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Biomedical subjects

D Hoffmann

Publications and source records attributed to D Hoffmann.

At least 271 records · Page 15Linked to original sources

Growth of epizootic hemorrhagic disease, akabane, and ephemeral fever viruses in Aedes albopictus cells maintained at various temperatures.

The growth curves of one epizootic hemorrhagic disease (EHD) virus serotype (Reoviridae), two Akabane virus strains (Bunyaviridae) and three bovine ephemeral fever (BEF) group viruses (Rhabdoviridae) were determined in Aedes albopictus cells maintained at 15, 20, 28 and 33 degrees C. Ae albopictus cells supported the growth of all the viruses although not necessarily at all temperatures. Because none of the viruses exhibited cytopathic effect in Ae albopictus cells, growth was assayed in baby hamster kidney 21 (BHK21) cells maintained at 37 degrees C. The temperature at which the Ae albopictus cells were maintained had a marked effect on the growth and yield for each virus studied. EHD virus was heat-stable and grew after 4 days at 28 and 33 degrees C, and after 8 days at 20 degrees C. No growth was recorded up to 12 days at 15 degrees C. The two Akabane viruses were heat-sensitive and exhibited different growth patterns. One strain (B8935) showed no growth at 15 degrees C and only minimal growth at 20, 28 and 33 degrees C. The other strain (CSIRO 16) showed growth after 1-2 days at all temperatures with higher titres reached at 15 and 20 degrees C than at 28 and 33 degrees C. The BEF group viruses grew to approximately the same titres at all temperatures. At the higher temperatures (28 and 33 degrees C) most of BEF group viruses had disappeared within 9 days. In contrast at the lower temperatures (15 and 20 degrees C), there was still virus present 18 days after inoculation.(ABSTRACT TRUNCATED AT 250 WORDS)

Aedes↗

Dose-response study of the carcinogenicity of tobacco-specific N-nitrosamines in F344 rats.

Tobacco and tobacco smoke contain relatively high amounts of four tobacco-specific N-nitrosamines. Of these, N-nitrosonornicotine (NNN), 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK), and N'-nitrosoanatabine (NAT) were bioassayed at three dose levels by subcutaneous injections into male and female F344 rats in 60 subdoses amounting in total to 9,3, and 1 mmol/kg. Compared with the solvent control group (trioctanoin), both NNN and NNK induced significant numbers of tumors of the nasal cavity (P less than 0.01) at all three dose levels in both male and female rats. Significant numbers of tumors were also induced by NNK in the lung at all three dose levels and in the liver at the highest dose level (P less than 0.05). In addition to nasal tumors NNN also induced esophageal tumors at a significant rate in male rats at the high and medium dose levels and in female rats at the high level (P less than 0.05); NAT was inactive at the three doses tested. Bioassays at lower dose levels as well as biochemical studies are strongly indicated for NNN and NNK since these nitrosamines occur in relatively high amounts in both chewing tobacco and tobacco smoke.

Animals↗

A study of betel quid carcinogenesis. IV. Analysis of the saliva of betel chewers: a preliminary report.

Betel quid chewing is strongly associated with cancer of the oral cavity, especially when tobacco is added to the quid. It is our working hypothesis that, during chewing, Areca-derived N-nitrosamines are formed and, in the presence of tobacco, Nicotiana-specific N-nitrosamines are formed as well and further that these agents may contribute to the high risk of oral cancer in betel-quid chewers. This preliminary report presents our finding of N-nitrosoguvacoline in the saliva of betel-quid chewers (2.2-350 ppb). When the quid contains tobacco, the tobacco-specific N-nitrosamines, N'-nitrosonornicotine (1.2-38.3 ppb), N'-nitrosoanatabine (3.2-39.5 ppb), and 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (1.0-2.3 ppb) are also found in the saliva.

Areca↗

Detection of distant antigenic relationships between insect and bird lysozymes by ELISA.

We used an indirect enzyme-linked immunosorbent assay (ELISA) for measuring the immunological cross-reactivities between bird lysozymes and a lysozyme isolated from the blood of the insect Locusta migratoria. The degrees of cross-reactivity among five avian lysozymes measured by ELISA agreed approximately with those observed in earlier work using microcomplement fixation tests. This latter technique is not suitable for detecting immunological cross-reactivity between proteins that differ in sequence by more than 30%-40%. In contrast, ELISA is able to detect distant relationships between antigens such as lysozymes that differ in sequence by as much as 60%. It seems likely that the use of ELISA procedures will extend the range of homologous proteins that can be compared by immunochemical means.

Animals↗

Tumor-initiating activity of quinoline and methylated quinolines on the skin of SENCAR mice.

Quinoline and all 7 positional isomers of methylquinoline were assayed for tumor-initiating activity on the skin of SENCAR female mice with promotion by tetradecanoyl phorbol acetate. The total initiation dose of either quinoline or the isomeric methylquinolines was 7.5 mg per mouse. Quinoline induced tumors in 53% of the mice (0.73 tumors per animal). While 2-, 3-, 5- and 7-methylquinoline did not exhibit significant tumorigenic activity in this assay, 4-methylquinoline induced tumors in 45% of the mice (0.90 tumors per animal). 8-Methylquinoline induced tumors in 45% of the mice (0.66 tumors per animal).

Animals↗

Tobacco sidestream smoke: uptake by nonsmokers.

Some epidemiological studies indicate an association between passive smoking and an increased risk for cancer, especially for cancer of the lung. Other reports, however, have failed to confirm these findings. Biochemical analyses of the physiological fluids for markers of exposure to tobacco smoke are needed as measurements of the uptake of smoke components by nonsmokers and for the estimation of relative cancer risk to passively exposed persons compared with that to active cigarette smokers. This communication reports the uptake of carbon monoxide, hydrogen cyanide, and nicotine after passive smoke exposure under controlled conditions. The results indicate that salivary nicotine values reflect the level of recent passive smoke exposure within an hour and that urinary cotinine values indicate the level of passive smoke exposure in the preceding hours. N-Nitrosoproline has been shown to serve as an indicator of endogenous N-nitrosamine formation in cigarette smokers: yet, preliminary studies do not indicate that urinary excretion of N-nitrosoproline is increased following short-term passive smoke exposure. In infants, first field studies suggest a correlation between exposure to tobacco-smoke-polluted environments and levels of cotinine in both serum and urine.

Carboxyhemoglobin↗

Carcinogenic agents in cigarette smoke and the influence of nitrate on their formation.

The nitrate level of a nonfilter reference cigarette was elevated from 0.52% to 1.2, 1.8, 2.4 and 3.05%, respectively, by addition of sodium nitrate. Data from the mainstream smoke analyses of these cigarettes were compared. Yields of carbon monoxide and carbon dioxide were not significantly altered as a result of nitrate elevation. Tar, nicotine, benzo[a]pyrene (BaP) and catechol in mainstream smoke were reduced while yields of nitrogen oxides (NOx), volatile N-nitrosamines (VNA) and tobacco-specific N-nitrosamines (TSNA) were significantly increased. On the basis of previous bioassays with smoke condensates from high-nitrate cigarettes, it was expected that the cutaneous tumorigenicity of these tars would be reduced due to lower levels of BaP (and other carcinogenic PAH) and catechol. However, the total carcinogenic potential of whole smoke from high nitrate cigarettes is considered by us to be significantly increased due to the elevated yields of Nox, VNA and TSNA. The nitrosamines are regarded as a major group of carcinogens in tobacco smoke; the nitrogen oxides are the most important precursors for the endogenous formation of N-nitrosamines upon smoke inhalation. The findings of this model study support the recommendation that the nitrate content of tobacco products should be reduced.

Carcinogens↗

A study of betel quid carcinogenesis. 3. 3-(Methylnitrosamino)-propionitrile, a powerful carcinogen in F344 rats.

3-(Methylnitrosamino)propionitrile (MNPN) is formed in vitro under mild nitrosation conditions from the major areca alkaloid arecoline. It appears likely that MNPN is generated during betel quid chewing especially when tobacco is added to the quid. Upon subcutaneous injection of 1.1 mmol of MNPN in 60 subdoses, all of the 15 male and of the 15 female F344 rats developed tumors within 24 weeks. Twenty-six of the rats had tumors in two different organs at least. Twenty-seven rats had esophageal tumors, 21 nasal tumors, 11 had tongue tumors and two animals had either pharyngeal carcinomas or papillomas of the forestomach. No tumors were observed in the solvent control group. These data indicate that MNPN is a potent carcinogen.

Animals↗

The clinico-pathology of a malignant catarrhal fever syndrome in the Indonesian swamp buffalo (Bubalus bubalis).

Between September 1979 and May 1982, 50 of 177 swamp buffaloes became sick and died 83 to 719 days (mean 271) after being transferred to a research facility and housed in quarters adjacent to where sheep and goats were kept. The major clinical signs were anorexia, fever, conjunctivitis, scleral hyperaemia, ocular discharge, hyperaemia of skin, enlargement of lymph nodes and depression. Postmortem and histopathological lesions were observed in most of the tissues and organs of the body. A vasculitis with adventitial mononuclear cell infiltration and lymphoreticular reactions suggested a relationship to malignant catarrhal fever. The occurrence of serofibrinous epicarditis and myocarditis, which was seen in buffaloes in all cases, has not been a common finding in ruminants with malignant catarrhal fever.

Animals↗

Transmission and virological studies of a malignant catarrhal fever syndrome in the Indonesian swamp buffalo (Bubalus bubalis).

A malignant catarrhal fever-like syndrome in indonesian swamp buffalo was experimentally transmitted to one of 2 Bos indicus and 3 of 3 Bos javanicus cattle by intravenous inoculation of 250 ml of citrated, whole blood from affected buffaloes. The 4 cattle developed clinical signs of disease on average 32.5 days after receiving the inoculation of blood. The 4 cattle died after a variable period of illness. None of a further 3 B. javanicus cattle inoculated intravenously with a spleen homogenate prepared from another affected buffalo developed the disease. The experimental disease was clinically and pathologically similar to the natural disease in buffaloes although differences were noted. Attempts to adapt the agent to mice, guinea pigs and rabbits failed. A cytopathic agent (Japanese encephalitis virus) was isolated from the spleen of one buffalo with clinical signs but was not considered significant. Sixty-three B. indicus, 7 B. javanicus (and 6 of their crosses), 3 B. taurus and 4 Bubalus bubalis (Murrah buffalo) were kept in the same quarters where 50 of 177 swamp buffaloes died between September 1979 and May 1982. Four of the 7 B. javanicus cattle developed the clinical signs of disease and died. All the other cattle in contact remained healthy.

Animals↗

Carcinogenicity and metabolic activation of tobacco-specific nitrosamines: current status and future prospects.

Over the past decade, research on the carcinogenicity and metabolism of tobacco-specific nitrosamines has provided a basis for understanding their possible roles in human cancer. 4-(N-Nitrosomethylamino)-1-(3-pyridyl)-1-butanone appears to be the most important tobacco-specific nitrosamine, because of its strong carcinogenicity. A large population of smokers and snuff dippers is exposed to significant quantities of this and the other tobacco-specific nitrosamines on a daily basis. Further research should now focus on the relationship between human exposure to tobacco-specific nitrosamines and the risk of developing tobacco-related cancers. Several important areas can be identified: we need to develop sensitive assays that can be used routinely to quantify the levels of tobacco-specific nitrosamines or their metabolites in human blood, and the levels of their DNA adducts in human tissues; we need to establish, through comparative metabolic and DNA-binding studies, the relationships between the organospecificity of tobacco-specific nitrosamines in experimental animals and that in humans; we may also be enabled to identify naturally-occurring substances that can inhibit carcinogenesis by tobacco-specific nitrosamines. These research approaches will hopefully lead to a reduction in the incidence of tobacco-related cancers.

Animals↗

Anomalies of the external urethral orifice in girls.

In analyzing 1,000 of 1,475 micturating cystourethrograms in girls, the absolute number and the percentages of the different variations of the urethra were related to the frequency of urethrovaginal reflux and to anomalies of the meatus. This allowed the following deductions: There are no radiological findings in these girls that indicate the presence of subvesical obstruction. Anomalies of the meatus cannot be related to variations of the urethra as seen in the micturating cystourethrogram. They can, however, be the cause of enuresis, chronic urinary infection, urethrovaginal reflux, and disturbances in micturition. The marked susceptibility for chronic urinary infection seen in girls between the ages of 3 to 13 years is as yet not fully explained. The fact that the urethra opens near the anus and the vagina, inadequate hygiene, a too short urethra, and possibly missing hormonal protection against ascending infection, as well as the special urological anomalies described above, may all be responsible. Therefore, in girls there are a number of other disturbances micturition apart from of organic subvesical obstruction. These other disturbances may be termed functional, or the urethra syndrome.

Adolescent↗

Pharmacokinetics of tobacco-specific N-nitrosamines.

Methods were developed to determine the biological half-life of N'-nitrosonornicotine (NNN) and 4-(N-nitrosomethylamino)-1-(3-pyridyl)-1-butanone (NNK) in Syrian golden hamsters and Fischer rats. The formation and elimination of 4-(N-nitrosomethylamino)-1-(-3-pyridyl)-1-butanol (NNA1), the major metabolite of NNK, was determined in the context of this study. The method consisted of extraction of the nitrosamine with ethyl acetate, elution through a Clin-Elut column, and concentration of the sample, followed by gas chromatography-thermal energy analysis. Biological half-lives of NNN, NNK and NNA1 in hamsters were found to be 0.77, 0.25 and 1.78 h, respectively; in rats they were 5.78, 1.78 and 3.56 h. These findings clearly indicate species differences in the pharmacokinetics associated with the distribution and elimination of the tobacco-specific N-nitrosamines.

Animals↗

Endogenous formation of N-nitrosoproline upon cigarette smoke inhalation.

It was the goal of this study to assay the potential of inhaled cigarette smoke for endogenous N-nitrosation of amines in smokers by measuring urinary excretion of N-nitrosoproline (NPRO). Nonsmoking and smoking men were placed on a controlled diet which was low in proline and in ascorbic acid. On days 1-3, the volunteers received the controlled diet alone (Group I); on days 4-6, the diet was supplemented by a single daily dose of 300 mg proline (Group II); on days 7-9, the diet was supplemented by a single daily dose of 1 g ascorbic acid followed by 300 mg proline (Group III); and for the last three days, a single daily dose of 1 g ascorbic acid was given (Group IV). Collections of 24-h urine were made on days 3, 6, 9 and 12 of the study. The urine was analysed for NPRO, creatinine and cotinine. The mean 24-h NPRO excretion for 13 nonsmokers in Group I was 3.6 micrograms, whereas the NPRO excretion in 13 smokers was 5.9 micrograms/24 h, significantly higher than that of the nonsmokers (p less than 0.05). Urinary NPRO in 14 nonsmokers of Group II was significantly lower than that of the 14 smoking volunteers (p less than 0.05). In Group III smokers had reduced urinary levels of NPRO as a consequence of ascorbic acid intake. Differences in NPRO excretion by smokers and nonsmokers in Group IV were insignificant. These findings suggest that the documented endogenous N-nitrosation of proline which occurs as a result of cigarette smoke inhalation may also apply to other N-nitrosatable amines, including nicotine, and thus lead to in-vivo formation of carcinogenic N-nitrosamines. Four nonsmokers exposed to passive smoke for 80 min three times per day did not exhibit elevated NPRO levels in their 24-h urine.

Adult↗

Identification of the major adducts formed by reaction of 5-methylchrysene anti-dihydrodiol-epoxides with DNA in vitro.

5-Methylchrysene is metabolically converted to the bay-region dihydrodiol-epoxides, trans-1,2-dihydroxy-anti-3,4-epoxy-1,2,3,4-tetrahydro-5-methylchrysene (DE-I), in which the methyl group and the epoxide ring are in the same bay region, and trans-7,8-dihydroxy-anti-9,10-epoxy-7,8,9,10-tetrahydro-5-methylchrysene (DE-II). Previous studies have indicated that DE-I is more important in 5-methylchrysene carcinogenesis than is DE-II. Both DE-I and DE-II were individually reacted with calf thymus DNA in vitro. The DNA was enzymatically hydrolyzed to deoxyribonucleosides, and the modified deoxyribonucleosides were separated by chromatography on Sephadex LH-20 and analyzed by high-performance liquid chromatography. One major adduct and seven minor adducts were formed from each dihydrodiol-epoxide. The major adduct was, in each case, characterized by its pH-dependent partition coefficient, stability to base, mass spectrum, ultraviolet spectrum, and nuclear magnetic resonance spectrum as a deoxyguanosine derivative resulting from addition of the exocyclic amino group of deoxyguanosine to the benzylic carbon of the epoxide ring of the dihydrodiol-epoxide. The results of this study show that the major DNA adducts formed from 5-methylchrysene via DE-I and DE-II are structurally similar.

Animals↗