Search PubMed⌕ Search

Biomedical subjects

D Hoffmann

Publications and source records attributed to D Hoffmann.

At least 19 recordsLinked to original sources
PubMed1992

A study of tobacco carcinogenesis. XLVII. Bioassays of vinylpyridines for genotoxicity and for tumorigenicity in A/J mice.

3-Vinylpyridine is formed from nicotine during the smoking of tobacco products. Consequently it is found in mainstream and side-stream smoke of cigarettes and cigars and in environmental tobacco smoke. In this study, 3-vinylpyridine and its isomers 2- and 4-vinylpyridine as well as styrene (vinylbenzene) were bioassayed for mutagenicity in Salmonella typhimurium strains TA 1535, TA 1538, TA 98 and TA 100 and for their genotoxicity in the rat hepatocyte DNA-repair test. In both in vitro assays-all three vinylpyridines and styrene were inactive. In a test for tumorigenicity in which the test compounds were injected intraperitoneally into A/J mice (total dose 200 mumol/animal) there was no significant incidence of lung adenoma nor of any other type of tumors.

Animals↗
PubMed1992

Insect immunity: developmental and inducible activity of the Drosophila diptericin promoter.

Diptericins are 9 kDa inducible antibacterial peptides initially isolated from immune haemolymph of Phormia (Diptera). Following the isolation of a Drosophila cDNA encoding a diptericin homologue, we have now cloned a genomic fragment containing the Drosophila diptericin gene. To dissect the regulation of this gene, we have transformed flies with a fusion gene in which the reporter beta-galactosidase gene is under the control of 2.2 kb upstream sequences of the diptericin gene. We show that such a fusion gene is inducible by injection of live bacteria or complete Freund's adjuvant and respects the tissue specific expression pattern of the resident diptericin gene. Our analysis reveals at least four distinct phases in the regulation of this gene: young larvae, late third instar larvae, pupae and adults. This complexity may be related to the presence in the upstream sequences of multiple copies of response elements previously characterized in genes encoding acute phase response proteins in mammals (e.g. NK-kappa B, NF-kappa B related, NF-IL6 response elements).

Acute-Phase Proteins↗
PubMed1992

Potential use of robots in endoscopic neurosurgery.

A 6-axis stereotactic robot has been designed and linked to a stereotactic frame for routine use. Robot software allows the positioning of a probe holder in order to reach a given target. A calibration step enables the robot to compute the position of the x-ray beam and correct its final position to avoid parallax errors. The co-ordinates of the target are presently taken from anteroposterior and lateral X-rays using a digitizing table. Connection with a digitized angiography system is in progress and will allow direct sampling of numerical data from the x-ray data. Further steps will include connections with a 3D-reconstructed image from MRI and CAT as well as with a resident computerized atlas. Present experience after 14 months of daily practice represents 140 stereotactic procedures which can be extended to any special use, including endoscopic approaches.

Brain Diseases↗
PubMed1992

Stereotactic approach to intracranial lesions.

The diagnostic and therapeutic approach to intracranial lesions must be different considering the different possibilities offered by the various methods. The diagnostic reliability and safety of stereotactic biopsy are often indispensable in order to optimize the subsequent therapy. The results obtained in selected pathologies allow us to propose the stereotactic approach to treat: -various kind of cysts by aspiration and/or Beta endocavitary radiation therapy; -blood or abscessual collections that can be aspirated in a similar way; -arterio venous malformations or tumours by radiosurgery; -tumours by brachicurietherapy or by computer assisted stereotactic surgery. We present some cases treated at the C.H.S.A. of Paris and at the C.H.R.U. of Grenoble utilizing Talairach methodology.

Adolescent↗
PubMed1992

A study of tobacco carcinogenesis XLVIII. Carcinogenicity of N'-nitrosonornicotine in mink (Mustela vison).

During tobacco processing and smoking, nicotine and nornicotine give rise to N'-nitrosonornicotine (NNN), a highly abundant, strong carcinogen. NNN is known to exert carcinogenic activity in mice, rats and hamsters. Major target organs for NNN carcinogenicity in the rat are the esophagus and the nasal mucosa, and in the Syrian golden hamster trachea and nasal mucosa. In comparison with the rat, the mink (Mustela vison) has a markedly expanded nasal mucosa. Therefore, we explored in this study whether the mink could serve as a non-rodent model for nasal carcinogenesis using NNN as the carcinogen. Twenty random-bred mink, beginning at the age of 3 weeks, received twice weekly s.c. injections of NNN, a total dose of 11.9 mM per animal over a 38 week period. All of the 19 mink at risk developed malignant tumors of both the respiratory and the olfactory region of the nose within 3.5 years. In most animals the malignant tumors, primarily esthesioneuroepithelioma, invaded the brain. Remarkably, NNN induced no other tumors in the mink. None of the control animals developed nasal tumors nor tumors at other sites during the 3.5 years of the assay. The historical data from the farm did not reveal any spontaneous occurrence of nasal tumors in mink at any age. This study supports the concept that NNN is a proven carcinogen for multiple species of mammals and that the mink can serve as a non-rodent, non-inbred animal model for nasal carcinogenesis, especially since NNN induces only tumors in the nasal cavity in this species and not at other sites, as it does in mice, rats and hamsters.

Animals↗
PubMed1992

Analysis of tobacco-specific N-nitrosamines in indoor air.

A method was developed and applied for the assessment of tobacco-specific N-nitrosamines (TSNA) in indoor air polluted with tobacco smoke. Air samples were collected on Cambridge filters treated with 0.01 M potassium bisulfate, extracted with dichloromethane and enriched by column chromatography. The fraction containing the TSNA was concentrated and placed on a thermal desorption cartridge packed with Tenax GR. The sample was thermally desorbed and analyzed by capillary GC using a thermal energy analyzer. When the method was applied in a test laboratory in which one, two and four cigarettes were smoked during 30 min, linearity was observed. Field studies included sampling in bars, restaurants and trains. The concentration of N'-nitrosonornicotine (NNN) ranged from not detected to 23 pg/l, that of N'-nitrosoanatabine ranged from not detected to 9 pg/l, while 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) was detected in concentrations ranging from 1 to 29 pg/l. This means an exposure to NNN and NNK of 0.1-0.3 cigarette equivalents. Thus, non-smokers can be exposed to highly carcinogenic TSNA.

Air Pollution, Indoor↗
PubMed1992

A study of betel quid carcinogenesis--VIII. Carcinogenicity of 3-(methylnitrosamino)propionaldehyde in F344 rats.

In assays of Areca-specific N-nitrosamines, 3-(methylnitrosamino)propionaldehyde (MNPA) exhibits higher cytotoxicity than nitrosoguvacine (NGC), nitrosoguvacoline (NG) and 3-(methylnitrosamino)propionitrile (MNPN). NGC is not mutagenic. However, NG is a weak carcinogen in F344 rats while MNPN is a potent carcinogen; MNPA had thus far not been tested. In this study MNPA was injected s.c. at a dose of 6.57 mg three times weekly for 15 weeks (total dose 2.6 mmol/rat). During the 100 weeks of the bioassay, the treated F344 rats, and especially the females, showed significantly less weight gain than the control animals, indicating high toxicity for MNPA at the tested dose. Upon termination of the bioassay, the MNPA-treated animals were found to have tumors of the lung, liver, nasal cavity, forestomach and kidneys. The control animals showed no tumors in these organs. The incidence of lung tumors in the MNPA group was statistically significant (P less than 0.025). The results of this study show that MNPA is a carcinogen in F344 rats.

Adenocarcinoma↗
PubMed1992

Bioavailability of tobacco-specific N-nitrosamines to the snuff dipper.

Use of supercritical carbon dioxide extraction in the analysis of smokeless tobacco for tobacco-specific N-nitrosamines revealed the presence of higher levels of 4-(methylnitros-amino)-1-(3-pyridyl)-1-butanone (NNK) than had been determined with conventional methods. Whether human saliva may be similarly capable of releasing apparently bound NNK during chewing or snuff dipping was tested by incubating smokeless tobacco with enzymatically active saliva and with heat-treated saliva respectively. Enzymatically active human saliva was found to liberate up to twice the amount of the highly carcinogenic NNK than did heat-treated saliva. This is of major consequence for the cancer risk assessment of snuff dippers and tobacco chewers.

Biological Availability↗
PubMed1992

[The EGF receptor pathway in human cerebral tumors].

The epidermal growth factor receptor gene is the most frequently involved proto-oncogene in human glial brain tumors, in the present series in agreement with previous reports in literature. It is therefore important to study this gene from DNA to the protein product. The vicinity of cystic fluid (C.F.) to tumor cells of the cystic wall has suggested investigation of possible "E.G.F.-like" autocrine activities in C.F. In 40% of gliomas, E.G.F.-R. gene is amplified and overexpressed. This is never observed in low grade astrocytomas. In 12% of the cases, mutations of the E.G.F.-R. gene are observed. In correlation with genomic abnormalities, E.G.F.-R. is immunoprecipitated in 40% gliomas. The basal phosphorylation of the receptor is increased in 50% gliomas. In C.F., unexpectedly, E.G.F.-R. phosphorylation inhibitory effect is observed. Its biochemical analysis suggests an anti-tyrosine kinase activity. The observation of anti-tyrosine kinase activity in C.Fs suggests the presence of negative modulatory factors of the proto-oncogene activation in tumor tissues. This could have therapeutical interest.

Blotting, Northern↗
PubMed1992

[An unusual bone scintigram in osteomyelitis. A case report].

Despite hyperemia in the blood-pool phase of bone scintigraphy with 99mTc-MDP there was an decreased concentration of the nuclide in a 7-year-old boy with acute osteomyelitis of the femur. In addition to inflammatory destruction of the bone tissue, the other reason for this surprising scintigraphic finding might be a reduced blood flow because of thrombotic occlusion or compression of bone-supplying vessels.

Acute Disease↗
PubMed1991

Insect immunity. Isolation from a coleopteran insect of a novel inducible antibacterial peptide and of new members of the insect defensin family.

Injection of heat-killed bacteria into larvae of the large tenebrionid beetle Zophobas atratus (Insecta, Endopterygota, Coleoptera) results in the appearance in the hemolymph of a potent antibacterial activity as evidenced by a plate growth inhibition assay. We have isolated three peptides (A-C) from this immune hemolymph which probably account for most of this activity. Their primary structures were established by a combination of peptide sequencing and molecular mass determination by mass spectrometry. Peptide A, which is bactericidal against Gram-negative cells, is a 74-residue glycine-rich molecule with no sequence homology to known peptides. We propose the name coleoptericin for this novel inducible antibacterial peptide. Peptides B and C are isoforms of a 43-residue peptide which contains 6 cysteines and shows significant sequence homology to insect defensins, initially reported from dipteran insects. This peptide is active against Gram-positive bacteria. The results are discussed in connection with recent studies on inducible antibacterial peptides present in the three other major orders of the endopterygote clade of insects: the Lepidoptera, Diptera, and Hymenoptera.

Amino Acid Sequence↗
PubMed1991

Tumorigenicity of the tobacco-specific carcinogen 4-(methyl-nitrosamino)-1-(3-pyridyl)-1-butanone in infant mice.

The tobacco-specific nitrosamine, 4-(methyl-nitrosamino)-1-(3-pyridyl)-1-butanone (NNK), is a potent carcinogen in adult rodents and variably effective transplacentally, depending on species. In pursuit of the thesis that human infants may be especially vulnerable targets for tumor initiation by tobacco smoke constituents, we tested the efficacy of NNK as a tumor initiator in infant mice. Cr:NIH(S) (NIH Swiss outbred) mice were given 50 mg/kg NNK i.p. on postnatal days 1, 4, 7, 10 and 14, with saline to controls. At an average age of 13-15 months, 57% of the NNK-exposed male offspring had hepatocellular tumors, with a multiplicity of 1.15 +/- 1.4, including 4 with carcinoma. Liver tumors including 2 carcinomas were found in 8 (14%) of the NNK-exposed female offspring. There were no hepatocellular neoplasms in any control. A significant increase in primary lung tumors also occurred in the NNK-treated males, with an incidence of 30/55 (57%) and a multiplicity of 0.7 +/- 0.2, vs. 7/33 (21%), multiplicity 0.3 +/- 0.6, in controls (P less than 0.025). An apparent increase in the incidence of lung tumors in NNK-treated females, 21/57 (37%) vs. 7/32 (22%) in controls, approached significance (P less than 0.1). Thus NNK was a moderately potent neonatal carcinogen for liver and lung in infant Swiss mice and more efficacious in this regard than when received transplacentally by mice of the same strain.

Animals↗
PubMed1991

Long-term suppression of tremor by chronic stimulation of the ventral intermediate thalamic nucleus.

The usefulness of high-frequency stimulation of the ventral intermediate nucleus (Vim) as the first neurosurgical procedure in disabling tremor was assessed in 26 patients with Parkinson's disease and 6 with essential tremor. 7 of these patients had already undergone thalamotomy contralateral to the stimulated side, and 11 others had bilateral Vim stimulation at the same time. Chronic stimulating electrodes connected to a pulse generator were implanted in the Vim. Tremor amplitude at rest, during posture holding, and during action and intention manoeuvres was assessed by means of accelerometry. Of the 43 thalami stimulated, 27 showed complete relief from tremor and 11 major improvement (88%). The improvement was maintained for up to 29 months (mean follow-up 13 [SD 9] months). Adverse effects were mild and could be eradicated by reduction or cessation of stimulation. This reversibility and adaptability, allowing control of side-effects, make thalamic stimulation preferable to thalamotomy, especially when treatment of both sides of the brain is needed.

Aged↗
PubMed1991

Assessment of major carcinogens and alkaloids in the tobacco and mainstream smoke of USSR cigarettes.

Tobacco and mainstream smoke of USSR cigarettes were analyzed for carcinogens. The pH values of suspensions of the tobacco (5.4-5.6) and the nitrate content of the tobaccos (0.4-1.7%) were as expected for flue-cured and sun-cured tobaccos and mixtures thereof. The nicotine levels of the cigarette tobaccos (0.76-0.94%) and total alkaloid content (0.85-1.08%) were relatively low compared with tobaccos used in Western European and US cigarettes. The concentrations of tobacco-specific N-nitrosamines in the cigarette tobaccos were also low (N'-nitrosonornicotine 0.36-0.85 microgram/g) compared with those in bright, oriental and blended cigarette tobaccos in Western countries (0.3-19 microgram/g). The 2 non-filter and 4 filter cigarettes from the USSR had slow burning rates and yielded 14.0-16.7 puffs/cigarette, while puff yields for commercial cigarettes in Western countries average less than or equal to 11 puffs/cigarette. Consequently, tar and benzo(a)pyrene yields in the smoke of all cigarettes as well as nitrosamine yields were high, especially in the smoke of the filter cigarettes. It appears that an increase in the burning rates of these cigarettes should lead to lower smoke yields.

Alkaloids↗
PubMed1991

Composition of popular tobacco products in Thailand, and its relevance to disease prevention.

BACKGROUND: This report presents new findings on the composition of the three best-selling brands of commercially produced Thai cigarettes, representing about 80% of market share in Thailand, and six best-selling tobacco products, including hand-rolled cigarettes and cigars. RESULTS: With one exception, all Thai cigarettes yielded higher levels of tar and nicotine than U.S. brands sold in Thailand. High levels of tar, nicotine, and carbon monoxide (CO) were found in the smoke of popular Thai cigars (Khiyo) and Burmese cigars sold in Thailand. All tobacco products tested were ranked in order of smoke yields of tar (cigarettes, 4.5 to 40.8 mg/cigarette), nicotine (0.19 to 5.77 mg/cigarette), and CO (3.1 to 9.5 mg/cigarette). The labels "very strong," "strong," and "mild," used in rating the tobacco quality by the growers in Thailand, were not found to reflect the relative nicotine and tar yields. From 1985-1990, per capita consumption of cigarettes in Thailand increased 1.4-fold. CONCLUSION: This report provides information that may prove helpful in the evaluation of the tar, nicotine, and carbon monoxide yields of cigarettes and cigars in Thailand compared with levels in U.S. cigarettes. It is our goal to offer the scientific basis for voluntary and/or regulated reduction of the smoke yields of tobacco products in Thailand.

Advertising↗