Fibromyalgia and abdominal pain.
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Abdominal Pain↗
Biomedical subjects
C Alonso
Publications and source records attributed to C Alonso.
[Objectives, methods, and resources for undergraduate internal medicine learning].
The teaching of knowledge and clinical skills, considered the classical function of internal medicine professors, is changing towards a new orientation that guides the medical student's apprenticeship and involves strategic changes of both parts. Undergraduate internal medicine teaching must pursue an effective training that will allow an adequate medical practice as a general practitioner, emphasizing the soundness of the clinical method. This methodology requires knowledge in human communications that students must learn and improve during their studies. To allow an adequate clinical training, internal medicine courses must have the necessary duration and schedules and teaching and practicing resources, that facilitate this apprenticeship. Present time hospitals are not the most favorable environment for this purpose, professors must encourage the clinical vocation of their students.
Clinical Competence↗
Analysis of two cycloplatinated compounds derived from N-(4-methoxyphenyl)-alpha-benzoylbenzylidenamine. Comparison of the activity of these compounds with other isostructural cyclopalladated compounds.
In the present paper we report the synthesis, structural characterization, biochemical properties, and antiproliferative activity of two organo-cis-platinum cyclometalated compounds of formula [M(4-OMeC6H4N=C(COC6H5)C6H4)X]2, where M = Pt and X=Cl (4) or OAc (5). The IR and 1H and 13C NMR data of the chloro-bridged compound 4 showed that it has a planar structure. As indicated by IR and 1H and 13C NMR, the acetate-bridged compound 5 has an open-book shape structure. This structure was further confirmed by X-ray diffraction. The comparison of the biochemical properties and antiproliferative activity of these compounds relative to the isostructural palladium compounds [Pd(4-OMeC6H4N=C(COC6H5)C6H4)X]2 [X = AcO (1) and (2) or Cl (3)] indicated that the activity of compounds 4 and 5 is higher than that of the corresponding isostructural compounds 3 and 1-2, respectively, since their ID50 are 2-9-fold lower. It seems that there are not differences in the antiproliferative activity of all these compounds against leukemia HL-60 cells or mammary cancer MDA-MB 468 cells. Compounds 4 and 5 modify also the DNA structure of the oc and ccc forms of plasmid DNA. The acetate-bridged compound 5 showed the highest antiproliferative activity which is even higher than that of cis-DPP. Our data indicate that the Pt(II) compounds are more active than those having Pd(II) as the metal center.
Antineoplastic Agents↗
The anti Z-DNA reactivity of Z-DNA forming sequences is affected by platinum antitumor drugs.
The effect of binding of platinum antitumor drugs, cis-diamminedichloroplatinum (II) (cis-DDP) and Pt-pentamidine, on the Z-DNA reactivity of potential Z-DNA forming sequences has been studied by enzyme-linked immunosorbent assay. The results indicate that cis-DDP and Pt-pentamidine increase the Z-DNA reactivity of plasmids containing a (dG-dC)16 insert (pUCZ8) and a native Z-DNA forming sequence of Drosophila hydei (pF18). The molar ratio of platinum bound to nucleotides (rb) to produce 50% of Z-DNA reactivity was 0.10 for cis-DDP:pF18, 0.15 for Pt-pentamidine:pF18, and 0.10 for cis-DDP:pUCZ8 and Pt-pentamidine:pUCZ8. The efficacy of Pt-pentamidine to provoke Z-DNA reactivity is 2.5-fold higher than that of cis-DDP. While Pt-pentamidine was capable of inducing Z-DNA reactivity in a GC-rich DNA sequence of the hsp 70 protein of Trypanosoma cruzi (p2M4EO3) and in sequences of pUC8, cis-DDP suppresses Z-DNA reactivity. CD spectra of poly(dG-me5dC).poly(dG-me5dC) modified by the drugs suggest that the increase in Z-DNA reactivity observed in plasmids upon drug binding may be due to shifting towards Z-DNA or a Z-DNA like conformation.
Antineoplastic Agents↗
Cytoplasmic-nuclear translocation of the Hsp70 protein during environmental stress in Trypanosoma cruzi.
The present study provides immunological evidence of the constitutive presence of the Hsp70 protein in the cytoplasm of logarithmically growing T. cruzi parasites cultured at the normal temperature of 28 degrees C and of the translocation of the protein to the nucleus upon a heat shock treatment (2 hours at 37 degrees C). The nuclear translocation of the protein must depend on other factors beside the temperature per se since at 28 degrees C, in stationary phase growing parasites, the Hsp70 protein was present in both the cytoplasm and the nucleus. During recovery at 28 degrees C the protein leaves the nuclei but the nuclear-cytoplasmic translocation of the protein is a much more gradual process than its initial transport to the nucleus. Since the isoform of the nuclear Hsp70 is different from that found in the cytoplasm it is likely that before translocation to the nucleus the cytoplasmic Hsp70 nuclear precursor must undergo a specific modification.
Animals↗
Genomic organization and expression of two independent gene arrays coding for two antigenic acidic ribosomal proteins of Leishmania.
In the present paper we describe the isolation and characterization of four novel genes of the parasitic protozoan Leishmania infantum. These genes are organized as two independent gene clusters, and they are related by nucleotide sequence to eukaryotic genes encoding acidic ribosomal proteins. Each gene cluster contains two tandemly linked genes coding for identical proteins. Each of the proteins coded by the gene clusters (called LiP and LiP') are highly divergent in sequence, showing the characteristic features of eukaryotic P-proteins from the P2 group. In spite of the sequence conservation of the coding regions of each of the genes in the cluster, the 5'- and 3'-untranslated regions are heterogeneous in sequence. The analysis of the expression of these genes indicates that logarithmic phase promastigotes show increased levels of LiP- and LiP'-specific transcripts compared with stationary phase promastigotes. The steady state RNA levels of the LiP and LiP' genes show a similar dependence of the growth phase of the parasite. Using specific probes for the divergent 3'-untranslated regions of each of the genes, it was found that the abundance of the mature transcripts is different even when the transcripts are derived from the same gene cluster. These findings probably indicate that the 3'-untranslated regions may influence the stability or turnover of the transcripts derived from both LiP and LiP' gene clusters.
Amino Acid Sequence↗
Palladium (II) compounds of putrescine and spermine. Synthesis, characterization, and DNA-binding and antitumor properties.
The reaction of putrescine (Put) with K2PdCl4 and PdCl2 resulted in the synthesis of compounds of formula [PutH2][PdCl4] and [Pd2Cl4(Put)2]. Compounds of formula [PdCl2(SpermH2)][PdCl4] and [Pd2Cl4(Sperm)] have been also synthesized by reaction of spermine (Sperm) with K2PdCl4. The structure of all these compounds has been analyzed by IR and 1H NMR. UV and CD spectroscopic data have shown that all the Pd(II)-polyamine compounds synthesized induce conformational changes in the circular forms of plasmid DNA. Determinations by electrophoresis in agarose gels of the mobility of the DNA in drug:DNA complexes indicated that only the Pd(II)-putrescine compounds have the ability to induce significant conformational changes in the covalently closed circular (ccc) form of the pUC8 plasmid DNA. The Pd(II)-putrescine and Pd(II)-spermine compounds were also assayed for in vitro antiproliferative activity against MDA-MB 468 and HL-60 human cancer cells. The results suggest that the putrescine complexes may be regarded as potential antitumor agents because the ID50 value of all of the Pd(II)-putrescine complexes is twofold lower than the ID50 of cis-DDP. Our data also show that, on the other hand, the Pd(II)-spermine compounds have low antiproliferative activity.
Antineoplastic Agents↗
Prospective study of bacteremia during transesophageal echocardiography.
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Bacteremia↗
Binding of Pt-pentamidine to nucleosomal DNA. Studies of the antiproliferative activity of the drug against human cancer cells.
In the present paper we present data showing that the effect of the binding of the antitumour drug Pt-pentamidine to nucleosomal DNA is the opposite to that of the cis-DDP compound since it causes strong stabilization of the double helix to heat denaturation and because in nucleosome:Pt-pentamidine complexes the nucleosomal denatured DNA is able to reassociate at 71 degrees C. Upon binding, the pentamidine ligand, by itself, also produces stabilization of the nucleosomal DNA but the effect is lower than that induced by Pt-pentamidine. It seems that in Pt-pentamidine:nucleosome complexes about 50% of the adducts are formed during the first hour of incubation of the nucleosomes with the drug since the increase in Tm of the DNA of these complexes is 53% of the total increase in Tm of the DNA of the Pt-pentamidine:nucleosome complexes formed in 48 h. The 'in vitro' screening of the antiproliferative activity of Pt-pentamidine against 60 tumour cell lines indicated that this antitumour compound shows higher antiproliferative activity against small cell lung, non-small cell lung and melanoma cancer lines than against the rest of the cell lines.
Antineoplastic Agents↗
Mapping of antigenic determinants of the T. cruzi hsp70 in chagasic and healthy individuals.
In the present paper we describe the analysis of the immunological recognition by sera of healthy individuals and chagasic patients of the Trypanosoma cruzi heat shock 70 kDa protein. By a Falcon Assay Screening Test, using as antigen an ATP-agarose purified T. cruzi hsp70, it has been found that the sera of infected patients as well as of that of healthy individuals show reactivity against the hsp70 protein but that the reactivity of the sera of patients is in general significantly higher than that of healthy individuals. The analysis of the reactivity of the chagasic sera against a collection of peptides covering 92% of the protein has shown that more than 50% of the peptides gave a positive response but only against a few peptides did we observe high reactivity in a wide spectrum of sera. Only four peptides (numbers 9, 12, 14 and 47) were recognized by all sera tested with high reactivity values. The sera of healthy individuals also showed reactivity against a large percentage of peptides but with lower values. It was observed that particular peptides showing high reactivity against the sera of healthy donors also show high reactivity against patients' sera. However, the general pattern of reactivity against the peptides is different in chagasic and healthy sera. The immunodominant peptides map in the highly conserved as well as in the less conserved part of the hsp70 molecule. The 1/3 C-terminal, being the least conserved part of the molecule, seems to be the least immunogenic. Mapping of the epitopes led to the identification of particular immunogenic motifs within individual peptides.
Amino Acid Sequence↗
Isolation, characterization and analysis of the expression of the Leishmania ribosomal PO protein genes.
Two tandemly linked genes are present in the Leishmania infantum genome that code for the acidic ribosomal PO protein. The genes are identical in the coding region, although a striking lack of nucleotide sequence conservation is observed when the boundaries of the coding regions between both genes are compared. The 3' untranslated regions of the two genes are, moreover, different in size. The deduced amino acid sequence of the L. infantum PO protein (LiPO) shows a high degree of sequence conservation, including the highly charged conserved C-terminal domain, with the ribosomal PO proteins of other eukaryotic organisms. Northern blot experiments showed that two different size class transcripts are expressed in the gene cluster and that the steady state level of each of the transcripts in logarithmic phase promastigotes is markedly different. The abundance of both transcripts is down-regulated in parasite cultures on reaching stationary phase. Since it seems that the two Leishmania ribosomal PO genes are expressed in a single polycistronic transcript, it is likely that the different levels of PO mRNAs observed in cultured cells is due to a postranscriptional regulatory mechanism.
Amino Acid Sequence↗
Bacteriophage lambda: long-term stored stocks ready for lysis.
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Bacteriophage lambda↗
Epithelioid sarcoma of penis simulating Peyronie's disease.
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Adult↗
Diagnostic markers of viral hepatitis B and C.
Hepatitis B virus (HBV) serology has become extremely refined. As well as the recognised hepatitis B surface (HBs), hepatitis B core (HBc), and hepatitis B e (HBe) antigen-antibody systems, new markers have been introduced including pre-S1, pre-S2 for the envelope and the functional X protein. New automates have been introduced allowing flexibility in the different tests according to precise needs. The monitoring of pre-S1 antigen provides a relevant correlate of viral replication. The quantitative determination of HBV-DNA, pre-S1 Ag, and IgM anti-HBc seem most useful for the decision to use, and the monitoring of, antiviral treatment. Second generation ELISAs detect antibodies to three sets of hepatitis C virus (HCV) protein including the c22 core, and c33, and c100, which correspond to the non-structural regions (NS3 and NS4, respectively). Second generation ELISAs require confirmation by supplement assays, but their biggest limitation is the delayed appearance of anti-HCV after primary infection. In addition 10% of chronic infections with liver disease still remain seronegative despite circulating HCV RNA in serum or liver, or both. Much progress still has to be made before HCV serology can reach the level of sophistication of HBV.
Biomarkers↗
Time-dependent rheological behavior of blood at low shear in narrow vertical tubes.
The time-dependent flow behavior of normal human blood after a sudden reduction of wall shear stress from 5,000 mPa to a low level (2-100 mPa) was studied during perfusion of vertical tubes (internal diam 28-101 microns) at constant driving pressures. Immediately after the implementation of low-shear flow conditions the concentration of red blood cells (RBCs) near the tube wall started to decrease, and marginal plasma spaces developed as a result of the assembly of RBC aggregates. This was associated with a time-dependent increase of flow velocity by up to 200% within 300 s, reflecting a reduction of apparent viscosity. These time-dependent changes of flow behavior increased strongly with decreasing wall shear stress and with increasing tube diameter. A correlation between the width of the marginal plasma layer and relative apparent viscosity was obtained for every condition of tube diameter, wall shear stress, and time. Time-dependent changes of blood rheological properties could be relevant in the circulation, where the blood is exposed to rapid and repeated transitions from high-shear flow conditions in the arterial and capillary system to low-shear conditions in the venous system.
Blood Flow Velocity↗
Alternating combination VCMP/VBAP chemotherapy versus melphalan/prednisone in the treatment of multiple myeloma: a randomized multicentric study of 487 patients.
PURPOSE: To determine whether combination chemotherapy with alternating cycles of vincristine, cyclophosphamide, melphalan, and prednisone (VCMP) and vincristine, carmustine (BCNU), Adriamycin (doxorubicin; Farmitalia, Carlo-Erba Laboratories, Spain), and prednisone (VBAP) is better than the standard melphalan-prednisone (MP) regimen in multiple myeloma (MM). PATIENTS AND METHODS: From January 1985 to December 1989, 28 institutions of the Spanish Cooperative Group for Hematological Malignancies Treatment, Spanish Society of Hematology (PETHEMA) entered 487 eligible patients with symptomatic MM into the study. Patients were randomized to receive either MP or alternating courses of VCMP and VBAP. Logistic regression and the Cox proportional hazards models were used to assess the association between patients' characteristics and response rate and survival, respectively. RESULTS: Among 449 patients who were assessable for response, the overall response rate to MP was 51.8% (31.5% objective response plus 20.3% partial response) as compared with 62.7% (45.2% objective response plus 17.5% partial response) to VCMP/VBAP (P = .025). Also, a significantly higher proportion of objective responses was observed with combination chemotherapy (45.2% v 31.5%; P = .004). The factors associated with an unfavorable response rate in the overall series were low platelet count, treatment with MP, high creatinine level and immunoglobulin, (IgG) monoclonal (M)-component. No significant differences were found when survival rates of both groups of patients were compared. However, patients with IgA myeloma treated with VCMP/VBAP survived significantly longer than those who received MP (median, 20.2 v 38.4 months; P < .005). CONCLUSION: These results indicate that combination chemotherapy improves response rate in MM. However, this does not result in a significantly different survival rate, except for patients with IgA myeloma, who survive significantly longer with combination chemotherapy.
Aged↗
Myocyte cell damage after administration of doxorubicin or mitoxantrone in breast cancer patients assessed by indium 111 antimyosin monoclonal antibody studies.
PURPOSE: To compare myocyte cell damage induced by doxorubicin or mitoxantrone, we performed left ventricular ejection fraction (LVEF) measurements and indium 111 antimyosin antibody studies in a group of patients with advanced breast cancer who had been treated with these anthracycline derivatives. PATIENTS AND METHODS: We studied 35 patients eligible to receive chemotherapy including the anthracyclines: doxorubicin or mitoxantrone (cumulative dose of doxorubicin, 500 mg/m2; or mitoxantrone, 120 mg/m2). LVEF was measured before and after 10 cycles of chemotherapy. Antimyosin uptake in the myocardium was quantified by means of a heart-to-lung ratio (HLR). RESULTS: Patients treated with doxorubicin presented with a significant decrease in LVEF after chemotherapy (before, 60.4% +/- 8.92%; after, 49.8% +/- 9.71%; P = .001). Antimyosin uptake was observed in all patients with a HLR of 2.03 +/- 0.25. Seven of eight patients with a HLR greater than 2.03 had a greater than 10% decrease in LVEF. Patients treated with mitoxantrone did not present with a decrease in LVEF after chemotherapy (before, 55.4% +/- 6.25%; after, 55.8% +/- 7.25%; not significant). Antimyosin uptake was observed in 14 of 17 patients with a HLR of 1.77 +/- 0.18 (P < .05). CONCLUSION: 111In antimyosin monoclonal antibodies defect myocardial cell damage produced by doxorubicin and mitoxantrone. In patients with advanced breast cancer, cumulative doses of 120 mg/m2 of mitoxantrone produce less myocardial cell damage than cumulative doses of 500 mg/m2 of doxorubicin. 111In antimyosin uptake without decrease in LVEF after treatment with mitoxantrone indicates the presence of myocyte cell damage, but not to the extent necessary to deteriorate function. These results indicate that 111In antimyosin antibody studies are useful in the noninvasive comparative assessment of cardiotoxicity produced by different anthracycline derivatives.
Adult↗
Isolation of Trypanosoma cruzi specific nuclear repeated DNA sequences.
We described the isolation of two genomic fragments, called E12 and E22, containing highly repeated DNA sequences from Trypanosoma cruzi. The E12 and E22 fragments have molecular sizes of about 1.1 and 0.8 Kb, respectively. Copy number determinations indicate that each one of these sequences are repeated about 5 x 10(3) times in the parasite genome. E12 and E22 elements do not cross-hybridize indicating that they are not related in nucleotide sequence. The Southern blot analysis of total DNA digested with a variety of restriction enzymes shows the existence of a complex pattern of hybridization bands with the repeated elements indicating that they are interspersed along the T. cruzi genome. In fact, pulsed field gel electrophoresis together with hybridization evidenced that both sequences are present in all or nearly all the chromosomal bands. Clones bearing these repetitive elements could be useful for diagnostic of the Chagas' disease and strain classification purposes.
Animals↗