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Biomedical subjects

B Bullock

Publications and source records attributed to B Bullock.

15 recordsLinked to original sources
PubMed2001

Uterine adenocarcinoma in mice treated neonatally with genistein.

The developing fetus is uniquely sensitive to perturbation with estrogenic chemicals. The carcinogenic effect of prenatal exposure to diethylstilbestrol (DES) is the classic example. Because phytoestrogen use in nutritional and pharmaceutical applications for infants and children is increasing, we investigated the carcinogenic potential of genistein, a naturally occurring plant estrogen in soy, in an experimental animal model previously reported to result in a high incidence of uterine adenocarcinoma after neonatal DES exposure. Outbred female CD-1 mice were treated on days 1-5 with equivalent estrogenic doses of DES (0.001 mg/kg/day) or genistein (50 mg/kg/day). At 18 months, the incidence of uterine adenocarcinoma was 35% for genistein and 31% for DES. These data suggest that genistein is carcinogenic if exposure occurs during critical periods of differentiation. Thus, the use of soy-based infant formulas in the absence of medical necessity and the marketing of soy products designed to appeal to children should be closely examined.

Adenocarcinoma↗
PubMed1998

Neuropeptide regulation of proinflammatory cytokine responses.

Severe traumatic injuries and infections are frequently accompanied by life-threatening shock and are associated with increases in the proinflammatory cytokines, particularly tumor necrosis factor alpha (TNF-alpha). The body's first perception of injury is the nociceptive or pain response. This response is induced at the site of injury and is transmitted systemically by sensory neuropeptides, the tachykinins, released from sensory afferent c-fiber neurons. We studied the role of tachykinins in regulating the production of proinflammatory cytokines induced by the administration of bacterial lipopolysaccharide. Destruction of terminal sensory nerve endings before lipopolysaccharide administration abrogates tachykinin synthesis and down-regulates TNF-alpha transcription and secretion. In contrast, the responses of interleukins-1 and -6 are unaffected. Pretreating animals with an antagonist for the substance P-specific NK-1 receptor also down-regulated the TNF-alpha response, whereas blockade of the NK-2 receptor had no effect. These findings indicate that substance P contributes to the induction of those cytokines that are involved in precipitating the shock response.

Animals↗
PubMed1997

Mechanisms of DES carcinogenicity: effects of the TGF alpha transgene.

Inappropriate estrogen exposure during critical periods of development will cause numerous abnormalities in the female reproductive tract. Epigenetic effects on the expression of estrogen-regulated genes is proposed to be one of the mechanisms by which neonatal estrogen elicits teratogenic and carcinogenic effects. Of note is the existence of an integral relationship between the regulation of members of the epidermal growth factor (EGF) gene family and estrogen effects on the growth and differentiation of the reproductive tract. To determine whether the EGF gene family plays a critical role in mediating the pathogenic effects of estrogen, we have used transforming growth factor-alpha (TGF alpha) transgenic mice to investigate the effects of constitutive TGF alpha expression in the reproductive tract and whether TGF alpha would potentiate carcinogenesis induced by the potent estrogen, diethylstilbestrol (DES), and by the carcinogen, 7,12-dimethylbenz[a]anthracene (DMBA). The animals were homozygous TGF alpha transgenic female mice from the MT42 line and the parental CD-1 outbred mice. Constitutive TGF alpha expression was found to augment the effects of both DES and DMBA in eliciting hyperplastic and differentiation changes in the reproductive tract. The presence of the TGF alpha transgene significantly increased the incidence of DES-induced vaginal adenosis, uterine endometrial hyperplasia, hypaspadia, and benign ovarian cysts. In addition TGF alpha potentiated the effects of DMBA in eliciting uterine polyps and benign ovarian cysts, and in the retention of Wolffian Duct remnants. However, the incidence of reproductive tract neoplasia was not promoted by the presence of the TGF alpha transgene. This study indicates that TGF alpha plays a role in the developmental and morphogenic events of both the Müllerian duct and urogenital sinus, and that deregulation is associated with pathogenesis of these tissues. Furthermore, the fact that constitutive expression of the TGF alpha did not substitute for DES as a reproductive tract carcinogen or act as a promoter of DES-induced uterine neoplasia suggest that DES carcinogenesis involves more than aberrant expression of this single growth factor.

9,10-Dimethyl-1,2-benzanthracene↗
PubMed1996

Potentiation of diethylstilbestrol-induced alterations in the female mouse reproductive tract by transforming growth factor-alpha transgene expression.

Neonatal estrogen exposure causes numerous abnormalities in the female reproductive tract, including carcinogenesis. One mechanism by which neonatal estrogen elicits teratogenic and carcinogenic effects is epigenetic and involves the modulation of a number of estrogen-regulated genes including epidermal growth factor (EGF). Because of the evidence that there is an integral relationship between the EGF family, estrogen action, and the regulation of the growth and differentiation of the reproductive tract, we used transforming growth factor-alpha (TGF alpha) transgenic mice to investigate the interaction of constitutive TGF alpha expression with the potent estrogen diethylstilbestrol (DES) in the induction of reproductive-tract alterations. Our study was designed to determine whether TGF alpha expression could modulate DES-induced carcinogenesis of the female mouse reproductive tract. The animals were homozygous TGF alpha transgenic female mice from the MT42 line and the parental CD-1 outbred mice. The presence of the TGF alpha transgene significantly increased the incidence of DES-induced vaginal adenosis, uterine endometrial hyperplasia, uterine polyps, hypospadia, benign ovarian cysts, and pituitary adenomas. However, constitutive TGF alpha expression did not promote reproductive-tract neoplasia. This study demonstrates that TGF alpha participates in the regulation of developmental and morphogenic events in the Müllerian duct and urogenital sinus, suggesting a role for TGF alpha in the pathogenesis of reproductive-tract diseases. Furthermore, we showed that although constitutive expression of the TGF alpha transgene did have an effect on the reproductive tract, TGF alpha overexpression alone could not substitute for DES as a reproductive-tract carcinogen or as a promoter of uterine neoplasia, indicating that DES-induced carcinogenesis requires events in addition to the overexpression of this single peptide growth factor.

Animals↗
PubMed1989

The aldo-keto reductase superfamily. cDNAs and deduced amino acid sequences of human aldehyde and aldose reductases.

Aldehyde reductase [EC 1.1.1.2] and aldose reductase [EC 1.1.1.21] are monomeric NADPH-dependent oxidoreductases having wide substrate specificities for carbonyl compounds. These enzymes are implicated in the development of diabetic complications by catalyzing the reduction of glucose to sorbitol. Enzyme inhibition as a direct pharmacokinetic approach to the prevention of diabetic complications resulting from the hyperglycemia of diabetes has not been effective because of nonspecificity of the inhibitors and some appreciable side effects. To understand the structural and evolutionary relationship of these enzymes, we cloned and sequenced cDNAs coding for aldose and aldehyde reductases from human liver and placental cDNA libraries. Human placental aldose reductase (open reading frame of 316 amino acids) has a 65% identity (identical plus conservative substitutions) to human liver and placental aldehyde reductase (open reading frame of 325 amino acids). The two sequences have significant identity to 2,5-diketogluconic acid reductase from corynebacterium, frog rho-crystallin, and bovine lung prostaglandin F synthase (reductase). Southern hybridization analysis of human genomic DNA indicates a multigene system for aldose reductase, suggesting the existence of additional proteins. Thus, the aldo-keto reductase superfamily of proteins may have a more significant and hitherto not fully appreciated role in general cellular metabolism.

Alcohol Oxidoreductases↗
PubMed1989

Effects of a 7-cent tobacco tax hike.

Texas health and human services programs could receive nearly half a billion dollars in additional funding over the state's 1990-1991 budget period under proposals being advocated by Comptroller of Public Accounts Bob Bullock. The proposals center on a 7-cent rise in the state's cigarette tax, with equivalent increases in other tobacco taxes. Revenue from the additional tax--estimated at $166 million in 1990-1991--would be directed into state health and human services programs eligible for federal matching funds. By directing the money in this way, the state could receive $274 million in additional federal aid. The $166 million in additional cigarette tax revenue, combined with the $274 million in increased federal aid, would yield $440 million that could be used in a variety of ways in state health and social programs.

Health Planning Organizations↗
PubMed1988

The rat gene encoding neurotensin and neuromedin N. Structure, tissue-specific expression, and evolution of exon sequences.

Recombinant DNA clones encoding the neurotensin/neuromedin N precursor protein have been isolated from both bovine hypothalamus cDNA and rat genomic libraries using a heterologous canine cDNA probe. Nucleotide sequence analysis of these clones and comparison with the previously determined canine sequence has revealed that 76% of the amino acid residues are conserved in all three species. The protein precursor sequences predicted from bovine hypothalamus and canine intestine cDNA clones vary at only 9 of 170 amino acid residues suggesting that within a species identical precursors are synthesized in both the central nervous system and intestine. The rat gene spans approximately 10.2 kilobases (kb) and is divided into four exons by three introns. The neurotensin and neuromedin N coding domains are tandemly positioned on exon 4. RNA blot analysis has revealed that the rat gene is transcribed to yield two distinct mRNAs, 1.0 and 1.5 kb in size, in all gastrointestinal and all neural tissues examined except the cerebellum. There is a striking variation in the relative levels of these two mRNAs between brain and intestine. The smaller 1.0-kb mRNA greatly predominates in intestine while both mRNA species are nearly equally abundant in hypothalamus, brain stem, and cortex. Sequence comparisons and RNA blot analysis indicate that these two mRNAs result from the differential utilization of two consensus poly(A) addition signals and differ in the extent of their 3' untranslated regions. The relative combined levels of the mRNAs in various brain and intestine regions correspond roughly with the relative levels of immunologically detectable neurotensin except in the cerebral cortex where mRNA levels are 6 times higher than anticipated.

Amino Acid Sequence↗
PubMed1984

Ion transport characteristics in rhesus monkey erythrocytes: relationship to age and blood pressure.

Erythrocyte (RBC) ion transport characteristics were examined in six young Rhesus monkeys (RM) age 3.3 +/- .3 (means +/- S.D.) years and seven mature RM 15.4 +/- 1 (means +/- S.D.) years. It was found that the older RM when compared to the younger RM demonstrated significantly elevated mean arterial pressures (MAP) (96 +/- 15 versus 75 +/- 11 mmHg), RBC intracellular sodiums (RBC Nai) (16.2 +/- 4 versus 11 +/- 3 mEq/liter RBC) and NaK ATPase pump rates per RBC (PR) (PR = ouabain sensitive K uptake divided by ouabain binding sites per RBC) (104 +/- 18 versus 83 +/- 18 K+ ions/sec/pump unit). However, it was also found that when the data from both groups were pooled and collectively analyzed a significantly positive correlation could be found between MAP and RBC Nai (p less than .001, r = .82), MAP and PR (p less than .01, r = .67) as well as PR and RBC Nai (p less than .001, r = .76). The fact that positive correlations exist among these parameters, independent of age, would suggest that while MAP, RBC Nai and PR tend to be elevated with advancing age, these abberations are not invariable consequences of age and best reflect the pivotal abberration of rising Nai. While insufficient data exist to account for the rise in Nai and no cause-effect relationship can be established it is clear that rising MAP and PR correlate best with rising Nai.

Age Factors↗
PubMed1984

The effect of manganese inhalation on basal ganglia dopamine concentrations in rhesus monkey.

Manganese (Mn) may produce neurotoxicity in man through inhalation of Mn dust. Animals exposed to excessive Mn develop neurological abnormalities, and neuropathological lesions in the brain mainly in the globus pallidus with decreased concentrations of the neurotransmitter, dopamine (DA), in the brain. Monkeys exposed to Mn by inhalation did not produce any abnormal movements. After two years, the animals were sacrificed and certain brain areas were compared to controls. There were significant decreases in DA concentration in caudate and globus pallidus, and there was a 60-80% increase in Mn concentration in the basal ganglia of the brain. The DA system in the basal ganglia is vulnerable to the effects of Mn, but the amount of Mn inhaled and the period of exposure would appear to determine whether abnormal neurological signs develop.

Animals↗
PubMed1975

Reproductive tract lesions in male mice exposed prenatally to diethylstilbestrol.

Sixty percent of the male offspring from pregnant mice treated with diethylstilbestrol during gestation were sterile. The affected animals had gonadal changes which included intra-abdominal or fibrotic testes, or both. Additionally, nodular masses in the ampullary region of the reproductive tract were observed in 6 of 24 animals; one of these appeared to be preneoplastic.

Abnormalities, Drug-Induced↗
PubMedDate not supplied

Sequence of cDNA encoding human insulin-like growth factor I precursor.

Somatomedins (SM) or insulin-like growth factors (IGF) constitute a heterogeneous group of peptides with important growth-promoting effects in vitro as well as in vivo. Amino acid sequences have been determined for only two of them, IGF-I and IGF-II, which are highly homologous. IGF-I, which is identical with SM-C, is composed of 70 amino acid residues and IGF-II contains 73 amino acids and may be identical with SM-A. Other peptides with different charge properties but with similar SM-like or insulin-like behaviour in biological and receptor assays, have been described but have not yet been fully characterized. The liver is known to be a major site of production of these peptides, but many other tissues--especially in the fetus--may synthesize them as well. We report here the nucleotide sequence of a human liver cDNA encoding the complete amino acid sequence of IGF-I. The IGF-I coding region is flanked by sequences encoding an amino-terminal peptide of at least 25 amino acid residues and a carboxyl-terminal peptide of 35 amino acids. This provides evidence that IGF-I is synthesized as a precursor protein and that formation of IGF-I from this precursor requires proteolytic processing at both ends.

Base Sequence↗