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PubMedDate not supplied

CFS transferrin in various neurological diseases.

The introduction of isoelectrofocusing on polyacrylamide gel followed by direct immunofixation, in the analysis of CSF proteins, emphasized the interest in transferrin examination, mainly in order to find eventual abnormalities in patients with neurological diseases. Stibler (1979), using these techniques, demonstrated the presence in CSF of two subtypes of transferrin C, called C1 and C2, transmitted by autosomal codominant inheritance, according to the C1, C2 and C2-1 phenotypes. The rather frequently occurring variant of transferrin in CSF is the C2-1 subtype: a double banded pattern, which is focused at pH 5.9, consisting of two very closely spaced bands with a pI difference of less than 0.1. This transferrin pattern is peculiar to CSF and is absent in the serum of the same subjects. This subtype of transferrin has been observed in various neurological disorders, as well as in healthy populations, by several investigators. They also found a much higher incidence of double tau-transferrin in inherited degenerative neurological diseases, such as Friedreich's ataxia and hereditary spastic paraplegia, than in neurological ailments without a hereditary component. The aim of our study is to verify the incidence of the C2-1 variant of transferrin in a control group and in a mixed group of neurological patients, with particular attention to hereditary degenerative pathologies.

Humans↗
PubMed1983

Variants of type-C retroviruses from DBA/2 mice: protein-structural and biological properties.

Ecotropic murine leukemia viruses isolated from normal and carcinogen-treated DBA/2 mice can be classified into three main groups that differ in structure and biology. Two groups, called Ea and Eb, consist of N-tropic viruses related to the standard endogenous ecotropic virus of AKR mice. Ea viruses replicate with reduced efficiency in cell lines derived from C3H mice, while Eb viruses essentially replicate normally in these cells. As elsewhere reported, Ea viruses appear apathogenic in C3H mice, while Eb viruses cause a moderate incidence of late leukemias. The biological differences are associated with modulations of the fine structure of the gag gene-encoded proteins. A third group of viruses, called Ec, is clearly more diverged. They differ extensively from Ea and Eb viruses in the products of the gag and env gene, and are related to Rauscher leukemia virus. Ec viruses are NB-ecotropic; they replicate efficiently in all mouse cells tested, and induce leukemias in C3H mice with shorter latency periods than Eb viruses. Since published nucleic acid hybridization data indicate that DBA/2 mice only carry one ecotropic provirus, we assume that the DBA/2 viruses represent a developmental series of variants evolving during the life of the animals.

Animals↗
PubMed2006

A novel PtdIns3P and PtdIns(3,5)P2 phosphatase with an inactivating variant in centronuclear myopathy.

In eukaryotic cells, phosphoinositides are lipid second messengers important for many cellular processes and have been found dysregulated in several human diseases. X-linked myotubular (centronuclear) myopathy is a severe congenital myopathy caused by mutations in a phosphatidylinositol 3-phosphate (PtdIns3P) phosphatase called myotubularin, and mutations in dominant centronuclear myopathy (CNM) cases were identified in the dynamin 2 gene. The genes mutated in autosomal recessive cases of CNMs have not been found. We have identified a novel phosphoinositide phosphatase (hJUMPY) conserved through evolution, which dephosphorylates the same substrates as myotubularin, PtdIns3P and PtdIns(3,5)P(2), in vitro and ex vivo. We found, in sporadic cases of CNMs, two missense variants that affect the enzymatic function. One of these appeared de novo in a patient also carrying a de novo mutation in the dynamin 2 gene. The other missense (R336Q) found in another patient changes the catalytic arginine residue of the core phosphatase signature present in protein tyrosine/dual-specificity phosphatases and in phosphoinositide phosphatases and drastically reduces the enzymatic activity both in vitro and in transfected cells. The inheritance of the phenotype with regard to this variant is still unclear and could be either recessive with an undetected second allele or digenic. We propose that impairment of hJUMPY function is implicated in some cases of autosomal CNM and that hJUMPY cooperates with myotubularin to regulate the level of phosphoinositides in skeletal muscle.

Amino Acid Sequence↗
PubMed2002

Ichthyosiform mycosis fungoides.

BACKGROUND: Mycosis fungoides (MF) is a skin malignancy of T helper lymphocytes with a wide clinical spectrum. Among the atypical variants of MF, there is an ichthyosis-like presentation. However, to date, only 1 case of ichthyosiform MF has been reported. OBJECTIVE: Our goal was to summarize the clinical characteristics and course, and the pathological, immunohistochemical and molecular genetic findings on 4 patients with ichthyosiform MF. METHODS: A retrospective study was conducted. RESULTS: The 4 patients represented 1.8% of the 221 patients with MF seen by us since 1975. None progressed to systemic disease in up to 12 years (median, 10 years) after the onset of the cutaneous manifestations. Interestingly, skin lesions typical of so-called follicular MF (FMF) were associated in 3 of 4 cases, whereas cutaneous manifestations of classic MF were absent in all 4 patients. CONCLUSION: Ichthyosiform MF represents a rare variant within the clinicopathologic spectrum of MF usually featuring a benign course and a tendency to be associated with lesions of FMF but not with lesions of classic MF.

Adult↗
PubMed2000

Isoform-specific exon skipping in a variant form of ClC-2.

A new form of the widely expressed, volume-regulated chloride channel, ClC-2, has been cloned from a pig ileal cDNA library. This ClC-2 homologue, called ClC-2i, has interesting variability within its cDNA sequence, including the deletion of bases that correspond to positions 1326 through 1401 in rat ClC-2 cDNA sequence. This 75 bp deletion corresponds to the complete loss of exon 13 plus the first four bases of exon 14, and involves an atypical intron-exon splice site. Tissue-specific mRNA expression patterns in the pig show variable degrees of exon 13 skipping in ClC-2i. Exon 13 skipping was also observed in rat ClC-2i, albeit at a higher frequency than in the pig in tissues that were examined. A relatively purine-rich 76 bp insertion in the pig genomic sequence of ClC-2i, close to the 3' end of intron 12, may be responsible for the relatively high frequency of exon 13 skipping during the processing of this mRNA.

Animals↗
PubMed1976

Cis-dominant regulatory mutations affecting the formation of glucose-repressible alcohol dehydrogenase (ADHII) in Saccharomyces cerevisiae.

The formation of ADHII in Saccharomyces cerevisiae is regulated by carbon catabolite repression. There are two genes involved in the formation of ADHII: ADR2, the structural gene as identified by electrophoretic variants and ADR1, possibly a regulatory gene. A new genetic element involved in the regulation of ADHII was identified by three allelic mutants insensitive to strong glucose repression. They were called ADR3c (wild type designation ADR3) and found to be tightly linked to the structural gene, ADR2. The alcohol dehydrogenase found in ADR3c mutants could not be distinguished electrophoretically from the ADHII of the glucose-sensitive wild type, ADR3. Dominance relations between ADR3c and ADR3 were established in diploids heterozygous for ADR3 and the two alleles of ADR2 (ADR2-S: slow ADHII, ADR2-F: fast ADHII). During growth on 10% glucose, an ADR3c adr2-F/ADR3 ADR2-Sheterozygous diploid formed only the fast ADHII variant wheras an ADR3c ADR2-S/ADR3 ADR2-F heterozygote produced only the slow form. This was taken as evidence of the cis-dominance of all ADR3c alleles. The cis-effect of ADR3c was also demonstrated in glucose-derepressed diploids. The ADR3c mutations do not only cause glucose-insensitive ADHII frmation, but also reduce the activity of the adjacent structural gene during derepression. Thus ADR3c alleles were considered to be controlling site mutations. No pleiotropic effects were observed on the formation of enzymes related to the function of ADHII. An adr1 ADR2 ADR3 single mutant did not form ADHII. In contrast to this, an adr1 ADR2 ADR3c double mutant formed ADHII at a similar level as double mutant formed ADHII at a similar level as an ADR1 ADR2 ADR3c mutant. This showed that ADR3c was epistatic over adr1 (previously suggested as a positive regulatory gene). From this it was concluded that ADR1 is the fact a positive regulatory gene the function of which is required for the expression of the structural gene for ADHII, ADR2. ADR3 is the controlling site for the structural gene ADR2. Mutations at this site, ADR3c, alleviate the requirement for the ADR2 gene product. Adr3c is discussed as a promotor or operator site.

Alcohol Oxidoreductases↗
PubMed1998

Indirect radiation leukemogenesis in DBA/2 mice: increased expression of B2 repeats in FDC-P1 cells transformed by intracisternal A-particle transposition.

We have previously reported that granulocyte-macrophage colony-stimulating factor (GM-CSF)- and interleukin-3 (IL-3)-dependent FDC-P1 cells undergo leukemic transformation when injected into sublethally irradiated DBA/2 mice. Transformation is related to aberrant activation of growth-regulatory genes by insertion of intracisternal A-particle (IAP) genomes. To elucidate the transformation process further, a subtracted cDNA library was constructed from a factor-independent leukemic FDC-P1 variant and the parental FDC-P1 cells. Screening for clones that were preferentially recognized by a total cDNA probe from the transformed cell line (in comparison to a similar probe from untransformed FDC-P1 cells) led to the isolation of 14 clones, of which six contained cDNA inserts encoding so-called B2 repeats, a class of short interspersed nucleotide elements. The expression of B2 repeats was significantly increased not only in the cell line from which the subtracted library was constructed, but also in all other leukemic FDC-P1 variants analyzed. B2 repeats can act as insertional mutagens and may have a role in the stabilization of certain oncogene and cytokine mRNAs. Interestingly, B2 repeats contain a 14-nucleotide region that is almost completely complementary to an AU-rich sequence in a region of the IAP mRNA encoding the enzyme reverse transcriptase. Although preliminary experiments to demonstrate stabilization of IAP mRNA by hybridization to B2 repeat sequences remained inconclusive, it is intriguing to speculate that B2 repeat sequences may have a causative role in the transformation process.

Animals↗
PubMed1982

Morphology of primary axosomatic endings in the anteroventral cochlear nucleus of the cat: a study of the endbulbs of Held.

The central axons of Type I spiral ganglion neurons travel in the auditory nerve and terminate in the cochlear nucleus. The ascending branches of these axons innervate the anteroventral cochlear nucleus and give rise to large axosomatic endings, called the endbulbs of Held, and smaller boutons. This paper reports a study of the endbulbs of Held, stained by horseradish peroxidase and variants of the Golgi method in kittens 2, 5, 10, 20, and 45 days postnatal and adult cats. Endbulbs tend to fall into two extreme groups with some endbulbs having an intermediate appearance; consequently, we have defined three descriptive stages of endbulbs that are conceived of as representing a developmental sequence. One group of endbulbs is found mostly in kittens younger than 10 days postnatal and is similar to the classic description of endbulbs by Ramón y Cajal ('09). The other extreme group of endbulbs is found mostly in adult cats. In these cases, the parent axonal trunk divides into several thick, gnarled branches that in turn branch again, sometimes repeatedly. These branches display irregular varicosities and form a cup-shaped arborization into which the postsynaptic cell body nestles. A chronology of postnatal endbulb development has been inferred from the relative proportions of the different endbulb stages at various ages. Maturation transforms the endbulb of Held from a large, spoon-shaped swelling having many filipodia into an elaborate tree with broad trunks and many smaller branches. Some implications of the proposed development sequence are discussed.

Aging↗
PubMed1995

Analysis of prostatic fluid: evidence for the presence of a prospective marker for prostatic cancer.

In an endeavor to identify marker(s) for prostatic cancer, proteins in prostatic fluids were analyzed by two-dimensional (2-D) gel electrophoresis. The fluids were obtained from five males who had no prostate lesions and five patients each with benign prostatic hyperplasia (BPH) and prostatic carcinoma (PCA). The specimens were collected directly over a mixture of protease inhibitors and centrifuged, and the supernatants were lyophilized and solubilized in sodium dodecyl sulfate mix. Identical amounts of proteins were pooled according to donors' prostate disease and the resulting samples were subjected to 2-D gel analysis employing the ISO-DALT system. The electrophoretograms were developed by silver or double stain. The samples of each group exhibited distinctive profiles with the exception of similar relative positions of major protein spots. A predominant protein occurring as several charge variants was consistently present in prostatic fluids of patients with PCA. This protein appeared to be a previously unknown constituent that we have called protein D (molecular weight approximately 22 kDa and isoelectric point approximately 4), and was undetectable in the fluids of "normal" men and patients with BPH. An analysis of pooled, unprocessed urine from PCA patients revealed that perhaps this protein is excreted in urine in very low quantities. These results strongly suggest that the potential of this protein as a marker for prostatic cancer should be further explored.

Biomarkers, Tumor↗
PubMed1975

The subcutaneous fascial analogue of myositis proliferans: electron microscopic examination of two cases and comparison with myositis ossificans localisata.

Two cases of the so-called fascial analogue of myositis proliferans were investigated by histological and electron microscopic methods. It was found that the structure of the fascial variant corresponds almost completely to the true myositis proliferans localized within the musculature. The electron microscopic observations show a preponderantly histiocytic differentiation of the cells and strongly activated proliferating capillaries, and exclude a myogenic origin of the characteristic ganglion-like giant cells. Ultrastructurally a traumatic genesis appears possibly, the cells of the lesion could derive from multipotent cells of the microvasculature. The relations to myositis ossificans and fascitis nodularis are discussed.

Adult↗
PubMed2004

A computational framework for cortical learning.

Recent physiological findings have revealed that long-term adaptation of the synaptic strengths between cortical pyramidal neurons depends on the temporal order of presynaptic and postsynaptic spikes, which is called spike-timing-dependent plasticity (STDP) or temporally asymmetric Hebbian (TAH) learning. Here I prove by analytical means that a physiologically plausible variant of STDP adapts synaptic strengths such that the presynaptic spikes predict the postsynaptic spikes with minimal error. This prediction error model of STDP implies a mechanism for cortical memory: cortical tissue learns temporal spike patterns if these spike patterns are repeatedly elicited in a set of pyramidal neurons. The trained network finishes these patterns if their beginnings are presented, thereby recalling the memory. Implementations of the proposed algorithms may be useful for applications in voice recognition and computer vision.

Action Potentials↗
PubMed1991

Regulation of plaque size and host range by a vaccinia virus gene related to complement system proteins.

A vaccinia virus variant, LC16m8, and its parental Lister (Elstree) strain (LO) were employed to identify the viral gene(s) responsible for plaque size and host range: the large-plaque-forming LO strain but not the small-plaque-forming LC16m8 strain can actively proliferate in Vero (YTV) cells. Previously, we suggested that some particular gene(s) present in the HindIII D fragment of LO DNA was responsible for these biological activities. In the present experiment, the mapping of the putative gene was done by introducing various subfragments of the HindIII D fragment of LO DNA into the gene of LC16m8 strain and screening of the resultant virus variants for the capability of forming large plaques or of proliferating well in Vero cells. The results indicated that an open reading frame (called ps/hr gene) in LO HindIII D fragment was responsible for either plaque size or host range. This gene encoded a polypeptide of 317 amino acids related to the regulators of complement activation (RCA) gene family of mammals. Thus, the present genetic analysis provided direct evidence for a previously unrecognized function of RCA-related proteins encoded by the virus.

Amino Acid Sequence↗
PubMed1999

Monogenic traits are not simple: lessons from phenylketonuria.

The classification of genetic disease into chromosomal, monogenic and multifactorial categories is an oversimplification. Phenylketonuria (PKU) is a classic 'monogenic' autosomal recessive disease in which mutation at the human PAH locus was deemed sufficient to explain the impaired function of the enzyme phenylalanine hydroxylase (enzymic phenotype), the attendant hyperphenylalaninemia (metabolic phenotype) and the resultant mental retardation (cognitive phenotype). In the era of molecular genetics, expectations for a consistently close correlation between the mutant genotype and variant phenotype have been somewhat disappointed, and PKU is used here to illustrate how and why this might be the case. So-called monogenic traits do, indeed, conform to long-accepted ideas about the expression of 'major' loci and their importance in determining parameters of phenotype, but the associated features are as complex, in their own ways, as those in so-called complex traits.

Alleles↗
PubMed2002

Elephantiasic pretibial myxedema: a novel treatment for an uncommon disorder.

Pretibial myxedema is a known manifestation of Graves' disease. Much less common is the elephantiasis nostras variant, which is often refractory to treatment. We therefore elected to try a new therapy, often used for the management of chronic lymphedema, called complete decongestive physiotherapy. After 6 weeks of intensive treatment, our patient lost 37 pounds and had reduced her edema volume by 47%. Her skin softened with decreased lymph seepage and she became mobile for the first time in years. At a 2-year follow-up visit, she exhibited sustained improvement. This case demonstrates that complete decongestive physiotherapy can provide effective, long-term control of this disease process. We suggest that complete decongestive physiotherapy be considered in patients with severe forms of pretibial myxedema, as well as those with refractory lymphedema.

Aged↗
PubMed1997

Spectroscopic studies of cobalt(II) binding to Escherichia coli bacterioferritin.

The iron storage protein bacterioferritin (BFR) consists of 24 identical subunits, each containing a dinuclear metal binding site called the ferroxidase center, which is essential for fast iron core formation. Cobalt(II) binding to wild-type and site-directed variants of Escherichia coli BFR was studied by optical and magnetic techniques. Data from absorption spectroscopy demonstrate the binding of two cobalt(II) ions per subunit of wild-type and heme-free BFR, each with a pseudotetrahedral or pentacoordinate geometry, and EPR studies show that the two cobalt(II) ions are weakly magnetically coupled. Studies of variants of BFR in which a single glutamic acid residue at the ferroxidase center is replaced by alanine confirm that this is the site of cobalt(II) binding, since the altered centers bind only one cobalt(II) ion. This work shows that the electroneutrality of the ferroxidase center is preserved on binding a pair of divalent metal ions. Optical and EPR data show that cobalt(II) binding to BFR exhibits positive cooperativity, with an average Kd of approximately 1 x 10(-5) M. The favored filling of the ferroxidase center with pairs of metal ions may have mechanistic implications for the iron(II) binding process. Discrimination against oxidation of single iron(II) ions avoids odd electron reduction products of oxygen.

Bacterial Proteins↗
PubMedDate not supplied

Deciduoid mesothelioma: a report of 5 cases and literature review.

Deciduoid mesothelioma was first described in young females and in the peritoneum, which led to the suggestion that deciduoid mesothelioma was a distinct subtype with specific clinical and pathologic features. Later reports, however, have shown that this type of mesothelioma may also occur in elderly people and in the pleura. Cases reported in the literature so far are limited, and the disease is not well defined. The authors report the histologic, immunohistochemical, ultrastructural, and clinical findings of 5 cases of deciduoid mesothelioma, and review the literature reports. The results demonstrate that the presence of numerous cytoplasmic intermediate filaments, either dispersed or bundled, appear to be the likely ultrastructural basis for the deciduoid histologic appearance. Twenty-one cases of deciduoid mesothelioma were identified in the literature. Analyses of these 21 cases and the authors' 5 cases showed an age range of 13-78 years (median 53 years) and a slight female predominance (female to male ratio of 1.4:1). Fourteen of 26 cases (54%) occurred in the peritoneum. Seven of 20 patients (35%) had a documented history of asbestos exposure. Fifteen of 20 patients died, with a mean survival time of 7.33 months (range 1-21 months). Five of 20 patients were alive at a follow-up time of 8 months to 5 years. These findings suggest that the so-called deciduoid mesothelioma has some clinical and pathologic features that are dissimilar to mesothelioma in general. Whether it truly represents a pathogenetically distinct variant or merely an expansion of the morphologic spectrum awaits further studies.

Abdominal Neoplasms↗
PubMed1999

Two single nucleotide polymorphisms (SNPs) in the CALL gene for association studies with IQ.

A number of genes underlie the molecular bases of intelligence. Among these is probably CALL, a novel member of the L1 gene family of neural cell adhesion molecules. By using the single strand conformation polymorphism (SSCP) protocol, we screened the regions of the CALL gene corresponding to the 5' and 3' untranslated regions (UTRs) of the CALL mRNA, searching for polymorphisms that could be useful in association studies in the field of intelligence. We report the finding of T-to-A and T-to-C single nucleotide polymorphisms (SNPs) in the 3' UTR of CALL. These SNPs have an index of heterozygosity of 0.13 and 0.10, respectively. Research is in progress to understand the association between these variants and high IQ.

3' Untranslated Regions↗
PubMed1996

Variation of viroid profiles in individual grapevine plants: novel grapevine yellow speckle viroid 1 mutants show alterations of hairpin I.

This is the first report which gives a general survey about viroid variant composition in a vineyard and within single plants. A German vineyard with 20-year-old grapevines (Vitis vinifera) of the cultivars 'Bacchus' and 'Kerner' was analysed for viroid infections. Only grapevine yellow speckle viroid 1 (GYSVd1) and the grapevine isolate of hop stunt viroid (HSVdg) were detected. Both viroids occur in several sequence variations. Eighteen novel GYSVd1 variants and two previously published HSVdg main variants with six new minor variants were found. They were randomly spread in the vineyard. The distribution of GYSVd1 and HSVdg main variants and their accompanying subvariants differed even in neighbouring plants. We conclude that these individual viroid variant profiles are the result of 20 years of independent evolution, i.e. mutation and selection, in each single plant. Four of the nine GYSVd1 main variants were mutated in the inverted repeats bordering the central conserved region. These base substitutions decreased the thermodynamic stability of a metastable structure called hairpin I.

Base Sequence↗