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PubMed1990

Treatment of prolactin-secreting pituitary macroadenomas with the long-acting non-ergot dopamine agonist CV 205-502.

STUDY OBJECTIVE: Evaluation of the effects of an experimental long-acting non-ergot dopamine agonist, CV 205-502, on serum prolactin, tumor size, gonadal function, visual abnormalities, and tolerability in patients with macroprolactinomas. DESIGN: Prospective, unblinded, dose escalation as needed. SETTING: Four university medical centers; patients referred for treatment. PATIENTS: Twenty-six hyperprolactinemic patients (prolactin greater than 150 micrograms/L) with a pituitary macroadenoma were treated for 24 weeks with CV 205-502 given once daily. MEASUREMENTS AND MAIN RESULTS: Serum prolactin was measured at regular intervals. Prolactin levels decreased in all patients during treatment (mean pretreatment level, 2051.7 +/- 1077 micrograms/L [+/- SE]; 24 weeks, 39.0 +/- 11.3 micrograms/L; P = 0.0001); normal prolactin levels were achieved in 15 (58%). Tumor size decreased in 21 of 26 patients and ranged from 6% to 67% (mean, 19.2% +/- 3.4%). Onset or return of regular menses occurred in 11 of 15 premenopausal women, accompanied by an increase in estradiol concentrations (pretreatment, 186.5 +/- 25.0 pmol/L; on treatment, 690.9 +/- 104.3 pmol/L; P = 0.0003). Serum testosterone increased in 6 of 8 men; sexual function improved in 5 of 7 with pretreatment abnormalities. Two patients with reversible visual abnormalities improved within 2 weeks of starting treatment. Side effects occurred in 11 patients and abated over 1 to 2 weeks or after the dose was reduced. There was no evidence of toxicity as indicated by serial serum chemistries, liver function tests, hematologic profiles, thyroxine levels, and electrocardiogram studies. CONCLUSIONS: CV 205-502 reverses hyperprolactinemia and promotes reduction in tumor size with reversal of visual abnormalities and restoration of gonadal function in most patients. This compound will probably be useful in treating prolactinomas.

Adenoma↗
PubMed2005

A novel function of differentiation revealed by cDNA microarray profiling of p75NTR-regulated gene expression.

The expression of the p75 neurotrophin receptor (p75NTR) is diminished in epithelial cells during progression of prostate cancer in vivo and in vitro. Previous studies have demonstrated a role for p75NTR as a tumor suppressor in prostate growth. To better understand the molecular mechanism of p75(NTR) on tumor suppression, we utilized a complementary deoxyribonucleic acid microarray composed of approximately 6,000 human cancer-related genes to determine the gene expression pattern altered by re-introduction of p75NTR into PC-3 prostate tumor cells. Comparison of the transcripts in the neo and p75NTR-transfected cells revealed 52 differentially expressed genes, of which 21 were up-regulated and 31 were down-regulated in the presence of p75NTR. Based on the known biological functions of the p75NTR-regulated genes, we observed that p75NTR modulated the expression of genes that are critically involved in the regulation of differentiation as well as cell adhesion, signal transduction, apoptosis, tumor cell invasion, and metastasis. Several differentially expressed genes identified by microarray were selected for confirmation using quantitative real-time polymerase chain reaction. Immunoblot analysis further confirmed increased cellular retinoic acid-binding protein I (CRABPI) and IGFBP5 protein levels and decreased level of PLAUR protein with increasing p75NTR protein expression. As CRABPI was elevated far more than any other genes, we observed that the retinoids, all-trans retinoic acid and 9-cis retinoic acid, that bind CRABPI, promoted nitroblue tetrazolium-associated functional cell differentiation in p75NTR PC-3 cells, but not in neo control PC-3 cells. Subsequent examination of the retinoic acid receptors (RARs) expression levels demonstrated an absence of RAR-beta in the neo control cells and re-expression in the p75NTR expressing cells, consistent with previous findings where RAR-beta is believed to play a critical role as a tumor suppressor gene that is lost during de-differentiation of prostate epithelial cells. Whereas the RAR-alpha and -gamma protein levels remained unchanged, retinoid X receptor (RXR)-alpha and -beta also exhibited increasing protein levels with re-expression of the p75NTR protein. Moreover, the ability of p75NTR siRNA to knockdown levels of RAR-beta, RXR-alpha, and RXR-beta supports the specificity of the functional involvement of p75NTR in differentiation. Hence, re-expression of the p75NTR appears to partially reverse de-differentiation of prostate cancer cells by up-regulating the expression of CRABPI for localized sequestration of retinoids that are available to newly up-regulated RAR-beta, RXR-alpha, and RXR-beta.

Cell Differentiation↗
PubMed2026

Integrative Multiomics and Drug Sensitivity Profiling Reveal Potential Biomarkers and Therapeutic Strategies in Pediatric Solid Tumors.

UNLABELLED: Cure rates for childhood malignancies using established therapy protocols have increased to an average of 80% but have reached a plateau. Moreover, survival rates are particularly low for some pediatric tumors-such as high-risk group 3 medulloblastomas, osteosarcomas, Ewing sarcomas, high-risk neuroblastomas, and high-grade gliomas-and dismal for patients with relapsed malignancies. A functional drug response profiling platform for pediatric solid and brain tumors has been established within the INFORM program to identify patient-specific vulnerabilities and biomarkers and to unravel molecular mechanisms associated with drug response profiles for clinical translation. In this study, we performed a multiomics analysis using drug sensitivity profiles, as well as genomic and transcriptomic data, of 81 pediatric solid tumor samples. The integrative analysis suggested two multiomics signatures associated with drug sensitivity. One signature distinguished neuroblastoma samples with sensitivity to navitoclax, a BCL2 family inhibitor. A second signature was specific to a subset of Wilms tumors harboring the SIX1 (Q177R) hotspot mutation that displayed high expression of MGAM, PTPN14, STAT4, and KDM2B and high sensitivity to MEK inhibitors. A patient-specific causal interaction network analysis suggested possible molecular interactions between MEK inhibitors and the SIX1 mutation in Wilms tumor samples. In conclusion, the integration of drug sensitivity profiling and multiomics data revealed potential biomarkers that may be associated with drug sensitivity in pediatric solid tumors. Patient-specific causal interaction network analysis further elucidated the interaction between inhibitors and signature biomarkers, providing insights that may inform clinical translation. SIGNIFICANCE: The combination of multiomics analysis and drug sensitivity profiling identified two signatures related to drug sensitivity in pediatric solid tumors, contributing to the advancement of functional precision medicine and personalized treatment strategies. This article is part of a special series: Driving Cancer Discoveries with Computational Research, Data Science, and Machine Learning/AI .

Humans↗
PubMed2003

Flattening the glucocorticoid rhythm causes changes in hippocampal expression of messenger RNAs coding structural and functional proteins: implications for aging and depression.

Subtle changes in glucocorticoid levels, including a flattening of the diurnal rhythm with raised nadir, are prevalent, being characteristic of both aging and major depression. Both these conditions are also associated with deficits in hippocampally mediated cognitive functions. We hypothesized that this profile of glucocorticoid levels causes structural and functional changes in the hippocampus, which in turn may engender cognitive deficits. We implanted slow-release corticosterone pellets into adrenally intact adult male rats to produce a flattened glucocorticoid rhythm with levels clamped midway between the normal nadir and zenith. Using density profile analysis we measured hippocampal expression of messenger RNAs encoding structural and functional proteins. In rats with a flattened glucocorticoid rhythm, the expression of the mRNA coding for microtubule associated protein-2b (MAP2b) was reduced in CA3 relative to sham-operated controls, but unchanged in dentate gyrus and CA1. In contrast, the expression of the mRNA coding the alpha subunit of calcium-calmodulin dependent kinase (CAMKIIalpha) was reduced in dentate gyrus in animals with a flattened glucocorticoid rhythm, but unchanged in CA3. The expression of the mRNA coding the synaptic vesicle protein synaptophysin was unchanged in both CA3 and dentate gyrus. The data indicate that a flattening of the normal diurnal glucocorticoid rhythm decreases the hippocampal expression of mRNAs coding key structural and functional proteins, and does so in a regionally selective manner. The data may have relevance for cognitive deficits characteristic of aging and depression.

Aging↗
PubMedDate not supplied

[Evaluating the quality of life before and after implantation of a total hip endoprosthesis].

PURPOSE OF THE STUDY: Quality of Life of patients with Total Hip Arthroplasty is analysed before and one year after surgery. The evaluation included the functional capacity of our patients in every day life comparing the preoperative situation with the result one year after surgery. Age and duration of symptoms were analysed with respect to their influence on the success of the procedure. Finally the question should be answered, if clinical examinations and questionnaires concerning Quality of Life result in comparable data. METHOD: 101 patients with an average age of 64.2 years were included into this study. All patients were evaluated preoperatively and one year after surgery using the Harris Hip Score, questionnaires for Quality of Life of the patients included the Nottingham Health Profile and the Functional Questionnaire Hannover. RESULTS: The pre- and postoperative means of the Nottingham Health Profile showed in five of the six dimensions a significant improvement of Quality of Life (pain, mobility, energy, emotional reaction, sleep). Only the scale "social isolation" remained unchanged between the pre- and postoperative situation. The means of the functional capacity according to the Hannover questionnaire improved from 57.92 to 39.79, a highly significant result. The Harris Hip Score was poor in 97% of the preoperative evaluations. This score improved to 80.2% excellent or good, 7.9% fair and 11.9% poor at one year after surgery. Age and duration of symptoms had no influence in any parameter of Quality of Life. A classification of parameters on Quality of Life according to the Harris-Hip-Score at the 1-year results demonstrates a clear grading concerning the excellent and poor results. Based on the patients evaluations a differentiation between good and poor results is not recorded. CONCLUSIONS: The objective evaluation of results after implantation of a total hip joint-endoprosthesis should not be based only on clinical scores (f.e. Harris-Hip-Score). Subjective informations by the patients using questionnaires on Quality of Life (f.e. NHP, FFbH-R) have to be included into these evaluations. The different judgments of the outcome of surgery underline the necessity, not only to use clinical scores but also to include the patients' feeling into the interpretation of the clinical result.

Activities of Daily Living↗
PubMed2004

Fenofibrate lowers adiposity and corrects metabolic abnormalities, but only partially restores endothelial function in dietary obese rats.

In humans, dietary-induced obesity markedly increases plasma lipid profile and impairs vascular function leading to increased incidence of cardiovascular events. We have recently reported that chronic withdrawal of obesity-inducing diet attenuates obesity and completely corrects endothelial function. The aim of this study was to investigate whether fenofibrate-induced decrease in adiposity would also correct vascular function in the presence of obesity-inducing diet. Wistar rats were fed with either standard laboratory chow (lean, n = 9) or given a highly palatable diet (diet-fed, n = 18) for 15 weeks. After 7 weeks, half of the diet-fed group was treated with fenofibrate (fenofibrate-treated, n = 9) for 8 weeks before being sacrificed. Untreated diet-fed (n = 9) rats had significantly higher body weight, total fat mass (by up to two-fold, p < 0.001 for both), and raised fasting plasma levels of insulin, leptin and triglycerides (up to 110%; p < 0.001), but not glucose or nonesterified fatty acids (NEFA) than both lean control and fenofibrate-treated groups. Resistance mesenteric arteries responses to KCl- and noradrenaline-induced vasoconstriction were similar in all three groups. However, compared with lean controls, endothelium-dependent vasorelaxation responses were shifted to the right in both untreated and fenofibrate-treated diet-fed groups. Fenofibrate treatment improved endothelium-dependent vasorelaxation at only high carbamycholine concentrations (10 microM). There were no differences in endothelium-independent vasorelaxation between the three groups. These results indicate that, in the presence of obesity-inducing diet, fenofibrate markedly reverses obesity and corrects insulin resistance and lipid profile, but it only has a limited beneficial effect on vascular function. Therefore, it seems that diet component rather than obesity per se plays a key role in the genesis of vascular abnormalities.

Animals↗
PubMed1997

In vivo dielectric analysis of free water content of biomaterials by time domain reflectometry.

A method of in vivo analysis of the free water content in living organisms by dielectric analysis in the time domain is described. Human skin is chosen as an example of living tissue. The cells suitable for the measurement of various layers of human skin and calculation procedures for the waveform reflected from the probe end are described. The approach was confirmed to be effective for the determination of the water content through measurement of the standard samples, keratin-water mixtures. This method was also applied to human skin in vivo. Water content data measured with a probe specially designed for surface layer analysis were sensitive to humidity around the subject. The formula expressing the relation between the electrical field character of the probe, the permittivity depth profile, and the measured permittivity was used to analyze the water content profile as a function of the depth from the skin surface. The use of several kinds of probes, differing in their electric field characteristics, permitted evaluation of the water content depth profile of human skin. This procedure is easy and applicable to any sample due to its simplicity. The measurement needs only a touch of the probe on a sample spot. It is therefore a promising method of physicochemical research on living organisms and biomaterials.

Body Water↗
PubMed1994

Quality-of-life assessment in patients with headache.

Although headache is the most common pain complaint seen by primary care physicians, the measurement of quality of life in patients with headache is in its earliest stages. Most of the research has been published within the past 2 years, much of it only in abstract form. Quality-of-life data derived from the Medical Outcomes Study instrument (SF-20) demonstrate that chronic headache disorders are associated with significant limitations in all 6 health categories of patient well-being and functioning. The outcomes profile for each of the common benign headache disorders appear to be unique for the specific headache diagnosis. Migraine is primarily associated with an impairment in role (work) functioning. Chronic tension-type headache is associated with a marked impairment in mental health and a generalised impairment in functioning. Cluster headache is associated with the greatest amount of pain, but with little impairment in physical functioning. The economic toll of recurrent headache is considerable. Lost productivity in the US due to migraine is estimated at $US6.5 to 17.2 billion per year. Chronic headache disorders cause significantly more morbidity, impairment of function, and economic loss than has previously been recognised.

Cost of Illness↗
PubMed2000

[Psychophysiologic tests for early diagnosis of central nervous system's chronic exposure to organic solvents].

The authors studied value of laboratory CNS tests in early diagnosis of chronic exposure to organic solvents. The tests include quantitative and qualitative evaluation of personal profile, higher psychic functions and bioelectric activity of brain. Findings are objective parameters of early CNS response to solvents--EEG signs characteristic for hypothalamic irritation, moderate diffuse increase in MMPI personal profile with secondary neurotic type and marked disorder of attention that is considerably influenced by nonspecific activating system of brain.

Adult↗
PubMed2004

Analysis of the function of mycobacterial DnaJ proteins by overexpression and microarray profiling.

Regulation of expression of the Hsp70/DnaK chaperone plays an important role during infection with Mycobacterium tuberculosis. We have examined the effect of manipulating the level of expression of DnaJ, one of the components of the chaperone apparatus. Overexpression of DnaJ1 resulted in elevated transcription of both the hsp70/dnaK and hsp60/groE chaperone genes, consistent with an increase in the cellular content of nascent and unfolded peptide substrates. There was also an increase in transcription of genes flanking the origin of chromosomal replication, suggesting an important role for DnaJ1 in controlling interaction of the Hsp70 chaperone with the DnaA protein. Overexpression of DnaJ2 had no detectable effect on transcription of other genes. Overexpression in combination with microarray profiling provides a complementary approach to gene deletion for exploring the function of essential genes in M. tuberculosis.

Amino Acid Sequence↗
PubMed2001

Isolation and study of the functional properties of pea proteins.

Proteins of pea seeds were isolated after defatting with hexane using alkaline (0.1 M sodium hydroxide) extraction and acid (HCl) precipitation. Concentrates were also prepared by hexane extraction and ethanolic extraction (pH = 5). Gross chemical composition amino acid content and functional properties (solubility profile, emulsifying--and foaming properties, water--and oil absorption) were studied. The results were compared with the same parameters of soy and lupin protein products. Although the majority of functional characteristics of isolates were lower in comparison to soy isolates, pea protein concentrate and isolate could be successfully used in bakery products for enrichment in protein and improvement of biological value. Their utilization as meat protein substitute in some Frankfurter type sausages is also possibly.

Amino Acids↗
PubMed2001

The C1 domain of protein kinase C as a lipid bilayer surface sensing module.

The activity of membrane-associated protein kinase C (PKC) is tightly controlled by the physical properties of the membrane lipid bilayer, in particular, curvature stress, which is induced by bilayer-destabilizing lipid components. An important example of this is the weakened lipid headgroup interactions induced by phosphatidylethanolamine (PE) and cholesterol. In this work our previous observation with a mixed isoform PKC showing a biphasic dependence of activity as a function of membrane curvature stress [Slater et al. (1994) J. Biol. Chem. 269, 4866-4871] was here extended to individual isoforms. The Ca(2+)-dependent PKCalpha, PKCbeta, and PKCgamma, along with Ca(2+)-independent PKCdelta, but not PKCepsilon or PKCzeta, displayed a biphasic activity as a function of membrane PE content. The fluorescence anisotropy of N-(5-dimethylaminonaphthalene-1-sulfonyl)dioleoylphosphatidylserine (dansyl-PS), which probes the lipid environment of PKC, also followed a biphasic profile as a function of PE content for full-length PKCalpha, PKCbetaIotaIota, and PKCgamma as did the isolated C1 domain of PKCalpha. In addition, the rotational correlation time of both PKCalpha and PKCdelta C1-domain-associated sapintoxin D, a fluorescent phorbol ester, was also a biphasic function of membrane lipid PE content. These results indicate that the C1 domain acts as a sensor of the bilayer surface properties and that its conformational response to these effects may directly underlie the resultant effects on enzyme activity.

Animals↗
PubMed2000

Effect of bulk magnetic field on critical Ising films

Two-dimensional Ising films L x infinity in a nonvanishing bulk magnetic field H are studied at the bulk critical temperature Tc for two choices of surface fields (a) H1 = HL = 0 (ordinary transition), and (b) H1 = HL = infinity (normal transition) by the density-matrix renormalization-group method. Universal scaling functions for magnetization profiles, the excess magnetization gamma, the longitudinal correlation length xi parallel, and for the analog of the solvation force fsolv are found and discussed. When H1 = 0 the scaling function for fsolv has two symmetric minima at y = sgn(H)L magnitude of H nu/delta approximately +/- 1 with an amplitude at the minimum about 3.8 times the value at H = 0, the Casimir amplitude. For the normal transition the scaling function for fsolv has a single minimum near the continuation of the pseudocoexistence (capillary condensation) line, with an amplitude about 100 times the Casimir amplitude.

Journal Article↗
PubMed2003

Baroreflex function in vasodepressive syncope: detection of early impairment.

BACKGROUND: Defective baroreflex function has been suggested as a potential mechanism accounting for the development of syncopal episodes. The present study was therefore aimed at assessing the non-invasive, indirect hemodynamic profile and baroreflex function by means of tilting, which is a natural stimulation crucial to physiological baroreflex activity, in syncopal patients and healthy controls. MATERIAL/METHODS: Seventeen consecutive patients with a positive response to head-up tilting and fourteen healthy subjects as controls underwent continuous and non-invasive beat-to-beat heart rate and arterial pressure measurements in order to evaluate systolic, diastolic, and dicrotic pressures, as well as heart rate. Baroreflex function was calculated as the slope of the linear regression line relating systolic arterial pressure to RR interval changes during upward and downward phases of tilting, respectively. RESULTS: When compared to healthy subjects, vasodepressive patients showed a significantly weaker correlation between systolic pressure and RR interval changes both in upward tilting, (r = 0.68 vs r = 0.91, p<0.05) and downward tilting (r = 0.48 vs r = 0.93, p<0.01). CONCLUSIONS: Our results show that an impairment in baroreflex-mediated adjustment to postural challenge can be detected in syncopal patients also during upward tilting, that is, in the early phase of the test. Moreover, our investigation emphases the utility of a noninvasive, complete hemodynamic evaluation of the early phase of tilting in order to detect peculiar behaviours of pulse wave contour and related parameters.

Adult↗
PubMed1994

Effector mechanisms activated by human IgG subclass antibodies: clinical and molecular aspects. Review article.

Secondary systemic immune responses are predominantly of the IgG class and passive administration of intravenous IgG, from pooled normal serum, is an effective prophylactic and/or therapeutic treatment for patients with defined immunodeficiencies. However, the proportions of each IgG subclass present within a specific antibody response may differ dramatically from that of the total IgG pool. For some antigens the response may be essentially restricted to a single subclass and it may be presumed that the antibody isotype produced has an optimal protective role. The clinical consequences of selective IgG subclass deficiency appears to validate this presumption. In this review we emphasize the differences in effector functions activated by the IgG subclasses and hence the mechanisms responsible for the removal and destruction of antigen/antibody complexes. These studies are relevant to diagnosis and treatment of patients with recurrent infection; the IgG isotype of monoclonal antibodies selected for passive in vivo therapy; the generation of customized antibodies having a pre-determined profile of effector functions and 'immuno-direction' with new vaccines to provoke an antibody response having an isotype profile optimal for the proposed application.

Complement Activation↗
PubMed2004

Expression profiling with arrays of randomly disrupted genes in mouse embryonic stem cells leads to in vivo functional analysis.

DNA arrays are capable of profiling the expression patterns of many genes in a single experiment. After finding a gene of interest in a DNA array, however, labor-intensive gene-targeting experiments sometimes must be performed for the in vivo analysis of the gene function. With random gene trapping, on the other hand, it is relatively easy to disrupt and retrieve hundreds of genes/gene candidates in mouse embryonic stem (ES) cells, but one could overlook potentially important gene-disruption events if only the nucleotide sequences and not the expression patterns of the trapped DNA segments are analyzed. To combine the benefits of the above two experimental systems, we first created approximately 900 genetrapped mouse ES cell clones and then constructed arrays of cDNAs derived from the disrupted genes. By using these arrays, we identified a novel gene predominantly expressed in the mouse brain, and the corresponding ES cell clone was used to produced mice homozygous for the disrupted allele of the gene. Detailed analysis of the knockout mice revealed that the gene trap vector completely abolished gene expression downstream of its integration site. Therefore, identification of a gene or novel gene candidate with an interesting expression pattern by using this type of DNA array immediately allows the production of knockout mice from an ES cell clone with a disrupted allele of the sequence of interest.

Adenosine↗
PubMed2003

Combined cDNA array/RT-PCR analysis of gene expression profile in rat gastrocnemius muscle: relation to its adaptive function in energy metabolism during fasting.

We evaluated the effects of fasting on the gene expression profile in rat gastrocnemius muscle using a combined cDNA array and RT-PCR approach. Of the 1176 distinct rat genes analyzed on the cDNA array, 114 were up-regulated more than twofold in response to fasting, including all 17 genes related to lipid metabolism present on the membranes and all 10 analyzed components of the proteasome machinery. Only 7 genes were down-regulated more than twofold. On the basis of our analysis of genes on the cDNA array plus the data from our RT-PCR assays, the metabolic adaptations shown by rat gastrocnemius muscle during fasting are reflected by i) increased transcription both of myosin heavy chain (MHC) Ib (associated with type I fibers) and of at least three factors involved in the shift toward type I fibers [p27kip1, muscle LIM protein (MLP), cystein rich protein-2], of which one (MLP) has been shown to enhance the activity of MyoD, which would explain the known increase in the expression of skeletal muscle uncoupling protein-3 (UCP3); ii) increased lipoprotein lipase (LPL) expression, known to trigger UCP3 transcription, which tends, together with the first point, to underline the suggested role of UCP3 in mitochondrial lipid handling (the variations under the first point and this one have not been observed in mice, indicating a species-specific regulation of these mechanisms); iii) reduced expression of the muscle-specific coenzyme Q (CoQ)7 gene, which is necessary for mitochondrial CoQ synthesis, together with an increased expression of mitochondrial adenylate kinase 3, which inactivates the resident key enzyme for CoQ synthesis, 3-hydroxy-3-methylglutaryl CoA reductase (HMGR), the mRNA level for which fell during fasting; and iv) increased transcription of components of the proteasomal pathways involved in protein degradation/turnover.

Animals↗
PubMed1991

Biophysical models of protein denaturation. I. An improvement of the model of two states.

The model of two states (native and denatured), frequently used for the description of protein denaturation, has been complemented by relations defining, on theoretical grounds, the temperature dependence of the relevant thermodynamic functions. In essence, this was achieved by assuming that the temperature dependence of Gibbs free energies of the native protein and of denaturation can be approximated, within the interval (0 degree C, 100 degrees C), by second-order partial sums of Taylor series. The improved model operates with four parameters: the temperature of denaturation, the heat capacities of the native and denatured protein at the temperature of denaturation, and the entropy of denaturation at that temperature. A theoretical treatment is included of the temperature dependence of total heat capacity, the variable recorded in the form of continuous thermograms by means of differential scanning calorimetry. Our model correctly reproduces experimental thermograms of proteins and provides for the biophysical interpretation of a number of their geometric components. Fitting procedures were complemented by a newly devised method for estimating starting values of model parameters from calorimetric data. The phenomenon of cold denaturation was also reproduced quantitatively by our model, which supplies explicit proof of the exothermal nature of this phenomenon. Finally, the relationship between temperature profiles of thermodynamic functions describing denaturation has been defined by sequences of profile magnitudes at points where the profiles intersect the temperature axis and/or cross each other. Model-derived sequences of profile magnitudes, representative of cross-point temperatures and of intervals in between, together constitute a general characteristics of denaturation, uninfluenced by differences in thermodynamic stability between protein species.

Mathematics↗

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