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Biomedical subjects

A Romero

Publications and source records attributed to A Romero.

At least 127 records · Page 7Linked to original sources

[Chlamydia pneumoniae infection associated with autoimmune hemolytic anemia due to warm antibodies].

Chlamydia pneumoniae has often been implicated in respiratory tract infections concomitant with other pathogens. Although this agent has also been associated with other nonrespiratory diseases, to our knowledge it has never been described with autoimmune hemolytic anemia. We present a case of pneumonia in which C. pneumoniae was found in association with another important respiratory pathogen, Legionella, and with hemolytic autoimmune IgG to warm antibodies, an entity that has not been reported previously with this or any other germ of the genus Chlamydia.

Anemia, Hemolytic, Autoimmune↗

Ifosfamide and cisplatin as neoadjuvant chemotherapy for advanced cervical carcinoma.

A phase II trial was performed to evaluate the efficacy and toxicity of a combination of cisplatin (CDDP) and ifosfamide (IFX) as neoadjuvant chemotherapy in advanced cervical carcinoma (ACC). Between August 1991 and September 1993, 57 untreated patients with stages IIB to IVA were entered into this study. Median age was 44 years (range, 25 to 74 years). The distribution by stages (International Federation of Gynecology and Obstetrics) was as follows: IIB, 31 patients; IIIB, 21 patients; and IVA, 5 patients. Therapy consisted of IFX 2000 mg/m(2) 1-h i.v. infusion days 1 to 3; mesna 400 mg/m(2) i.v. bolus at hours 0 and 4, and 800 mg p.o. at hour 8; and CDDP 100 mg/m(2) on day 3. Cycles were repeated every 28 days for a total of three courses. Both staging and response assessment were performed by a multidisciplinary team. An objective response was observed in 30 of 56 patients (54%; 95% confidence interval, 41 to 67%). Four patients (7%) had a complete response (CR) and 26(46%) had a partial response (PR). Patients with CR or operable PR underwent surgery, otherwise received definitive radiotherapy. Toxicity was mild to moderate. There were no toxicity related deaths. These results indicate that IFX/CDDP is an active combination for ACC with mild toxicity. The results of phase III studies that evaluate the real impact of neoadjuvant chemotherapy are awaited.

Adult↗

Ifosfamide and vinorelbine as first-line chemotherapy for advanced non-small cell lung carcinoma.

We evaluated the efficacy and toxicity of the novel combination of ifosfamide (IFX) and vinorelbine (VNB) as first-line chemotherapy in patients with stage IIIB and IV non-small cell lung cancer (NSCLC). Between March 1993 and November 1994, 44 patients (17 stage IIIB; 27 stage IV) received a regimen consisting of IFX, 2 g/m2 in a 1-h infusion, days 1-3; mesna, 400 mg/m2 in an i.v. bolus at hours 0 and 4 and 800 mg orally at hour 8, days 1-3; and VNB, 35 mg/ m2 in a 20-min infusion, days 1 and 15. During the first course only, a half dose of VNB (17.5 mg/m2) was administered on days 8 and 22. Courses were repeated every 28 days. Forty patients were fully evaluable for response, and 44 were assessable for toxicity. Objective regression was recorded in 13 of 40 patients (33%). No patient achieved a complete response. Thirteen patients presented a partial response (33%); 17 (42%) had no change; and progressive disease was observed in 10 (25%). The median duration of response was 10 months, and the median time to treatment failure for the whole group was 4 months. Median survival was 11 months. The dose-limiting toxic effect was myelosuppression. Leukopenia occurred in 25 patients (57%) and was grade 3 or 4 in 8 patients (18%). Twelve patients (27%) developed peripheral neurotoxicity, while five had mild IFX-induced CNS toxicity. Phlebitis was observed in 15 of 30 patients (50%) who did not have central implantable venous systems. The IFX-VNB combination exhibited an activity against NSCLC that was among the highest reported for non-cisplatin-containing regimens, with a toxicity profile that was easily managed.

Adult↗

Prenatal cocaine and neonatal outcome: evaluation of dose-response relationship.

OBJECTIVE: The aim of this study was to evaluate the hypothesis that prenatal cocaine exposure would negatively affect newborn behavior. METHODS: A prospective observational study of term infants recruited from the low-risk nursery used a structured, standardized interview to obtain maternal data. Cocaine exposure was determined by radioimmunoassay of the infant's meconium stool. An examiner blinded to the infant's cocaine status administered the Brazelton Neonatal Behavioral Assessment Scales. RESULTS: The sample was composed of 23 exposed and 29 nonexposed infants. On six of the seven Brazelton Neonatal Behavioral Assessment Scale clusters, cocaine-exposed infants performed less well than control infants, with significant differences observed for autonomic stability. In addition, a dose-response relationship was suggested. Significant negative, within-group relationships were evident in the exposed group, indicating poorer performance with increasing meconium cocaine concentration for orientation (r = -.40) and regulation of state (r = -.40). Regression model testing of the influence of meconium cocaine concentration on neurobehavioral outcomes, after controlling for significant confounders, identified a significant independent, negative effect of meconium cocaine concentration on two clusters-motor and regulation of state. CONCLUSION: In otherwise healthy full-term infants, prenatal cocaine exposure identified by quantitative analysis of cocaine concentration in meconium had a significant, independent negative association with motor and regulation of state that remained after controlling for other significant confounders. A dose-response relationship was evident.

Adult↗

The crystal structure of nickel(II)-azurin.

The nickel(II)-azurin metalloderivative has been crystallized and its structure solved at 0.205-nm resolution by X-ray diffraction. The overall structure is not modified by the metal exchange and the only differences with regard to the native copper(II)-azurin occur in the metal site region. These variations affect principally the axial ligands. Nickel co-ordinates more strongly to the carbonyl oxygen of Gly45 while its distance to the Met121 S4 enlarges up to 0.330 nm. The resulting metal center structure is intermediate between those of the Cu(II) and Zn(II) azurins, and can be described as distorted tetrahedral. However, the existence of contact interaction between Met121 and the nickel ion is still possible as has been shown by paramagnetic 1H-NMR studies in solution.

Azurin↗

Effect of ebrotidine on the density of antral G-cells in the gastric mucosa in the rat.

Two groups of male rats were treated orally for 60 days with ebrotidine and cimetidine, used as reference standard, respectively. The dose used of both drugs was 500 mg/kg. A third group, used as control, received 10 ml/kg of an aqueous agar suspension. After receiving the last dose, the animals were killed by inhalation of CO2 in a sealed chamber and the stomachs were removed for histological preparation. The purpose of this study was to count antral G-cells throughout the gastric mucosa by light microscope. A PAP system-associated antigastrin immunohistochemical method was used for cell identification. Cell density, with respect to their location in the gastric mucosa and the treatments given, was calculated using image analysis techniques. The results showed that ebrotidine did not cause any significant differences in the density of the population of these cells compared with the control group, while cimetidine induced a significant proliferation of antral G-cells.

Animals↗

Occupational allergic contact dermatitis in construction workers.

We report the patch test results of 449 construction workers who came as patients to the Occupational Dermatology Service of the Instituto Nacional de Medicina y Seguridad del Trabajo in Madrid between 1989 and 1993. 90.8% of them were patch tested, because they had cutaneous lesions or a clinical history suggestive of occupational dermatitis. 65.5% (268) of those patch tested showed one or more reactions connected with their work. Chromate at 42.1% was the main allergen, followed by cobalt, 20.5%, nickel, 10%, and epoxy resin, 7.5%. 25.9% (106) of patients showed sensitization to rubber components, the majority at 23.7% to thiuram mix, with TETD being the main allergen.

Adolescent↗

Localization and structural characterization of an oligosaccharide O-linked to bovine PDC-109. Quantitation of the glycoprotein in seminal plasma and on the surface of ejaculated and capacitated spermatozoa.

PDC-109 (13 kDa) is the most abundant component, and the major heparin-binding protein, of bovine (Bos taurus) seminal plasma. Here, we show that PDC-109 contains a single O-linked oligosaccharide (NeuNAc alpha(2-6)-Gal beta(1-3)-GalNAc-) attached to Thr11. Immunoquantitation of PDC-109 indicates that its concentration in seminal plasma is 15-20 mg/ml. Though PDC-109 is not present on epididymal sperm, ejaculated spermatozoa on average are coated with (9.5 +/- 0.3) x 10(6) molecules of PDC-109/cell. This value remained constant in swim-up sperm and decreased to (7.7 +/- 0.4) x 10(6)/spermatozoon after incubation for 24 h in capacitation medium at 39 degrees C. These data substantiate the hypothesis that PDC-109 may be one of the seminal plasma components that enhance the fertilizing capacity of bull spermatozoa upon interaction with heparin-like glycosaminoglycans present in the female genital tract.

Amino Acid Sequence↗

Crystallization and preliminary X-ray diffraction analysis of a type I beta-glucosidase encoded by the bgIA gene of Bacillus polymyxa.

The enzyme encoded by the bgIA gene of Bacillus polymyxa, a type I beta-glucosidase belonging to family I of glycosyl hydrolases, has been purified to homogeneity from an Escherichia coli culture which overexpressed the gene, and crystallized. The crystals, which diffract to 3.0 A resolution, belong to the orthorhombic space group C222(1). The cell dimensions are a = 155.4 A, b = 209.4 A, c = 209.7 A.

Bacillus↗

Crystal structure analysis and refinement at 2.15 A resolution of amicyanin, a type I blue copper protein, from Thiobacillus versutus.

The crystal structure of the type I blue copper protein amicyanin from Thiobacillus versutus has been determined by Patterson search techniques on the basis of the molecular model of amicyanin from Paracoccus denitrificans, and refined by energy-restrained least-squares methods. Amicyanin crystallizes in the trigonal space group P3(2) with unit cell dimensions of a = b = 87.40 A, c = 38.20 A. The asymmetric unit is composed of three independent molecules centred on the crystallographic 3(2) axes. The final R-value is 17.4% for 15,984 reflections to a resolution of 2.15 A. The polypeptide fold in amicyanin is based on the beta-sandwich structure commonly found in blue copper proteins. Nine beta strands are folded into two twisted beta-sheets that pack together with a filling of non-polar residues between them. The geometry of the copper site is similar to that of plastocyanin. There are four ligands, arranged approximately as a distorted tetrahedron, to the copper atom: His54, Cys93, His96 and Met99. One of the copper ligands, His96, is exposed to the surface and lies in the centre of a cluster of seven hydrophobic residues.

Amino Acid Sequence↗

Meconium analysis to assess fetal exposure to nicotine by active and passive maternal smoking.

We measured nicotine metabolites (cotinine and trans-3'-hydroxycotinine) in meconium of infants of passive or active smokers as a direct marker of fetal exposure to tobacco smoke. Meconium was collected from 55 infants whose mothers were nonsmokers, passive smokers, or light or heavy active smokers. Nicotine metabolite concentration (NMC) in meconium was analyzed by radioimmunoassay and gas chromatography-mass spectrometry. Radioimmunoassay showed the following mean meconium NMCs (in nanograms per milliliter); nonsmoker, 10.9; passive smoker, 31.6; light active smoker; 34.7, and heavy active smoker, 54.6. Analysis of available samples by gas chromatography-mass spectrometry confirmed the presence of cotinine. Correlation between meconium NMC and the degree of maternal smoking was 0.54 (p < 0.001). Meconium NMCs in infants of passive and active smokers were significantly higher than in those of nonsmokers (p < 0.05). Meconium NMC in passive smokers was not significantly different from that in light active smokers (p > 0.05). Thus exposure of the fetus to tobacco smoke is substantial, even by passive maternal smoking. Meconium analysis for nicotine metabolites may be useful for clinical and research purposes.

Cotinine↗

Minoxidil (Mx) as a prophylaxis of doxorubicin--induced alopecia.

BACKGROUND: Minoxidil (Mx) is known to induce hair growth in men with male-pattern baldness. Based on this potential, the effectiveness of Mx 2% topical solution was evaluated in cancer patients (pts) to prevent doxorubicin-induced alopecia. PATIENTS AND METHODS: 48 female pts with different types of solid tumors treated with doxorubicin-based chemotherapy in a dose range of 50-60 mg/m2/cycle were randomly assigned to receive Mx 2% topical solution or placebo. RESULTS: 88% and 92% of pts in both arms showed severe alopecia (p = ns). No adverse effects were observed. CONCLUSION: In this study Mx 2% topical solution was non-toxic but was not effective in the prevention of chemotherapy-induced alopecia.

Adult↗

Carboxy-terminal deletion analysis of the major pneumococcal autolysin.

Autolysins are endogenous enzymes that specifically degrade the covalent bonds of the cell walls and eventually can induce bacterial lysis. One of the best-characterized autolysins, the major pneumococcal LytA amidase, has evolved by the fusion of two domains, the N-terminal catalytic domain and the C-terminal domain responsible for the binding to cell walls. The precise biochemical role played by the six repeat units that form the C-terminal domain of the LytA amidase has been investigated by producing serial deletions. Biochemical analyses of the truncated mutants revealed that the LytA amidase must contain at least four units to efficiently recognize the choline residues of pneumococcal cell walls. The loss of an additional unit dramatically reduces its hydrolytic activity as well as the binding affinity, suggesting that the catalytic efficiency of this enzyme can be considerably improved by keeping the protein attached to the cell wall substrate. Truncated proteins lacking one or two repeat units were more sensitive to the inhibition by free choline than the wild-type enzyme, whereas the N-terminal catalytic domain was insensitive to this inhibition. In addition, the truncated proteins were inhibited by deoxycholate (DOC), and the expression of a LytA amidase lacking the last 11 amino acids in Streptococcus pneumoniae M31, a strain having a deletion in the lytA gene, conferred to the cells an atypical phenotype (Lyt+ DOC-) (cells autolysed at the end of the stationary phase but were not sensitive to lysis induced by DOC), which has been previously observed in some clinical isolates of pneumococci. Our results are in agreement with the existence of several choline-binding sites and suggest that the stepwise acquisition of the repeat units and the tail could be considered an evolutionary advantage for the enzyme, since the presence of these motifs increases its hydrolytic activity.

Base Sequence↗

Vinorelbine as first-line chemotherapy for metastatic breast carcinoma.

PURPOSE: A phase II trial was performed to evaluate the efficacy and toxicity of vinorelbine (VNB) as first-line chemotherapy for metastatic breast carcinoma. PATIENTS AND METHODS: Between August 1991 and February 1993, 45 patients with metastatic breast cancer were entered onto the study. Therapy consisted of VNB 30 mg/m2 diluted in 500 mL of normal saline administered as a 1-hour intravenous infusion. Injections were repeated weekly until evidence of progressive disease (PD) or severe toxicity developed. RESULTS: One patient was considered not assessable for response. An objective response (OR) was observed in 18 of 44 patients (41%; 95% confidence interval, 26% to 56%). Three patients (7%) had a complete response (CR) and 15 (34%) had a partial response (PR). The median time to treatment failure for the entire group was 6 months (range, 1 to 15), and the median duration of response was 9 months (range, 1 to 15). The median survival duration has not been reached yet. There were no treatment-related deaths. The dose-limiting toxicity was myelosuppression. Leukopenia occurred in 35 patients (78%) and was grade 3 or 4 in 16 (36%). Phlebitis was observed in 19 of 29 patients (66%) who did not have central implantable venous systems. Fifteen patients (33%) developed peripheral neurotoxicity. Myalgia occurred in 20 patients (44%). CONCLUSION: VNB is an active drug against metastatic breast cancer with moderate toxicity, which justifies further evaluation in association with other agents.

Adult↗

Lytic action of cloned pneumococcal phage lysis genes in Streptococcus pneumoniae.

The genes hbl3, cpl1 and cpl7 coding for the pneumococcal phage lytic enzymes HBL3, CPL1 and CPL7, respectively, have been cloned into shuttle plasmids that can replicate in Streptococcus pneumoniae and Escherichia coli. All these genes were expressed in E. coli under the control of either the lytP promoter of the lytA gene, which codes for the major pneumococcal autolysin, or the promoter of the tetracycline-resistance gene (tetP). In contrast, cpl1 and cpl7 genes that code for lysozymes were expressed in pneumococcus only under the control of tetP, whereas the hbl3 gene that codes for an amidase can be expressed using either promoter. The phage lysozymes or amidase expressed in S. pneumoniae M31, a mutant deleted in the lytA gene coding for short chains, were placed under physiological control since these transformed bacteria grew as normal 'diplo' cells during the exponential phase and underwent autolysis only after long incubation at 37 degrees C. The lysis genes appear to be expressed constitutively in the transformed pneumococci, since sharply defined lysis of these cultures could be induced prematurely during the exponential phase of growth by addition of sodium deoxycholate.

Amidohydrolases↗