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Biomedical subjects

M Rojas

Publications and source records attributed to M Rojas.

At least 91 records · Page 5Linked to original sources
PubMed1996

Barriers to follow-up of abnormal screening mammograms among low-income minority women. Cancer Control Center of Harlem.

OBJECTIVE: To describe factors related to compliance diagnostic follow-up among minority women of low socioeconomic status with abnormal screening mammograms. METHODS: A retrospective cross-sectional survey using a structured telephone interview. Three cancer screening clinics at an urban inner-city public hospital. All women with abnormal screening mammograms between September 1990 and January 1992 were eligible; women were interviewed in August 1992. Abnormal mammograms were those requiring specific, non-routine clinical follow-up; non-compliance was defined as delayed follow-up (four to six months after the date of the mammogram), or no follow-up at the time of interview (more than 6 months after abnormal). RESULTS: Sixty-two of 442 screened women had abnormal results; the overall rate of non-compliance with follow-up was 50%. Among the 42 (68%) women who agreed to be interviewed, non-compliers were less likely to state that they had been told to receive follow-up than compliers (65% versus 100%; p = 0.008). Non-compliant women were less likely to have suspicious mammography interpretations (p = 0.05), and more likely to report barriers to follow-up, such as cost of lost wages and medical care, system barriers, or fears, than compliant women (61.9% versus 9%, p = 0.01). There were no differences between the two groups for age, education, insurance, source of care, family history, knowledge or attitudes. CONCLUSIONS: These preliminary results suggest that follow-up of low income, minority women with abnormal screening mammograms could be enhanced by improved communication of results. Future studies should extend these findings with larger samples and in other settings and populations.

Adolescent↗
PubMed1996

Evidence of anti-benzo[a]pyrene diolepoxide-DNA adduct formation in human colon mucosa.

As risk factors for colorectal cancer include consumption of foods potentially contaminated with polycyclic aromatic hydrocarbons (PAHs), the level of (+)-r-7,t-8-dihydroxy-t-9,10-oxy-7,8,9,10-tetrahydrobenzo[a]pyrene [(+)-anti-BPDE] bound to DNA of human colon mucosa samples was quantified by a sensitive and specific HPLC/fluorescence method (Alexandrov et al., Cancer Res. 51, 6248-6253, 1992). (+)-anti-BPDE-DNA adducts were detected in four out of seven colon mucosa samples but not in any of 11 human pancreas samples from smokers and non-smokers. Adduct levels in human colon varied between 0.2 and 1.0 (+)-anti-BPDE-DNA adducts/10(8) nucleotides. Our results provide evidence that: (i) the DNA in human colon cells can be damaged by benzo[a]pyrene, possibly derived from diet and/or tobacco smoke; (ii) DNA adduct formation in human colon epithelium proceeds via the diol epoxide pathway; (iii) benzo[a]pyrene and other PAHs could play a role in the etiology of human colorectal cancer.

7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide↗
PubMed1996

Colonization by lactobacilli of piglet small intestinal mucus.

The colonization potential of lactobacilli was investigated using small intestinal mucus extracts from 35-d-old pigs. Mucus-secreting tissue from the small intestine of piglets was gently rinsed to remove contents and then shaken in buffer to release mucus from the surface. Numbers of lactobacilli in different portions of the small intestine of 35-d-old pigs were enumerated. Also, mucus isolated from the small intestine of pigs was investigated for its capacity to support the growth of lactobacilli. Results indicated that Lactobacillus spp. inhabit the mucus layer of the small intestine and can grow and adhere to ileal mucus. From adhesion studies of Lactobacillus fermentum 104R to mucus analysed by Scatchard plot, it is suggested that an associating system showing positive cooperativity is involved. Proteinaceous compounds(s) involved in the adhesion to mucus were detected in the spent culture fluid from the growth of strain 104R. Studies are continuing in order to identify and characterize the adhesion-promoting protein(s). From the data, it is proposed that lactobacilli colonize the mucus layer of the small intestine of pigs.

Animals↗
PubMed1996

Abnormal expression of galactosyl(alpha 1-->3) galactose epitopes in squamous cells of the uterine cervix infected by human papillomavirus.

This study describes the presence of alpha-galactosyl epitopes on 12 cervical biopsy samples with features of human papillomavirus infection (HPV) and different stages of cervical intraepithelial neoplasia. An avidin-biotin-peroxidase assay with a monoclonal antibody recognizing gal(alpha 1-->3)gal residues was strongly positive in 5 of 12 cases. None of the controls stained (p = 0.02). Immunostaining was intense in the areas with the highest viral load (koilocytes and keratinocytes) and absent in malignant foci. Immunostaining was also absent in normal exo- and endocervical epithelium of 12 controls with no features of HPV infection. A faint background staining in cases and controls was evident, but similar. These initial findings suggest that alpha-galactosyl epitopes are expressed in cervical squamous cells infected with HPV, turning them vulnerable to lysis by natural anti-alpha-galactosyl antibodies.

Adolescent↗
PubMed1996

Radical differences in functions of closely related members of the human carcinoembryonic antigen gene family.

The immunoglobulin superfamily represents an ancient, highly diversified group of cell surface and extracellular molecules responsible for a wide range of molecular and cellular recognition functions. The human carcinoembryonic antigen (CEA) subfamily of the immunoglobulin superfamily presents evidence of continuing diversification of the immunoglobulin family, in that some of its members, including CEA itself and nonspecific cross-reacting antigen (NCA), are expressed only in primates and not in rodents. These "new" members are glycophosphatidylinositol linked to the external cell membrane and are up-regulated in cancer, unlike members present in both rodents and primates, i.e., biliary glycoprotein (BGP), which are transmembrane linked and down-regulated in cancer. CEA, NCA, and BGP have all been shown to function in vitro as intercellular adhesion molecules. We show here that the properties of adhesion are radically different, in that BGP-mediated adhesion is reversibly Ca2+ and Mg2+ dependent, temperature dependent, and ATP inhibitable, whereas CEA- and NCA-mediated adhesion is the opposite in all aspects. Also, the novel double-reciprocal, antiparallel binding observed for CEA-CEA interactions is not seen for BGP. Finally, the myogenic differentiation block demonstrated for the ectopic expression of CEA in myoblasts was also observed for NCA but not for BGP, which is consistent with the changes in expression seen in cancer. The appearance of new CEA family members with such different properties is discussed in the context of evolution and cancer.

Adenosine Triphosphate↗
PubMed1995

Stimulation of a memory B cell response does not require primed helper T cells.

The use of universally immunogenic T cell epitopes, such as those identified in tetanus toxin or malaria circumsporozoite protein, could represent a major improvement in the development of synthetic vaccines. However, one limitation of this approach is the lack of T cell cross-reactivity between the vaccine and the pathogen. To determine whether the memory B cell response elicited by immunization with a synthetic peptide containing a B cell epitope linked to a T cell epitope can be restimulated by the same B cell epitope linked to different T cell epitope(s), we used a synthetic peptide which contains non-overlapping B and T cell determinants from hepatitis B surface antigen (HBsAg) of hepatitis B virus (HBV). The results of this study clearly show that primed T cells can increase the antibody response against a B cell epitope linked to the priming T cell determinant. However, the antibody response obtained was weaker than that obtained after two injections of the peptide containing both B and T cell epitopes, showing the important role played by memory B cells in secondary antibody responses. Moreover, a strong antibody response against the B cell epitope was elicited by boosting mice with the B cell epitope linked to a heterologous carrier, thus demonstrating that a strong B cell memory response can be revealed in the absence of primed T cells. These results therefore provide new important information for the design of synthetic or recombinant vaccines.

Animals↗
PubMed1995

Anti-benzo[a]pyrene diolepoxide--DNA adduct levels in peripheral mononuclear cells from coke oven workers and the enhancing effect of smoking.

The level of (+/-)-r-7,t-8-dihydroxy-t-9,10-oxy-7,8,9,10-tetrahydrobenzo[a]pyrene (anti-BPDE) bound to DNA of lymphocytes plus monocytes in 39 coke oven workers exposed to polycyclic aromatic hydrocarbons (PAH) and 39 non-exposed persons (controls) were investigated, each of the groups consisting of smokers and non-smokers. The adduct level was measured by an improved HPLC/fluorescence method (Rojas, M., Alexandrov, K., van Schooten, F. J., Hillebrand, M., Kriek, E. and Bartsch, H., Carcinogenesis, 15, 557-560, 1994) through the release of the corresponding benzo[a]pyrene (B[a]P) tetrols. The anti-BPDE-DNA adduct was detected in 51% of coke oven workers exposed to PAH and in 18% of the non-exposed (control) subjects. The mean level of anti-BPDE-DNA adducts/10(8) nucleotides in coke oven workers (15.7 +/- 37.8) was approximately 8 times higher than in non-exposed subjects (2.0 +/- 8.7). The interindividual variation of adduct levels was approximately 100-fold in coke oven workers and approximately 50-fold in controls respectively. Smokers in the exposed group had 3.5 times more DNA adducts than non-smokers. With the exception of one non-smoker with very high adduct levels (52.8 adducts/10(8)), the control subjects showed the presence of barely detectable adducts in only 16% of the samples examined. The increased in vivo formation in some smokers and high variability of anti-BPDE-DNA adducts in coke oven workers suggests variations in genetically controlled activation/inactivation reactions of PAH metabolism.

7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide↗
PubMed1995

Metabolic polymorphism affecting DNA binding and excretion of carcinogens in humans.

A case-control study on lung cancer patients demonstrated the pronounced effect of tobacco smoke on pulmonary carcinogen metabolism and suggested the existence of a metabolic phenotype at higher risk for tobacco-associated lung cancer. Lung cancer patients who were recent smokers showed in their lungs (i) significantly induced CYP1A1-related enzyme activity vs smoking non-lung cancer patients; (ii) increased benzo(a)pyrene (BP) tetrol formation from BP 7,8-diol by lung microsomes; and (iii) high levels of cytochrome P4501a1 by immunohistochemical staining. Levels of bulky aromatic DNA adducts (by 32P-postlabelling) and of BP-diol-epoxide (BPDE) adducts (by HPC/fluorometry) were quantified in lung parenchyma. Aryl hydrocarbon hydroxylase activity and the level of BPDE-DNA adducts (r = 0.91; p < 0.001) and to a lesser degree bulky DNA adducts were correlated. Thus pulmonary CYP1A1 expression (inducibility) controls in part polycyclic aromatic hydrocarbon-DNA adduct formation in tobacco smokers and, therefore, appears to be associated with lung cancer risk. High risk subjects for lung cancer among smokers may be identifiable through genotyping for polymorphic drug metabolizing enzymes in combination with molecular dosimetry of carcinogen-DNA adducts and mutation analysis in target (surrogate) cells. Such studies in a Finnish cohort of lung cancer patients and controls are in progress. Interim results of the effect of metabolic polymorphism on the level of PAH-DNA adducts and on the excretion of mutagens in urine are summarized.

Biotransformation↗
PubMed1995

Opposite functions for two classes of genes of the human carcinoembryonic antigen family.

The human carcinoembryonic antigen (CEA) family can be divided into two subgroups according to the means of anchorage of member glycoproteins to the cell membrane: glycophosphatidyl inositol (GPI) linkage and transmembrane linkage. The GPI-linked members tend to be up-regulated in human tumours, whereas the transmembrane-linked members tend to be down-regulated. Thus the question as to whether the GPI members could be formally considered to function as oncogenes and the transmembrane members as tumour suppressors deserves consideration. Members of both subgroups function in vitro as intercellular adhesion molecules, but the characteristics of this adhesion, including temperature and divalent-cation dependence, differ markedly between the groups. Even the mechanism of intermolecular adhesion appears to differ fundamentally in that GPI-linked CEA-CEA binding involves a double reciprocal bonding between two domains, whereas transmembrane-linked biliary glycoprotein (BGP)-BGP binding requires only one domain. Finally, the ectopic expression of CEA in myoblasts can block myogenic differentiation leaving the cells with the ability to divide, while expression of BGP does not affect or may even accelerate myogenic differentiation. These differences in phenotypic effects in vitro thus mirror the differences observed in expression in tumours and support the view that the GPI and transmembrane groups have opposite effects on cells in relation to the malignant phenotype.

Antigens, CD↗
PubMed1995

Cancer biomarkers in human atherosclerotic lesions: detection of DNA adducts.

Since somatic mutations are suspected to contribute to the pathogenesis not only of cancer but also of atherosclerotic plaques, we measured DNA adducts in the smooth muscle layer of atherosclerotic lesions in abdominal aorta specimens taken at surgery from seven patients. DNA adducts were evaluated in three laboratories by means of different molecular dosimetry methods, including: (a) HPLC/fluorescence, which specifically identifies the DNA adducts of the anti-benzo(a)pyrene (BPDE) isomer; (b) two- and three-dimensional synchronous fluorescence spectrophotometries, which detect DNA adducts of BPDE and other reactive metabolites of polycyclic aromatic hydrocarbons; and (c) 32P postlabeling, which reveals the presence of a variety of types of DNA adducts. The HPLC/fluorescence method provided for the first time evidence for the presence of BPDE-DNA specific adducts in three of six specimens tested. Synchronous fluorescence spectrophotometry displayed broad areas of fluorescence in all seven specimens, thereby suggesting the occurrence not only of BDPE-DNA but also of other DNA adducts with similar fluorescence characteristics. All specimens were also positive at 32P postlabeling, which revealed multiple spots detectable following enrichment either with nuclease P1 or butanol, indicative of the presence of different aromatic DNA adducts. Thus, the data obtained by applying typical cancer biomarkers provide further support to the hypothesis that there may be similarities between the carcinogenic and the atherogenic processes, and in particular that genetic alterations caused by DNA-binding agents in the artery wall may be detected in atherosclerotic lesions.

Aged↗
PubMed1994

Comparison of the effects of acetazolamide and aminophylline on apnea incidence and on ventilatory response to CO2 in preterm infants.

Acetazolamide (ACTZ) reduces sleep apnea in adults exposed to high altitude and augments the ventilatory response to CO2. In order to determine the effect of ACTZ on the ventilatory response to CO2 and the incidence of apnea in preterm infants, 7 infants (BW, 1070 +/- 191 g; postnatal age, 9 +/- 7 days) were randomized to receive ACTZ (5 mg/kg/dose Q6h for 36 hr) and 7 infants (BW, 1092 +/- 292 g; post-natal age, 5 +/- 2 days) received aminophylline (AMINO; 8 mg/kg bolus then 2.5 mg/kg Q12h for 36 hr). Minute ventilation (VE), end-tidal CO2 (PETCO2), ventilatory response to CO2, number of apneic episodes (> or = 15 sec duration), and arterial blood gases were measured before and 24-36 hr after starting therapy. In the AMINO group there was a significant decrease in apnea frequency from 6 +/- 1 to 2 +/- 2 episodes over an 8 hr epoch (P < 0.05), while no significant change was observed in the ACTZ group. The end-tidal CO2 decreased significantly from 44 +/- 7 to 38 +/- 6 mmHg in the AMINO group and from 47 +/- 5 to 36 +/- 5 mmHg in the ACTZ (P < 0.05), which lead to a shift to the left of the CO2-response curve in both groups. The slope of the CO2 response curve did not change significantly in the AMINO group and decreased in the ACTZ group. There was a significant decrease of pH from 7.43 to 7.26 in the ACTZ group, whereas in the AMINO group pH increased from 7.38 to 7.44.(ABSTRACT TRUNCATED AT 250 WORDS)

Acetazolamide↗
PubMed1994

Validation of a new fluorometric assay for benzo[a]pyrene diolepoxide-DNA adducts in human white blood cells: comparisons with 32P-postlabeling and ELISA.

A new fluorometric assay was validated for quantification of benzo[a]pyrene diolepoxide (BPDE)-DNA adducts in white blood cells (WBC) from humans exposed to polycyclic aromatic hydrocarbons (PAH). This assay has a detection limit of 2 pg of r-7,c-10,t-8,t-9-tetrahydroxy-7,8,9,10-tetrahydrobenzo[a]pyrene derived from acid hydrolysis of BPDE-DNA, and can measure 1 BPDE adduct per 10(8) unmodified nucleotides. The quantity of WBC DNA required depends on the modification level and varies between 5 and 500 micrograms. The assay was applied to seven WBC DNA samples from lung cancer patients, six of whom were heavy smokers, and to three WBC DNA samples from healthy subjects employed in an aluminum production plant. High levels of BPDE-DNA adducts, ranging from 62 to 533 adducts/10(8) nucleotides were found in six out of seven DNA samples from the lung cancer patients. In WBC DNA from healthy persons BPDE-DNA adducts were detected only in two non-smokers, but at a much lower level than in lung cancer patients (4-10 adducts/10(8) nucleotides). Using coded WBC DNA samples, BPDE-DNA adduct levels measured by fluorometry of the B[a]P-tetrols, were compared with the results obtained by 32P-postlabeling (nuclease P1 enrichment) and ELISA measurements. A good correlation and proportionality was found between the levels of BPDE-DNA adducts measured by fluorometry and 32P-postlabeling (r = 0.95, P < 0.001, n = 8). The correlation between fluorometry and ELISA was much lower and not significant (r = 0.61, P = 0.1, n = 6). Moreover, the ELISA grossly overestimated BPDE-DNA adduct levels measured by the other two methods. The results demonstrate that the highly sensitive and specific fluorometric assay is suitable for measuring BPDE-DNA adducts in WBC from humans exposed to benzo[a]pyrene.

Benzo(a)pyrene↗
PubMed1994

Upper airway stability and respiratory muscle activity during inspiratory loading in full-term neonates.

To investigate the role of genioglossus and posterior cricoarytenoid (PCA) activity in stabilizing the extrathoracic airway (ETA) of full-term infants during inspiratory flow-resistive loading (IRL), 10 unsedated full-term infants were evaluated in quiet sleep. IRLs were randomly imposed (L2, 125 cmH2O.l-1.s; L3, 250 cmH2O.l-1.s). Ventilation, total respiratory resistance (a correlate of ETA resistance), and moving time averages of PCA, submental activity of the genioglossus (SM), and diaphragm electromyogram were obtained. Results revealed no phasic activity in the SM during baseline breathing or with either IRL. Phasic PCA activity was always observed; burst duration increased with L2 and L3 (P < 0.01) and commenced earlier in relation to the onset of inspiratory airflow with both loads (P < 0.05). PCA activity always preceded that of the diaphragm and invariably outlasted it other than with L3. The upper airway negative pressure changes induced by IRL were insufficient to recruit SM activity; other potential stimuli such as transcutaneous PO2, transcutaneous PCO2, and pulmonary stretch receptor activation (increase in tidal volume) remained unchanged. Ventilation decreased with both loads (L3: P < 0.01), esophageal and mouth pressures increased (P < 0.01), and inspiratory time and inspiratory time divided by total time were both prolonged (P < 0.01). Total respiratory resistance remained unchanged with L2 but increased with L3 (P < 0.01). We concluded that ETA narrowing may be induced in full-term infants during quiet sleep with moderately large-sized IRL and that it is not entirely ameliorated by activation of the SM or PCA or by arousal.

Airway Resistance↗
PubMed1994

[Magnetic resonance in the diagnosis, characterization, and assessment of renal carcinoma extension].

Many authors discussed the reliability of MR imaging in the diagnosis of small tumoral masses (less than 1.5 cm) affecting the kidney, and stressed its low diagnostic power. On the other hand, MR imaging is a useful technique in the study of renal masses, for its capability in the differentiation of adipose tissue (angiomyolipomas), fluid content (cystic lesions), parenchymatous tissues (neoplastic lesions). The distinction between malignant and benign masses is often impossible on the basis of MR except in the cases of invasion of the adjacent structures. MR imaging is, at present, the most accurate method in the staging of neoplastic masses of the kidney.

Humans↗