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Biomedical subjects

H G Müller

Publications and source records attributed to H G Müller.

At least 19 recordsLinked to original sources
PubMed2000

Pretransplant systemic inflammation and acute rejection after renal transplantation.

BACKGROUND: There are presently no established pre-transplant tests that consistently identify patients who may be at increased risk for acute rejection episodes after renal transplantation. We studied whether pretransplant serum levels of C-reactive protein (CRP), a marker for the presence of systemic inflammation, would predict the occurrence of acute rejection episodes after renal transplantation. METHODS: Pretransplant serum was tested for CRP level in 97 consecutive renal transplant recipients. Time to acute rejection after transplantation was stratified by CRP level and compared using the Kaplan-Meier method. In addition, Cox regression multivariate analysis was performed to assess whether any pretransplant covariates could independently predict the subsequent occurrence of acute rejection episodes. RESULTS: Pretransplant mean CRP levels were higher in patients who subsequently had a rejection episode versus those who had no rejection (22.2+/-2.9 vs. 11.7+/-1.8 microg/ml, respectively, P=0.003). Patients less than the median CRP value had a significantly longer time to rejection compared to those with higher CRP levels (P=0.002). Similarly, patients within the lowest CRP quartile had longer times to rejection when compared with the highest quartile (P=0.006). Cox proportional hazards regression multivariate analysis identified CRP level as the only independent pretransplant risk factor for rejection identified (P=0.044). CONCLUSIONS: Pretransplant systemic inflammation as manifested by elevated serum CRP level independently predicts the risk of acute rejection after renal transplantation and may be useful in stratifying patients at the time of transplantation according to immunological risk. Thus, assessment of pretransplant systemic inflammatory status may be helpful in prospective individualization of immunosuppression therapy after renal transplantation.

Acute Disease↗
PubMed2000

The acute-phase response varies with time and predicts serum albumin levels in hemodialysis patients. The HEMO Study Group.

BACKGROUND: Cross sectional studies have established that the serum albumin level is dependent on serum levels of acute-phase proteins (APPs) or cytokine levels in hemodialysis patients. While the acute-phase response is generally associated with acute inflammatory events, a cross sectional analysis relating laboratory values to outcomes assumes these values to be unchanging. The longitudinal relationship among laboratory measurements and how they vary over time in a population of patients are unknown. METHODS: Patients who were enrolled in the HEMO Study were recruited into an ancillary longitudinal study to establish the predictive effect of temporal variation in the levels of APPs and of temporal variation in normalized protein catabolic rate (nPCR) on the serum albumin concentration. nPCR was measured monthly using a double-pool method. The positive APPs-C-reactive protein (CRP), alpha1 acid glycoprotein (alpha1-AG), and ceruloplasmin-and the negative APP-transferrin (Trf)-were measured in serum obtained before each dialysis session for six weeks and then monthly in 37 hemodialysis patients. A random coefficient regression analysis was used to assess the association of serum albumin with other measured parameters at each time point, as well as fixed patient characteristics. RESULTS: The within-subject coefficients of variation of albumin (median, range of 25th to 75th percentiles; median, 0.0614; range, 0.0485 to 0.0690) were significantly less than that of APPs (CRP, median, 0.878; range, 0.595 to 1.314, P < 0. 05; and alpha1 AG, median, 0.173; range, 0.116 to 0.247, P < 0.05). The levels of APPs and albumin varied considerably over time. The primary predictor of current albumin was the current CRP level (P = 0.0014). nPCR also was a significant predictor for albumin levels (P = 0.0440) after controlling for the effect of APPs, suggesting an effect of nPCR on serum albumin concentration irrespective of the acute-phase response. Age and the presence of an arteriovenous graft were significant predictors that were associated with reduced albumin. CONCLUSIONS: The acute-phase response is intermittent and is not a continuous feature in individual dialysis patients. Levels of APPs are the most powerful predictors for the levels of albumin concentration in hemodialysis in a longitudinal setting. Since variations in albumin are small, measurement of variations in APPs may provide greater insight into the dynamics of clinically relevant processes.

Acute-Phase Reaction↗
PubMed1999

Mortality oscillations induced by periodic starvation alter sex-mortality differentials in Mediterranean fruit flies.

Sex-specific mortality rates of medflies were monitored in cages containing individuals of both sexes and with food (either sugar-only or full diet) removed every 2nd, 3rd, or 4th day (plus ad libitum controls). The general finding is that periodic starvation led to marked oscillations in raw mortality rates. The specific findings are as follows: (i) female medflies live longer than male medflies when they are subjected to periodic starvation; (ii) male medflies maintained on a full diet experience a catastrophic increase in mortality (40%) on the first day food is removed. This mortality surge was not observed for females on either diet or for males maintained on a sugar-only diet; (ii) life expectancy is inversely related to the amplitude of mortality oscillations caused by food deprivation; and (iv) the large perturbations in mortality at younger ages caused by periodic starvation has little effect on the amplitude of mortality at older ages. In general, our data shed new light on the complexity of the mortality response of medflies to both the type and availability of food and thus provide a complimentary perspective to findings from dietary restriction studies on both vertebrate and invertebrate systems.

Adaptation, Physiological↗
PubMed1998

Dual modes of aging in Mediterranean fruit fly females.

The life history of medflies is characterized by two physiological modes with different demographic schedules of fertility and survival: a waiting mode in which both mortality and reproduction are low and a reproductive mode in which mortality is very low at the onset of egg laying but accelerates as eggs are laid. Medflies stay in waiting mode when they are fed only sugar. When fed protein, a scarce resource in the wild, medflies switch to reproductive mode. Medflies that switch from waiting to reproductive mode survive longer than medflies kept in either mode exclusively. An understanding of the physiological shift that occurs between the waiting and reproductive modes may yield information about the fundamental processes that determine longevity.

Aging↗
PubMed1998

Statistical models for quantitative bioassay.

We discuss various statistical approaches useful in the analysis of nutritional dose-response data with a continuous response. The emphasis is on the multivariate case with several predictors. The methods which will be discussed can be classified into parametric models, including change-point models, and nonparametric models, which rely on smoothing methods such as weighted local linear fitting. The methods will be illustrated with the analysis of data generated from a folate depletion-repletion bioassay experiment conducted on rats, where the measured growth rate of the rate is the response variable. We also discuss the biological conclusions that can be drawn from applying various statistical methods to this data set.

Animal Nutritional Physiological Phenomena↗
PubMed1998

Statistical tools for the analysis of nutrition effects on the survival of cohorts.

We discuss various methods which can be employed for the comparative analysis of samples of response curves. In the application discussed here, these curves are hazard functions, each generated by the survival data obtained for a cohort of experimental subjects which are fed a specific diet. It is demonstrated how comparisons of the effects of different diets on survival can be carried out by employing statistical techniques for inference on samples of curves. The methods are illustrated with data on the survival of large cohorts of male and female Mediterranean fruit flies under full diet and under protein deprivation. These statistical methods allow one to investigate differences between the samples of hazard functions generated by the four groups defined by combinations of sex and diet.

Analysis of Variance↗
PubMed1998

Characterization of factor VIII/von Willebrand factor concentrates using a modified method of von Willebrand factor multimer analysis.

In order to provide patients with von Willebrand disease a factor VIII (FVIII)/von Willebrand factor (vWF) concentrate of reproducible quality, an SDS-agarose gel electrophoresis method has been established to determine the content of the high molecular weight multimers (band 11 and higher) of vWF. This method has been used to characterize the content of high molecular weight vWF multimers in Humate P/Haemate P, a commercial FVIII/vWF concentrate. The average content of high molecular weight vWF multimers of 47 batches of Humate P/Haemate P has been determined to be 84.1% of the corresponding bands in normal human plasma. Use of this multimer analysis method for the characterization of five further commercial products revealed clear differences with respect to the high molecular weight vWF multimer content. Furthermore, there is a linear correlation (r2 = 0.73) between the content of high molecular weight vWF multimers and the specific activity of vWF (determined as vWF:RCoF/vWF:Ag). The method described here for analysis of the content of high molecular weight vWF multimers is a reliable and reproducible method to characterize this class of factor concentrates with respect to vWF multimer composition.

Electrophoresis↗
PubMed1998

Comparative in vitro investigation of prothrombin complex concentrates.

Three commercial prothrombin complex concentrates (PCC) were compared in vitro. Differences in the activities or contents, respectively, of the PCC factors FII, FVII, FIX, FX and the proteins C, S, and Z (antigen) in particular were found. Global tests of activated factors did not reveal marked differences between the products. Neither free thrombin nor elevated levels of activated FX were detected. In contrast, analyses of FVIIa, of residual amidolytic activities, and of concentrations of unwanted ingredients demonstrated considerable differences between the products. While antithrombin III was detected only in two of three concentrates, heparin was found in all PCCs but in markedly different concentrations. Although the homogeneity of the products has been clearly improved in comparison with former comparative investigations, the products can be distinguished by their compound profile and by a couple of in vitro assays.

Biological Products↗
PubMed1998

Estimating the concentration of beta-carotene required for maximal protection of low-density lipoproteins in women.

The reportedly inconsistent antioxidant protective effect of beta-carotene on plasma LDL may depend on LDL's beta-carotene concentration. We measured carbonyl production by CuSO4-challenged LDL from nine healthy women living at the US Department of Agriculture-Western Human Nutrition Research Center and consuming a natural food diet that provided only 0.14 micromol beta-carotene/d for 120 d. During the first 60 d, four women received a placebo and the remaining five women received too small a supplement (0.93 micromol beta-carotene/d) to increase plasma or LDL beta-carotene; therefore, the data for all nine women during this time were pooled. From days 61 to 120, all subjects received the small supplement. From days 101 to 120 they all received an additional, larger, mixed carotenoid supplement (6.16 micromol beta-carotene/d). Plasma beta-carotene dropped from 0.76 +/- 0.21 micromol/L (x +/- SEM) on day 2 to 0.33 +/- 0.08 on day 60 (P = 0.035) and rose to 1.73 +/- 0.18 (P = 0.001) on day 120. LDL beta-carotene dropped from 1.67 +/- 0.53 micromol/g LDL protein on day 2 to 1.27 +/- 0.28 micromol/g LDL protein on day 60 (P = 0.650) and rose to 10.04 +/- 1.07 micromol/g LDL protein (P = 0.001) on day 120. Plasma lycopene dropped from 0.20 micromol/L on day 2 to 0.02 micromol/L on day 60 and did not increase by day 120. Carbonyl production rose from 24 +/- 6 micromol/g LDL protein on day 2 to 42 +/- 4 micromol/g LDL protein (P = 0.001) on day 60 and dropped to 6 +/- 1 micromol/g LDL protein (P = 0.001) on day 120. LDL seemed fully protected with 9.7 +/- 2.5 micromol beta-carotene/g LDL protein, or 2.3 +/- 1.8 micromol beta-carotene/L plasma.

Adolescent↗
PubMed1997

Early mortality surge in protein-deprived females causes reversal of sex differential of life expectancy in Mediterranean fruit flies.

Experiments based on over 400,000 medflies revealed that females maintained on a normal diet (sucrose plus protein) have a higher life expectancy than males maintained on a normal diet, with a difference of 1.30 +/- 0.27 days in favor of females. However, this sex differential reverses under protein deprivation, with a difference of 2.24 +/- 0.18 days in favor of males. The reversal of the male-female life expectancy differential is caused by a sustained surge in early female mortality under protein deprivation that is tied to egg-laying and physiological processes. In contrast, male mortality and life expectancy are only mildly affected by protein deprivation. The surge in early mortality for female medfly cohorts is an instance of a vulnerable period. These vulnerable periods are linked with patterns in hazard rates.

Aging↗
PubMed1996

Statistical interaction model for exchangeability of food folates in rat growth bioassay.

The comparative value of several sources of dietary folate in promoting growth of folate-depleted rats was determined in a folate depletion-repletion rat growth bioassay. Folate-depleted rats were fed an amino acid-based diet supplemented with 11 different concentrations of folate (227, 272, 317, 363, 408, 454, 499, 544, 590, 635 and 680 nmol/kg) from each of 12 different sources of folate (folic acid, fried beef liver, cooked pinto beans individually, or as 1/3, 1/1, or 3/1 combinations of folate from the folic acid/beans, folic acid/beef liver and beans/beef liver) for a total of 132 treatments. Growth response to folic acid and bean folate was linear, whereas that to beef liver folate was distinctly nonlinear, beef liver folate being more potent at lower dietary concentrations but less potent at higher concentrations compared with folic acid and bean folate. Folic acid and bean folate were equivalent to and exchangeable with one another in promoting growth. Beef liver folate and folic acid/bean folate had an interactive effect in promoting growth. The nature of the interaction was antagonistic in that the presence of folic acid and/or bean folate reduced the efficacy of beef liver folate and vice versa. Beef liver folate is not exchangeable with either folic acid or bean folate. We conclude that food folates generally are not exchangeable and do interact adversely. A statistical interaction model that predicted the growth-promoting effect of several sources of dietary folate was developed and validated.

Animals↗
PubMed1996

[Nanofiltration in production of Beriplex P/N: increasing the capacity of virus elimination while maintaining product quality].

For the manufacture of the PCC Beriplex P/N, nanofiltration was introduced into the production process of Beriplex HS providing an additional means to heat treatment for the clearance/inactivation of viruses. By nanofiltration, large enveloped viruses (HSV-1, HIV-1) were completely eliminated by a factor of more than 7 log10. While medium-sized enveloped viruses (HBV, BVDV) were cleared by a factor of approximately 4 log10, small non-enveloped viruses (poliovirus) were not removed. The product profile remained, no thrombogenic activities were detected.

Blood Coagulation Factors↗
PubMed1995

Estimating derivatives of pharmacokinetic response curves with varying bandwidths.

A kernel-smoothing method with locally varying bandwidths for the nonparametric estimation of derivatives of a function is proposed for highly nonequidistant data as they occur in pharmacokinetic response curves. We construct estimates having the particular property that the derivative estimates correspond exactly to the corresponding derivatives of the curve estimate even under locally varying bandwidth choice. The effects on the estimation of peak location (characteristic points) are investigated. In an example, characteristic points are estimated for a recently developed in vivo isotope dilution assay for vitamin A (retinol) nutritional status. The in vivo kinetics of appearance and disappearance of isotopically labeled retinol can be described with the proposed method.

Anticarcinogenic Agents↗
PubMed1994

Hazard rate estimation under random censoring with varying kernels and bandwidths.

We discuss the estimation of hazard rates under random censoring with the kernel method. Two practically relevant problems that occur when applying unmodified kernel estimators are boundary effects near the endpoints of the support of the hazard rate, and a substantial increase in the variance from left to right over the range of abscissae where the hazard rate is estimated. A new class of boundary kernels is proposed for the first problem. Explicit formulas for these kernels are developed, and it is shown that this boundary correction works well in practice. A data-adaptive varying bandwidth selection procedure is proposed for the second problem. This procedure generally will lead to increasing bandwidths near the left endpoint and toward the right endpoint, and will lead to smaller integrated mean squared error of the hazard rate estimator as compared to a fixed bandwidth method. A practically feasible method incorporating the new boundary kernels and local bandwidth choices is implemented and illustrated with survival data from a leukemia study.

Algorithms↗
PubMed1993

A depletion-repletion folate bioassay based on growth and tissue folate concentrations of rats.

To improve standardization of a folate bioassay, folate-depleted rats were repleted with a folate-free amino acid-based diet supplemented with 29 levels of folic acid. Growth was the main response variable and body tissue folate concentrations were also assessed. Because a positive correlation was observed between low levels of dietary folic acid and growth and little or no correlation was observed between high levels and growth, six regression models with a steep slope for low levels and a shallow or zero slope for high levels of dietary folic acid were evaluated. The model referred to as the "two-phase regression" or "change-point" model best described the relationship. Depleted rats needed 674 +/- 71 nmol folic acid/kg diet to reach their full growth potential. This value is biologically sensible, and this regression model is well established in the statistical literature. The change-point model is highly recommended to characterize the growth response, because growth is a functional response and, in the range of 226 to 680 nmol folic acid/kg, this response is linear, which is an additional advantage. Linear responses are easier to interpret because of complicated issues of interpretation and confidence intervals with nonlinearities. Linear regressions described serum and liver folate responses, whereas exponentials described whole blood and carcass folate responses. Depleted rats needed 5920 and 5780 nmol folic acid/kg diet to maximize their whole blood and carcass folates, respectively.

Animals↗
PubMed1992

Quality control in routine chromosome analysis: prediction of total number of bands for the individual case analyzed.

In routine diagnosis it is of importance for each single analysis to provide information about the level of quality at which the chromosomal analysis has been performed. The number of bands counted can be used as a direct criterion for the level of quality. Statistical prediction methods via linear regression were employed in order to predict the total number of bands of a haploid set of the metaphase (TNB) from those of single chromosomes or pairs of chromosomes. It was demonstrated that TNB can be predicted successfully by counting bands on just one chromosome, where chromosomes C2, C4, C5 or C7 were found suitable for prediction. If pairs of chromosomes are used to predict TNB, we would recommend C4/C7, C5/C6, and C2/C9.

Chromosome Banding↗
PubMed1992

Immunocytochemical localization of alkane-inducible cytochrome P-450 and its NADPH-dependent reductase in the yeast Candida maltosa.

Antibodies directed against cytochrome P-450Cm1 and the NADPH-cytochrome P-450 reductase were used to study the induction and intracellular localization of these components of the alkane monooxygenase system in the yeast Candida maltosa. Transition from glucose to n-hexadecane utilization resulted in an about 100-fold increase of the immunodetectable P-450 form whereas the reductase was only moderately induced by a factor of about 5. P-450 but not the reductase was further increased by oxygen limitation during cultivation on n-hexadecane. Using an immunogold technique on ultrathin cryosections, P-450 was found to be concentrated in the nuclear envelope during the early phase of the induction process. However, after maximal induction, the highest labeling was observed in membranes of the endoplasmic reticulum closely associated with the peroxisomes and the plasma membrane. Double-labeling experiments revealed that P-450 and its reductase were distributed in the same regions of the endoplasmic reticulum.

Alkanes↗