[Invasive disease by Haemophilus influenzae type b: current state of prevention by vaccination].
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Biomedical subjects
Publications and source records attributed to A Nieto.
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Cisplatin-fluorouracil (PF) is the most frequently used combination as induction chemotherapy (CT) for the treatment of locally advanced squamous cell head and neck cancer. This study was designed to evaluate the role of leucovorin (L) in the modulation of the therapeutic activity of PF continuously infused for 4 days. Between June 1990 and June 1992, stage III and IV previously untreated patients received PFL induction chemotherapy followed by surgery, radiotherapy, or both. The chemotherapy consisted of P 25 mg/m2, F 1000 mg/m2 both continuously infused for 4 days and L 250 mg/m2 infused for 2 hours before each daily infusion of PF. PFL was administered every 3 weeks for 4 cycles. The overall response rate at the completion of PFL was 91%, with 54% CR and 37% PR. Locoregional treatment was performed on 68 patients, 11 (16%) underwent surgery, 20 (29%) surgery plus radiotherapy, and 37 (54%) radiotherapy. Complete response status after both induction and locoregional therapy was 71%. Biopsies of the primary tumor or definitive resection specimens immediately after PFL therapy were available in 25 patients in CR. Pathological CR was found in 11 (44%). With a maximum follow-up of 44 months, the overall survival rate is 51% and the median survival has not been reached. PFL is highly active as induction chemotherapy. A randomized comparison between PF and PFL is necessary to define the place of leucovorin modulation in the treatment of head and neck cancer.
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Two isoforms of a retinoic acid-binding protein have been purified from rabbit epididymal secretions using a combination of gel filtration and ion-exchange chromatography. The two polypeptides (EP21a and b) present similar molecular mass (21 kDa), under native or denaturing conditions and have very similar amino-acid composition and tryptic peptide maps but differ in net charge. Both isoforms are glycosilated though to a different extent (9.2% and 6.3% of carbohydrate content) and are major components of the epididymal fluid. Binding of retinoic acid to EP21s appears to be specific, since they do not bind retinol, but is non-saturable. EP21s seem to present some similarity to two retinoic acid-binding proteins from rat epididymal secretions (site of biosynthesis, androgen dependence, ligand specificity and association to the spermatozoa) but differ from the rat proteins in amino-acid composition and glycosilation.
Uteroglobin, a progesterone-binding secretory protein, was shown to bind retinoic acid and retinol in a non-saturable manner, at least up to concentrations of retinoids of 20 microM. Binding is increased about 10-fold by previous reduction of uteroglobin with 10 mM dithiothreitol and it is not affected by previous saturation of the progesterone binding site, suggesting different binding sites for the steroid and the retinoids. The results are discussed in relation to a possible physiological role for this protein.
Levels of specific antibodies (Ab) and circulating antigens (CAg) were tested by ELISA in sera from 115 surgically confirmed hydatid patients, 41 individuals exhibiting other parasitic and unrelated diseases and 69 healthy subjects. Addition of CAg data to Ab detection in this sera collection increased sensitivity from 85% (only Ab) to 89% (Ab + CAg). Combination of ultrasonography with Ab and CAg serology for diagnosis of asymptomatic population in endemic areas was analyzed. One field survey (163 persons) involved both blood extraction and ultrasonography to all the population. Three people exhibited cyst images and all of them were Ab positive, while 6 Ab and 1 CAg positive individuals exhibited no cyst image. Another survey (1620 persons) involved a selection of 85 subjects for serology according to ultrasound data and record of family hydatid history. Twelve per cent exhibited no hydatid image being serologically positive and 14% were serologically negative but exhibited cyst image. Ultrasonography and serology (Ab and CAg) should be used in combination to maximize the diagnostic yield in asymptomatic population.
OBJECTIVE: To analyse the relative effect of the risk factors related to fetal growth retardation (FGR) in the central area of Spain. STUDY DESIGN: This is a case-control survey of 370 full-term gestations. Of the 370 women, 185 were diagnosed with intrauterine growth retardation, and 185 were in the normal group. All came from a central region of Spain. We took into account 25 possible risk factors. RESULTS: In the FGR group we found 12 risk factors with statistical significance in the univariate analysis (tobacco, drugs, low pre-pregnancy weight, low maternal height, little gestational weight gain, excessive physical activity during pregnancy, low socioeconomic status, low educational level, unmarried, urinary infection, mother's haematological changes, and previous infertility). After the multiple logistic regression analysis, five factors were shown to exist as independent risks (tobacco: OR, 23.50; 95% CI, 3.01-183.18; P < 0.01; low pre-pregnancy weight: OR, 4.01; 95% CI, 2.14-7.51; P < 0.001; low socioeconomic status: OR, 2.91; 95% CI, 1.72-4.90; P < 0.001; little gestational weight gain: OR, 2.52; 95% CI, 1.21-5.22; P < 0.05; and urinary infection: OR, 3.83; 95% CI, 1.49-9.87; P < 0.01). CONCLUSIONS: (i) Tobacco, low pre-pregnancy weight and low socioeconomic status are the three main cause-effect factors of relative importance in our sanitary zone for FGR. (ii) Disproportionate FGR is related more to older mothers and maternal previous illness than to the proportionate FRG.
BACKGROUND: Assessing the relationship between plasma fatty acids, specially polyunsaturated fatty acids in the mother and the fetus and intrauterine growth retardation (IUGR) in an apparently well-nourished population. DESIGN: Case-control intrapartum analysis. SETTING: Academic tertiary hospital. PATIENTS, PARTICIPANTS: There were 17 IUGR newborn cases (23 mothers) and 34 newborn control cases (46 mothers). MAIN OUTCOME MEASURE: Eleven fatty acids were blindly analysed in plasma by means of gas chromatography. RESULTS: Percentage values of eicosapentaenoic acid among mothers from the IUGR group were significantly higher than controls, whereas stearic absolute values were significantly reduced. On the other hand there were no differences in percentage values nor in absolute values regarding the 11 fatty acids analysed in newborn infants. CONCLUSION: In an apparently well-nourished population IUGR is not associated with an alteration in plasma fatty acids on the fetal side. However, on the maternal side some imbalance in eicosapentaenoic and stearic acids were found which will require further study.
Fibronectin and its integrin receptor alpha 5 beta 1 were studied by immunohistochemical methods in five normal canine mammary glands, four dysplastic glands and 18 mammary tumours. The aim of the study was to evaluate the possible changes in the alpha 5 beta 1 integrin receptor and its ligand fibronectin in relation to the metastatic capacity of canine mammary neoplasms. The immunostaining of alpha 5 beta 1 was very uniform in the hyperplastic glands but uneven in the mammary tumours. The expression of alpha 5 and beta 1 was diminished in metastatic tumours but there were some alpha 5-positive cells with pronounced features of malignancy and immaturity. Stromal fibronectin was increased in most cases and cytoplasmic staining of fibronectin was observed in epithelial and myoepithelial cells in mammary neoplasms but not in normal or dysplastic mammary tissue. There was no relationship between the content of alpha 5 beta 1 and the expression of fibronectin in canine mammary tumours.
In this study, 79 patients with locally advanced head and neck cancer were treated with induction chemotherapy. Cisplatin, 25 mg/m2, and 5-fluorouracil (5-FU), 1000 mg/m2, were employed, both of them in 24-hour continuous infusion over 96 hours, four cycles. The patients later underwent surgery and/or radiation therapy. The response to chemotherapy was 49%: of the complete responses (CR), 56% were histological; 29% were partial responses (PR). With the administration of the fourth cycle, CR increased from 30% to 49%. Once the complete treatment had been finished, 75% of CR and 5% PR were achieved. With a maximum follow-up period of 44 months, overall survival stands at 50%.
The protein regions involved in the nuclear translocation of the influenza virus PA polymerase subunit have been identified by deletion analysis of the protein expressed from a recombinant simian virus 40. Two regions seem to play a role in the process: region I (amino acids 124 to 139) and region II (amino acids 186 to 247). A nucleoplasmin-like nuclear translocation signal (NLS) has been identified in region I and an additional NLS appears to be present in region II, although no consensus targeting sequence can be detected. Alteration in any of the regions identified by short deletions completely prevented nuclear transport, whereas elimination of the regions I or II by large amino- or carboxy-terminal deletions did not prevent nuclear targeting of the truncated protein. In addition, a point mutation at position 154 completely eliminated nuclear transport. A beta-galactosidase fusion protein containing the 280 amino acid terminal region of the PA protein was partially transported to the nucleus and mutant PA proteins with a cytoplasmic phenotype could not be rescued by superinfection with influenza virus. These results suggest that the PA protein contains a functional nuclear targeting region which is required in influenza virus infection, with two independent NLSs, one in region I and the other in region II.
An in vivo system in which expression of a synthetic influenza virus-like chloramphenicol acetyltransferase (CAT) RNA is driven by influenza virus proteins synthesized from cloned cDNAs has been developed. Expression of the four influenza virus core proteins (nucleoprotein, PA, PB1 and PB2) was performed by transfection of four pGEM recombinant plasmids, each containing one of the four viral genes, into cell cultures previously infected with a vaccinia virus recombinant encoding the T7 RNA polymerase (vTF7-3). When a naked negative-sense influenza virus-like CAT RNA was transfected into cells expressing the four influenza virus proteins, CAT activity was detected in the cell extracts, demonstrating that the expressed proteins had RNA-synthesizing activity. In this system, CAT RNA templates containing additional nucleotides at the 3' end were also expressed, resulting in CAT activity. This showed that the influenza virus polymerase can recognize its promoter when located internally on an RNA template. In influenza virus-infected cells however, CAT activity was detected only when the CAT RNA contained the viral promoter at the exact 3' end and was transfected as in vitro assembled ribonucleoprotein. These results are discussed in terms of the different requirements of the two helper systems for expression of an exogenously added RNA.
Significant protective immunity against secondary hydatidosis in mice was achieved by immunization with a preparation of surface molecules of E. granulosus protoscoleces with Freund's incomplete adjuvant (PSEx-IFA). Study of PSEx-IFA immunogenicity demonstrates that glucidic epitopes evoked mainly IgM responses while peptidic epitopes evoke mainly IgG responses; however both types of epitopes elicit both types of responses. Analysis of the possible association between susceptibility or resistance to infection and antibody responses after challenge was also performed. Cyst fluid antigen (CFAg) specific antibody titres on month eight after challenge correlated with number and size of cysts. On the other hand no correlation was observed between protection and PSEx specific IgG titres either on the day of challenge or one month later. Nonetheless, immunoblot analysis revealed that some PSEx molecules were recognized on day 30 after challenge only by sera from immunized mice.
Two panels of monoclonal antibodies (MAbs) specific for the influenza A virus PA and PB2 polypeptides have been obtained from mice immunized with denatured proteins produced in Escherichia coli. All MAbs (13 specific for the PA polypeptide and 8 specific for the PB2 protein) reacted to the corresponding influenza virus protein in Western blotting (immunoblotting), immunoprecipitation, and immunofluorescence assays. To gain information about the roles of the nucleoprotein (NP) and PB2 and PA proteins during viral mRNA synthesis, the 21 anti-P antibodies and 3 anti-NP antibodies (J. A. López, M. Guillen, A. Sánchez-Fauquier, and J. A. Melero, J. Virol. Methods 13:255-264, 1986) were purified and tested for their ability to inhibit the transcriptase activity associated with viral cores purified from virions. Four of the antibodies (one anti-PB2 and the three anti-NP MAbs) inhibited transcription by more than 50% compared with unrelated control antibodies. The inhibitory effect was not due to a nonspecific effect of the antibody preparations, because these MAbs did not inhibit transcription when tested on influenza B virus nucleocapsids, which are not recognized by the antibodies. To determine whether the antibodies were acting on an early transcription step, transcription reactions were carried out in the presence of globin mRNA (a mixture of alpha- and beta-globin chains) and only one labeled nucleoside triphosphate (either GTP or CTP). The results obtained showed that MAbs to the PB2 and NP polypeptides interfered with the initiation step of mRNA-primed transcription. The implications of these results regarding initiation of viral mRNA synthesis are discussed.
UNLABELLED: The aim of this study was to evaluate the fluctuation of fetal pH in blood samples taken at the beginning of labor and at the moment of birth as related to intrauterine growth retardation syndrome. This is a prospective follow-up of term gestations, of which 41 were diagnosed as intrauterine growth retardation (IUGR) and 61 as normal ones. pH was measured in scalp blood sample at the beginning of the labor and in umbilical artery right after birth in both groups respectively. The rate of decrease of pH value in relation to duration of labor was determined for each case. Our results are: 1) Lower baseline pH were found in the IUGR group (pH 7.32 vs 7.34, p < 0.01), lower arterial blood pH at birth/.23 +/- 0.08 vs 7.27 +/- 0.08, p < 0.05). 2) Faster decrease of the pH during the labor (0.019 unit/hour vs 0.012, p < 0.05) as related to IUGR. CONCLUSION: IUGR fetuses are more acidotic at the beginning of the labor, and the rate of decrease of the fetal pH per unit of time during the labor is faster at least in a theoretical situation nevertheless it will require more studies if any practical applications are thought of.
The aim of this paper is to describe the clinical characteristics of the infection by the human immunodeficiency virus (HIV) in 13 aged patients with more than 60 years of age. In all the cases, the first clinical manifestation causing the visit to the doctor was an opportunistic infection with criteria of acquired immunodeficiency syndrome (AIDS), standing out the low CD4 rate in all the patients, a delay in the diagnosis and a short survival.
Thirty-two factors related to childhood asthma were studied in 200 asthmatic children. Remission of asthma was defined as a period of at least 2 years free of asthma while receiving no treatment. Univariate analysis showed significant associations between persistence of asthma and perennial symptoms with an odds ratio (OR) of 2.5 (95% confidence intervals 1.2 to 5.5); sensitization to house dust mites OR 3.5 (1.2 to 9.6); sensitization to molds, OR 7.9 (2.9 to 21.6); sensitization to pollen, OR 4.8 (1.4 to 16.3); and sensitization to milk protein, OR 5.4 (1.8 to 15.9). There was a positive association of remission of asthma with good treatment compliance, OR 12.1 (1.6 to 91.6). A stepwise logistic regression analysis selected the variables: perennial symptoms (S: 0 = no, 1 = yes), length of follow-up time (T: number of months), treatment compliance (C: 0 = poor, 1 = good), sensitization to fungi (F: 0 to 4), and sensitization to milk protein (M: 0 to 4). The analysis yielded the following formula for calculation of probability of asthma remission P(R): [formula: see text] where S indicates perennial symptoms; T, follow-up time in months; C, compliance; F, allergy to fungi; and M, allergy to milk.