Biomedical subjects

M S Bryant

Publications and source records attributed to M S Bryant.

At least 19 recordsLinked to original sources

PubMed1992

Hemoglobin adduct and hepatic- and urinary bladder-DNA adduct levels in rapid and slow acetylator Syrian inbred hamsters administered 2-aminofluorene.

The levels of covalently bound arylamine-hemoglobin and DNA adduct formation were used as dosimeters to measure the effect of acetylator genotype and sex on the metabolic conversion of the carcinogen, 2-aminofluorene, to reactive intermediates. A single high dose of 2-aminofluorene (60 mg/kg b.wt. i.p.) was administered to male and female homozygous rapid (Patr/Patr) acetylator hamsters (MHA/SsLaK) and homozygous slow (Pats/Pats) acetylator hamsters (Bio. 82.73/H). By using 32P-postlabeling assay methodology, a sole nonacetylated DNA adduct, which cochromatographed with authentic N-(deoxyguanosin-8-yl)-2-aminofluorene was detected at 3, 6, 12, 18 or 24 hr postdosing in liver and urinary bladder DNA of both rapid and slow acetylator hamsters. The highest levels were detected at 18 hr post 2-aminofluorene injection at which time the average levels of hepatic 2-aminofluorene-DNA adducts were similar between male and female rapid and slow acetylators. By comparison, the levels of 2-aminofluorene-DNA adducts in the urinary bladder at 18 hr were about 4-fold lower than in the liver, and were significantly greater in homozygous rapid than in homozygous slow acetylator counterparts (P less than .01). In both the liver and urinary bladder, the levels of 2-aminofluorene-DNA adducts were independent of sex. In contrast to the DNA adduct data, the levels of 2-aminofluorene-hemoglobin adducts, evaluated by capillary gas chromatography-mass spectrometry, were significantly higher in the homozygous slow acetylators than in homozygous rapid acetylators. However, there again were no differences between males and females.(ABSTRACT TRUNCATED AT 250 WORDS)

Acetylation↗

PubMed1991

Formation of C8-modified deoxyguanosine and C8-modified deoxyadenosine as major DNA adducts from 2-nitropyrene metabolism mediated by rat and mouse liver microsomes and cytosols.

2-Nitropyrene, the geometric isomer of the most studied nitropolycyclic aromatic hydrocarbon (nitro-PAH), 1-nitropyrene, is an environmental contaminant detected in ambient air and a potent direct-acting mutagen. Its metabolic activation leading to the formation of DNA adducts was studied. The activated metabolite, N-hydroxy-2-aminopyrene, was prepared and reacted with calf thymus DNA. Upon enzymatic hydrolysis of the DNA, the resulting nucleosides were separated by HPLC, and the adducts were characterized by mass and proton NMR spectral analysis. Both N-(deoxyguanosin-8-yl)-2-aminopyrene and N-(deoxyadenosin-8-yl)-2-aminopyrene, in a 5:2 ratio, were identified. These adducts were then utilized as standards to identify the DNA adducts formed from reaction of [3H]2-nitropyrene with DNA mediated by liver microsomes and cytosols of mouse and rat. In all cases, both adducts were formed. The quantities of the two adducts formed in each system were: mouse liver microsomes (11.3 pmol [3H]2-nitropyrene/mg DNA), rat liver microsomes (23), mouse liver cytosol (11.4) and rat liver cytosol (5.1). Thus, these adducts were formed in highest yield from rat liver microsomes and the lowest from rat liver cytosol. The deoxyguanosine/deoxyadenosine adduct ratio was higher from rat and mouse liver microsomes (7.8:9.2) than from rat and mouse liver cytosols (2.5:3.1). Our results represent the first direct demonstration of a C8-deoxyadenosine adduct being formed as a major product from the reaction of a nitro-PAH metabolite with DNA.

Animals↗

PubMed1990

Decline of the hemoglobin adduct of 4-aminobiphenyl during withdrawal from smoking.

The hemoglobin adduct of the human bladder carcinogen 4-aminobiphenyl (4ABP-Hb) declined in the blood of 34 smokers enrolled in a withdrawal program, from a mean of 120 +/- 7 (SE) pg/g of hemoglobin at the start to a mean of 82 +/- 6 pg/g after 3 weeks and a mean of 34 +/- 5 pg/g among the 15 exsmokers who had not resumed smoking after 2 months. Although 4ABP-Hb declined faster than expected under the assumption that the human erythrocyte has a life span of 120 days, it persisted much longer than cotinine. Therefore, 4ABP-Hb may complement the use of cotinine as a marker of exposure to tobacco smoke. The strength of the within-person association of 4ABP-Hb with smoking, coupled with the weakness of the between-person association (correlation coefficient, 0.33), is evidence that between-person variation in modifying factors is substantial. Study of the modifiers of 4ABP-Hb levels may help elucidate the etiology of human susceptibility to aromatic amine-induced bladder cancer.

Adult↗

PubMed1990

Haemoglobin adducts formed by aromatic amines in smokers: sources of inter-individual variability.

In a previous study we found that aromatic amines, particularly 4-aminobiphenyl, formed haemoglobin adducts at higher concentrations in the blood of smokers compared to non-smokers. We re-analyse here data on haemoglobin adducts of 14 aromatic amines in order to ascertain if the inter-individual variability left unexplained by tobacco smoking could be attributed to differences in individual metabolic patterns. For this purpose we computed residuals from analysis of variance in order to adjust for individual smoking habits (type and amount of tobacco). Residuals were correlated within two clearly distinct groups: one formed by binuclear compounds (4-aminobiphenyl, 3-aminobiphenyl and 2-naphthylamine) and the other formed by all other (i.e. mononuclear) compounds. Within each group, highly statistically significant correlation coefficients were found, whereas compounds belonging to one group were not correlated to compounds in the other group. These results can be interpreted as a suggestion that two different metabolic pathways exist, one for binuclear and one for mononuclear arylamines, and that inter-individual differences in such pathways can explain part of inter-individual variability in adduct levels. This interpretation is consistent with recent animal experiments suggesting that there are different enzyme systems for the two classes of compounds.

2-Naphthylamine↗

PubMed1989

Lability of steroid hormone receptors following devascularization of breast tumors.

Ischemia may invalidate hormone-receptor analyses. This study determined the effects of progressive ischemia on steroid hormone-receptor analyses. Breast cancer was induced in 50- to 60-day-old female Holtzman rats by intragastric administration of 25 mg of 7,12-dimethylbenz[a]anthracene. After 90 days, rats were anesthetized and breast tumors were devascularized in vivo. At 0, 30, 60, 90 and 150 minutes, a biopsy specimen from each tumor was taken and rapidly frozen. Steroid binding capacity for estrogen (ER), progesterone (PR), and androgen (AR) receptors was determined by incubation with tracer receptor ligand. Ischemia decreased ER and AR levels by 30 minutes, whereas PR levels were unchanged through 150 minutes of ischemia. Following mastectomy, tylectomy, or breast biopsy, PR may be the most reliable of the hormone receptors for determining endocrine-responsive breast cancer. However, for accurate determination of all hormone receptors, specimens should be frozen in liquid nitrogen immediately, then preserved at -70 degrees C, or processed immediately.

9,10-Dimethyl-1,2-benzanthracene↗

PubMed1989

Correlation of estrogen, progesterone, and androgen receptors in breast cancer.

Breast cancer was induced in female Holtzman rats by intragastric administration of 7,12-dimethylbenz[a]antracene (DMBA). At tumor maturity, biopsies of viable tissue were obtained, frozen, and then assayed for estrogen, progesterone, and androgen receptor content. By simple linear regression analysis, progesterone receptor levels significantly correlated with both estrogen and androgen receptor levels, whereas estrogen and androgen receptor levels did not correlate with each other. Multiple regression analyses further substantiated the predictive value of the progesterone receptor for the other two hormone receptors. Knowledge of breast tumor androgen receptor levels may further enhance the value of the estrogen receptor and progesterone receptor in hormonal responsiveness. Further, the progesterone receptor may be the most sensitive of the steroid hormone receptors for selecting patients likely to respond to hormonal therapy.

9,10-Dimethyl-1,2-benzanthracene↗

PubMed1989

Elevated blood levels of carcinogens in passive smokers.

The hypothesis that involuntary exposure to tobacco smoke--passive smoking--results in greater risk of cancer was assessed by measuring the levels of two known carcinogens in the blood of 57 nonsmokers with varying degrees of involuntary exposure, including six heavily exposed bartenders. The concentrations of hemoglobin adducts of 4-aminobiphenyl, a bladder carcinogen, were significantly higher in subjects with confirmed involuntary exposure (plasma cotinine concentrations between 2 and 23 ng/ml) compared with subjects with undetectable levels of cotinine. Similarly, adducts of 3-aminobiphenyl were significantly elevated in subjects with confirmed exposure. The odds of 3-aminobiphenyl adduct levels exceeding 2 pg/g of hemoglobin were 6:7 among the confirmed exposed, compared with the odds of 2:42 among subjects with undetectable cotinine (odds ratio = 18; 95 percent confidence interval = 3.3, 94). The validity of the assay was demonstrated by showing striking declines in adduct levels among quitting smokers.

Adult↗

PubMed1989

The effect of initial operative repair on the recovery of intestinal function in gastroschisis.

Recent reports concerning the treatment of gastroschisis suggest that primary closure results in more rapid return of gastrointestinal function, a shortened hospitalization, diminished perinatal complications, and improved long-term survival. A 4-year retrospective review of infants treated for gastroschisis at the University of Florida yielded 30 infants requiring repair of this abdominal wall defect. The series included 19 males and 11 females, and the average abdominal wall defect measured 4 cm in its greatest dimension. Nine infants (mean weight, 2,275 gm) were repaired using a staged closure using a silastic (six) or cutaneous (three) silo. Complete fascial closure was accomplished in an average of 8 days in the silastic group and 15 days in the infants with skin flaps. Mean age at start of enteral feeds was 23 days, with complete oral feedings at 43 days. Twenty-one infants (mean weight, 2,127 gm) underwent primary fascial closure. Three deaths occurred in the perioperative period: one from acute renal failure and two from sepsis secondary to a segment of necrotic intestine. An additional infant developed postoperative necrotizing entercolitis but recovered. Two infants in this group also had jejuno-ileal atresia requiring extensive small bowel resection. In the remaining 15 infants, oral alimentation was initiated for an average of 23 days, with full oral alimentation at 46 days. The data suggest that the recovery of the gastrointestinal system, adequate enough to support total oral alimentation, is unrelated to the initial surgical procedure chosen to obtain fascial closure in the newborn with gastroschisis. In addition, vigorous attempts at primary fascial closure may jeopardize intestinal viability, diminish ventilatory function, and result in unnecessary morbidity and mortality.

Abdominal Muscles↗

PubMed1988

Partial hepatectomy decreases pancreatic parenchymal enzyme activity.

In previous studies of liver regeneration following partial hepatectomy (PH) in rats, we noted a decrease in serum amylase activity. The present study was carried out to determine if the decrease in serum amylase following PH corresponds to a decrease in pancreatic parenchymal exocrine enzyme activity. Male Wistar rats (275 g) underwent either 60% PH or sham laparotomy (SL). A third group, serving as controls (CON), received no surgical procedure. All groups were pair-fed a nutritionally balanced diet. After 48 hr, pancreas, blood, and liver were removed for analysis. Results showed that PH decreased pancreatic parenchymal protein by 43%, lipase by 44%, and trypsin by 22% compared to controls. Serum amylase decreased by 28%, a finding similar to previous experiments. However, pancreatic parenchymal amylase activity was not affected. It remains to be determined whether the reduced pancreatic function affects digestion and absorption.

Amylases↗

PubMed1988

Hemoglobin adducts of aromatic amines: associations with smoking status and type of tobacco.

Hemoglobin adducts of 15 aromatic amines were determined in nonsmokers and smokers of blond- or black-tobacco cigarettes living in Turin, Italy. The subjects were all males age 55 or less and were representative of the population previously examined in a case/control study of bladder cancer. 4-Aminobiphenyl adduct levels were found to be significantly different in the three groups, and the differences were approximately proportional to the relative risk of each group. Adjustment for age and cigarette consumption did not materially influence the differences. A significant correlation of adduct levels with cigarette consumption was also observed for all smokers as well as for smokers of blond tobacco. Other amines for which significant differences between smokers and nonsmokers were observed were 3-aminobiphenyl, 2-naphthylamine, o- and p-toluidine, 2,4-dimethylaniline, and 2-ethylaniline. Some of these amines are human bladder carcinogens, and their occurrence in blood as hemoglobin adducts is evidence for their metabolic activation. Thus, by a combination of traditional epidemiological methods and modern chemical analyses, we have provided evidence for a biochemical basis for the often observed association between cigarette smoking and bladder cancer.

Adult↗

PubMed1988

Impact of emergency room laboratory studies on the ultimate triage and disposition of the injured child.

One hundred sixty six surviving pediatric trauma patients were retrospectively studied to assess the contribution of initial laboratory evaluations to clinical decision making in the emergency department (ED). All laboratory tests ordered, the results of those tests and the number of test results available before patient disposition from the ED were reviewed. A total of 626 laboratory studies were ordered in 166 patients. Results from only 68.5 per cent of the laboratory tests were available in the ED prior to the patient's transfer from the ED. Only 6.4 per cent of these results were abnormal. This low incidence of abnormal test results and preadmission availability questions the utility of extensive initial routine laboratory evaluations of the pediatric trauma patient. Based on this data, the current protocol has been revised to include hemoglobin/hematocrit determinations, type and screen, and urinalysis. Additional blood is obtained and appropriately labeled so that further studies can be performed if the patient's management should require baseline laboratory evaluations. This approach is more efficient, cost-effective, and no less sensitive in the initial evaluation and management of the injured child.

Adolescent↗

PubMed1988

Haemoglobin adducts of aromatic amines in people exposed to cigarette smoke.

In a population-based study in Turin, Italy, smokers of blond tobacco showed 4-aminobiphenyl (4-ABP) adduct levels some three times higher than nonsmoking subjects, and smokers of black tobacco showed levels about five times greater than nonsmokers. A dose-response relationship between the number of cigarettes smoked per day and 4-ABP adduct level was observed, but did not account for the higher adduct levels observed in smokers of black tobacco. Smoking-related increases in haemoglobin adducts were also observed for o-toluidine, p-toluidine, 2,4-dimethylaniline and 2-ethylaniline. Smoking subjects showed 3-aminobiphenyl adduct levels about 12 times greater than those of nonsmokers, who rarely showed a detectable level. This may indicate that there are fewer sources of 3-aminobiphenyl exposure not related to tobacco smoke. Smokers of black tobacco showed higher adduct levels than smokers of blond tobacco for 4-ABP, p-toluidine and 2,4-dimethylaniline.

2-Naphthylamine↗

PubMed1988

Abdominal complications of ventriculoperitoneal shunts. Case reports and review of the literature.

Ventriculoperitoneal (VP) shunting of cerebrospinal fluid (CSF) is the standard therapy for the management of hydrocephalus. Before the advent of silastic, early abdominal complications were frequent and finally led to the abandonment of this technique for management of hydrocephalus. With the use of silastic shunt tubing, VP shunts have once again gained favor as the procedure of choice. Although there are now considerably fewer complications from VP shunts, the presence of an intraperitoneal catheter can still initiate various complications. Abdominal complications of VP shunts are reported to be from 10-30 per cent, thus remaining clinically important for early recognition and treatment in patient management. An awareness of these complications is necessary in creating an index of suspicion for the primary physician whose patients harbor a VP shunt and present with abdominal symptoms. This report presents five cases of children with abdominal complications of VP shunts (four pseudocysts and one umbilical granuloma with spontaneous drainage of CSF). Additional abdominal complications of VP shunts are discussed, as well as diagnostic and therapeutic alternatives in order to improve and expedite accuracy in diagnosis and provide simplicity and efficiency in treatment.

Abdomen↗

PubMed1987

Hemoglobin adducts of 4-aminobiphenyl in smokers and nonsmokers.

A quantitative method has been developed for the analysis of 4-aminobiphenyl (4-ABP) covalently bound as the sulfinic acid amide to the 93 beta cysteine of human hemoglobin. The method uses mild basic hydrolysis of hemoglobin to release the parent amine, derivatization to form the pentafluoropropionamide, and capillary gas chromatography with detection by negative-ion chemical ionization mass spectrometry. The method is precise and gives reproducible results on multiple blood samples taken from individuals over 48 h. Application of this method to blood samples from cigarette smokers and nonsmokers revealed consistently higher adduct levels in smokers. The mean value for smokers was 154 pg 4-ABP per g Hb compared to 28 pg/g Hb for nonsmokers, with no overlap of adduct levels between the two groups. Studies on quitting smokers revealed that adduct levels declined over a period of 6-8 weeks to nonsmoker levels. The finding of 4-ABP adducts in all nonsmokers was not anticipated but is consistent with low-level ubiquitous contamination of air, food, or water. In other animals sampled, rats and dogs had measurable adduct levels, but monkeys and fish did not. The hemoglobin adduct of 4-ABP is the product of a series of reactions between the hemoprotein and N-hydroxy-4-ABP. The formation of hydroxylamines from carcinogenic aromatic amines and their subsequent reactions with DNA are generally thought to be critical events in the initiation of bladder tumors. We suggest that the observed hemoglobin adduct levels formed by this proximate carcinogen will reflect the extent to which these steps have occurred. This is the first report of 4-ABP adducts in human blood.

Aminobiphenyl Compounds↗

PubMed1987

GC/MS analysis of biologically important aromatic amines. Application to human dosimetry.

Human exposure to aromatic amines may be monitored by measuring the amount of sulfinamide adduct bound to hemoglobin. In order to develop a sensitive and selective method for measuring aromatic amines present in low concentrations the mass spectra of the pentafluoropropionamide derivatives of a series of aromatic amines were determined under various ionization conditions. With electron ionization the aromatic amine derivatives typically yield intense molecular ions with fragmentation leading to elimination of C2F5 and COC2F5. Higher molecular weight polycyclic aromatic amines, e.g., 6-aminochrysene, give prominent molecular ions as well as intense ions corresponding to M - 174 (loss of CNHCOC2F5). With positive chemical ionization using methane as reagent gas the derivatives give protonated molecular ions as the base peaks, as well as the associated ions at M + 29 and M + 41. Negative ion chemical ionization yields, primarily, peaks corresponding to the loss of HF from the molecular anions. Negative ion chemical ionization with selected ion monitoring is generally more suitable than positive chemical ionization or electron ionization for the quantitative analysis of aromatic amines present in biological samples in the mid femtomolar range. Exposure of human subjects to aromatic amines was determined via basic hydrolysis of the isolated sulfinic acid amide hemoglobin adducts. Analysis of the derivatized extracts by gas chromatography/negative ion chemical ionization/mass spectrometry demonstrated the presence of aniline, ortho-, meta-, and para-toluidine, 2-naphthylamine, and 4-aminobiphenyl. The hemoglobin adduct levels of these amines in both cigarette smokers and nonsmokers were determined.(ABSTRACT TRUNCATED AT 250 WORDS)

Amines↗

PubMed1987

Causative factors for decreased pulmonary metastasis in parenterally fed mice.

Total parenteral nutrition (TPN) with fat and/or glucose as the caloric source is associated with a decrease in pulmonary metastasis in mice bearing subcutaneously implanted Lewis lung carcinoma. Five groups of white mice bearing Lewis lung carcinoma were assigned to receive various isocaloric and isonitrogenous oral and parenteral feedings: TPN, utilizing all nonnitrogen energy from glucose; per os, utilizing all nonnitrogen calories from glucose; electrolyte, utilizing nonnitrogen calories provided from a balanced casein diet and receiving an isovolemic infusion of electrolytes in the same composition as the TPN formula; 1/4 normal saline, also consuming the casein diet and receiving an isovolemic infusion of 1/4 normal saline; and an oral casein control (CON) without infusion. Results showed that there were no significant differences in tumor volume changes or tumor doubling time among the groups. However, tumor weight was significantly lower in groups receiving the TPN solution either orally or parenterally in comparison to the oral casein control. Pulmonary metastases were significantly lower in all parenteral groups, irrespective of solution composition, compared to the CON group. Thus it appears that parenteral fluid load rather than composition of the solution is the causative factor for the decrease in pulmonary metastases.

Administration, Oral↗

PubMed1986

Analytical methods for assessing exposure to 4-aminobiphenyl based on protein adduct formation.

Past studies with animals have demonstrated that 4-aminobiphenyl (ABP) administration results in the formation of appreciable amounts of adducts between the carcinogen and both serum albumin and hemoglobin. The hemoglobin adduct is relatively stable in vivo, but may be readily hydrolyzed in vitro to regenerate ABP. The formation of this adduct reflects a mixed-function oxidase-mediated metabolic pathway operating directly on the amine. The predominant albumin adduct, 3-(tryptophan-N1-yl)-4-acetylaminobiphenyl, reflects the contribution of N-acetyltransferase activity as well as mixed function oxidase activity to the overall metabolism. The simultaneous measurement of these two different adducts thus offers an opportunity to investigate the role of both ABP and acetylator phenotype in bladder carcinogenesis. An analytical method, using gas chromatography coupled with electron capture detection, was developed to quantitate ABP adducted to hemoglobin.

Aminobiphenyl Compounds↗

PubMed1984

In vivo dosimetry of 4-aminobiphenyl in rats via a cysteine adduct in hemoglobin.

The feasibility of monitoring doses of 4-aminobiphenyl (ABP) via adduction to hemoglobin was investigated. Rats dosed with ABP (from 0.5 micrograms/kg to 5 mg/kg) formed a stable covalent hemoglobin:ABP adduct. Approximately 5% of a single dose was bound as hemoglobin:ABP; chronic dosing led to an accumulation of the adduct to a level 30 times greater than that found after a single dose. Facile in vitro hydrolysis of the adduct regenerated ABP, allowing detection at the sub-ng level. Human hemoglobin was also readily adducted, using N-hydroxy-ABP in vitro. The predominant site of adduction appeared to be the cysteine residue in hemoglobin. The use of such adducts as dosimeters for arylamine exposures in humans is discussed.

Aminobiphenyl Compounds↗