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Biomedical subjects

P Lad

Publications and source records attributed to P Lad.

7 recordsLinked to original sources
PubMed1998

Urinary IL-6 is elevated in patients with urolithiasis.

PURPOSE: To evaluate the possible role of cytokines interleukin (IL)-1beta, IL-1alpha and IL-6 in patients with urolithiasis. MATERIALS AND METHODS: Fifty-six patients currently with stone disease, 63 patients with bacterial cystitis, and 66 normal individuals were evaluated for urinary IL-1alpha, IL-1beta and IL-6. Clean catch urine samples were obtained and evaluated for cytokine levels using enzyme immunoassays for the respective cytokines. Statistical analysis of the results was carried out using the Kruskal-Wallis test followed by Newman-Keuls test and the chi-squared test. RESULTS: The patients with stone disease had significant elevations in IL-6 (p value< 10(-7)) relative to normal subjects. The levels of IL-6 in stone patients were lower than those of patients with bacterial cystitis. Neither IL-1beta nor IL-1alpha was elevated in stone patients relative to normals. By contrast, bacterial cystitis patients showed significant elevations in all three cytokines relative to normal subjects. Chi-squared analysis confirmed that stone patients had elevated IL-6 without elevation in either IL-1alpha or IL-1beta relative to normal subjects. CONCLUSIONS: Stone patients show significant elevations in IL-6 without marked increases in either IL-1beta or alpha relative to normal subjects. This elevation in IL-6 is not from infection as is seen in bacterial cystitis subjects. The elevation in IL-6 may be useful in the understanding of the pathogenesis of urolithiasis or as a potential marker for stone disease and we are currently investigating these possibilities.

Cystitis↗
PubMed1994

Identification of two aspartates and a glutamate essential for the activity of endo-beta-N-acetylglucosaminidase H from Streptomyces plicatus.

In order to identify groups essential for the activity of endo-beta-N-acetylglucosaminidase H (Endo H), all 8 glutamate residues, all 19 aspartates, and both tryptophans were individually substituted with glutamines, asparagines, and phenylalanines, respectively, by oligonucleotide site-directed mutagenesis. Only variants D170N, D172N, and E174Q were found to have specific activities significantly less than wild-type Endo H. Another variant, D173N, did not produce detectable amounts of protein. Wild-type enzyme was found to have a bell-shaped pH activity profile, which was retained in the essential aspartate mutants, but E174Q lost the basic pH limb of the curve, indicating that E174 is good candidate for the proton donating group necessary for catalysis. The general base needed for activity could not be unambiguously identified; although, of the essential aspartates, D172 is the only one conserved in other related glucosidases.

Amino Acid Sequence↗
PubMed1989

Superoxide generation and its modulation by adenosine in the neutrophils of subjects with asthma.

Airway inflammation with neutrophil infiltration may play a role in airway hyperreactivity. Neutrophils may exert their effects through the generation of superoxide O2- anion and other oxygen-derived free radicals. O2- generation by neutrophils has been demonstrated to be modulated by adenosine at physiologic concentrations. Therefore, we have investigated the function of peripheral blood neutrophils with respect to O2- anion generation and its regulation by adenosine in both subjects with asthma and normal subjects and also the relationship between O2- anion generation and airway hyperresponsiveness in subjects with asthma. Purified neutrophils were obtained from eight subjects with stable asthma and seven normal control subjects not taking chronic medications. O2- anion generation in subjects with asthma was significantly higher compared with that of normal subjects after stimulation with either N-formyl-methionyl-leucyl-phenylalanine (mean, 14.8 nmol/10(6) cells for subjects with asthma versus mean, 9.6 nmol/10(6) cells for normal subjects; p less than 0.01) or phorbol myristate acetate (mean, 13.6 nmol/10(6) cells versus mean, 8.1 nmol/10(6) cells; p less than 0.05). Adenosine inhibited N-formyl-methionyl-leucyl-phenylalanine-stimulated O2- anion generation in a dose-related fashion in subjects with asthma and normal subjects to a similar degree. Adenosine had no effect on O2- anion generation after phorbol myristate acetate stimulation. These results indicate that neutrophils from subjects with asthma produce more O2- anion when they are stimulated than do neutrophils from normal subjects and that this difference is not due to adenosine modulation. In subjects with asthma, O2- anion generation correlated with the degree of airway hyperresponsiveness to inhaled methacholine.

Adenosine↗
PubMed1983

Ethanol activation of human natural cytotoxicity.

Human lymphocytes cultured with ethanol and subsequently assayed for natural killer (NK) activity to K562 cells have enhanced NK activity compared to lymphocytes cultured without exposure to ethanol. Optimal enhancement occurred at 0.64% (v/v) ethanol, and required several hours of culture. Lymphocytes retained their enhanced cytolytic ability for several hours after removal from the ethanol-containing medium. The enhancement correlated with a faster rate of cytolysis by ethanol-treated lymphocytes, rather than recruitment of an increased number of killer cells, as measured with single cell assays. Inclusion of ethanol directly in the NK assays was inhibitory. Cells that had been cultured with ethanol were less sensitive to inhibition of NK activity by the proteinase substrate acetyl tyrosine ethyl ester than were control cells cultured without ethanol. Although this observation and the increased rate of cytolysis in the single cell assays are consistent with increased production of a chymotrypsin-like proteinase involved in cell-mediated cytotoxicity, no alteration in protein synthesis was detected concomitant with ethanol treatment. This report demonstrates that even without hepatic metabolism, ethanol can produce effects on lymphocyte function which remain after exposure to the reagent is discontinued.

Alcohol Oxidoreductases↗
PubMed1982

Blood alcohol levels in rats: non-uniform yields from intraperitoneal doses based on body weight.

1 Sprague-Dawley rats (n = 72) weighing from 125 to 450 g were injected intraperitoneally (i.p.) with 16% (w/v) ethanol to provide 1, 2 or 3 g/kg doses. 2 Resulting blood alcohol levels (BALs) demonstrated a general inadequacy of dose/body weight (g/kg) formulations of ethanol to provide uniform BALs in animals of different weights. 3 BAL differences between heavier and lighter rats were not well accounted for by developmental changes in liver weight or alcohol dehydrogenase activity. 4 From the data, a table was derived of more appropriate ethanol injection volumes to produce 0-300 mg% BALs (20 mg% increments) in rats from 100-500 g (10 g increments).

Animals↗