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D M Smith

Publications and source records attributed to D M Smith.

At least 343 records · Page 19Linked to original sources
PubMed1984

Inhibition of transforming growth factor-induced cell growth in soft agar by oxidized polyamines.

An inhibitor of the transforming growth factor-induced growth in soft agar of normally anchorage-dependent rat kidney fibroblasts has been detected in the acid-ethanol extracts of human placenta, bovine lung and kidney, and human rhabdomyosarcoma cells (A673). The inhibitor has been purified from human placenta by gel-filtration and cation-exchange chromatography followed by acetylation and HPLC. Acetylation destroys inhibitory activity and deacetylation, by treatment with 6 N HCl at 110 degrees C for 16 h, restores full activity. The purified compound has been identified as spermine by mass spectral and NMR analyses and by cochromatography on HPLC of the acetylated material with acetylated spermine. Both the compound isolated from the placenta and spermine and spermidine show approximately equal activity in inhibiting the transforming growth factor-induced growth of cells in soft agar with an ED50 of 0.7-1.1 microM, while putrescine displays no inhibitory activity. Evidence suggests that the polyamines must first be oxidized by serum polyamine oxidase before inhibition will occur. Acrolein, a product of polyamine oxidation, will also inhibit cell growth in soft agar with an ED50 of 6.8 microM. It is concluded that an oxidation product of spermine is responsible for the previously reported inhibition of colony growth in soft agar following treatment of normal fibroblasts with transforming growth factors.

Agar↗
PubMed1984

A comparison of alternative distributions of postimplantation death in the dominant lethal assay.

Statistical analysis of dominant lethal assay data has been the subject of much discussion, a large part of which has been concerned with the distributional form displayed by postimplantation embryonic deaths. The purpose of this study was to compare the fit of the frequently suggested distributions and some others, and to comment on the effect of distribution upon interpretation of results, using a particular set of dominant lethal assay data. The data set used included experiments involving a known mutagen (cyclophosphamide). For these experiments the parameters of the best fitting distributions were reviewed to consider how a dominant lethal effect is displayed.

Animals↗
PubMed1984

Conformational change in the DNA associated with an unusual promoter mutation in a tRNA operon of Salmonella.

We describe two novel types of mutations which decrease transcription of a tRNA operon in Salmonella typhimurium. One mutation consists of a 3 bp deletion at position -70 from the transcription start site. The second mutation is a single bp insertion between the -10 region and the transcription start site. The region around position -70 shows unusual physical properties. DNA fragments carrying the wild-type version of this region exhibit abnormally low electrophoretic mobility in polyacrylamide gels. This anomalous electrophoretic behavior is corrected if gels are run at high temperature or if the fragments contain the 3 bp deletion at -70. Our results indicate the existence of an unusual DNA conformation, probably involving DNA bending, in the region preceding the tRNA operon promoter. This structure is apparently disrupted by the 3 bp deletion. The transcriptional defect of the -70 mutant suggests a role for the unusual conformation in promoter function.

Base Sequence↗
PubMed1984

Suppressor sufJ: a novel type of tRNA mutant that induces translational frameshifting.

We describe the DNA sequence change responsible for the creation of a frameshift-suppressor gene in Salmonella typhimurium. The suppressor, sufJ, results from a base-pair insertion in the gene coding for a threonine transfer RNA (tRNA3Thr). Unlike previously studied frameshift suppressor mutations, the sufJ insertion does not fall within the sequence corresponding to the tRNA anticodon. The insertion (a G.C base pair) occurs within a run of three G.C base pairs in that region of the gene coding for one strand of the anticodon stem. In the secondary structure of the mature tRNA, the net result is that an extra, unpaired cytidine residue is pushed into the anticodon loop, thus increasing the size of the loop to eight nucleotides. These findings are discussed in connection with the peculiar "three-out-of-four" method of reading by the sufJ suppressor. A unifying model is presented accounting for the contrasting decoding behaviors of tRNAs with eight-nucleotide-long anticodon loops.

Alleles↗
PubMed1984

Protein turnover in the in vitro perfused working rat heart.

We have examined the effects of various interventions on protein degradation and synthesis in the in vitro left side perfused working rat heart preparation of Taegtmeyer, Hems and Krebs. In the absence of insulin, we could not detect any effects of increased pressure workload or of increased volume workload on protein degradation. In the presence of insulin, increased pressure workload may inhibit protein degradation by about 30%. Hypoxia did not inhibit protein degradation when cardiac output was not deleteriously affected even though lactate output was greatly increased. A trebling of left atrial filling pressure stimulated protein synthesis in the left atrium by about 30%. This effect was observed when protein synthesis was expressed either relative to protein or relative to RNA. Right atrial protein synthesis was unaffected by the increased left atrial filling pressure and could be used as an internal control. We suggest that this acute effect of filling pressure on left atrial protein synthesis may be important in the development of left atrial hypertrophy which can occur in conditions where raised left atrial pressures are encountered, for example, in mitral stenosis.

Animals↗
PubMed1984

The prevalence and prognostic significance of argyrophil cells in colorectal carcinomas.

The presence of argyrophil cells in the proliferative compartment of noncarcinoid carcinomas of the GI tract is well-documented; however, their prevalence and prognostic significance in colorectal carcinomas have never been systematically investigated and reported in the English literature. We applied the Churukian-Schenk argyrophil stain, a histochemical technique previously shown to be the most effective for demonstrating argyrophil cells, to 94 carcinomas of the colon and rectum from patients in whom a minimum 5-year follow-up was available. The 94 cases included 25 nonmucinous colonic and 25 nonmucinous rectal adenocarcinomas; 25 mucinous adenocarcinomas from all sites; and 19 undifferentiated carcinomas from all sites. Twenty control colorectal carcinoids all gave a positive argyrophil stain. Nineteen (20%) of the 94 carcinomas contained argyrophil cells as follows: adenocarcinoma of the colon, 52%; adenocarcinoma of the rectum, 16%; mucinous adenocarcinoma, 4%; and undifferentiated carcinoma, 5%. Crude 5-year survival rates were: carcinoids 80%; all carcinomas containing argyrophil cells, 37%; all without argyrophil cells, 27%. Chi-square between the later two groups was 0.723 (p less than 0.5). Because of the intrinsically poorer prognosis of mucinous and undifferentiated carcinomas, a comparison of survival rates was made excluding these tumors; chi-square was 0.095 (p less than 0.8). We conclude that argyrophil cells are commonly present in nonmucinous adenocarcinoma of the colon, but are less common in nonmucinous adenocarcinomas of the rectum and rare in mucinous and undifferentiated carcinomas. The presence of argyrophil cells did not influence prognosis in this series of cases.

Adenocarcinoma↗
PubMed1984

Ethylene thiourea: thyroid function in two groups of exposed workers.

Ethylene thiourea is manufactured at one factory in the United Kingdom and is mixed into masterbatch rubber at another. Clinical examinations and thyroid function tests were carried out over a period of three years on eight process workers and five mixers and on matched controls. The results show that the exposed mixers, but not exposed process workers, have significantly lower levels of total thyroxine (T4) than the controls. One mixer had an appreciably raised level of thyroid stimulation hormone (TSH).

Adult↗
PubMed1984

Methylprednisolone increases the toxicity of oxygen in adult mice. Mechanical and biochemical effects on the surfactant system.

Because previous studies have suggested that some of the toxic effects of oxygen may result from impaired surfactant phospholipid metabolism, we examined the effects of methylprednisolone on the surfactant system in adult mice exposed to greater than 98% O2. Mice pretreated for 7 days with methylprednisolone, 10 mg/kg/day, had a significantly greater mortality in hyperoxia than saline-pretreated, oxygen-exposed control mice. Their bronchoalveolar lavage fluid contained significantly less desaturated phospholipid, and static pressure-volume curves with air and saline showed decreased lung compliance caused by stiffness of the surface layer. The synthesis of desaturated phospholipids by lung slices in vitro was markedly impaired by the first day of hyperoxia, although in the absence of hyperoxia, it was mildly increased. The increased inhibition of phospholipid synthesis in steroid-treated mice was present even when mice were first given steroids on the day of entry into hyperoxia. These results suggest that methylprednisolone has an unfavorable effect on the surfactant system in oxygen toxicity by accentuating the inhibition of phospholipid synthesis. The possibility that these results could have been due to infection promoted by steroid treatment was considered. No cultural, histologic, or serologic evidence in support of this possibility was found, although infection cannot be conclusively excluded.

Animals↗
PubMed1984

Foot loading in amputee stance.

A survey has been carried out to establish information on foot loading in amputee stance. The parameters measured are percentage body weight and the positions of the centres of pressure under each foot. The data was collected in a clinical environment by the use of a Double Video Forceplate (DVF), a tool developed at the Bioengineering Centre. The objective of the survey is to provide background information for the use of the DVF in static alignment of lower-limb prostheses. Results are presented from a number of patients attending the Roehampton Walking Training School, and for a small group of patients attending the Bioengineering Centre for delivery of an experimental below-knee prosthesis. Scattergrams and averaged results provide normative data which can assist in interpretation of DVF displays during individual alignment.

Adolescent↗
PubMed1984

Reminders to physicians from an introspective computer medical record. A two-year randomized trial.

We developed a computer-stored medical record system containing a limited set of the total clinical data base--primarily diagnostic studies and treatments. This system responds to its own content according to physician-authored reminder rules. To determine the effect of the reminder messages generated by 1490 rules on physician behavior, we randomly assigned practitioners in a general medicine clinic to study or control groups. The computer found indications for six different actions per patient in 12 467 patients during a 2-year study: 61 study group residents who received computer reminders responded to 49% of these indications; 54 control group residents, to only 29% (p less than 0.0001). Preventive care (occult blood testing, mammographic screening, weight reduction diets, influenza and pneumococcal vaccines) was affected. The intentions of the study group to use a given action for an indication predicted their response to the indications (p less than 0.03, r2 = 0.33). The intentions of the control residents did not.

Computers↗
PubMed1984

The elimination of selected drug products from the Michigan Medicaid formulary: a case study.

The purpose of this study was to evaluate the prescribing behavior, recipient response, and economic impact of the removal of selected prescription drug products from the Michigan Medicaid formulary. The frequency with which alternate legend drugs were prescribed and the frequency of continuous therapy via out-of-pocket cash were determined. From 17 independent Michigan pharmacies, a total of 137 patients with prescriptions for at least one eliminated drug product was identified. Of the Medicaid recipients on continuous therapy, 46% discontinued therapy. Over 23% had an alternate legend drug prescribed still covered under the Medicaid drug benefit. The alternate drug resulted in significantly higher acquisition costs. Over 30% of the recipients continued therapy at their own expense, representing a cost savings to the Medicaid program.

Drug Utilization↗
PubMed1983

Stimulation of left-atrial protein-synthesis rates by increased left-atrial filling pressures in the perfused working rat heart in vitro.

We investigated the effect of an increase in the left-atrial filling pressure on the rate of left-atrial protein synthesis in the left-side-perfused working rat heart preparation of Taegtmeyer, Hems & Krebs [(1980) Biochem. J. 186, 701-711]. An increase in filling pressure (preload) at a constant aortic pressure (afterload) increased both the intra-atrial pressure and the atrial stroke volume. The aortic pressure (afterload) was held constant. An increase in filling pressure from 5 to 20 cmH2O at an aortic pressure of 70 cmH2O, or an increase in filling pressure of 7.5 to 20 cmH2O at an aortic pressure of 100 cmH2O, significantly stimulated the rates of left-atrial protein synthesis by 30-40%. The stimulation was observed when the rates of protein synthesis were expressed relative to either protein or RNA content. Since perfusate entering the right atrium from the coronary circulation left that atrium passively, the rate of protein synthesis in this compartment can be used as an internal control. Rates of right-atrial protein synthesis were similar to those in the left atria exposed to the lower filling pressures and were unaffected by the increases in left-atrial filling pressure. We suggest that the acute effects of increased left-atrial filling pressure on protein synthesis in that compartment may be important in the development of left-atrial hypertrophy. This condition is seen in patients who have raised pulmonary venous pressures in, for example, mitral stenosis.

Animals↗
PubMed1983

Differential rates of protein synthesis in vitro and RNA contents in rat heart ventricular and atrial muscle.

The rates of protein synthesis in perfused rat heart ventricular or atrial muscle were measured by incorporation of [U-14C]phenylalanine in the presence of the remaining plasma amino acids. Atrial protein-synthesis rates were about twice the ventricular rates. Atrial RNA contents were also about twice the ventricular contents. Thus the efficiencies of protein synthesis (protein-synthesis rate/RNA) in the two compartments were similar. There were marked differences in ventricular and atrial RNA contents during the course of rat growth. Atrial RNA content was always greater than ventricular content and declined more slowly during growth, producing a 2-fold change in atrial/ventricular RNA-content ratio between the 88 g and 370 g rat groups.

Animals↗
PubMed1983

Effect of insulin and lack of effect of workload and hypoxia on protein degradation in the perfused working rat heart.

1. Protein degradation was studied in the glucose (5 mM)-perfused working rat heart preparation of Taegtmeyer, Hems & Krebs [(1980) Biochem. J. 186. 701-711]. 2. The effects of cardiac workload were investigated in three different preparations: (a) control (low workload), (b) increased pressure workload (simulating conditions of aortic pressure in vivo) and (c) increased volume workload. There was no effect of increased workload on protein degradation in preparation (b) or (c) when compared with preparation (a). Insulin inhibited protein degradation in all three preparations. Significantly greater inhibition by insulin was observed in the increased-pressure-workload preparation (b). 3. Hypoxia was induced by the partial replacement of O2 in the gaseous phase by N2. Hearts maintained their cardiac output when O2 content was decreased from 95% to 55% by volume, but the stability of the preparation was less at 50% O2. Lactate output was significantly increased at O2 contents of 65% or less. The rate of protein degradation was not different from control values (95% O2) in perfusions with 65, 55 or 50% O2. 4. We conclude that acutely increased workload or acute hypoxia does not affect protein degradation in the perfused working rat heart when cardiac output is relatively stable.

Animals↗
PubMed1983

Purification and initial characterization of a type beta transforming growth factor from human placenta.

A polypeptide transforming growth factor (TGF) that induces anchorage-dependent rat kidney fibroblasts to grow in soft agar has been isolated from human placenta and purified to homogeneity. This polypeptide is classified as a type beta TGF because it does not compete with epidermal growth factor (EGF) for membrane receptor sites but does require EGF for induction of anchorage-independent growth of indicator cells. Purification of this peptide was achieved by acid/ethanol extraction of the placenta, followed by gel filtration, cation exchange, and HPLC of the acid-soluble proteins. Homogeneity of the TGF-beta from the final column was shown by its constant specific activity and amino acid composition across the peak of soft agar colony-forming activity and by its migration as a single band at Mr 23,000-25,000 on NaDodSO4/polyacrylamide gel electrophoresis. Under reducing conditions, the protein migrated on a gel as a single band at Mr 13,000. The purified placental TGF-beta caused half-maximal growth stimulation of indicator cells in soft agar at 64-72 pg/ml (3 pM) in the presence of EGF at 2 ng/ml (0.34 nM).

Amino Acids↗
PubMed1983

Selective IgA deficiency in blood donors.

The frequency of selective IgA deficiency was determined in a healthy population of 6,240 blood donors. Screening for IgA deficiency was performed by double-diffusion analysis in agarose gel. Confirmation testing was performed with the more sensitive passive hemagglutination inhibition assay. Prevalence of IgA deficiency, characterized by a serum level of below 50 mg/L, was 0.30% (1 in 328), which is the highest prevalence of selective IgA deficiency reported in a healthy population. Antibodies to IgA were detected in sera of 36.8% of the blood donors with selective IgA deficiency, which also is the highest prevalence of anti-IgA antibodies reported in any previous study. The literature on IgA deficiency in healthy populations is reviewed. Current concepts in treatment of IgA-deficient patients requiring blood products are described.

Adolescent↗