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PubMed1998

Demand theory of gene regulation. I. Quantitative development of the theory.

The study of gene regulation has shown that a variety of molecular mechanisms are capable of performing this essential function. The physiological implications of these various designs and the conditions that might favor their natural selection are far from clear in most instances. Perhaps the most fundamental alternative is that involving negative or positive modes of control. Induction of gene expression can be accomplished either by removing a restraining element, which permits expression from a high-level promoter, or by providing a stimulatory element, which facilitates expression from a low-level promoter. This particular design feature is one of the few that is well understood. According to the demand theory of gene regulation, the negative mode will be selected for the control of a gene whose function is in low demand in the organism's natural environment, whereas the positive mode will be selected for the control of a gene whose function is in high demand. These qualitative predictions are well supported by experimental evidence. Here we develop the quantitative implications of this demand theory. We define two key parameters: the cycle time C, which is the average time for a gene to complete an ON/OFF cycle, and demand D, which is the fraction of the cycle time that the gene is ON. Mathematical analysis involving mutation rates and growth rates in different environments yields equations that characterize the extent and rate of selection. Further analysis of these equations reveals two thresholds in the C vs. D plot that create a well-defined region within which selection of wild-type regulatory mechanisms is realizable. The theory also predicts minimum and maximum values for the demand D, a maximum value for the cycle time C, as well as an inherent asymmetry between the regions for selection of the positive and negative modes of control.

Animals↗
PubMed1991

Food intake, eating-related complaints, and smell and taste sensations in patients with cancer of the lung, ovary and breast undergoing chemotherapy.

Nutritional status and energy and protein intake were studied in 52 patients with cancer of the breast, ovary or lung before, after 1, and after 3 cycles of aggressive chemotherapy. Pre-treatment intakes were somewhat lower than recommended and did not change after 3 cycles of chemotherapy, neither did nutritional status. Many patients had eating-related complaints, but these complaints did not increase significantly with chemotherapeutic treatment. In 31 patients electrical taste detection thresholds and chemical smell detection thresholds were measured before and after 3 cycles of chemotherapy. Changes in thresholds had no relation to changes in energy and protein intake. Perceived taste and smell changes were not reflected in chemosensory threshold values.

Journal Article↗
PubMed2004

Comparison of real-time PCR methods for detection of Salmonella enterica and Escherichia coli O157:H7, and introduction of a general internal amplification control.

The objectives of this study were to compare different real-time PCR-based methods for detection of either Salmonella spp. or E. coli O157:H7 with respect to sensitivity, precision and accuracy. In addition, a general internal amplification control (IAC) is presented, allowing prevention of false negative results. The IAC allows insight in amplification efficiency and enables a more accurate quantification with the evaluated real-time PCR methods. Implementation of the IAC with the different PCR methods did not affect the precision of the methods, but the sensitivity was reduced 10-fold. Introduction of an IAC with the Salmonella enterica specific detection method showed a shift in Ct-value (increase of target Ct-value with 0.45+/-0.17 cycles), while with the method to detect E. coli O157:H7 no influence of IAC co-amplification was observed. The quantification threshold of the methods in which the IAC was included was determined at 1 pg of target DNA (equal to 200 CFU) per reaction. Qualitative detection was feasible down to 10 fg of target DNA per reaction using both methods in which the IAC was incorporated. The adjusted methods have the potential to provide fast and sensitive detection of Salmonella spp. or E. coli O157:H7, enabling accurate quantification and preventing false negative results by using the general IAC.

DNA, Bacterial↗
PubMed1981

"The vibrometer". An electro magnetic transducer as an attempt to examine sensibility of the hand in quantitative terms.

Large myelinated nerve fibres are quick adapting, and mediate moving touch or vibration sensation. The study of their function is valuable in sensory evaluation and re-education. An instrument is described which allows measurement in terms of decibels of the thresholds at which the sensation is felt in the skin of the hand. This is done for value of thirty and two hundred and fifty six cycles per second. Improvement of sensation as recovery progresses can be recorded as the decibel values fall.

Adult↗
PubMed2006

Novel method for estimating viable Salmonella cell counts using real-time PCR.

A novel method for estimating viable Salmonella Enteritidis cell counts with 5'-nuclease real-time PCR was developed in this study. Our method was based on the increase kinetics of the target DNA region (invA) of the microorganism growing in a food/clinical sample in a culture medium during incubation. The index of increase in the target DNA region studied here was threshold cycle, CT. A test Salmonella strain was grown in buffered peptone water at the optimal temperature (39 degrees C). As Salmonella cells were grown, the value of CT decreased with time, generating a downward sigmoidal curve. The slope of the curve was constant at various initial cell concentrations. With higher initial cell concentration, the CT value evaluated from the slope at a given time was lower. With this relationship, a novel method for estimating the initial viable cell concentration of a sample was developed. Dead Salmonella cells or bacteria other than the target cell caused deviation in the CT curve. Incubation in a selective media suppressed the deviation caused by other bacterial cells. We think that this method could be applied to many other microorganisms cultivable in a suitable medium.

Colony Count, Microbial↗
PubMed1994

Ventilatory threshold and work efficiency during exercise on cycle and paddling ergometers in young female kayakists.

The aim of this study was to assess the effects of increasing specific (paddling ergometer) and non-specific (cycle ergometer) exercise on parameters relating to the ventilatory threshold (Th(vent)) and work efficiency in 11 young female flat-water kayakists. When these trained subjects were tested using non-specific workloads, their oxygen uptake (VO2) values at Th(vent), as a percentage of VO2max (%VO2max), were close to those of untrained subjects [74.2 (5.6) % VO2max, mean (SD)]. However, when we tested the same subjects using specific exercise, we recorded values typical of highly trained athletes [84.8 (4.7) % VO2max). For the non-specific exercise on the cycle ergometer, we recorded work efficiency values close to those of untrained subjects [22.3 (2.5) %]; however, for the specific exercise on the paddling ergometer, we recorded much lower values [13.4 (3.0) %] both at the level of Th(vent). The work efficiency at two warm-up submaximal exercise loads on the paddling ergometer was non-significantly lower than values at Th(vent) [12.3 (2.8) % and 12.9 (2.9) % respectively]. Significant correlations were found between maximal-performance VO2 (ml.kg-1.min-1) and performance at Th(vent) during paddling and race performance (0.623, 0.630 and 0.648 respectively, all P < 0.05). Because the results of both specific and non-specific submaximal exercise tests are different, we suggest caution in the interpretation of physiological variables that may be sensitive to training status. The evaluation of Th(vent) and work efficiency as supplementary parameters during laboratory studies enables the determination of the effectiveness of the training process and the specific adaptation of the subjects.

Adaptation, Physiological↗
PubMed1999

Analysis of the aerobic-anaerobic transition in elite cyclists during incremental exercise with the use of electromyography.

OBJECTIVES: To investigate the validity and reliability of surface electromyography (EMG) as a new non-invasive determinant of the metabolic response to incremental exercise in elite cyclists. The relation between EMG activity and other more conventional methods for analysing the aerobic-anaerobic transition such as blood lactate measurements (lactate threshold (LT) and onset of blood lactate accumulation (OBLA)) and ventilatory parameters (ventilatory thresholds 1 and 2 (VT1 and VT2)) was studied. METHODS: Twenty eight elite road cyclists (age 24 (4) years; VO2MAX 69.9 (6.4) ml/kg/min; values mean (SD)) were selected as subjects. Each of them performed a ramp protocol (starting at 0 W, with increases of 5 W every 12 seconds) on a cycle ergometer (validity study). In addition, 15 of them performed the same test twice (reliability study). During the tests, data on gas exchange and blood lactate levels were collected to determine VT1, VT2, LT, and OBLA. The root mean squares of EMG signals (rms-EMG) were recorded from both the vastus lateralis and the rectus femoris at each intensity using surface electrodes. RESULTS: A two threshold response was detected in the rms-EMG recordings from both muscles in 90% of subjects, with two breakpoints, EMGT1 and EMGT2, at around 60-70% and 80-90% of VO2MAX respectively. The results of the reliability study showed no significant differences (p > 0.05) between mean values of EMGT1 and EMGT2 obtained in both tests. Furthermore, no significant differences (p > 0.05) existed between mean values of EMGT1, in the vastus lateralis and rectus femoris, and VT1 and LT (62.8 (14.5) and 69.0 (6.2) and 64.6 (6.4) and 68.7 (8.2)% of VO2MAX respectively), or between mean values of EMGT2, in the vastus lateralis and rectus femoris, and VT2 and OBLA (86.9 (9.0) and 88.0 (6.2) and 84.6 (6.5) and 87.7 (6.4)% of VO2MAX respectively). CONCLUSION: rms-EMG may be a useful complementary non-invasive method for analysing the aerobic-anaerobic transition (ventilatory and lactate thresholds) in elite cyclists.

Adult↗
PubMed1999

Gustatory changes associated with the menstrual cycle.

We studied changes in the palatability and gustatory functions as they correlate with the menstrual cycle in 30 healthy females with regular menstrual cycles. The gustatory function was investigated by conducting electrogustometry and by the filter-paper disk method with taste solutions in the follicular and luteal phases of the same subjects. The responses to a questionnaire revealed that appetite was enhanced prior to menstruation in 14 cases (46.7%). The results of electrogustometry showed that the threshold in the domain of the chorda tympani nerve was 0.3 +/- 3.4 dB in the follicular phase and -0.9 +/- 2.8 dB in the luteal phase. Although the threshold in the luteal phase indicated a statistically significant decrease (p < 0.05), the difference was so small that the change could not be subjectively discriminated. The threshold in the domain of the glossopharyngeal nerve was 2.6 +/- 4.0 dB in the follicular phase and 1.7 +/- 3.9 dB in the luteal phase, with no significant difference between the two values. Gustatory thresholds as obtained by the filter-paper disk testing were not significantly different between the follicular and luteal phases. Thus, although the taste function may change through the menstrual cycle, changes in gustatory thresholds are minimal and remain within the normal range.

Adult↗
PubMed2002

Modeling extracellular matrix degradation balance with proteinase/transglutaminase cycle.

Extracellular matrix mass balance is implied in many physiological and pathological events, such as metastasis dissemination. Widely studied, its destructive part is mainly catalysed by extracellular proteinases. Conversely, the properties of the constructive part are less obvious, cellular neo-synthesis being usually considered as its only element. In this paper, we introduce the action of transglutaminase in a mathematical model for extracellular matrix remodeling. This extracellular enzyme, catalysing intermolecular protein cross-linking, is considered here as a reverse proteinase as far as the extracellular matrix physical state is concerned. The model is based on a proteinase/transglutaminase cycle interconverting insoluble matrix and soluble proteolysis fragments, with regulation of cellular proteinase expression by the fragments. Under "closed" (batch) conditions, i.e. neglecting matrix influx and fragment efflux from the system, the model is bistable, with reversible hysteresis. Extracellular matrix proteins concentration abruptly switches from low to high levels when transglutaminase activity exceeds a threshold value. Proteinase concentration usually follows the reverse complementary kinetics, but can become apparently uncoupled from extracellular matrix concentration for some parameter values. When matrix production by the cells and fragment degradation are taken into account, the dynamics change to sustained oscillations because of the emergence of a stable limit cycle. Transitions out of and into oscillation areas are controlled by the model parameters. Biological interpretation indicates that these oscillations could represent the normal homeostatic situation, whereas the other exhibited dynamics can be related to pathologies such as tumor invasion or fibrosis. These results allow to discuss the insights that the model could contribute to the comprehension of these complex biological events.

Animals↗
PubMed2005

Lower excess postexercise oxygen consumption and altered growth hormone and cortisol responses to exercise in obese men.

CONTEXT: Obesity is associated with altered patterns of substrate utilization at rest and during exercise. OBJECTIVE: The relationship between obesity and fat oxidation during recovery from exercise was examined. HYPOTHESIS: The postexercise shift toward fat oxidation is blunted in the obese state, reflected by higher respiratory exchange ratio (RER), blunted GH, and increased cortisol values compared with lean controls. DESIGN: Each subject completed two 160-min protocols (baseline and exercise). During baseline, subjects rested for 160 min; during exercise, they completed 30 min of cycling at ventilatory threshold, followed by 130 min of rest. SETTING: This study was performed at the University of Alberta. SUBJECTS: Healthy untrained (maximal oxygen consumption, <45 ml/kg.min or <3.35 liter/min) lean (<16% body fat; n = 6) and obese (>25% body fat; n = 7) men, aged 30-39 yr, were studied. MAIN OUTCOME MEASURES: RER, GH, cortisol, oxygen consumption, heart rate, tympanic temperature, and lactate were obtained during both protocols at matched time intervals and analyzed by repeated measures ANOVA. RESULTS: During baseline, there were no differences detected between lean and obese groups for any of the measured variables. In contrast, during exercise, peak GH levels were blunted (P < 0.05) and cortisol levels were elevated (P < 0.05) in the obese compared with the lean subjects, but RER values were similar in the two groups. The differences in GH and cortisol persisted during the postexercise period accompanied by higher RER values (P < 0.05) and reduced total oxygen consumption (P < 0.05) in the obese group. CONCLUSION: These findings indicate that exercise-induced fat oxidation is diminished in obese men.

Adult↗
PubMedDate not supplied

A bimolecular mechanism for the cell size control of the cell cycle.

A molecular model for the control of cell size has been developed. It is based on two molecules, one (I) acts as an inhibitor of the entrance into S phase, and it is synthetised just after cell separation in a fixed amount per nucleus. The other (A) is an activator of the S phase, and it is synthetised at a ratio proportional to the overall protein accumulation. The activator reacts stoichiometrically with (I), and after all the (I) molecules have been titrated, (A) begins to accumulate. When it reaches a threshold value, it triggers the onset of DNA replication. This model was tested by simulation and when applied to the case of unequal division explains a number of features of an exponentially growing yeast cell population: (a) the lengths of TP (cycle time of parent cells) and TD (cycle time of daughter cells) verify the condition exp(- KTP ) + exp(- KTD ) = 1; (b) the changes of the average cell size of populations at different growth rates; (c) the frequency of parents and daughters at various growth rates; (d) the increase of cell size at bud initiation for cells of increasing genealogical age; (e) the existence of a TP - TB period (difference between the cycle time of parents and the length of budded phase) that depends linearly upon the doubling time of the population.

Cell Cycle↗
PubMed1989

Lactate, oxygen uptake, and cycling performance in triathletes.

To assess the relationship of exercise test variables to each other and to bike race times in an ultra-distance triathlon, we studied 24 participants (14 men, 10 women) in the 1985 Hawaii Ironman Triathlon, using a graded, maximal cycle ergometer test with gas exchange and blood lactate (LA) measurements at each work load. Exercise test variables were oxygen uptake (VO2) and heart rate (HR) at the lactate and ventilatory thresholds. Lactate threshold (LT-1) was defined as the exercise intensity that elicited a 1 mM increase in blood lactate concentration above the value measured during the first work load for each subject. Variables were also examined at the lactate thresholds of 2 mM and 4 mM. Ventilatory thresholds (VT) were identified as the points at which the ventilatory equivalent of oxygen (VE/VO2) increased without a corresponding increase in the ventilatory equivalent of carbon dioxide (VE/VCO2). Mean peak oxygen uptake (peak VO2) for this sample of Ironman triathletes was 57.4 ml.kg-1.min-1. Cycle peak VO2 was inversely correlated, r = 0.68 (P less than 0.0002) with bike finish time. VO2 and HR as well as the respective percentages of maximum were higher at all lactate thresholds than at VT (P less than 0.0001). Therefore VT should not be used to identify a lactate threshold in ultra-endurance triathletes. VO2 values at the lactate and ventilatory thresholds were not highly related to bike finish time (r = -0.26 to -0.58). Fractional utilization of peak VO2 (% peak VO2), HR, and % peak HR at thresholds were not related to bike finish time (r = -0.01 to 0.06).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed2005

Follicular phase serum levels of luteinizing hormone do not influence delivery rates in in vitro fertilization cycles down-regulated with a gonadotropin-releasing hormone agonist and stimulated with recombinant follicle-stimulating hormone.

OBJECTIVE: To assess the value of serum LH measurements in early and late follicular phase as predictors of ovarian response and IVF outcome in patients treated with recombinant FSH with GnRH agonist (GnRH-a) pituitary down-regulation. DESIGN: Retrospective cohort analysis. SETTING: Institutional. PATIENT(S): Women undergoing 157 consecutive IVF cycles suppressed with leuprolide acetate (LA) started in the midluteal phase and stimulated with recombinant FSH. Only women <40 years of age and with a basal cycle day 3 serum FSH </=9 IU/L were included. INTERVENTION(S): Serum LH levels were measured on cycle days 3 (D3) and 10 (D10). MAIN OUTCOME MEASURE(S): Delivery rates. Other secondary outcome measures included fertilization rate, clinical pregnancy rate, and parameters of ovarian response (peak E(2), number of metaphase II oocytes, and number of ampules of recombinant FSH). RESULTS: No significant differences were found with respect to ovarian response, fertilization rate, and outcome of pregnancy, when three threshold values of D3 and D10 serum LH (1, 1.5, and 2 mIU/mL) were analyzed. In addition, no significant differences were found between conception (n = 87) and no conception (n = 71) groups with respect to D3 or D10 LH. Receiver operator characteristic (ROC) analysis showed that neither the serum LH concentration on D3 nor on D10 was able to discriminate between conception and nonconception cycles (area under the curve [AUC](ROC)= 0.54, AUC(ROC)= 0.56), or between delivered pregnancies and first trimester pregnancy loss (AUC(ROC)= 0.53, AUC(ROC) = 0.61). CONCLUSIONS: The suppressed levels of early and late follicular serum LH in women <40 years of age with normal ovarian function desensitized with a GnRH-a and treated with recombinant FSH are not predictive of ovarian response, pregnancy, or delivery. These data do not support the use of exogenous LH supplementation in this clinical scenario.

Adult↗
PubMed2005

Preoperative ultrasound to predict infraumbilical adhesions: a study of diagnostic accuracy.

OBJECTIVE: The purpose of this study was to determine the test characteristics of preoperative abdominal ultrasound in predicting infraumbilical adhesions in women. STUDY DESIGN: This was a diagnostic test study of 60 women at risk for intra-abdominal adhesions undergoing laparoscopy or vertical laparotomy. Participants underwent periumbilical sonographic measurement of visceral slide (longitudinal movement of the viscera during a cycle of respiration). RESULTS: Prevalence of infraumbilical bowel adhesions was 12%. A visceral slide threshold <1 cm to predict adhesions had sensitivity = 86%, specificity = 91%, positive predictive value = 55%, and negative predictive value = 98%. On stratifying visceral slide (<0.8 cm, > or =0.8 and <1 cm, and > or =1 cm), the likelihood ratios for detecting adhesions were 15.1, 5.0, and 0.2, respectively. CONCLUSION: Measuring visceral slide improves preoperative prediction of both presence and absence of bowel adhesions in patients with previous abdominal operations or infection; this technique may assist in avoiding iatrogenic bowel injury.

Adult↗
PubMed1983

Failure of high intensity auditory stimuli to affect behavioral arousal in children during the first sleep cycle.

Behavioral and physiologic indices of arousal to auditory stimuli were examined during the first cycle of sleep in 8-12-year-old hyperactive children and nonhyperactive controls. No behavioral responses or sustained awakenings were obtained for any child during the first cycle of sleep to stimuli at intensities up to 123 dB sound pressure level re 0.0002 dynes/cm2), i.e., at intensities more than 90 dB above waking threshold values. Half of the arousal attempts in stage 2 and a quarter of those in stage 4 elicited a partial or momentary physiologic arousal response (i.e., EEG desynchronization and/or change in skin potential response or respiratory activity rates). These arousals were shortlived, with the subjects returning to sleep even with continuing or increased stimulus intensity. Neither the incidence of partial arousals nor the associated threshold intensities differentiated subject groups. Although increased skin potential response activity and decreased respiratory rates were observed during sleep relative to wakefulness, and a predominance of skin potential response activity was noted in stage 4 sleep, no significant differences in frequency (rate/min) of autonomic response measures were obtained when rates before and during auditory stimulation were compared.

Acoustic Stimulation↗
PubMed2006

A systematic review of tests predicting ovarian reserve and IVF outcome.

The age-related decline of the success in IVF is largely attributable to a progressive decline of ovarian oocyte quality and quantity. Over the past two decades, a number of so-called ovarian reserve tests (ORTs) have been designed to determine oocyte reserve and quality and have been evaluated for their ability to predict the outcome of IVF in terms of oocyte yield and occurrence of pregnancy. Many of these tests have become part of the routine diagnostic procedure for infertility patients who undergo assisted reproductive techniques. The unifying goals are traditionally to find out how a patient will respond to stimulation and what are their chances of pregnancy. Evidence-based medicine has progressively developed as the standard approach for many diagnostic procedures and treatment options in the field of reproductive medicine. We here provide the first comprehensive systematic literature review, including an a priori protocolized information retrieval on all currently available and applied tests, namely early-follicular-phase blood values of FSH, estradiol, inhibin B and anti-Müllerian hormone (AMH), the antral follicle count (AFC), the ovarian volume (OVVOL) and the ovarian blood flow, and furthermore the Clomiphene Citrate Challenge Test (CCCT), the exogenous FSH ORT (EFORT) and the gonadotrophin agonist stimulation test (GAST), all as measures to predict ovarian response and chance of pregnancy. We provide, where possible, an integrated receiver operating characteristic (ROC) analysis and curve of all individual evaluated published papers of each test, as well as a formal judgement upon the clinical value. Our analysis shows that the ORTs known to date have only modest-to-poor predictive properties and are therefore far from suitable for relevant clinical use. Accuracy of testing for the occurrence of poor ovarian response to hyperstimulation appears to be modest. Whether the a priori identification of actual poor responders in the first IVF cycle has any prognostic value for their chances of conception in the course of a series of IVF cycles remains to be established. The accuracy of predicting the occurrence of pregnancy is very limited. If a high threshold is used, to prevent couples from wrongly being refused IVF, a very small minority of IVF-indicated cases (approximately 3%) are identified as having unfavourable prospects in an IVF treatment cycle. Although mostly inexpensive and not very demanding, the use of any ORT for outcome prediction cannot be supported. As poor ovarian response will provide some information on OR status, especially if the stimulation is maximal, entering the first cycle of IVF without any prior testing seems to be the preferable strategy.

Anti-Mullerian Hormone↗
PubMed1988

Serial evaluation of vasopressin release and thirst in human pregnancy. Role of human chorionic gonadotrophin in the osmoregulatory changes of gestation.

Serial studies were designed to characterized changes in osmoregulation throughout gestation. Eight women underwent a 2-h infusion of hypertonic saline before conception, during gestational weeks 5-8, 10-12, and 28-33, and then 10-12 wk postpartum. Basal plasma osmolality (Posmol) was already significantly decreased by 5-8 wk (P less than 0.001) and remained 10 mosmol.kg-1 below nonpregnant values throughout pregnancy. The apparent threshold for AVP release (defined as the abscissal intercept of the regression line relating plasma AVP [PAVP] to Posmol) was also decreased significantly throughout gestation, as was the osmotic threshold for thirst (derived from analogue scales relating desire to drink to Posmol). The decrement in osmotic thirst threshold appeared to precede that for AVP release, and consistent with this 24-h urine volumes were significantly greater at 5-8 wk gestation (P less than 0.05). The slopes of each regression equation defining PAVP vs. Posmol (whose r values ranged from 0.79 to 0.99), very reproducible before and after pregnancy, were similar at 5-8 and 10-12 wk, but were markedly reduced in the third trimester (P less than 0.001). These volunteers had randomly undergone an additional infusion before conception (both tests in the luteal phase of the menstrual cycle) when 10,000 IU of human chorionic gonadotrophin (hCG) had been given intramuscularly over a 5-d period. Serum hCG values between 0.2 and 3.3 U.ml-1 were lower than usually seen in pregnancy, but the osmotic thresholds for AVP release and thirst decreased by 3 and 4 mosmol.kg-1, respectively (P less than 0.05). Finally we studied a patient with a molar pregnancy in whom thresholds for hormone release and thirst were both decreased to values resembling normal gestation and remained so for approximately 6 wk postevacuation, only normalizing when hCG had virtually disappeared from her serum. In contrast, thresholds increased within the first two puerperal weeks in two women with normal pregnancies. These data demonstrate (a) osmotic thresholds for both AVP release and thirst decrease within the very first gestational weeks; (b) increment in PAVP per unit increase in Posmol is reduced late in gestation; and (c) hCG may be involved in the osmoregulatory changes of pregnancy.

Adolescent↗
PubMed1987

Hydrophobic strip-of-helix algorithm for selection of T cell-presented peptides.

In extension of the hypothesis that an amphipathic alpha helix of Ii (Phe146-Val164) bound to the foreign antigen-presenting site (desetope) of class II MHC molecules through hydrophobic amino acid residues (Phe146, Leu150, Leu153, Met157, Ile160, Val164) which were present in an axial strip along one side of the Ii helix, we developed an algorithm to search for T cell-presented peptides showing a similar hydrophobic strip-of-helix. Such peptides might bind to the class II MHC molecule site which was complementary to the Ii hydrophobic strip-of-helix. The strip-of-helix hydrophobicity index was the mean hydrophobicity (from Kyte-Doolittle values) of sets of amino acids in axial strips down sides of helices for 3-6 turns, at positions, n, n + 4, N + 7, n + 11, n + 14, and n + 18. Peptides correlating well with T cell responsiveness had: (1) 12-19 amino acids (3-5 cycles or 4-6 turns of an alpha helix), (2) a strip with highly hydrophobic residues, (3) adjacent, moderately hydrophilic strips, and (4) no prolines. The degree of hydrophilicity of the remainder of a putative antigenic helix above a threshold value did not count in this index. That is, the magnitude of amphipathicity was not judged to be the principal selecting factor for T cell-presented peptides. This simple algorithm to quantitate strip-of-helix hydrophobicity in a putative amphipathic alpha helix, allowing otherwise generally hydrophilic residues, predicted 10 of 12 T cell-presented peptides in seven well-studied proteins. The derivation and application of this algorithm were analyzed.

Algorithms↗