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Biomedical subjects

P Adams

Publications and source records attributed to P Adams.

At least 91 records · Page 5Linked to original sources
PubMed1993

Allosteric inhibition of human lymphoblast and purified porphobilinogen deaminase by protoporphyrinogen and coproporphyrinogen. A possible mechanism for the acute attack of variegate porphyria.

Variegate porphyria (VP) is characterized by photocutaneous lesions and acute neuropsychiatric attacks. Decreased protoporphyrinogen oxidase activity results in accumulation of protoporphyrin (ogen) IX and coproporphyrin (ogen) III. During acute attacks delta-aminolevulinic acid and porphobilinogen also increase, suggesting that porphobilinogen deaminase (PBG-D) may be rate limiting. We have examined the effects of porphyrinogens accumulating in VP on PBG-D activity in Epstein-Barr virus-transformed lymphoblast sonicates from 12 VP and 12 control subjects. Protoporphyrinogen oxidase activity was decreased and protoporphyrin increased in VP lymphoblasts. PBG-D in control lymphoblasts obeyed Michaelis-Menten kinetics (Vmax 28.7 +/- 1.8 pmol/mg per h, Hill coefficient 0.83 +/- 0.07). VP sonicates yielded sigmoidal substrate-velocity curves that did not obey Michaelis-Menten kinetics. Vmax was decreased (21.2 +/- 2.0 pmol/mg per h) and the Hill coefficient was 1.78 +/- 0.17. Addition of protoporphyrinogen IX and coproporphyrinogen III to control sonicates yielded sigmoidal PBG-D substrate-velocity curves and decreased PBG-D Vmax. Addition of porphyrins or uroporphyrinogen III did not affect PBG-D activity. Removal of endogenous porphyrin (ogens) from VP sonicates restored normal PBG-D kinetics. Purified human erythrocyte PBG-D obeyed Michaelis-Menten kinetics (Vmax 249 +/- 36 nmol/mg per h, Km 8.9 +/- 1.5 microM, Hill coefficient 0.93 +/- 0.14). Addition of protoporphyrinogen yielded a sigmoidal curve with decreased Vmax. The Hill coefficient approached 4. These findings provide a rational explanation for the increased delta-aminolevulinic acid and porphobilinogen during acute attacks of VP.

Cell Line, Transformed↗
PubMed1992

Formation of proline thiohydantoin with ammonium thiocyanate: progress towards a viable C-terminal amino-acid-sequencing procedure.

Pure amino acid thiohydantoins are required as reference standards for development of C-terminal-sequencing procedures based on thiohydantoin formation of the C-terminal amino acids of peptides and proteins. Proline thiohydantoin was prepared using a straightforward method involving reaction of acetylproline with ammonium thiocyanate. It was characterized by UV spectrophotometry, mass spectrometry and back-hydrolysis to the free amino acid. These data establish unequivocally that the thiocyanate procedure is applicable to proline as well as to the other common amino acids. This work also validates earlier claims that proline thiohydantoin can be prepared by reaction with thiocyanic acid.

Amino Acid Sequence↗
PubMed1991

Dopamine D1 receptor stimulation of cyclic AMP accumulation in COS-1 cells.

Dopamine is shown to stimulate cAMP accumulation in COS-1 cells via endogenously expressed dopamine D1 receptors. A dissociation of dopamine and beta-adrenoceptor responses is demonstrated by the use of selective antagonists and different desensitization patterns following exposure of the cells to dopamine or the beta-adrenoceptor agonist, isoproterenol. The dopamine response in COS-1 cells exhibits a pharmacological profile similar to that found in dopamine D1 tissues such as rat striatum and fish retina. The presence of DARPP-32 (dopamine- and cAMP-regulated phosphoprotein, Mr 32,000) immunoreactivity in COS-1 cells is shown by Western blotting and is consistent with the endogenous expression of a dopamine D1 receptor in these cells. It is concluded that a dopamine D1 receptor is expressed in COS-1 cells and the implications of this are discussed.

2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-ben↗
PubMed1991

Fibroblast growth factor receptors from liver vary in three structural domains.

Changes in heparin-binding fibroblast growth factor gene expression and receptor phenotype occur during liver regeneration and in hepatoma cells. The nucleotide sequence of complementary DNA predicts that three amino-terminal domain motifs, two juxtamembrane motifs, and two intracellular carboxyl-terminal domain motifs combine to form a minimum of 6 and potentially 12 homologous polypeptides that constitute the growth factor receptor family in a single human liver cell population. Amino-terminal variants consisted of two transmembrane molecules that contained three and two immunoglobulin-like disulfide loops, as well as a potential intracellular form of the receptor. The two intracellular juxtamembrane motifs differed in a potential serine-threonine kinase phosphorylation site. One carboxyl-terminal motif was a putative tyrosine kinase that contained potential tyrosine phosphorylation sites. The second carboxyl-terminal motif was probably not a tyrosine kinase and did not exhibit the same candidate carboxyl-terminal tyrosine phosphorylation sites.

Amino Acid Sequence↗
PubMed1991

Inhibition of iron absorption by omeprazole in rat model.

Since gastric acid is an important luminal factor in the absorption of non-heme iron, the effect of omeprazole on the absorption of iron in a rat model was studied. Iron absorption studies were performed on rats on a normal diet (N = 42) and rats fed an iron-deficient diet (N = 43) for three weeks. Rats were orally dosed with 40 mumol/kg of omeprazole or placebo daily for two days prior to iron absorption studies. Rats were orally dosed with 1 mmol of ferrous chloride, ferric chloride or food iron (dietary suspension) containing 11 micrograms of iron and labeled with 1 microCi of 59Fe. Omeprazole-treated rats on the normal diet had no significant reduction in the absorption of ferric, ferrous, or food iron. In the rats on the iron-deficient diet, the absorption of ferrous iron decreased from 76 +/- 7.5% (mean +/- SE) in control rats to 38 +/- 8.5% in the omeprazole-treated rats (P less than 0.003) and the absorption of food iron decreased from 65 +/- 7.5% in control rats to 37 +/- 6.5% in the omeprazole-treated rats (P less than 0.016). There was no significant reduction in the absorption of ferric iron. Omeprazole therapy is unlikely to be associated with significant iron malabsorption in normal patients but may reduce iron absorption in pathological states associated with increased iron absorption such as iron deficiency.

Absorption↗
PubMed1990

Replication of the dihydrofolate reductase genes on double minute chromosomes in a murine cell line.

The purpose of this study is to determine the kinetics of the replication of intrachromosomal versus extrachromosomal amplified dihydrofolate reductase (DHFR) genes. Previous studies reported that the DHFR gene, when carried intrachromosomally on a homogeneously staining region, replicates (as a unit) within the first 2 h of the S phase of the cell cycle. We wished to determine if the extrachromosomal location of the amplified genes carried on double minute chromosomes effects the timing of their replication. Equilibrium cesium chloride ultracentrifugation was used to separate newly replicated (BUdR-labeled) DNA from bulk DNA in a synchronized cell population. Hybridization with the cDNA for the DHFR gene allowed us to determine the period of time within the cell cycle in which the DHFR DNA sequences were replicated. We found that, in contrast to intrachromosomal dihydrofolate reductase genes that uniformly replicate as a unit at the beginning of the S phase of the cell cycle, dihydrofolate reductase genes carried on double minute chromosomes (DMs) replicate throughout the S phase of the cell cycle. These results suggest that control of replication of extrachromosomal DNA sequences may differ from intrachromosomal sequences.

Animals↗
PubMed1990

The antigen-limited nature of microtiter ELISAs requires partial depletion of IgG to permit reliable determination of rabbit serum IgA antibody activity.

The antigen-limiting nature of microtiter ELISAs predicts that antibodies of minor classes may be underestimated when the same specimen contains large amounts of IgG antibodies specific for the same antigen. Such competitive inhibition can be diagnosed from ELISA titration plots. A method is described to eliminate the negative effects of this competition on the detection of IgA antibodies in rabbit serum. The detectability of rabbit serum antibodies to ovalbumin and bovine serum albumin is increased 10-fold by prior treatment of 1:100 dilutions of serum with 1% Cowan I S. aureus. High concns of S. aureus, e.g. 10%, completely deplete serum IgG without loss of IgA. However, concns higher than 1% do not lead to additional improvement in the detectability of IgA antibodies in the systems studied. The method is rapid, inexpensive and shows no non-specific depletion of IgA from either serum or bronchoalveolar lavage fluid.

Animals↗
PubMed1990

Primary biliary cirrhosis and polymyositis.

We document the rare occurrence of primary biliary cirrhosis (PBC) and polymyositis in a 68-year-old woman. The diagnosis was confirmed by liver biopsy, antimitochondrial antibody, muscle biopsy, and electromyography. We discuss the possible common immunological basis for these two diseases and the risks and benefits of immunosuppressive therapy.

Aged↗
PubMed1990

Synovial fluid pH, cytologic characteristics, and gentamicin concentration after intra-articular administration of the drug in an experimental model of infectious arthritis in horses.

Chemical and cytologic effects and bactericidal activity of gentamicin in septic synovial fluid were evaluated in an experimental model of infectious arthritis in horses. Septic arthritis was induced by inoculation of approximately 7.5 X 10(6) colony-forming units of Escherichia coli into 1 antebrachiocarpal joint in each of 16 clinically normal adult horses. Clinical signs of septic arthritis were evident 24 hours after inoculation. Horses were allotted to 3 groups: group-1 horses (n = 5) each were given 150 mg of gentamicin (50 mg/ml; 3 ml) intra-articularly (IA); group-2 horses (n = 5) each were given 2.2 mg of gentamicin/kg of body weight, IV, every 6 hours; and group-3 horses (n = 6) each were given buffered gentamicin, consisting of 3 mEq of sodium bicarbonate (1 mEq/ml; 3 ml) and 150 mg of gentamicin (50 mg/ml; 3 ml), IA. Synovial fluid specimens were obtained at posttreatment hour (PTH) 0, 0.25, 1, 4, 8, 12, and 24 via an indwelling intra-articular catheter. Synovial fluid pH was evaluated at PTH 0, 0.25, and 24. Microbiologic culture and cytologic examination were performed on synovial fluid specimens obtained at PTH 0 and 24, and gentamicin concentration was measured in all synovial fluid specimens. At PTH 0, E coli was isolated from synovial fluid specimens obtained from all horses. Synovial fluid pH was lower (range, 7.08 to 7.16) and WBC count was higher (range, 88,000 to 227,200 cells/microliters) and predominantly neutrophilic (95 to 99%) at PTH 0 than before inoculation.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1990

Saliva and serum lithium monitoring in hospitalized children.

Serum and saliva lithium levels are presented for 30 inpatients, ages 5.12 to 11.95 years, diagnosed as having conduct disorder of the undersocialized aggressive type. Maintenance doses of lithium carbonate ranged from 600 mg to 1,500 mg/day. Serum and saliva lithium levels were significantly correlated at optimal dose (r = .78, p less than .001) and overall (r = .83, p less than .001), lending support to the use of saliva lithium levels as an adjunct to serum lithium determinations. However, because saliva/serum lithium ratios reveal wide ranges between subjects, the use of saliva levels is limited, and laboratory assessments should be combined with careful clinical monitoring.

Child↗
PubMed1989

Heparin-binding growth factor gene expression and receptor characteristics in normal rat prostate and two transplantable rat prostate tumors.

Heparin-binding polypeptide growth factors (HBGF) are essential mitogens for isolated prostate cells. HBGF type one (HBGF-1) mRNA was expressed specifically in the epithelial cells of prostates from normal 6- to 8-week-old rats. Expression declined significantly at 14 weeks and was undetectable in 35-week-old animals. Slow-growing, androgen-responsive, nonmetastatic Dunning R3327PAP tumors, which are composed of a well-defined epithelium and stroma, expressed HBGF-1 mRNA constitutively in specifically the mesenchymal cells. A rapid-growing, androgen-independent, metastatic variant (Dunning R3327AT-3), which was composed of a single clonogenic cell type, expressed both HBGF-1 and HBGF type two (HBGF-2) mRNA. HBGF activity in the extracts of normal and tumor tissues correlated with mRNA levels. Epithelial cells from the R3327PAP tumor and the single cell type that composed the R3327AT-3 tumor exhibited alterations in HBGF receptor characteristics that correlated with increased sensitivity to mitogenic effects of HBGF. The results suggest that alterations in HBGF gene expression in both prostate epithelial and mesenchymal cells and in properties of the receptor in specifically epithelial cells may contribute to differential growth rates and malignancy of different prostatic tumors.

Animals↗
PubMed1989

The effects of haloperidol on discrimination learning and behavioral symptoms in autistic children.

This double-blind and placebo-controlled clinical trial in autistic children had three objectives: (a) to replicate earlier findings that haloperidol administration is associated with a significant reduction of behavioral symptoms; (b) to further assess its safety when given on a short-term basis; and (c) to assess whether it has an effect on discrimination learning. Forty-five children, 2.02 to 7.58 years old (M = 4.49), completed this crossover design, with random assignment to treatment sequences. Haloperidol was shown to be a powerful therapeutic agent when administered for 4 weeks and free of side effects; at doses ranging from 0.25 to 4.0 mg/day (M = 0.844), there was a clinically and statistically significant reduction of a variety of symptoms. Under the given conditions, the children failed to learn on either haloperidol or placebo.

Autistic Disorder↗
PubMed1989

Long-term efficacy of haloperidol in autistic children: continuous versus discontinuous drug administration.

The aim of this study was to evaluate the long-term efficacy of haloperidol in autistic children and to determine whether discontinuous drug administration was as effective as continuous drug administration. Sixty children, 48 males and 12 females, ages 2.3 to 7.9 years (X 5.1) completed the study. They received haloperidol over a period of 6 months followed by a 4-week drug withdrawal/placebo period. Haloperidol remained effective, and the discontinuous treatment schedule did not diminish its efficacy. Children with prominent symptoms of irritability, angry and labile affect, and uncooperativeness were the best responders to haloperidol.

Autistic Disorder↗