Search PubMed⌕ Search

Biomedical subjects

F Fisher

Publications and source records attributed to F Fisher.

At least 37 records · Page 2Linked to original sources

Gene-regulatory properties of Myc helix-loop-helix/leucine zipper mutants: Max-dependent DNA binding and transcriptional activation in yeast correlates with transforming capacity.

Max is a basic helix-loop-helix/leucine zipper (bHLH/LZ) protein that forms sequence-specific DNA-binding complexes with the c-Myc oncoprotein (Myc). Using Saccharomyces cerevisiae, we have shown that the Max bHLH/LZ domain enables Myc to activate transcription through CACGTG and CACATG sequences in vivo, and that the number and context of such sites determines the level of activation. In addition, we have used yeast to investigate the role of the Myc helix-loop-helix (HLH) and leucine zipper (LZ) motifs in mediating Max-dependent DNA-binding and transcriptional activation in vivo using HLH/LZ mutants generated by site-directed mutagenesis. The results show that, while both motifs are essential for Myc to activate transcription, helix 2 of the HLH together with the contiguous LZ suffice to mediate complex formation with Max, whilst helix 1 is essential for sequence-specific DNA binding of Myc-Max complexes. Furthermore, the ability of Myc HLH/LZ mutants to bind DNA and activate transcription in collaboration with Max correlates closely with their neoplastic transforming activity in higher eukaryotic cells.

Base Sequence↗

Single amino acid substitutions alter helix-loop-helix protein specificity for bases flanking the core CANNTG motif.

While all basic region/helix-loop-helix (bHLH) proteins bind the consensus CANNTG motif, other factors must be involved in determining regulatory specificity. In this report we show that bases outside this core 6 bp are involved in determining the specificity of binding. Thus, binding of the yeast bHLH protein PHO4, but not CPF-1, is inhibited by the presence of a T residue immediately 5' to their common CACGTG recognition sequence. PHO4 binding specificity is altered by mutation at any of three different positions in the basic region, including a single Glu to Asp substitution. The significance of these data for DNA-binding and transcription regulation by the bHLH family of transcription factors is discussed.

Amino Acid Sequence↗

The use of cardiac and eye blink measures to determine flight segment in F4 crews.

Discriminant analysis techniques were used to classify 8 flight segments for 19 F4 crewmembers and to classify pilots from Weapons Systems Officers (WSOs). Heart rate and eye blink data were used as variables. Pilots and WSOs were correctly classified 84% of the time, while 92% of the flight segments were correctly classified for pilots and 89% for WSOs. The percent correct classifications of flight segments using the jackknife procedure were 69% and 68%, respectively. The advantage of collecting multiple physiological signals was demonstrated. Combined cardiac and eye blink data produced better classifications than when each was used alone. Application of this technique to the flight environment is discussed.

Aerospace Medicine↗

C-myc and the yeast transcription factor PHO4 share a common CACGTG-binding motif.

The basic-helix-loop-helix (b-HLH) motif is common to a number of proteins involved in transcriptional regulation and cell-type determination. The b-HLH motif is also present in the S. cerevisiae transcription factor PHO4 which positively regulates the acid phosphatase gene PHO5. In this report we show that the b-HLH region of PHO4 is sufficient to confer specific DNA-binding to the sequence CACGTG and, by comparison of the basic regions of PHO4 with those of other recently isolated CACGTG-binding proteins, we identify a specific subset of conserved amino acids in the basic region likely to confer DNA-binding specificity. On the basis of these observations we predict successfully the effect of substituting the PHO4 basic region with that from c-myc and show that the chimaeric protein activates transcription from the CACGTG elements present in the PHO5 UAS. From these data it is clear that the myc basic region confers specific binding to the sequence CACGTG.

Amino Acid Sequence↗

Multiple transcription factors interact with the adenovirus-2 EII-late promoter: evidence for a novel CCAAT recognition factor.

Multiple cellular transcription factors have been shown to interact with the upstream region of the adenovirus-2 EIIa-late promoter. One of these factors recognises each of the three CCAAT motifs present in the EIIL promoter at positions -72, -135 and -229, as well as the CCAAT elements in the rat albumin and herpes virus thymidine kinase promoters. A mutation known to reduce thymidine kinase promoter activity in vivo and in vitro abolishes binding of the factor, termed CCAAT recognition factor (CRF), which appears to be distinct from previously identified CCAAT factors. In addition, another protein, termed upstream factor II (USFII), shares binding sites at position -110 in the EIIL promoter and in the c-fos enhancer adjacent to the serum regulatable element. The recognition site for USFII is also found in the c-fos promoter and in the adenovirus early region EIV and EIIa-early promoters. An Sp1 recognition site has also been identified at position -41, and the binding sites for Sp1, USFII and CRF are all required for efficient EIIa-late promoter function. Finally, an additional factor recognising the consensus GGGGGGNT has been detected.

Adenovirus Early Proteins↗

Mutational analysis of the adenovirus E1a gene: the role of transcriptional regulation in transformation.

To determine whether the transcription regulatory activities of the adenoviral E1a gene play a role in its ability to transform primary cells we have constructed an extensive series of mutations within the E1a gene. The mutants have been characterized for their ability to transactivate the adenoviral early promoters, repress the transcriptional stimulation of the polyoma virus enhancer, establish primary baby rat kidney cells in culture and cooperate with the activated Ha-ras oncogene in morphologically transforming these cells. The mutant phenotypes reveal that: (i) the two transcription regulatory activities of E1a are separable since essential protein domains map within different regions of the protein; (ii) transactivation is unlikely to contribute significantly to E1a-mediated transformation since several isolated mutants lost the ability to transactivate but were nevertheless efficient at transformation; and (iii) both establishment and oncogene cooperation are linked to enhancer repression suggesting that E1a transforms cells by the repression of a cellular enhancer.

Adenoviridae↗

Self-charting for patients in recreation therapy.

Recently, the Ingleside Recreation Therapy department instituted a method of self-charting with thirty-nine adolescent inpatients in which both the patient and the therapist chart the patient's behavior in activities daily. The patient reads the therapist's chart note and may respond in any way he desires. The primary purpose of self-charting was to explore the possibility of establishing ongoing treatment goals with input from both the patient and the therapist, and of increasing communication and understanding between the two. Oftentimes, this did occur especially with distrustful or angry patients. Other results noted included the expression of a variety of feelings and the establishment of treatment goals by the patient--either on his own or in response to the therapist's written expectations.

Adolescent↗

Hemoglobin A1c levels in a diabetes detection program.

Hemoglobin A1c concentration (HbA1c) was compared to the plasma glucose responses at 1 and 2 h of an oral glucose tolerance test (OGTT) in 63 subjects preselected because of postprandial hyperglycemia. HbA1c concentrations were correlated with 1- and 2-hour plasma glucose responses during the OGTT (r = 0.776 and 0.8602, respectively). The OGTT responses were diabetic-like in 21, indeterminate in 15, and normal in 27 subjects. HbA1c values were within normal limits in all subjects who had a normal or indeterminate OGTT response and in 10 out of 21 with a diabetic OGTT. The 2-h OGTT response among the 10 diabetic responders with normal HbA1c was 200 +/- 31 mg/100 ml (mean +/- SD), while that of the 11 diabetic responders with elevated HbA1c was 352 +/- 122 mg/100 ml. All subjects with an elevated HbA1c had a 2-h plasma glucose above 228 mg/100 ml, whereas only 7% of subjects with a normal HbA1c had a 2-h glucose above this value. It is concluded that only about half of the patients currently diagnosed as having mild or chemical diabetes by OGTT have elevated HbA1c and that an elevated HbA1c is usually associated with 2-h OGTT levels above 228 mg/100 mg.

Blood Glucose↗

Networking: a managerial strategy for research development in a service setting.

An innovative managerial strategy--networking--used to establish and promote a nursing research program within three teaching hospitals in Boston is outlined in this article. Networking provides an opportunity for research and program development experts to share resources to meet common needs and goals. One of the advantages of a research network is that it can provide educational offerings that will stimulate all levels of professional nursing staff independent of their research background. Results of a survey the network conducted to determine a citywide profile of nursing research needs are presented.

Boston↗