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Biomedical subjects

N L Henry

Publications and source records attributed to N L Henry.

15 recordsLinked to original sources
PubMed2000

Onchocerciasis in a nonendemic population: clinical and immunologic assessment before treatment and at the time of presumed cure.

Although suppressive therapy for onchocerciasis with intermittent ivermectin prevents the development of pathology in endemic populations, the clinical and immunologic effects of therapy in the absence of continued exposure are unknown. To address this question, 14 patients treated with ivermectin for onchocerciasis acquired >10 years ago during temporary residence in Africa were reevaluated. None had evidence of continued infection or pathology at follow-up. Although eosinophilia, serum IgE, and antifilarial antibody levels decreased after ivermectin therapy, none of these parameters was useful in predicting the resolution of symptoms in infected patients. Peripheral blood mononuclear cells isolated from patients at follow-up were more responsive to parasite antigen in vitro, which is as assessed by proliferation and production of interferon-gamma and interleukin (IL)-5. In contrast, antigen-induced levels of IL-10 were significantly decreased at follow-up, consistent with diminished down-regulatory factors rather than a switch from type 2 to type 1 immune responses.

Animals↗
PubMed1997

Genes for Tfb2, Tfb3, and Tfb4 subunits of yeast transcription/repair factor IIH. Homology to human cyclin-dependent kinase activating kinase and IIH subunits.

Genes for the Tfb2, Tfb3, and Tfb4 subunits of yeast RNA polymerase transcription factor IIH (TFIIH) are described. All three genes are essential for cell viability, and antibodies against Tfb3 specifically inhibit transcription in vitro. A C-terminal deletion of Tfb2 caused a defect in nucleotide excision repair, as shown by UV sensitivity of the mutant strain and loss of nucleotide excision repair activity in cell extracts (restored by the addition of purified TFIIH). An interaction between Tfb3 and the Kin28 subunit of TFIIH was detected by the two-hybrid approach, consistent with a role for Tfb3 in linking kinase and core domains of the factor. The deduced amino acid sequence of Tfb2 is similar to that of the 52-kDa subunit of human TFIIH, while Tfb3 is identified as a RING finger protein homologous to the 36-kDa subunit of murine CAK (cyclin-dependent kinase activating kinase) and to the 32-kDa subunit of human TFIIH. Tfb4 is homologous to p34 of human TFIIH and is identified as the weakly associated 37-kDa subunit of the yeast factor. These and other findings reveal a one-to-one correspondence and high degree of sequence similarity between the entire set of yeast and human TFIIH polypeptides.

Amino Acid Sequence↗
PubMed1996

A yeast transcriptional stimulatory protein similar to human PC4.

A yeast protein has been identified that stimulates basal transcription by RNA polymerase II, binds both single- and double-stranded DNA, and interacts with both a general transcription factor and a transcriptional activator. Phosphorylation appears to regulate these interactions. The gene for the transcriptional stimulatory protein, termed TSP1, was cloned and found to be dispensable for yeast cell viability. The deduced amino acid sequence is similar to that of mammalian coactivator protein PC4.

Amino Acid Sequence↗
PubMed1996

TFG/TAF30/ANC1, a component of the yeast SWI/SNF complex that is similar to the leukemogenic proteins ENL and AF-9.

The SWI1/ADR6, SWI2/SNF2, SWI3, SNF5, and SNF6 gene products are all required for proper transcriptional control of many genes in the yeast Saccharomyces cerevisiae. Genetic studies indicated that these gene products might form a multiprotein SWI/SNF complex important for chromatin transitions preceding transcription from RNA polymerase II promoters. Biochemical studies identified a SWI/SNF complex containing these and at least six additional polypeptides. Here we show that the 29-kDa component of the SWI/SNF complex is identical to TFG3/TAF30/ANC1. Thus, a component of the SWI/SNF complex is also a member of the TFIIF and TFIID transcription complexes. TFG3 interacted with the SNF5 component of the SWI/SNF complex in protein interaction blots. TFG3 is significantly similar to ENL and AF-9, two proteins implicated in human acute leukemia. These results suggest that ENL and AF-9 proteins interact with the SNF5 component of the human SWI/SNF complex and raise the possibility that the SWI/SNF complex is involved in acute leukemia.

Amino Acid Sequence↗
PubMed1994

Relationship of CDK-activating kinase and RNA polymerase II CTD kinase TFIIH/TFIIK.

KIN28, a member of the p34cdc2/CDC28 family of protein kinases, is identified as a subunit of yeast RNA polymerase transcription factor IIH (TFIIH) on the basis of sequence determination, immunological reactivity, and copurification. KIN28 is, moreover, one of three subunits of TFIIK, a subassembly of TFIIH with protein kinase activity directed toward the C-terminal repeat domain (CTD) of the largest subunit of RNA polymerase II. Itself a phosphoprotein, KIN28 interacts specifically with the two largest subunits of RNA polymerase II. Previous work of others points to two further associations: KIN28 interacts in vivo with the cyclin CCL1, and KIN28 and CCL1 are homologous to human MO15 and cyclin H, which form the cyclin-dependent kinase-activating kinase (CAK). We show that human CAK possesses the CTD kinase activity characteristic of TFIIH.

Amino Acid Sequence↗
PubMed1994

TFIIF-TAF-RNA polymerase II connection.

RNA polymerase transcription factor IIF (TFIIF) is required for initiation at most, if not all, polymerase II promoters. We report here the cloning and sequencing of genes for a yeast protein that is the homolog of mammalian TFIIF. This yeast protein, previously designated factor g, contains two subunits, Tfg1 and Tfg2, both of which are required for transcription, essential for yeast cell viability, and whose sequences exhibit significant similarity to those of the mammalian factor. The yeast protein also contains a third subunit, Tfg3, which is less tightly associated and at most stimulatory to transcription, dispensable for cell viability, and has no known counterpart in mammalian TFIIF. Remarkably, the TFG3 gene encodes yeast TAF30, and furthermore, is identical to ANC1, a gene implicated in actin cytoskeletal function in vivo (Welch and Drubin 1994). Tfg3 is also a component of the recently described mediator complex (Kim et al. 1994), whose interaction with the carboxy-terminal repeat domain of RNA polymerase II enables transcriptional activation. Deletion of TFG3 results in diminished transcription in vivo.

Amino Acid Sequence↗
PubMed1994

Yeast TFIIE. Cloning, expression, and homology to vertebrate proteins.

Genes encoding both the 66- and the 43-kDa subunits of yeast RNA polymerase II initiation factor a, designated TFA1 and TFA2, have been isolated. Both genes are essential for cell viability. The bacterially expressed gene products could replace factor a in transcription in vitro, and both recombinant subunits were required for activity. The deduced amino acid sequences of the TFA1 and TFA2 gene products were homologous to those of the large and small subunits of human TFIIE, respectively, identifying factor a as the yeast homolog of TFIIE.

Base Sequence↗
PubMed1994

A versatile synthetic peptide-based ELISA for identifying antibody epitopes.

A simple, versatile and very inexpensive procedure for cross-linking synthetic peptides to the polystyrene surfaces of micro-well assay plates for use in ELISA was developed. The method is based on the use of poly-L-lysine (PLL) as the anchor protein for synthetic peptides which were then easily and covalently linked to the PLL using glutaraldehyde. The synthetic peptides used for the study were based on the amino acid sequence of the equine infectious anemia virus (EIAV) envelope sequence and evaluated as antigens in an ELISA designed to detect antibodies in serum of EIAV-infected horses and ponies. The ELISA using cross-linked peptides proved to be significantly more sensitive when compared to assays where passively coated peptides were used. In one instance, a peptide was identified that was not recognized by any of our antisera and appeared not to bind to the assay plates. However, once this peptide was cross-linked to the assay plate it proved to be very useful for detecting EIAV-specific antibodies. This cross-linking approach functioned equally well with peptides of various charges and sizes and did not appear to alter epitopes contained in the peptides.

Amino Acid Sequence↗
PubMed1992

Purification and characterization of yeast RNA polymerase II general initiation factor g.

Yeast RNA polymerase II general initiation factor g was purified to near homogeneity on the basis of its function in a reconstituted transcription system. Polypeptides of 30, 54, and 105 kDa co-purified with transcriptional activity, forming a complex with a mass of 300 kDa as judged by gel filtration, but only 100 kDa based on sedimentation in glycerol gradients, suggesting an elongated shape. Transcription activity could be reconstituted after separation of the three polypeptides under denaturing conditions; the 54- and 105-kDa subunits were both essential, while the 30-kDa subunit was slightly stimulatory. Factor g was required for initiation at all promoters tested, including those from Saccharomyces cerevisiae, Schizosaccharomyces pombe, and adenovirus. Factor g can stably associate with RNA polymerase II, as shown by cosedimentation in a glycerol gradient.

Chromatography↗
PubMed1990

A self-study of clinical evaluation in the McMaster clerkship.

The McMaster University Undergraduate MD Program participated with nine other schools in a pilot self-study of clinical evaluation under the auspices of the Association of American Medical Colleges. Clerkship planners and teaching faculty responded to questionnaires provided by the AAMC Clinical Evaluation Program, dealing with evaluation system problems. Top ranked problems, as perceived by the McMaster faculty, are presented and compared with the major problem areas seen by the overall group of the nine other schools. Two of these items deal with: (1) the lack of transmission of evaluative information about clerks from one unit to subsequent ones; and (2) faculty unwillingness to record negative evaluations. The former is seen as a serious problem both at McMaster and at the other schools; the latter only at McMaster. The discussion focuses on attempts to explain why these problems exist at McMaster and offers some suggestions for dealing with them.

Clinical Clerkship↗
PubMed1987

Factors underlying performance on written tests of knowledge.

The study compares two popular forms of written tests; the multiple choice test (MCQ) and the Modified Essay Question (MEQ). Two factors were varied in the experiment: the format of the questions (multiple choice, directed free response, or open-ended free response) and the context of the questions (in a patient problem or in random sequence). Six problems were developed in each version, and administered to a total of 36 medical students at three educational levels using a Latin-square design. The results showed a significant effect of each factor in the design, amounting to a difference of 8.7% between MCQ and directed free response, 4.2% between directed and open-ended free response and 4.3% between problem and random context. However, the correlation of scores based on content across the formats approached unity after correction for attenuation. A process score, based on the style and presentation in the undirected format, correlated more strongly with the free-response questions. The results suggest that, although the MCQ and MEQ may assess different skills, there is a very strong relationship between content scores derived from the two formats. The free response formats may present the opportunity for assessment of other factors related to presentation if scoring procedures are modified. Finally, the effect of randomizing questions is a deterioration of performance when compared to placing questions in the problem context.

Education, Medical, Undergraduate↗
PubMed1974

Copyright: its adequacy in technological societies.

What the United States does about the data explosion is likely to be copied on a global basis. America is the archetype of the coming technological society; we have all the advantages of being first, but others may avoid our mistakes. Let us hope that our errors are few

Copying Processes↗
PubMed1974

Copyright, public policy, and information technology.

Photocopying, computing, and other neopublishing technologies may threaten the traditional foundations of the creation of knowledge and simultaneously promise ever-faster creation of scholarly insights and social decision-making. Conversely, copyright law maintains accepted patterns of data-production and may hinder increased rates of research and information-based decision-making. These are multiple dilemmas, and must be faced squarely in formulating new policies for new technologies.

Authorship↗