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Biomedical subjects

D Hoffmann

Publications and source records attributed to D Hoffmann.

At least 181 records · Page 10Linked to original sources
PubMed1990

Differential effects of cigarette smoke condensate and its fractions on cultured normal and malignant human bronchial epithelial cells.

The differential effects of cigarette smoke condensate (CSC) and its fractions (neutral, basic, and acidic fractions) on proliferation and squamous differentiation of normal human bronchial epithelial (NHBE) cells versus human lung carcinoma cells were investigated. CSC, and the neutral and acidic fractions inhibited cellular proliferation more than the basic fraction. When compared to the acidic and basic fractions, CSC and the neural fraction were more effective in causing squamous differentiation of NHBE cells and inhibiting specific binding of phorbol dibutyrate (PDBU). There were no significant changes in ionized cytosolic calcium concentration when NHBE cells were treated with CSC. In contrast to the normal epithelial cells, neither HUT-292 nor the 3 other carcinoma cell lines examined showed marked squamous morphological changes when exposed to either CSC or its fractions and the carcinoma cells were more resistant to their inhibiting effects on cellular proliferation. These results are consistent with the hypothesis that differential effects of tobacco smoke components on cellular proliferation may allow clonal expansion of preneoplastic and neoplastic human bronchial epithelial cells during lung carcinogenesis.

Bronchi↗
PubMed1990

Structure-activity relationship of anthracyclines in vitro.

The cytotoxic activities of several natural and semisynthetic anthracyclines against L1210 leukemia and two human colon tumor cells (Colon 4, HT 29) in vitro were examined after short (1 h) and long (7 days) incubation times and correlated with the water/octanol partition coefficients and the DNA-binding affinity of the compounds. Analysis of equation in which cytotoxicity against L1210 (1-h incubation) was parabolically related to the partition coefficient revealed an almost exclusive correlation (r = 0.80) between the cytotoxicity and the parameters, and this correlation was only slightly improved by addition of DNA-binding affinity (r = 0.85). On the other hand, cytotoxic activities displayed after continuous incubation were partially related to both partition coefficients (parabolic dependence) and DNA-binding affinities (linear dependence). In this case the correlation between the activity and partition coefficient (r = 0.67) was significantly improved by addition of DNA-binding affinity (r = 0.90). Similar results were also obtained for human colon tumor cells although the corresponding correlation coefficients were generally of lower value, indicating that cytotoxic activity of anthracyclines against these primary resistant cells may be influenced by additional factors not yet determined.

Animals↗
PubMed1990

Analysis of 1,3-butadiene and other selected gas-phase components in cigarette mainstream and sidestream smoke by gas chromatography-mass selective detection.

An analytical procedure was developed for the analysis of 1,3-butadiene, acrolein, isoprene, benzene and toluene in the gas phase of cigarette smoke and environmental tobacco smoke (ETS) utilizing cryogenic gas chromatography-mass selective detection (GC-MSD). The MSD was operated in the selective ion monitoring (SIM) mode. The compounds of interest eluted in less than 15 min. The gas phase of freshly generated mainstream smoke was introduced into the GC-MSD via a 10-port gas sampling valve on a puff-by-puff basis. This method minimizes the ageing of tobacco smoke. The levels of 1,3-butadiene in the mainstream smoke ranged from 16 to 75 micrograms/cigarette. The gas phase of sidestream smoke was trapped in methanol using three midget impingers at -78 degrees C. The amount of 1,3-butadiene in the sidestream smoke ranged from 205-361 micrograms/cigarette. The concentration of 1,3-butadiene in ETS in a smoke-filled bar amounted to 2.7-4.5 micrograms/m3.

Acrolein↗
PubMed1990

Experimental infection of normal and immunosuppressed pigs with Pseudomonas pseudomallei.

A single dose of 5 x 10(8) bacilli of Pseudomonas pseudomallei by intratracheal injection resulted in acute (21 cases) or chronic (19 cases) melioidosis in 40 of 48 pigs. Fifteen (10 acute and 5 chronic) had been immunosuppressed by cyclophosphamide before inoculation. The major clinical signs were initial fever, marked neutrophilia and, in the acute cases, respiratory distress. There were no signs of the nasal and ocular discharge, paresis or diarrhoea seen in acute cases in south-east Asia. The cyclophosphamide treatment caused a significant decrease in the neutrophil count by 7 d after inoculation in all 15 immunosuppressed pigs, and all were culture positive at necropsy. Eight of the 33 non-treated pigs were culture negative at necropsy. Pigs overcoming the initial phase of infection had more abscess-like nodules that were bacteriologically sterile at necropsy than the pigs with acute cases of melioidosis. P. pseudomallei was isolated predominantly from the spleen, lungs and the injection site. Although only one strain was used in this study, it is likely that Australian strains of P. pseudomallei are not as virulent as the south-east Asian isolates.

Acute Disease↗
PubMed1990

Evaluation of a modified complement fixation test and an indirect hemagglutination test for the serodiagnosis of melioidosis in pigs.

A complement fixation test modified by the addition of porcine serum and an indirect hemagglutination test were used to detect antibodies to Pseudomonas pseudomallei in pigs. These tests together with cultural examinations were carried out with 250 pigs. The sensitivity and specificity values were 79.3 and 99.5% and 82.8 and 93.2% for the modified complement fixation and hemagglutination tests, respectively. When results from the combination of both tests were considered, the values were 86.2 and 92.8%, respectively.

Animals↗
PubMed1990

Improved therapeutic index of cisplatin analogue: B-85-0040 by circadian timing.

1. B-85-0040 is a new cisplatin analogue with dose limiting myelosuppression. 2. The maximum tolerated dose ranges between 300 and 525 mg/kg for single i.p. bolus injection in mice. 3. Its toxicity is circadian-stage dependent with optimal tolerance between 16 and 17 hours after lights on. 4. B-85-0040 is active in L1210 leukemia. Anti-tumor activity seems to be unrelated to the circadian stage of treatment. Optimal drug timing can therefore increase its therapeutic index.

Animals↗
PubMed1989

Evaluation of the transplacental tumorigenicity of the tobacco-specific carcinogen 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone in mice.

The transplacental tumorigenicity of the tobacco-specific carcinogen 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) was assessed in three strains of mice: A/J; C3H/He x C57BL/6 F1 (hereafter called C3B6F1); and Swiss outbred [Cr:NIH(S)]. NNK (100 mg/kg) was administered i.p. on Days 14, 16, and 18 of gestation to A/J and C3H/He mice and on Days 15, 17 and 19 of gestation to the Swiss mice. The effects of postnatal treatment with tumor-promoting agents, including 0.05% sodium barbital in the drinking water until death or a single dose of Aroclor 1254 (a mixture of polychlorinated biphenyls, PCB) given on Postnatal Day 8 or 56, were also examined. Progeny were sacrificed at age 24 wk (A/J) or 72 wk (C3B6F1 and Swiss). Significant incidences of tumors occurred in the lungs of strain A/J progeny and in the livers of male C3B6F1 and Swiss progeny. Lung tumor incidence was 8 of 34 (24%) in the female offspring of the A/J mice treated with NNK, compared with 1 of 39 (3%) in controls (P less than 0.05). A 2-fold difference in lung tumor incidence in male offspring of NNK-treated (4 of 23, 13%) versus control (3 of 48, 6%) A/J mice was not of statistical significance. However, the incidence of lung tumors in NNK-exposed progeny A/J mice in both sexes combined (12 of 66, 18%) was also significantly greater than in controls (4 of 87, 5%). The incidence of liver tumors in the male C3B6F1 mice exposed transplacentally to NNK was 12 of 30 (40%) compared to 8 of 46 (17%) in controls (P less than 0.05). No effects of postnatal sodium barbital or PCB were observed on transplacental NNK tumorigenicity in C3B6F1 mice. The combined incidence of liver carcinoma in male mice in all NNK-treated groups (13 of 141, 9%) was significantly greater (P less than 0.05) than in controls (5 of 144, 3%). In male Swiss mice exposed transplacentally to NNK, the incidence of liver tumors was 3 of 57 (5%) compared to 0 of 35 controls, and postnatal treatment with PCB on Day 56 caused a significant increase (5 of 26, 19%) (P less than 0.05) in the incidence of NNK-induced liver tumors. The combined incidence of liver tumors in the male offspring of the Swiss mice treated with NNK, with or without PCB, was 8 of 83 (10%) which was significantly greater (P less than 0.05) than in controls (0 of 66).(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1989

Insect immunity. Isolation of cDNA clones corresponding to diptericin, an inducible antibacterial peptide from Phormia terranovae (Diptera). Transcriptional profiles during immunization.

We have previously isolated and characterized a family of novel 8-kDa cationic antibacterial peptides synthesized by larvae of Phormia terranovae (Diptera) in response to various injuries. These molecules have been named diptericins. The peptide sequence of diptericin A was used to prepare oligonucleotides for screening cDNA libraries and we report in the present paper the isolation of several cDNA clones encoding diptericin. The analysis of the nucleotide sequences indicates that diptericin is synthesized as a prepeptide which is matured in two steps: (a) cleavage of a signal peptide and (b) amidation of the C-terminal residue. Interestingly, the 3' untranslated region of the mRNA contains a consensus sequence TTATTTAT which is also observed in the mRNA of another insect antibacterial peptide (attacin-related sarcotoxin IIA) and in mRNAs encoding proteins related to the inflammatory response in mammals. Our data illustrate that diptericins form a polymorphic family of immune peptides. The transcription of the diptericin genes is rapidly induced in the fat body after inoculation of bacteria, as evidenced by the transcriptional profile.

Amino Acid Sequence↗
PubMed1989

Canavanine incorporation into the antibacterial proteins of the fly, Phormia terranovae (Diptera), and its effect on biological activity.

In response to microbial infection or mechanical injury, larvae of the fly, Phormia terranovae (Diptera), can induce de novo production of a group of antibacterial proteins including: peak I protein, diptericin A, diptericin B, diptericin C, and peak V protein. Administration of L-canavanine at the time of mechanical injury results in the incorporation of this arginine antagonist into these proteins. Canavanine replacement for arginine causes a total loss of detectable antibacterial activity for diptericin B and diptericin C, whereas diptericin A and peak V protein are severely inhibited. This loss in biological activity occurs in spite of the fact that canavanine stimulates induced protein synthesis. Analysis of the hydrolysate of diptericin A reveals that one-third of the 3 arginyl residues are replaced by canavanine. This investigation provides the first evidence that canavanine incorporation into a protein can impair its function.

Amino Acids↗
PubMed1989

Metabolism of benzo[a]pyrene and 7 beta,8 alpha-dihydroxy-9 alpha, 10 alpha-epoxy-7,8,9,10-tetrahydrobenzo[a pyrene in lung and liver of newborn mice.

Although the newborn mouse has been extensively used to test the tumorigenic activities of polynuclear aromatic hydrocarbons and their diol epoxide metabolites, no information is available on their metabolism in the newborn mouse in vivo. Therefore, we have investigated the metabolism and distribution of [3H]benzo[a]pyrene ([3H]BaP) and (+/-)-7 beta,8 alpha-[3H]dihydroxy-9 alpha, 10 alpha-epoxy-7,8,9, 10-tetrahydrobenzo[a]pyrene ([3H]BPDE) in liver and lung of mice given i.p. injections of these compounds on their 1st, 8th and 15th days of life. In lung, identified metabolites of [3H]BaP included diols, quinones, and phenols. Their levels were higher on the 1st day compared to the 8th and 15th days of life. The pattern of organic extractable metabolites detected in mouse liver was different from that in lung, being dominated by unidentified polar metabolites, the levels of which increased with age. Levels of [3H]BPDE in liver and lung were measured by trapping with 2-mercaptoethanol. It was demonstrated that [3H]BPDE rapidly reaches the lung after i.p. injections. The half-lives of [3H]BPDE in lung and liver were similar to those observed in vitro. The results are discussed with respect to the known tumorigenic activities of BaP and BPDE in newborn mice and in mouse skin.

7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide↗
PubMed1989

Determination of benzene, toluene and 1,3-butadiene in cigarette smoke by GC-MDS.

An analytical procedure was devised for the determination of selected gas phase constituents in cigarette smoke utilizing capillary gas chromatography and mass selective detection (GC-MSD); the MSD was used in the selective ion monitoring mode (SIM). The gas of freshly generated mainstream smoke was analyzed via a 10-port gas sampling valve on a puff-by-puff basis. Benzene, toluene, and 1,3-butadiene were found in the range of 6-73, 5-88, and 16-75 micrograms/cigarette, respectively. The gas phase of sidestream smoke was trapped in methanol using 3 midget impingers at -78 degrees C. Benzene in sidestream smoke was found in the range of 490-840 micrograms/cigarette; toluene and 1,3-butadiene levels were 1,090-1,690 and 300-470 micrograms/cigarette, respectively. Environmental tobacco smoke (ETS), sampled in a smoke-filled bar, was analyzed using the cold trap method. The concentrations of benzene and toluene in this indoor air were found to be 26-36 and 41-80 micrograms/m3, respectively, while 1,3-butadiene was present at 3.3-4.5 micrograms/m3.

Benzene↗
PubMed1989

Catechol-induced alterations in metabolic activation and binding of enantiomeric and racemic 7,8-dihydroxy-7,8-dihydrobenzo[a]pyrenes to DNA in mouse skin.

Catechol (1,2-dihydroxybenzene) is a potent co-carcinogen with benzo[a]pyrene (BaP) and with (+/-)-7,8-dihydroxy-7,8- dihydrobenzo[a]pyrene (BaP-7,8-diol) in mouse skin. The effects of catechol on the metabolic activation of (+)- and (-)-[3H]BaP-7,8-diols and on epidermal DNA adduct formation of racemic and enantiomeric [3H]BaP-7,8-diols were examined by applying the tritiated diols to mouse skin. The major metabolite of the (+)-[3H]BaP-7,8-diol was the hydrolysis product of (-)-[3H]-7 alpha, 8 beta-dihydroxy-9 beta, 10 beta-epoxy-7,8,9,10-tetrahydrobenzo[a]pyrene (anti-BPDE). This suggests that a peroxyl radical-mediated pathway is predominantly responsible for the epoxidation of this diol. Formation of (-)-anti[3H]BPDE from (+)-[3H]BaP-7,8-diol was greater than that of (+)-anti-BPDE from (-)-[3H]BaP-7,8-diol. Co-application of catechol with [3H]BaP-7,8-diols inhibited epoxidation of the (+) enantiomer to a greater extent than that of the (-) enantiomer. Catechol decreased the total DNA-binding and the formation of the major adduct with (+)-[3H]BaP-7,8-diol metabolites but catechol had no significant effect on the binding and formation of (+)-anti-[3H]BPDE-deoxyguanosine, the major DNA adduct derived from (-)-[3H]BaP-7,8-diol. Co-administration of catechol with (+/-)-[3H]BaP-7,8-diol increased the ratio of (-)- to (+)-[3H]BaP-7,8-diol derived major DNA adducts in mouse skin suggesting that catechol selectively inhibits certain pathways of metabolic activation of (+/-)-[3H]BaP-7,8-diol. Thus, catechol modifies the tumorigenic activity of (+/-)-BaP-7,8-diol either by alteration of the relative proportion of various hydrocarbon:DNA adducts or by a totally different as yet unexplored mechanisms.

7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide↗
PubMed1989

Effects of catechol on the induction of tumors in mouse skin by 7,8-dihydroxy-7,8-dihydrobenzo[a]pyrenes.

Catechol (1,2-dihydroxybenzene) is a major phenolic compound present in the co-carcinogenic fraction of cigarette tar. It has been shown to be a potent co-carcinogen with benzo[a]pyrene (BaP) in mouse skin. In this study we have examined the co-carcinogenic and co-initiating activities of catechol with racemic and enantiomeric 7,8-dihydroxy-7,8-dihydrobenzo[a]pyrenes (BaP-7,8-diols) in mouse skin. Similar to enhancement of BaP carcinogenesis, repeated concurrent applications of catechol and (+/-)-BaP-7,8-diol to mouse skin strongly enhanced (+/-)-BaP-7,8-diol tumor multiplicity and tumor incidence, and decreased latency. Co-application of catechol with the racemic or either of the enantiomers of BaP-7,8-diol in a two-stage initiation--promotion protocol increased the tumor initiating activity of racemic BaP-7,8-diol, similar to that of BaP, by approximately 50%, but had no statistically significant effect on the tumor initiating activity of the (+)- or (-)-enantiomers in mouse skin. Thus, catechol is as potent a co-carcinogen with (+/-)-BaP-7,8-diol as it is with BaP. However, as tested here catechol is a weak co-initiator when applied with (+/-)-BaP-7,8-diol or BaP.

7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide↗
PubMed1989

Identification and analysis of a nicotine-derived N-nitrosamino acid and other nitrosamino acids in tobacco.

Research on carcinogenic, tobacco-specific N-nitrosamines (TSNA) led to the identification and analysis of 4-(methylnitrosamino)-4-(3-pyridyl)butyric acid (iso-NNAC) in tobacco and tobacco smoke. In order to isolate iso-NNAC, an aqueous tobacco extract at pH 4 was partitioned with ethyl acetate after the other N-nitrosamino acids and TSNA were removed at pH 2 and pH 9 respectively. The structure of iso-NNAC was confirmed by GC-MS after enrichment of the methylated pH 4 fraction by chromatography on an alumina column. Iso-NNAC, 3-(methylnitrosamino)propionic acid, 4-(methylnitrosamino)butyric acid, N-nitrosoproline and TSNA were determined by GC-TEA in various smokeless tobaccos as well as in reference cigarettes. The levels of iso-NNAC in tobacco products ranged from 0.01 p.p.m. in chewing tobacco to 0.95 p.p.m. in dry snuff. The transfer rate of unchanged iso-NNAC into the mainstream smoke of a non-filter cigarette amounted to 0.85%. Iso-NNAC does not induce DNA repair in primary rat hepatocytes and is inactive as a tumorigenic agent in strain A mice.

Carcinogens↗
PubMed1989

The relationship of scrotal circumference to testicular weight in rams.

Scrotal circumference (SC), testicular diameter (TD) and testicular weight (TW) were measured at necropsy of 148 Merino rams of varying age (yearling: 110, 2- to 3-year-old: 5, 4-year-old: 28, greater than 7-year-old: 5). These rams, although culled from flocks in north western Queensland for poor conformation or advancing age, had no clinically palpable or gross necropsy lesions of the genitalia. Despite the fact that SC measurement was performed at necropsy on scrota with greatly varying wool cover and its diverse content of plant material (burrs and grass seeds), the correlation of SC with TW was positive, high and significant (r = 0.92, P less than 0.01). This correlation was greater than that between TD and TW (r = 0.91, P less than 0.01) even though both were measured after dissection of the scrotal contents. The clinically convenient SC measurement deserves wider application as an estimate of testicular weight and therefore fertility in rams.

Age Factors↗
PubMed1989

Immunoglobulin containing cells in normal and inflamed accessory sex glands of bulls.

The peroxidase-antiperoxidase (PAP) technique was used to identify cytoplasmic immunoglobulins in the accessory sex glands of 15 normal bulls and 13 bulls with inflammation of the ASG. Immunoglobulin containing cells (ICC) of the types IgA, IgM, total IgG, IgG1 and IgG2 were measured and their percentages expressed. In accessory sex glands from normal bulls, IgA containing cells were the most frequent in prostate and bulbourethral glands (86.7% and 86.1%, respectively of all ICC present) whereas in the ampulla, IgG containing cells comprised 78.6% of the ICC. IgG1 and IgG2 containing cells were present in all the accessory sex glands in approximately equal numbers. Frequencies of IgM containing cells in the ampulla, prostate and bulbourethral glands were 6.3%, 4.0% and 3.7%, respectively. Although all isotypes of ICC were present in the seminal vesicle, the very low number precluded accurate quantification. In inflamed ampulla, seminal vesicle, bulbourethral gland and colliculus seminalis, IgG containing cells were the most frequent ICC with values of 66.2%, 83.0%, 69.0% and 53.5%, respectively; IgA containing cells were the second in prevalence with values of 21.5%, 10.3% 19.3% and 40.5%, respectively. The contribution of ICC to the locally protective immunoglobulins in accessory sex gland secretions is discussed.

Animals↗