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PubMed2006

Transcriptional control of different acetylcholinesterase subunits in formation and maintenance of vertebrate neuromuscular junctions.

Acetylcholinesterase (AChE; EC 3.1.1.7) is a highly polymorphic enzyme (Massoulié, 2002). Asingle ACHE gene produces several types of catalytic subunits by alternative splicing, but a single splice variant, called type T (AChET), is expressed in adult mammalian muscle and brain. Catalytic subunits of AChET produce amphiphilic monomers and dimers, nonamphiphilic homotetramers, as well as heteromeric associations with anchoring proteins, ColQ (collagenous subunit) and PRiMA (proline-rich membrane anchor), which allow their functional localization in cholinergic synapses (Massoulié, 2002). ColQ characterizes the collagen-tailed forms (Aforms) of AChE and butyrylcholinesterase (BChE), which are localized in the basal lamina at neuromuscular junctions (NMJs) of vertebrates (Krejci et al., 1999); in these molecules (A4, A8, A12), one, two, or three tetramers of catalytic subunits are disulfide-linked to the strands of a triple helix of ColQ collagen. The cDNAs encoding ColQ, which have two transcripts, have been cloned: ColQ-1a predominantly in fast-twitch muscle, and ColQ-1 predominantly in slow-twitch muscle. The tetrameric globular (G4) form of AChE is characterized by linkage to PRiMA. PRiMAcDNA encodes a single-pass approximately 20-kDa type-I transmembrane protein and, similar to that of ColQ, contains a short PRAD (proline-rich attachment domain) that is able to organize AChE catalytic subunits into tetramers and anchor the enzyme at the surface of neuron and muscle (Massoulié, 2002).

Acetylcholinesterase↗

PubMedDate not supplied

Structural variants of chromosome 9: a possible association with hypogonadotropic hypogonadism.

We report two cases of structural variations of chromosome 9 associated with hypogonadotropic hypogonadism and azoospermia in adolescent boys. One patient also had a partially imperforated urethral meatus. Histological examination revealed that both had hypotrophic and underdeveloped testes. There was no LH and FSH response to LH-RH stimulation nor was there any response to naloxone tests. Basal and HCG stimulated plasma testosterone values were below normal prepubertal levels. As the administration of gonadotrophins did not improve the clinical and hormonal findings, alternative androgen therapy was necessary to achieve secondary sexual characteristics. Although they reached a good level of androgenization, their testes were still very small and azoospermia remained, as confirmed by repeated semen analyses. A possible association between chromosome 9 polymorphisms and hypothalamo-pituitary axis abnormalities is suggested. It is hypothesized that structural variants of chromosome 9 are not unrelated occurrences. Furthermore, and in view of the fact that they can lead to a high risk of azoospermia and infertility, such variants call for clinical investigation.

Child↗

PubMed1987

Progress in peritoneal dialysis (PD).

In the last decade Peritoneal Dialysis treatment has grown specially due to the new technique known as CAPD. However, there are still a lot of problems that need to be solved such as: infection rate, new solutions and improvement of catheters and devices in order to make it safer and to decrease the complications resulted from variants called Peritoneal Dialysis on Alternate Days (PDAD) and Equilibrium Peritoneal Dialysis used in the cases of acute renal failure. Improved PD is suitable to treat the patients in many parts of the world who do not receive any treatment at present.

Acute Kidney Injury↗

PubMed1988

Cloning and nucleotide sequence of placental hGH-V cDNA.

We have previously demonstrated the presence in human placenta and maternal serum of a GH variant, called human placental growth hormone (hPGH). We have also shown that the hGH-V gene is expressed at the placental level thus possibly coding for hPGH. The hGH-V cDNA has now been isolated from a lambda gt 11 human placenta cDNA library. Its sequence has been determined which firmly establishes the GH-V gene mode of splicing as well as the GH-V protein structure. Our data give final evidence of placental hGH-V gene expression and reinforce the hypothesis of identity between the hGH-V protein and hPGH.

Amino Acid Sequence↗

PubMed2002

Vitamin E but not 17beta-estradiol protects against vascular toxicity induced by beta-amyloid wild type and the Dutch amyloid variant.

Amyloid beta-peptide (Abeta) fibril deposition on cerebral vessels produces cerebral amyloid angiopathy that appears in the majority of Alzheimer's disease patients. An early onset of a cerebral amyloid angiopathy variant called hereditary cerebral hemorrhage with amyloidosis of the Dutch type is caused by a point mutation in Abeta yielding Abeta(Glu22-->Gln). The present study addresses the effect of amyloid fibrils from both wild-type and mutated Abeta on vascular cells, as well as the putative protective role of antioxidants on amyloid angiopathy. For this purpose, we studied the cytotoxicity induced by Abeta(1-40 Glu22-->Gln) and Abeta(1-40 wild-type) fibrils on human venule endothelial cells and rat aorta smooth muscle cells. We observed that Abeta(Glu22-->Gln) fibrils are more toxic for vascular cells than the wild-type fibrils. We also evaluated the cytotoxicity of Abeta fibrils bound with acetylcholinesterase (AChE), a common component of amyloid deposits. Abeta(1-40 wild-type)-AChE fibrillar complexes, similar to neuronal cells, resulted in an increased toxicity on vascular cells. Previous reports showing that antioxidants are able to reduce the toxicity of Abeta fibrils on neuronal cells prompted us to test the effect of vitamin E, vitamin C, and 17beta-estradiol on vascular damage induced by Abeta(wild-type) and Abeta(Glu22-->Gln). Our data indicate that vitamin E attenuated significantly the Abeta-mediated cytotoxicity on vascular cells, although 17beta-estradiol and vitamin C failed to inhibit the cytotoxicity induced by Abeta fibrils.

Acetylcholinesterase↗

PubMed1976

[Clinical coronarographic characteristics and pathogenetic mechanism of angina pectoris with s-t elevation (author's transl)].

The study of 46 patients with frequent anginal episodes characterized by S-T elevation (so called "variant angina pectoris") demonstrated that this type of electrocardiographic pattern does not characterize a homogeneous group of patients. In fact, while in some patients angina occurred only at rest, in others it occurred also on exercise. Sometimes ecgraphic alterations characterized by S-T depression were observed on the same leads which on other occasions had shown S-T elevation. The angiographic picture revealed: absence of significant coronary alterations in 10% of cases, stenosis greater than 75% in one main branch in 29%, in two branches in 39% and in three branches in 22% of cases. The hemodynamic monitoring carried out on 14 of these patients demonstrated that the ecgraphic modifications occur before the onset of the hemodynamic parameters which control myocardial O2 consumption. This suggests a primitive reduction of regional myocardial blood supply as a cause of the ischaemic episodes. The study of the regional myocardial perfusion with 201Tl technique in 6 patients confirmed this hypothesis. Coronary angiography carried out during an ischemic episode showed that the reduction of myocardial blood supply was caused by a spasm of a large coronary artery involving a long segment of the vessel, reversible by nitroglycerin administration. Aorto-coronary by-pass operation performed on 6 patients was followed by the disappearance of pain in two patients, even though the "by-pass" patency was angiographically proved in two patients.

Adult↗

PubMed2001

[Toxocariasis in an adult manifested as hypereosinophilic syndrome with predominant neurological involvement. Clinical case].

Hypereosinophilic syndrome is characterized by persistent hypereosinophilia and signs or symptoms due to organ involvement, specially nervous system, heart and skin. It can be primary or secondary to allergies, parasites or cancer. Toxocariasis is an uncommon parasitic disease in adults. There is a variant, called visceral larva migrans, that can involve different organs, and among those, the central nervous system. We report a 61 years old male, with a cerebrovascular disease. There were focalizing symptoms, the CAT scan showed multiple ischemic lesions and a peripheral eosinophilia of 12,152 cells/mm3 was present. Anti toxocara IgG antibody titers were 1/1000. The patient was treated with albendazole for 14 days. After a 2 years follow up the patients is in good conditions and, for the first time, his eosinophil count is within normal limits.

Animals↗

PubMed1992

Spectrin beta Tandil, a novel shortened beta-chain variant associated with hereditary elliptocytosis is due to a deletional frameshift mutation in the beta-spectrin gene.

An Argentinian family with hereditary elliptocytosis (HE) associated with a shortened beta-spectrin (Sp) chain was studied. As with most of the other shortened Sp beta-chains that have been described, this variant, called SpTandil, has impaired ability to participate in Sp dimer self-association, has lost its ability to become phosphorylated, and is associated with the presence of increased amounts of the alpha I 74-Kd fragment after partial tryptic digestion of Sp. The 3' ends of the beta-Sp gene of affected patients were analyzed. cDNA was prepared by reverse transcription of peripheral blood mRNA and amplified by the polymerase chain reaction (PCR) using primers corresponding to sequences 400 bp apart on the cDNA, spanning the last three exons (X, Y, Z) of the beta-Sp gene. Agarose gel electrophoresis of the cDNA amplification showed the presence of one band, the size of which was apparently the same as the band amplified from mRNA of a normal control. cDNA from one HE patient was subcloned and sequenced. Several clones showed the presence of a 7-bp deletion at codon 2041 in exon X. Genomic DNA of all the affected members of the family were amplified by PCR using primers flanking the deletion and corresponding to sequences 128 bp apart on exon X. Analysis of the PCR products using electrophoresis on polyacrylamide gel showed the presence of 121- and 128-bp bands in all HE subjects, and an additional doublet migrating more slowly than the two bands, which corresponded to the presence of heteroduplexes. The mutation results in a shift of the normal reading frame and leads to a new amino acid sequence at the C-terminus of the mutant beta-Sp chain. A new in-frame stop codon is encountered downstream, leading to premature chain termination. The identification of the molecular defect in Sp beta Tandil provides information regarding the region of the beta-Sp chain that is important for both Sp dimer self-association and an indication of potential sites of phosphorylation of the chain.

Amino Acid Sequence↗

PubMed2006

Known and new delta globin gene mutations and their diagnostic significance.

Mutations in the delta-globin gene (HBD, MIM# 142000) are not pathologically relevant. However, since high HbA2 levels are diagnostic for beta-thalassemia trait and a lowered level for an alpha- or delta-mutation, co-inheritance of delta- and beta-gene defects may lead to misinterpretation of diagnostic results. We examined 29 cases with low HbA2 level diagnosed in our laboratory, in the presence or absence of a second HbA2 fraction. We found a delta globin gene mutation in 20 cases. In total four different known mutations were found, three structural and one expressional. Moreover, two new defects were observed, one causing a structural abnormality and one a beta-thalassemia. The structural abnormality HBD c.431A->G (p.His144Arg)(dcd 143 CAC->CGC) was homologous to the beta-globin gene variant called Hb-Abruzzo and we have named this mutation HbA2 -Abruzzo. The new delta-thalassemia defect HBD c.-118C->T (d -68 C->T) has no homology on the beta-globin gene (HBB, MIM# 141900). All mutations caused a low HbA2 level and through this could lead to misdiagnosis when inherited together with a beta-thalassemia.

Globins↗

PubMed1991

[Morphological and structural aspects of solid drug forms].

As a follow-up to a previous article, where the characteristics of the solid state and the X-ray properties and pharmaceutical applications were described ("X-rays, diffractometry in the analysis of drugs and pharmaceutical forms", Boll. Chim. Farm. 128, 149; 1989), the Author has more specifically considered the so-called "variants" of a drug's solid state, which can be employed in the dosage forms (polymorph, solvate, crystalline habitus, amorphous). In addition, mention is made of drugs' isomorphism and the difference between a polymorphic solvate and the polymorphism of a solvate is clearly stressed.

Chemistry, Pharmaceutical↗

PubMedDate not supplied

Isolation of mammalian cell autotrophs able to grow indefinitely in protein-free chemically defined medium.

A selection procedure is described for obtaining cell variants, called autotrophs, which are able to grow from low-molecular-weight metabolic precursors in the absence of macromolecules and serum replacement factors. These autotrophs can readily be isolated from a variety of cell lines, including normal (nontransformed) NIH3T3 cells, their spontaneous or tre oncogene-transfected tumor-producing derivatives, and HeLa cells. Tre-transfected autotrophs grew faster than their normal or spontaneously transformed counterparts, and much faster than autotrophic HeLa cells. Chinese hamster autotrophs, which have now been cultured for nearly two years, grow with a population doubling time of 30 h.

Animals↗

PubMed1987

Genome analysis of small cell lung cancer (SCLC) and clinical significance.

A chromosome analysis of three cell lines derived from SCLC showed deletions of the short arm of chromosome 3 with bands p21-p23 as the shortest region of overlap. Hybridization of a polymorphic 3p21 probe to DNA from leukocytes of seven SCLC patients revealed heterozygosity for two of them. In the tumours of both these patients the probe detected homozygosity. This suggests the presence of a mutant cancer gene in the short arm of chromosome 3 which might express itself and/or activate some oncogene(s) after deletion of a suppressing normal allele. Amplification of the oncogene C-MYC was found in four cell lines including the ones cytogenetically analyzed. Amplification of C-MYC, though to a lesser degree, was also found in an available pleural effusate from which one of these lines had been established. As shown by in situ hybridization, the amplified oncogene was present in double minutes in three of the cell lines. In the remaining line it was in a homogeneously staining chromosome region. All patients from whom cell lines with C-MYC amplification were obtained had a negative response to chemotherapy. The observed correlation between amplification of C-MYC, occurrence of so-called variant type SCLC-derived cell lines, and negative response to chemotherapy indicates that a genome analysis of SCLC might provide further criteria for the characterization and subdivision of this highly malignant cancer and thereby a base for an optimal selection of therapy for distinct cases of SCLC.

Carcinoma, Small Cell↗

PubMed1988

Stability and electrophoretic characteristics of creatine kinase BB extracted from human brain and intestine.

Creatine kinase (CK; EC 2.7.3.2) isoenzyme BB extracted from brains of rats reportedly undergoes modification at 37 degrees C, leaving an electrophoretic variant that accounts for most of the residual CK activity. This variant, called CK-BB', migrates on electrophoresis similarly to creatine kinase isoenzyme MB. Using electrophoresis and immunoinhibition with antiserum to creatine kinase isoenzyme MM, we found CK-BB to be the only identifiable cytoplasmic isoenzyme in surgical samples from human brain and intestine. In contrast, we found that some samples of brain obtained at autopsy contain CK-BB'. We also found that CK-BB extracted from human brain was converted to CK-BB' upon incubation in serum or plasma at 37 degrees C. We found a similar development of CK-BB' in incubation mixtures of serum or plasma containing CK-BB obtained from surgical samples of human intestine. The development of CK-BB' during infarction of the gastrointestinal system may thus be a source of false-positive CK-MB in the laboratory verification of myocardial infarction when electrophoresis is used as the only method to identify CK isoenzymes.

Brain↗

PubMed1988

Highly pigmented human melanoma variant which metastasizes widely in nude mice, including to skin and brain.

The properties of a highly malignant human melanoma variant cell line which metastasizes in nude mice in a tissue-specific pattern are described. The variant, called 70-W, was isolated from the MeWo malignant melanoma by exposure of the latter to stepwise increasing concentrations of the toxic lectin, wheat germ agglutinin. After nine cycles of treatment a population of wheat germ agglutinin-resistant cells was obtained that manifested a 4-fold resistance to wheat germ agglutinin, a property which was found to be stable in culture for over 6 months in the absence of the lectin. Intravenous inoculation of 70-W cells into 4-6-week-old nude mice revealed remarkable differences in metastatic (organ colonization) behavior. Whereas the parent MeWo cells gave rise only to lung metastases, most of which were amelanotic, injection of the 70-W cells resulted in multiple skin (s.c.) and brain and, to a lesser extent, bone marrow, ovarian, mesenteric (gut-associated), muscle, and abdominal metastases all of which were highly melanotic. This is the first report of brain metastases of a human tumor in nude mice. They were found to be bilateral and confined to the deeper layers of the cerebral cortex. The unique malignant behavior of 70-W cells in nude mice should facilitate studies of host and tumor cell factors involved in human melanoma metastasis, melanogenesis, and development of new treatment strategies for disseminated human malignant melanoma.

Animals↗

PubMed1980

Demonstration of a large molecular weight variant of the gamma chain of normal human plasma fibrinogen.

A previously undescribed gamma chain variant of human fibrinogen has been identified by application of a sensitive sodium dodecyl sulfate-polyacrylamide gradient gel electrophoretic technique to separate the polypeptide chains. This variant, called gamma B, clots and cross-links as well as the major species (gamma A), is similarly degraded by plasmin, and has a molecular weight of 53,100 as compared to 50,100 for gamma A. Cross-linked dimers of Mr = 100,100 and 108,500 are identified after action of thrombin and Factor XIIIa, suggesting the formation of gamma A-gamma A and gamma B-gamma B dimers rather than gamma A-gamma B hybrid species. The gamma B chain dimers represent 16% of the total cross-linked gamma chain forms. Two early plasmic derivatives of gamma A and gamma B chains have been demonstrated to have lost fragments of Mr = approximately 4,000 and 5,000 without loss of 5-dimethylaminonaphthalene-1-sulfonyl cadaverine fluorescence. Since the difference in molecular weight of gamma A and gamma B chains is maintained during plasmic degradation of both monomer and dimeric fluorescent forms, this suggests that the additional sequence of amino acids in gamma B is located at or near the COOH-terminal end of this polypeptide chain.

Electrophoresis, Polyacrylamide Gel↗

PubMed1980

A mutation of the B220 subunit gene affects the structural and functional properties of yeast RNA polymerase B in vitro.

The Saccharomyces cerevisiae mutant rpo B1 produces a DNA-dependent RNA polymerase B defective in RNA synthesis in vitro. RNA polymerase B purified from the mutant is altered both structurally and functionally. The enzyme is defective in the RNA chain initiation and elongation reactions. Enzyme-DNA binding is comparatively much less affected. These enzymological defects in the mutant enzyme are enhanced at elevated ionic strengths. Purified rpo B1 RNA polymerase B is lacking B32 and B16.5 subunits. However, the low activity of the mutant enzyme cannot be accounted for only by the loss of these two polypeptides. Wild type enzyme devoid of B32 and B16.5 subunits can be obtained after a mild urea treatment. This enzyme variant, called RNA polymerase B, does not share the enzymological properties of the mutant RNA polymerase. Immunoprecipitation of the enzyme from crude extracts shows that, in the rpo B1 mutant, a normal amount of RNA polymerase B is synthesized which contains the full complement of subunits. The polypeptide chain altered by the rpo B1 mutation was identified by partial proteolysis with proteinase K in the presence of sodium dodecyl sulfate. The 35S-labeled peptide pattern generated from the B220 subunit of the mutant enzyme differs markedly from the peptide pattern of the wild type subunit. The rpo B1 mutation therefore alters the B220 subunit, suggesting a role for this subunit in RNA chain elongation and in the association of the B32 and B16.5 subunits to the RNA polymerase molecule.

Ammonium Sulfate↗

PubMed1980

[Mixed essential cryoglobulinemia. Report of five cases (author's transl)].

Cryoglobulins are serum immunoglobulins which precipitate in the cold and redissolve on warming at 37 degrees C. According to its immunochemical composition three different types have been described. Cryoglobulins have been reported associated with hematologic disorders, systemic diseases, infectious conditions, and diseases of the liver and kidneys. There is also an idiopathic variant called essential cryoglobulinemia. Five patients (four males) with mixed essential cryoglobulinemia are reported. Common clinical manifestations included fever, articular symptoms, purpura, glomerulonephritis, Raynaud's phenomenon, erythematomacular cutaneous eruption, polyneuritis and abdominal pain. Serum activity of rheumatoid factor has been detected in three cases; in other three decreased levels of serum complement have been found. Serum HBsAg was negative in four cases (passive hemagglutination technique). It is possible that all cases of mixed essential cryoglobulinemia may correspond to bacterial, viral or fungal occult infections.

Adult↗

PubMed1994

Novel prenylated hemes as cofactors of cytochrome oxidases. Archaea have modified hemes A and O.

A series of novel hemes with modifications of the isoprenyl side chain has been detected in archaea. Heme A(S) was isolated from cytochrome oxidases of the thermoacidophilic archaeon, Sulfolobus acidocaldarius. Heme A(S) has the same spectroscopic features as heme A but has a hydroxyethylgeranylgeranyl side chain instead of the hydroxyethylfarnesyl group. This variant is also present in other archaeal oxidases as well as in the cytochrome oxidases of a thermophilic eubacterium. Other archaea (Thermoplasma, Pyrobaculum) were also shown to have cytochrome oxidases. From these organisms, three novel prenylated heme variants (called OT, OP1, and OP2) were isolated. They are structurally related to heme O; OP2 has a hydroxyethylgeranylgeranyl instead of the hydroxyethylfarnesyl side chain. In OP1 and OT, the hydroxyethylprenyl group is altered to ethenylprenyl by elimination of a water molecule. Most probably, the novel hemes are cofactors binding to the binuclear reaction centers of archaeal cytochrome oxidases.

Archaea↗