Search PubMed⌕ Search

Biomedical subjects

R Smith

Publications and source records attributed to R Smith.

At least 523 records · Page 29Linked to original sources
PubMed1996

Adenomatoid odontogenic tumour: an unusual cause of gingival swelling in a 3-year-old patient.

The adenomatoid odontogenic tumour (AOT) is an uncommon, benign lesion of the jaws. It has been subdivided into two broad categories: central AOT and peripheral AOT. A case of peripheral AOT in a 3-year-old female with a history of congenital adrenal hyperplasia is reported. The lesion presented as a gingival mass associated with a fully erupted deciduous canine tooth. This is the eleventh reported case of peripheral AOT and the first in a 3-year-old patient.

Adrenal Hyperplasia, Congenital↗
PubMed1996

Identification of cGMP-dependent protein kinase and its specific substrates in the anterior pituitary.

In the anterior pituitary, cGMP is produced in response to a number of stimuli, but intracellular events distal to cGMP production are obscure. Since cGMP-dependent protein kinase (PKG) is a major effector of cGMP actions in other tissues we have determined whether PKG and its specific substrates might be present and responsive to external signals in the ovine anterior pituitary. Photoaffinity labelling with [32P]cGMP revealed a specific 78 kDa protein in ovine anterior pituitary that comigrated with purified bovine lung PKG-I. PKG in protein extracts from anterior pituitary or cultured anterior pituitary cells was enriched by DEAE ion-exchange chromatography and assayed for activity. Both tissue and cultured cells had a relatively high PKG activity by comparison with aortic smooth muscle (known high activity) and brain (known low activity). Subcellular distribution studies showed that in anterior pituitary, aortic and brain, PKG activity was present in both cytosol and triton-extracted membrane fractions, while in platelets the activity was associated with only the membrane fraction. To determine if this PKG might be responsive to extracellular signals an activity ratio assay was used. Incubation of cultured cells with atrial natriuretic peptide (ANP) and sodium nitroprusside, activators of membrane and cytosolic guanylate cyclases respectively, increased the activity of PKG. To determine events distal to PKG activation, a search for potential substrates of PKG was performed. Few substrates were detectable upon addition of purified PKG to tissue lysates due to the high background activity of endogenous protein kinases in the anterior pituitary. However, 19 substrates of PKG were detected in heat-stable and 14 in acid-soluble protein extracts of the anterior pituitary, in which background phosphorylation was almost abolished. After partial purification through Q-Sepharose ion-exchange chromatography some of these proteins were preferentially phosphorylated by addition of PKG-I, while the others were additionally substrates of exogenous cAMP-dependent protein kinase (PKA) or Ca2+ and phospholipid-dependent protein kinase (PKC). A 132-kDa substrate showed an identical phosphopeptide map to a PKG substrate previously described in vascular smooth muscle and platelets. These data demonstrate for the first time the presence of functional PKG activity and multiple PKG substrates in the anterior pituitary where they may play a role in mediating the intracellular actions of cGMP.

Affinity Labels↗
PubMed1996

Chromatographic analysis of photodynamically significant porphyrin dimers and trimers.

Two porphyrin dimers, dihematoporphyrin dimer (DHD) and divinyl dimer (DVD), and two porphyrin trimers, dihematoporphyrin trimer (DHT) and divinyl trimer (DVT), have been analyzed utilizing isocratic ion-pair reversed-phase high-performance liquid chromatography. Results indicate that the vinyl porphyrins can be distinguished by three peaks appearing near 15, 38, and 42 min. The hematoporphyrin complexes are identified by the appearance of a peak located at 35 min. The DVT and DVD complexes present unique chromatographic markers at 28 and 15 min, respectively. Based on the location of these chromatographic markers, it was found that the Photofrin drug must contain the DVD and the DHT complexes, but does not contain the DVT complex. The purity of the DVT complex is compromised by the presence of DHD and DHT impurities.

Chromatography, High Pressure Liquid↗
PubMed1996

A deletion in the first cysteine-rich repeat of the low-density-lipoprotein receptor leads to the formation of multiple misfolded isomers.

The ligand-binding domain of the low-density-lipoprotein (LDL) receptor comprises seven cysteine-rich repeats, each approximately 40 amino acids long. The deletion of two amino acids (Asp26 and Gly27) from the first of these repeats (LB1), leads to a defective LDL receptor, and the clinical syndrome of familial hypercholesterolemia [Leitersdorf, E., Hobbs, H. H., Fourie, A. M., Jacobs, M., van der Westhuyzen, D.R. & Coetzee, G.A. (1988) Proc. Natl Acad. Sci. USA 85, 7912-7916]. Receptors which reach the cell surface fail to bind IgG-C7, a conformation-specific monoclonal antibody directed to LB1. To determine the effects of the two-amino-acid deletion on the folding of the LB1 of the LDL receptor, we have expressed LB1 and the mutant repeat, des-Asp26, Gly27-LB1, as recombinant (rLB1 and des-Asp26, Gly27-rLB1) peptides, and have determined their ability to fold in vitro. Unlike rLB1, which folded into a single isomer that was recognized by IgG-C7 and had three disulfide bonds, des-Asp26, Gly27-rLB1 folded into an equilibrium mixture of four isomers. Each of these isomers contained three disulfide bonds, but none were recognized by IgG-C7. We suggest that LDL receptors in the endoplasmic reticulum (ER) of the cell also fold into an equilibrium mixture of distinct receptor molecules, each with an abnormally folded isomer of des-Asp26, Gly27-LB1, and that the retarded transport of receptors to the cell surface arises because only a subset of the isomers reaches the cell surface.

Amino Acid Sequence↗
PubMed1996

Fadrozole HCL (CGS-16949A) versus megestrol acetate treatment of postmenopausal patients with metastatic breast carcinoma: results of two randomized double blind controlled multiinstitutional trials.

BACKGROUND: Breast cancer patients with prior response to endocrine therapy achieve subsequent benefit from additional endocrine therapies. The efficacy and safety of an aromatase inhibitor, fadrozole HCL, were compared with megestrol acetate in post menopausal patients who had disease progression after receiving antiestrogen therapy either for metastatic disease or as adjuvant therapy. METHODS: In 2 multiinstitutional prospective trials, 683 postmenopausal patients were randomized to receive either fadrozole HCL, 1 mg twice daily, or megestrol acetate, 40 mg 4 times daily, in a double blind fashion after progression on first-line hormonal therapy. Objective response rates, time to progression, survival and safety of the two regimens were compared. RESULTS: Results of intent-to-treat analyses are presented in this study. No significant differences were detected between the two treatment groups in time to progression, objective response rates, duration of response, and survival in either trial. There were no clinically meaningful differences between the treatment groups in the incidence and severity of adverse experiences, except that weight gain, fluid retention, and dyspnea were observed in more patients in the megestrol acetate group compared with those receiving fadrozole HCL, whereas nausea and vomiting were observed in more patients in the fadrozole HCL group compared with those receiving megestrol acetate. CONCLUSIONS: Fadrozole HCL was as efficacious as megestrol acetate in postmenopausal patients with metastatic breast carcinoma after one hormonal therapy. Adverse experiences were mild with both therapies, but megestrol acetate was associated wiht a higher frequency of weight gain, fluid retention and dyspnea, whereas fadrozole HCL was associated with a higher frequency of nausea and vomiting.

Adult↗
PubMed1996

Fatty acid composition in major depression: decreased omega 3 fractions in cholesteryl esters and increased C20: 4 omega 6/C20:5 omega 3 ratio in cholesteryl esters and phospholipids.

Recently, there were some reports that major depression may be accompanied by alterations in serum total cholesterol, cholesterol ester and omega 3 essential fatty acid levels and by an increased C20: 4 omega 6/C20: 5 omega 3, i.e., arachidonic acid/eicosapentaenoic, ratio. The present study aimed to examine fatty acid composition of serum cholesteryl esters and phospholipids in 36 major depressed, 14 minor depressed and 24 normal subjects. Individual saturated (e.g., C14:0; C16:0, C18:0) and unsaturated (e.g., C18:1, C18:2, C20:4) fatty acids in phospholipid and cholesteryl ester fractions were assayed and the sums of the percentages of omega 6 and omega 3, saturated, branched chain and odd chain fatty acids, monoenes as well as the ratios omega 6/omega 3 and C20:4 omega 6/C20:5 omega 3 were calculated. Major depressed subjects had significantly higher C20:4 omega 6/C20:5 omega 3 ratio in both serum cholesteryl esters and phospholipids and a significantly increased omega 6/omega 3 ratio in cholesteryl ester fraction than healthy volunteers and minor depressed subjects. Major depressed subjects had significantly lower C18:3 omega 3 in cholesteryl esters than normal controls. Major depressed subjects showed significantly lower total omega 3 polyunsaturated fatty acids in cholesteryl esters and significantly lower C20:5 omega 3 in serum cholesteryl esters and phospholipids than minor depressed subjects and healthy controls. These findings suggest an abnormal intake or metabolism of essential fatty acids in conjunction with decreased formation of cholesteryl esters in major depression.

Adjustment Disorders↗