Search PubMed⌕ Search

Biomedical subjects

W J Martin

Publications and source records attributed to W J Martin.

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

Acquired methemoglobinemia from multiple oxidants.

Phenazopyridine has been associated with methemoglobinemia in patients who have received an overdose, have decreased renal function, or are discovered to be unusually susceptible to the drug (ie, they may have an undetected NADH methemoglobin reductase deficiency). The case we have presented is unusual in that normal doses of phenazopyridine were given, no renal dysfunction was evident, and our patient had previously been given this drug without complication. Methemoglobinemia appeared to be the result of metabolic overload by multiple oxidants (phenazopyridine and lidocaine) of the normal reductase pathways in the erythrocytes. We saw no evidence to indicate that bupivacaine contributed to its development. Enzyme pathway changes induced by chemotherapy should be considered, though few studies have linked alterations of enzyme levels and pathways with chemotherapy and malignancy.

Administration, Topical↗
PubMed1993

Use of soft heat-molded orthoses in sports. A clinical analysis.

Podiatrists have had considerable success with the use of orthoses in the treatment of athletic injuries and faulty biomechanics. In-office fabrication of soft orthoses out of heat-moldable plastics provides an alternative to the more rigid, prescription device. Easily constructed in 15 to 30 min, the soft heat-molded orthoses have shown favorable results when used clinically with injured athletes. Although the need for more comprehensive studies exists, podiatrists should consider the use of soft heat-molded orthoses with their athletic patients and possibly in combination with the more permanent, rigid orthoses.

Adult↗
PubMed1993

Interlobar variation in the recovery of bronchoalveolar lavage fluid, cell populations, and angiotensin-converting enzyme in normal volunteers.

Although bronchoalveolar lavage (BAL) is useful in studying a variety of lung diseases, it results in substantial dilution of cells and soluble proteins recovered from the lower respiratory tract. Surprisingly little is known about regional differences in BAL recovery in normals and patients with lung disorders. In order to assess regional differences in BAL in normals, we performed a prospective study of BAL in twenty non-smoking volunteers. With the subjects supine, BAL was performed in the right middle lobe (RML), right lower lobe (RLL) and Lingula (LING). The volumes recovered, cell numbers, and angiotensin converting enzyme (ACE) activities were determined separately for each BAL site. ACE was chosen as a representative soluble protein found in the lower respiratory tract which was easily measured in the BAL of normals. BAL volumes recovered from the RLL were significantly smaller than from the RML or LING, perhaps related to the dependent location of the RLL (P = 0.0002). The concentration of ACE and cells recovered per ml of BAL were significantly greater in the RLL than either the RML or LING (P = 0.05). In contrast, the total numbers of cells and total ACE recovered were similar from all sites sampled. This suggests that the differences in measured concentrations were due to different fluid recovery from these sites, resulting in variable dilution of proteins and cells. Urea measurement has been proposed as a means to quantify the epithelial lining fluid (ELF) volume sampled by BAL and estimate the actual concentrations of proteins present in the lower respiratory tract (J Appl Physiol 1986; 60:532-538).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1993

Mechanism of putrescine transport in human pulmonary artery endothelial cells.

Effective lung repair requires optimal replication of critical cell populations in the lung. Endogenous polyamines such as putrescine, spermidine and spermine play important roles in cell proliferation and differentiation, and may arise due to intracellular synthesis or transport into the cell. To determine the mechanism of polyamine transport in lung endothelial cells, the uptake of putrescine in human pulmonary artery endothelial cells was examined. Putrescine (7 nM) uptake into the cells approached equilibrium at 1 hr and was inhibited by methylglyoxal bis(guanylhydrazone). Kinetic studies revealed that uptake occurred via both a high- and low-affinity system. The effect of several amines (700 microM) on the 15-min uptake of putrescine was examined and a rank order of inhibition was determined: methylglyoxal bis(guanylhydrazone) > putrescine > spermine > spermidine > gentamicin > mepiperphenidol. alpha-Aminoisobutyric acid, a prototype system A amino acid, and tetraethylammonium, an organic cation, had no effect. N-ethylmaleimide inhibited transport 71%, whereas dinitrophenol did not. A reduction in temperature from 37 degrees C to 5 degrees C resulted in a 42% decrease in putrescine transport. Additionally, removing fetal bovine serum from the uptake medium reduced transport 38%. These data indicate that human pulmonary artery endothelial cells possess a specific transport system for polyamines. An improved understanding of this pathway in pulmonary endothelial cells may permit development of strategies to facilitate growth and repair of this critical cell population.

Amines↗
PubMed1992

Acetylator genotype-dependent N-acetylation of arylamines in vivo and in vitro by hepatic and extrahepatic organ cytosols of Syrian hamsters congenic at the polymorphic acetyltransferase locus.

Our laboratory recently reported the successful construction of homozygous rapid (Bio. 82.73/H-Patr) and homozygous slow (Bio. 82.73/H-Pat(s)) acetylator congenic Syrian hamsters. These hamsters are isogenic except for the polymorphic acetylator gene locus (Pat) and perhaps other closely linked loci. The purpose of the present investigation was to assess the expression of acetylator genotype both in vivo and in vitro in a variety of hepatic and extrahepatic organ cytosols. Levels of arylamine N-acetyl-transferase were generally high and in the relative order: liver greater than colon greater than kidney greater than pancreas greater than prostate, urinary bladder, and lung. However, an acetylator gene dose-response was clearly expressed in each tissue, with highest levels in homozygous Patr acetylators, intermediate levels in heterozygous Patr/Pat(s) acetylators, and lowest levels in homozygous Pat(s) acetylators. The magnitude of the acetylator genotype-dependent differences in N-acetyltransferase activity were substrate specific, wherein p-aminobenzoic acid showed the largest differences and p-aminophenol the smallest. The N-acetylation of p-aminobenzoic acid in vivo also reflected acetylator genotype in the congenic hamsters. These results further document the successful construction of rapid and slow acetylator congenic hamsters which should prove very valuable in future studies to assess the role of acetylator genotype in the toxicity and carcinogenicity of arylamine chemicals.

Acetylation↗
PubMed1992

Inhibition of human immunodeficiency virus-1 proliferation by liposome-encapsulated sense DNA to the 5' tat splice acceptor site.

A liposome formulation containing a distearoylphosphatidylethanolamine analog was developed that was endocytosed by both lymphocytes and monocytes. This formulation was used to encapsulate sense and antisense 20-mer oligodeoxynucleotides to the 5' tat splice acceptor site of human immunodeficiency virus type 1. At a DNA concentration of 140 nM, the liposome-encapsulated sense DNA inhibited p24 production by as much as 84% in human peripheral blood leukocytes infected with "wild-type" virus. This treatment also reduced the number of peripheral blood leukocytes producing intracellular viral antigen by 71%. Of interest, no reduction in either parameter was observed for the antisense-containing liposomes. The results demonstrate the promise of a new liposomal delivery vehicle to inhibit human immunodeficiency virus replication by an entrapped oligodeoxynucleotide.

Antiviral Agents↗
PubMed1992

120-kD surface glycoprotein of Pneumocystis carinii is a ligand for surfactant protein A.

Pneumocystis carinii is the most common cause of life-threatening pneumonia in immunocompromised patients. In the current study, surfactant protein A (SP-A), the major nonserum protein constituent of pulmonary surfactant, is demonstrated to bind P. carinii in a specific and saturable manner. SP-A is surface bound and does not appear to be internalized or degraded by the P. carinii organism. Furthermore, SP-A binding to P. carinii is time- and calcium-dependent and is competitively inhibited by mannosyl albumin. In the absence of calcium or the presence of excess mannosyl albumin, SP-A binding to P. carinii is reduced by 95 and 71%, respectively. SP-A avidly binds P. carinii with a Kd of 8 x 10(-9) M and an estimated 8.4 x 10(6) SP-A binding sites per P. carinii organism, as determined from Scatchard plots. SP-A is shown to bind P. carinii in vivo, and a putative binding site for SP-A on P. carinii is demonstrated to be the mannoserich surface membrane glycoprotein gp120. These findings suggest that P. carinii can interact with the phospholipid-rich material in the alveolar spaces by specifically binding a major protein constituent of pulmonary surfactant.

Animals↗
PubMed1991

Extrahepatic expression of the N-acetylation polymorphism toward arylamine carcinogens in tumor target organs of an inbred rat model.

An N-acetylation polymorphism is described that is expressed toward arylamine carcinogens in tumor target organs of an inbred rat model. High levels (rapid acetylator phenotype) of arylamine carcinogen N-acetyltransferase activity were observed in kidney, colon, prostate and urinary bladder cytosols derived from Fischer (F-344) inbred rats, the strain most commonly used for tumor bioassay studies and the strain most particularly used in arylamine-induced colon and prostate cancer studies. Significantly lower (slow acetylator phenotype) levels of arylamine carcinogen N-acetyltransferase activity were observed in corresponding tissue cytosols derived from Wistar-Kyoto inbred rats. Intermediate levels of arylamine carcinogen N-acetyltransferase activity significantly different from both the parental strains were observed in F1 hybrids of the parental strains, consistent with codominant expression of two alleles at a single gene locus. The arylamine substrates exhibiting the acetylator phenotype-dependent N-acetyltransferase activities included p-aminobenzoic acid, p-aminosalicylic acid, p-phenetidine, p-aminophenol, 2-aminofluorene, 3,2'-dimethyl-4-aminobiphenyl, beta-naphthylamine and 4-aminobiphenyl, but not procainamide. Highest levels of arylamine carcinogen N-acetyltransferase were expressed consistently in colon cytosol, but expression of the N-acetylation polymorphism toward arylamine carcinogens was observed in each (kidney, colon, prostate and urinary bladder) of the tumor target organs. The expression of the N-acetylation polymorphism in tumor target organs suggests that the inbred rat model will be useful in assessing the role of acetylator phenotype in arylamine-induced cancers of the colon and prostate.

Acetylation↗
PubMed1991

Pneumocystis carinii attachment to cultured lung cells by pneumocystis gp 120, a fibronectin binding protein.

Pneumocystis carinii is an extracellular organism which is thought to require attachment to alveolar epithelial cells for its growth and replication in humans. Fibronectin (Fn) binding to P. carinii is essential for optimal P. carinii attachment. This study demonstrates that gp120, a 110-120-kD membrane glycoprotein on P. carinii, mediates attachment of the organism to cultured lung cells and is the site of Fn binding to P. carinii. A 51Cr-labeled P. carinii binding assay was used to quantify attachment of the organism to the alveolar epithelial cell line A549. Addition of free gp120, purified from whole P. carinii organisms, caused a significant decrease in attachment of P. carinii to A549 cells from 44.2 +/- 5.5% to 22.4 +/- 4.2% (P less than 0.01). Preincubation of the P. carinii organisms with a polyclonal antibody to gp120 also resulted in a marked decrease in P. carinii attachment to A549 cells from 46.8% +/- 5.2% to 21.3 +/- 4.8% (P less than 0.01). Furthermore, addition of free gp120 to P. carinii organisms caused a significant reduction in specific binding of 125I-Fn to P. carinii (from 83.3 +/- 8.5 ng to 47.1 +/- 5.9 ng, P less than 0.01). Similarly, anti-gp 120 antibody decreased specific Fn binding to P. carinii from 74.3 +/- 8.4 ng to 25.5 +/- 5.3 ng (P less than 0.001). Solubilized P. carinii organisms separated by gel electrophoresis and blotted with 125I-Fn demonstrated specific binding of the 125I-Fn to gp120. In addition, a specific anti-beta 1-integrin antiserum reacted with gp120 by Western blot, suggesting structural homology between gp120 and the beta-subunit of integrins. Thus, the data suggest that the P. carinii membrane glycoprotein gp120 functions as a Fn binding protein and is required for optimal P. carinii attachment to alveolar epithelial cells.

Adhesiveness↗
PubMed1991

Modulation of Pneumocystis carinii adherence to cultured lung cells by a mannose-dependent mechanism.

Pneumocystis carinii is an opportunistic parasite that attaches to the alveolar epithelium during the initiation of pneumonia. It is unknown whether P. carinii recognizes specific receptors on the surface of lung cells. Our study indicates that concanavalin A (Con A), a lectin that recognizes mannose-containing glycoproteins, binds to P. carinii organisms in a saturable manner with a binding affinity of Kd = 11 x 10(-6) mol/L and with 18.5 x 10(6) Con A binding sites per P. carinii organism. Con A binds predominantly to glycoprotein 120, a mannose-rich glycoprotein on the surface of P. carinii. Treatment of cultured target lung cells (A549 cells) with Con A resulted in dramatic reduction of P. carinii attachment, from 34.9% +/- 4.1% to 8.1% +/- 1.3% (p less than 0.001), suggesting that mannose-containing cell surface molecules may be important in P. carinii adherence to target lung cells. In contrast, treatment of P. carinii with Con A resulted in slightly increased adherence of P. carinii when compared with controls. The effects of Con A on P. carinii adherence were reversed when Con A treatments were conducted in the presence of excess mannose, the sugar ligand for Con A. Further, pretreatment of A549 cell monolayers with excess mannose (5000 micrograms/ml) resulted in significant reduction of P. carinii adherence to A549 cells, from 39.4% +/- 2.5% to 28.4% +/- 1.3% (p = 0.003). These studies, for the first time, implicate mannose-containing cell surface molecules as important mediators of attachment between P. carinii and target lung cells.

Adenocarcinoma, Bronchiolo-Alveolar↗