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Biomedical subjects

K Lange

Publications and source records attributed to K Lange.

At least 163 records · Page 9Linked to original sources
PubMed1985

Accurate and superaccurate gene mapping.

Highly accurate gene mapping techniques need to be developed to clone disease genes with unknown defective products. The classical pedigree method and methods based on cytologically observable chromosome aberrations share definite limits in resolution. We quantify the limits in resolution for the pedigree method. We also discuss a technique for gene localization that exploits the possible presence of minute depletions overlapping the disease locus. One can search for such submicroscopic deletions by aiming random probes at them. We show quantitatively that relatively few probes may suffice to hit a target deletion. Choosing which probes to aim should be guided by pedigree studies and by close examination of relevant cytologically observable translocations and deletions.

Chromosome Deletion↗
PubMed1985

Significance of endostreptosin antibody titers in poststreptococcal glomerulonephritis.

Endostreptosin (ESS) is an immunologically well defined cytoplasmic antigen of group A and some group C streptococci. ESS is probably the pathogenetic antigen of poststreptococcal glomerulonephritis (ASGN). Antibodies to ESS (ESS-Ab) were determined by microcomplement fixation in 1,102 patients and by ELISA in 105 patients. In 168 patients with ASGN (90 from the U.S.A. and 78 from Kuwait) the arithmetic mean titer was 45.2 (log10 1.40 +/- 0.606) and 50.2 (log10 1.51 +/- 0.394) respectively, both significantly elevated compared to 347 age matched children and adults from the U.S.A. whose arithmetic mean titer was 9.1 (log10 0.83 +/- 0.635) and 7.5 (log10 0.55 +/- 0.492) respectively and 139 children from Kuwait whose arithmetic mean titer was 15.7 (log10 0.92 +/- 0.495). In 51 patients with ASGN, the mean ELISA value was 67.5% higher than the values obtained from 54 normal age matched controls. Patients with streptococcal infections without renal involvement had only transiently and mildly elevated values. ESS-Abs in patients with other types of glomerulonephritides were in the range of normal. ESS-Ab titers do not parallel the titers of streptococcal exoenzymes. ESS-Ab titers are of importance for the differential diagnosis of renal diseases and of similar significance for the understanding of the pathogenetic mechanism of ASGN. They are possibly of significance for therapy in the form of an active vaccine.

Adult↗
PubMed1984

Statistical analysis of single sodium channels. Effects of N-bromoacetamide.

Currents were obtained from single sodium channels in outside-out excised patches of membrane from the cell line GH3. The currents were examined in control patches and in patches treated with N- bromoacetamide ( NBA ) to remove inactivation. The single-channel current-voltage relationship was linear over the range -60 to + 10 mV, and was unaffected by NBA . The slope conductance at 9.3 degrees C was 12 pS, and the Q10 for single channel currents was about 1.35. The currents in both control and NBA -treated patches showed evidence of a slow process similar to desensitization in acetylcholine-receptor channels. This process was especially apparent at rapid rates of stimulation (5 Hz), where openings occurred in clusters of records. The clustering of records with and without openings was analyzed by runs analysis, which showed a statistically significant trend toward nonrandom ordering in the responses of channels to voltage pulses. NBA made this nonrandom pattern more apparent. The probability that an individual channel was "hibernating" during an activating depolarization was estimated by a maximum likelihood method. The lifetime of the open state was also estimated by a maximum likelihood method, and was examined as a function of voltage. In control patches the open time was mildly voltage-dependent, showing a maximum at about -50 mV. In NBA -treated patches the open time was greater than in the control case and increased monotonically with depolarization; it asymptotically approached that of the control patches at hyperpolarized potentials. By comparing channel open times in control and NBA -treated patches, we determined beta A and beta I, the rate constants for closing activation gates and fast inactivation gates. Beta I was an exponential function of voltage, increasing e-fold for 34 mV. beta A had the opposite voltage dependence. The probability of an open channel closing its fast inactivation gate, rather than its activation gate, increased linearly with depolarization from -60 to -10 mV. These results indicate that inactivation is inherently voltage dependent.

Acetamides↗
PubMed1984

The future of nephrologic research: significance and urgent problems.

The problems in the diagnosis and especially the pathogenetic mechanism of IgA nephropathy are discussed and suggestions are made that this entity may not be a renal disease of primary renal immunogenetic origin but may be a disease of disturbed mesangial transport mechanism for IgA. Suggestions are made for intensive studies on the pathogenesis and differential diagnosis of focal glomerulosclerosis vs. minimal change disease (lipoid nephrosis) especially by immunohistology and T Cell sub-set abnormalities. It is suggested to study minimal change disease from the viewpoint of a T Cell immunodeficiency with lymphokines as a permeability changing factor. Depressed antibody formation in such partially immunodeficient patients may be important for differential diagnosis from other nephrotic stages. The immunology of acute glomerulonephritis as caused by cytoplasmic streptococcal antigens requires further study together with resultant chronic glomerulonephritis on an auto-antibody basis. The disputed merits of plasmapheresis require further detailed studies. The investigation of the suggested importance of nephrectomies on the renal function of kidney donors is of utmost importance in view of its relation to the future of live donor transplantations.

Diagnosis, Differential↗
PubMed1984

[Necrobiosis lipoidica in a patient with bronze diabetes].

A case of necrobiosis lipoidica in a patient with idiopathic hemochromatosis and diabetes mellitus is presented. Histologic examination revealed excessive amounts of iron pigment in macrophages in the corium of the necrobiotic skin. There were no iron deposits in the normal skin.

Diabetes Mellitus, Type 1↗
PubMed1984

Ascertainment and goodness of fit of variance component models for pedigree data.

The multivariate normal parameterization of the polygenic model (Lange et al., 1976) provides a great deal of flexibility for analyzing quantitative data on pedigrees. The likelihood approach employed ensures statistical efficiency and allows for hypothesis testing using the likelihood ratio criterion. The parameterization also facilitates ascertainment correction and goodness-of-fit testing (Spence et al., 1977; Ott, 1979; Hopper and Mathews, 1982; Boehnke, 1983). We reviewed these results and then described a simulation study undertaken to determine their utility when applied to data. Pedigree data were generated under polygenic and mixed models and sampled either randomly or via probands. We found that the variance components of the model were accurately estimated for random sampling, but less so for ascertained data analyzed by conditioning on probands. Goodness-of-fit tests employing test statistics corresponding to individual phenotypes and entire pedigrees were conservative, but pedigree tests did demonstrate reasonable power to reject a variety of mixed model alternatives. In addition, we found that the pedigree test statistics could be used to enrich a sample of pedigrees for those pedigrees segregating at a major locus, providing an objective criterion for choosing pedigrees to be included in a linkage analysis.

Chromosome Mapping↗
PubMed1984

EM reconstruction algorithms for emission and transmission tomography.

Two proposed likelihood models for emission and transmission image reconstruction accurately incorporate the Poisson nature of photon counting noise and a number of other relevant physical features. As in most algebraic schemes, the region to be reconstructed is divided into small pixels. For each pixel a concentration or attenuation coefficient must be estimated. In the maximum likelihood approach these parameters are estimated by maximizing the likelihood (probability of the observations). EM algorithms are iterative techniques for finding maximum likelihood estimates. In this paper we discuss the general principles behind all EM algorithms and derive in detail the specific algorithms for emission and transmission tomography. The virtues of the EM algorithms include (a) accurate incorporation of a good physical model, (b) automatic inclusion of non-negativity constraints on all parameters, (c) an excellent measure of the quality of a reconstruction, and (d) global convergence to a single vector of parameter estimates. We discuss the specification of necessary physical features such as source and detector geometries. Actual reconstructions are deferred to a later time.

Fourier Analysis↗
PubMed1983

Nephritis caused by Streptococcus zooepidemicus (Lancefield group C).

Three cases of nephritis after mild upper-respiratory-tract infection occurred in five members of a family running a small dairy farm in North Yorkshire, Streptococcus zooepidemicus (Lancefield group C) was cultured from the throats of three of those affected. The organisms were shown to produce endostreptosin, a recently discovered cytoplasmic antigen of certain beta-haemolytic streptococci that has been shown to be of prime importance in the development of poststreptococcal glomerulonephritis (PSGN). Serological testing of the patients showed raised and persistent antibody tires to this substance. These findings substantiate the association, suggested by the epidemiological features of a similar outbreak that occurred in Rumania in 1968, between Strep zooepidemicus and nephritis. As in several previous reports of Strep zooepidemicus in man, infection appeared to have been acquired by the consumption of unpasteurized milk. This outbreak implicates non-group-A streptococci in the aetiology of PSGN.

Adolescent↗
PubMed1983

Estimating kinetic constants from single channel data.

The process underlying the opening and closing of ionic channels in biological or artificial lipid membranes can be modeled kinetically as a time-homogeneous Markov chain. The elements of the chain are kinetic states that can be either open or closed. A maximum likelihood procedure is described for estimating the transition rates between these states from single channel data. The method has been implemented for linear kinetic schemes of fewer than six states, and is suitable for nonstationary data in which one or more independent channels are functioning simultaneously. It also provides standard errors for all estimates of rate constants and permits testing of smoothly parameterized subhypotheses of a general model. We have illustrated our approach by analysis of single channel data simulated on a computer and have described a procedure for analysis of experimental data.

Animals↗
PubMed1983

Extensions to pedigree analysis. V. Optimal calculation of Mendelian likelihoods.

Mendelian likelihoods are computed from human pedigree data for purposes of gene mapping, risk prediction in genetic counseling, and hypothesis testing in genetic epidemiology. The Mendelian likelihood of an extended pedigree can be written as a sum of products, the sum ranging over all possible genotypic combinations for the individuals in the pedigree. Exclusion of genotypes incompatible with the phenotypic information and pedigree structure reduces the ranges of summation and simplifies the likelihood calculation. To evaluate the likelihood with the fewest possible arithmetic operations requires carrying out the summations over one individual at a time and the intervening multiplications in some appropriate order. Each such removal of an individual reduces the likelihood evaluation to another evaluation of the same numerical form. Greedy-type algorithms are suggested for determining an order in which the summations and multiplications may be carried out. The greedy methods are fast and appear to generate good removal sequences. They are shown to work well when applied to a large, complex pedigree.

ABO Blood-Group System↗
PubMed1983

Two models for a maternal factor in the inheritance of Huntington disease.

Huntington disease is a classic example of an autosomal dominant trait. Over the years, however, a number of investigators have reported anomalies regarding the age of onset of the disease that are inconsistent with this paradigm. We propose two models in which a maternal factor--cytoplasmic in one case, autosomal or X-linked in the other--acts to delay onset in a manner consistent with the previously reported anomalies. Relevant data from the Huntington's Disease Research Roster are presented that reinforce and extend the previous observations.

Adolescent↗
PubMed1983

Statistical analysis of multilocus recombination.

A general formula for the frequency of different recombinant gamete types, in terms of the underlying distribution of crossovers, is derived. This formula may be applied to any theoretical model of recombination in which it is assumed that there is no chromatid interference. Multiple-locus recombination data may be evaluated by using this formula in conjunction with a maximum likelihood procedure. The validity of any model of recombination may be tested in such a fashion. The possibilities are demonstrated through application to a generalized noninterference model of crossing over described in a previous paper (Risch and Lange, 1979, Annals of Human Genetics 43, 61-70).

Animals↗