Molecular targets in the National Cancer Institute drug screen.
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Antineoplastic Agents↗
Biomedical subjects
M Alvarez
Publications and source records attributed to M Alvarez.
Neurosyphilis in HIV-infected patients.
To determine the prevalence and the clinical and serological findings of neurosyphilis in HIV-infected patients, Treponema pallidum hemagglutination (TPHA) tests, CD4+ lymphocyte counts and determination of rapid plasma reagin (RPR) titers were performed in 972 HIV-infected patients over a period of 3.5 years. Patients were scored according to the Centers for Disease Control's classification for HIV infection. Reactive serum syphilis tests and positive cerebrospinal fluid (CSF)-Venereal Disease Research Laboratory (VDRL) tests, with or without clinical symptoms, were used as the criteria for diagnosis of neurosyphilis. The TPHA test was positive in 31 patients, representing 3.1% of all HIV-infected patients included in the study. Of these, 13 were intravenous drug addicts, 14 were homosexuals and 4 were heterosexuals. Diagnosis of syphilis was concurrent with HIV infection in 19 patients, prior to HIV infection in 6 patients and after HIV infection in 6 patients. CSF examinations were performed in 28 of the 31 (90.3%) patients with serologically evident syphilis. Four patients had positive CSF-VDRL tests with pleocytosis (23.5% of untreated syphilis patients in whom CSF was examined), three of whom reported mild headache, which was considered a doubtful manifestation of neurosyphilis. Patients with syphilis diagnosed and treated prior to diagnosis of HIV infection did not have evidence of neurosyphilis. Seven patients had pleocytosis with a negative CSF-VDRL test, without any clinical manifestations of neurosyphilis. There was no significant difference in the mean CD4+ lymphocyte count between patients with and without neurosyphilis (p = 0.5). RPR titers in neurosyphilis patients were greater than those in patients previously treated for syphilis and in those with pleocytosis only (p = 0.046 and 0.036, respectively). All neurosyphilis patients had an RPR titer > 1:8. After therapy, neurosyphilis patients had negative CSF-VDRL tests with a lower level of pleocytosis. The prevalence of neurosyphilis was 0.4% in HIV-infected patients and 23.5% in HIV-infected patients with untreated syphilis. This high prevalence of neurosyphilis warrants CSF examination in HIV-infected patients with syphilis, regardless of the stage of syphilis.
Adult↗
Fetal and maternal plasma endothelin levels during the second half of pregnancy.
OBJECTIVE: Our objective was to evaluate maternal and fetal endothelin concentrations in uncomplicated pregnancies across the second half of pregnancy. STUDY DESIGN: Paired (n = 64) maternal venous and fetal umbilical venous or arterial samples were obtained during cordocentesis. In addition, eight neonatal umbilical vein samples were obtained immediately after delivery. Samples were assessed for hematocrit and pH, and concentrations of endothelin were measured by sensitive enzyme immunoassay. RESULTS: No significant correlation was found between either fetal or maternal endothelin levels and gestational age (r = 0.01, p = 0.91 and r = 0.07, p = 0.5, respectively). Fetal plasma endothelin concentrations were significantly lower than neonatal umbilical vein endothelin levels [median 2.5 pg/ml (range 0.9 to 5.73) vs 15.77 pg/ml (8.12 to 19.58), respectively; p < 0.0001] but significantly higher than maternal levels [1.3 pg/ml (0.8 to 3.25); p < 0.0001]. In addition, endothelin values were higher in the umbilical artery than in the umbilical vein, but this difference failed to achieve statistical significance [2.89 pg/ml (1.61 to 5.73) vs 2.29 pg/ml (0.9 to 5.70), respectively; p = 0.06]. No correlation was noted between fetal and maternal endothelin levels (r = 0.12, p = 0.36). CONCLUSION: Fetal endothelin levels were significantly higher than maternal levels, but neither correlated with gestational age across the second half of pregnancy.
Endothelins↗
Long term effects of ritodrine on blood pressure and heart rate of adolescents exposed during the prenatal stage.
OBJECTIVE: To determine the long term cardiovascular effects in adolescents exposed to ritodrine during prenatal stage. STUDY DESIGN: Twenty-seven ritodrine-exposed subjects and 19 controls, of both sexes, clinically healthy, and born at normal term, were evaluated for systolic blood pressure (SBP), diastolic blood pressure (DBP) and heart rate (HR) each during 48 hours, with a Colin Ambulatory monitor. Data analysis were performed by individual Cosinor method, and non-parametric Mann Whitney's test and Lamotte procedures. RESULTS: Adolescents who were exposed to ritodrine showed losses in the HR rhythm and rising middle pulse values. Although SBP and DBP rhythm remains constant, the increase of maximum and minimum values for SBP as well as a rise of maximal rates of DBP suggest a possible hypertensive effect mediated by beta mimetic exposure. CONCLUSION: This study suggests a hypertensive effect mediated by beta mimetic exposure.
Adolescent↗
An outbreak of diarrhoea associated with atypical rotaviruses in goat kids.
The presence of rotaviruses was investigated in the faeces of 31 goat kids in a dairy herd that experienced an outbreak of severe diarrhoea which caused dehydration, anorexia and prostration in seven (22.6 per cent) of them. All the affected animals were two to three days old. A group A-specific ELISA failed to detect rotaviruses in any of the samples but the characteristics electropherotype of group B rotaviruses was observed by electrophoresis in polyacrylamide gels in six of the animals. A highly significant statistical association between the shedding of rotavirus and the occurrence of diarrhoea was demonstrated. All the rotaviruses were detected in animals three to four days old. Cryptosporidium parvum, Clostridium perfringens and enterotoxigenic Escherichia coli were not detected in the seven diarrhoeic animals.
Animals↗
HLA allele and haplotype frequencies in Algerians. Relatedness to Spaniards and Basques.
The powerful genetic polymorphism of the HLA system has been used to identify individuals and populations. Ethnic groups may be characterized by specific HLA allele frequencies and particular extended HLA haplotypes; also, genetic relationships among these groups may be deduced. In the present study, serology and DNA typing were used to detect HLA-A, -B, -C, -DR, and -DQ alleles in each individual and to calculate characteristic haplotypes in Algerians. These results were compared to those previously obtained in other populations, particularly northern Mediterraneans; genetic distances and their respective dendrograms place Basques and Spaniards closer to Algerians than to other Europeans. Also, characteristic Basque and/or Spanish haplotypes are found in Algerians; i.e., A30-B18-Cw5-DR3-DQ2 and A1-B57-Cw7-DR7-DQ2. This supports the evidence that the Algerian population, mainly its paleo-North African component (Berbers), has a common descent with Basques and Spaniards, probably reflecting a preneolithic relationship between Iberians and paleo-North Africans.
Africa, Northern↗
Prevalence of neutralizing antibodies to 9 rotavirus strains representing 7 G-serotypes in sheep sera.
Neutralizing antibodies to 9 rotavirus strains representing serotypes G1, G3, G5, G6, G8, G9, and G10 were investigated in 212 ovine serum samples from 3 age groups, 1-week-old lambs, 2- to 3-months-old lambs and adult sheep. All sera from 1-week-old lambs had neutralizing antibodies to all 9 rotavirus strains. Both neutralizing antibody titers and prevalences to all 9 strains markedly decreased in the 2- to 3-months-old lamb group and increased again in the adult sheep group. Also, adult sheep sera neutralized a larger number of rotavirus strains than 2- to 3-months-old lamb sera. The highest neutralizing antibody titers and prevalences were found to strains B223 and K923, representing serotype G10, to strain RRV, representing serotype G3, and to strain NCDV, representing serotype G6, indicating that these could be the predominant 3 rotavirus serotypes in Spanish sheep. The rotavirus serotypes infecting sheep observed by us differ from those described for cattle, where G6 is the most prevalent serotype followed by G10, and G3 has been seldom found. Very low prevalences were observed for strains WA and OSU representing serotypes G1 and G5 respectively, suggesting that they probably do not infect sheep and neutralizing antibodies found are derived from heterotypic responses to other serotypes. Intermediate prevalences and titers were found to strains UK (serotype G6), 69M (serotype G8) and WI61 (serotype G9). Neutralizing antibodies distinguished between different strains sharing their VP7 specificity: B223 and K923, a bovine and an ovine serotype G10 strains, and NCDV and UK, two serotype G6 bovine rotavirus strains with different VP4 antigen.
Aging↗
Accuracy of ultrasound estimation of fetal weight in multiple pregnancies.
Our objective was to assess the accuracy of ultrasonographic estimation of fetal weight in twins and triplets as compared to singleton pregnancies. Retrospective analysis was undertaken of ultrasound data of all fetuses who underwent an examination within 1 week of delivery (singletons 1832, twins 518, triplets 51). At birth weights below 2500 g, there was a significant overestimation of fetal weight in twins as compared to singletons, but the accuracy of the estimate was the same, except in twins between 1500 and 2499 g, when the weight was based on abdominal circumference and femur length alone. At birth weights of more than 2500 g, no difference was detected between twins and singletons. At all birth weights below 2500 g, the accuracy of weight estimation in triplets was equal to that in singletons and there were no triplets above this weight. We conclude that ultrasonographic estimation of fetal weight is as accurate in twins and triplets as it is in singletons.
Body Weight↗
Incidence of pregnancy-induced hypertension among gestational diabetics.
Although hypertensive disorders of pregnancy are more likely to occur in pregestational diabetics, the question of whether they occur more frequently in gestational diabetics or certain subsets of gestational diabetics remains unclear. This study compared 197 gestational diabetics with 197 control patients matched on the basis of age, race, parity, and prepregnancy weight. No significant difference was found between the two groups in the incidence of either pregnancy-induced hypertension or preeclampsia. There was, however, a small but significant elevation in mean arterial blood pressure in the third trimester in gestational diabetics compared with control patients (90.1 versus 87.5 mm Hg; p = 0.006). Mean arterial pressures were also higher in diabetic patients on insulin compared with those on diet, and higher in diabetic patients diagnosed early (less than 24 weeks) compared with those diagnosed late (more than 24 weeks) in pregnancy; however, there were larger numbers of chronic hypertensives in these two groups. We conclude that gestational diabetics do not develop pregnancy-induced hypertension more frequently. Small increases in blood pressure late in pregnancy in these patients achieve statistical significance, but their clinical relevance is unclear.
Adult↗
Bacteriuria and colonization of double-pigtail ureteral stents: long-term experience with 237 patients.
We prospectively studied 266 patients with indwelling double-pigtail ureteral stents to determine the incidence of stent colonization and associated bacteriuria. A urine culture was obtained just prior to stent insertion and was repeated at the time of its removal. The stent itself was also cultured. Of the 237 evaluable patients, 71 (29.9%) developed bacteriuria. Of the 237 stents, 161 (67.9%) became colonized with microorganisms. Pseudomonas aeruginosa was the most common pathogen isolated from the urine and the stents. Stents in female patients had a higher rate of colonization than those used in males (74.4% v 66.5%). The longer the duration of stenting, the higher was the rate of colonization (58.6% for stents left for < 1 month v 75.1% for those left for > 3 months). The rate of colonization according to catheter type was as follows: C-flex 55.5%, silicone 62.6%, urethane 100%, and Urosoft 56%. Long-term ureteric stenting is associated with a high rate of bacteriuria and stent colonization. The duration of stenting and the type of stent influence the results. We recommend that patients with double-J ureteral stents who could be at risk from bacteremia be covered by appropriate antibiotics, and the stents should be kept indwelling for the shortest possible time. If a patient with a stent develops symptomatic infection, an antibiotic should be started that covers the Pseudomonas species.
Adolescent↗
Absence of anomalous dispersion features in the inelastic neutron scattering spectra of water at both sides of the melting transition.
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Journal Article↗
Nosocomial outbreak caused by Scedosporium prolificans (inflatum): four fatal cases in leukemic patients.
Four cases of fatal disseminated Scedosporium prolificans (inflatum) infection occurring in neutropenic patients are reported. Because of hospital renovation, the patients were cared for in a temporary hematologic facility. S. prolificans (inflatum) was isolated from blood cultures of these four patients, two of whom underwent full necropsy, and revealed abundant vegetative hyphae and ovoid conida with truncate bases in many organs. In vitro susceptibility testing of fungal strains showed all isolates to be resistant to amphotericin B, flucytosine, miconazole, ketoconazole, fluconazole, and itraconazole, with MICs greater than 16 micrograms/ml. The reported infections, two in each of two rooms, occurred over a period of 1 month, with very similar clinical outcomes. Circumstancial evidence suggested a nosocomial outbreak, but the environmental samples collected from the rooms, corridors, and adjacent areas did not yield S. prolificans (inflatum). Nevertheless, circumstantial evidence suggested a nosocomial outbreak of S. prolificans (inflatum) infection.
Adult↗
Generation of a drug resistance profile by quantitation of mdr-1/P-glycoprotein in the cell lines of the National Cancer Institute Anticancer Drug Screen.
Identifying new chemotherapeutic agents and characterizing mechanisms of resistance may improve cancer treatment. The Anticancer Drug Screen of the National Cancer Institute uses 60 cell lines to identify new agents. Expression of mdr-1/P-glycoprotein was measured by quantitative PCR. Expression was detected in 39 cell lines; the highest levels were in renal and colon carcinomas. Expression was also detected in all melanomas and central nervous system tumors, but in only one ovarian carcinoma and one leukemia cell line. Using a modified version of the COMPARE program, a high correlation was found between expression of mdr-1 and cellular resistance to a large number of compounds. Evidence that these compounds are P-glycoprotein substrates includes: (a) enhancement of cytotoxicity by verapamil; (b) demonstration of cross-resistance in a multidrug-resistant cell line, (c) ability to antagonize P-glycoprotein, increasing vinblastine accumulation by decreasing efflux; and (d) inhibition of photoaffinity labeling by azidopine. Identification of many heretofore unrecognized compounds as substrates indicates that P-glycoprotein has a broader substrate specificity than previously recognized. This study confirms the validity of this novel approach and provides the basis for similar studies examining a diverse group of gene products, including other resistance mechanisms, putative drug targets, and genes involved in the cell cycle and apoptosis.
ATP Binding Cassette Transporter, Subfamily B, Mem↗
Normal p53 status and function despite the development of drug resistance in human breast cancer cells.
Loss of or mutations in p53 protein have been shown to decrease both radio- and chemosensitivity. The present study assessed the p53 gene status, ability to arrest in G1 of the cell cycle, the functionality of the p53 transduction pathway, and apoptosis following treatment with radiation in a series of drug-resistant human breast cancer cells to determine whether p53 alterations occur during the development of drug resistance. We used 13 sublines derived from MCF-7, ZR75B, and T47D cells, which were resistant to doxorubicin, paclitaxel, vinblastine, cisplatin, etoposide, and amsacrine. Eleven of 12 drug-resistant sublines retained the parental p53 gene status, as determined by sequence analysis and functional yeast assay; only one subline was found to have acquired a mutation in the p53 gene. The MCF-7 TH subline was found to both acquire mutated p53 and to have major changes in p53 protein expression and function. In 12 other drug-resistant sublines, the G1 checkpoint was conserved or only slightly impaired. A normal accumulation of p53, p21Cip1/Waf1, and Mdm2 proteins and hypophosphorylation of Rb protein occurred in response to radiation with only small differences noted in the kinetics of p53 and p21Cip1/Waf1 induction. Increased susceptibility to apoptosis was found in the ZR75B drug-resistant sublines, whereas no evidence for apoptosis was observed in the ZR75B, MCF-7, and T47D parentals and the MCF-7 and T47D drug-resistant sublines. This effect could not be explained by alterations in bcl-2 or bax expression. Our results demonstrate that alterations in: (a) p53 gene status; (b) ability to arrest in G1; (c) induction of p53 protein and p53-dependent genes; and (d) decreased activation of apoptosis is not a requirement for the onset of drug resistance. The function of p53 appears to be dissociated from drug resistance in our model system.
Apoptosis↗
Bone marrow cryptococcosis in an AIDS hemophiliac (morphological aspect in routine hematology)
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Acquired Immunodeficiency Syndrome↗
[Cuban epidemic neuropathy. II. The antigenic characteristics of the viral isolates].
With the aim of characterizing antigenically isolations producing mild cytopathogenic effect obtained from the cerebrospinal fluid of patients presenting with epidemic neuropathy, neutralization tests and western blot analysis were performed using hyperimmune sera of patients and hyperimmune sera of rabbits. It was confirmed that isolations with mild cutopathogenic effect studied have the same antigenic characteristics and that they are related to Coxsackie A9 and B4 viruses. Structural proteins were not detected in the strains with mild cytopathogenic effects, only antigens having a high molecular weight which were considered as precursor proteins for viral replication were confirmed.
Animals↗
[Cuban epidemic neuropathy. IV. The antigenic relationship of the viral isolates to the structures of the central nervous system. A possible etiopathogenic mechanism?].
Results which allow to state the existence of antigenic relationships between viruses isolated from the cerebrospinal fluid of patients presenting with epidemic neuropathy and structures of the human central nervous system are reported. These evidences were obtained by 2 different and independent ways: 1) by the double diffusion method in agarose, immunoblot analysis, and immunohistochemical analysis it was confirmed that antibodies induced by isolated viruses react with antigens of the central and peripheral nervous system, 2) serum obtained by the immunization of a rabbit with human brain extract neutralizes the same viruses as those neutralized by hyperimmune sera obtained by isolations. The possible role of viruses as mediators of an autoimmune process in the pathogenesis of the disease is discussed.
Animals↗
[The physicochemical characterization of the agents isolated during the outbreak of epidemic neuropathy in Cuba. I].
This paper reports on the physical and chemical characteristics of agents isolated from serum samples of patients presenting with epidemic neuropathy. The behaviour of isolated enteroviruses was as described for such viruses. Mild cytopathogenic effects-producing agents behaved in a variable form regarding sensitivity to chloroform; on the other hand they were neither sensitive to phosphonoacetic acid (PAA) nor to guanidine hydrochloride (GHC1) and grew in cells previously treated with bromodeoxyuridine (BDUR). These results suggest the presence of agents resembling enteroviruses and enveloped viruses. Further studies for the characterization of such agents need to be performed.
Acyclovir↗