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Biomedical subjects

L Villa

Publications and source records attributed to L Villa.

At least 55 records · Page 3Linked to original sources
PubMed1994

Dipeptidyl aminopeptidase yspI mutants of Schizosaccharomyces pombe: genetic mapping of dpa1+ on chromosome III.

A mutant strain of Schizosaccharomyces pombe lacking dipeptidyl aminopeptidase yspI was isolated from a strain already defective in aminopeptidase activity by means of a staining technique with the chromogenic substrate ala-pro-4-methoxy-beta-naph-thylamide to screen colonies for the absence of the enzyme. The defect segregated 2+:2- in meiotic tetrads, indicating a single chromosomal gene mutation, which was shown to be recessive. Gene dosage experiments indicated that the mutation resides in the structural gene of dipeptidyl aminopeptidase yspI, dpa1+. The dpa1+ gene was located on chromosome III by using m-fluorophenylalanine-induced haploidization and mitotic analysis. dpa1 mutants did not show any obvious phenotype under a variety of conditions tested.

Chromosome Mapping↗
PubMed1994

Molecular properties of the WB4101 enantiomers and of its chiral methyl derivatives for alpha 1-adrenoceptor recognition.

The optical isomers of the well known alpha 1-antagonist WB4101 and of its derivatives with a methyl group in the oxyethyl moiety were prepared for the evaluation of their alpha-adrenoceptors binding affinity. By means of a detailed computational analysis, the present work shows that the introduction of a methyl group affects the behaviour of WB4101 in different ways. A limitation of the conformational freedom in certain regions of the torsional subspace of the potential energy function, differences in the reactivity of the protonated species towards a model proton acceptor and the quality of the superposition with the rigid template for alpha 1 antagonists, corynanthine, are examined and discussed in order to select a candidate bioactive form and possible features which act as modulators of the recognition process at the alpha 1-adrenoceptors.

Adrenergic alpha-1 Receptor Antagonists↗
PubMed1993

Increasing the immunogenicity of protein antigens through the genetic insertion of VQGEESNDK sequence of human IL-1 beta into their sequence.

The immunogenicity of two recombinant protein Ag containing the immunostimulatory sequence of human IL-1 beta 163-171 (VQGEESNDK) genetically engineered into their structure has been evaluated. The IL-1 beta sequence was inserted into the loop between alpha helices D and E of recombinant human ferritin H chain and into the hypervariable region of recombinant flagellin from Salmonella muenchen. The chimeric proteins were injected into mice and the level of humoral immune response developed against the native proteins was assessed by measuring the number of Ag-specific plaque forming cells/spleen or as the level of serum IgG response. The response was compared to that of mice receiving injections with wild-type protein Ag not containing the VQGEESNDK sequence or with hybrid constructs containing unrelated foreign peptide sequences of the same length. A significantly higher immune response was observed in mice immunized with chimeric constructs containing the human IL-1 beta 163-171 sequence. These data suggest that the insertion of the VQGEESNDK sequence may prove useful to increase the immune response against poorly immunogenic recombinant proteins.

Adjuvants, Immunologic↗
PubMed1993

The relationship of total body bone mineral (TBBMC) to anthropometric variables in postmenopausal women, and contribution of chronological age and years since menopause to TBBMC loss.

Dual energy X-ray absorptiometry measurements of total body bone mineral content (TBBMC), fat body mass (FBM) and fat mass percentage (%FM), lean body mass (LBM) and body weight (BW) were performed on 168 normal postmenopausal females. They were matched regarding life style and habits and had body mass index under 30. Their TBBMCs were correlated with these measurements, with chronological age (CA) and with the number of years since menopause (YSM). There was no correlation between TBBMC and %FM and LBM, but there was with BW (p < 0.001). There was a significant and negative correlation (r = -0.453, p < 0.001) between TBBMC and CA and to a higher range (r = -0.697, p < 0.001) with YSM. Menopausal females over 60 (n = 87) presented less bone mass than younger females (n = 81) (p < 0.01). These data suggest that regarding TBBMC, menopausal onset is a more important factor in bone mass loss, which persists rather markedly even during periods of time far from menopause and that TBBMC depends more on BW than on LBM and FM in women.

Adipose Tissue↗
PubMed1993

Agonistic activity and charge driven interaction potentiality of PAF derivatives.

Taking into account the contribution of the C2 substituent to the interaction ability of PAF derivatives, an investigation has been undertaken on: i) the role of the presence of two unitary charges of opposite sign in the molecule; ii) the role of the spacing of the same charged moieties. For this purpose, the theoretical analysis of model compounds for newly synthesized and already known compounds has been performed by means of computer-aided modelling, molecular mechanics and semiempirical quantum chemical computational methods. The combination of the results with the available pharmacological data allows a discussion about the stereoelectronic features required for agonist interaction at the PAF receptor.

Animals↗
PubMed1993

Chiral PAF agonists: synthesis, theoretical analysis of their stereoelectronic properties and structure activity relationships.

A series of chiral PAF agonists were synthesized. Modifications at the PAF structure were undertaken as far as the C2 substituents and the onium head groups are concerned. In parallel, molecular modelling studies including a MOPAC geometry optimization and the analysis of the electrostatic potential were performed on the newly synthesized and on already known PAF agonists, in order to gain a better insight into the stereoelectronic features required for interaction with the PAF receptor.

Chemical Phenomena↗
PubMed1992

Conformational behaviour and molecular similarity of some beta 1-adrenergic ligands.

The conformational behaviour of a series of aryloxypropanolamines was investigated by means of a new procedure which allows the sampling of the molecular torsional surface in a very efficient way. The combination of such a procedure with the standard molecular mechanics algorithms for the geometry optimization gives, as a result, the definition of a powerful computational scheme for the detailed analysis of the potential energy surface of complex molecules. The compounds studied show a remarkable tendency to form intra-molecular hydrogen bonds, which seem to play a key role in determining the lowest energy structures. The indices of molecular similarity proposed by Carbó, computed for the most stable conformers, do not account for differences between diastereoisomers, and, as a consequence, can hardly be used to attempt a structure-activity correlation.

Hydrogen Bonding↗
PubMed1992

Binding and internalization of the 163-171 fragment of human IL-1 beta.

The mechanisms of cell association of the human interleukin (IL-1 beta) immunostimulatory fragment 163-171 have been studied. The fragment was able to associate abundantly to both IL-1R- and IL-1R+ cells. Binding was strictly temperature dependent, was not saturable and could be inhibited by excess amounts of unlabelled 163-171 peptide but not by IL-1 beta, suggesting that the 163-171 fragment is not an IL-1R-binding domain of IL-1 beta. The fragment is readily internalized by cells by a cytochalasin-insensitive mechanism and it localizes mainly in the cytoplasm. It is concluded that the active domain 163-171 of IL-1 beta can be taken up by cells through a receptor-independent, temperature-dependent mechanisms and that its ability to activate cellular functions is based on IL-1R-independent intracellular pathways.

Amino Acid Sequence↗
PubMed1992

Superovulation with human menopausal gonadotropins in the treatment of infertility associated with minimal or mild endometriosis: a controlled randomized study.

OBJECTIVE: To determine the efficacy of superovulation with buserelin acetate, human menopausal gonadotropins (hMG), and human chorionic gonadotropin (hCG) in the treatment of infertility associated with minimal or mild endometriosis. DESIGN: Prospective, randomized, controlled study. SUBJECTS: Forty-nine infertile women with a laparoscopic diagnosis of endometriosis stage I (n = 29) or II (n = 20) according to the revised American Fertility Society classification, randomly assigned to three superovulation cycles (n = 24) or 6 months' expectant management (n = 25). MAIN OUTCOME MEASURES: Cycle fecundity rates and cumulative pregnancy rates (CPR) in the two groups. RESULTS: Nine pregnancies were obtained in the superovulation-treated patients and six in the nontreated ones. The cycle fecundity rates and CPR were 0.15% and 37.4% after three superovulation cycles and 0.045% and 24% after 6 months of expectant management (P less than 0.05 and P = not significant, respectively). The women who did not achieve a pregnancy after three cycles of superovulation were followed for a total of 50 months during which no therapy was given. One pregnancy started in this period (cycle fecundity rate = 0.020). One spontaneous abortion occurred in each group. Three treated patients had multiple pregnancies, and four had ovarian hyperstimulation syndrome. CONCLUSION: Superovulation seems to be associated with a better cycle fecundity rate but not a better CPR than expectant management in infertile women with endometriosis stages I and II. The efficacy and side effects of this therapeutic approach should be evaluated in larger series.

Adult↗
PubMed1992

Molecular variants of human papillomavirus type 16 from four continents suggest ancient pandemic spread of the virus and its coevolution with humankind.

We have amplified by the polymerase chain reaction, cloned, and sequenced genomic segments of 118 human papillomavirus type 16 (HPV-16) isolates from 76 cervical biopsy, 14 cervical smear, 3 vulval biopsy, 2 penile biopsy, 2 anal biopsy, and 1 vaginal biopsy sample and two cell lines. The specimens were taken from patients in four countries--Singapore, Brazil, Tanzania, and Germany. The sequence of a 364-bp fragment of the long control region of the virus revealed 38 variants, most of which differed by one or several point mutations. Phylogenetic trees were constructed by distance matrix methods and a transformation series approach. The trees based on the long control region were supported by another set based on the complete E5 protein-coding region. Both sets had two main branches. Nearly all of the variants from Tanzania were assigned to one (African) branch, and all of the German and most of the Singaporean variants were assigned to the other (Eurasian) branch. While some German and Singaporean variants were identical, each group also contained variants that formed unique branches. In contrast to the group-internal homogeneity of the Singaporean, German, and Tanzanian variants, the Brazilian variants were clearly divided between the two branches. Exceptions to this were the seven Singaporean isolates with mutational patterns typical of the Tanzanian isolates. The data suggest that HPV-16 evolved separately for a long period in Africa and Eurasia. Representatives of both branches may have been transferred to Brazil via past colonial immigration. The comparable efficiencies of transfer of the African and the Eurasian variants to the New World suggest pandemic spread of HPV-16 in past centuries. Representatives of the African branch were possibly transferred to the Far East along old Arab and Indonesian sailing routes. Our data also support the view that HPV-16 is a well-defined virus type, since the variants show only a maximal genomic divergence of about 5%. The small amount of divergence in any one geographic location and the lack of marked divergence between the Tanzanian and Brazilian African genome variants two centuries after their likely introduction into the New World suggest a very slow rate of viral evolution. The phylogenetic tree therefore probably represents a minimum of several centuries of evolution, if not an age equal to that of the respective human races.

Base Sequence↗
PubMed1991

The proteolytic system of the fission yeast Schizosaccharomyces pombe.

Proteinase and peptidase activities of the fission yeast Schizosaccharomyces pombe were investigated. Several intracellular proteolytic enzymes were found: two endoproteinases, one carboxypeptidase, one aminopeptidase and one dipeptidyl-aminopeptidase. In addition, proteinase inhibitors were detected. In fresh crude extracts an activation procedure is needed to measure maximal activities of endoproteinases and carboxypeptidase, whose level is markedly dependent on growth medium composition and on growth phase, while aminopeptidase and dipeptidyl-aminopeptidase activities are very little, if at all, regulated by the carbon source.

Aminopeptidases↗
PubMed1991

Re-examination of the anatomic indications for hysteroscopic metroplasty.

Until now the indication for hysteroscopic metroplasty has been based on laparoscopic findings and thus depended on the operator's experience. Using ultrasound and magnetic resonance images of double uteri it should be possible to find more objective indications for this operation. When three points are identified on longitudinal scans of the uterine fundus, the two tubal ostia and the mid-point of the fundal perimetrium, hysteroscopic metroplasty is indicated only in uteri in which the third point is at least 5 mm above a straight line drawn between the tubal ostia. This classification criterion includes more cases than laparoscopic criteria in this study; we performed hysteroscopic metroplasty in 23 double uteri and had we followed the laparoscopic criteria the operation would have been performed only in 19.

Diagnosis, Differential↗
PubMed1991

Argon laser versus microscissors for hysteroscopic incision of uterine septa.

We performed hysteroscopic metroplasty in 21 women with repeated abortion and subseptate uterus. The patients were randomly allocated to septal incision with the argon laser (group I, 10 subjects) or microscissors (group II, 11 subjects) to compare these instruments in terms of surgical feasibility and anatomic results. The mean operating time was 57% longer in group I than in group II (p = 0.001), the intra- and postoperative morbidity of the whole series was negligible, and the anatomic results at abdominal ultrasonography and hysteroscopy performed 2 months postoperatively were similar in the two groups. This study confirms that microscissors are the simplest, fastest, most effective, and least expensive instrument to correct a septate uterus. The complete agreement of the findings at follow-up hysteroscopy and ultrasonography suggest the use of the latter as the method of choice to check the surgical results.

Adult↗
PubMed1991

Clinical applicability of the radiographic method for determining the thickness of calcified crown tissues.

A previously developed radiologic method for determining the thickness of the mineralized crown tissues was applied clinically to 10 teeth diagnosed for extraction. The thickness of the mineralized crown tissues as measured radiographically was compared with that measured directly on the extracted tooth. A statistical analysis indicated accuracy of 4.46%, equivalent to an error of 0.12 mm.

Dental Cementum↗
PubMed1991

Risk of recurrence after myomectomy.

The risk of recurrence of uterine myomas was analyzed in 622 patients who underwent myomectomy between 1970 and 1984 at the First Department of Obstetrics and Gynecology of the University of Milan. The cumulative 10-year recurrence rate was 27%, and this increased steadily up to the end of the observation period. Differences were not observed in frequency of recurrence by age at diagnoses or by the site of the myomas at surgery. Patients with a single myoma tended to experience a lower rate, but this finding was not statistically significant. Women who gave birth to a child after myomectomy had a 10-year recurrence rate of 15%, against 30% for those who did not; this difference was statistically significant.

Adult↗
PubMed1991

Differential inhibition of IL-1 beta activities and receptor binding by monoclonal antibodies mapping within a discrete region of the protein.

The importance of the region in position 148-192 for the biological activities and receptor-binding capacity of the human IL-1 beta protein has been assessed by the use of mAbs. Four mAbs have been used, which recognize different epitopes within the 148-192 region. None of the mAbs could inhibit binding of IL-1 beta to IL-1RI (expressed on T cells and fibroblasts), suggesting that the 148-192 region does not contain IL-1RI binding sites. Conversely, mAbs Vhp20 (recognizing the fragment 166-169) and BRhD2 (directed to an epitope in the sequence 177-186) recognize sites partially involved in binding to IL-1RII (expressed on B cells, macrophages, and PMN). Only mAbs BRhD2 and FIB 1 (which recognizes an epitope in the sequence 174-186) can inhibit IL-1 beta-induced thymocyte proliferation, whereas all four can inhibit the adjuvant capacity of IL-1 beta in vivo. It is concluded that the region 148-192 encompasses domains important for T cell activation but not for binding to the IL-1RI on T cells, others involved in immunostimulation in vivo, and others important for binding to IL-1RII, although not directly involved in it.

Amino Acid Sequence↗