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[Validation of a method of blood pressure measurement for a study of hypertension in a black African population].

Hypertension is a major public health issue in Black Africa. It is also an important factor of cardiovascular risk. To determine the prevalence of hypertension in a large population in Burkina Faso, it is more practicable to use an automatic device for the measurement of BP. Before the start of the study, we tested the reliability of an automatic technique for the measurement of BP in sitting position according to the reference technique. The manometer of reference was a manual, aneroid, and calibrated manometer. The automatic manometer was oscillometric, validated according to the protocol of the British Hypertension Society. The study was held on voluntary healthy persons, or patients hospitalized in the cardiology department of the national university hospital of Ouagadougou (high blood pressure, valvulopathy, cardiac insufficiency). BP measurement was made in a sequential way, with the manual manometer, and with the automatic manometer, by a single observer. Measurement by the manual manometer was based on the auscultation of Korotkoff's murmurs. Systolic blood pressure (SBP) corresponded to phase I, and diastolic blood pressure (DBP) to phase V. Measurement by the automatic manometer was made by reading the BP shown on the device screen. The 10.0 version of the SPSS software was used for data analysis. Statistical tests were concluded with a risk of 0.05. Confidence intervals included 95% of the subjects. The percentage comparison of hypertensive subjects observed in the population by both methods was made with a paired khi2 test. We used Pearson's correlation to quantify the relation between the measures taken using the two methods. In order to quantify the degree of agreement of the two methods, we used the intraclass correlation coefficient (ICC) for quantitative BP measurements, and Kappa's coefficient for qualitative measurements (determination of normotensive or hypertensive subjects). The study was held on 50 black African subjects, with the average age of 38.54 4.83 (18 years-77 years); 55% were male subjects. With the reference method in the sleeping position, the mean SBP and DBP values were respectively 122.60 8.52 and 70.36 5.22 mmHg. The minimal and maximal SBP observed were 80 and 240 mmHg respectively, and the DBP, 30 and 130 mmHg respectively. With the automatic method in the sitting position, the mean values SBP and DBP was 119.88+7.50 and 74.80 4.36 mmHg. SBP minimal was of 75, the maximal of 210 mmHg, and the minimal and maximal DBP was respectively 51 and 121 mmHg. Pearson's correlation coefficients for SBP and DBP between the two methods were statistically different from zero; 0.92 (p<0.001), and of 0.82 (p<0.001) respectively. The ICC was 0.91 for SBP and 0.78 for DBP. Kappa's coefficient was calculated to estimate agreement for the determination of normotensive or hypertensive subjects; among the 50 subjects, 36 were classified normotensive by the two methods, and eight, hypertensive. The differences of classification concerned five hypertensive subjects and one normotensive subject, according to the referenced method. Kappa's coefficient was 0.65. The distribution of the subjects in hypertensive and normotensive did not differ significantly in the two methods (p=0.22). The agreement between the two methods was found very good for the measurement of SBP and DBP; it was good for the determination of an hypertensive or normotensive subject. It is important to test the reliability of a technique of BP measurement before the evaluation of hypertension prevalence in a large population. The reliability of the technique ensures a good estimation of the disease prevalence. It is also important to use statistically adapted tests, to avoid any wrong conclusion as to the reliability of the technique.

Adolescent↗
PubMed2003

[Assessment of high blood pressure in 24-hours Holter records in hypertensive pregnant patients].

DESIGN: The aim of our study was to established possible a correlation between Holter blood pressure measurements and BP levels measured incidentally by the medical personnel. We also tried to evaluate usefulness of ABPM in monitoring intensification of the hypertension. MATERIALS AND METHODS: The research was performed on 57 pregnant women where pregnancies were complicated by hypertension (PIH or chronic hypertension). All patients were divided into four groups conforming with JNC VI protocol according to BP level measured in the time of the admission to hospital. Therefore circadian blood pressure profile was done by using ABPM SpaceLab device. After that BP load indicator was estimated in each group to assess intensification of the disease. However, we compared those results between groups by using t-Student test (p < 0.05). RESULTS: We qualified 22 patients to group 0 with SBP = 129,45 + 6.31 mmHg and DBP = 80.59 + 5.45 mmHg in the time of admission. There were 21 pregnant women with mild hypertension (group I SBP = 144,14 + 7.32 mmHg, DBP = 93.14 + 4.52 mmHg), moderate (group II, N = 8 with SBP = 153,88 + 5.54 mmHg and DBP = 101,34 + 3.78 mmHg) and severe hypertension (group III, N = 6 with SBP = 175,83 + 33.23 mmHg, DBP = 121 + 11.92 mmHg). BP load value measured in group 0 was 14.57 + 21.3% of SBP and 13.92 + 22.99% of DBP inappropriate results. In group I was found SBP 24.91 + 30.3%, DBP 23.12 + 26.01%, group II SBP 38.11 + 33.66%, DBP 26.31 + 22.75% and in group III SBP 59.3 + 38.76% and DBP 61.37 + 35.72%, respectively. CONCLUSIONS: Only between the group with normal blood pressure and the group with severe hypertension the obtained results were statistically significant (p < 0.05). We've also found a statistical correlation between BP values measured in the time of admission to the hospital and BP load indices in each group.

Adult↗
PubMed2003

[Study on biodegraded characteristics of endocrine disruptor di-n-butyl phthalate].

The biodegraded Characteristics of di-n-butyl Phthalate (DBP), endocrine disruptor were studied. The activated sludge was acclimated using DBP as the only carbon in the culture medium. DBP concentration was increased progressively from 0.05 g/L to 0.5 g/L. The degradation tests were carried out on the constant temperature table using the acclimated sludge at different PH, temperature, DBP concentration and hydraulic residence time. The results showed that DBP could be rapidly degraded-nearly 90% in 48 hours. The appropriate condition for DBP degradation was pH 6.0-8.0, temperature 25 degrees C-35 degrees C, DBP concentration no more than 300 mg/L, and hydraulic residence time 12 h-24 h. The form of biodegradation of DBP can be described as the first-order reaction model.

Biodegradation, Environmental↗
PubMed2004

[Effects of di-butyl phthalate on sperm motility and oxidative stress in rats].

OBJECTIVE: To evaluate the effects of di-butyl phthalate(DBP) on the sperm motility and oxidative stress in rats. METHODS: Healthy 6-week-old male Sprague Dawlay rats were randomly divided into 4 groups with 8 in each group. DBP dissolved in peanut oil was administered by gavage at dosage of 0, 250, 500, 1,000 mg/(kg.d). After 4-week DBP exposure, the animals were killed and the organs were selected and weighed. The sperm VCL, VSL, VAP, BCF, ALH, LIN, MAD and STR in the cauda epididymis were assessed by computer assisted sperm analysis (CASA), and the activities of superoxide dismutase (SOD) and the contents of malondialdehyde (MDA) in serum and testis homogenate were measured simultaneously. The increase of body weight per day and the organ body weight ratio changes of the liver, testes and epididymides were also observed. RESULTS: The liver organ body weight ratios of the treated groups were higher than those of the control (P < 0.01), while the testis organ body weight ratios were lower at dosage of 1,000 mg/(kg.d) DBP. Compared with the control group, the parameters of rat sperm VCL and ALH declined significantly at dosage of 1,000 mg/(kg.d) DBP. In addition, DBP showed inhibiting effect on SOD activities in the testis, and it was significant in the highest exposure group compared with the control (P < 0.05). However, there were no differences in serum SOD activities between the treated groups and the control. CONCLUSION: DBP exposure may affect the sperm motility and the anti-oxidative systems. The testis is a vital target organ influenced by DBP.

Animals↗
PubMed2004

Relationship between serum gamma-glutamyl transferase and pulse pressure in apparently healthy middle-aged subjects.

UNLABELLED: Higher values of pulse pressure (PP)--the difference between systolic blood pressure (SBP) and diastolic blood pressure (DBP)--are associated with an increased cardiovascular risk; SBP and DBP values are correlated with serum levels of gamma-glutamyl transferase (GGT), both in drinkers and non-drinkers subjects. Moreover, some studies showed that high levels of serum GGT might be related with an increased cardiovascular risk. However, few studies analyzed the relationship between GGT and PP. In 72 subjects (18 male; 54 women), middle-aged (mean age: 36.63 yrs; limits: 24-54 yrs), apparently healthy, we performed the measurements of: weight, height (from which we calculated the body mass index [BMI]), SBP, DBP, PP, standard biochemical workup, including GGT (UI/l). RESULTS: PP values are correlated with SBP (r=0.74, p<0.001), but not with DBP (r=0.15, p=NS) values. GGT is significantly correlated with SBP (r=0.28, p=0.01), DBP (r=0.29, p=0.01), and BMI (r=0.41, p<0.001). Mean values of PP are significantly higher in those with a GGT>20 than those with GGT<20 (48.69 vs. 43.85 mmHg, p<0.05); similarly, mean values of SBP (131.66 vs. 116.81 mmHg, p=0.0004) and DBP (82.59 vs. 73.52 mmHg, p=0.0008) are higher in the group with GGT>20. We observed an ascending trend of the mean value of GGT in the different groups of PP; therefore, mean value of GGT was 19.21, 22.65, 23.18 in the PP<40, PP=40-60, respectively PP>60 groups. However, the correlation between PP and GGT was not significant, both in univariate analysis (r=0.14, p=NS) and after adjusting for SBP, DBP, BMI (r=0.12, p=NS). When we analyzed subgroups, the relationship between GGT and PP was more evident in women and in subjects with increased values of BMI. CONCLUSIONS: GGT values are significantly correlated with SBP and DBP, but not with PP, in middle-aged, apparently healthy subjects; even though the highest values of GGT are associated with an increased PP value, further studies would be necessary in order to explain this link.

Adult↗
PubMed2005

[Effects of dibutyl phthalate on sertoli cells of rat testis].

OBJECTIVE: The present study was performed to examine functional and structural impairment of rat sertoli cells following dibutyl phthalate (DBP) exposure. METHODS: The 6-week-old healthy male Sprague Dawley rats were randomly divided into 4 groups with 16 animals in each group. DBP dissolved in peanut oil was administered by gavage at doses of 0, 250, 500 and 1 000 mg/kg. After 2-week DBP treatment, half of the rats were sacrificed. The rest were killed following 4-week DBP exposure. Follicle stimulating hormone (FSH) was analysed by radioimmunoassay. The relative expression levels of androgen binding protein (ABP) mRNA and inhibin (INH)alpha mRNA were determined by semi-quantitative reverse transcription-polymerase chain reaction (RT-PCR). The sertoli cell ultrastructures were observed by using transmission electron microscope (TEM). RESULTS: FSH levels were increased after 4-week DBP exposure with significance at doses of 250 and 1 000 mg/kg. Sperm head count and daily sperm product were decreased significantly in 500 and 1 000 mg/kg groups. The expression levels of ABP mRNA were 0.89 +/- 0.15, 0.85 +/- 0.23, 0.54 +/- 0.17, 0.52 +/- 0.16 and 0.88 +/- 0.16, 0.61 +/- 0.12, 0.48 +/- 0.15, 0.47 +/- 0.11 for 0, 250, 500 and 1 000 mg/kg after 2- and 4-week DBP treatments respectively with significance at doses of 500 and 1 000 mg/kg (P < 0.01), while the levels of INHalpha mRNA were 0.88 +/- 0.16, 0.61 +/- 0.12, 0.48 +/- 0.15, 0.47 +/- 0.11 and 0.75 +/- 0.19, 0.56 +/- 0.16, 0.53 +/- 0.08, 0.45 +/- 0.10 with significance at all exposure groups (P < 0.01 or P < 0.05). In sertoli cells of rats exposed to 1 000 mg/kg DBP, TEM photos showed more lysosomes in cytoplasm, proliferated and expanded endoplasmic reticulum and nuclei malformation. CONCLUSIONS: Sertoli cell should be one of the major toxic targets. Impairment of spermatogenesis caused by DBP should be partly due to the suppression of ABP and INHalpha biosynthesis.

Androgen-Binding Protein↗
PubMed1986

Rat vitamin D binding protein. Determination of the full-length primary structure from cloned cDNA.

Vitamin D binding protein (DBP) is an abundant serum glycoprotein secreted by the liver which transports vitamin D sterols, binds to actin, and is found on the surface of B-lymphocytes and subpopulations of T-lymphocytes. In the current study, a cDNA to rat DBP mRNA was cloned from a bacteriophage lambda gt 11 rat liver expression library. This DBP cDNA clone was identified by immunoblotting and its identity was confirmed by immunoprecipitation of a 54-kDa protein after hybrid-assisted translation. Northern analysis and primer extension mapping of rat liver mRNA indicated that the full-length DBP mRNA contains 1700 bases. By DNA sequence analysis this 1655-base pair clone contains a single open reading frame encoding the 476-amino acid containing full-length DBP and includes its 16-amino acid signal sequence. Analysis of the sequence reveals about 40% nucleotide and 23% amino acid homology to both albumin and alpha-fetoprotein. The encoded DBP contains a characteristic placement of cysteine residues, identical to that in albumin, suggesting a similar secondary folding structure. Albumin and alpha-fetoprotein are composed of three internally homologous domains. DBP mRNA terminates 122 amino acids before the larger albumin mRNA in the third internal domain, but retains the characteristic homology among the first two domains and the truncated portion of the third domain. These data support the conclusion that DBP is a member of a multigene family which includes albumin and alpha-fetoprotein.

Albumins↗
PubMed1994

Ambulatory blood pressure monitoring in normotensive children.

OBJECTIVE: To assess reference values of ambulatory blood pressure in normotensive children. SUBJECTS AND DESIGN: Twenty-four-hour non-invasive ambulatory blood pressure monitoring (ABPM) was carried out in 241 healthy normotensive children aged from 6 to 16 years (126 boys, mean +/- SD age 11.2 +/- 2.7 years; 115 girls, mean +/- SD age 10.9 +/- 2.9 years). The subjects were subdivided into three age-sex groups: 6-9, 10-12 and 13-16 years. SETTING: Primary care. MAIN OUTCOME MEASURES: ABPM was performed using an oscillometric device (SpaceLabs model 90207) and appropriate cuff size during a regular school day. Blood pressure was measured every 20 min from 0600 to 2400 h, and thereafter every 30 min. At each monitoring session the following parameters were calculated for both systolic (SBP) and diastolic blood pressure (DBP): means and centiles for 24-h, daytime (0800-2200 h) and night-time (2400-0600 h); circadian variability, estimated as the blood pressure fall between the day and the night periods and the day: night ratio; and load, as the percentage of measurements above the age- and sex-specific 95th centile (P95). RESULTS: The upper limits of 'normality' for the mean of 24-h SBP and DBP estimated as the P95 in each age subgroup were 121/71 and 119/71 mmHg, 123/78 and 120/74 mmHg, and 124/78 and 125/75 mmHg, for boys and girls, respectively. A progressive increase in SBP with age was observed in both sexes, in contrast, DBP was similar throughout the age range. A nocturnal blood pressure fall of approximately 11 mmHg was observed for both SBP and DBP in all subgroups. The day:night ratio was 1.12 and 1.22 for SBP and DBP, respectively. The upper limit of blood pressure load, estimated as the P95 in all children, was 39% for SBP and 26% for DBP. A significant positive correlation was observed between casual blood pressure and 24-h ambulatory blood pressure (SBP: r = 0.61, P < 0.0001; DBP: r = 0.31, P < 0.0001). In general, mean ambulatory blood pressure, during the 24-h or the daytime period, was higher than casual blood pressure for both SBP and DBP. CONCLUSION: ABPM is feasible in children, and the values obtained are useful as a departure point in establishing reference values.

Adolescent↗
PubMed1993

Coordinated inhibition of actin-induced platelet aggregation by plasma gelsolin and vitamin D-binding protein.

Actin is an abundant intracellular protein that is released into the blood during tissue injury and its injection into rats causes microthrombi to form in the vasculature. This report and others have shown that actin filaments are able to aggregate platelets in an adenosine diphosphate (ADP)-dependent manner. The effects on this process of two plasma actin-binding proteins, vitamin D-binding protein (DBP) and gelsolin, were examined separately and together. The addition of DBP, a monomer-binding protein, to actin filaments did not affect their ability to induce platelet aggregation. However, severing of actin filaments with gelsolin resulted in an increased degree of platelet aggregation. Preincubation of F-actin with both gelsolin and DBP resulted in a significant inhibition of aggregation. The effects of DBP and gelsolin on actin-induced aggregation paralleled their effects on exchange of actin-bound adenine nucleotides. DBP inhibited 1, N6-ethenoadenosine 5' triphosphate (epsilon-ATP) exchange with G-actin but not with F-actin. Gelsolin increased epsilon-ATP exchange with F-actin, which was largely abrogated by the addition of DBP. These results suggest that gelsolin's severing (and subsequent capping) of actin filaments not only results in an increase in the number of pointed filament ends but also in the dissociation of actin monomers containing ADP. Phalloidin, which stabilizes actin filaments while decreasing both monomer and nucleotide exchange, inhibited actin-induced aggregation, as well, indicating that depolymerization of actin filaments is not required to inhibit aggregation. Platelet activation by either G- or F-actin may thus be regulated by the local concentrations of the plasma actin-binding proteins gelsolin and DBP. Together, these proteins inhibit platelet aggregation in a manner that can be explained by their effects on actin's filament structure and the accessibility of its bound ADP. Depletion of DBP or gelsolin may allow actin released from injured tissues to stimulate purinergic receptors on platelets, and perhaps other cells, via its bound adenine nucleotides.

Actins↗
PubMed2007

Dibutyl phthalate biodegradation by the white rot fungus, Polyporus brumalis.

In this study, white rot fungus, Polyporus brumalis, was applied to degrade dibutyl phthalate (DBP), a major environmental pollutant. The degradation potential and resulting products were evaluated with HPLC and GC/MS. As DBP concentration increased to 250, 750, and 1,250 microM, the mycelial growth of P. brumalis was inhibited. However, growth was still observed in the 1,250 microM concentration. DBP was nearly eliminated from culture medium of P. brumalis within 12 days, with 50% of DBP adsorbed by the mycelium. Diethyl phthalate (DEP) and monobutyl phthalate (MBP) were detected as intermediate degradation products of DBP. In culture medium, the concentration of DEP was higher than that of MBP during the incubation period. After 12-15 days, the concentrations of both decreased rapidly in the culture medium. The primary final degradation product of DBP in culture medium was phthalic acid anhydride, as well as trace amounts of aromatic compounds, such as alpha-hydroxyphenylacetic acid, benzyl alcohol, and O-hydroxyphenylacetic acid. According to these results, the degradation of DBP in culture medium by the white rot fungus, P. brumalis, may be completed through two pathways-transesterification and de-esterification-which successively combine into an intracellular degradation pathway.

Basidiomycota↗
PubMed1989

Co-operative interactions between NFI and the adenovirus DNA binding protein at the adenovirus origin of replication.

The DNA-protein and protein-protein interactions proposed for the stability of nucleoprotein complexes at the origin of replication in prokaryotes are also thought to impart regulatory precision in eukaryotic DNA replication. This type of specificity can be observed, for example, during adenovirus DNA replication where efficient initiation requires that nuclear factor I (NFI) binds to the origin of DNA replication. Addition of purified NFI stimulates the initiation of adenovirus DNA replication in vitro in a reaction that is dependent on the concentration of the adenovirus DNA binding protein (DBP). However, the molecular basis for the synergistic action of NFI and DBP during replication is at present unknown. We report here that DBP increases the affinity of NFI for its binding site in the replication origin. DBP did not, however, increase the affinity of another eukaryotic sequence-specific DNA binding protein, EBP1, for its recognition site. Other single-stranded DNA binding proteins could not substitute for DBP in increasing NFI affinity for its binding site. In addition, DBP was found to alter the binding kinetics of NFI, both by increasing the rate of association and decreasing the rate of dissociation of NFI with the DNA template. The co-operativity between NFI and DBP was also demonstrated on another DNA template, a human NFI site (FIB2), suggesting that this interaction is of general occurrence and not restricted to the adenovirus origin of replication.

Adenoviridae↗
PubMed2006

Prevention of oxidative degradation of polyurethane by covalent attachment of di-tert-butylphenol residues.

Polyurethane (PU) components of cardiovascular devices are subjected to oxidation-initiated surface degradation, which leads to cracking and ultimately device failure. In the present study, we investigated a novel bromoalkylation chemical strategy to covalently attach the antioxidant, di-tert-butylphenol (DBP), and/or cholesterol (Chol) to the PU urethane nitrogen groups to hypothetically prevent oxidative degradation. These experiments compared PU, PU-DBP, PU-Chol, and PU-Chol-DBP. A series of comparative oxidative degradation studies involved exposing PU samples (modified and unmodified) to H2O2-CoCl2 for 15 days at 37 degrees C, to cause accelerated oxidative degradation. The extent and effects of degradation were assessed by attenuated total reflectance Fourier transformation infrared spectroscopy (FTIR), scanning electron microscopy (SEM), surface contact angle measurements, and mechanical testing. Both the Chol and DBP modification conferred significant resistance to oxidation related changes compared to unmodified PU per FTIR and SEM results. SEM demonstrated cavitation only in unmodified PU. However, contact angle analysis showed significant oxidation-induced changes only in the Chol-modified PU formulations. Most importantly, uniaxial stress-strain testing revealed that only PU-DBP demonstrated bulk elastomeric properties that were minimally affected by oxidation; PU, PU-Chol, PU-Chol-DBP showed marked deterioration of their stress-strain properties following oxidation. In conclusion, these results demonstrate that derivatizing PU with DBP confers significant resistance to oxidative degradation compared with unmodified PU.

Butanes↗
PubMed2001

Genotoxicity of di-butyl-phthalate and di-iso-butyl-phthalate in human lymphocytes and mucosal cells.

The genotoxicity of phthalates, widely used plasticizers, has been shown previously for di-butyl-phthalate (DBP) and di-iso-butyl-phthalate (DBP) in human mucosal cells of the upper aerodigestive tract in a previous study using the Comet assay. Furthermore, higher genotoxic sensitivities of patients with squamous cell carcinomas of either the larynx or the oropharynx compared to non-tumor patients were described. Other authors have demonstrated DNA damage by a different phthalate in human lymphocytes. It was the aim of the present study to determine whether there is a correlation between the genotoxic sensitivities to DBP and its isomer DiBP in either mucosal cells or lymphocytes. The single-cell microgel electrophoresis assay (Comet assay) was applied to detect DNA strand breaks in human epithelial cells of the upper aerodigestive tract (n=132 specimens). Human mucosa was harvested from the oropharynx in non-tumor patients and patients with squamous cell carcinomas of the oropharynx. Laryngeal mucosa of patients with laryngeal squamous cell carcinomas was harvested as well. Peripheral lymphocytes (n=49 specimens) were separated from peripheral blood. Xenobiotics investigated were DBP, DiBP, and N'methyl-N'-nitro-N-nitrosoguanidine (MNNG) as positive control, respectively. For statistical analysis, the SPSS correlation analysis according to Pearson and the Wilcoxon test were performed. Genotoxicity was found for DBP and DiBP in epithelial cells and lymphocytes (P<0.001). MNNG caused severe DNA damage. In analyzing DBP and DiBP results, genotoxic impacts in mucosal cells showed an intermediate correlation (r=0.570). Correlation in lymphocytes was the same (r=0.570). Phthalates have been investigated as a potential health hazard for a variety of reasons, including possible xenoestrogenic impact, peroxisome proliferation, and membrane destabilization. The present investigation suggests a correlated DNA-damaging impact of DBP and DiBP in human mucosal cells and in lymphocytes, respectively.

Comet Assay↗
PubMed1994

Structure of a repilian plasma thyroxine binding protein indicates homology to vitamin D-binding protein.

Biochemical analyses revealed that a thyroxine (T4)-binding protein (TBP) in the blood of some turtles exhibits a high degree of structural homology to mammalian vitamin D-binding protein (DBP), instead of mammalian T4-binding protein (TBG). Like DBP, TBP is rich in Cys (ca. 28/molecule). The 31 NH2-terminal amino acids of TBP show 68% identity to the corresponding region of mammalian (rat, mouse, and human) DBP and one peptide from Lys-C proteolysis shows similar homology to residues 35-49 of DBP (the predicted sterol binding domain). Another peptide shows a 75% identity to a sequence corresponding to residues 134-154 of DBP, but seven others showed no homology to any proteins in GenBank. Digestion with N-glycosidase F reduced the M(r) of TBP by only 4.5K compared with 14K for TBG; T4-binding activity of TBP was unaffected. TBP (and DBP) also behaves as a much smaller molecule (approximately 57 kDa) than TBG (> 70 kDa) by size-exclusion chromatography, despite similarities in their estimated sizes from sodium dodecyl sulfate electrophoresis (approximately 60 kDa). Binding studies confirm that the turtle T4-binding protein likely also represents the major blood DPB. Thus, in the turtle, a single binding protein resembling DBP performs two major transport functions which are normally served by proteins representing two different multigene families in mammals.

Amino Acid Sequence↗
PubMed1996

Influence of dibutyl phthalate on dermal sensitization to fluorescein isothiocyanate.

What limited evidence there is indicates that the formulation in which a chemical allergen is encountered on the skin can have a marked impact upon the induction of cutaneous immune responses and the subsequent development of contact sensitization. The purpose of the present investigations was to examine further this phenomenon by analysis of the influence of dibutyl phthalate (DBP) on dermal sensitization to fluorescein isothiocyanate (FITC), a skin sensitizing fluorochrome. Addition of DBP augmented very substantially, in a dose-dependent fashion, the ability of topically applied FITC to stimulate proliferative responses in mice by draining lymph node cells (LNC), a correlate of skin sensitizing potential. Under these conditions, exposure of mice to DBP alone failed to elicit significant LNC responses. The influence of DBP on the accumulation of dendritic cells (DC) induced by FITC was examined also. Although 10% DBP had little effect on the numbers of DC found within draining nodes 18 hr following exposure of mice to FITC, the phthalate did result in a very substantial increase in the frequency of lymph node DC bearing detectable antigen (FITC+ DC). Furthermore, in the presence of DBP the median amount of FITC associated with antigen-bearing DC was higher. In vitro skin absorption studies indicated that DBP was associated with a small increase in percutaneous absorption of FITC. Collectively these data demonstrate that the vehicle formulation can exert a marked influence on dermal sensitization and that one mechanism which may be relevant is the increased acquisition of antigen by DC, associated possibly with altered penetration of the allergen into or through the skin.

Administration, Topical↗
PubMed1995

Mutations in the adenovirus-encoded single-stranded DNA binding protein that result in altered accumulation of early and late viral RNAs.

Adenovirus encodes a 72-kDa single-stranded DNA binding protein (DBP) that is necessary for viral DNA replication and is involved in controlling viral RNA metabolism. Studies of temperature-sensitive (ts) and site-directed mutants of the DBP have identified at least four regions of the protein involved in binding to single-stranded DNA and hence in DNA replication. Two of the ts mutants, Ad2ts111A and Ad2ND1+ts23, are deficient in DNA binding and in supporting in vitro DNA replication. Their effects on viral RNA metabolism are presented here. At early and late times of infection, accumulation of RNAs from the viral E3 region is increased up to sevenfold in Ad2ts111A- and Ad2ND1+ts23-infected cells relative to wild-type virus. This effect is temperature-independent and seems to involve nuclear RNA stability. Steady-state levels of the viral E1B and E4 RNAs increase following the onset of viral DNA replication in cells infected by the wild-type virus, but not in cells infected by ts111A or ts23. The increase in E1B and E4 RNAs at late times of infection is due to a stabilization of the mRNA. The steady-state levels of L3 and L5 RNAs are two- to fourfold higher in cells infected with ts23 and ts111A than with wild-type virus. None of these differences were observed following infection of cells with a temperature-independent revertant of ts111, indicating that the mutations in the DBP were responsible for the phenotypes. However, for the E3 effect, the change brought about by the mutations in the DBP does not seem to be the result of a change in the normal function of the protein, as an essentially DBP-negative virus (Ad5d/802) shows no differences in E3 RNA metabolism compared to wild-type virus at early times of infection. These results demonstrate that mutation of amino acids 280 and 282 of the DBP significantly perturbs the normal regulation of viral RNA metabolism. These effects clearly differ from the phenotypes observed with adenoviruses containing mutations in other early genes and from those ascribed to the ts125 mutation by others. These results are discussed in terms of the mechanisms by which early and late viral RNA metabolism are controlled and the possible effects of the DBP mutations on them.

Adenoviruses, Human↗
PubMed2005

Demineralized bone promotes chondrocyte or osteoblast differentiation of human marrow stromal cells cultured in collagen sponges.

Demineralized bone implants have been used for many types of craniomaxillofacial, orthopedic, periodontal, and hand reconstruction procedures. In previous studies, we showed that demineralized bone powder (DBP) induces chondrogenesis of human dermal fibroblasts in a DBP/collagen sponge system that optimized interactions between particles of DBP and target cells in cell culture. In this study, we test the hypothesis that DBP promotes chondrogenesis or osteogenesis of human marrow stromal cells (hMSCs) in 3-D collagen sponge culture, depending upon the culture conditions. We first confirmed that hMSCs have chondrogenic potential when treated with TGF-beta, either in 2-D monolayer cultures or in 3-D porous collagen sponges. Second, we found that DBP markedly enhanced chondrogenesis in hMSCs in 3-D sponges, as assessed by metachromasia and expression of chondrocyte-specific genes AGGRECAN, COL II, and COL X. Human dermal fibroblasts (hDFs) were used to define mechanisms of chondroinduction because unlike hMSCs they have no inherent chondrogenic potential. In situ hybridization revealed that hDFs vicinal to DBPs express chondrocyte-specific genes AGGRECAN or COL II. Macroarray analysis showed that DBP activates TGF-beta/BMP signaling pathway genes in hDFs. Finally, DBP induced hMSCs to express the osteoblast phenotype when cultured with osteogenic supplements. These studies show how culture conditions can influence the differentiation pathway that human marrow stromal cells follow when stimulated by DBP. These results support the potential to engineer cartilage or bone in vitro by using human bone marrow stromal cells and DBP/collagen scaffolds.

Aggrecans↗
PubMed1993

Increased prevalence of abnormal signal-averaged electrocardiograms in older patients who have hypertension with low diastolic blood pressure.

Greater mortality in hypertensive patients with the lowest diastolic blood pressure (DBP) values has been reported and may be partially explained by more fatal arrhythmias. The records of 135 patients were reviewed to determine whether the prevalence of an abnormal signal-averaged electrocardiogram (SAECG+), a risk marker for ventricular arrhythmias, was greater in patients who have hypertension with DBP < 85 mm Hg. SAECG+ was present in 31 (39%) of 80 patients with hypertension and 13 (24%) of 55 subjects with normotension p < 0.05. Hypertensive patients were more likely than normotensive subjects to have left ventricular hypertrophy (LVH, p = 0.01) and LV dysfunction (p < 0.01). In multivariate analysis only age and systolic dysfunction emerged as significant predictors of SAECG+. Among 68 hypertensive patients and for whom recent DBP data were available, SAECG+ was present in 18 of 37 with DBP < 85 mm Hg (group 1), 1 of 12 with DBP 85 to 94 mm Hg (group 2, p < 0.05 vs group 1), and 4 of 19 with DBP > 95 mm Hg (group 3, p < 0.05 vs group 1, p = 0.08 vs group 2). There were no significant differences between the three groups of hypertensive patients for coronary artery disease, LVH, systolic dysfunction, or left-sided cardiac chamber enlargement. Multivariate analysis in hypertensive patients indicated that age and DBP were each independently predictive of SAECG+, whereas the indexes of heart disease were not. Within group 1, those with SAECG+ were significantly older (68 +/- 1 vs 59 +/- 1 years, p < 0.01) and more likely to have LVH (p < 0.03).(ABSTRACT TRUNCATED AT 250 WORDS)

Arrhythmias, Cardiac↗