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Biomedical subjects

G T Bryan

Publications and source records attributed to G T Bryan.

At least 19 recordsLinked to original sources
PubMed1992

Inhibition of murine tumor growth by an interferon-inducing imidazoquinolinamine.

The low-molecular-weight imidazoquinolinamine derivative, 1-(2-methylpropyl)-1H-imidazo[4,5-c]quinolin-4-amine (imiquimod, previously described as R-837), induced alpha-interferon (IFN-alpha) in mice. IFN induction was identified at oral doses as low as 3 mg/kg. The 10% lethal dose for daily treatment with imiquimod was 200 mg/kg. Oral treatment with 30 mg/kg imiquimod once every three days significantly inhibited MC-26 colon carcinoma. Delay of treatment from day 1 to day 5, when tumors were easily palpable, did not reduce benefits. Ten daily treatments were slightly more effective than five. However, delivery of the same total dose of imiquimod either once every day for 20 days, once every 4 days, once every 7 days, or once every 10 days inhibited tumor growth to the same level. The antitumor effects of imiquimod were significantly abrogated by an antiserum to murine IFN-alpha, suggesting that the antitumor effect was to a substantial extent mediated by IFN induction. Imiquimod also significantly reduced the number of lung colonies in mice inoculated i.v. with MC-26 tumor cells. Combination of treatment with imiquimod and cyclophosphamide was significantly (P less than 0.01) better than treatment with either drug alone. Combination treatment with cyclophosphamide led to cures in some of the mice inoculated either s.c. or i.v. with MC-26 cells. Treatment with imiquimod also inhibited the growth of RIF-1 sarcoma and Lewis lung carcinoma but was ineffective for P388 leukemia. Imiquimod is an oral IFN-alpha inducer with antitumor effectiveness for transplantable murine tumors.

Aminoquinolines↗
PubMed1992

Trimetrexate in advanced renal cell carcinoma. An ECOG phase II trial.

Thirty-four chemotherapy-naive, ambulatory patients with advanced renal cell cancer were treated with the non-classical antifol trimetrexate at the intravenous dose of 12 mg/m2 daily x 5 every three weeks (8 mg/m2 qd x 5 for greater than 30% bone marrow previously irradiated). One patient experienced a partial response lasting 24 weeks for a response rate of 3% (exact 95% CI, 0.1 to 15.3%). Toxicity was manageable and primarily myelosuppression, gastrointestinal, and mucosal. Trimetrexate has little activity in advanced renal cell carcinoma at this dose and schedule.

Adult↗
PubMed1992

Nucleotide sequence of the coat protein gene of a strain of clover yellow vein virus from New Zealand: conservation of a stem-loop structure in the 3' region of potyviruses.

The sequence of the 3'-terminal 1492 nucleotides of the genome of a New Zealand isolate of clover yellow vein potyvirus (CYVV) has been determined. This sequence encodes a large open reading frame of 1314 nucleotides, the start of which was not identified, but which encodes a putative 272 amino acid coat protein. Downstream of the coat protein coding region is a 177 nucleotide untranslated sequence terminated by a polyadenylate tract. Comparison of the deduced CYVV-NZ coat protein amino acid sequence with two other strains of CYVV showed 86-93% similarity, suggesting CYVV-NZ should be regarded as a separate CYVV strain. CYVV-NZ shares with other CYVV strains a direct repeat of 14-16 nucleotides that is capable of forming a stem-loop structure. Examination of 35 strains of 15 other potyviruses showed a similar stem-loop structure conserved in all cases. A possible role in replication is hypothesized for the structure.

Amino Acid Sequence↗
PubMed1992

Height, infant-feeding practices and cardiovascular functioning among 3 or 4 year old children in three ethnic groups.

Barker recently hypothesized that factors affecting prenatal and infant growth are related to adult blood pressure and CVD mortality. Predictions from Barker's hypothesis in regard to infant feeding were tested among a sample of 3 or 4 year old children. The relationship of infant-feeding characteristics (duration of breast-feeding, times of introduction of high fat, high carbohydrate, high potassium foods and table salt) to indicators of cardiovascular functioning (resting blood pressures and heart rates, and heart rate response to graded activity) while controlling for anthropometric (height, sum of seven skinfolds, BMI) and demographic (ethnicity, gender, social status) characteristics revealed that infant-feeding practices were not related to CV functioning in the predicted directions among this sample of 3 or 4 year old children. Furthermore, the positive relationship between height and systolic blood pressure was inconsistent with the Barker hypothesis.

Black or African American↗
PubMed1991

Mutagenicity of N- and O-acetyl derivatives of methyl 3,4-diphenyl-5-hydroxylamino-2-furoate and N-hydroxy-4-aminobiphenyl in Salmonella typhimurium.

Methyl 3,4-diphenyl-5-hydroxylamino-2-furoate (N-OH-MDPF) (I), methyl 3,4-diphenyl-5-acetoxyamino-2-furoate (N-OAc-MDPF) (II), methyl 3,4-diphenyl-N-hydroxy-5-acetylamino-2-furoate (N-OH-MDPAF) (III), and methyl 3,4-diphenyl-N-acetoxy-5-acetylamino-2-furoate (N-OAc-MDPAF) (IV) were synthesized and tested for mutagenic activity for Salmonella typhimurium TA98 and TA100. The hydroxylamine (I) and acetyl derivatives (II-IV) did not show mutagenic activity in TA98 or TA100. In contrast, the parent nitro compound, methyl 3,4-diphenyl-5-nitro-2-furoate (MDPNF) (V) was found to be equally active in TA98 and TA98-DNP, and more active in TA100 and TA104. The mutagenic activity in TA100 and TA104 decreased significantly under anaerobic conditions. Additionally, MDPNF was previously shown to be less mutagenic in the nitroreductase-deficient derivatives TA100NR and TA98NR, suggesting a requirement for nitro reduction. Incubation of V with NADPH and bacterial lysates of TA98 or TA98NR yielded a metabolite which was identified as I based on chromatographic and mass spectral characteristics. The rate of reduction by the lysate of TA98NR was about one-third that of TA98, showing a correlation between mutagenicity and nitroreductase activity. The lysates of TA98 did not reduce N-OH-MDPF further to the amine. In contrast to the lack of mutagenic activity of I-IV, N-hydroxy-4-aminobiphenyl (N-OH-ABP) and its acetyl derivatives were active in TA98, but less so in TA98-DNP. These data suggest that mechanisms involving O-acetylation of N-hydroxylamine to the acetoxyamine or acyl transfer reactions are not involved in the generation of mutagen from MDPNF. Furthermore, the differential mutagenic response of V in TA98 and TA98NR, its reduction to I, and the lack of activity of I suggest that the intermediates of reduction between the nitro and hydroxylamine, such as nitro or nitroso free radical anions, may be involved in mutagenesis. The decreased response of V under anaerobic conditions and increased response in TA104 suggest that secondary oxygen radicals generated from reduction intermediates may be responsible for the mutagenicity of MDPNF.

Aminobiphenyl Compounds↗
PubMed1990

Protection from carcinogen-induced murine bladder carcinoma by interferons and an oral interferon-inducing pyrimidinone, bropirimine.

Interferons (IFNs) have established activities as antivirals and inhibitors of viral and transplantable tumors. To establish whether IFNs or their inducers can affect induction of carcinogenesis in vivo, the bladder-specific carcinogen N-[4-(5-nitro-2-furyl)-2-thiazolyl]formamide (FANFT) was administered in the diet at 0.11 or 0.13% (w/w) to female C3H/He mice beginning at 7 weeks of age. Mice treated with the IFN-inducing bropirimine [2-amino-5-bromo-6-phenyl-4(3H)-pyrimidinone] i.p. twice a week for 14 weeks starting on day 30 of start of FANFT feeding developed fewer transitional cell carcinomas (TCC) than mice treated with the vehicle. Bropirimine (200 mg/kg twice a week) orally resulted in even greater effectiveness: 6 of 43 bladders with TCC for bropirimine-treated mice versus 24 of 39 for control glycine buffer-treated mice (P less than 0.01, x2 test). Mice treated i.p. daily on days 29 through 210 with 5,000 units of beta interferon (specific activity, 2.0 x 10(8) units/mg) had 0 of 15 TCC while control mice had 7 of 13 TCC (P less than 0.001). Bladders of untreated mice were also significantly heavier than those of beta interferon- or bropirimine-treated mice. This dose of IFN treatment was confirmed as effective in a second experiment, in which mice were treated daily on days 30-223 with 5,000 units alpha/beta interferon (specific activity, 1.2 x 10(7) units/mg). This resulted in 4 of 25 bladders with TCC versus 24 of 39 for control mice (P less than 0.001). A higher dose of IFN (50,000 units alpha/beta interferon daily) was toxic; 24 of 30 mice died within 2 months. IFN and an IFN inducer, bropirimine, inhibited development and progression of FANFT-induced bladder TCC in vivo and thus may have roles as chemopreventive modalities.

Animals↗
PubMed1990

Ethnicity, infant-feeding practices, and childhood adiposity.

There has been professional concern that the type of milk used for infant-feeding may lead to adiposity. Studies of the relationship between infant milk-feeding and adiposity, however, have led to inconsistent results. This study investigated the relationship of infant-feeding practices to three indicators of adiposity: body weight, body mass index (BMI) and sum of seven skinfolds. The sample includes children at 3 or 4 years of age, in three ethnic groups. Multivariate techniques assessed the relationship among practices of infant-feeding with three indicators of adiposity, while considering potential confounding variables. Although a weak bivariate relationship was detected between the duration of breastfeeding and body weight, none of the measures of infant-feeding were related to the three indicators of adiposity. Black-American girls had smaller skinfolds than Anglo- or Mexican-American girls, with no ethnic group differences among boys. Concerns about adiposity due to methods of infant-feeding can be allayed, at least among 3- or 4-year-old children.

Black or African American↗
PubMed1989

Hexachlorobenzene episode in Turkey.

During the period 1955-1959, approximately 4000 people in southeast Anatolia developed porphyria due to the ingestion of hexachlorobenzene (HCB), a fungicide added to wheat seedlings. These HCB exposures subsequently led to the development of bullae on sun-exposed areas, hyperpigmentation, hypertrichosis, and porphyrinuria. The condition was called kara yara or "black sore." Many of the breast-fed children under the age of 2 years whose mothers had ingested HCB-treated grain died from a disease known as pembe yara or "pink sore." In this follow-up study of 252 patients, 20-30 years postexposure, there were 162 males and 90 females, with an average current age of 35.7 years, an average of onset of 7.6 years, and a duration of 2.2 years. Many patients had dermatologic, neurologic, and orthopedic symptoms and signs. The observed clinical findings include scarring of the face and hands (83.7%), hyperpigmentation (65%), hypertrichosis (44.8%), pinched facies (40.1%), painless arthritis (70.2%), small hands (66.6%), sensory shading (60.6%), myotonia (37.9%), cogwheeling (41.9%), enlarged thyroid (34.9%), and enlarged liver (4.8%). Urine and stool porphyrin levels were determined in all patients, and 17 have at least one of the porphyrins elevated. A total of 56 specimens of human milk obtained from mothers with porphyria were analyzed for HCB. The average value was 0.51 ppm in HCB-exposed patients compared to 0.07 ppm in unexposed controls. Offspring of mothers with three decades of HCB-induced porphyria appear normal.

Adolescent↗
PubMed1988

Schedule-dependent variations in the response of murine P388 leukemia to cyclophosphamide in combination with interferons-alpha/beta.

Positive therapeutic effects of interferons (IFNs) in combination with other therapies will depend on defining modalities, doses, and timing of treatment in the setting of varied tumor burdens. When 10(4) P388 leukemia cells were inoculated i.p. on day 0 in BALB/c x DBA/2 F1 mice, all mice died within 18 days if left untreated. Murine IFN-alpha/beta (5 x 10(5) units) injected daily i.p. on days 5-9 resulted in 20% increase in life span (ILS) (P less than 0.0001). Cyclophosphamide (CY) (100, 33, or 15 mg/kg) was injected i.p. once 2 days before start (day 3), simultaneously with start (day 5), or 2 days after cessation of IFN treatment (day 11). When 100 mg/kg CY alone were injected on day 3 or 5, all mice survived more than 90 days and were considered cured. When IFN was given after this curative dose of CY, more tumor deaths occurred; up to 100% of the mice died when 100 mg/kg CY on day 3 were combined with IFN on days 5-9. Increased mortality with the combination was not due to added toxicity of CY and IFN since the mice developed abdominal tumors and ascites. Mice not inoculated with tumor cells and treated similarly suffered only a transient weight loss, had only moderate white count depression, and did not die. When IFN was injected before CY on days 1-5 (instead of days 5-9), IFN did not alter the effectiveness of CY (100 mg/kg on day 5). In contrast to these results, when CY (100 mg/kg) was administered on day 11, after IFN (days 5-9), an augmented survival occurred with 119% ILS and 40% cures (CY alone on day 11 resulted in 69% ILS but no cures). In addition, when CY at a lower dose of 15 mg/kg was injected in combination with IFN, survival was consistently augmented by IFN; e.g., CY alone on day 3 caused 40% ILS and with IFN (days 5-9) 60% ILS (P less than 0.0001). Qualitatively similar findings were obtained when P388 leukemia cells were inoculated s.c. and the drugs delivered i.p. Inhibition by IFN of antitumor effects of a second alkylating agent, 1,3-bis(2-chloroethyl)-1-nitrosourea, was also identified. Thus, IFN-alpha/beta potentiated suboptimal CY effects for P388 leukemia, had neutral effects when injected before CY treatment, and inhibited antitumor activity of curative CY or nitrosourea schedules.

Animals↗
PubMed1988

Recontacting subjects in mutagen-exposure-monitoring studies: II. Results of a questionnaire study of mutagenesis researchers, with review of the pertinent literature.

A questionnaire on the attitudes of mutagenesis researchers regarding the health significance of and the use of data from tests of human mutagen exposure or genetic damage was completed by 71 of 312 (23%) individuals who had been participants in meetings or organizations concerned with mutagenesis research. On a point scale of 0 to 10, with 0 indicating strong disagreement, 5 indicating uncertainty, and 10 indicating strong agreement, the average respondent felt (8.31 +/- 2.27) that data indicating a probable health hazard should be shared automatically with the subjects, but was also moderately concerned about psychological distress of subjects learning of study results indicating abnormally high mutagen exposure (6.14 +/- 2.57) or genetic damage (6.94 +/- 2.48). The average respondent felt that follow-up of subjects could improve the quality of mutagen-exposure-monitoring studies (8.33 +/- 1.49), disagreed that subjects whose laboratory data suggested unusually severe exposure or damage should not be asked about possible sources of exposure (1.15 +/- 1.32), and disagreed that it was ethical to follow up but not discuss results with subjects having laboratory evidence of abnormal mutagen exposure (3.78 +/- 3.43) or genetic damage (3.06 +/- 3.17) to see how many developed cancer relative to a control group. Fifteen specific tests for measuring mutagen exposure or genetic damage were rated on a scale of 0 to 10, with 0 being "totally experimental" and 10 being "absolutely diagnostic of degree of exposure or genetic damage." Values ranged from 6.13 +/- 2.67 for karyotyping leukocytes to 3.43 +/- 2.43 for quantifying frequency of rare red cells with mutant protein. This study may help in decision making regarding follow-up of mutagen-exposed subjects.

Attitude↗
PubMed1987

Presence and measurement of sample histidine in the Ames test: quantification and possible elimination of a source of false-positive mutagenicity test results.

Both histidine and dipeptides that can be converted to histidine can potentially interfere with the Ames test by increasing the number of spontaneous revertants. Such interference might be especially evident when urine and other biological samples are studied in this assay. We have developed a turbidimetric bioassay that utilizes a nonrevertible Salmonella typhimurium histidine auxotroph, NS1135. The assay is linear with histidine over at least a 300-fold range (0.015-5 micrograms/ml of L-histidine.HCl.H2O). Data indicate that several histidine-containing dipeptides can be utilized as efficiently as free histidine. Our data suggest that this assay may be used to measure biological samples accurately for their histidine content and thereby permit an adjustment for sample histidine during the setup of Ames assays, thus eliminating increased reversion caused by sample histidine.

Biological Assay↗
PubMed1987

Effect of interferon alpha, interferon beta, and interferon gamma on the in vitro growth of human renal adenocarcinoma cells.

Interferon-alpha, interferon-beta, and interferon-gamma differ in their antiproliferative effects for several cell lines. Interferons were thus assessed for their activity in inhibiting proliferation of three renal cell carcinoma cell lines. The malignant epithelial phenotype of each of these cell lines was confirmed by electron microscopy, histology, karyotype and tumorigenicity. When compared on an anti-viral unit basis, naturally produced interferon-beta was more effective than natural interferon-alpha for all cell lines and clones. Proliferation of each of the cell lines was inhibited by interferon-gamma. In all cases, removal of interferons from culture media resulted in resumption of the rate of cell growth after a variable delay of 6-10 days. If the antiproliferative effects of interferons predominate in mediating tumor regression, clinical response may depend upon the type of interferon to which the tumor is exposed.

Adenocarcinoma↗
PubMed1987

Escherichia coli infection of the urinary bladder: induction of tumours in rats receiving nitrosamine precursors and augmentation of bladder carcinogenesis by N-nitrosobutyl (4-hydroxybutyl)amine.

Experimental introduction of Escherichia coli type 04 into the subserosa of the urinary bladder of female Fischer 344 rats produced chronic bacterial infection in more than 90% of animals. Groups of rats with bacterial infection were given sodium nitrate and either piperazine (Group 1) or dibutylamine (Group 2) in the drinking-water. Control, noninfected animals received nitrate and either piperazine (Group 3) or dibutylamine (Group 4). At 40 weeks, transitional-cell carcinomas of the bladder were detected in 9/30 rats in Group 1 compared to 0/34 in Group 3 (p less than 0.0005), and in 11/34 rats in Group 2 compared to 0/32 in Group 4 (p less than 0.0003). Early changes were examined by scanning and transmission electron microscopy as well as autoradiography. Preneoplastic liver foci were detected in infected groups of animals receiving amine and nitrate, indicating reabsorption of the carcinogen synthesized in situ to induce distant organ transformation. In another experiment, E. coli infection augmented bladder carcinogenesis by N-nitrosobutyl(4-hydroxybutyl)amine (NBHBA), as indicated by earlier appearance of bladder tumours (six weeks compared to nine weeks) and, after 25 weeks, higher incidences of transitional-cell carcinomas (41/46 compared to 39/53, p less than 0.05), squamous metaplasia (43% compared to 9%, p less than 0.0001), glandular metaplasia (26% compared to 13%, p less than 0.05) and muscle invasion (30% compared to 11%, p less than 0.01) in the E. coli-infected group receiving carcinogen compared to the noninfected group receiving carcinogen, respectively. These results indicate that bacterial infection of the urinary bladder may play a major role in bladder carcinogenesis, both by helping in-situ nitrosamine synthesis and by augmenting carcinogenesis by nitrosamines.

Amines↗
PubMed1986

Urine recovery experiments with quercetin and other mutagens using the Ames test.

Recovery from urine of the mutagenic activity of 2-anthramine, cyclophosphamide, 7,12-dimethylbenz[a]anthracene, 6-chloro-9-((3-(2-chloroethylamino)-propyl)amino)-2-methoxyacridin e dihydrochloride (ICR-191), mitomycin-C, nitrofurantoin, and quercetin was studied with several of the Ames tester strains using acetone-extracted XAD-2 columns with yields ranging from 27% to 79%. Dose responses of the pure chemicals were also studied, and results showed TA 97 to be far more susceptible to quercetin mutagenesis than TA 1537. Reducing pour plate agar volume enhanced mutagenesis.

9,10-Dimethyl-1,2-benzanthracene↗
PubMed1986

A protocol for the combined biochemical and serological identification of the Ames mutagen tester strains as Salmonella typhimurium.

Previously published reports have noted biochemical reactions atypical of Salmonella among the Ames tester strains of Salmonella typhimurium, and an inability to assign the strains to a specific Salmonella O (heat-stable cell wall) antigen group. We studied the biochemistry and serology of strains TA97, 98, 100, 102, 104, 1535, 1537, and 1538 in an attempt to develop a protocol to correctly speciate the strains. Biochemical reactions of all eight strains using standard media supplemented with histidine and biotin were consistent with those of the genus Salmonella. Strains TA100, 104, and 1535 were assigned to Salmonella O groups using bacteria treated with hot ethanol (White schema). H (flagellar) antigen assignments were performed successfully with seven of the eight strains. Two H antigen assignments required the use of the Craigie tube test for selection of motile revertants. Combining our biochemical and serological results obtained by this protocol, we were able to correctly speciate TA100, 104, and 1535 as Salmonella typhimurium. Our results demonstrate that representatives of the tester strains can be correctly speciated provided that procedures are followed that allow for the unusual nutrient requirements, the deep rough cell wall mutation, and the variably deficient motility of these organisms.

Antigens, Bacterial↗
PubMed1986

The influence of niacin and nicotinamide on in vivo carcinogenesis.

Data concerning effects of the essential vitamin niacin and its active form nicotinamide were evaluated. Dietary deficiencies and excesses of these nutrients by themselves do not appear to exert any influence on in vivo carcinogenesis in animals. Varying results were produced when nicotinamide was administered at pharmacologic doses concurrently with or following carcinogen administration to mice or rats. Some investigators found significantly increased tumor formation, whereas others reported a decreased effect or no effect. Epidemiologic studies have not investigated the relationship between niacin deficiency or excess and carcinogenesis in humans.

Animals↗