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PubMed1994

Calculation of the molecular weight of proteins from electrophoretic and gel exclusion chromatographic experiments.

The molecular weights of proteins or protein subunits are frequently estimated from the electrophoretic mobility in the presence of sodium dodecyl sulphate, or from the elution volume in gel filtration chromatography. Using a series of standards of known size, a calibration curve is prepared which often yields a straight line in a semilogarithmic plot; interpolation from this line then gives the size of the sample. While this method is simple to apply, it does not give any estimate of the accuracy of the determined size. Furthermore there is no objective criterion for deciding if the calibration curve is linear, or a procedure for dealing with non-linear calibration curves. Here I report a method and a computer program which uses appropriate statistical methods to select the best straight or curved calibration line. The size of the unknown is then interpolated and an estimate or the error in this value is calculated.

Calibration↗
PubMed2001

[Pharmacokinetics of high-dosage naftopidil capsules in dogs].

OBJECTIVE: To establish a high-performance liquid chromatography (HPLC) for the determination of naftopidil in plasma, and make a study of pharmacokinetics of high-dose naftopidil capsules in dogs. METHODS: Five healthy dogs were treated with naftopidil capsules in an oral single dose of 200 mg. Naftopidil in dog plasma was determined by HPLC. The mobile phase consisted of acetonitrile and 0.05 mol.L-1 phosphate buffer (pH 6.5) (60:40), verapamil was selected as internal standard, and the eluate was monitored at 230 nm. Pharmacokinetics calculations were carried out by practice pharmacokinetics programs (Version 97, 3P97). RESULTS: The calibration curve of naftopidil was linear within the range of 10-1,200 ng.ml-1, and the correlation coefficient was 0.9992, the recovery rate of HPLC was (100.23 +/- 3.00)%, within day RSD and between day RSD were no more than 5.56% and 3.30% respectively. The plasma drug concentration-time course in dogs conformed to the one-compartment model. T1/2Ke value was (1.91-4.99) h, Tmax was (1.87-3.21) h, Cmax was (338.79-414.04) ng.ml-1. CONCLUSION: HPLC is accurate and reliable, and can be used for studying the pharmacokinetics of high-dose naftopidil capsules in dogs.

Adrenergic alpha-Antagonists↗
PubMedDate not supplied

Is Na+ modeling necessary in high flux dialysis?

One important pathogenic factor in dialysis hypotension is the drop in plasma osmolality. Increasing the dialysate Na+ concentration decreases hypotensive episodes. The authors studied 39 patients being treated with high flux dialysis. During a 9 week period, the patients were on a standard Na+ dialysate (Na+ = 140 meq/L) basal period (B); 9% (Na+ = 149 meq/L) linear (L); step drop (S); and exponential drop (E). The Na+ program was changed weekly at random. The results obtained with the three Na+ modeling programs were similar. We compared the periods with and without Na+ modeling: no differences were found in weight gained interdialysis, mean blood pressure predialysis and postdialysis, and hemoconcentration. Serum Na+ levels were significantly higher predialysis and postdialysis for those patients on Na+ modeling. Hypotensive episodes and cramps decreased 50% with Na+ modeling. The amount of hypertonic and normal saline given during dialysis was markedly reduced. Na+ modeling should always be used in patients being maintained on high flux dialysis.

Adult↗
PubMed1990

The effects of sleep loss on cognitive performance of resident physicians.

Although the long hours worked by resident physicians have raised concern in the public, legislators, and members of the medical profession, the consequences of sleep loss on the ability of residents to perform in clinical settings is unknown. The present study examined the effects of various amounts of reported sleep on cognitive performance measured by the American Board of Family Practice in-training examination. A total of 353 family practice residents in 21 programs who took the examination in Pennsylvania in 1988 were studied. Linear regression analysis demonstrated a statistically significant (P less than .05) decline in composite test score with decreasing sleep on the night before the examination for residents in each year of training. Loss of one night's sleep resulted in changes in test scores that were approximately equivalent in magnitude to the change that occurred in test scores between residents in the first and third year of training. The results suggest that prolonged testing over several hours may be necessary to detect the subtle but significant differences in cognitive performance that are present with relatively mild degrees of sleep loss.

Cognition↗
PubMedDate not supplied

[Statistical analysis of data from glaucoma examinations].

Early detection of glaucoma can be achieved through prophylactic screening of population. This leads to a sharp increase in the patients' flow and deprives the physician of a possibility to examine them by routine methods. Such examinations will be feasible if to reduce the procedure time by automation, or to cut the examination program after the analysis of the existing medical programs by mathematical methods. The authors have used the method of linear discriminant functions which permits one on the basis of the medical data statistical analysis to learn the informativeness of diagnostic symptoms and decisive rules to form risk-groups of the patients who need more thorough medical examination. The analysis accomplished has indicated that there is no closely interlaced symptoms. Among most informative there are signs considerably differing in their statistical characteristics. The diagnostic rules proposed in this article provide adequately high accuracy in selection of healthy people groups and, as well, the patients with suspected glaucoma or suffering this disease.

Glaucoma↗
PubMed1993

Lack of CD24 antigen expression in B-lineage acute lymphoblastic leukemia is associated with intrinsic radiation resistance of primary clonogenic blasts.

The radiation sensitivity of primary clonogenic blasts from 27 children with immunologically classified CD2-CD5-CD7-CD19+slg- B-lineage acute lymphoblastic leukemia (ALL) was analyzed using leukemic progenitor cell (LPC) colony assays. Radiation survival curves of primary clonogenic blasts (ie, LPC) were constructed for each patient using computer programs for the single-hit multitarget as well as the linear quadratic models of cell survival. The D0 values ranged from 49 to 891 cGy (median, 239 cGy; mean +/- SE, 307 +/- 44 cGy) and the alpha values ranged from 0.000 to 2.047 Gy-1 (median, 0.156 Gy-1; mean +/- SE, 0.284 +/- 0.078 Gy-1). Patients were divided into groups according to sex, age, white blood cell count (WBC) at diagnosis, plating efficiency of primary bone marrow blasts, and immunophenotype. Patient sex, age, WBC at diagnosis, or in vitro plating efficiency was not associated with radiation resistance. Notably, freshly isolated primary clonogenic blasts from patients with a CD19+CD24-CD34+ composite immunophenotype (stage I B-cell precursor [BCP]) had 2.2-fold higher D0 values (P = .005) and 3.4-fold lower alpha values (P = .05) than those from patients with a CD19+CD24+CD34+ (stage II BCP) or CD19+CD24+CD34- (stage III BCP) immunophenotype. The relative values for CD24- primary clonogenic blasts signify greater intrinsic radiation resistance. Furthermore, the CD19+CD24-CD34+ immunophenotype had a larger radiation resistant fraction. Whereas only 60% of CD19+CD24+CD34+ and 33% of CD19+CD24+CD34- cases had clonogenic blasts with alpha < or = 0.2, 100% of CD19+CD24-CD34+ cases had clonogenic blasts with alpha < or = 0.2. Furthermore, clonogenic blasts from established CD19+CD24- B-lineage ALL cell lines were significantly more radiation resistant than CD19+CD24+ B-lineage ALL cell lines. Notably, radiation doses sufficient to induce apoptosis of CD24- B-lineage ALL cells were higher than those capable of inducing apoptosis in CD24+ B-lineage ALL cells. Thus, the lack of CD24 surface antigen expression in B-lineage ALL is associated with intrinsic radiation resistance at the level of primary clonogenic blasts.

Antigens, CD↗
PubMedDate not supplied

[Cortisol determination in human plasma by a modified method of competitive protein binding].

The authors described a simple and economic modification of the competitive protein binding method of cortisol determination in human blood plasma satisfying the current requirements presented to the saturation analysis. Blood plasma of women given combined contraceptive the preparation was used as a binding system. Analysis of experimental results using a programmed computer was carried out on the basis of standard curve linearization. Preeision sensitivity and specificity of this modified method are assessed. This modification was approved in measuring the cortisol level in the blood plasma of various groups of patients. Comparison with routine competitive binding methods and their analysis is presented.

Dexamethasone↗
PubMed1990

Intensity-based domain refinement of oriented but unpositioned molecular replacement models.

A program is described that performs least-squares group refinement of oriented molecular replacement models whose positions in the unit cell are unknown. The program (INTREF) is designed to produce improved models for use in a translation function by optimizing the orientations and relative translations of the model domains. The molecular contents of the asymmetric unit are refined as a small number of rigid bodies whose origins relative to each other may be unknown. More than one molecule in the asymmetric unit can be accommodated. The refinement seeks to minimize the residual error between the observed and calculated intensities that have been modified to produce the equivalent of a radial weighting in Patterson space. Calculated intensities include contributions from all symmetry-related molecules, enabling meaningful refinement in high-symmetry space groups. Derivatives of the intensities with respect to the rigid-body parameters are evaluated numerically using fast Fourier transforms and the shifts are obtained by non-linear least-squares analysis. Results with test cases show that the program is capable of adjusting the orientations and relative translations of protein domains to give models that more closely resemble the known structures. Consequently, the resulting models produce more accurate and more interpretable results in translation functions. The importance of including all crystallographically related molecules and of downweighting the contribution of the longer-radius region of the Patterson function is demonstrated.

Antibodies, Monoclonal↗
PubMed1983

Stratified trend and homogeneity analyses of proportions and life table data.

Tests for linear trend and homogeneity among proportions and analogous time adjusted tests for life table data are programmed for stratified data. For proportions, the maximum likelihood estimator of the common logistic slope and its approximate standard error is given. This parameter is related to the relative risk for the factor under test. The model is a simpler and more relevant subcase of the general linear multiple logistic model. Tests of fit include a chi-square test of departure from trend for both types of data, and, for proportions, a test for the equality of slopes among groups of strata. The program is particularly useful for large prospective studies in epidemiology, but may also prove helpful for case-control studies, clinical trials, and combining animal studies. Several optional analyses are included. The program generalizes most aspects of a previously published program by Thomas, Breslow, and Gart (Trend and homogeneity analyses of proportions and life table data. Comp. Biomed. Res. 10, 373 (1977)). A FORTRAN card deck with documentation is available upon request.

Actuarial Analysis↗
PubMed1991

National sheep improvement program: age adjustment of weaning weight.

Lamb weaning weights at 30 +/- 14, 60 +/- 28, and 90 +/- 28 d were used to evaluate the effect of birth weight on the linear adjustment of weaning weight to a constant age and the effect of deviations from target dates on the accuracy of linear age adjustment. The data consisted of 13,501 birth weights, 3,721 30-d records, 10,988 60-d records, and 3,285 90-d records from the National Sheep Improvement Program data base for the Dorset, Polypay, Rambouillet, Columbia, Hampshire and Suffolk breeds. The effect of using constant vs actual birth weights in a standard linear age adjustment was evaluated using various sex, type-of-birth, and breed type constants. Product moment and rank correlations indicated that a constant birth weight should be used when the actual birth weight is not known, but the choice of constant makes little difference in average bias or maximum adjustment error. The linear age adjustment procedure and the optimal age range for recording weaning weight were examined using a model including effects for contemporary group, sex, type of birth and rearing, age of dam, and breed. The linear age adjustment did not remove the effect of age for the small breed type (Dorset, Polypay, and Rambouillet breeds) at 30 d and the large breed type (Columbia, Hampshire, and Suffolk breeds) at 60 d for age ranges greater than +/- 7 d (P less than .01) but was adequate for all lambs weaned at 30 +/- 7 d, 60 +/- 7 d, and 90 +/- 28 d of age.

Age Factors↗
PubMed2004

Male breast cancer: is the incidence increasing?

BACKGROUND: Male breast cancer is rare, and little is known about state population-level patterns of incidence. The primary objective of this study was to determine the incidence of MBC in Florida in comparison with the Surveillance, Epidemiology, and End RESULTS (SEER) program data. METHODS: Study data were obtained from the Florida Cancer Data System (FCDS). All males with pathologically confirmed invasive breast carcinoma diagnosed from 1985 to 2000 were included. Age-adjusted incidence rates, regional incidence rates, and descriptive statistics were calculated. Annual percent change (APC) for the study period was calculated with a linear model. Results were compared with the SEER data. RESULTS: A total of 1396 cases of MBC were identified. Age-adjusted incidence rates increased from 0.9 cases per 100,000 in 1990 to 1.5 cases per 100,000 in 2000. In 2000, the highest rates were in the age groups of 70 to 75 years (7.9) and > or =85 years (12.5). Infiltrating ductal was the most common subtype (92%); less common subtypes included mucinous (2%) and papillary (2%). Localized disease accounted for 45% of all cases, with regional disease in 33%, distant metastases in 7%, and unstaged in 15%. Most incident cases were diagnosed in the Palm Beach-Broward region (23%). The number of cases increased from 56 in 1985 to 132 new cases in 2000. The APC for this 16-year period was 2.0% (95% confidence interval [CI], 1.05-3.01; P <.005). SEER data indicated no change in MBC incidence rates (APC, 0.5; NS). CONCLUSIONS: The incidence of MBC in Florida increased significantly between 1985 and 2000. This finding is discordant with SEER incidence data. Further epidemiologic studies are warranted to investigate regional variation.

Adult↗
PubMed2000

Circular and linear DNA molecules in the Entamoeba histolytica complex molecular karyotype.

Entamoeba histolytica genome was analysed by pulsed field gel electrophoresis under conditions to separate linear chromosomes in the 170-1400 kb range. We identified linear DNA molecules of 227, 366, 631, 850, 1112 and 1361 kb (mean sizes obtained by three different methods) and we estimated their reorientation times and migration velocities at various experimental conditions. DNA shift mobility assays, using ethidium bromide, suggested that bands migrating at 227 and 631 kb contain linear and circular DNA, whereas a band at 436 kb has only circular DNA. We obtained a regression equation relating sizes of supercoiled DNA molecules with their migration velocities during a pulse at constant electric field and temperature. We also developed a computer program (EHPATTERNS) that predicts the migration per pulse and the resolution order of circular and linear E. histolytica DNA at different pulse times and constant driving and frictional forces. The simulation showed that linear DNA molecules frequently co-migrate with circular molecules, but circular molecules change when the pulse time varies. This molecular mixture generates broad bands and difficulties in the interpretation of the molecular karyotype of E. histolytica.

Animals↗
PubMed2001

Interactions among program, placement, and services in educational planning for students with disabilities.

Although IDEA and its corresponding federal regulations provide an underlying philosophy and procedures to help design education for students with disabilities, the law remains open to widely varying interpretations. One aspect of IDEA, namely, the relationship among the program, placement, and services for a student with disabilities when planning an appropriate education is discussed here. An analysis of how these three interrelated components can be applied in different sequences highlights drawbacks to some sequence variations. A conceptualization of how program, placement, and services can be approached in an interactive manner, rather than a strict linear one, is offered within a framework that is consistent with IDEA, its corresponding regulations, and educational logic.

Adolescent↗
PubMed1988

The antigenic index: a novel algorithm for predicting antigenic determinants.

In this paper, we introduce a computer algorithm which can be used to predict the topological features of a protein directly from its primary amino acid sequence. The computer program generates values for surface accessibility parameters and combines these values with those obtained for regional backbone flexibility and predicted secondary structure. The output of this algorithm, the antigenic index, is used to create a linear surface contour profile of the protein. Because most, if not all, antigenic sites are located within surface exposed regions of a protein, the program offers a reliable means of predicting potential antigenic determinants. We have tested the ability of this program to generate accurate surface contour profiles and predict antigenic sites from the linear amino acid sequences of well-characterized proteins and found a strong correlation between the predictions of the antigenic index and known structural and biological data.

Algorithms↗
PubMed2004

Cartilage thickness in cadaveric ankles: measurement with double-contrast multi-detector row CT arthrography versus MR imaging.

PURPOSE: To test the accuracy of double-contrast multi-detector row computed tomographic (CT) arthrography for measurement of cartilage thickness in cadaveric ankles and to compare this technique with three-dimensional (3D) fat-suppressed spoiled gradient-echo in the steady state (FS-SPGR) magnetic resonance (MR) imaging. MATERIALS AND METHODS: Five cadaveric ankles were used. In the ankle specimens, five to nine 1.5-mm-diameter holes were drilled across the joint traversing the tibial subchondral bone, tibial articular cartilage, talar dome cartilage, and talar subchondral bone. The ankle specimens were obtained and used according to institutional policies. Each ankle specimen was imaged first by using 3D FS-SPGR MR imaging with a 1.5-T magnet and then by using double-contrast arthrography followed by CT with a four-detector row scanner (ie, double-contrast multi-detector row CT arthrography). The section thickness used for CT scanning was 1.0 mm reconstructed in 0.5-mm intervals. The MR and CT images obtained in the five specimens were then downloaded to a workstation, where a measurement tool was used to measure the cartilage thickness at each hole. The physical measurement of cartilage thickness at each hole was used as the reference standard with which the MR imaging and CT measurements were compared. Linear regression and correlation analyses were performed by using a statistical computer program. RESULTS: Double-contrast arthrography followed by multi-detector row CT, as compared with 3D FS-SPGR MR imaging, enabled more accurate measurement of the physical cartilage thickness in the ankle (P < .001). CONCLUSION: In this study of five cadaveric ankles, multi-detector row CT arthrography was more accurate than 3D FS-SPGR MR imaging for measurement of articular cartilage thickness in the ankle.

Adult↗
PubMed2006

[Optimum separation conditions of catechin compounds by HCI program in reversed-phase high performance liquid chromatography].

An efficient optimization method was used to separate catechin compounds by reversed-phase high performance liquid chromatography (RP-HPLC). The binary mobile phase of water and methanol was utilized with the buffer of acetic acid (AA). The elution profiles were calculated by the plate theory based on the linear and quadratic equations of retention factor, In k = ln kw + SF, k = A + B/F, ln k = L + MF + NF2, where F is the volume fraction of methanol in the mobile phase. The retention theory was modified to calculate the elution profile in both isocratic and gradient modes. Based on the retention theory, elution profiles were predicted by introducing the concept of solute migration in the mobile phase with the linear and quadratic dependence of ln k in terms of the organic modifier content. Using the HCI program (a software designed by Inha University), the recommended experimental conditions of mobile phase composition and gradient step were suggested, and the elution profiles calculated by the quadratic relationship of ln k showed better coincidence with the experimental data than the linear correlation did. The calculated results of mobile phase condition for separation of catechin compounds suggested that the mobile phase composition was 0.1% AA in water/0.1% AA in methanol, 75/25 (v/v), then after 15 min, the composition was linearly changed to 50/50 (v/v) in 10 min and held at the isocratic mode to the end. In the experimental conditions, the agreement between the experimental elution profiles and the calculated values of eluted concentration was relatively good.

Algorithms↗
PubMed1999

Design, construction, and validation of a large capacity rodent magnetic field exposure laboratory.

A magnetic field exposure laboratory has been constructed to support National Toxicology Program studies for the evaluation of the toxicity and carcinogenicity of pure, linearly polarized, 60 Hz magnetic fields in rodents. This dual corridor, controlled access facility can support the simultaneous exposure of 1200 rats and 1200 mice. The facility contains fully redundant electrical and environmental control systems and was constructed using non-metallic materials to maintain low levels of background (ambient), stray, and cross-talk magnetic fields. The exposure module design provides for large uniform exposure volumes with good control of stray and cross-talk fields, while allowing the use of roll-around cage racks for simplified animal husbandry. Stray fields and cross-talk have been further reduced by the inclusion of "steering coils" in each exposure module. Ambient 60 Hz fields (less cross-talk) in all exposure rooms are <0.1 microT (1 mG), and static magnetic fields have been mapped extensively. Magnetic field strength, waveform, temperature, relative humidity, light intensity, noise level, vibration, and air flow in all animal holding areas are tightly regulated, and are monitored continuously during all studies. Field uniformity in the animal exposure volumes is better than -/+l0%; a systematic program of cage, rack, and room rotation controls for possible positional effects within the exposure system. Magnetic fields are turned on and off over multiple cycles to prevent the induction of transients associated with abrupt field level changes. Total harmonic distortion is <3% at all field strengths. The facility has been used to study magnetic field bioeffects in rodent model systems in experiments ranging in duration from 8 weeks to 2 years.

Air Movements↗
PubMed1998

Population pharmacokinetics of vancomycin in Japanese adult patients.

Population pharmacokinetic parameters of vancomycin (VCM) in Japanese adult patients infected with methicillin-resistant Staphylococcus aureus (MRSA) were estimated using 1253 items of serum concentration data from 190 patients obtained in routine drug monitoring. The two-compartment linear model was adopted, and VCM clearance (CL) was correlated with the creatinine clearance (CLcr), which was observed or estimated by the Cockcroft-Gault equation. The population pharmacokinetic analysis program NONMEM with first-order conditional estimation method was used. The results showed VCM clearance to be linearly correlated with CLcr (CL [ml/min] = 0.797 x CLcr) when the estimated CLcr was <85 ml/min, but no linear relationship at higher than this level because of the lack of accuracy in the CLcr estimates. The interindividual variability of CL was 38.5%; K12 and K21 were 0.525 hr(-1) and 0.213 hr(-1), respectively. The distribution volume at steady state (V[SS]) was 60.71, with no significant dependence on the actual body weight. The interindividual variability of Vss was 25.4%. The calculated half-life (t1/2,beta) in a typical patient with CLcr of 85 ml/minute was 12.8 hours. Residual variability was 23.7%. These results were compared to those of healthy volunteers, and guidelines for dosage adjustment in VCM therapy are discussed.

Adult↗