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Biomedical subjects

W Y Chen

Publications and source records attributed to W Y Chen.

At least 19 recordsLinked to original sources

Characterization of biologic properties of wound fluid collected during early stages of wound healing.

The clinical effects of occlusive dressings on wound healing are well documented. However, the underlying biologic mechanisms associated with moist healing are not well understood. Experimental studies and clinical experience have shown enhanced eschar and clot removal, re-epithelialization, and collagen synthesis under occlusion, suggesting the possibility of elevated activities of proteinases and other effectors, e.g., growth factors, in the moist wound environment. To gain an insight into the biology of early wounds under occlusion, we have carried out biologic and biochemical analyses on fluids from occluded full- and partial-thickness wounds. Metalloproteinase activities were detected in the wound fluid samples. When applied to cultured dermal fibroblasts, mitogenic activity was observed with fluids from full-thickness wounds. Wound fluid-stimulated accumulation of urokinase-type plasminogen activator by fibroblasts was also observed in a time-dependent manner. Stimulation of metalloproteinase accumulation by fibroblasts was also observed. We have further demonstrated the presence of platelet-derived growth factor-like and basic fibroblast growth factor-like factors in wound fluid by antibody neutralization of their biologic activities. Proteinase presence and proteinase stimulatory activity of wound fluid retained in the occluded wound may contribute to an enhanced proteolytic environment in these wounds in comparison to non-occluded "dry" wounds. The presence of growth factors and the potential abilities of proteinases to activate latent growth factors and generate chemotactic peptides through connective tissue breakdown may also contribute to the enhanced healing of occluded wounds.

Animals

A growth hormone (GH) analog can antagonize the ability of native GH to promote differentiation of 3T3-F442A preadipocytes and stimulate insulin-like and lipolytic activities in primary rat adipocytes.

The effect of amino acid substitutions introduced to the third alpha-helix in bovine GH (bGH) was investigated. A GH analog (bGH-M8), in which three amino acids were substituted to form an idealized amphiphilic alpha-helix, possessed the same specific binding affinity as wild-type bGH to cell membranes prepared from 3T3-F442A cells or rat adipocytes. However, bGH-M8 failed to stimulate preadipocyte differentiation, as measured by the level of glycerol-3-phosphate dehydrogenase activity. An equimolar concentration of bGH-M8 was inhibitory for this adipogenic effect caused by bGH at a concentration of 30 pM. bGH-M8 also failed to induce an insulin-like response and reduced lipolytic potency in rat primary adipocytes. A 10-fold excess of bGH-M8 abolished the effect of wild-type bGH in the insulin-like and lipolytic assays. Thus, bGH-M8 inhibited these actions of wild-type bGH and, therefore, appears to be a competitive antagonist. These results suggest that a major biologically active domain resides in the third alpha-helix of bGH, which is independent of amino acids important in the initial interaction of GH with its receptor.

3T3 Cells

Effects of age and posture on plasma active renin and plasma inactive renin in normal subjects.

To investigate the effects of age and posture on plasma active and inactive renin, we measured the plasma active renin concentration (ARC) and inactive renin concentration (IRC) in 81 healthy subjects. The subjects were divided into five groups according to age and body position at the time the blood was taken. Group I included 15 five-day-old newborns in a supine position. Group H included 18 adults, aged from 20 to 50 years, who were in a supine position. Group III included 21 adults, over 50 years old, who were in a supine position. Group IV included 20 adults, aged from 20 to 50 years, who were in an upright position. Group V included 19 adults, over 50 years old, who were in an upright position. Twelve subjects were included in Groups II and IV. Plasma active renin was measured by the amount of angiotensin I general when an exogenous renin substrate was added. Plasma inactive renin was activated by trypsin. The results showed that, in a supine position, both ARC and IRC were significantly higher in newborns (Group I) than in the two adult groups (Groups II and III). The mean of the ARC/TPRC (total plasma renin concentration) ratio was lower in adults over 50 years old (Group III) than in those from 20 to 50 years old (Group II), but the difference was not statistically significant.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult

Urinary kallikrein excretion in non-insulin-dependent diabetes mellitus.

To investigate the status of urinary kallikrein excretion (UKE) in patients with non-insulin-dependent diabetes mellitus (NIDDM), we measured UKE in 31 NIDDM patients. They ranged in age from 40 to 70 years (mean, 54.3 +/- 7.8 years), comprising 18 males and 13 females. Their creatinine clearance (Ccr) was 91.6 +/- 5.5 mL/min, and the daily excretion rate of protein was 1.15 +/- 0.72 g/24 hours. Twenty-five normal persons, aged from 37 to 63 years (mean, 51.7 +/- 8.2 years), comprising 14 males and 11 females, were enrolled as controls. The NIDDM patients were further divided into two groups. Group A (n = 21) had regular blood sugar control, while Group B (n = 9) had poor blood sugar control. The autonomic nervous function was tested in 15 patients to study its relationship with UKE. UKE was measured by spectrophotometric assay of the kallikrein enzymatic product on the synthetic substrate S-2266. Autonomic function was evaluated by cardiovascular reflex tests. The results showed that UKE was elevated in Group B, but depressed in Group A (normal vs A vs B: 9.6 +/- 1.0 vs 4.8 +/- 0.9 vs 14.4 +/- 2.7 nkat/24 hours). The UKE/Ccr ratio was similarly elevated in Group B and reduced in Group A (normal vs A vs B: 0.1 +/- 0.01 vs 0.05 +/- 0.01 vs 0.18 +/- 0.04 nkat. mL/day.minute). There was no significant correlation between UKE or the UKE/Ccr ratio and the Valsalva ratio, the 30:15 ratio, or postural blood pressure change. These results suggest that NIDDM patients have abnormal urinary kallikrein excretion levels that are influenced by blood sugar control. The abnormal UKE/Ccr ratio suggests that intrarenal abnormality in the renal kallikrein-kinin system exists in NIDDM patients.

Adult

Inhalant allergens in asthmatic children in Taiwan: comparison evaluation of skin testing, radioallergosorbent test and multiple allergosorbent chemiluminescent assay for specific IgE.

The multiple allergosorbent chemiluminescent assay (MAST-CLA) is a method for measuring total and allergen-specific IgE in human serum by a chemiluminescent immuno-enzymatic system. To compare the results of MAST tests with those of radioallergosorbent (RAST) and skin tests as an adjunct to the diagnosis of inhalant allergens in Taiwan, 195 asthmatic children, aged 5 to 15 years, were studied. All MAST tests had valid positive and negative control threads. The most important allergens in our patients were the two mite species: Dermatophagoid pteronyssinus and Dermatophagoid farinae (87.5% and 82.1%, respectively). There were also large responses (MAST-CLA class > or = 2) to the cockroach mix (28.45%), Alternaria (24.3%), and Eucalyptus (32.6%). The individual efficiency percentage between MAST-CLA and skin tests was D. pteronyssinus 91%, D. farinae 88%, cockroach mix 85%, feather mix 75%, dog dander 64%, Candida 75%, Aspergillus 79%, Alternaria 88%, ragweed mix 62% and Eucalyptus 76%. Comparison of the results of allergen-specific IgE measured by MAST-CLA and RAST were also significantly correlated for all four allergens (D. farinae, Candida, Alternaria and grass mix, r = 0.79-0.92). MAST-CLA was randomly duplicated and proven reproducible in 89% of the tests. Changes between positive and negative results occurred in only 3.6% of the tests. MAST-CLA is a simple in vitro test for specific IgE to 35 allergens, which compares favorably with RAST. It is concluded that MAST-CLA and RAST are similar in their ability to measure allergen-specific IgE, and correlate equally well with skin tests and clinical history in asthmatic children.

Administration, Inhalation

Selenomethionyl analog of recombinant human choriogonadotropin.

Selenomethionyl and high mannose type analog of recombinant human choriogonadotropin (hCG) to solve the crystallization and phase problems has been obtained by gene transfer methodology. SF9 insect cells were infected with the recombinant viruses containing hCG alpha and hCG beta cDNAs in selenomethionine containing methionine-free Grace's medium. The selenomethionyl hCG (SehCG) was purified from the culture medium by one step immunoaffinity chromatography using an immobilized monoclonal antibody against hCG beta. The presence of selenomethionine was demonstrated by amino acid analysis of SehCG. The amino acid composition indicated that more than 84% of methionine residues were substituted by selenomethionine. Its sodium dodecyl sulfate-polyacrylamide gel electrophoresis analysis yielded a single 38-kDa protein band under nonreducing conditions. The carbohydrate analysis of SehCG was consistent with the presence of four N-linked high mannose type carbohydrates and four O-linked simple disaccharide chains. The in vitro immunological and biological studies of SehCG indicated that selenomethionine substitution had no effect on the immunopotency, receptor binding, and steroidogenic activities of the hormone.

Amino Acids

Recombinant carbohydrate variant of human choriogonadotropin beta-subunit (hCG beta) descarboxyl terminus (115-145). Expression and characterization of carboxyl-terminal deletion mutant of hCG beta in the baculovirus system.

A recombinant analog of human choriogonadotropin beta-subunit descarboxyl-terminal peptide (115-145 residues, delhCG beta) was obtained by the expression of corresponding beta cDNA in the baculovirus expression system. The efficiency of expression and secretion was high. The recombinant delhCG beta was purified by immunoaffinity using a specific monoclonal antibody against hCG beta and reverse phase high performance liquid chromatography. The hCG beta analog lacked the carboxyl-terminal 31-residue peptide as well as the four O-linked carbohydrates. Also, the N-linked "complex" type carbohydrates in the deletion mutant were modified to the high mannose type. The apparent molecular weights of delhCG beta in sodium dodecyl sulfate-polyacrylamide gel electrophoresis under reducing and nonreducing conditions were found to be 19,000 and 27,500 respectively. delhCG beta on hydrolysis with endo N-acetylglucosaminidase F or H yielded a 17,500 protein band whereas treatment with N-glycanase gave a protein band with a molecular weight of 16,000. The carbohydrate analysis of delhCG beta, calculated on the basis of 4 residues of N-acetylglucosamine, showed 3 or 4 fucose, 0.6 N-acetylgalactosamine, and 11.4 mannose residues, indicating the high mannose type structures of the two N-linked carbohydrate chains. Despite the carbohydrate modification of the N-linked carbohydrates and the carboxyl-terminal deletion, the delhCG beta had about 87% of the immunological activity of the native hCG beta, indicating no significant conformational alteration induced by the mutation. The delhCG beta combined readily with native hCG alpha, and the reconstituted hCG alpha del beta required 0.031 pmol to achieve 50% inhibition of binding of the tracer with rat lutropin/choriogonadotropin receptor compared with 0.039 pmol by native hCG. Like native hCG, hCG alpha del beta also had most comparable ability to stimulate cAMP accumulation and progesterone production in rat Leydig cells. Thus it is clear from the data that the carboxyl-terminal deletion and thereby the deletion of four O-linked carbohydrates had no effect on its in vitro immunological and biological properties.

Baculoviridae

Carbohydrate variant of the recombinant beta-subunit of human choriogonadotropin expressed in baculovirus expression system.

The beta-subunit of human choriogonadotropin (hCG) has two complex type N-linked and four O-linked carbohydrate chains. To further evaluate the specificity of the carbohydrate moiety on the hCG function, we have expressed hCG beta subunit in the baculovirus insect cell system to modify its carbohydrate structures. The recombinant hCG beta (rhCG beta) was efficiently secreted in the medium and was purified to homogeneity by immunoaffinity chromatography using a highly specific monoclonal antibody against hCG beta. The homogeneity of the recombinant subunit was established by sodium dodecyl sulfate-polyacrylamide gel electrophoresis performed under reducing and nonreducing conditions and reverse phase high performance liquid chromatography. rhCG beta had molecular weights of 22,500 and 33,000 under reducing and nonreducing conditions, respectively. Digestion with N-glycanase cleaved the Mr = 22,500 protein to 18,000, while digestion with Endo H or Endo F yielded an additional protein band of 20,500 on sodium dodecyl sulfate-polyacrylamide gel electrophoresis. The carbohydrate analysis by pulse amperometry yielded the relative number of 2.5, 2.4, 3.7, and 11.3 residues of fucose, N-acetylgalactosamine, galactose, and mannose, respectively, based on a value of 4 residues for N-acetylglucosamine. Lectin binding studies showed rhCG beta to bind with concanavalin A with a high affinity and not with wheat germ agglutinin. In the studies with endoglycosidases together with the carbohydrate analysis and lectin binding properties, rhCG beta appears to have two high mannose-type N-linked and three to four O-linked carbohydrate simple disaccharide chains. The carbohydrate modification of the beta-subunit did not alter its immunopotency and its ability to combine with hCG alpha. The reconstituted hormone made up of rhCG beta and hCG alpha was found to be similar to hCG in biological properties such as receptor binding and in its ability to stimulate cAMP and steroidogenesis.

Animals

Mutations in the third alpha-helix of bovine growth hormone dramatically affect its intracellular distribution in vitro and growth enhancement in transgenic mice.

To investigate the relationship between the secondary structure of the third alpha-helix (amino acids 109-126) of bovine growth hormone (bGH) and the biological activity of the molecule, proline or glycine residues have been used as substitutes for native amino acids at positions 114, 118, 121, and 126, respectively. Mutations at the positions 114, 118, and 121 resulted in a dramatic decrease in bGH secretion by transiently transfected mouse L cells whereas the substitution of glycine for glutamate at position 126 (bGH-E126G) did not affect secretion. Immunofluorescence staining revealed that those nonsecretory bGH mutations possessed a different intracellular location as compared with wild-type bGH or the mutated secretory forms of bGH. Similar results were seen in the distribution of these mutated bGH molecules in transfected rat GH-3 cells. Transgenic mice that express wild-type bGH or bGH-E126G grew to approximately 1.6 times the mass of nontransgenic littermates. Transgenic mice that express two nonsecretory forms of mutated bGHs were found to lack the enhanced mouse growth phenotype in spite of elevated levels of serum bGH. These results suggest that the secondary structure in the third alpha-helix of bGH may be important for efficient intracellular targeting in vitro and in growth promotion in transgenic mice.

Animals

Dupuytren's disease among the Chinese in Taiwan.

A retrospective study was made of 41 cases of Dupuytren's disease observed from 1970 to 1988 at the Veterans General Hospital-Taipei, Taiwan. The patients' ages ranged from 49 to 78 years; 21 patients had only one hand involved; 20 patients showed bilateral involvement. Thirty-three of 35 diseased hands with contracture were treated by regional fasciectomy. A follow-up study was done in 32 hands. The operative results of 30 hands were rated as good (94%); 3 showed extension of the disease and 1 had evidence of recurrence. Treatment was not given to 26 hands without contracture; 14 of these showed no change in the lesions, 3 improved, and 6 were worse when seen on subsequent visits. Seventeen of 33 excised thickened palmar fasciae contained nodules. All histological sections of nodule-free specimens showed dense connective tissues. Based on the fibroblastic activity and the amount of collagen, three easily discernible features of the histological make-up of the nodules were found.

Aged

Effects of salivary bicarbonate content and film velocity on pH changes in an artificial plaque containing Streptococcus oralis, after exposure to sucrose.

Chewing-gum stimulation of salivary flow (at the time of the pH minimum following exposure of plaque to carbohydrate) has been shown to cause a rapid increase in plaque pH. The objective of this study was to determine whether the rise in plaque pH is primarily due to the increased buffering capacity of stimulated saliva, or to the fact that an increased flow rate increases the concentration gradient for acid to diffuse from the plaque into the overlying salivary film, which will be moving at a higher velocity. This was investigated with an in vitro technique in which artificial plaque (0.5 or 1.5 mm deep) containing S. oralis cells was exposed to 10% sucrose for one min. The pH values at the proximal and distal undersurfaces of the plaque were then monitored during the passage of a 0.1-mm-thick film of a sucrose-free artificial saliva over the surface, at a range of film velocities (0.8-8 mm/min) that have been estimated to occur in vivo. When a minimum plaque pH had been achieved, the salivary film velocity was either (a) kept the same, with or without 15 mmol/L HCO3 (the concentration measured in chewing-gum-stimulated saliva), (b) increased to 86.2 mm/min, or (c) increased to 86.2 mm/min with 15 mmol/L HCO3 added to the artificial saliva. The findings suggest that after sucrose ingestion, the rapid rise from minimum plaque pH values, which can occur with gum-chewing stimulation of salivary flow, is due to the combined effects of the increase in salivary film velocity, and of a greater availability of bicarbonate.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult

Functional antagonism between endogenous mouse growth hormone (GH) and a GH analog results in dwarf transgenic mice.

A dwarf transgenic mouse (DTM) line has been established in which mice express relatively high levels of a mutated bovine (b) GH gene. This bGH analog binds to mouse liver membrane preparations with an affinity similar to that of wild-type bGH. The mean growth ratio of these mice is approximately 0.7 relative to that of their nontransgenic littermates. Serum insulin-like growth factor-I (IGF-I) levels of DTM were found to be approximately half those in nontransgenic littermates. Liver GH receptor levels were up-regulated in DTM or wild-type bGH transgenic mice. Pituitary GH levels were negatively correlated with serum IGF-I concentrations. Wild-type bGH transgenic mice contain relatively high serum IGF-I and low pituitary GH levels, whereas DTM possess low serum IGF-I and high pituitary GH levels. The decrease in serum IGF-I resulting from the interaction between the bGH analog, the endogenous mouse GH, and GH receptor(s) apparently leads to a dwarf phenotype. These data suggest that this bGH analog has uncoupled GH ligand-receptor binding from IGF-I production and acts as a functional antagonist to the action of endogenous mGH.

Animals

Glycine 119 of bovine growth hormone is critical for growth-promoting activity.

Bovine GH (bGH) analogs with single amino acid substitutions at positions 117 (bGH-E117L), 119 (bGH-G119R), and 122 (bGH-A122D) were generated. These analogs bind to mouse liver membrane preparations with affinities similar to native bGH. However, transgenic mice which express the analogs demonstrate different phenotypes ranging from dwarfism to gigantism. For example, expression of bGH or bGH-E117L result in large transgenic mice. In contrast, transgenic mice with a growth phenotype similar to nontransgenic animals result from expression of bGH-A122D. Surprisingly, transgenic mice with relatively high serum levels of bGH-G119R possessed a dwarf phenotype. Together these results suggest that Gly 119 and Ala 122 are involved in growth-promoting activity of GH.

Alanine

Effect of sodium depletion on urinary excretion of active and inactive kallikrein in glomerulonephritic patients.

To investigate the response of urinary active and inactive kallikrein excretion to sodium depletion in golmerulonephritic (GN) patients, we measured the excretion of urinary active and inactive kallikreins in 10 primary GN patients before and after a low sodium (17 mEq/day), constant potassium (40 mEq/day) diet. They ranged in age from 24 to 47 years with 7 men and 3 women. The etiology included 4 IgA nephropathy, 4 mesangial proliferative GN, 1 minimal change disease and 1 focal sclerosis. The active urinary kallikrein activity was measured by assay of its enzymatic activity on synthetic chromogenic substrate S-2266. The urinary inactive kallikrein excretion was determined indirectly by substracting active kallikrein activity from total kallikrein activity. The latter was measured after trypsin activation of inactive kallikrein. The results showed a significant increase in total and active urinary kallikrein excretion following a low salt diet. Yet, the inactive urinary kallikrein excretion and the ratio of active/total kallikrein excretion showed no significant change. There was no correlation between active and inactive urinary kallikrein excretion either before or after a low sodium, constant potassium diet. These findings suggest that the renal kallikrein-kinin system of GN patients responds normally to the stimulation of sodium depletion.

Adult

Plasma active renin, inactive renin and kallikrein in patients with disseminated intravascular coagulation.

To investigate the role plasma kallikrein plays in the in vivo activation of inactive renin, we measured plasma active renin, inactive renin, kallikrein and prekallikrein levels in 10 patients with disseminated intravascular coagulation (DIC), with 16 normal persons as controls. The plasma active renin concentration was expressed by the angiotensin I generation rate after the addition of sheep renin substrate. Plasma inactive renin was activated by trypsin. The plasma total kallikrein level was measured by an assay of kallikrein activity on synthetic substrate S-2302 after the addition of a prekallikrein activator. Plasma kallikrein was assayed by its activity on S-2302 without addition of the activator. The prekallikrein level was obtained by subtracting the kallikrein activity from the total kallikrein activity. A significant decrease in the plasma prekallikrein concentration was observed in DIC patients, as compared to that of controls (p less than 0.01). There was no significant difference in plasma levels of kallikrein, inactive renin, and the proportion of active renin between DIC patients and normal controls, but the active renin level was higher in DIC patients. There was no significant correlation between the level of plasma kallikrein and the proportion of active renin in either normal controls or DIC patients. These results are compatible with, but do not prove, the theory that plasma kallikrein plays a role in the in vivo activation of inactive renin.

Adolescent

Urinary kallikrein excretion in chronic renal disease with respect to salt intake and renal reserve.

In order to investigate the status of urinary kallikrein excretion (UKE) in various chronic renal diseases, we measured the UKE in 56 patients with chronic renal diseases. They ranged in age from 19 to 80 with 26 males and 30 females. Among them were 31 patients with primary glomerulonephritis (GN) without nephrotic syndrome, 8 with nephrotic syndrome, 10 with various renal diseases in the azotemic stage, 3 in the uremic stage and 4 with type I renal tubular acidosis (RTA) due to Sjögren syndrome. The primary GN patients who were on a low salt diet were classified as group II GN, while those who partook freely of salt were classified as group I GN. Thirty-six normal volunteers were enrolled as controls. Kallikrein activity was determined by enzymatic hydrolysis of synthetic chromogenic substrate S-2266. Urinary electrolytes were measured by flame photometry. The results showed that UKE was lower in patients with group I GN, azotemic or uremic patients and in patients with RTA, as compared with normal controls. If UKE was corrected by creatinine clearance (CCr), the UKE/CCr ratio was still lower in group I GN patients, but became higher in patients with azotemia and uremia. The UKE/CCr ratio was not different from that of controls or patients with RTA. In nephrotic patients, the UKE and UKE/CCr ratio were both higher than that for normal controls. However, in group II GN patients, neither UKE nor the UKE/CCr ratio differed from that of controls.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult

Comparison between spot urine and overnight urine in the estimation of 24-hour excretion of urine protein, sodium and kallikrein.

To compare the value of spot urine and overnight 9-hour urine in the estimation of 24-hour urinary sodium excretion (UNaV), protein excretion (UpV) and kallikrein excretion (UKaV), we measured the concentration of sodium, protein, kallikrein and creatinine in spot urine, overnight 9-hour urine, and 24-hour urine samples obtained from 21 patients with various renal diseases. They ranged in age from 16 to 75 years with 10 males and 11 females. Urinary protein was measured by the Coomassie Blue dye-binding method. Urinary kallikrein activity was measured by assay of its amidase activity on synthetic substrate S-2266. The results showed that the 9-hour UpV and 9-hour urine P/Cr ratio was better correlated with the 24-hour UpV than the spot urine P/Cr ratio (at 9-11 AM), and the 9-hour UKaV and spot urine Ka/Cr ratio were better correlated with the 24-hour UKaV than the 9-hour Ka/Cr ratio. Only the 9-hour UNaV was correlated with the 24-hour UNaV. We conclude that overnight 9-hour urine, in view of its lower cost, equal effectiveness and convenience, is the best method to substitute for 24-hour urine collection in the evaluation of Na, P and Ka excretion in patients with renal diseases.

Adolescent

Changes in plasma active and inactive renin and prekallikrein during hemodialysis.

To investigate the physiologic role of plasma inactive renin and its relationship to plasma kallikrein, we measured the changes in plasma active renin, inactive renin and prekallikrein levels in 14 uremic patients before and after hemodialysis. Blood was collected before, during and after hemodialysis, and prior to the next dialysis session. Plasma active renin was measured by radioimmunoassay of generated angiotensin I after addition of an exogenous substrate. Plasma inactive renin was activated by trypsin. Plasma prekallikrein was measured by the kallikrein-like activity on synthetic substrate S-2302 after activation of prekallikrein. The results showed that there was no change in blood pressure before, during or after dialysis, whereas the change in body weight after dialysis was significant. There was also no significant difference in the plasma active renin, inactive renin and prekallikrein levels for any of the collection periods. Plasma active renin was significantly correlated with inactive renin. The correlation between the active renin/total renin ratio and the plasma prekallikrein level was also not significant. These results suggest that in uremic patients undergoing chronic hemodialysis, the response of the renin system to acute plasma volume change is blunted. These data only provide evidence that plasma active renin is linked with inactive renin, but provide no evidence to support the idea that plasma inactive renin is a precursor of active renin or that plasma kallikrein is related to activation of inactive renin in vivo.

Adult