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Biomedical subjects

J Carey

Publications and source records attributed to J Carey.

At least 19 recordsLinked to original sources
PubMed1992

Recombinant human erythropoietin in the treatment of anemia associated with human immunodeficiency virus (HIV) infection and zidovudine therapy. Overview of four clinical trials.

OBJECTIVE: To assess the effect of recombinant human erythropoietin (r-HuEPO) on anemia in patients with the acquired immunodeficiency syndrome (AIDS) who are receiving zidovudine therapy. DESIGN: Combined analysis of four 12-week, randomized, double-blind, controlled clinical trials. SETTING: Multiple centers in the United States. PATIENTS: Two hundred and ninety-seven anemic (hematocrit < 30%) patients with AIDS who were receiving zidovudine therapy. Of the 297 patients, 255 were evaluable for efficacy, but all patients were included in analysis of safety. INTERVENTION: Patients were randomly assigned to receive either r-HuEPO (100 to 200 U/kg body weight) or placebo, intravenously or subcutaneously, three times per week for up to 12 weeks. MEASUREMENTS: Changes in mean hematocrit, transfusion requirement, and quality of life. RESULTS: Sixty-nine percent of patients had endogenous serum erythropoietin levels less than or equal to 500 IU/L, and 31% had erythropoietin levels greater than 500 IU/L. In patients with low erythropoietin levels (< or equal to 500 IU/l), r-HuEPO therapy decreased the mean number of units of blood transfused per patient when compared with placebo (3.2 units and 5.3 units, respectively; P = 0.003) and increased the mean hematocrit from the baseline level (4.6 percentage points and 0.5 percentage points, respectively; P <0.001). Overall quality of life improved in patients on r-HuEPO therapy (P = 0.13). Patients with erythropoietin levels greater than 500 IU/L showed no benefit from r-HuEPO in any outcome variable. Placebo and r-HuEPO recipients did not differ in the incidence of adverse effects or opportunistic infections. CONCLUSION: Therapy with r-HuEPO can increase the mean hematocrit and decrease the mean transfusion requirement in anemic patients with AIDS who are receiving zidovudine and have endogenous low erythropoietin levels (< or equal to 500 IU/L). Such therapy is of no apparent benefit in patients whose endogenous erythropoietin levels are higher than 500 IU/L.

Acquired Immunodeficiency Syndrome↗
PubMed1992

Binding of the arginine repressor of Escherichia coli K12 to its operator sites.

In the arginine regulon of Escherichia coli K12 each of the eight operator sites consists of two 18-base-pair-long palindromic sequences called ARG boxes. In the operator sites for the structural genes of the regulon the two ARG boxes are separated by three base-pairs, in the regulatory gene argR they are separated by two base-pairs. The hexameric arginine repressor, the product of argR, binds to the two ARG boxes in an operator in the presence of L-arginine. From the results of various kinds of in vitro footprinting experiments with the ARG boxes of argF and argR (DNase I protection, hydroxyl radical, ethylation and methylation interference, methylation protection) it can be concluded that: (1) the repressor binds simultaneously to two adjacent ARG boxes; (2) that it binds on one face of the double helix; and (3) that it forms contacts with the major and minor grooves of each ARG box, but not with the central three base-pairs. The repressor can bind also to a single ARG box, but its affinity is about 100-fold lower than for two ARG boxes. From gel retardation experiments with 3H-labeled repressor and 32P-labeled argF operator DNA, it is concluded that the retarded DNA-protein complex contains no more than one repressor molecule per operator site and that most likely one hexamer binds to two ARG boxes. The bound repressor was shown to induce bending of argF operator DNA. The bending angle calculated from the results of gel retardation experiments is about 70 degrees and the bending center was located within the region encompassing the ARG boxes. The main features that distinguish the arginine repressor from other repressors studied in E. coli are its hexameric nature and the simultaneous binding of one hexameric molecule to two palindromic ARG boxes that are close to each other.

Arginine↗
PubMed1992

Anatomical organization of the brainstem octavolateralis area of the oyster toadfish, Opsanus tau.

Anatomical studies were undertaken to analyze the brainstem organization of the auditory, vestibular, and lateral line nuclei in a teleost, the oyster toadfish, Opsanus tau. Neuronal cytoarchitectonics and horseradish peroxidase label of cranial nerves were utilized to delineate the borders of the five octavus and two lateralis brainstem nuclei. Each of the eight octavolateralis nerves were labeled individually to compare and contrast their central projections. Projections of the three semicircular canals were found to be largely overlapping. Terminal fields were observed within the eminentia granularis and in each of the octavus nuclei. The nucleus anterior octavus was reciprocally innervated by the semicircular canals and the saccule. The canals terminated heavily in the ventral portions of the anterior octavus, whereas the saccule terminated extensively in the dorsal nuclear portions. The saccule also distributed terminals throughout the octavus cell column, including a light terminal field within the dorsal, medial, and anterior portions of the descending octavus nucleus, a region densely innervated by this end-organ in other species. These results suggest that the anterior octavus nucleus may have a dual function. The dorsal portions may be an auditory relay nucleus, whereas the ventral portions may subserve vestibular function. Utriclar and lagenar afferents also terminated throughout the octavus cell column. Afferents of the anterior and posterior lateral lines ended within the eminentia granularis and the lateral line nuclei. Semicircular canal afferents and lateral line afferents appeared completely segregated within the eminentia. The above results are useful as an aid in the understanding of an ongoing, comprehensive functional analysis of auditory and vestibular mechanisms in toadfish and complement previous work on the efferent vestibular and sound-producing motor systems. Examination of toadfish contributes to a more general and complete overview of the octavolateralis area of teleosts and the eventual identification of primitive and derived patterns of octaval organization. Additionally, this work may permit the further demonstration of species-typical characters that may indicate adaptations to particular behavioral repertoires.

Animals↗
PubMed1992

Ordered self-assembly of polypeptide fragments to form nativelike dimeric trp repressor.

Subdomain-size proteolytic fragments of Escherichia coli trp repressor have been produced that assemble in defined order to regenerate fully native dimers. By characterization of the secondary and tertiary structures of isolated and recombined fragments, the structure of assembly intermediates can be correlated with the kinetic folding pathway of the intact repressor deduced from spectroscopic measurement of folding rates. The nativelike structure of these intermediates provides further evidence that protein folding pathways reflect the stabilities of secondary structural units and assemblies found in the native state. The proteolytic method should be generally useful in adding structural detail to spectroscopically determined folding mechanisms.

Amino Acid Sequence↗
PubMed1992

What makes information important and its influence on learning in self-directed study.

This study investigated what makes text-based information important and what is its influence on learning. College students studied an expository text following their own self-directed study procedures. Data from Exp. 1 (n = 60) and Exp. 2 (n = 40) showed that information was considered important if it (a) began and ended text, (b) began a paragraph, (c) appeared at somewhat equal intervals in text, and (d) contained enumerations of concepts. Subjects recalled information that (a) began the text and (b) contained examples of enumerations. It appeared that text-based variables established what was important and this influenced learning. Implications for the selective attention hypothesis and its volume-of-attention corollary, the cycles hypothesis, and the slot-filling hypothesis are discussed.

Achievement↗
PubMed1992

Treatment of cryptosporidiosis with paromomycin. A report of five cases.

Cryptosporidiosis continues to be one of the most devastating complications of the acquired immunodeficiency syndrome, causing severe, chronic diarrhea that is largely refractory to treatment. More than 60 drugs have been tried in the treatment of cryptosporidiosis, none of which have been consistently successful. We describe the successful treatment of cryptosporidiosis in five patients with acquired immunodeficiency syndrome with oral paromomycin at a dose of 1500 to 2000 mg/d. All five patients had resolution of symptoms and normalization of bowel movements, although one patient later relapsed while receiving paromomycin. Three of five patients cleared Cryptosporidium from the stool. Paromomycin is a promising therapy for cryptosporidiosis in acquired immunodeficiency syndrome and further prospective clinical trials are warranted.

AIDS-Related Opportunistic Infections↗
PubMed1991

How does trp repressor bind to its operator?

Three explanations have been advanced to account for the unexpected absence of direct hydrogen bonds and presence of a buried water layer in the co-crystal-line complex of Escherichia coli trp repressor with DNA. We present results of physical and biochemical measurements that address the testable predictions of each model. We find that the DNA oligomer used for co-crystallization binds to the repressor with high affinity and specificity, and 1:1 stoichiometry, consistent with other evidence that this sequence represents the true operator target for a single repressor dimer. A proposed alternative DNA sequence binds weaker and with higher stoichiometry, consistent with a cooperative binding mode. The operator DNA in solution has a B-form helical structure in the presence and absence of repressor. Affinity of repressor for operator is altered under the conditions used for cocrystal growth.

Bacterial Proteins↗
PubMed1991

Clindamycin and primaquine as primary treatment for mild and moderately severe Pneumocystis carinii pneumonia in patients with AIDS.

The combination of clindamycin and primaquine was investigated as primary treatment for mild or moderately severe Pneumocystis carinii pneumonia (alveolar-arterial oxygen gradient less than 40 torr) in 36 AIDS patients. All patients were treated with primaquine 30 mg (base) orally for 21 days. The first 22 patients were treated with clindamycin 900 mg i.v. q8h for the first 10 days, followed by clindamycin 450 mg q6h orally for 11 days. Twenty of these 22 patients (91%) showed a marked clinical response by day 7. Four patients were later withdrawn from the study due to toxicity. An additional 14 patients were treated with an entirely oral regimen of clindamycin and primaquine. Thirteen of the 14 patients (93%) showed a marked therapeutic response and 12 (86%) successfully completed treatment. The combination of clindamycin and primaquine appears to be an effective and well-tolerated treatment for mild to moderately severe Pneumocystis carinii pneumonia in AIDS patients.

Acquired Immunodeficiency Syndrome↗
PubMed1991

Gel retardation.

Explore the source record for details and available documents.

Acrylamides↗
PubMed1991

Histologic and immunophenotypic evaluation of pretreatment renal biopsies in OKT3-treated allograft rejections.

The histologic features immunophenotype of intragraft mononuclear populations, and HLA-Dr expression in pretreatment formalin-fixed renal allograft biopsies were correlated with outcome of OKT3 therapy in 35 steroid resistant renal transplant rejections. Therapeutic response (63% overall) was better in pure acute cellular rejections (ACR) (13/15, 87%) than ACR with interstitial fibrosis (4/12, 33%) or with vascular injury (5/8, 62%). Intragraft T lymphocytes were more numerous in vascular rejection (mean 566/mm2) compared with pure ACR (mean 265/mm2, P = .049), and macrophages were greater in pure ACR (203/mm2) compared with ACR with interstitial fibrosis (83/mm2, P = .051). Distribution of T cells, B cells, plasma cells, and macrophages among various histologic categories was otherwise statistically similar. There was no correlation between therapeutic response to OKT3 and intragraft concentrations of individual mononuclear cell subsets. Vascular and/or epithelial HLA-Dr expression was present in 17/25 (68%) cases and was not associated with histologic features or treatment response. Follow-up graft function (median 7 months) correlated significantly with therapeutic response to OKT3 (P = .0004) and histologic presence of interstitial fibrosis (P = .031), but was not related to concentration of individual mononuclear subsets or HLA-Dr expression. We conclude that intragraft concentrations of major mononuclear cell types may relate to histology, but that these do not predict treatment response or graft outcome, and thus poorly reflect intensity or possible heterogeneity of host immunologic rejection mechanisms.

Antibodies, Monoclonal↗
PubMed1991

The gene encoding the oligodendrocyte-myelin glycoprotein is embedded within the neurofibromatosis type 1 gene.

In the course of efforts to identify the neurofibromatosis type 1 gene (NF1), three genes were found embedded within an intron of NF1. The cDNA sequence of one of these genes (OMGP) encodes oligodendrocyte-myelin glycoprotein. OMGP spans at least 2.7 kb of genomic DNA, and it maps within 4 kb of the breakpoint of a balanced chromosomal translocation carried by an individual with NF1. OMGP is similar in genomic structure to two other expressed genes, EVI2A and EVI2B, which lie approximately 20 and 5 kb telomeric of the OMGP locus, respectively. All three genes have the same transcriptional orientation and are contained within one intron of NF1, which is transcribed off the opposite strand. Whether altered expression of OMGP might play a role in the clinical heterogeneity of NF1 is as yet unclear.

Amino Acid Sequence↗
PubMed1990

Paternal origin of new mutations in von Recklinghausen neurofibromatosis.

Von Recklinghausen neurofibromatosis (NF-1) is a common autosomal dominant disorder. The estimated new mutation rate (1 x 10(-4] is one of the highest for a human disorder. Here we report that in 12 of 14 families we have analysed, the new mutation is of paternal origin. This result is similar to that recently obtained for retinoblastoma. In other genetic disorders that show a bias towards paternal origin of new mutations, there is a marked increase in the incidence of mutations with paternal age, consistent with the mutations arising from replication errors in mitosis of spermatogonial stem cells. In retinoblastoma and NF-1, however, such paternal age effects are slight or absent. The mechanism or timing of germline mutation could therefore be different in the two cases.

Adult↗
PubMed1990

Subarachnoid hemorrhage in sickle cell disease.

Subarachnoid hemorrhage occurs in 1%-2% of patients with neurological complications from sickle cell disease. The authors report a case of subarachnoid hemorrhage in a 13-year-old black girl with sickle cell disease. Computed tomography of the brain demonstrated diffuse subarachnoid hemorrhage in the right sylvian fissure and the right frontoparietal cortical region. Angiography revealed no evidence of aneurysm but multiple stenosis and/or occlusions of the distal branches of the anterior and middle cerebral arteries bilaterally. Rupture of leptomeningeal collateral vessels is a possible cause of subarachnoid hemorrhage in our patient.

Adolescent↗
PubMed1990

A multicentre double-blind comparison of auranofin, intramuscular gold thiomalate and placebo in patients with psoriatic arthritis.

The efficacy and safety of the oral gold compound auranofin and intramuscular gold thiomalate have been compared in a placebo-controlled, double-blind, four-centre trial in 82 patients with psoriatic arthritis requiring remittive drug therapy. There were statistically significant falls in Ritchie articular index, visual analogue pain score and ESR at 12 and 24 weeks following i.m. gold but no significant changes in the auranofin group. Intramuscular gold was safe and more effective than auranofin as a second-line, suppressive antirheumatic agent for patients with psoriatic arthritis when followed for 6 months.

Adult↗
PubMed1990

Osteomyelosclerosis with granulocytic sarcoma of chest wall. Morphological, ultrastructural, immunologic, and cytogenetic study.

A case of granulocytic sarcoma presenting as a soft-tissue tumor in the chest wall in a patient with osteomyelosclerosis is reported. The tumor mass was detected by a computed tomographic scan during an investigation of the cause of chest pain in a 58-year-old man. Biopsy of the mass showed findings compatible with either a large-cell lymphoma or a granulocytic sarcoma. The latter was confirmed by naphthol-ASD-chloracetate esterase stain and electron microscopic examination. Immunologic study of the tumor mass showed expressions of membrane/cytoplasmic CD 13 and CD 15 antigens. In addition, the tumor cells coexpressed CD 19, although all other T- and B-cell-associated antigens were absent. Cytogenetic study showed translocation t(1;7)(q11;q11) with a net deletion of the entire long arm of chromosome 7 and duplication of the long arm of chromosome 1. Peripheral blood examination showed typical leukoerythroblastosis with teardrop poikilocytosis, large hypogranular platelets, and 0.11 myeloblasts. A bilateral iliac bone marrow biopsy at this time showed osteomyelosclerosis. The patient was treated with hydroxyurea followed by local irradiation, resulting in marked reduction in the size of the tumor and in the pain. He was asymptomatic without any progression in hematologic parameters 10 months after the initial diagnosis.

Humans↗
PubMed1989

NMR assignments for the amino-terminal residues of trp repressor and their role in DNA binding.

The trp repressor of Escherichia coli specifically binds to operator DNAs in three operons involved in tryptophan metabolism. The NMR spectra of repressor and a chymotryptic fragment lacking the six amino-terminal residues are compared. Two-dimensional J-correlated spectra of the two forms of the protein are superimposable except for cross-peaks that are associated with the N-terminal region. The chemical shifts and relaxation behavior of the N-terminal resonances suggest mobile "arms". Spin-echo experiments on a ternary complex of repressor with L-tryptophan and operator DNA indicate that the termini are also disordered in the complex, although removal of the arms reduces the DNA binding energy. Relaxation measurements on the armless protein show increased mobility for several residues, probably due to helix fraying in the newly exposed N-terminal region. DNA binding by the armless protein does not reduce the mobility of these residues. Thus, it appears that the arms serve to stabilize the N-terminal helix but that this structural role does not explain their contribution to the DNA binding energy. These results suggest that the promiscuous DNA binding by the arms seen in the X-ray crystal structure is found in solution as well.

Bacterial Proteins↗
PubMed1989

trp repressor arms contribute binding energy without occupying unique locations on DNA.

The amino-terminal arms of dimeric Escherichia coli trp repressor were removed by chymotryptic cleavage of the first 6 residues from each subunit. The role of the arms in structure and function of the repressor was probed by comparing the properties of intact and proteolyzed forms. The armless protein retains the ability to form stable dimers and to bind the corepressor L-tryptophan, but its affinity for both operator and nonoperator DNA is reduced by about 50-fold. Footprinting analysis shows that the intact repressor makes contacts with nucleotides on only one face of operator DNA. Thus, the arms do not wrap around the DNA as is the case for several other DNA binding proteins. All the contact sites identified by footprinting using the intact repressor are preserved in the complex formed with the armless repressor. This result indicates that the arms do not occupy a unique position on the DNA although they contribute substantially to the energy of DNA binding.

Bacterial Proteins↗