PubMed Health⌕ Search

Biomedical subjects

B A Smith

Publications and source records attributed to B A Smith.

At least 19 recordsLinked to original sources
PubMed1992

Loss of NF1 alleles in phaeochromocytomas from patients with type I neurofibromatosis.

Type I neurofibromatosis (NF1) is a common autosomal dominant disorder that affects tissues derived from the neural crest. The manifestations are varied, comprising generalised disorders of growth and development as well as an increased risk of benign and malignant tumours including phaeochromocytomas and neurofibrosarcomas. The NF1 locus has been mapped to chromosome bands 17q11-12, and recently the NF1 gene has been cloned. Deletions identified in the constitutional genotype of some patients have suggested that the NF1 phenotype may arise from loss of function mutations of the NF1 gene, consistent with the hypothesis that it is a tumour suppressor gene. To date, however, analysis of NF1 tumours has not revealed the frequent allele losses encompassing the NF1 locus, implying loss of the wild-type NF1 allele, which would support this hypothesis. We report allele losses with markers flanking the NF1 region in each of 7 NF1 phaeochromocytomas. In each of the 3 tumours for which this could be determined, the loss involved the wild-type chromosome. These results provide strong evidence that, in cells of the adrenal medulla at least, the NFI gene may act as a tumour suppressor.

Adrenal Gland Neoplasms↗
PubMed1992

Thrombin and albumin adsorption to PVA and heparin-PVA hydrogels. I. Single protein isotherms.

More radiolabeled thrombin was adsorbed to heparin-polyvinyl alcohol (PVA) than to PVA, consistent with a specific interaction with the immobilized heparin. The maximum surface concentration on heparin-PVA was estimated to be approximately 450 nmol/m2 with an apparent affinity constant (Ka) of 2.5 microM-1; on PVA, the plateau concentration was 10 nmol/m2 with a Ka less than 1 nM-1. There was little difference in bovine serum albumin (BSA) adsorption between PVA and heparin-PVA. Interestingly, thrombin adsorption to polyethylene was indistinguishable from that to PVA despite the large difference in surface chemistry. BSA adsorbed to polyethylene with higher affinity than to the hydrogels, although the plateau concentrations were comparable. The adsorbed thrombin was biologically inactive at least towards chromogenic substrate, with the residual activity on PVA unaffected by subsequent incubations with antithrombin III. PVA and heparin-PVA presented a heterogeneous and complex substrate for interaction with proteins. The adsorbed protein was likely present in multiple states depending on the groups with which it interacted.

Adsorption↗
PubMed1992

Profound alkalemia during treatment of tricyclic antidepressant overdose: a potential hazard of combined hyperventilation and intravenous bicarbonate.

Two patients with cardiovascular and neurologic toxicity from intentional tricyclic antidepressant overdose received bicarbonate infusions in association with hyperventilation for alkalinization. Both patients developed profound alkalemia. One patient died, and the other patient's alkalemia resolved prior to her death. Bicarbonate infusions have become the standard of care for symptomatic tricyclic antidepressant toxicity. Severe alkalemia (pH greater than 7.60) in other settings has been reported to correlate with higher rates of mortality. Careful monitoring of the pH is imperative when bicarbonate therapy is used. It is probably prudent to keep the pH level in the range 7.45 to 7.60. Capnography may also be useful in monitoring patients during alkalinization.

Adult↗
PubMed1992

Acute hydralazine overdose: marked ECG abnormalities in a young adult.

Although hydralazine is a commonly prescribed antihypertensive agent, reports of acute human poisoning are uncommon. Most of the literature focuses on chronic toxicity, most notably, the drug-induced systemic lupus erythematosus syndrome. A case of acute hydralazine overdose associated with marked ECG ST segment depression in a young adult is presented. Although the patient also had mild hypotension, acidemia, and ethanol intoxication, the ECG abnormality was alarming and suggestive of myocardial ischemia. The patient was managed conservatively in an ICU setting, and the metabolic and ECG abnormalities resolved. No reports of such marked ECG changes associated with acute hydralazine poisoning in a young adult could be found. Clinical and experimental data on acute hydralazine exposure suggest that the possibility of direct drug effects, including positive inotropic and chronotropic effects and myocardial cell injury, should be considered.

Adult↗
PubMed1992

Klippel-Feil syndrome.

Klippel-Feil syndrome is characterized by congenital fusion of two or more cervical vertebrae and may be associated with other organ system anomalies. Although many congenital anomalies are of little clinical importance to the emergency physician, Klippel-Feil syndrome is associated with both spontaneous and progressive neurologic sequelae as well as a predisposition for serious neurologic injury after relatively minor neck trauma. Such patterns of skeletal abnormalities as an unstable fusion pattern, craniocervical anomalies, and associated spinal stenosis are associated with a higher risk of neurologic sequelae. We report the case of a patient with a previously undiagnosed type II Klippel-Feil syndrome who presented after neck trauma to illustrate how further diagnostic imaging modalities may be required to elucidate the presence or absence of acute injury. Key considerations in the emergency management of such patients include radiographic evaluation for hypermobile cervical segments, the anticipation of difficult tracheal intubation, and proper follow-up and referral because of the associated other organ system anomalies and progression of the skeletal pathology.

Adolescent↗
PubMed1992

Metronidazole in periodontitis: reduced need for surgery.

A considerable amount of circumstantial evidence indicates that most forms of periodontitis are due to the presence or dominance of a finite number of bacterial species in the subgingival plaque. Almost all of the putative pathogens are anaerobic species, indicating that most forms of periodontitis could be diagnosed as anaerobic infections. In this double-blind investigation, patients with elevated proportions or levels of spirochetes in 2 or more plaque samples, i.e., 60% spirochetes, were randomly assigned to receive either metronidazole, 250 mg 3 x a day for 1 week, or placebo (positive-control) after the completion of all debridement procedures. When the patients were re-examined 4 to 6 weeks later, the patients in the metronidazole group (n = 15) exhibited a highly significant (p less than 0.01) reduction in probing depth and apparent gain in attachment levels relative to the patients (n = 18) in the positive-control group about those teeth that initially had probing depths of 4 to 6 mm. This pattern was also observed about teeth that initially had probing depths greater than or equal to 7 mm. This reduction in probing depths and apparent gain in attachment was associated with a significant reduction in the need for periodontal surgery in the metronidazole-treated patients (difference 8.4 teeth per patient) compared to the positive-control patients (2.6 teeth per patient). These clinical improvements in the metronidazole group were associated with significantly lower proportions of spirochetes, selenomonads, motile rods, and P. intermedius, and a significantly higher proportion of cocci in the plaques. These findings indicate that systemic metronidazole, when given after all the root surface debridement is completed, leads to additional treatment benefits, including a reduced need for surgery, beyond that which can be achieved by debridement alone.

Adult↗
PubMed1992

Ontogeny of baroreflex control of renal sympathetic nerve activity and heart rate.

The purpose of this study was to characterize the developmental changes in baroreflex function during fetal and postnatal life in sheep. Resting mean arterial blood pressure increased significantly from 55 +/- 2 mmHg in fetuses to 86 +/- 3 mmHg in newborn lambs and to 105 +/- 4 mmHg in 4- to 6-wk-old lambs. The sensitivity (gain) of the renal sympathetic nerve activity (RSNA) response to baroreceptor stimulation was greater (P < 0.05) in fetuses (-7.7 +/- 1.9%/mmHg) than in newborn (-2.9 +/- 0.1%/mmHg) and 4- to 6-wk-old lambs (-2.2 +/- 0.2%/mmHg). The threshold and saturation pressures for the baroreflex function curve were lower (P < 0.05) in fetuses (44 +/- 2 and 61 +/- 2 mmHg) than in newborn (59 +/- 4 and 106 +/- 5 mmHg) or 4- to 6-wk-old lambs (78 +/- 5 and 132 +/- 6 mmHg). Similar findings were observed when the heart rate response to baroreceptor stimulation was examined. Additional experiments were performed in newborn and 4- to 6-wk-old lambs to determine whether the rise in arterial blood pressure associated with postnatal maturation contributed to baroreflex resetting. Sustained elevation of arterial blood pressure by 15-20 mmHg for over 90 min did not reset the baroreflex function curve in either newborn or 4- to 6-wk-old lambs.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1991

Male saliva cues and female social choice in Mongolian gerbils.

Adult female Mongolian gerbils (Meriones unguiculatus) are preferentially attracted to saliva from adult nonsibling males when paired with saliva from male siblings. The focus of the present study was to evaluate the potential role of saliva in the formation of reproductive units. In Experiment 1, olfactory-directed investigations and mate choices of estrous females housed with their brothers and unrelated males were examined. Females sniffed unrelated males more frequently than siblings and were more interested in sniffing the mouth area than other body areas. Importantly, they also solicited and mated exclusively with unrelated males. The purpose of Experiment 2 was to ascertain the origin of the behaviorally active components of saliva by transecting the parotid salivary duct (PDT). When either sibling saliva or water was paired with saliva from a nonsibling PDT male, females did not show the typical preference for saliva from nonsiblings. When social preferences were examined in Experiment 3, virtually all females preferred intact nonsibling males to either PDT nonsibling males or siblings. Results from this study support the hypothesis that saliva is an important oral cue used by females in the selection of sociosexual partners. Furthermore, the parotid gland appears to be a significant source of salivary chemosignals.

Animals↗
PubMed1991

Mutagenesis and DNA adduct formation by 1-nitropyrene in Chinese hamster ovary cells without exogenous metabolic activation.

The direct-acting mutagenicity of 1-nitropyrene (1-NP), a tumorigenic environmental pollutant and model nitropolycyclic aromatic hydrocarbon, was studied in Chinese hamster ovary (CHO) cells. Previous reports indicated that 1-NP, a potent direct-acting mutagen in Salmonella typhimurium, was mutagenic in CHO cells only in the presence of an exogenous activation system. In this study, a DNA-repair-deficient CHO cell line, CHO-UV5, and the repair-proficient CHO-K1-BH4 cell line were used to measure the direct-acting mutagenicity of highly purified samples of 1-NP. Exposure of CHO-K1-BH4 cells for 5, 12, and 24 hr did not increase mutations at the hypoxanthine-guanine phosphoribosyl transferase (hprt) locus (p greater than 0.1; paired t test; n = 5-6), while treatment of CHO-UV5 cells for 24 hr produced a statistically significant induction of mutants (22 +/- 6 mutants per 10(6) clonable cells vs a solvent control value of 9 +/- 3 per 10(6) cells; p less than 0.01; n = 6). 32P-Postlabeling analysis of the DNA adducts formed in CHO-UV5 cells following 1-NP exposure revealed the presence of a single major adduct. Based on its chromatographic properties, its sensitivity to nuclease P1 digestion, and its resistance to hydrazine treatment, the adduct appeared to be N-(deoxyguanosin-8-yl)-1-aminopyrene, which was presumably produced by nitroreduction of 1-NP to N-hydroxy-1-aminopyrene. These results suggest that the use of extended treatment times and DNA-repair-deficient cells may be required to assess adequately the mutagenicity of nitropolycyclic aromatic hydrocarbons in CHO cells.

Animals↗
PubMed1991

Pre-excited RR intervals during atrial fibrillation in the Wolff-Parkinson-White syndrome: influence of the atrioventricular node refractory period.

The ventricular rate and percent of pre-excited QRS complexes during atrial fibrillation were compared in two groups of patients with the Wolff-Parkinson-White syndrome. Group A consisted of 22 patients whose anterograde effective refractory period of the accessory pathway was longer than that of the atrioventricular (AV) node. Group B consisted of 23 patients in whom this relation was reversed. No patient had organic heart disease. Both groups had a similar effective refractory period of the accessory pathway (288 +/- 37 vs. 280 +/- 26 ms), whereas that of the AV node was shorter in group A than group B (242 +/- 25 vs. 285 +/- 27 ms, p = 0.0001). Patients in group A had a lower percent of pre-excited QRS complexes during atrial fibrillation (39 +/- 43% vs. 93 +/- 20%, p = 0.0001). In the 21 patients whose refractory period was measured, the difference was plotted against the percent of pre-excited QRS complexes; there was a significant correlation between the two (r = -0.83, p less than 0.001). In patients in whom pre-excited RR intervals were present, the pre-excited RR intervals were compared between the two groups. Both groups had similar effective refractory periods of the accessory pathway (265 +/- 22 vs. 280 +/- 27 ms) and ventricle (200 +/- 17 vs. 211 +/- 26 ms). The effective refractory period of the AV node was shorter in group A (248 +/- 22 vs. 285 +/- 28 ms, p = 0.0005). The shortest pre-excited RR interval did not show any difference (244 +/- 37 vs. 265 +/- 41 ms). However, both the average (328 +/- 39 vs. 397 +/- 56 ms, p = 0.001) and longest (495 +/- 109 vs. 666 +/- 205 ms, p = 0.02) pre-excited RR intervals were shorter in group A.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1991

Disposition of spontaneous pneumomediastinum.

In the evaluation of spontaneous pneumomediastinum, it is important to exclude pathological causes of pneumomediastinum, including Boerhaave's syndrome, which carries a high mortality rate. The literature varies greatly as to the care of patients with presumed spontaneous pneumomediastinum. The authors present an illustrative case of spontaneous pneumomediastinum treated with intravenous antibiotics and intensive care unit (ICU) admission despite a normal esophagram. Spontaneous pneumomediastinum is a benign entity that may not require observation in an ICU, and patients may do as well with close outpatient follow-up. For those patients in which the etiology of the pneumomediastinum is unclear, a contrast esophagram is recommended to assess for esophageal disruption. The signs, symptoms, pathophysiology, and disposition of spontaneous pneumomediastinum are discussed.

Adult↗
PubMed1991

Effect of microgravity modeling on interferon and interleukin responses in the rat.

Rats were placed in whole-body harness suspension in three configurations: antiorthostatic hypokinetic/hypodynamic suspension (AAH) to induce headward body fluid redistribution and unload the limbs, orthostatic hypokinetic/hypodynamic suspension (OHH) to unload the limbs without fluid redistribution, and harness restraint (HR) to produce the restraint stress of the model without fluid redistribution or musculoskeletal disuse. AHH and OHH suspension transiently increased interferon-gamma (IFN-gamma) production in response to the mitogen concanavalin A. Harness restraint alone did not affect IFN-gamma response. However, both suspension modeling and harness restraint caused a transient reduction in interleukin-1 (IL-1) and IL-2 responses to mitogen. This suggests that factors associated with musculoskeletal unloading affected IFN-gamma responses, while IL-1 and IL-2 responses were affected by the physiological stress of restraint.

Animals↗
PubMed1991

Kinds of mutations found when a shuttle vector containing adducts of 1,6-dinitropyrene replicates in human cells.

To gain insight into the mechanisms by which carcinogens induce mutations in human cells, we have been comparing the frequency and spectrum of mutations induced when a shuttle vector, pS189, carrying covalently bound residues of structurally related carcinogens, replicates in human 293 cells. In the present study, we investigated the mutagenic effects of N-hydroxy-1-amino-6-nitropyrene, a partially reduced derivative of 1,6-dinitropyrene (1,6-DNP). The results were compared with what was found previously in the same assay with N-hydroxy-1-aminopyrene, the partially reduced derivative of 1-nitropyrene. The shuttle vector plasmids were exposed to tritiated 1-nitro-6-nitrosopyrene for 1 h in the presence of ascorbic acid, which served as a reducing agent to generate N-hydroxy-1-amino-6-nitropyrene. 32P-Postlabeling showed that only a single adduct was formed, i.e. N-(deoxyguanosin-8-yl)-1-amino-6-nitropyrene. There was a linear increase in the number of adducts per plasmid as a function of applied concentration and also in the frequency of supF mutants as a function of adducts per plasmid, reaching 58.8 x 10(-4) above a background of 0.8 x 10(-4). When the frequency of mutants induced when plasmids carrying residues of 1,6-DNP replicated in the human cells was compared with that induced by 1-NP residues, the former was 1.8 times more mutagenic than the latter. Both carcinogens induced mainly base substitutions, primarily G.C----T.A transversions; but 1,6-DNP adducts produced a significant fraction of -1 frameshifts, with most of these located in a unique run of five Gs in the gene. Polymerase termination reactions indicated that 1,6-DNP adducts were formed at every guanine, but not elsewhere in the gene. The 'hot spots' for adduct formation were not perfectly correlated with 'hot spots' for mutation induction. This indicates that the ultimate biological effect of the chemical depends not only on the number of adducts originally formed, but also on such processes as cellular DNA repair, which may remove such adducts from the plasmids before DNA replication occurs, as well as on the structure of the neighboring bases at the site of the adduct.

Base Sequence↗
PubMed1991

S9-mediated metabolism of 1-nitropyrene to a mutagen in Chinese hamster ovary cells by ring-oxidation under aerobic conditions and by nitroreduction under anaerobic conditions.

Both nitroreduction and ring-oxidation appear to be important pathways for the in vivo metabolic activation of 1-nitropyrene (1-NP), a tumorigenic environmental contaminant. Previous studies, however, suggest that ring-oxidation is primarily responsible for the S9-mediated mutagenicity of 1-NP in Chinese hamster ovary (CHO) cells. In this study, an anaerobic rat liver S9 metabolizing system was used to facilitate the nitroreduction of 1-NP to a mutagen in repair-proficient CHO-K1-BH4 cells and excision-repair-deficient CHO-UV5 cells, and results using this system were compared with those obtained from the aerobic S9 metabolism of 1-NP. Anaerobic S9 metabolism of 2.5-15 micrograms/ml of 1-NP produced 15 +/- 3 mutants/10(6) cells/microgram 1-NP/ml with CHO-UV5 cells and 3 +/- 1 mutants/10(6) cells/microgram 1-NP/ml with CHO-K1-BH4 cells (different at P less than 0.001). When the assays were conducted with CHO-K1-BH4 cells, the number of mutants produced by 1-NP using aerobic treatment conditions was similar to that found using anaerobic conditions. In contrast, the aerobic incubations resulted in significantly fewer 1-NP-induced mutants than the anaerobic treatments when the assays were conducted with CHO-UV5 cells. Examination of the metabolites produced during these incubations indicated that under anaerobic conditions 1-NP was efficiently converted to 1-aminopyrene, while aerobic metabolism resulted in the formation of 1-NP phenols and dihydrodiols. DNA adduct analysis by 32P-postlabeling revealed that 1-NP treatment using the anaerobic procedure produced CHO-cell adducts by the reduction of 1-NP to N-hydroxy-1-aminopyrene, while aerobic incubations resulted in adducts produced by other metabolic pathways, probably involving ring-oxidation. These findings indicate that the S9-mediated metabolism of 1-NP under anaerobic conditions produces mutations and DNA adducts in CHO cells that are the result of nitroreductive metabolism. The results with aerobic S9 metabolism were consistent with the previous conclusion that this system mediated the mutagenicity of 1-NP in CHO cells mainly through the generation of ring-oxidized metabolites. The combination of the anaerobic and aerobic S9 metabolism procedures provides a new approach for evaluating the mutagenicity of nitropolycyclic aromatic hydrocarbons in mammalian cells.

Aerobiosis↗
PubMed1991

Comparison between DNA adduct formation and tumorigenesis in livers and bladders of mice chronically fed 2-acetylaminofluorene.

Female BALB/c mice continuously fed 2-acetylaminofluorene (AAF) develop liver and bladder tumors. The incidence of liver tumors is linearly related to the carcinogen concentration in the diet, while the tumor response in the bladder is markedly non-linear. In the current experiments, liver and bladder DNA adducts were measured in female BALB/c mice fed several different concentrations of AAF for 28 days. The adduct concentrations were then compared to the previously reported incidences of neoplastic and preneoplastic lesions in these tissues. In initial experiments, mice were fed either 30 or 150 mg [ring-3H]AAF/kg diet for 21 days. Liver DNA adducts were identified by HPLC, which indicated the presence of one major adduct, N-(deoxyguanosin-8-yl)-2-aminofluorene (dG-C8-AF). This adduct was also the major product detected by 32P-postlabeling in liver and bladder DNA from mice fed the same concentrations of AAF for 28 days. Radioimmunoassays, conducted with an antibody specific for dG-C8-AF, showed that steady-state concentrations of dG-C8-AF were obtained at 28 days of AAF feeding; thus, this time point was used to determine the relationship between the dose of AAF and the adduct levels. In mice fed nine concentrations of AAF (5-150 mg AAF/kg diet), the adduct concentrations after 28 days of feeding were linearly related to dose in both the liver and bladder, with the adduct concentration being approximately 3-fold greater in the bladder. These results indicate that a linear correlation exists between the hepatic concentration of dG-C8-AF and the liver tumor incidence. In the bladder however, a linear relationship was not observed, which suggests that additional tissue-specific factors, such as toxicity, are essential components for tumorigenesis in this tissue.

2-Acetylaminofluorene↗
PubMed1991

Role of renal sympathetic nerves in lambs during the transition from fetal to newborn life.

To determine the role of renal sympathetic nerves in influencing renal function during the transition from fetal to newborn life, studies were carried out in conscious, chronically instrumented fetal sheep with either bilateral renal denervation (n = 11) or intact renal nerves (n = 12), 3-6 d after surgery. Endocrine, renal, and cardiovascular parameters were measured before and after delivery of lambs by cesarean section. Blood pressure and heart rate were similar in intact and denervated fetuses, and increased after delivery in both groups. There was also a transient diuresis and natriuresis, in the immediate postnatal period, the response being significantly greater in denervated than intact lambs (P less than 0.05). By 24 h postnatally, fluid and electrolyte excretions were similar in both groups, and significantly less than fetal levels. In the absence of renal nerves, the normal rise in plasma renin activity at birth was attenuated. These data provide evidence that renal sympathetic nerves play an important role during the transition from fetal to newborn life, and support the premise that birth is associated with sympathetic activation.

Animals↗