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Biomedical subjects

J Kay

Publications and source records attributed to J Kay.

At least 199 records · Page 11Linked to original sources
PubMed1989

CGP 38 560: orally active, low-molecular-weight renin inhibitor with high potency and specificity.

CGP 38 560 is a low-molecular-weight (730) inhibitor of human renin that contains only one natural amino acid. In vitro, it is a potent inhibitor of human renin (Ki with tetradecapeptide, 0.4 X 10(-9) M). It has a high enzyme specificity (Ki values against human pepsin, gastricsin, and cathepsin D are 5 X 10(-6), 3 X 10(-6), and 0.6 X 10(-6) M) and is also species specific (IC50 values against human, marmoset, dog, and rat plasma renins are 7 X 10(-10), 7 X 10(-10), 7 X 10(-9), and 1 X 10(-6) M). In vivo, CGP 38 560 inhibits plasma renin activity (PRA) and lowers blood pressure (BP) after oral administration to conscious, normotensive, furosemide-pretreated marmosets. A dose of 10 mg/kg induces complete inhibition of PRA and a decrease in BP of 23 +/- 3 mm Hg (n = 4) after 30 min. These effects persist for up to 2 h. Blockade of the renin-angiotensin system appears to cause the hypotensive response since it is completely prevented by pretreatment with a converting-enzyme inhibitor. These findings demonstrate that the molecular size of renin inhibitors may be reduced to improve their oral activity without loss of potency or specificity.

Animals↗
PubMed1989

Immunolocalisation of aspartic proteinases in the developing human stomach.

The distribution and time of appearance in the developing human stomach of the 4 aspartic proteinases, pepsinogen, progastricsin, slow-moving protease and cathepsin D, all present in gastric carcinoma, has been determined by the peroxidase-antiperoxidase method on formalin fixed paraffin embedded sections of fetal stomach. Slow-moving protease appears to be the dominant enzyme from 12 weeks gestation onward, although progastricsin is also present at this time. Pepsinogen and cathepsin D do not appear until 17-18 weeks.

Aspartic Acid Endopeptidases↗
PubMed1988

Identification of the aspartic proteinases from human erythrocyte membranes and gastric mucosa (slow-moving proteinase) as catalytically equivalent to cathepsin E.

Three aspartic proteinases with similar Mr values (approx. 80,000) but from distinct sources (human gastric mucosa, human erythrocyte membranes and rat spleen) were shown to have immunological cross-reactivity and comparable mobilities when subjected to polyacrylamide-gel electrophoresis under non-denaturing conditions. Kinetic parameters (kcat, Km and Ki) were determined for the interactions of the three enzymes with two synthetic chromogenic substrates and five inhibitors (naturally occurring and synthetic). On this basis it would appear that all of the enzymes should be considered equivalent to cathepsin E. pH-activity measurements indicated that the aspartic proteinase that originated from the erythrocyte membranes retained activity at a higher pH value than either of its readily soluble counterparts.

Animals↗
PubMed1988

Synovial fluid eosinophilia in Lyme disease.

We describe three 14-year-old boys who developed synovial fluid eosinophilia associated with Lyme disease. One patient, with arthritis that began in 1975, had the first documented case of Lyme disease in New Jersey. Lyme disease should be considered when eosinophilia is noted on analysis of synovial fluid from patients with undiagnosed arthritis.

Adolescent↗
PubMed1988

Forehead pulse oximetry compared with finger pulse oximetry and arterial blood gas measurement.

Usual monitoring sites for pulse oximetry involve the fingers, toes, ear lobe, and nasal septum. This study examined the performance of a forehead sensor compared with a finger sensor for the pulse oximeter and arterial blood gas (ABG) analysis. Ten healthy adult volunteers and 22 ventilator-dependent patients were studied. The arterial oxygen saturation detected by forehead pulse oximetry (SpO2) correlated well with finger SpO2 and arterial oxygen saturation (SaO2) determined by arterial blood gas analysis in the healthy volunteers. Forehead SpO2 in mechanically ventilated patients correlated well with finger SpO2 and SaO2 when heart rate detected by pulse oximeter differed less than 10% from apical heart rate. Factors that caused a difference in oximeter-detected heart rate and apical heart rate were extensive tissue edema, head movement, and difficulty securing good tape placement. This suggests that when signal strength is weak, causing poor pulse rate detection, there will also be problems associated with accurate SpO2. The forehead pulse oximeter sensor works well on healthy, well-oxygenated volunteers. Difficulty was experienced when applying and using the sensor on critically ill patients. The reliability of the forehead pulse oximeter sensor has not been established at low saturations.

Adolescent↗
PubMed1988

Respiratory distress after a Nadbath block.

Dysphagia and respiratory distress developed in three patients after administration of a Nadbath block. This complication may have resulted from inadvertent paralysis of the vagus, ipsilateral glossopharyngeal, and spinal accessory nerves causing pooling of oropharyngeal secretions and laryngospasm. Respiratory distress after a Nadbath block may be managed by properly positioning the patient. Short hypodermic needles (less than 12 mm), small volumes of anesthetic solution (less than 3 ml), and omission of hyaluronidase may reduce the incidence of this complication.

Aged↗
PubMed1988

Patterns of psychoactive drug prescriptions by house officers for nonpatients.

Substance abuse may be an occupational hazard for physicians, yet the mechanisms of this hazard remain obscure. The present authors tested the hypothesis that a potential source of psychoactive drugs for the physician trainees and other health professionals is prescription writing by house officers. Furthermore, the hypothesis was advanced that house officers may write significant numbers of psychoactive prescriptions for their family members and friends. Of 565 house officers at a medical center, 339 responded to a questionnaire designed to determine the number of prescriptions each had written for nonpatients in the previous eight months for several categories of psychoactive drugs. The largest number of such prescriptions was written for family members and friends, and the second largest number was for fellow house officers. Narcotics were the most frequently prescribed psychoactive drugs. When compared with their representation in the sample, first-year residents and residents in surgery and surgical subspecialties wrote significantly more psychoactive drug prescriptions than other residents. Implications of these findings for residents are discussed.

Academic Medical Centers↗
PubMed1988

Changes in proteinase/proteinase inhibitor levels in rat skeletal muscle tissue during diabetes and fasting.

The skeletal muscle content of three rat proteinase inhibitors, a 1-proteinase inhibitor, contrapsin and a 1-cysteine proteinase inhibitor was measured by immunochemical techniques following streptozotocin-induced diabetes. When compared with normal rats, a 1-cysteine proteinase inhibitor and a 1-proteinase inhibitor levels remained essentially unchanged, whereas the content of rat contrapsin was reduced by nearly 80% after the onset of diabetes. Similarly, fasting of rats for three days resulted in a lowering of the levels of contrapsin in skeletal muscles. Under these conditions, levels of chymotrypsin-like activity (chymase) were increased by 150%, whereas the content of the trypsin-like, neutral proteinase was unchanged. Kinetic studies in vitro with Tosyl-Gly-Pro-Arg-4-nitroanilide as substrate showed no inhibition of the trypsin-like proteinase by a 1-proteinase inhibitor, while contrapsin inhibited the enzyme with a Ki value of 40nM. The changing pattern of these proteinases and their potential inhibitors (chymase/a 1-proteinase inhibitor and trypsin-like proteinase/contrapsin) may be a factor contributing to muscle wasting as observed in diabetes and fasting.

Animals↗
PubMed1988

Purification and properties of cathepsin D from rat Yoshida ascites hepatoma AH-130.

Cathepsin D was affinity-purified on pepstatin-Sepharose from control rat liver, from Yoshida ascites hepatoma (AH-130) cells, and from the liver of AH-130 tumour-bearing rats. Apparent molecular mass and immunological reactivity, as determined by SDS-PAGE and immunoblotting, were identical for the three enzyme preparations. The active enzyme concentrations were determined by active-site titration. Catalytic parameters were measured for the three enzymes using two synthetic chromogenic peptides as substrates, and inhibition constants were determined for the proteinases with a number of naturally-occurring as well as synthetic inhibitors. All three enzymes were clearly distinguished from cathepsin E, since none of them was affected by the protein inhibitor from Ascaris lumbricoides. The cathepsin D isolated from AH-130 cells was indistinguishable in its kinetic properties from rat liver cathepsin D, except in its susceptibility to inhibition by isovaleryl-pepstatin. On isoelectrofocusing, the isoenzyme pattern of the tumour enzyme was shifted somewhat towards more basic pI values by comparison with rat liver cathepsin D. These findings are considered with respect to the possibility of an alteration in the S4 subsite of the enzyme active site cleft.

Animals↗
PubMed1987

The pH dependence of the hydrolysis of chromogenic substrates of the type, Lys-Pro-Xaa-Yaa-Phe-(NO2)Phe-Arg-Leu, by selected aspartic proteinases: evidence for specific interactions in subsites S3 and S2.

Variation in the kinetic parameters, kcat and Km, with pH has been used to obtain evidence for significant acid-dissociation processes in the hydrolysis of octapeptide substrates by three aspartic proteinases. These substrates are all cleaved at the peptide bond between a Phe (P1) and a p-nitroPhe (P1') residue resulting in a shift in absorbance at 300 nm that facilitates kinetic measurements. The substrates differ in the amino-acid residues present in the P3 and the P2 positions. Porcine pepsin, calf chymosin, and the aspartic proteinase from Endothia parasitica all show pH dependencies that imply that favorable or unfavorable interactions can occur with the S3 or S2 areas of the enzyme-active site. Examination of the crystallographically determined structure of the E. parasitica proteinase and consideration of the amino-acid sequence differences between the three enzymes suggests that the origin of the pH effects arises from favorable interactions between Glu-13 (COO-) of pig pepsin and Thr (OH) or His (ImH+) in P3 of a substrate. Similarly, Lys-220 (NH3+) of chymosin and a Glu (COO-) in P2 of a substrate may produce a favorable interaction and Asp-77 (COO-) of E. parasitica proteinase and a Glu (COO-) in P2 of a substrate may produce an unfavorable interaction. These results lead to possible explanations for subtle specificity differences within a family of homologous enzymes, and suggest loci for study by site-directed mutagenesis.

Amino Acid Sequence↗
PubMed1987

Metallothionein gene expression and cadmium toxicity in freshwater fish.

Certain species of fish e.g. rainbow trout, are particularly susceptible to poisoning by cadmium in their aquatic environment whereas others e.g. roach and stone loach, are much more resistant. It is postulated that the vulnerability of the salmonids arises because 1) existing metallothionein (MT) in the tissues of these fish is unable to bind cadmium and 2) the toxic metal (in contrast to zinc) cannot switch on the gene(s) for apo-thionein production de novo. Consequently, cadmium is sequestered in the liver, kidney and gills of these fish by two low mol.wt. non-metallothionein proteins for which no excretion mechanism appears to exist.

Animals↗