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PubMed1988

Comparison of the different variants of the current source density analysis methods in neurophysiological studies.

Computer calculations and theoretical studies of different variants of current-source density analysis (CSDA) for neurophysological studies were carried out. The different variants of the method are compared by estimating equiweight surfaces and equiweight lines in particular planes. The decrease in the distance between the different points of measurement has been found to result in more selective presentation of the neuronal activity. It is shown that this distance cannot be very small--50 micron seems a reasonable limit. Bidimensional and especially unidimensional CSD-analysis produces considerable volumes with negative weights, these weights being rather high in absolute value. Errors in the interpretation of the results are possible, such as incorrect calculation of the current density and even erroneous determination of its sign.

Mathematics↗
PubMed1980

The structure of the market for physicians' services.

In this paper, structural equations for the supply of and the demand for general practitioners' services are derived. Two variants of the model, based on alternative specifications of the role of health insurance, are tested, using data drawn from the American Medical Association's Eighth Periodic Survey of Physicians (PSP8). While results of the estimation require the rejection of the hypothesis that the market for general practitioners' service is perfectly competitive, the elasticities of demand implied are quite high. Estimates of the supply relationships support the presence of "backward bending" supplies of physicians' services, but this finding should be interpreted cautiously.

Fees, Medical↗
PubMed1980

Malignant lymphoma with a high content of epithelioid histiocytes: report of T-cell variant of so-called Lennert lymphoma and review of the literature.

The present report describes the first case of well-differentiated nodular lymphocytic lymphoma evolving into Lennert lymphoma of T-cell origin. A 58-year-old white female developed malignant lymphoma, well-differentiated, lymphocytic type, nodular, with focal bone marrow involvement (stage IV) in May 1975. She received 16 cycles of cyclophosphamide and prednisone combination chemotherapy which was completed in October 1976. A complete remission was achieved. In December 1976, she relapsed and was treated with cyclophosphamide, vincristine, bleomycin, and prednisone until May 1977. Lymphadenopathy decreased until August 1978, but then increased again. Biopsy of an axillary lymph node was interpreted as Lennert lymphoma. She received methotrexate, cyclophosphamide, vincristine, adriamycin, and prednisone beginning in September 1978. When last seen in November 1979, she was in partial remission. Lymphoid cells obtained from lymph node which was involved with Lennert lymphoma consisted of 93% standard E-rosettes and 83% gravity E-rosettes. Cytoplasmic immunoglobulin on frozen sections was negative, but acid phosphatase (ACP) and alpha-naphthyl acetate esterase reactions were strongly positive. These findings support a T-cell proliferation in Lennert lymphoma. A review of the literature reveals only four cases of Lennert lymphoma of T-cell origin.

Drug Therapy, Combination↗
PubMed2006

Periodic electroencephalogram complexes in a patient with variant Creutzfeldt-Jakob disease.

OBJECTIVE: Based on the current criteria, the diagnosis of "possible" or "probable" variant Creutzfeldt-Jakob disease (vCJD) implies the absence of periodic sharp wave complexes (PSWCs) in the electroencephalogram (EEG). To verify this point, we investigated the development of the EEG changes along the course of the disease in a pateint with vCJD. METHODS: Long-lasting EEG-polygraphic recordings were performed once a month during the last year of illness. RESULTS: We found the occurrence of a typical EEG periodic pattern in the late clinical stage of the vCJD patient. INTERPRETATION: In the light of our finding, the diagnostic criteria for vCJD should be amended to include the possibility of a typical periodic EEG in advanced stages of disease in cases with long survival.

Adult↗
PubMed1984

Structure and function of Hb Saint-Jacques (alpha 2 beta 2 140 (H18) Ala----Thr): a new high-oxygen-affinity variant with altered bisphosphoglycerate binding.

A low P50 value in a fresh red blood cell suspension was discovered in a polycythemic patient (Hb 19 g X dl-1). Routine acid and alkaline electrophoreses of the hemolysate were identical to normal hemolysate. Isoelectrofocusing (pH gradient 6-8) did not reveal any abnormal band whether performed with the fully liganded or deoxygenated samples. Precise analyses of the oxygen dissociation curves of the propositus' red cells demonstrated a biphasic Hill plot, a normal Bohr effect and low interaction with 2,3-bisphosphoglycerate (2,3-DPG). Studies on the unfractionated hemolysate confirmed these observations and the inhibition of the effect of organic phosphates. Structural studies were carried out on the mixture of beta A + beta X chains and revealed the presence of two beta Tp14 peptides. Sequencing the abnormal beta Tp14 peptide showed the substitution Ala----Thr of the beta 140 (H18) residue. This new variant was named Hb Saint-Jacques. Examination of the three dimensional model of HbAo indicates that the substitution beta 140 (H18) Ala----Thr induces van der Waals interactions with the nearby lysine-82 (EF6) and leucine-81 (EF5) and a displacement of the EF corner of the beta chains. This is likely to change the normal position of the lysine-82 (EF6), a major anionic binding site in the central cavity between the two beta chains. Functional studies confirm the interpretation of a steric hindrance inhibiting the binding of large organic phosphates to Hb Saint-Jacques.

2,3-Diphosphoglycerate↗
PubMed2005

Ultraviolet resonance Raman studies reveal the environment of tryptophan and tyrosine residues in the native and partially folded states of the E colicin-binding immunity protein Im7.

Understanding the nature of partially folded proteins is a challenging task that is best accomplished when several techniques are applied in combination. Here we present ultraviolet resonance Raman (UVRR) spectroscopy studies of the E colicin-binding immunity proteins, Im7* and Im9*, together with a series of variants of Im7* that are designed to trap a partially folded state at equilibrium. We show that the environments of the tryptophan and tyrosine residues in native wild-type Im7* and Im9* are indistinguishable, in contrast with models for their structures based on X-ray and NMR methods. In addition, we show that there is a general increase in the hydrophobicity in the environment of Trp75 in all of the variants compared with wild-type Im7*. These data suggest that a significant rearrangement of the tryptophan pocket occurs in the variants, which, together with an overall decrease in solvent accessibility of Trp75 as judged by time-resolved fluorescence lifetime measurements and fluorescence quenching experiments, rationalize the unusual fluorescence properties of the variants reported previously. The data highlight the power of UVRR in analyzing the structural properties of different conformational states of the same protein and reveal new information about the structural rearrangements occurring during Im7* folding, not possible using other spectroscopic methods alone. Finally, we describe a previously unreported dependence of the tryptophan Fermi doublet on excitation wavelength in the ultraviolet region revealed by these protein spectra. We corroborated this observation using tryptophan-containing model compounds and conclude that the conventional interpretation of this UVRR feature at these wavelengths is unreliable.

Colicins↗
PubMed2003

Application of isomorphous replacement in the structure determination of a cubic liquid crystal phase and location of counterions.

A second generation monodendron with dodecyl end-groups based on the AB(3) monomer 3,4,5-trihydroxy benzoate has previously been shown to form a thermotropic cubic phase with Pmthremacr;n symmetry (Balagurusamy et al., J. Am. Chem. Soc. 1997, 119, 1539). A structure consisting of spherical "micelles" was proposed originally, but an alternative choice of structure factor phases, giving a structure of interlocked squashed columns, could not be ruled out by diffraction data on the original material alone. We have therefore synthesized two selectively fluorinated equivalent compounds, the carboxylic acid and its Rb salt, to be able to apply a variant of the isomorphous replacement crystallographic technique. On the basis of the electron density maps of the new labeled compounds, reconstructed using small-angle X-ray diffraction intensities, the interlocking columns model is unequivocally rejected and the spheres model is upheld. Furthermore, the location of the metal cation in the center of the "micelles" is directly confirmed. Micellar diameter was shown to decrease on fluorination of the dodecyl chain ends, and increase significantly on introduction of Rb. This is interpreted in terms of changes in the number of wedge-shaped dendrons fitting into a spherical micelle due to their changing taper angle. It was found that the Rb-rich regions at the centers of six out of eight "micelles" in the unit cell are elongated in the direction of their closest packing. This adds support to the suggestion of a partial "column-like" character of stacked rows of such micelles, consistent with the position of the Pmthremacr;n phase next to the columnar phase in the phase sequence of most taper-shape compounds. The results illustrate the potential of isomorphous replacement, used a great deal in protein crystallography, in structure investigation of liquid crystals and supramolecular soft matter.

Journal Article↗
PubMedDate not supplied

Evaluation of a new blood grouping instrument.

A fully automated blood grouping machine, that has recently been introduced was evaluated. The instrument incorporates bar-coded sample identification and a laser scanning device to eliminate potential sample/result errors. A microprocessor interprets results, thus eliminating subjective interpretation. Ninety-seven percent of the 17,549 samples tested were correctly grouped. One-third of the initially rejected samples were correctly grouped upon retesting. The laser scanner failed to read 239 labels (1.6%). Of the original samples tested, 72 were Du positive as detected by manual methods and the automated grouper recognized 33 percent of them as Rh positive. By reducing the percent light transmission affecting Rh discrimination, it was possible to increase the percentage recognition of Du variant samples but it did not detect all. The apparatus is fitted with small diameter tubing and reagent consumption was 30 to 35 percent less than with previously available similar machines. Additional reagent savings were realized if diluted manual reagents were used. Our evaluation of the instrument has shown it to be highly accurate and reliable.

Blood Grouping and Crossmatching↗
PubMed1989

Phenotypes of rotavirus reassortants depend upon the recipient genetic background.

We have previously characterized the biological and immunological properties of a simian rotavirus SA11 variant (4F) with an altered genome segment 4. The SA11-4F variant formed large plaques in the presence of protease, formed small clear plaques in the absence of protease, and grew to high titer in the presence of protease when compared to our standard wild type (SA11 clone 3). To determine the genome segment of the rotavirus SA11 variant 4F that encoded the unique protease-associated phenotypes of the variant, reassortants were generated that segregated the outer capsid genes of 4F onto a genetic background derived from either the bovine rotavirus B223 or our standard SA11 wild type (clone 3), both of which have contrasting protease-associated phenotypes. The parental and reassortant viruses were examined to determine which genes from the 4F variant encoded the ability (i) to form large plaques in the presence of protease, (ii) to form small clear plaques in the absence of exogenous protease, and (iii) to grow to significantly higher titer in the presence of protease. These phenotypes could be transferred to a clone 3 genetic background by a single genome segment from the 4F variant segment 4. However, in the 4F/B223 reassortants a different and unexpected situation was found. On a B223 genetic background the same phenotypes segregated with a combination of a minimum of two 4F genome segments, segments 4 and 9. These results indicate that the recipient genetic background onto which the genes of a donor rotavirus are reassorted can affect the phenotypes conferred by the presence of the donor segments. Thus, the results of segregation mapping experiments using reassortant viruses should be interpreted with caution.

Cell Line↗
PubMed2005

Variants of human immunodeficiency virus type 1 that efficiently use CCR5 lacking the tyrosine-sulfated amino terminus have adaptive mutations in gp120, including loss of a functional N-glycan.

By selecting the R5 human immunodeficiency virus type 1 (HIV-1) strain JR-CSF for efficient use of a CCR5 coreceptor with a badly damaged amino terminus [i.e., CCR5(Y14N)], we previously isolated variants that weakly utilize CCR5(Delta18), a low-affinity mutant lacking the normal tyrosine sulfate-containing amino-terminal region of the coreceptor. These previously isolated HIV-1(JR-CSF) variants contained adaptive mutations situated exclusively in the V3 loop of their gp120 envelope glycoproteins. We now have weaned the virus from all dependency on the CCR5 amino terminus by performing additional selections with HeLa-CD4 cells that express only a low concentration of CCR5(Delta18). The adapted variants had additional mutations in their V3 loops, as well as one in the V2 stem (S193N) and four alternative mutations in the V4 loop that eliminated the same N-linked oligosaccharide from position N403. Assays using pseudotyped viruses suggested that these new gp120 mutations all made strong contributions to use of CCR5(Delta18) by accelerating a rate-limiting CCR5-dependent conformational change in gp41 rather than by increasing viral affinity for this damaged coreceptor. Consistent with this interpretation, loss of the V4 N-glycan at position N403 also enhanced HIV-1 use of a different low-affinity CCR5 coreceptor with a mutation in extracellular loop 2 (ECL2) [i.e., CCR5(G163R)], whereas the double mutant CCR5(Delta18,G163R) was inactive. We conclude that loss of the N-glycan at position N403 helps to convert the HIV-1 envelope into a hair-trigger form that no longer requires strong interactions with both the CCR5 amino terminus and ECL2 but efficiently uses either site alone. These results demonstrate a novel functional role for a gp120 N-linked oligosaccharide and a high degree of adaptability in coreceptor usage by HIV-1.

Adaptation, Biological↗
PubMed1998

Variants of the fatty acid-binding protein 2 gene are not associated with coronary heart disease in nondiabetic subjects and in patients with NIDDM.

OBJECTIVE: To investigate the association of variants of the fatty acid-binding protein (FABP) 2 gene with coronary heart disease (CHD) in nondiabetic subjects and in patients with NIDDM. RESEARCH DESIGN AND METHODS: Cross-sectional study included 135 nondiabetic and 79 NIDDM subjects with stenosis (> 50%) in at least two coronary arteries. A group of 81 healthy nondiabetic men without CHD served as a control population. All exons and intron-exon junctions of the FABP2 gene were amplified with the polymerase chain reaction, and variants were screened with the single-strand conformation polymorphism analysis. RESULTS: The allele frequency of an amino acid polymorphism (alanine-->threonine) in codon 54 of exon 2 of the FABP2 gene was 0.26 in nondiabetic subjects with CHD and 0.27 in NIDDM subjects with CHD. Other variants (GTA 118 GTC, GCGCA-->GCACA in the 3'-noncoding region, and the number of ATT repeats in intron 2) also did not associate with CHD. CONCLUSIONS: The variants of the FABP2 gene are not likely to contribute to the risk of CHD in Finnish nondiabetic and NIDDM subjects.

Alleles↗
PubMedDate not supplied

Automated white blood cell classification revisited.

A novel approach to the problem of automated white blood cell classification is described. Whereas in most earlier attempts the segmentation of the cells has been recognized as the most difficult and most critical step in the sequence of operations resulting in the classification, the method described here eliminates the necessity of the detection of the contour of the nucleus and of the cytoplasm, and is therefore less sensitive to such disturbing factors as the presence of granules, of other cells touching the cell of interest, etc. The multiple sequential threshold method to be described here in two slightly different variants yields a correct classification rate of 94.7% for a 4 class problem (90 cells in the test set), and 91.8% for an 8 class problem (279 cells in the test set). Both experiments include immature cell types.

Densitometry↗
PubMed2002

Immunohistochemical expression of galectin-3 in benign and malignant thyroid lesions.

CONTEXT: The expression of galectin-3, a human lectin, has been shown to be highly associated with malignant behavior of thyroid lesions. DESIGN: We studied the immunohistochemical expression pattern of galectin-3 in a variety of follicular-derived thyroid lesions (13 benign and 62 malignant), including Hürthle cell and follicular carcinoma, papillary carcinomas and variants, and anaplastic and poorly differentiated carcinomas. RESULTS: Immunoreactivity was strongest in papillary thyroid carcinomas, whereas staining was less intense in Hürthle cell and anaplastic carcinomas, and even weaker in the follicular variant of papillary thyroid carcinoma. Staining was absent or weak in the 3 follicular thyroid carcinomas and was negative in both insular carcinomas. In several tumors, staining was stronger at the advancing invasive edge of the lesion than in the central portion of the tumor. Galectin-3 was also expressed focally and weakly in reactive follicular epithelium and entrapped follicles in chronic lymphocytic thyroiditis. A variety of thyroid lesions showed prominent endogenous, biotin-like activity, which could cause flaws in interpretation if a biotin-detection system were used. CONCLUSION: We conclude that galectin-3 immunostaining, when used in biotin-free detection systems, may be useful as an adjunct to distinguish benign from malignant thyroid lesions.

Adenoma, Oxyphilic↗
PubMed1976

On the transport of various endogenous plasma proteins from blood to peripheral lymph in man.

A method to prepare peripheral lymph out of the foot of clinically healthy patients with respect to their blood capillaries and lymph vessels is presented. Following electrophoresis in molecular sieving polyacrylamide gel the lymph/plasma quotients of precentages of identical protein fractions in both body fluids as well as of their concentrations were graphically displayed dependent on their migration velocity within the gel. As the high or low lymph-plasma-relations are necessarily to be interpreted in the sense of a relatively high or low blood-lymph permeation the findings are speaking against an exclusive effect of the molecular sieving principle at the blood-tissue-barrier. An explanation for special lymph-plasma-relations would be provided by the assumption of a gel-filtration effect in the extravascular circuit of plasma-proteins. The results affirm the findings of former experiments on animals in an analogue model. The method as well as simplified variants might be useful for the investigation of peripheral nutritive disorders as well as of clinicopharmacological questionings.

Adult↗
PubMed1990

Computer diagnosis of skin disease.

A transferable computer program for the differential diagnosis of diseases of the skin, CLINDERM, has been produced for use by physicians on standard IBM and compatible personal microcomputers. This program lists the differential diagnosis and definitive diagnosis of any presented disease of the skin, except single tumors. The physician operator indicates the distribution and detailed description of lesions, which the interactive system integrates with a comprehensive knowledge base. The computer diagnosis in 129 cases was compared with independent interpretation of the same information by an academic dermatologist. Results were synonymous in 66.7% of all diseases and similar in an additional 4.7%. A common differential diagnosis was obtained in 24%, for a 95.3% rate of synonymous, similar, or common differential diagnoses. Diagnosis was different in 3.9% and description was inadequate for diagnosis in 0.8%. The variation in diagnosis showed that some descriptive terms are prejudicial of certain diagnoses; that diagnostic terms are not all completely standardized; that some diagnoses are variants of another disease; and that drug-induced eruptions simulate many other diseases. A skin disease can usually be diagnosed by specific description. Most lesions that are not diagnostic from inspection are nodular. A computer can be programmed to list diagnoses according to morphologic description.

Dermatology↗
PubMed2025

Evaluating selection at intermediate scales within genes provides robust identification of genes under positive selection in M. tuberculosis clinical isolates.

Multiple studies have reported genes in the M. tuberculosis (Mtb) genome that are under diversifying selection, based on genetic variants among Mtb clinical isolates. These might reflect adaptions to selection pressures associated with modern clinical treatment of TB. Many, but not all, of these genes under selection are related to drug resistance. Most of these studies have evaluated selection at the gene-level. However, positive selection can be evaluated on different scales, including individual sites (codons) and local regions within an ORF. In this paper, we use GenomegaMap, a Bayesian method for calculating selection, to evaluate selection of genes in the Mtb genome at all three levels. We present evidence that the intermediate analysis (windows of codons) yields the most credible list of candidate genes under selection (excluding PPE and PE_PGRS genes, which are predicted less reliably due to frequent sequencing errors). A further advantage of this approach is that it identifies specific regions within proteins that are under selective pressure, which is useful for structural and functional interpretation. In an analysis of two separate collections of Mtb clinical isolates (from Moldova; and a globally-representative set), we observed 53 and 173 significant genes under selection, with 36% overlap. The lists of genes under selection include many drug-resistance genes, as well as other genes that have previously been reported to be under selection (resR, phoR). The specific regions under selection identified within drug-resistance genes are shown to correspond to protein structural features known to be involved in resistance, supporting accuracy of the method. Positive selection in several ESX-1-related genes was also observed, suggesting adaptation to immune pressure.

adaptation↗
PubMedDate not supplied

[Effect of the medium on the functional and structural properties of serum albumins. I. Effect of ionic strength on N-variant of human serum albumin].

The effect of ionic strength on the 1-anilino-8- naphtalene sulfonate (ANS) binding sites of the N-form of human serum albumin (HSA) was studied by means of the protein and ligand fluorescence. The parameters of the binding of ANS to HSA (the number of sites and the binding constants) were determined by two methods: by measuring the ANS fluorescence either (i) at increasing protein concentrations and constant ANS concentration, or (ii) at increasing ANS concentration and two constant protein concentrations (9.6 and 2.53 microM). An increase in the NaCl concentration results in a monotonous decrease of the ANS fluorescence yield of HSA-ANS complex, which could be interpreted in terms of two different effects: first, the direct collisional quenching interaction of Cl-ions with bound ANS located on the surface of HSA and, second, the ca. 10 per cent decrease of the number of bound ANS molecules due to the lowering of the ANS-HSA association constant values. The fluorimetric titration showed that at low ionic strength (0.008 M NaCl) HSA molecule has one strong ( lgKaI = 6.75-7.25) and two secondary sites with lower affinity ( lgKaII = 6.35). The increase in the NaCl concentration results in a decrease of the affinity for both kinds of binding sites (in 0.2 NaCl lgKaI = 6.3-6.7; lgKaII = 5.6-5.9). In contrast with NaCl, Na2SO4 induces only a limited decrease of the ANS fluorescence occurring within a narrow concentration range (from ca. 0.02 to 0.05 M Na2SO4, e. i. at ionic strengths from 0.07 to 0.15) and which can be described as a cooperative interaction of six SO4(2)-ions with a HSA molecule.(ABSTRACT TRUNCATED AT 250 WORDS)

Anilino Naphthalenesulfonates↗
PubMed2000

Up-regulation of novel intermediate filament proteins in primary fiber cells: an indicator of all vertebrate lens fiber differentiation?

The early embryonic development and expression patterns of the eye lens specific cytoskeletal proteins, CP49 and CP95, were determined for the chick and were found to be similar in both human and mouse. These proteins, as well as their homologs in other species, are obligate polymerization partners which form unique filamentous structures termed "beaded filaments." CP49 and CP95 appeared as protein products after 3 days of embryonic development in the chick during the elongation of primary fiber cells. Although limited data were obtained for human embryos at these early developmental timepoints, they were consistent with the interpretation that the up-regulation of these lens specific proteins began only after the initiation of lens vesicle closure. In situ hybridization with the mouse lens confirmed that message levels for beaded filament proteins were greatly elevated in differentiating primary fiber cells. Nuclease protection assays established that mRNA levels for CP49 remained relatively constant while CP95 mRNA levels increased once the process of secondary fiber formation was under way. Although present in relatively low abundance, the mRNA for a unique splice variant of CP49, CP49(INS), was also detected early in embryonic development and into adulthood. Peptide-specific antibodies directed against unique predicted sequences were able to confirm the protein expression of CP49(INS) in both embryonic and adult chick lens cells. These data present the first detailed study of the expression of CP49 and CP95 during early lens development. They suggest that the up-regulated expression of CP49 and CP95 could serve as pan-specific markers for all vertebrate lens fiber development.

Animals↗