Search PubMed⌕ Search

Biomedical subjects

D Proud

Publications and source records attributed to D Proud.

At least 181 records · Page 10Linked to original sources
PubMed1985

Nasal challenge with ragweed pollen in hay fever patients. Effect of immunotherapy.

Challenge of the nasal mucosa of allergic subjects with specific allergen induces not only the expected sneezing and rhinorrhea, but also the appearance in nasal secretions of mediators commonly associated with activation of mast cells or basophils: histamine, leukotrienes, prostaglandin D2 (PGD2), kinins, and TAME ([3H]-N-alpha-tosyl-L-arginine methyl ester)-esterase. To determine whether specific immunotherapy alters mediator release in vivo, nasal pollen challenge was used to compare 27 untreated highly sensitive ragweed (RW)-allergic subjects with 12 similarly sensitive patients receiving long-term immunotherapy (3-5 yr) with RW extract (median dose, 6 micrograms RW antigen E). The two groups were equally sensitive based on skin tests and basophil histamine release. The immunized group had a diminished response as demonstrated by (a) the treated group required higher pollen doses to excite sneezing or mediator release; (b) significantly fewer subjects in the treated group released mediators at any dose (TAME-esterase [P = 0.005], PGD2 [P = 0.04]), and (c) the treated group released 3-5-fold less mediator (TAME-esterase [P = 0.01], and histamine [P = 0.02]).

Adult↗
PubMed1984

Human plasma prekallikrein and high molecular weight kininogen decrease during parturition.

Prekallikrein and high molecular weight kininogen were measured in plasma taken from nine women during parturition. Prekallikrein decreased significantly (p less than 0.01) from 1.49 +/- 0.15 S-2302 U/ml (mean +/- SEM) in early labor to 1.26 +/- 0.13 S-2302 U/ml in the immediate postpartum period. Immunoreactive high molecular weight kininogen also significantly decreased from 76 +/- 5 micrograms/ml to 68 +/- 5 micrograms/ml one day postpartum (p less than 0.01). Both proteins rose to normal levels within two days. The data suggest that the kallikrein-kinin system is utilized during parturition.

Adult↗
PubMed1984

Kallikrein-kinin and renin-angiotensin systems in rat renal lymph.

Rat renal lymph contains 254 +/- 17 ng/ml (means +/- SEM, N = 20) of immunoreactive glandular kallikrein. Like the immunoreactive glandular kallikrein in plasma, it is biologically inactive. Gel filtration of renal lymph reveals profiles for immunoreactive glandular kallikrein, protein, and inhibition of trypsin and kallikrein which resemble those seen for plasma except that high molecular weight plasma components are reduced or missing in renal lymph. In contrast, gel filtration of thoracic lymph reveals immunoreactive glandular kallikrein and protein profiles which are indistinguishable from those seen with plasma. Renin levels are 170-fold higher in renal lymph than in thoracic lymph while angiotensin-converting enzyme levels are only 16% those of thoracic lymph. In keeping with the high renin and low converting enzyme activities, renal lymph contains high levels of angiotensin I. Immunoreactive glandular kallikrein levels in renal lymph, thoracic lymph and plasma do not show the striking differences observed for renin.

Angiotensin I↗
PubMed1984

Human lung macrophages enhance and inhibit lymphocyte proliferation.

To evaluate the effector functions of human lung macrophages, cell preparations containing 70 to 95% macrophages were obtained from surgically resected lungs of cancer patients and were co-cultured with allogeneic or autologous peripheral blood mononuclear cells (PBMC) and Con A. In contrast to previous reports of either marked stimulatory or inhibitory effects of human lung macrophages on lymphocyte function, the present results demonstrate that the proliferative response was a complex function of both the numbers of PBMC and macrophages. In the presence of low numbers of PBMC, small numbers of macrophages enhanced proliferation, whereas larger numbers inhibited proliferation; in the presence of larger numbers of PBMC, macrophages only inhibited. Inhibition was not mediated by cyclo-oxygenase products of arachidonic acid metabolism, because indomethacin did not reverse it. The enhancing effect of macrophages was greater when tested with PBMC depleted of monocytes. Lung macrophages were 10-fold more potent in mediating enhancement than corresponding numbers of peripheral blood monocytes. Both the enhancing and the inhibitory activities could be reproduced by lung macrophage lysates or supernatants derived from macrophages cultured in serum-free medium. Macrophages cultured at high density yielded inhibitory supernatants, which on dilution resulted in enhancing activity. The enhancing activity appeared in supernatants maximally after 24 hr, and its appearance was not inhibited by culturing macrophages in the presence by culturing macrophages in the presence of cycloheximide. Sephacryl S-200 chromatography of such supernatants yielded two peaks of enhancing activity, with apparent m.w. of 160,000 and 40,000, which we call lung macrophage-derived lymphocyte-activating factors (LM-LAF). Fractions with LM-LAF activity contained no IL 1 activity (assessed by augmentation of mitogen-induced proliferation of mouse thymocytes), but IL 1 activity was present in a peak of m.w. of 15,000. The 15,000 m.w. fraction did not enhance the proliferation of human PBMC. These results demonstrate that human lung macrophages are potent modulators of lectin-mediated proliferation of human PBMC. The effects are mediated in part by the release of soluble, pre-formed factors that appear to be distinct from previously described monokines.

Cells, Cultured↗
PubMed1983

Distribution of immunoreactive kallikrein along the rat nephron.

We have used a direct radioimmunoassay to localize kallikrein along the corticomedullary axis of the rat kidney and in microdissected rat cortical nephron segments. As previously seen in rat and dog, kallikrein content was highest in the outer cortex and decreased progressively toward the papillary tip. In microdissected cortical nephron segments, the highest kallikrein content was found in the connecting tubule [176 +/- 16 (SE) pg/mm tubule length (n = 12)]. In addition, a significant amount of kallikrein was found in distal convoluted tubules [53 +/- 4 pg/mm (n = 14)], initial collecting tubules [75 +/- 10 pg/mm (n = 14)], and cortical collecting ducts [37 +/- 4 pg/mm (n = 13)]. Little or no kallikrein was found in glomeruli, proximal convoluted tubules, proximal straight tubules, and cortical thick ascending limbs. These results are compatible with a site of action of the kallikrein-kinin system in the cortical segments of the rat distal nephron.

Animals↗
PubMed1983

Kinins are generated in vivo following nasal airway challenge of allergic individuals with allergen.

Using a recently developed model of nasal challenge, we have obtained data that clearly demonstrate, for the first time, kinin generation during a local allergic reaction in vivo. Allergic individuals (n = 8) and matched nonallergic controls (n = 8) were challenged intranasally with the appropriate antigen and nasal washes were taken before and after challenge. Washes were assayed for kinin, histamine, and [3H]-N-alpha-tosyl-L-arginine methyl ester (TAME)-esterase activity. Increased kinin generation was found by radioimmunoassay (RIA) in the nasal washes of all the allergics (5,560 +/- 1,670 pg/ml) but in none of the controls (38 +/- 16 pg/ml). The presence of kinin was highly correlated with that of histamine and TAME-esterase activity and with the onset of clinical symptoms (P less than 0.001). Serial dilutions of nasal washes produced RIA displacement curves that paralleled the standard curve, and recovery of standard kinins that were added to nasal washes was 100 +/- 4% (n = 14). Kinin recovery was identical in both allergics and controls and did not vary significantly with antigen challenge. The immunoreactive kinin in nasal washes was stable to boiling and not precipitated by ethanol, but completely destroyed by carboxypeptidase B. It was evenly distributed between the sol and gel phases of nasal washes. High performance liquid chromatography analysis of the immunoreactive kinin in nasal washes showed it to be a mixture of lysylbradykinin and bradykinin. We conclude that kinins are produced during local allergic reactions in the nose and may contribute to the symptomatology of the allergic response.

Administration, Intranasal↗
PubMed1982

Effects of restriction of sodium or administration of fludrocortisone on parotid salivary kallikrein in man.

Urinary kallikrein is increased by restriction of dietary sodium and by administration of fludrocortisone, a sodium-retaining steroid. In order to determine whether salivary kallikrein responds similarly, we studied 16 normal volunteers after 1-week periods of daily intake of 9, 109, and 259 mEQ of sodium; 10 subjects were studied after addition of 0.6 mg/day fludrocortisone for a week to a regimen of 109 mEq/day sodium. During sodium restriction, parotid saliva had a significantly higher mean concentration of kallikrein ad potassium and a significantly lower concentration of sodium than during periods of intake of 109 or 259 mEq/day sodium. Sodium restriction also caused significantly higher urinary excretion of kallikrein and aldosterone. Salivary amylase remained unchanged during the three sodium periods. Administration of fludrocortisone significantly increased the mean concentration of parotid kallikrein and excretion of urinary kallikrein in comparison with control levels, however the concentrations of parotid sodium and potassium did not change significantly. Four patients studied before and after removal of aldosterone-producing adenomas each showed decreased concentrations of parotid kallikrein and potassium and increased concentrations of parotid sodium after surgery. It is concluded that both salivary and urinary kallikrein increased in response to restriction of sodium and that these increases were mediated by levels of sodium-retaining steroid. Increased output of kallikrein in response to increased levels of sodium-retaining steroid may be a generalized response of organs that contain glandular kallikrein and can conserve sodium.

Adenoma↗
PubMed1981

Characterization and localization of human renal kininogen.

Kininogen was isolated from human urine by batch adsorption with immobilized antibody to the immunologically identical heavy (H) chains of both high molecular weight (HMW) and low molecular weight (LMW) human plasma kininogens. All releasable kinin in the guanidinium chloride eluate was associated with kininogen antigen in gel filtration fractions. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis of the eluate gave major stained and antigenic bands corresponding to the major form of plasma LMW kininogen. Also, the staining patterns and antigenic profiles obtained upon alkaline disc gel electrophoresis of the urinary and plasma LMW kininogens were strikingly similar. When antibody to H chain was used in an indirect immunofluorescence technique, cytoplasmic staining was observed in cells of distal tubules and c cortical and medullary collecting ducts of human kidneys. No fluorescence was observed using antibody to the unique light (L) chain of plasma HMW kininogen and no intact HMW kininogen was found in urine by radioimmunoassay. We conclude that the kidney is a source of urinary kininogen, while the L chain antigen in urine probably represents filtered degradation products of plasma HMW kininogen.

Humans↗
PubMed1980

Radioimmunoassay of human high molecular weight kininogen in normal and deficient plasmas.

An RIA for human HMW kininogen, capable of detecting 150 pg of antigen, has been developed. Antibody to HMW kininogen was purified by immunoaffinity chromatography, and double-antibody precipitation was used to separate free and bound antigen. Of the LMW kininogens only one of the forms tested (B3.2) showed significant cross-reaction (2%). Bradykinin and human plasma kallikrein both showed no cross-reaction, and monkey HMW kininogen showed identity to the human antigen. Intraassay and interassay coefficients of variation were 2% and 1.5%, respectively. Recovery of HMW kininogen added to 6 plasmas was 97.7% +/- 1.8%. Assay of 17 normal plasmas gave a level of 90.8 +/- 2.5 micrograms/ml HMW kininogen (mean +/- S.E.M.). A bioassay of the samples, based on specific release of kinin by purified plasma kallikrein, yielded a level of 90.2 +/- 2.8 micrograms/ml HMW kininogen (r = 0.83, p less than 0.001). In neither assay was any significant sex difference observed. No evidence of any antigenic fragments was seen upon gel filtration of normal plasmas. RIA measurements were also performed on seven plasmas reportedly deficient in HMW kininogen. Williams, Dayton, San Francisco, and Flaujeac plasmas all showed no significant cross-reaction, whereas Fitzgerald, Reid and Detroit plasmas showed 1.0%, 2.5%, and 3.5% of normal antigenic levels, respectively. This sensitive, convenient method should facilitate studies on the role of the kallikrein-kinin system in health and disease.

Animals↗
PubMed1977

The immunological similarity of rat glandular kallikreins.

The immunological properties of the submandibular kallikrein, urinary kallikrein, pancreatic kallikrein and pancreatic prekallikrein of the rat were studied by immunodiffusion, immunoelectrophoresis and radioimmunoassay. Although they behaved differently electrophoretically, all the antigens showed identical immunological behaviour. The implications of this are discussed.

Animals↗