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Biomedical subjects

K J Nelson

Publications and source records attributed to K J Nelson.

At least 19 recordsLinked to original sources
PubMed1995

Comparison of once daily doses of lansoprazole (15, 30, and 60 mg) and placebo in patients with gastric ulcer.

OBJECTIVES: A multicenter, double-blind study was conducted in 268 patients to compare the safety and efficacy of 15, 30, and 60 mg of lansoprazole and placebo in the treatment of gastric ulcer. METHODS: The study included an 8-wk treatment period to assess healing and a 6-month posttreatment period to evaluate ulcer recurrence. Endoscopies were performed, GI symptoms and antacid use were assessed, and safety evaluations were conducted, including serum gastrin and biopsies of the lesions and the greater curvature of the stomach. RESULTS: At week 4, healing rates were significantly higher with lansoprazole 15 and 30 mg (64.6 and 58.1%, respectively) compared with placebo (37.5%). By week 8, healing rates were 76.7% with placebo, 92.2% with 15 mg of lansoprazole, 96.8% with 30 mg, and 93.2% with 60 mg of lansoprazole (p < 0.05). The drug was well tolerated, with no significant differences from placebo in the incidence of adverse events. Fasting serum gastrin increased in all lansoprazole groups, reaching a plateau by week 2 and returning to baseline levels by month 1 posttreatment. No significant increase in Grimelius-positive cells or inflammation was evident. All but two patients had normal gastric morphology evaluated by Solcia classification. CONCLUSIONS: Lansoprazole, 15, 30, and 60 mg, administered once daily before eating, healed gastric ulcers to an approximately equal degree, and all were significantly better than placebo.

2-Pyridinylmethylsulfinylbenzimidazoles↗
PubMed1993

Bovine bronchial epithelial cells metabolize L-arginine to L-citrulline: possible role of nitric oxide synthase.

The conversion of L-arginine to L-citrulline is catalyzed by nitric oxide synthase (NOS), and results in the release of nitric oxide (NO). We hypothesized that bronchial epithelial cells metabolize L-arginine to L-citrulline. We found that cell lysates obtained from unstimulated, cultured bovine bronchial epithelial cells (BBECs) converted L-[3H]arginine to L-[3H]citrulline. This conversion was attenuated by three competitive NOS inhibitors and modulated by lipopolysaccharide and cigarette smoke extract (p < 0.01, all comparisons). These data demonstrate that BBECs metabolize L-arginine to L-citrulline and implicate a role for the L-arginine:NOS biosynthetic pathway in modulating airway responses.

Amino Acid Oxidoreductases↗
PubMed1993

Effects of age on serial recall of natural and synthetic speech.

The present study addressed the effects of aging on auditory serial-recall performance for natural and synthetic words. Word difficulty, measured in terms of frequency of occurrence and phonological similarity, and rate of presentation were also manipulated in an effort to determine which processes underlying serial-recall performance, if any, were affected by aging. Results indicated that age per se had little effect on short-term (working) memory as measured by the serial recall of monosyllabic words. Rate of presentation had little effect on recall for either subject group. Word difficulty, on the other hand, affected recall for both groups, with easy words being more readily recalled than hard words.

Acoustic Stimulation↗
PubMed1993

Inhibitors of nitric oxide synthase attenuate human neutrophil chemotaxis in vitro.

Products released through the L-arginine/nitric oxide biosynthetic pathway regulate soluble guanyl cyclase activity, which in turn modulates polymorphonuclear leukocyte chemotaxis. We hypothesized that inhibitors of nitric oxide synthase attenuate polymorphonuclear leukocyte chemotaxis in vitro. To test this hypothesis, unstimulated polymorphonuclear leukocytes were pretreated with buffer or the nitric oxide synthase inhibitors NG-monomethyl-L-arginine (L-NMMA), NG-nitro-L-arginine methyl ester, and L-canavanine before being exposed to three structurally unrelated chemoattractants, N-formyl-methionyl-leucyl-phenylalanine, C5a des arginine, and leukotriene B4. Polymorphonuclear leukocyte chemotaxis was quantified with a modified blind-well chamber technique. We found that L-NMMA and L-canavanine but not NG-nitro-L-arginine significantly attenuated polymorphonuclear leukocyte chemotaxis (p < 0.05). L-Arginine but not D-arginine, the nitric oxide donor sodium nitroprusside, and 8-bromo-cyclic guanosine monophosphate restored polymorphonuclear leukocyte chemotaxis attenuated by L-NMMA. Chemotaxis of polymorphonuclear leukocytes primed with lipopolysaccharide (Escherichia coli 0127:B8) or phorbol-13-butyrate was also significantly attenuated by pretreatment with L-NMMA and L-canavanine. Consistent with these observations, intracellular concentrations of cyclic guanosine monophosphate in polymorphonuclear leukocytes was decreased by L-NMMA during exposure to N-formyl-methionyl-leucyl-phenylalanine. These data indicate that nitric oxide synthase inhibitors attenuate chemotaxis of unstimulated and primed polymorphonuclear leukocytes in vitro. We suggest that the L-arginine/nitric oxide biosynthetic pathway plays an important role in regulating polymorphonuclear leukocyte emigration in vivo.

Amino Acid Oxidoreductases↗
PubMed1992

Regional distribution of emphysema: correlation of high-resolution CT with pulmonary function tests in unselected smokers.

High-resolution computed tomography (CT) was correlated with pulmonary function tests in the evaluation of regional emphysema in 59 smokers. The lung was divided into upper (above the carina tracheae) and lower (below the carina tracheae) zones, and the degree of emphysema was graded with a subjective and an objective measurement. Functional emphysema was defined as a diffusion capacity less than 75% of predicted and forced expiratory volume in 1 second less than 80% of predicted. Three of 15 (20%) subjects with functional emphysema had no subjective evidence of emphysema at high-resolution CT, and 10 of 25 (40%) with emphysema at high-resolution CT had no functional abnormalities consistent with emphysema. Even though the upper lung zones were more severely affected by emphysema, the degree of emphysema in the lower zones had a stronger correlation with pulmonary function abnormalities. The upper lung zones are a relatively silent region where extensive destruction may occur before functional abnormalities become known.

Aged↗
PubMed1992

Modulation of neutrophil and mononuclear cell adherence to bronchial epithelial cells.

Neutrophils and mononuclear cells have been associated with the lower respiratory tract inflammation observed in both acute and chronic bronchitis. In order to transit into and remain within the airways, neutrophils and mononuclear cells would likely need to adhere to bronchial epithelium. To test this hypothesis, bovine bronchial epithelial cells (BBECs) were isolated and cultured on a round coverslip. After 7 to 10 days, 51Cr-labeled neutrophils and mononuclear cells were evaluated for their capacity to adhere to the BBEC monolayer. Both neutrophils and mononuclear cells readily bound to the BBEC monolayer (10.8 +/- 1.2% bound neutrophils; 40.5 +/- 2.8% bound mononuclear cells). Stimulation of the neutrophils and mononuclear cells with phorbol 12-myristate 13-acetate (PMA) increased the adherence (45.8 +/- 10.6% bound neutrophils, P less than 0.01 compared with unstimulated cells; 58.7 +/- 6.2% bound mononuclear cells, P less than 0.01 compared with unstimulated cells). Importantly, stimulating the BBEC monolayer with PMA, bacterial lipopolysaccharide, or a cigarette smoke extract for 4 to 72 h also increased the adherence of both cell types (P less than 0.01, all comparisons at 24 h). The adherence was not decreased by exposure of either the BBEC monolayer, the neutrophils, or the mononuclear cells to cycloheximide or to the anti-CD11/CD18 monoclonal antibody 60.3 (P greater than 0.05). However, exposure of the BBEC monolayer to trypsin before addition of the neutrophils significantly decreased adherence (P less than 0.05). Because neutrophils and mononuclear cells are thought to mediate cell cytotoxicity by adhering to the target cells, BBECs were labeled with 51Cr, and 51Cr release was measured as an index of cytotoxicity. There was a modest increase in 51Cr release by the addition of unstimulated neutrophils and mononuclear cells, and culturing the BBEC monolayer with PMA before the addition of the neutrophils or mononuclear cells resulted in a further modest enhancement of 51Cr release (P less than 0.05). Similar results were obtained using lactate dehydrogenase release as a measure of cytotoxicity. These results demonstrate that inflammatory cells can adhere to BBECs and may be capable of mediating cytotoxicity and adherence and cytotoxicity can be increased by stimulating BBECs.

Animals↗
PubMed1991

Recognition of synthetic speech by hearing-impaired elderly listeners.

The Modified Rhyme Test (MRT), recorded using natural speech and two forms of synthetic speech, DECtalk and Votrax, was used to measure both open-set and closed-set speech-recognition performance. Performance of hearing-impaired elderly listeners was compared to two groups of young normal-hearing adults, one listening in quiet, and the other listening in a background of spectrally shaped noise designed to simulate the peripheral hearing loss of the elderly. Votrax synthetic speech yielded significant decrements in speech recognition compared to either natural or DECtalk synthetic speech for all three subject groups. There were no differences in performance between natural speech and DECtalk speech for the elderly hearing-impaired listeners or the young listeners with simulated hearing loss. The normal-hearing young adults listening in quiet out-performed both of the other groups, but there were no differences in performance between the young listeners with simulated hearing loss and the elderly hearing-impaired listeners. When the closed-set identification of synthetic speech was compared to its open-set recognition, the hearing-impaired elderly gained as much from the reduction in stimulus/response uncertainty as the two younger groups. Finally, among the elderly hearing-impaired listeners, speech-recognition performance was correlated negatively with hearing sensitivity, but scores were correlated positively among the different talker conditions. Those listeners with the greatest hearing loss had the most difficulty understanding speech and those having the most trouble understanding natural speech also had the greatest difficulty with synthetic speech.

Adult↗
PubMed1991

Complement activation by cigarette smoke.

Lung disease secondary to cigarette smoking is associated with an influx of neutrophils and monocytes into the lower respiratory tract. To determine whether cigarette smoke can generate chemotactic activity, human serum was exposed to cigarette smoke and evaluated for neutrophil and monocyte chemotactic activity. Serum exposed to cigarette smoke attracted significantly greater numbers of neutrophils and monocytes compared with normal human serum exposed to air (P less than 0.01, both comparisons). The increase in chemotactic activity was partially attenuated by EDTA but not by ethylene glycol-bis(beta-aminoethyl ether)-N,N,N',N'-tetraacetic acid (EGTA) and MgCl2 (P greater than 0.05, both comparisons), suggesting activation of the alternate complement pathway. To evaluate the capacity of cigarette smoke to activate the complement system, smoke-exposed serum was evaluated for cleavage of properdin factor B and C3 using immunoelectrophoresis and for C5a using a radioimmunoassay. Cleavage of properdin factor B and C3 was observed in the smoke-exposed serum and C5a was detected in the smoke-exposed serum (112 +/- 31 ng/ml). These data suggest that complement activation may play a role in directing the influx of neutrophils and monocytes into the lungs of cigarette smokers.

Chemotaxis, Leukocyte↗
PubMed1991

Gcglobulin functions as a cochemotaxin in the lower respiratory tract. A potential mechanism for lung neutrophil recruitment in cigarette smokers.

Activation of the complement pathway with generation of the potent chemotaxin C5a may play a significant role in the neutrophil accumulation seen in the lungs of patients with smoking-associated diseases. Although C5a is rapidly degraded to the less potent chemotaxin C5a des Arg, binding of this peptide with its cochemotaxin Gcglobulin (GcG) can restore its chemotactic potency. Therefore, modulation of Gcglobulin levels in smoking-induced lung disease could affect the accumulation of neutrophils seen in this disorder. To test this hypothesis GcG was measured by an enzyme-linked immunosorbent assay in bronchoalveolar lavage fluids (BALF) obtained from non-smokers, asymptomatic smokers, and patients with chronic obstructive pulmonary disease (COPD). Antigenic amounts of GcG in BALF were increased in COPD patients and asymptomatic smokers compared with nonsmokers (6.35 +/- 1.02 and 5.15 +/- 1.07 versus 2.82 +/- 0.37 micrograms/mg albumin, p less than 0.05). In addition, we found that BALF enhanced C5a des Arg-mediated chemotaxis (48.3 +/- 5.6 versus 11.2 +/- 1.6 cells/high power field, p less than 0.05), an effect that was not seen in the presence of GcG antibody. Furthermore, BALF GcG was similar to serum GcG using Western blot analysis, and the interaction of GcG with C5a des Arg was not inhibited by cigarette smoke. These data demonstrate that elevation of BALF GcG levels occurs in smoking-associated lung disease and that this protein is biologically active and capable of increasing C5a des Arg-mediated chemotaxis. This suggests that modulation of GcG levels may be important in smoking-associated lung diseases.

Adult↗
PubMed1990

Inactivation of chemotactic factor inactivator by cigarette smoke. A potential mechanism of modulating neutrophil recruitment to the lung.

Activation of the complement system with generation of the potent neutrophil chemotactic factor C5a has been proposed to play a significant role in the neutrophil accumulation in the lungs of cigarette smokers. Chemotactic factor inactivator (CFI) can inhibit C5a-directed neutrophil chemotaxis by binding to the C5a cochemotaxin GcGlobulin (GcG), a vitamin-D-binding protein, and inhibiting the capacity of GcG to enhance the chemotactic activity of C5a. Because cigarette smoke can inhibit the function of some proteins, a loss of CFI functional activity induced by cigarette smoke would allow an increased capacity of GcG to augment C5a-directed neutrophil chemotaxis. In order to test this hypothesis, cigarette smoke was bubbled through a CFI solution, and the solution was evaluated for its ability to inhibit the chemotactic activity of C5a and GcG. Smoke-treated CFI inhibited only 36% of the C5a-GcG chemotactic activity. In contrast, a CFI solution treated with air inhibited 62% of the chemotactic activity (p less than 0.001). Consistent with these observations, smoke-treated CFI exhibited a decreased capacity to bind to GcG and a decreased capacity to inhibit the binding of C5a des Arg to GcG. CFI contained in the bronchial lavage fluids obtained from patients with chronic obstructive pulmonary disease secondary to cigarette smoking and asymptomatic smokers exhibited a decreased capacity to inhibit C5a-GcG neutrophil chemotaxis and to bind to GcG (p less than 0.05, both comparisons). Furthermore, smoke bubbled through normal bronchial lavage fluid decreased the capacity of CFI to bind to GcG.(ABSTRACT TRUNCATED AT 250 WORDS)

Aminopeptidases↗
PubMed1985

Inducible transcription of the unrearranged kappa constant region locus is a common feature of pre-B cells and does not require DNA or protein synthesis.

Transcription of unrearranged kappa constant region (kappa 0) loci is dramatically induced in pre-B cells transformed by the Abelson murine leukemia virus when the cells are exposed to bacterial lipopolysaccharide (LPS). Transcriptional activity, detected both by accumulation of the 8-kilobase kappa 0 RNA product and by nuclear run-on measurements, is evident within a few hours after exposure to LPS and continues to increase over a 24-hr period. During this time, transcription of rearranged mu heavy-chain loci remains at the basal constitutive level. In accord with previous studies of the B-cell lymphoma 70Z/3, this transcriptional activation is accompanied by the appearance of a DNase I-hypersensitive site in the kappa enhancer region but not by any detectable hypomethylation of the locus. Moreover, the present studies demonstrate that induction of kappa transcription can occur in the absence of DNA or protein synthesis. These results have led us to propose a model in which an external signal such as LPS or a functionally equivalent lymphokine may initiate kappa transcription in pre-B cells by modifying or overriding the activity of an enhancer-specific factor.

Abelson murine leukemia virus↗
PubMed1985

Nonproductive kappa immunoglobulin genes: recombinational abnormalities and other lesions affecting transcription, RNA processing, turnover, and translation.

Six nonproductive kappa immunoglobulin genes (kappa- alleles) were cloned and sequenced. The structural abnormalities discerned from sequence analysis were correlated with functional lesions at the level of transcription, RNA processing, turnover, and translation. Four kappa- alleles, three containing V kappa genes and one not, are transcribed at normal or even greater than normal rates, the defects in these genes being expressed at various posttranscriptional levels. The other two kappa- alleles, both of which lacked V genes, exhibited greatly depressed yet clearly detectable transcriptional activity. These results are consistent with a hierarchical relationship between enhancer and promoter elements in which the enhancer establishes transcriptional competence at the kappa locus and the promoter (or pseudopromoter) determines the relative level of transcriptional activity. One of the structural abnormalities discovered in this study, a large deletion which removes the entire J kappa region, also provides new insight into the mechanism of VJ and VDJ recombination.

Alleles↗
PubMed1984

Lipopolysaccharide-induced transcription of the kappa immunoglobulin locus occurs on both alleles and is independent of methylation status.

The transcriptional activity of the kappa immunoglobulin genes in a B-cell lymphoma line, 7OZ/3 was measured before and after stimulation by lipopolysaccharide (LPS). Analyses of accumulated nuclear RNA components and of nascent transcripts showed that LPS induces transcription of both the productively rearranged (kappa+) and the unrearranged (kappa) allele in these cells. This pattern of transcriptional activation correlates well with the LPS induced appearance of a DNAase I hypersensitive site on both alleles in the vicinity of a putative enhancer element (Parslow and Granner, Nucl. Acids Res. 11, 4775, 1983). However, the transcriptional activation is not accompanied by detectable hypomethylation at Hha I and Hpa II sites which are normally undermethylated when kappa genes are constitutively expressed. These findings have enabled us to evaluate the relative importance of various structural parameters to the transcriptional competence of the kappa locus.

Alleles↗
PubMed1984

Mode of regulation of immunoglobulin mu- and delta-chain expression varies during B-lymphocyte maturation.

The transcription, processing, and accumulation of mu and delta mRNA was studied in several cell lines representing different stages of B-lymphocyte maturation. Our results indicate that the relative content of mu and delta mRNA is the major determinant of the IgM versus IgM + IgD phenotype and that the production of delta mRNA is regulated at distinctly different levels of gene expression in early and later developmental stages. In B cell lymphomas typical of early stages, transcription extends over the entire 25 kb of the mu- delta locus and the relative content of mu and delta mRNA is determined at the level of mRNA processing. In contrast, in cells typical of mature IgM secretors, transcription is terminated abruptly between the mu and delta genes, precluding the production of delta mRNA. We propose a model that accounts for qualitative and quantitative changes in mu-delta expression in the developing B lymphocyte.

Animals↗
PubMed1984

Intraoperative antibiotic irrigation as prophylaxis in abdominal hysterectomy: a preliminary report.

A preliminary report regarding the use of an intraoperative, intraperitoneal antibiotic solution in patients having transabdominal hysterectomy reveals that the postoperative morbidity assessed by the diagnosis of cuff cellulitis or pelvic abscess was 4.7%. This morbidity represents a substantial reduction in the incidence of cuff cellulitis (27.0%) noted in a comparison group of 367 patients having abdominal hysterectomy at our institution during a two-year period. These preliminary data strongly suggest that antibiotic solutions given intraperitoneally at the time of abdominal hysterectomy reduce morbidity due to cuff cellulitis.

Abscess↗
PubMed1984

Ectopic pregnancy subsequent to sterilization: histologic evaluation and clinical implications.

Ten ectopic pregnancies subsequent to tubal sterilization were histologically evaluated. In seven of the ten cases, the sites for the ectopic implantation appeared to be related to the presence of a distal remaining tubal segment that had a tuboperitoneal fistula on the medial side. As against a currently held opinion that the ectopic implantation occurs secondary to a relative disparity in the size of the sperm, the fertilized ovum, and the proximal tuboperitoneal fistula, we believe that the implantations are influenced by probable fluid movements within the remaining tubal segments. The need to consider conservative surgical approaches and good intraoperative notations in patients with an ectopic pregnancy subsequent to sterilization is stressed.

Body Fluids↗