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Biomedical subjects

J Knight

Publications and source records attributed to J Knight.

At least 199 records · Page 11Linked to original sources
PubMed1978

Radioimmunoassay and radioenzymatic assay of a new aminoglycoside antibiotic, netilmicin.

A radioimmunoassay and a radioenzymatic assay for netilmicin, a new aminoglycoside, were developed in our laboratories to assist in the study of the pharmacology of the drug and to establish values for use in its monitoring. The assays are sensitive, precise, and rapid, giving results that correlate (r = 0.90) with each other and with those of a microbiological assay in which Klebsiella pneumoniae is used as the test organism. Preliminary pharmacological studies show the drug to have a biological half-life of 135 min. which is comparable to that for other aminoglycosides.

Biological Assay↗
PubMed1976

Effects of leached mirex on experimental communities of estuarine animals.

Experimental communities of various estuarine animals in outdoor tanks were exposed to a continuous flow of water containing mirex for 10 weeks. The mirex was leached from fire ant bait (0.3% active ingredient) by fresh water which was then mixed with salt water to yield exposure concentrations averaging 0.038 mug/L. The experiment simulated runoff from treated land into estuarine areas. Mortality of grass shrimp (Palaemonetes vulgaris), pin, shrimp (Penaeus duorarum), common mud crabs (Panopeus herbstii), and striped hermit crabs (Clibanarius vittatus) was significantly high in tanks containing the toxicant. Mortality of ribbed mussels (Modiolus demissus) and American oysters (Crassostrea virginica) was significantly lower in treated tanks, probably because numbers of both species of crabs, which ate the bivalves, were reduced. Sheepshead minnows (Cyprinodon variegatus) were least affected by mirex. Almost all deaths occurred after 10 or more days of exposure. All exposed animals accumulated mirex, with maximum concentrations ranging from 5,500X (pink shrimp) to 73,700X (soft tissues of oysters) above the concentration in the water. Sand substratum contained mirex up to 1,500X that in the water. The study demonstrated that mirex can be leached from bait by fresh water and concentrated by and affect survival of members in an experimental estuarine community.

Animals↗
PubMedDate not supplied

Acetaldehyde inhibits serum aminopeptidases.

Aminopeptidase A (APA)- and aminopeptidase M (APM)-like activity were assayed in Moni-Trol ES with L-alpha-aspartyl-beta-naphthylamide and L-alanyl-beta-naphthylamide, respectively. Upon preincubation of the serum with 89.4, 223.5, and 447 mM acetaldehyde at room temperature for 30 min, a reduction in 26.8%, 55.3%, and 75.8% aminopeptidase A activity was observed. Similarly, aminopeptidase M activity was reduced by 26.5% and 53.1% upon preincubation with 223.5 and 447 mM acetaldehyde. Ethanol at 84.9, 212.3, and 427.9 mM did not significantly affect the enzymic activity. Because aminopeptidase A and aminopeptidase M also degrade the pressor substance, angiotensin II, it is suggested that inhibition of aminopeptidase A- and aminopeptidase M-like activity by acetaldehyde, the product of ethanol metabolism, may lead to higher levels of circulating angiotensin II and, consequently, hypertension, in alcoholics. The hydrolysis of lysine-p-nitroanilide, an aminopeptidase B substrate, was also inhibited upon addition of acetaldehyde to Moni-Trol ES serum.

Acetaldehyde↗
PubMedDate not supplied

Preclinical antitumor activity of XK469 (NSC 656889).

XK469 (NSC 656889) is a water-soluble member of the novel quinoxaline family of antitumor agents. In vitro, XK469 demonstrated selective cytotoxicity for several murine solid tumors including colorectal and mammary adenocarcinoma cell lines, when compared to both leukemia and normal epithelial cells. In vivo, XK469 was active against 7/7 murine tumors tested, including pancreatic ductal carcinomas #02 and #03, colon adenocarcinomas #38 and #51/A, mammary adenocarcinoma #16/C and the Adriamycin resistant mammary adenocarcinomas #16/C/ADR and #17/ADR. XK469 was efficacious both intravenously and orally. Regardless of dosing schedule, conventional mice tolerated higher total doses than SCID or nu/nu mice did. Despite these reduced doses, XK469 was active against xenografts of 4/6 human tumor lines including mammary adenocarcinoma MX-1, the small cell lung cancer DMS 273, the prostate model LNCaP and the CNS tumor SF295. The lower doses in the xenograft studies were below curative levels. The dose-limiting toxicity appeared to be myelosuppression with rapid host recovery (5-8 days), and in vitro assays of XK469 toxicity to murine bone marrow neutrophil progenitors CFU-GM (colony forming unit-granulocyte/macrophage) demonstrated concentration-dependent toxicity from 0.5-30 microg/mL. The difference in drug tolerance between BDF1 and SCID mice was detected in vitro as a 3-fold difference in the IC90 for CFU-GM, despite similar IC50 values. Comparative in vitro hematotoxicology studies revealed that human bone marrow CFU-GM tolerated XK469 as well as their SCID counterparts (IC90 values 5.7 vs. 7.4 microg/mL). Based on comparison with previously tested anti-cancer agents, these data suggest that humans will be able to tolerate XK469 doses that are efficacious against human tumor xenografts.

Animals↗