Search PubMed⌕ Search

Biomedical subjects

J B Smith

Publications and source records attributed to J B Smith.

At least 127 records · Page 7Linked to original sources
PubMed1994

Value of preoperative PSA in predicting pathologic stage of patients undergoing salvage prostatectomy.

OBJECTIVE: To evaluate the relationship of prostate-specific antigen (PSA) levels and pathologic stage in patients with prostate cancer treated with radiation therapy and undergoing salvage radical prostatectomy. METHOD: Retrospective analysis of preoperative PSA levels and final pathology in 24 men undergoing salvage prostatectomy following prior radiation therapy. RESULTS: Although preoperative PSA values were significantly higher in patients with positive surgical margins, preoperative PSA levels failed to predict the presence of absence of extracapsular extension, seminal vesicle involvement, or lymph node metastasis. CONCLUSION: Our results suggest that PSA is not a reliable method of accurately predicting the pathologic stage of patients who are candidates for salvage radical prostatectomy.

Aged↗
PubMed1994

Antigenic specificity of antibodies from patients with linear basement membrane deposition of IgA.

We reviewed the immunoreactivity of sera binding to the epidermal side of basement membrane split skin from 13 adults and 8 children with IgA alone, 9 adults with IgA and IgG and 7 adults with IgA and ocular pemphigoid. Immunoblots were done against previously described 45-, 97-, 180- and 230-kD antigens, and reactivity was confirmed by elution of antibody from nitrocellulose and binding to the basement membrane. Ten of 13 adults and 7 of 8 children reacted with the 97-kD antigen. Sera with both IgA and IgG reacted in varying patterns and on occasion with more than 1 antigen. All 7 patients with ocular cicatricial pemphigoid reacted uniquely with a 45-kD antigen.

Adult↗
PubMed1994

Transmembrane signals and protooncogene induction evoked by carcinogenic metals and prevented by zinc.

Cd2+ provokes an immediate production of inositol trisphosphate and the release of Ca2+ from internal stores in human fibroblasts and some other mammalian cells. Ni2+, Co2+, Fe2+, and Mn2+ evoke the release of stored Ca2+, but are less potent than Cd2+ (apparent K0.5 = 40 nM). Zn2+ and Cu2+ competitively inhibit Ca2+ release evoked by Cd2+ without affecting Ca2+ release by hormones such as bradykinin. Zn2+ has the same apparent Ki value (80-90 nM) towards the five agonist metals, which suggests that the metals interact with the same site. Many other divalent cations neither released stored Ca2+ nor affected Cd(2+)-evoked Ca2+ release. The agonist metals appear to activate phospholipase C via a G protein rather than a tyrosine kinase. The production of reactive oxygen species is probably not involved in Ca2+ release by the metals. Cd2+ and other stimuli that raise cytosolic-free Ca2+ induce cyclic (AMP) production, apparently by activating a calmodulin-dependent adenylyl cyclase. We suggest that an orphan receptor mediates the hormonelike responses to Cd2+ and the other agonist metals. The receptor is referred to as an orphan because its physiological stimulus is unknown. Growth of the fibroblasts in high Zn2+ desensitizes them to the five agonist metals without affecting Ca2+ release by bradykinin or histamine. A several hour incubation in culture medium with normal Zn2+ fully restores responsiveness to the five active metals. Growth in high Zn2+ appears to repress the synthesis of the putative orphan receptor because inhibitors of RNA or protein synthesis, or asparagine-linked glycosylation, prevented the restoration of metal responsiveness.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1994

Identification of the major components of the high molecular weight crystallins from old human lenses.

High molecular weight aggregates from the water soluble portion of four lenses from older donors were examined by mass spectrometric techniques that permitted unambiguous identification of the principal components as alpha A-, alpha B- and gamma s-crystallins. Post-translational modifications that were located and identified included deamidations in alpha A and gamma s and an intramolecular disulfide bond in alpha A-crystallin. The C-terminus of alpha A was not found, supporting previous suggestions that this portion of the protein may be important in preventing aggregation.

Aged↗
PubMed1994

Collagen induces normal signal transduction in platelets deficient in CD36 (platelet glycoprotein IV).

The receptor involved in platelet activation by collagen has not been identified. Platelet glycoprotein IV, now known as CD36, has been implicated in interaction with collagen and also been shown to be associated with intracellular tyrosine kinases. In order to investigate the possible role of collagen-mediated signal transduction via CD36, platelets were obtained from a donor that were deficient in CD36. The collagen-induced intracellular mobilization of Ca2+ in the CD36 deficient cells was of the same magnitude as that seen in platelets from normal donors. In addition, serotonin secretion did not appear to be impaired. Tyrosine phosphorylation was also comparable between the CD36-deficient and normal platelets. Thus, it is unlikely that CD36 plays a major role in collagen-dependent platelet signal transduction.

Antigens, CD↗
PubMed1993

Cytokine production in first trimester chorionic villi: detection of mRNAs and protein products in situ.

Growth factor cytokines must play important roles in placental growth and differentiation. We used cDNA-mRNA in situ hybridization to examine whether human first trimester chorionic villi could produce these substances locally. IL-1 beta and IL-4 mRNA was found in both trophoblast layers, whereas CSF-1 and TNF alpha were found mostly in syncytiotrophoblast with much less localization to cytotrophoblast areas. IFN-gamma message was exclusively found in the cytotrophoblast. Immunohistochemical analysis confirmed that cytokines are produced by placental tissue, and the patterns of expression correlated well with the data obtained by in situ hybridization. These data are discussed regarding possible roles of cytokines in regulation of MHC antigen expression by trophoblasts and immunomodulation of decidual lymphocytes.

Chorionic Villi↗
PubMed1993

Reaction of aspirin with cysteinyl residues of lens gamma-crystallins: a mechanism for the proposed anti-cataract effect of aspirin.

Incubation of lens crystallins with aspirin inhibits the development of opacities caused by cyanate. Cyanate-induced opacities are thought to be due to carbamylation of the lysyl residues which causes a decrease in the protein charge and subsequent conformational changes that permit disulfide bonding. Because aspirin can also react with lysyl residues, it has been proposed that the aspirin inhibition of cataractogenesis is due to acetylation of the lysyl residues which would block their reaction with cyanate. However, acetylation of lysyl residues also lowers the protein charge and would be expected to effect changes in protein conformation similar to those caused by carbamylation. Therefore, acetylation of the lysyl residues is not a satisfactory explanation for the inhibitory effect of aspirin on lens opacification. Our investigations of the reactions of cyanate and aspirin with bovine gamma II-crystallins show that the cysteinyl residues are also carbamylated and acetylated at pH 7.4. At this pH, the carbamylation at the cysteinyl residues is reversible, leading to regeneration of the thiol group and disulfide bonding. In contrast, the acetylation at cysteinyl residues is stable at pH 7.4 and can prevent disulfide bonding. This difference in stability explains how cyanate promotes, and aspirin inhibits, cataractogenesis.

Acetylation↗
PubMed1993

Elevation of cAMP in human platelets inhibits thrombin- but not collagen-induced tyrosine phosphorylation.

Both thrombin and collagen induced the phosphorylation of tyrosine in numerous proteins in platelets, with collagen causing the phosphorylation of an additional 40 kDa protein. Thrombin-induced phosphorylation was markedly inhibited when cAMP was elevated with iloprost. Iloprost or the combination of iloprost, inhibitors of positive feedback and cytochalasin D also partially inhibited collagen-induced phosphorylation. By contrast, iloprost had no effect on phosphorylation induced by collagen in the presence of inhibitors of positive feedback by released ADP, TxA2 and fibrinogen and in platelets containing BAPTA to prevent increases in cytosolic Ca2+. The results indicate that collagen-induced tyrosine phosphorylation may be a fundamental pathway in hemostasis which can function even when platelet cAMP is elevated.

Blood Platelets↗
PubMed1993

The reaction of bovine lens alpha A-crystallin with aspirin.

Acetylation of the lysines of bovine lens alpha A-crystallin has been examined after 0-48-hr incubations of whole alpha-crystallins in 100 mM aspirin. The alpha A-crystallins were isolated after the incubation, proteolytically digested into peptides which were separated by reversed phase HPLC and analysed by mass spectrometry. For the reaction conditions used in this investigation, acetylated lysyl residues were the principal products. The extent of acetylation was quantified from the intensities of the peaks in the fast atom bombardment mass spectra of the modified and unmodified peptides. The modified lysine containing peptides demonstrated that all seven lysyl residues of alpha A-crystallin reacted with aspirin; the extent of acetylation at each lysyl residue varied. Plots of the extent of acetylation vs. time were used to calculate rate constants for the reaction at each lysyl residue. The rate constant for the acetylation of Lys 166, the most reactive, was about seven times greater than for Lys 88, the least reactive. These rate constants were used to calculate the yield of predicted products for the reaction of alpha-crystallin with therapeutic concentrations of aspirin. Comparison of the yield of acetylated alpha-crystallin with the yield of carbamylated alpha-crystallin that might occur due to renal failure indicates that aspirin is not likely to be an effective inhibitor of cataract due to carbamylation of lysyl residues.

Acetylation↗
PubMed1993

Abnormal T-cell function in patients with psoriatic arthritis: evidence for decreased interleukin 2 production.

Psoriatic arthritis (PSA) is an inflammatory arthritis associated with psoriasis. Although not considered an autoimmune process, there is evidence for humoral and cellular immune abnormalities similar to autoimmune diseases such as rheumatoid arthritis and systemic lupus (SLE). We investigated mitogen-induced proliferation and interleukin 2 (IL-2) production by peripheral blood mononuclear cells in patients with PSA. Both IL-2 production and proliferation were significantly decreased in PSA patients when compared to controls. Increased arachidonic acid metabolism has been reported in skin and peripheral mononuclear cells of patients with psoriasis and PSA. We therefore also investigated the effect of indomethacin and prostaglandin E2 (PGE2) on IL-2 production. Addition of indomethacin to cultures did not significantly change IL-2 production in patients with PSA, but did so in controls. PGE2 produced a significant reduction in IL-2 production in PSA and in controls.

Adult↗
PubMed1993

Primary structure of rabbit lens alpha-crystallins.

The primary structure and posttranslational modifications of rabbit lens alpha-crystallins were examined using electrospray ionization mass spectrometry to determine the molecular weights of the intact proteins and fast atom bombardment mass spectrometry to analyze proteolytic digests of the alpha A- and alpha B-crystallins. The previously determined primary structure of alpha A-crystallin was confirmed. Posttranslational modifications detected included one phosphorylation site and the presence of a truncated form minus the five C-terminal residues. The previously undetermined amino acid sequence of rabbit alpha B-crystallin was determined to be the same as the bovine alpha B-crystallin sequence except at three residues: Thr 40, Thr 132, and Pro 153. Rabbit alpha B-crystallin showed evidence of phosphorylation at the same three sites as bovine alpha B-crystallin. The molecular weights of the intact proteins indicated that any one molecule had a maximum of two phosphorylations. Also, there was a truncated form which did not include the five C-terminal residues.

Amino Acid Sequence↗
PubMed1993

Effects of reinforcer limitations on fixed-ratio responding during repeated administration of chlorpromazine.

Key-pecking was maintained under a 30-response fixed-ratio schedule of food presentation and pigeons received 30 mg/kg/day chlorpromazine immediately prior to experimental sessions. After responding stabilized during chronic drug and animals were receiving all available reinforcers, the time available for receiving reinforcers was systematically varied. When that time was decreased, animals initially received fewer reinforcers but responding subsequently increased to an extent that animals once more received all available reinforcers. When that time was again increased, responding once again decreased but only to an extent that animals continued receiving all available reinforcers. During subsequent reversals of the time for reinforcer availability, responding increased or decreased to an extent always resulting in the maximum number of reinforcers. When drug was discontinued, responding returned to predrug levels. These results demonstrate that effects of chronically administered chlorpromazine were influenced by both drug activity at its site of action and by the behavioral process of reinforcement.

Animals↗
PubMed1993

Stable expression of the cardiac sodium-calcium exchanger in CHO cells.

A line of Chinese hamster ovary (CHO) cells called CK1.4 was produced by transfection with the gene for the bovine cardiac Na(+)-Ca2+ exchanger. CK1.4 cells stably expressed substantial exchange activity and exchanger protein as shown by immunoprecipitation. Exchange activity was quantified as 45Ca2+ influx that depended on both increasing intracellular Na+ and lowering the concentration of external Na+. Replacing external Na+ with K+ slightly increased 45Ca2+ uptake by CK1.4 cells with basal Na+ and greatly increased 45Ca2+ uptake by Na(+)-loaded cells. Neither exchange activity nor exchanger protein was detected in the nontransfected parental line. By contrast to CK1.4 cells, replacing external Na+ with K+ decreased 45Ca2+ uptake in the nontransfected cells whether or not they were Na+ loaded. Changes in cytosolic free Ca2+ determined with fura-2 were consistent with the 45Ca2+ uptake data. Analysis of poly(A)(+)-RNA by Northern blot confirmed that CK1.4 cells, but not the parental line, expressed the exchanger. Expression of the exchanger was also observed in aortic myocytes and a renal epithelial cell line (LLC-MK2) but not in other lines of renal epithelial cells (MDCK, LLC-PK1) or human dermal fibroblasts. The cardiac exchanger produced substantial 45Ca2+ efflux from CK1.4 cells in response to hormone-evoked release of stored Ca2+. CK1.4 cells are an attractive model for studies of the regulation of the cardiac exchanger because they stably express sufficient exchanger for biochemical and immunological analysis.

Animals↗