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Biomedical subjects

F Fisher

Publications and source records attributed to F Fisher.

At least 19 recordsLinked to original sources

Cognitive task classification based upon topographic EEG data.

EEG from 19 electrodes was used to classify which of 14 tasks each of seven subjects had performed. Stepwise discriminant analysis (SWDA) was used to classify the tasks based upon training on one half of the spectrally analyzed 1 min of data. Eighty six percent correct classification was achieved using principle components analysis (PCA) to determine the EEG bands to be used by the SWDA. Other approaches to deriving the EEG bands met with lower levels of success. The results indicate that frequency and topographical information about the EEG provides useful knowledge with regard to the nature of cognitive activity. Higher frequencies provided much of the information used by the classifier. The utility of this approach is discussed with regard to evaluating operator state in the work environment.

Adult

The transcription factor, the Cdk, its cyclin and their regulator: directing the transcriptional response to a nutritional signal.

The Pho80-Pho85 cyclin-cdk complex prevents transcription of PHO5 by inhibiting the ability of the basic-helix-loop-helix transcription factor Pho4 to activate transcription in response to high phosphate conditions. In low phosphate the Pho80-Pho85 complex is inactivated and Pho4 is then able to activate the acid phosphatase gene PHO5. We show here that Pho4 and the homeobox protein Pho2 interact in vivo and act cooperatively to activate the PHO5 UAS, with interaction being regulated by the phosphate switch. In addition, we also demonstrate that an additional factor, Pho81, interacts in high phosphate with both the Pho80 cyclin and with Pho4. In low phosphate, Pho80 and Pho81 dissociate from Pho4, but retain the ability to interact with each other. The evidence presented here supports the idea that Pho81 acts as a phosphate-sensitive trigger that regulates the ability of the Pho80-Pho85 cyclin-cdk complex to bind Pho4, while DNA binding by Pho4 is dependent on the phosphate-sensitive interaction with Pho2.

Acid Phosphatase

Unexplained unilateral vision loss during centrifugation.

Vision loss during a centrifuge run is an expected occurrence given the G-profile, physical fitness of the subject, expected visual endpoint [central light loss (CLL) or peripheral light loss (PLL)] of the experimental protocol, and the cyclic nature of the anti-G straining maneuver (AGSM). During a relatively low level G exposure, a subject experienced a unilateral loss of vision that did not resolve spontaneously upon removal of the G load. An extensive medical workup did not reveal any medical explanation for the vision loss.

Adult

Factors influencing aeromedical decision-making: operational versus research environments.

The aeromedical research and operational flying communities have at least one common goal; ensuring the optimum combination of mission performance and safety for the aircrew. This is a continual challenge as aerospace technology leaps ahead while the human factor remains relatively constant. However, several issues interfere with the smooth interaction between these communities: 1) perceptions that the research and operational communities have towards human subjects and pilots respectively; 2) the legal and ethical considerations involved in exposing individuals to risk; and 3) the ever-present personality dynamics involved in any decision-making process (e.g., returning individuals to a centrifuge panel or flying duty after a medically disqualifying incident). All of these factors influence decisions made in both communities, and how they interact with each other. It is a dynamic process that varies between countries, individual services (e.g., Navy vs Air Force), and even between different geographical locations within the same service.

Aerospace Medicine

Transcription activation by Myc and Max: flanking sequences target activation to a subset of CACGTG motifs in vivo.

The Myc oncoprotein has been implicated in control of cell growth, division and differentiation. Although Myc contains a bHLH-LZ motif, it fails to bind DNA alone but can do so by forming heterodimers with an unrelated bHLH-LZ protein, Max. Max homodimers and Myc-Max heterodimers share the ability to bind CACGTG or CATGTG elements. Current models, based on experimentally induced overexpression of Myc and Max in mammalian cells, propose that Max-Max homodimers repress while Myc-Max heterodimers activate transcription through CACGTG binding sites. The interpretation of the results using mammalian cells is complicated by the presence of numerous unrelated CACGTG binding transcription activators and the existence of two alternative Max dimerization partners, Mad and Mxi-1. Thus, the mechanism whereby overexpression of Max leads to transcriptional repression remains to be established. Using a yeast system we show that Max homodimers have the potential to activate transcription through CACGTG motifs. Activation by Max requires DNA binding and amino acids outside the bHLH-LZ domain but is reduced compared with activation by Myc-Max heterodimers. Moreover, transcriptional activation by Myc-Max heterodimers, but not Max-Max homodimers, is strongly inhibited in vivo by specific sequences flanking the core CACGTG binding motif, presumably reflecting reduced DNA binding affinity. These results suggest a mechanism for directing the Myc-Max complex to a specific subset of CACGTG-containing target genes.

Amino Acid 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