[In utero hematopoietic stem cell transplantation: current status and future potential].
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Adult↗
Biomedical subjects
L Amat
Publications and source records attributed to L Amat.
Molecular electronic density fitting using elementary Jacobi rotations under atomic shell approximation
Fitted electron density functions constitute an important step in quantum similarity studies. This fact not only is presented in the published papers concerning quantum similarity measures (QSM), but also can be associated with the success of the developed fitting algorithms. As has been demonstrated in previous work, electronic density can be accurately fitted using the atomic shell approximation (ASA). This methodology expresses electron density functions as a linear combination of spherical functions, with the constraint that expansion coefficients must be positive definite, to preserve the statistical meaning of the density function as a probability distribution. Recently, an algorithm based on the elementary Jacobi rotations (EJR) technique was proven as an efficient electron density fitting procedure. In the preceding studies, the EJR algorithm was employed to fit atomic density functions, and subsequently molecular electron density was built in a promolecular way as a simple sum of atomic densities. Following previously established computational developments, in this paper the fitting methodology is applied to molecular systems. Although the promolecular approach is sufficiently accurate for quantum QSPR studies, some molecular properties, such as electrostatic potentials, cannot be described using such a level of approximation. The purpose of the present contribution is to demonstrate that using the promolecular ASA density function as the starting point, it is possible to fit ASA-type functions easily to the ab initio molecular electron density. A comparative study of promolecular and molecular ASA density functions for a large set of molecules using a fitted 6-311G atomic basis set is presented, and some application examples are also discussed.
Journal Article↗
Use of electron-electron repulsion energy as a molecular descriptor in QSAR and QSPR studies.
Electron-electron repulsion energy ( ) is presented as a new molecular descriptor to be employed in QSAR and QSPR studies. Here it is shown that this electronic energy parameter is connected to molecular quantum similarity measures (MQSM), and as a consequence can be considered as a complement to steric and electronic parameters in description of molecular properties and biological responses of organic compounds. The present strategy considers the molecule as a whole, thus there is no need to employ contributions of isolated fragments as in many calculations of molecular descriptors, like log P or the Free-Wilson analysis. The procedure has been tested in a widespread set of molecules: alcohols, alkanamides, indole derivatives and 1-alkylimidazoles. Molecular properties, as well as toxicity, are correlated using as a parameter, and extensions to the method are given for handling difficult systems. In almost all studied cases, satisfactory linear relationships were finally obtained.
Computer-Aided Design↗
Simple linear QSAR models based on quantum similarity measures.
A novel QSAR approach based on quantum similarity measures was developed and tested in this paper. This approach consists of replacing the usual physicochemical parameters employed in QSAR analysis, such as octanol-water partition coefficient or Hammett sigma constant, by appropriate quantum chemical descriptors. The methodological basis for this substitution is found in recent theoretical studies [J. Comput. Chem. 1998, 19, 1575-1583, J. Comput. -Aided Mol. Des. 1999, 13, 259-270], in which it was demonstrated that both molecular hydrophobic character and electronic substituent effect can be modeled by appropriately chosen quantum self-similarity measures (QS-SM). The most important aim of this study was to prove that selected QS-SM descriptors can be advantageously used in empirical QSAR analysis instead of classical descriptors. For this purpose several QSAR correlations are proposed, in which empirical descriptors such as Hammett sigma constants or log P values are replaced by the appropriate QS-SM. These examples involve: (i) a set of benzenesulfonamides which bind to human carbonic anhydrase, (ii) a set of benzylamines as competitive inhibitors of the enzyme trypsin, and (iii) a set of indole derivatives which are benzodiazepine receptor inverse agonist site ligands. Simple linear QSAR models were developed in order to obtain mathematical relationships between the biological activity and the pertinent quantum chemical descriptors. The validity of the obtained QSAR models is supported by comparison of the observed and predicted values of the biological activity and by a statistical analysis based on a randomization test.
Benzylamines↗
Molecular basis of quantitative structure-properties relationships (QSPR): a quantum similarity approach.
Since the dawn of quantitative structure-properties relationships (QSPR), empirical parameters related to structural, electronic and hydrophobic molecular properties have been used as molecular descriptors to determine such relationships. Among all these parameters, Hammett sigma constants and the logarithm of the octanol-water partition coefficient, log P, have been massively employed in QSPR studies. In the present paper, a new molecular descriptor, based on quantum similarity measures (QSM), is proposed as a general substitute of these empirical parameters. This work continues previous analyses related to the use of QSM to QSPR, introducing molecular quantum self-similarity measures (MQS-SM) as a single working parameter in some cases. The use of MQS-SM as a molecular descriptor is first confirmed from the correlation with the aforementioned empirical parameters. The Hammett equation has been examined using MQS-SM for a series of substituted carboxylic acids. Then, for a series of aliphatic alcohols and acetic acid esters, log P values have been correlated with the self-similarity measure between density functions in water and octanol of a given molecule. And finally, some examples and applications of MQS-SM to determine QSAR are presented. In all studied cases MQS-SM appeared to be excellent molecular descriptors usable in general QSPR applications of chemical interest.
Molecular Structure↗
Using molecular quantum similarity measures as descriptors in quantitative structure-toxicity relationships.
In this paper molecular quantum similarity measures (MQSM) are used to describe molecular toxicity and to construct Quantitative Structure-Toxicity Relationships (QSTR) models. This study continues the recently described relationships between MQSM and log P values, which permits to use the theoretical MQSM as an alternative to the empirical hydrophobic parameter in QSPR studies. In addition a new type of MQSM is presented in this work: it is based on the expectation value of electron-electron repulsion energy. The molecular properties studied here, as application examples are aquatic toxicity, toxicology on Bacteria and inhibition of a macromolecule employing four different molecular sets.
Quantum Theory↗
Diagnosis and follow-up of a case of peroxisomal disorder with peroxisomal mosaicism.
Peroxisomal disorder phenotypes are the result of mutations that cause defective peroxisomal assembly or alterations in the import mechanism of peroxisomal proteins that lead to multiple peroxisomal dysfunctions, or the result of a peroxisomal enzymatic deficiency with a single peroxisomal dysfunction. With complementation analysis, 16 groups have been found. Assignment of the genetic defect has been described for some of the complementation groups. We describe the clinical evolution and follow-up over 10 years of a patient who belongs to complementation group 4, although he showed a milder clinical course. It has been found in fibroblasts different peroxisome populations, normal processing and expression of beta-oxidation PTS1 and PTS2 proteins, abnormal ALD protein distribution and normal plasmalogen biosynthesis; abnormal beta-oxidation metabolites have also been detected in serum. Ultrastructural studies in liver showed peroxisomal mosaicism as in fibroblasts. It has been taken into account that peroxisomal mosaicism may lead to variability in peroxisomal diagnostic parameters, making difficult the final diagnosis in these patients.
Adolescent↗
Effect of glycosylation of recombinant human granulocytic colony-stimulating factor on expansion cultures of umbilical cord blood CD34+ cells.
BACKGROUND AND OBJECTIVE: Granulocytic colony-stimulating factor (G-CSF) is a cytokine widely used for several purposes such as stem cell mobilization, treatment of neutropenia or in vitro cultures. Recombinant human G-CSF (rh-G-CSF) is available in two forms: a non-glycosylated (E. Coli-derived), and a glycosylated CHO-derived rhG-CSF. As previously shown, glycosylation gives a higher degree of homology between the recombinant and the wild human G-CSF molecule. This study analyses the role of glycosylation in expansion cultures comparing the biological effects of the two forms of G-CSF. DESIGN AND METHODS: CD34+ cells from nine cord blood samples were positively selected (median purity 84%) and cultured in the presence of 50 ng/mL of stem cell factor and 1, 10 or 100 ng/mL of glycosylated rh-G-CSF (GG) or a deglycosylated form (DG). After 5 days of a static, serum-dependent culture fed on day 0, nucleated cells (NC), CD34+ cells and colony-forming units were evaluated and compared using the paired Student's t-test. RESULTS: For all concentrations tested, GG was able to generate more NC and progenitors than DG was able to (p<0.05). This effect was mainly observed in CFU-GM colonies, and in CFU-Mix, and indeed no influence was detected in terms of BFU-E expansion. The presence of GG in culture causes the generation of more mature granulocytic cells, assessed by the expression of CD11b/CD15 on CD13+ population, than the presence of DG. In order to check the role of the molecule's stability in this difference, the effect of daily supplementation was tested. Continuous presence of cytokines using either form of G-CSF (daily feeding) significantly increased the rate of expansion, but again GG produced higher generation than its DG counterpart. INTERPRETATION AND CONCLUSIONS: Our results suggest that the stability of the G-CSF molecule has a predominant effect on the higher biological activity found. A glycosylated form of G-CSF is recommended for in vitro cultures using serum-dependent conditions.
Antigens, CD34↗
Variability of biochemical and clinical phenotype in X-linked liver glycogenosis with mutations in the phosphorylase kinase PHKA2 gene.
X-linked liver glycogenosis (XLG) resulting from phosphorylase kinase (Phk) deficiency is one of the most common forms of glycogen storage disease. It is caused by mutations in the gene encoding the liver isoform of the Phk alpha subunit (PHKA2). In the present study, we address the issue of phenotypic and allelic heterogeneity in XLG. We have identified mutations in seven male patients. One of these patients represents the variant biochemical phenotype, XLG subtype 2 (XLG2), where Phk activity is low in liver but normal or even elevated in erythrocytes. He carries a K189E missense mutation, which adds to the emerging evidence that XLG2 is associated with missense mutations clustering at a few sites. Two patients display clinical phenotypes unusual for liver Phk deficiency, with dysfunction of the kidneys (proximal renal tubular acidosis) or of the nervous system (seizures, delayed cognitive and speech abilities, peripheral sensory neuropathy), respectively, in addition to liver glycogenosis. In the patient with kidney involvement, we have identified a missense mutation (P399S) and a trinucleotide deletion (2858del3) leading to the replacement of two amino acids by one new residue (N953/L954I), and a missense mutation has also been found in the patient with neurological symptoms (G1207W). These two cases demonstrate that PHKA2 mutations can also be associated with uncommon clinical phenotypes. Finally, in four typical XLG cases, we have identified three truncating mutations (70insT, R352X, 567del22) and an in-frame deletion of eight well-conserved amino acids (2452del24). Together, this study adds eight new mutations to the previously known complement of sixteen PHKA2 mutations. All known PHKA2 mutations but one are distinct, indicating pronounced allelic heterogeneity of X-linked liver glycogenosis with mutations in the PHKA2 gene.
Amino Acid Sequence↗
The placental blood program of the Barcelona Cord Blood Bank.
Cord blood has recently become an alternative to bone marrow transplantation, generating the need for cord blood banks where large numbers of frozen cord blood units can be stored. The Barcelona Cord Blood Bank (bcB) was created in October 1995. Initially, several methods for volume reduction were tested, including Ficoll, Percoll, Gelatin and HES sedimentation. Of these, HES sedimentation (88% +/- 11 CD34+ cells recovery) was the one chosen for routine banking. Up to November 1997, the bank has processed 754 units with a median of 1.05 x 10(9) nucleated cells and 2.5 x 10(6) CD34+ cells stored per unit. Nine of these units have been shipped for transplantation.
Adult↗
Treatment of chronic hepatitis B in children with recombinant alfa interferon. Different response according to age at infection.
The objective of this study was to investigate the possibility of predictive factors of response to treatment with interferon in children with chronic hepatitis B virus infection. We analyzed the influence on the response rate of age, sex, mode of acquisition of infection, severity, and duration of disease in 16 children with chronic hepatitis B treated with 3 MU of recombinant alpha-interferon 2b three times a week for 6 months. Six months after the end of treatment, eight patients (50%) had cleared HBV DNA, seroconverted to anti-HBe and normalized serum transaminase values. Response was significantly higher in those whose serum transaminase levels were > 100 IU/liter before treatment (70%) and those infected after birth (72%) compared with those with lower serum transaminase levels (16%) and those infected at birth (7%). Our findings indicate that a 6 month course of low dose interferon (3 MU) is highly effective in children with horizontally transmitted chronic hepatitis B virus infection, but noneffective in children infected at birth.
Adolescent↗
Computed tomography of infantile hepatic hemangioendothelioma.
Computed tomography (CT) was performed on five infants with hepatic hemangioendothelioma. Precontrast scans showed solitary or multiple, homogeneous, circumscribed areas with reduced attenuation values. Tiny tumoral calcifications were identified in two patients. Serial scans, after injection of a bolus of contrast material, showed early massive enhancement, which was either diffuse or peripheral. On delayed scans, multinodular tumors became isodense with surrounding liver, while all solitary ones showed varied degrees of centripetal enhancement and persistent central cleftlike unenhanced areas. The authors believe that these CT features are characteristic and obviate arteriographic confirmation.
Female↗
[Guidelines for clinical follow-up and immunoprophylaxis of pregnant carriers of hepatitis B virus and their children].
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Carrier State↗
[Neonatal intrahepatic cholestasis and alpha-1-antitrypsin deficiency (author's transl)].
A case of alpha-1-antitrypsin deficiency in an 11 month-old Pi ZZ infant is reported. The patient exhibited intrahepatic cholestasis in the first months of life, with jaundice and hepatomegaly. Liver biopsy confirmed the diagnosis and showed the presence of hepatic fibrosis. Pi phenotypes, serum levels of alpha-1-antitrypsin, and symptoms in the family of the patient are reported. Clinical, biochemical and pathologic findings in liver disease in alpha-1-antitrypsin deficiency are discussed.
Biopsy↗
[Malnutrition in congenital deficiency of enterokynase (author's transl)].
A case of Congenital deficiency of Enterokynase is presented. The main clinical findings are: Chronic diarrhea, malnutrition and edema. Diagnosis was made by determination of tripsine activity in duodenal juice before and later to confront it to Enterokynase. The patient was treated with pancreatic supplements and protein hidrolysate with favourable results.
Diagnosis, Differential↗
[Blue rubber bleb nevus (author's transl)].
A case of Blue Rubber Bleb Nevus in a 11 year-old boy is reported. The patient exhibited characteristic hemangiomas of the skin and gastrointestinal tract with an iron deficiency anemia. Historical, clinical, pathological, and surgical features of the condition are discussed. Value of fibroscopic examination in delineation of the cause of persistent gastrointestinal bleeding is pointed out.
Child↗
A comparative study of isodensity surfaces using ab initio and ASA density functions.
In this article, we report a visual comparison between several of the available methods for constructing electronic density functions. The density forms studied include ab initio, atomic shell approximation, and promolecular densities. A graphical comparison is made for six different molecules at different levels of density function values. The differences between the various density functions are analysed by considering a molecular quantum self-similarity measure and the required computational time for all molecules at all computation levels is considered.
Algorithms↗
Identification of active molecular sites using quantum-self-similarity measures.
A novel approach to construct theoretical QSAR models is proposed. This technique, based on the systematic use of quantum similarity measures as theoretical molecular descriptors, opens the possibility to localize and to identify the position of the bioactive part of drug molecules in situations, where the nature of the pharmacophore is not known. To test the reliability of this new approach, the method has been applied to the study of steroids binding to corticosteroid-binding human globulin. The studied molecules involved the set of 31 Cramer's steroids, often used as a benchmark set in QSAR studies. It has been shown that theoretical QSAR models based on the present procedure are superior to those derived from alternative existing approaches. In addition, a new method to measure the statistical significance of multiparameter QSAR models is also proposed.
Benzoates↗