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Biomedical subjects

A C Smith

Publications and source records attributed to A C Smith.

At least 145 records · Page 8Linked to original sources
PubMed1989

A partial methylation profile for a CpG site is stably maintained in mammalian tissues and cultured cell lines.

We wished to determine if a partial methylation profile for a specific CpG site was stably maintained in both mammalian tissues and cultured cell lines. To accomplish this, we identified a CpG site with a partial methylation profile located upstream of the mouse adenine phosphoribosyltransferase promoter region. This site was found to be methylated at a level of approximately 25% in mouse brain, kidney, lung, and skeletal muscle tissues, at a level close to 50% in liver, and at level close to 0% in testis. These tissue-specific methylation profiles were not altered during aging. A methylation profile of approximately 25% at this CpG site was also observed in five mouse teratocarcinoma stem cell lines and one additional cultured cell line. This profile, however, was altered upon cellular differentiation, adenine phosphoribosyltransferase hemizygosity, and a loss of adenine phosphoribosyltransferase activity in some of the cultured cell lines. We conclude that partial methylation of a specific CpG site can be stably maintained both in vivo and in vitro and that a mechanism exists for its maintenance. The functional significance of a partial methylation profile remains to be determined.

Adenine Phosphoribosyltransferase↗
PubMed1989

Use of high-resolution two-dimensional gel electrophoresis and affinity labeling to probe glucocorticoid receptor structure and function.

The possible role of posttranslational modification in glucocorticoid receptor regulation was investigated. Glucocorticoid receptor (GR), prepared from the human B-cell line IM-9 and affinity labeled with [3H]-dexamethasone 21-mesylate, was examined by a combination of one-dimensional sodium dodecyl sulfate-polyacrylamide gel electrophoresis and high-resolution two-dimensional gel electrophoresis. Two-dimensional electrophoresis of immunopurified [3H]dexamethasone 21-mesylate-labeled GR revealed the presence of two isoelectric species (apparent pI approximately to 5.7, and 6.0-6.5). Both forms were present in preparations of unactivated receptor. After GR activation, the pI of neither isoform was altered, indicating that activation does not involve covalent charge modification of the steroid-binding protein. However, only the pI 6.0-6.5 isoform bound to DNA, suggesting that covalent charge modification of the GR can alter its ability to bind to DNA. Two-dimensional electrophoresis of tryptic and chymotryptic fragments showed that the charge heterogeneity responsible for the two GR isoforms is located in a Mr 26,500 tryptic fragment derived from the steroid-binding domain of the protein. In addition, analysis of [3H]dexamethasone 21-mesylate-labeled tryptic fragments suggests that the Mr 26,500 fragment corresponds to residues 499-743 of the human GR. These results demonstrate that posttranslational modification of the steroid-binding domain may regulate the ability of the protein to bind to DNA.

Affinity Labels↗
PubMed1989

Allelic variation linked to adenine phosphoribosyltransferase locus in mouse teratocarcinoma cell line and feral-derived mouse strains.

Southern blot analysis reveals two distinct adenine phosphoribosyltransferase (APRT) alleles in the P-19 mouse teratocarcinoma cell line. One allele is identical to that observed in common laboratory mouse strains (Mus musculus domesticus). The restriction enzyme site variations between the two alleles occur in sequences located both upstream and downstream of the APRT gene, but not within it. Although the P-19 cell line was established from a C3H strain embryo (Mus musculus domesticus), a sixth generation ancestor of this embryo was a feral mouse (Mus musculus musculus). The restriction pattern of the variant APRT allele in P-19 is identical to that of a feral-derived Mus musculus musculus animal, establishing the origin of this allele in the P-19 cell line. A third, distinct APRT allele was found in a Mus spretus feral-derived mouse. Exploiting the differences between the two APRT alleles in the P-19 cell line, we have demonstrated their sequential loss in APRT-deficient clones.

Adenine Phosphoribosyltransferase↗
PubMed1989

Effect of water as a diluent on the glass transition behaviour of malto-oligosaccharides, amylose and amylopectin.

The glass transition behaviour of amorphous malto-oligomers from dimer to hexamer was investigated as a function of diluent (water) concentration using differential scanning calorimetry. The glass transition temperatures of the pure compounds ranged from 364 K for maltose to 448 K for maltohexaose. At low diluent concentrations the addition of water strongly depressed Tg. From the measurement of Tg and the heat capacity increment, delta Cp, of the transition for the pure compounds it was possible to predict the Tg of the malto-oligomer/water mixtures using a thermodynamic approach developed by Couchman. From the measurements on the malto-oligomers it was possible to obtain, by extrapolation, the high DP limits of delta Cp and Tg, which are appropriate to amylose and amylopectin. The predicted variation of Tg with diluent concentration for these materials was compared with the experimentally observed behaviour.

Amylopectin↗
PubMed1989

The pulmonary toxicity of nitrosoureas.

Drug-induced pulmonary fibrosis in cancer chemotherapy has become a more serious problem as treatment regimens are refined, larger total doses of cytotoxic drugs are administered and patient prognosis improves. The nitrosoureas are a class of chemotherapeutic agents whose clinical use is severely limited by drug-induced toxicities. The myelosuppression caused by nitrosourea administration can be managed clinically; however, the development of irreversible pulmonary fibrosis is a more serious clinical problem. Studies are needed to identify biochemical markers for early lung injury so that the amount of pulmonary tissue damage can be assessed and monitored. Additionally, considerable research is needed to understand the mechanisms by which these agents produce lung injury, so that therapeutic regimens can be developed to minimize or prevent lung toxicity. In understanding the mechanisms of toxicity, potentially the pulmonary injury caused by nitrosourea administration can be altered without affecting the clinical antitumor activity of this class of compounds. In the future, knowledge on mechanisms of drug-induced pulmonary injury can be used in the development of antineoplastic agents which are more disease specific and less pulmonary toxic.

Animals↗
PubMed1989

An approach to occupational health risk management for a diversified international corporation.

A risk management program is presented which is effective in handling occupational health risks in a diversified multinational corporation. The three-step program of plant reviews involves initial assessment visits designed to determine the compliance status and degree of sophistication of the occupational health program. These assessments are followed by more formal assurance reviews which include consultation, training, and program support. Finally, formal surveillance reviews are conducted to verify compliance with respect to company and regulatory agency requirements. Each type of review requires planning and adherence to a standardized process to allow comparability of the information generated. Critical elements of this approach include senior management support, knowledge of applicable regulations, and communication of results. Reporting is done on several levels and is designed to communicate relevant information to management from line supervisors to the board of directors. Corrective action, where indicated, is planned by local managers with assistance from other groups as required. Corrective action plan implementation is tracked in conjunction with other mechanisms of occupational health and medical services to assure effective management of these risks.

Environmental Monitoring↗
PubMed1989

Microcystic adnexal carcinoma (sclerosing sweat duct carcinoma).

Microcystic adnexal carcinoma (MAC) is a recently described malignant neoplasm of the adnexal structures of skin that shows a marked propensity for early infiltrative and locally aggressive growth. Its banal clinical appearance may lead to a delay in diagnosing the tumor by biopsy, and its multifaceted histologic features may lead to an incorrect tissue diagnosis. Confusion with benign tumors and less aggressive malignancies can lead to inadequate initial treatment and extensive recurrences. We describe three cases of microcystic adnexal carcinoma and review the clinical and histologic features, treatment, and prognosis of this neoplasm.

Adenocarcinoma↗
PubMed1989

Pernicious anaemia and Campylobacter like organisms; is the gastric antrum resistant to colonisation?

Gastric biopsies from 86 patients with pernicious anaemia were examined for Campylobacter like organisms with particular attention to those showing an antral gastritis in addition to the usual pattern of body gastritis. All the patients had chronic atrophic gastritis in the body but Campylobacter like organisms were found at this site in only three patients. Thus the Type A pattern of gastritis (autoimmune) seen in patients with pernicious anaemia is only rarely associated with Campylobacter like organisms. Forty four of these patients had biopsies from body and antrum, 16 showed an antral gastritis of whom only one had Campylobacter like organism present. Twenty five of this latter group of patients were rebiopsied after five years. There was no change in the pattern of gastritis, and the same single patient remained colonised. The frequency of an antral gastritis in patients with pernicious anaemia was 36% yet the frequency of antral colonisation by Campylobacter like organisms was very low (6%). These results show that, as in the body, Campylobacter like organisms are not associated with gastritis when it occurs at this site in pernicious anaemia. The antral gastritis that may accompany body gastritis in pernicious anaemia seems more likely therefore to be an extension of primary type A body gastritis (autoimmune) rather than a secondary type B (chronic) gastritis and, it is argued, the antrum may exhibit resistance to colonisation.

Adult↗
PubMed1989

Duodenal ulcer disease: what role does Campylobacter pylori play?

Duodenal ulcer is a chronic relapsing condition which only became common early this century. Many pathogenic factors have been identified including excess gastric acid secretion, cigarette smoking, non-steroidal anti-inflammatory drugs and reduced mucosal defence. There is a strong association of duodenal ulceration, gastric Campylobacter pylori and antral (type-B) gastritis. The link between ulceration in the duodenum and C. pylori-associated antral gastritis may lie in the formation of gastric-type epithelium in the duodenum (gastric metaplasia). This metaplastic tissue is susceptible to C. pylori colonization and therefore to the local effects of these bacteria. Several reports suggest that duodenal ulcer relapse is more frequent in patients infected with C. pylori. These data are reviewed and a brief history of duodenal ulcer disease is presented.

Campylobacter Infections↗
PubMed1989

Technical aspects of cardiac catheterization of swine.

Long-term cardiovascular studies requiring repeated cardiac catheterizations often pose technical problems for investigator using swine. The purpose of this paper is to describe two reliable methods of cardiac catheterization that are used in swine to acquire complete hemodynamic data. Due to the depth of the vessels, vascular cut-downs are usually required. Hemodynamic, angiographic, and interventional cardiac catheters are introduced into either the femoral vessels or the external jugular vein and internal carotid artery. An alternative technique that obviates the need for multiple surgeries involves implantation of silastic catheters into both atria. This allows the passage of catheters directly into the heart chambers. A disadvantage of repeated vascular cut-downs is that a reduction of vascular access occurs. Chronic lines require careful attention to prevent infection and maintain patency.

Animals↗
PubMed1989

The management of dermal necrosis after acute Neisseria infection.

Although the occurrence of dermal necrosis following Neisseria meningitidis is rare, it portends a grave prognosis with a high mortality rate. A child having this complication is described who sustained a loss of over 30% of the body skin surface. She was successfully treated with aggressive nutritional support, meshed split-thickness skin grafting, and early rehabilitation. The pathophysiology of this complication is discussed, along with principles that are important in the day-to-day management of the patient.

Child, Preschool↗
PubMed1988

Institutional screening for the fragile X syndrome.

Cytogenetic screening of mentally retarded patients for the fragile X (fra[X]) chromosome is helpful in identifying individuals who could benefit from genetic counseling and treatment. Previous studies have demonstrated a prevalence of the fra(X) syndrome as high as 6% in institutionalized retarded males. The physical and behavioral predictors of positive findings from cytogenetic testing have not been clarified, since many features of the fra(X) syndrome are found in other retarded populations. We performed physical and cytogenetic examinations on 440 patients at the Wheat Ridge (Colo) Regional Center. Twenty-eight (6.3%) demonstrated abnormal karyotypes. Seventeen of these were autosomal abnormalities or sex chromosome aneuploidies and 11 demonstrated the fra(X) chromosome (seven males, four females). In males, the physical features that were predictive of the fra(X) syndrome included the combination of ear lengths of 7.0 cm or greater, macroorchidism of 30 mL or greater, and the presence of hand calluses or lesions secondary to hand biting. The fra(X) chromosome was not seen in spastic quadriplegic patients. All seven males with the fra(X) syndrome were detected among the 141 ambulatory males who resided in the highest functioning units at this institution.

Adolescent↗
PubMed1988

Effect of vertical banded gastroplasty on the natural history of gastritis in patients with morbid obesity: a follow-up study.

Vertical banded gastroplasty is an accepted surgical treatment for morbid obesity. The aim of this study was to evaluate its effect on the natural history of gastritis, as the occurrence of gastritis and dysplasia have been reported after gastric bypass, another type of bariatric surgery. Thirty-four patients who underwent vertical banded gastroplasty between 1983 and 1987 were studied, and the follow-up varied from 1 to 47 months (mean 22 months). We found no increase of gastritis and intestinal metaplasia after surgery, and we did not observe any case of gastric dysplasia. Only one patient with pre- and postoperative specimens showed a deterioration in gastric histology after surgery, and this was of a minor degree. These initial results are encouraging for surgeons interested in the treatment of morbid obesity.

Adult↗
PubMed1988

Linkage analysis using multiple DNA polymorphic markers in normal families and in families with fragile X syndrome.

Linkage data, using the polymorphic markers 52A (DXS51), F9, 4D-8 (DXS98), and St14 (DXS52), are presented from 14 fragile X pedigrees and from 7 normal pedigrees derived from the collection of the Centre d'Etude du Polymorphisme Humaine. A multipoint linkage analysis indicates that the most probable order of these four loci in normal families is DXS51-F9-DXS98-DXS52. Recombination frequencies (theta) corresponding to maximum LOD scores (Z) were obtained by two-point linkage analysis for a number of linkage groups, including: DXS51-F9 (Z = 5.94, theta = 0.03), F9-DXS98 (Z = 0.51, theta = 0.26), F9-DXS52 (Z = 0.84, theta = 0.27), and DXS98-DXS52 (Z = 0.32, theta = 0.20). A multipoint linkage analysis of these loci, including the fragile X locus, was also performed for the fragile X population and the data support the relative order (DSX51, F9, DXS98)-FRAXA-DXS52. Recombination frequencies and maximum LOD scores, which again were derived from two-point linkage analyses, were obtained for the linkage groups DXS51-F9 (Z = 9.96, theta = 0) and F9-DXS52 (Z = 0.07, theta = 0.45) as well as for the groups DXS51-FRAXA (Z = 2.42, theta = 0.15), F9-FRAXA (Z = 1.30, theta = 0.18), DXS98-FRAXA (Z = 0.05, theta = 0.36), and DXS52-FRAXA (Z = 2.42, theta = 0.15). The linkage data was further tested for the presence of genetic heterogeneity both within and between the fragile X and normal families for the intervals DXS51-F9, F9-DXS52, F9-FRAXA, and DXS52-FRAXA using a modification of the A test. Except for the interval F9-FRAXA (P less than 0.10) there was no evidence of genetic heterogeneity for each of the various linkage groups examined. The heterogeneity detected for the interval F9-FRAXA, however, was most likely due to one family (Fx-28) that displayed very tight linkage between these two loci.

Cells, Cultured↗
PubMed1988

Effects of piperonyl butoxide on halothane hepatotoxicity and metabolism in the hyperthyroid rat.

A series of experiments were conducted to examine the potential role of phase I metabolism in halothane-induced liver injury in the hyperthyroid rat. The metabolism of halothane was determined in both hyperthyroid (triiodothyronine, 3 mg/kg per day, for 6 days) and euthyroid rats and in animals pre-treated with the cytochrome P-450 inhibitor piperonyl butoxide (75-100 mg/kg, i.p.). It was found that the hyperthyroid state, which is associated with a substantial increase in sensitivity to the hepatotoxic effects of halothane, decreases both oxidative and reductive routes of halothane metabolism in the rat. The production of trifluoroacetic acid (TFA), an oxidative metabolite, as well as that of chlorodifluoroethylene (CDF) and chlorotrifluoroethane (CTF), 2 reductive metabolites, was significantly reduced in hyperthyroid animals. Consistent with these findings serum and urinary bromide levels resulting from the formation of TFA, CDF or CTF were significantly reduced. The only route of halothane metabolism significantly increased by the hyperthyroid condition was the defluorination of halothane. Piperonyl butoxide administration did not render euthyroid animals sensitive to the halothane-induced hepatotoxicity and had no effect on the defluorination of halothane in euthyroid animals. However, piperonyl butoxide markedly increased the hepatotoxicity of halothane in hyperthyroid rats and, except for a modest increase in debromination reactions, decreased all measured indices of halothane metabolism including the defluorination of halothane. Thus, none of the observed changes in halothane metabolism produced by triiodothyronine or piperonyl butoxide treatment could be consistently correlated to the increases in hepatotoxicity linked to these 2 treatments. Based on these studies we suggest that the halothane hepatotoxicity induced in the hyperthyroid rat results from effects produced by either the parent compound or an as yet unidentified metabolite. In addition, these studies further demonstrate that considerable mechanistic differences exist for halothane-induced hepatotoxicity when comparing euthyroid and hyperthyroid animal models.

Administration, Inhalation↗
PubMed1988

Indirect tissue electrophoresis: a new method for analyzing solid tissue protein.

1. The eye lens core (nucleus) has been a valuable source of molecular biologic information. 2. In these studies, lens nuclei are usually homogenized so that any protein information related to anatomical subdivisions, or layers, of the nucleus is lost. 3. The present report is of a new method, indirect tissue electrophoresis (ITE), which, when applied to fish lens nuclei, permitted (a) automatic correlation of protein information with anatomic layer, (b) production of large, clear electrophoretic patterns even from small tissue samples and (c) detection of more proteins than in liquid extracts of homogenized tissues. 4. ITE seems potentially applicable to a variety of solid tissues.

Animals↗
PubMed1988

Substituted 1,3,4-thiadiazoles with anticonvulsant activity. 4. Amidines.

Two different structural types of 2-aryl-1,3,4-thiadiazole amidines were synthesized and evaluated for anticonvulsant activity. Enhancement of the inherent anticonvulsant activity therein and separation of this activity from the accompanying sedative action of these compounds were attempted. The most potent compounds occurred in the 2-(trifluoromethyl)phenyl series of type 3 amidines, but they also possessed a relatively high level of neurotoxicity and sedation as demonstrated in the rotorod test.

Amidines↗