PubMed Health⌕ Search

Biomedical subjects

R Daniel

Publications and source records attributed to R Daniel.

At least 91 records · Page 5Linked to original sources
PubMed1992

Specific immunological and bronchopulmonary responses following intradermal sensitization to free trimellitic anhydride in guinea pigs.

We have developed a guinea pig model of trimellitic anhydride-induced airway hypersensitivity responses. In one group of guinea pigs, injected intradermally with 0.1 ml 30% trimellitic anhydride (TMA), we examined the specificity of the bronchopulmonary response to TMA comparing the effect of intravenous TMA conjugated to guinea pig serum albumin (GPSA) with a control hapten (procion dye) protein conjugate (PD-GPSA). A significant increase in pulmonary inflation pressure (PIP) was provoked in sensitized animals following intravenous injection with TMA-GPSA (20%; 0-400, median; range) as compared to intravenous injection of PD-GPSA. In the second group we compared three different methods of sensitization: single injection of 0.1 ml of 0.3% TMA; four injections of 0.1 ml of 0.1% TMA; and a single high dose injection of 30% TMA. Following intravenous TMA-GPSA guinea pigs sensitized with a single injection 0.3% TMA had an increase in PIP of 395%; 220-600, while those given four repeat injections of 0.1% TMA had an increase in PIP of 343%; 315-490. These results were significantly higher than the increase in PIP (160%; 0-220) which occurred in guinea pigs sensitized with a single dose of 30% TMA. Four of 11 guinea pigs given low dose injections of TMA had bronchopulmonary responses to inhaled TMA-GPSA. All sensitized guinea pigs had specific IgG1 antibodies demonstrated by enzyme linked immunosorbent assay (ELISA) and confirmed by ELISA inhibition. Four guinea pigs sensitized by low dose injections of TMA had IgE antibodies demonstrated by passive cutaneous anaphylaxis.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1992

Characterization of a sporulation gene, spoIVA, involved in spore coat morphogenesis in Bacillus subtilis.

Mutations in the spoIVA locus of Bacillus subtilis abolish cortex synthesis and interfere with the synthesis and assembly of the spore coat. We have characterized the cloned spoIVA locus in terms of its physical structure and regulation during sporulation. The locus contains a single gene capable of encoding an acidic protein of 492 amino acids (molecular weight, 55,174). The gene is transcribed from a sigma E-dependent promoter soon after the formation of the spore septum. A genetic test indicated that expression of spoIVA is only necessary in the mother cell compartment for the formation of a mature spore. This, together with the phenotypic properties of spoIVA mutations, would be in accord with the hypothesis that sigma E is only active after septation and in the mother cell compartment.

Amino Acid Sequence↗
PubMed1992

Bronchoconstriction and airway microvascular leakage in guinea pigs sensitized with trimellitic anhydride.

We have developed a guinea pig model of immediate airway responses following intradermal sensitization with free trimellitic anhydride (TMA). Guinea pigs were given an intradermal injection with either 0.1 ml of 0.3% TMA in corn oil (n = 8) or 0.1 ml of corn oil alone (n = 6). A guinea pig serum albumin conjugate of trimellitic anhydride (TMA-GPSA) was prepared with a substitution ratio of 21:1. All sensitized guinea pigs had raised specific serum IgG1 antibodies (ELISA), and IgE antibodies were detected in six of the eight sensitized guinea pigs by passive cutaneous anaphylaxis. On Days 21 to 28, guinea pigs were anesthetized, tracheostomized, and ventilated. Evans blue dye (20 mg/ml), an albumin marker, was injected intravenously to quantify airway microvascular leakage (MVL). TMA-GPSA (50 microliters; 1%) in saline was instilled into the trachea. Lung resistance (RL) was measured for 6 min. The guinea pigs were killed, and the lungs were removed. Peak RL (cm H2O/ml x s-1) was significantly increased in sensitized guinea pigs from 0.26 +/- 0.01, mean +/- SEM to 21.3 +/- 6.9 (p < 0.05), compared with nonsensitized guinea pigs. There was a significant increase in Evans blue at all levels of the tracheobronchial tree in sensitized guinea pigs compared with the controls (p < 0.005). The site of MVL was localized to the postcapillary venules as assessed by extravasation of intravascular Monastral blue dye. We conclude that intradermal sensitization of guinea pigs to TMA induces a polyclonal immune response, associated with bronchoconstriction and airway microvascular leakage, when challenged specifically with TMA-GPSA.(ABSTRACT TRUNCATED AT 250 WORDS)

Airway Resistance↗
PubMed1992

Bronchial hyperreactivity after inhalation of trimellitic anhydride dust in guinea pigs after intradermal sensitization to the free hapten.

We have developed in the guinea pig, an animal model of bronchial hyperreactivity provoked by inhalation of trimellitic anhydride (TMA) dust, a known cause of occupational asthma in humans, after intradermal sensitization to the free hapten. Male Dunkin-Hartley guinea pigs (n = 6) were injected intradermally with 0.1 ml of 30% TMA in corn oil. Control animals (n = 7) were injected with 0.1 ml corn oil alone. On Days 21 to 28 after sensitization, guinea pigs were challenged (nose only) to 12 mg/m3 of inhalable TMA dust for 30 min. Bronchial reactivity was measured in sensitized animals and in control animals at 8 h after exposure to the dust. We also measured bronchial reactivity in sensitized exposed guinea pigs at 2 h (n = 5) and at 24 h (n = 5). Pulmonary inflation pressure (PIP) was used to assess bronchopulmonary response. Blood samples were taken for assessment of IgG-1 antibodies to TMA conjugated to guinea-pig albumin. The concentration of acetylcholine required to induce a 100% increase in PIP was used to assess bronchial reactivity. The lungs were eviscerated for histologic examination. All guinea pigs injected intradermally with TMA had high titers of specific IgG-1 antibodies to TMA conjugated to guinea-pig albumin. There was a significant increase in bronchial reactivity in sensitized guinea pigs 8 h after exposure to the TMA dust compared with that in the control animals. There was also a significant eosinophilic inflammatory influx in the subepithelium of the sensitized groups.(ABSTRACT TRUNCATED AT 250 WORDS)

Air Pollutants↗
PubMed1991

Peroxidase-like activity of lipoxygenases: different substrate specificity of potato 5-lipoxygenase and soybean 15-lipoxygenase and particular affinity of vitamin E derivatives for the 5-lipoxygenase.

Potato 5-lipoxygenase (5-PLO) catalyzes the reduction of 13(S)-hydroperoxy-9Z,11E-octadecadienoic acid (13-HPOD) in the presence of vitamin E. I mol of vitamin E is required to consume 2 mol of 13-HPOD. The mechanism of the 5-PLO-catalyzed oxidation of vitamin E by 13-HPOD is similar to that previously established for the soybean 15-lipoxygenase (L-1)-catalyzed oxidation of phenidone by 13-HPOD, and seems to involve a one-electron reduction of the O-O bond of 13-HPOD. 5-PLO and L-1 exhibit very different substrate specificities and pH profiles for their peroxidase-like activity. Actually, among the 20 compounds containing various reducible functions and the 10 derivatives of vitamin E which have been studied, only four products containing hydrophobic long chains, ascorbic acid 6-palmitate, the trolox esters of octanol and undecanol, and vitamin E exhibit high peroxidase-like activities for 5-PLO. On the contrary, much more compounds, even not very hydrophobic, are good substrates for the peroxidase-like activity of L-1.

Arachidonate 15-Lipoxygenase↗
PubMed1991

An open study to compare the pharmacokinetics, safety and tolerability of a multiple-dose regimen of azithromycin in young and elderly volunteers.

An open, parallel study was conducted to compare the pharmacokinetics of oral azithromycin in young and elderly healthy volunteers. A total of 12 young subjects (six males, six females) with a mean age of 29 (range 22-39) years and another 12 elderly subjects (six males, six females) with a mean age of 72 (range 67-80) years were given a standard five-day therapeutic regimen of azithromycin (500 mg single dose on day 1 and 250 mg once daily on days 2-5). Pharmacokinetic results indicated that Cmax, Cmin and urinary excretion were similar in the two age groups. Mean AUC0-24 was significantly greater (2.7 micrograms.h/ml) at day 5 in the elderly subjects compared with the younger age group (AUC0-24 = 2.1 micrograms.h/ml) (p = 0.041). Similarly, tmax values on days 1 and 5 were significantly greater in the elderly subjects; 3.8 h compared with 2.5 h in young subjects (p = 0.005) on day 1 and 4.4 h, compared with 3.2 h (p = 0.047) on day 5. There was also evidence of an inverse relationship between creatinine clearance and AUC0-24 (p less than 0.01) but not urinary excretion or Cmax. Despite these observations, it is concluded that the differences between the two age groups were of insufficient magnitude to warrant a dose modification in elderly subjects with only mild renal impairment. Side effects, chiefly headache and gastrointestinal symptoms, were reported by seven subjects in each group. No subject, however, was withdrawn from the study and there were no treatment-related abnormalities in any of the laboratory parameters measured.

Administration, Oral↗
PubMed1990

Soybean lipoxygenases-1, -2a, -2b and -2c do not contain PQQ.

Soybean isoenzymes lipoxygenases-1, -2a, -2b and -2c were examined spectroscopically for the presence of covalently bound pyrrolo quinoline quinone (PQQ) after derivatization by phenylhydrazine (PH), 2,4-dinitrophenylhydrazine (DNPH) and 3-methyl-2-benzothiazolinone hydrazone (MBTH). DNPH derivatization of PQQ after a pronase digestion step of lipoxygenase-1 in the presence of an anion exchange gel fixing the cofactor was also investigated. None of these experiments provided evidence for the presence of PQQ contrary to previous report by Van der Meer et al (1). We have checked, by EPR spectroscopy, that the three reactants used were able to reduce the active site ferric iron. Our results were confirmed by the absence of enzyme inhibition by cis- and trans-1,2-diaminocyclohexane or benzylamine in the presence of NaBH3CN which have been reported to react with PQQ and to inactivate quinoproteins (2,3).

Benzothiazoles↗
PubMed1990

Intraocular pressure profile during general anesthesia.

The effect of some anesthetic drugs on intraocular pressure (IOP) was studied in 120 normal healthy patients undergoing non-ophthalmic surgical procedures. IOP rose significantly following the injection of succinylcholine (SCh) alone, or when such injection had been preceded by a pretreatment with a "self-taming" dose of SCh or d-tubocurarine (d-Tc). Though the rise in IOP after diazepam pretreatment was significant, the magnitude was lower than that observed in the groups pretreated with the other two agents. Halothane brought the IOP down faster and lower than ether. SCh is unsafe for intubation for the administration of general anesthesia in cases involving penetrating ocular injuries. It can, however, be used safely for routine ophthalmic surgery, providing that 8 minutes are allowed to elapse between injection and corneal or scleral incision. Halothane is preferred to ether, since the former lowers IOP faster and in a greater amount than the latter.

Anesthesia, General↗
PubMed1989

Human papillomavirus and epithelial ovarian neoplasia.

In contrast to the strong association between human papillomavirus (HPV) and squamous cell carcinoma of the lower female genital tract, no viral DNA had been found in epithelial ovarian carcinoma. Recently, however, R. H. Kaufman, J. Bornstein, A. N. Gordon, E. Adam, A. L. Kaplan, and K. Adler-Storthy [Gynecol. Oncol. 27, 340-349 (1987)] reported the detection of HPV-6 DNA by in situ hybridization in 10 of 12 patients with advanced epithelial ovarian carcinoma. To further investigate the possible association between HPV and epithelial ovarian neoplasia, tumor from 12 patients with epithelial ovarian adenocarcinoma, 3 with epithelial ovarian tumors of low malignant potential, and 3 with epithelial ovarian tumors of low malignant potential, and 3 with epithelial ovarian adenomas was examined for HPV DNA by the Southern hybridization technique. All the tissues were tested under low stringency for HPV-6 and under high stringency for HPV-6, HPV-16, HPV-18, HPV-31, and HPV-35. In addition, all tissues were tested by polymerase chain reaction for the presence of HPV-6 and HPV-11. Of the 12 patients with adenocarcinoma, 5 were poorly differentiated, 4 serous, 1 endometrioid, 1 mucinous, and 1 mixed. The neoplasms were of grades 2-4 with a predominance of stages III and IV (83%). Of the 3 patients with tumors of low malignant potential, all were serous and stage I. Of the 3 patients with adenomas, 1 was mucinous, 1 serous, and 1 Brenner. We were unable to detect HPV-related sequences in any of the specimens. On the basis of these findings, there appears to be no association between HPV and epithelial ovarian neoplasia.

Adenocarcinoma↗
PubMed1989

Representativity and reproducibility of DNA malignancy grading in different carcinomas.

The reproducibility of the determination of the "DNA malignancy grade" (DNA-MG) was tested in 56 carcinomas of the colon, breast and lung while its representativity was tested on 195 slides from 65 tumors of the colon, breast and lung. DNA measurements were performed on Feulgen-stained smears with the TAS Plus TV-based image analysis system combined with an automated microscope. The variance of the DNA values of tumor cells around the 2c peak, the "2c deviation index" (2cDI), was taken as a basis for the computation of the DNA-MG, which ranges on a continuous scale from 0.01 to 3.00. The representativity, analyzed by comparison of the DNA-MGs measured in three different areas of the same tumor greater than or equal to 1.5 cm apart from each other, yielded an 81% agreement. No significant differences between DNA-MGs of these areas were found. The intraobserver and interobserver reproducibilities of the DNA grading system, investigated by repeated DNA measurements, were 83.9% and 82.2%, respectively. In comparison, histopathologic grading of the 27 breast cancers studied yielded 65% intraobserver and 57% interobserver reproducibilities and 66% representativity.

Breast Neoplasms↗
PubMed1988

The predominance of human papillomavirus type 16 in vulvar neoplasia.

Southern transfer analysis for human papillomavirus genomic sequences was conducted on 152 vulvar and vaginal tissue specimens obtained from 86 patients. Histopathologic diagnoses included condyloma acuminatum, intraepithelial neoplasia, and invasive cancer. In six patients, lesions of more than one pathologic type were identified. Vaginal lesions constituted less than 5% of tissues examined. Distribution of lesions was as follows: condyloma, 93 lesions from 57 patients; intraepithelial neoplasia, 47 lesions from 29 patients; and invasive carcinoma, 12 lesions from six patients. Seventy-five percent of the patients were white. The mean age of the patients increased from 25 years for condyloma to 38 years for vulvar intraepithelial neoplasia III to 56 years for invasive cancer. A viral diagnosis was made in 81% of condylomas, 84% of vulvar intraepithelial neoplasia III, and 58% of invasive carcinomas. Distribution of viral types differed markedly for the various histopathologies. Types 6/11 accounted for 77% of condylomas and 0% of vulvar intraepithelial neoplasia III. Type 16 was recovered from 12% of condylomas and 81% of vulvar intraepithelial neoplasia III. Type 18 was identified in a small proportion in both categories; type 31 was seen in a few vulvar intraepithelial neoplasia III lesions. In invasive carcinomas, type 16 was the predominantly identified virus. Papillomavirus type 16 emerges as the dominant oncogenic virus in vulvar neoplasms. Its presence in a large percentage of condylomas raises the issue of an "atypical condyloma" as a precursor of neoplasia.

Adult↗
PubMed1988

Search for human papillomaviruses in normal, hyperplastic, and neoplastic endometria.

Twenty-eight endometria, including seven normal, five hyperplastic, and 16 neoplastic tissues, were analyzed with the Southern blot hybridization technique for their possible association with human papillomaviruses (HPVs). Human papillomavirus probes with types 6/11, 16, 18, and 31 failed to identify HPV DNA in any of these tissues. The findings suggest that the endometrium is not a usual target for HPV infection, and that HPV is not likely to be a carcinogenic factor in the development of endometrial carcinoma.

Adenocarcinoma↗
PubMed1988

High prevalence of genital tract papillomavirus infection in female adolescents.

To investigate clinical condyloma, abnormal cervical cytologic findings, and evidence of human papillomavirus infections, 89 adolescent girls were examined. Cellular DNAs extracted from exfoliated cervical cells were examined for human papillomavirus genomic sequences by Southern transfer hybridization using 32P-labeled human papillomavirus DNA probes. Human papillomavirus sequences were detected in 12 (13%) young women, abnormal cytologic specimens in 21 (24%), and vulvar condylomas in 12 (13%). The human papillomavirus types identified included HPV-6/11 (four instances), which is known to be associated with benign lesions, and HPV-16, -18, and -31 (eight instances) which are considered to have oncogenic potential. Two young women were infected with both HPV-16 and -31. Human papillomavirus sequences were found in 48% of the young women with abnormal cytologic findings and in 3% of patients with normal cytologic findings (P less than .0001). Condylomatous changes in the cervical smear were associated with the presence of HPV-6/11 and mild dysplasia with the presence of HPV-16, -18, and -31. The presence of vulvar condylomas correlated with condylomatous changes in the cervical smear and with the recovery of HPV-6/11 from the cervical epithelium. The results indicate that the prevalence of human papillomavirus infections in this population is high and that a majority of the infections are with viruses associated with lower genital tract malignancies.

Adolescent↗
PubMed1986

Role of methionine-1 in ubiquitin conformation and activity.

Methionine-1 of ubiquitin was oxidized to the sulfone without significant effect on biological activity or conformation at neutral pH. However, at low pH, the oxidized protein expanded to a more open conformation, similar in gel sieving properties to denatured ubiquitin but similar in secondary structure to native ubiquitin. This conformational transition was absent in the native protein. Interpretation of these results in the light of X-ray data suggests that ubiquitin contains two independently folded domains that are held together in part by a hydrogen bond between Met-1 and Lys-63 and which can be separated when this bond is broken. It is suggested that separation of these domains may occur upon ubiquitin conjugation.

Animals↗
PubMed1986

Inhibition of ubiquitin-dependent proteolysis by non-ubiquitinatable proteins.

The effect in reticulocyte lysates of proteins with blocked amino groups on the ATP-dependent degradation of casein and serum albumin was studied in order to assess the extent to which proteins with blocked and with free amino groups share common paths of proteolytic degradation. Completely acetylated or succinylated casein and acetylated or succinylated serum albumin (reduced and carboxymethylated), in addition to other amino-modified proteins, inhibited the ATP-dependent proteolysis of both casein and reduced carboxymethylated serum albumin. Inhibition of serum albumin degradation by acetylated serum albumin was competitive, whereas inhibition of casein degradation by acetylated casein was largely competitive with evidence of mixed kinetics. The different amino-blocked proteins studied, which were largely unfolded under assay conditions, were similarly effective as inhibitors on a weight basis, with Ki values in the range 0.2-0.6 mg/ml; there was no correlation between the ability of the blocked proteins to serve as proteolysis substrates and their effectiveness as inhibitors. Studies of the effects of acetylated proteins on the conjugation of ubiquitin to serum albumin and casein demonstrated that the acetylated proteins blocked formation of ubiquitin-albumin conjugates and of selected casein conjugates; the steady state concentration of selected conjugates of endogenous lysate proteins was increased in the presence of amino-blocked proteins. The results suggest that proteins with blocked amino groups, which cannot serve as substrates for ubiquitin conjugation, can compete for binding to those ubiquitin conjugation factors that recognize and ubiquitinate potential substrates of the ubiquitin pathway. The similar inhibitory properties of the different blocked proteins in turn suggest that a common factor in binding to these conjugation factors may be recognition of the polypeptide backbone.

Acetylation↗