Search PubMed⌕ Search

Biomedical subjects

J Burton

Publications and source records attributed to J Burton.

At least 91 records · Page 5Linked to original sources
PubMed1988

Substrate analogue inhibitors of the IgA1 proteinases from Neisseria gonorrhoeae.

Substrate analogues based on the amino acid sequence of the hinge region of human IgA1 around the cleavage site of the IgA1 proteinases secreted by Neisseria gonorrhoeae are competitive inhibitors of these enzymes. The octapeptide Thr-Pro-Pro-Thr-Pro-Ser-Pro-Ser, which occurs between residues 233 and 240, has an IC50 value of 0.26 mM for the type 1 proteinase and 0.50 mM for the type 2 enzyme. Acetylation of the octapeptide N-terminal amino group lowers affinity for the type 1 proteinase sixfold but does not change binding to the type 2 enzyme. Amidation of the C-terminal carboxyl group does not change binding to the type 1 proteinase but improves IC50 for the type 2 enzyme. Simultaneous blockade of both the N- and C-termini drastically lowers affinity of the octapeptide for both proteinases. Sequential replacement of the hydroxy amino acids in the blocked octapeptide with cysteine yields a series of inhibitors that generally bind to the neisserial IgA1 proteinases as well as or better than the unblocked octapeptide. The most effective inhibitor contains a cysteine residue at position 6 (P3') and has an IC50 value for the type 2 IgA1 proteinase of 50 microM. Dimerization of the cysteine-containing octapeptides significantly diminishes inhibitory properties. The substrate analogues described here are the first synthetic inhibitors of the neisserial IgA1 proteinases to be reported.

Amino Acid Sequence↗
PubMed1988

The malignant B cells from B-chronic lymphocytic leukemia patients release TAC-soluble interleukin-2 receptors.

Both membrane (p55) and soluble (p45) forms of TAC-reactive interleukin-2 receptor (IL-2R) are expressed and/or released by activated lymphocytes or monocytes. Previous work has detected increased levels of circulating, TAC-soluble IL-2R (soluble TAC antigen) in the serum of most B-cell chronic lymphocytic leukemia (B-CLL) patients. We detected soluble TAC antigen in B-CLL patients (mean of 3,332 U/mL v 410 for controls). Serum soluble TAC antigen levels increased with stage (mean value of 1,187 U/mL for stage 0 v 2,527 for stage 2 and 5,410 for stages 3 and 4). We next attempted to determine whether the elevated serum levels of soluble TAC antigen in B-CLL patients might result from shedding or secretion of the receptor from the circulating, malignant B cells. Purified, malignant B cells from B-CLL patients were capable of producing easily detectable soluble TAC antigen after 48 hours of in vitro culture (range of 60 to 1,563 U/mL). IL-2R production by CLL B cells was dose dependent in most patients over a concentration of 10 x 10(6) to 60 x 10(6)/mL. In contrast, there was little or no detectable soluble TAC antigen when highly purified T cells from the same patients were cultured. Finally, despite elaboration of soluble IL-2R by CLL B cells, membrane expression of B-cell IL-2R was detected in only six of 11 patients. Thus, the cellular source of the elevated serum IL-2R levels is the malignant CLL B cell. Taken together these data suggest that (a) the malignant CLL B cell is "activated" in terms of release of soluble IL-2R and may serve as a tumor marker in this disease and (b) the elevated levels of circulating IL-2R may be an associated factor in the cellular immunodeficiency noted in B-CLL patients.

B-Lymphocytes↗
PubMed1987

In vivo assay of specific kallikrein inhibitors.

Kininogen sequence analogs containing amino acid residues around the Arg-Ser cleavage site of bovine kininogens were prepared with bulky aliphatic residues in the P3 position as specific inhibitors of tissue kallikrein. KKI-7 (containing a cyclohexylacetyl group) and KKI-8 (containing an adamantaneacetyl group) both inhibited human urinary kallikrein with KI = 4 microM. These inhibitors are 40 times more potent than the corresponding peptide containing the naturally occurring prolyl residue at P3 and one-seventh as susceptible to hydrolysis. KKI-7 and KKI-8 are poor inhibitors of human plasma kallikrein (KI = 244 and 358 microM, respectively) while their capacity to inhibit trypsin is 1/3 and 1/17, respectively, that of their inhibitory capacity for human urinary kallikrein. When KKI-7 was tested in a rat blood flow model, the infused peptide (50 micrograms/kg/min) depressed the response to injected rat submandibular kallikrein (200-500 ng) to 52% of the control response when it was injected less than 10 minutes after infusion was started and to 16% of the control response when it was injected between 10 and 30 minutes after infusion of the inhibitor, the response gradually returned toward normal. Similar results were obtained with porcine pancreatic kallikrein. Infusion of the inhibitor did not affect the response to bradykinin and infusion of the vehicle itself did not alter the response to either injected kallikrein or bradykinin. These analogs have greater specificity and stability than those previously developed and are appropriate for the in vivo inhibition of glandular kallikreins.

Animals↗
PubMed1987

Hypotensive effects of the renin inhibitor (RI-78) and the converting enzyme inhibitor (teprotide) in conscious monkeys.

Effects of the pentapeptide renin inhibitor (RI-78; Phe(4Cl)-Phe-Val-Tyr-Lys-NH2) and the angiotensin converting enzyme (ACE) inhibitor (teprotide) on mean arterial pressure (MAP) were examined in conscious monkeys (M. fascicularis). In salt depleted normotensive monkeys with a MAP of 95 +/- 4 mmHg and plasma renin activity (PRA) of 15.9 +/- 2.7 ngAI/ml/h, a bolus injection of a dose of 375 micrograms/kg of RI-78 caused a prompt hypotensive effect. Maximal hypotensive action was seen within 1 min, and MAP returned to the basal level within 15 min. With this dose, MAP was reduced by 20 +/- 6 mmHg. Teprotide (1 mg/kg) decreased MAP and reached a nadir after 13 min. There was no significant difference between maximal hypotensive responses seen with RI-78 (375 micrograms/kg) and with teprotide (1 mg/kg). Hypotensive effects of RI-78 and teprotide were also examined in acute renal hypertensive monkeys with a MAP of 125 +/- 5 mmHg and a PRA of 27.1 +/- 5.7 ngAI/ml/h. Again, similar hypotensive effects were observed. We conclude that antihypertensive effect of RI-78 is comparable to that seen with teprotide.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1986

The transport of an intact oligopeptide across adult mammalian jejunum.

The passage of an intact nonapeptide across adult rabbit jejunum mounted in an Ussing Chamber is demonstrated with an HPLC system which resolves the renin inhibitor Pro-His-Pro-Phe-His-Leu-Phe-Val-[3H]Phe from all labelled proteolytic cleavage products. Permeability of the peptide (0.016 cm hr-1) is approximately one-seventh that observed for the actively transported 3-0-methyl glucose (0.104 cm hr-1). Flux of the peptide is not changed by the absence of sodium. This study shows that adult mammalian intestine can transport intact oligopeptides and suggests that it will be feasible to develop orally active peptide drugs.

Animals↗
PubMed1984

Antisera to human renin normalize renin-dependent hypertension in the monkey: therapeutic implications.

Polyclonal antisera raised against pure human renin normalize renin-dependent blood pressure elevation in the monkey (M. fascicularis). In vitro, comparable inhibition of either human or monkey plasma renin by the antisera was demonstrated. In vivo, intravenous infusion of 2 ml of antisera did not change mean arterial pressure of salt-repleted monkeys, however, its administration to salt-depleted monkeys with elevated plasma renin activity lowered mean arterial pressure 10 Torr. A 25 Torr rise in mean arterial pressure and increase in plasma renin activity occurred promptly after inflation of a suprarenal aortic cuff in conscious uninephrectomized monkeys. Administration of 2 ml of antisera to these monkeys normalized mean pressure, which was reduced by an additional 10 Torr if the animals were previously salt-depleted. Maximal hypotension occurred within 1 hour and was sustained for approximately 10 hours. Because of the differing specificities of polyclonal antisera, sera raised in two laboratories against human renin purified from different sources were employed. Identical results were obtained. This is the first demonstration of the use of antisera to inhibit endogenous renin activity in primates and predicts the in vivo efficacy of renin antisera as experimental, diagnostic and therapeutic agents.

Animals↗
PubMed1984

Pantyhose prosthesis: a cosmetic alternative.

A cosmetic prosthesis for the nonambulatory patient with unilateral or bilateral above-knee amputation is described. This device can be made with minimal cost and difficulty, and it offers advantages of durability, flexibility, and excellent appearance. Cosmetic prostheses for patients with below-knee or hip disarticulation amputations can be made in a similar manner.

Artificial Limbs↗