aggregation of two purified proteins: single-chain monellin (SCM) at 80 degreesC and citrate synthase at 40 degreesC.
Animals↗
A common human beta globin splicing mutation modeled in mice.
The betaIVS-2-654 C-->T mutation accounts for approximately 20% of beta thalassemia mutations in southern China; it causes aberrant RNA splicing and leads to beta0 thalassemia. To provide an animal model for testing therapies for correcting splicing defects, we have used the "plug and socket" method of gene targeting in murine embryonic stem cells to replace the two (cis) murine adult beta globin genes with a single copy of the human betaIVS-2-654 gene. No homozygous mice survive postnatally. Heterozygous mice carrying this mutant gene produce reduced amounts of the mouse beta globin chains and no human beta globin, and have a moderate form of beta thalassemia. The heterozygotes show the same aberrant splicing as their human counterparts and provide an animal model for testing therapies to correct splicing defects at either the RNA or DNA level.
Animals↗
Natriuretic peptide receptor 1 expression influences blood pressures of mice in a dose-dependent manner.
Activation of the natriuretic peptide system lowers blood pressure and causes the excretion of salt. Atrial natriuretic peptide and B-type natriuretic peptide are the humoral mediators of this effect; they act primarily by binding to membrane-bound natriuretic peptide receptor A (NPRA) and stimulating its intrinsic guanylate cyclase activity. To study whether genetically determined differences in NPRA expression affect blood pressure we have generated mice with one, two, three, or four copies of the gene encoding NPRA (Npr1 in the mouse). Atrial natriuretic peptide-dependent guanylate cyclase activity ranged progressively from approximately one-half normal in one-copy animals to twice normal in four-copy animals (P < 0.001). On different diets (0.05%, 2%, and 8% NaCl), the blood pressures of F1 male mice having only one copy of Npr1 averaged 9.1 mmHg (1 mmHg = 133 Pa) above those of wild-type two-copy males (P < 0.001), whereas males with three copies of the gene had blood pressures averaging 5.2 mmHg below normal (P < 0.01). The blood pressures of the one-copy F1 animals were significantly higher (by 6.2 mmHg; P < 0.01) on the high-salt than on the low-salt diet. The blood pressures of four-copy F3 males were significantly lower (by 7 mmHg; P < 0.05) on the high-salt than on the low-salt diet. These results demonstrate that below normal Npr1 expression leads to a salt-sensitive increase in blood pressure, whereas above normal Npr1 expression lowers blood pressures and protects against high dietary salt.
Animals↗
Purification, crystallization, and preliminary X-ray crystallographic data analysis of small heat shock protein homolog from Methanococcus jannaschii, a hyperthermophile.
A gene coding for a small heat shock protein homolog from the hyperthermophilic methanogenic Archaeon Methanococcus jannaschii was cloned. This gene was overexpressed in Escherichia coli harboring rare codon tRNAs and its protein purified and crystallized. Crystals displayed the space group R3 with unit cell dimensions a = b = 171.46 A and c = 102.13 A in a hexagonal axis setting. These crystals grew in one week and diffracted to 3.2 A resolution. The presence of eight molecules in the asymmetric unit gives a Vm value of 2.2 A3/Da and a solvent content of 44% by volume. The 24-molecule complex is generated from a subunit by a combination of crystallographic threefold symmetry and three types of noncrystallographic symmetries (a two-, a three-, and a fourfold).
Archaeal Proteins↗
The Madurai Intraocular Lens Study. II: Clinical outcomes.
PURPOSE: To evaluate the safety and efficacy of extracapsular cataract extraction with posterior chamber intraocular lens (ECCE/PC-IOL) compared with intracapsular cataract extraction with aphakic glasses (ICCE-AG). METHODS: In a nonmasked randomized controlled clinical trial, 3,400 bilaterally vision-impaired patients aged 40 to 75 years with operable cataract were randomly assigned to receive either ICCE-AG or ECCE/PC-IOL at the Aravind Eye Hospital in India. The surgery was performed by one of four study surgeons. Patients were hospitalized for 5 postoperative days, with follow-up visits at 2, 6, and 12 months after discharge. Postsurgery evaluations were conducted by two independent study ophthalmologists. RESULTS: At any single postoperative follow-up time point, there were no statistically significant differences of clinical relevance between treatment groups for any complication of a serious nature except cystoid macular edema, which was more common with ICCE (4.2% vs 1.6%). In general, whether of a trivial, intermediate, or serious nature, complication rates were low at each evaluation time point. Cumulatively, the incidence of serious complications of all types throughout the 1-year study period was 14.5% for patients in the ICCE-AG group and 7.7% in the ECCE group (P < .001). Best-corrected visual acuity of 20/40 or better at 12 months was attained by 90.7% of ICCE-AG patients and 96.3% of ECCE/PC-IOL patients (P < .001). CONCLUSION: Although both operative procedures are safe and effective for cataract patients with bilateral impairment, ECCE/PC-IOL is superior to ICCE-AG in terms of both visual acuity restoration and safety.
Adult↗
Mycotic aneurysm of the ulnar artery distal to the wrist.
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Aneurysm, Infected↗
Simple dressing for nipple reconstruction.
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Bandages↗
Argon laser treatment for premacular hemorrhage.
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Adult↗
Age-related marrow conversion in the proximal metaphysis of the femur: evaluation with T1-weighted MR imaging.
PURPOSE: To determine the normal chronologic changes in fatty marrow conversion of the proximal femoral metaphysis at magnetic resonance (MR) imaging. MATERIALS AND METHODS: The "marrow conversion index," (signal intensity of the proximal femoral metaphysis divided by signal intensity of the greater trochanter) x 100, was measured in 182 hips of 91 patients who had no evidence of osteonecrosis or diseases involving bone marrow, no history of steroid treatment, and no other risk factors for osteonecrosis. The results were evaluated according to patient age and sex. RESULTS: The index showed a progressive linear increase with age regardless of sex. The index was 65.4% +/- 5.6 (standard deviation) in patients aged 15-19 years and increased monotonously with age to 87.5% +/- 7.0 in patients aged 60-79 years. Simple linear regression of the index according to age group showed that the marrow conversion index is roughly equal to 63 + 4 x Z (p < .001), where Z is 1.5 for patients aged 15-19 years, 2.0 for patients aged 20-29 years, 3.0 for patients aged 30-39 years, 4.0 for patients aged 40-49 years, 5.0 for patients aged 50-59 years, and 6.0 for patients aged 60-79 years. CONCLUSION: There is a linear association of marrow conversion index and age. The estimating equation may provide baseline information for the marrow conversion index.
Adolescent↗
The CXC-chemokine, H174: expression in the central nervous system.
H174 is a new member of the CXC-chemokine family. A cDNA probe containing the entire H174 coding region recognized a predominant inducible transcript of approximately 1.5 kb expressed in interferon (IFN) activated astrocytoma and monocytic cell lines. H174 message can be induced following IFN-alpha, IFN-beta, or IFN-gamma stimulation. H174 message was also detected in IFN treated cultures of primary human astrocytes, but was absent in unstimulated astrocytes. H174, like IP10 and Mig, lacks the ELR sequence associated with the neutrophil specificity characteristic of most CXC-chemokines. Preliminary experiments suggest H174, IP10 and Mig are independently regulated. Recombinant H174 is a weak chemoattractant for monocyte-like cells. H174 can also stimulate calcium flux responses. The data support the classification of H174 as a member of a subfamily of interferon-gamma inducible non-ELR CXC-chemokines. Brain tissues were obtained at autopsy from one patient with AIDS dementia, one patient with multiple sclerosis, and two normal control patients. H174 and Mig were detected by RT-PCR in brain tissue cDNA derived from the patients with pathological conditions associated with activated astrocytes but not in cDNA from control specimens.
AIDS Dementia Complex↗
Hypertension, cardiac hypertrophy, and sudden death in mice lacking natriuretic peptide receptor A.
Natriuretic peptides, produced in the heart, bind to the natriuretic peptide receptor A (NPRA) and cause vasodilation and natriuresis important in the regulation of blood pressure. We here report that mice lacking a functional Npr1 gene coding for NPRA have elevated blood pressures and hearts exhibiting marked hypertrophy with interstitial fibrosis resembling that seen in human hypertensive heart disease. Echocardiographic evaluation of the mice demonstrated a compensated state of systemic hypertension in which cardiac hypertrophy and dilatation are evident but with no reduction in ventricular performance. Nevertheless, sudden death, with morphologic evidence indicative in some animals of congestive heart failure and in others of aortic dissection, occurred in all 15 male mice lacking Npr1 before 6 months of age, and in one of 16 females in our study. Thus complete absence of NPRA causes hypertension in mice and leads to cardiac hypertrophy and, particularly in males, lethal vascular events similar to those seen in untreated human hypertensive patients.
Animals↗
Clinical usefulness and cost of echocardiography in patients admitted to a coronary care unit.
The usefulness and cost of echocardiography was evaluated in 133 consecutive patients admitted to the Coronary Care Unit. A useful echocardiogram was one that provided new information, which influenced diagnosis, prognosis, or treatment. The cost of a useful echocardiogram was defined as the unit cost ($476 the Medicare global fee) x units (i.e., total echocardiograms / useful echocardiograms). Admission diagnoses were unstable angina (34%), arrhythmia (14%), congestive heart failure (8%), postprocedure monitoring (7%), acute myocardial infarction (6%), and miscellaneous (20%). The echocardiogram provided new information in 29% of patients. Patients without a recent echocardiogram (within 3 months) were twice as likely to have a useful echocardiogram (33 of 99, 33%) as those with a recent echocardiogram (5 of 34, 15%, p <0.05). A cardiologist predicted the overall usefulness of echocardiography with a positive predictive accuracy of 52% and a negative predictive accuracy of 94% (p < 0.0001). The overall cost of a useful echocardiogram of 3.5 units or $1,666 per useful study was decreased to $904 (1.9 units) if only studies predicted to be useful were considered. The usefulness of echocardiography varied significantly (p <0.02) within the admitting diagnostic categories. The usefulness of an echocardiogram was underestimated in patients with congestive heart failure, where it was found to be most useful (64%; $762 or 1.6 units). Thus, usefulness relates to the admission diagnosis, the availability of a recent echocardiogram, and to clinical judgment.
Aged↗
Age and secular trends in bone lead levels in middle-aged and elderly men: three-year longitudinal follow-up in the Normative Aging Study.
The goal of this study was to examine age and secular trends in bone and blood lead levels of community-exposed men. Bone and blood lead levels were measured twice, with a 3-year interval between measurements, among participants in a longitudinal study of aging. Seventy subjects (mean age = 66 years, age range = 52-83 years) with repeated measurements of bone and blood lead levels were studied. At the first evaluation, geometric mean lead levels in patella, tibia, and blood were 29.1 (standard deviation (SD) 1.8) microg/g, 17.5 (SD 2.0) microg/g, and 6.7 (SD 1.8) microg/dl, respectively. At the second evaluation, these levels were 22.2 (SD 1.8) microg/g, 17.9 (SD 1.7) microg/g, and 5.1 (SD 1.4) microg/dl, respectively. Cross-sectional analysis of each set of measurements indicated that, on average, a 1-year-older individual would have 2.7% and 2.4-3.2% higher levels of lead in patella and tibia, respectively. In contrast to the increasing age trend in cross-sectional analysis, the secular trend over time was decreasing for patella lead levels and stable for tibia lead levels. The authors conclude that in community-exposed middle-aged and elderly men, the biomarkers of exposure to lead are decreasing in patella and blood and unchanging in tibia as of the early 1990s. The increasing age trend in bone lead levels in cross-sectional studies should be carefully interpreted in light of the birth cohort effect.
Aged↗