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Biomedical subjects

D L Delacroix

Publications and source records attributed to D L Delacroix.

At least 37 records · Page 2Linked to original sources
PubMed1985

Alpha-2-macroglobulin, monomeric and polymeric immunoglobulin A, and immunoglobulin M in bronchoalveolar lavage.

The concentrations of alpha 2-macroglobulin (alpha 2M), IgM, and the various molecular forms of IgA were measured in unconcentrated bronchoalveolar lavage (BAL) of normal subjects and in that of patients with interstitial lung disease. In BAL of control subjects, as previously observed in other external secretions, orosomucoid-coefficient of excretion relative to albumin (RCE) = 1.1 (albumin RCE = 1)-IgG (RCE = 0.7 in nonsmokers), and alpha 2M (RCE = 0.04) appeared to be secreted mainly by seepage from plasma according to molecular size. The secretion of p-IgA (RCE = 22), IgM (RCE = 0.09), and transferrin (RCE = 1.2) was selective, suggesting either local lung synthesis of these components or their active transepithelial transport. Concentrations of p-IgA, alpha 2M, and IgM in BAL displayed RCE at least 10 times lower than in other external secretions, reflecting the unsignificant local synthesis of these components in alveolar septa. In interstitial lung diseases, including sarcoidosis, hypersensitivity pneumonitis, and other lung fibroses, all protein concentrations in BAL were raised. Increased seepage of plasma proteins across the blood-gas barrier accounted for the elevation of orosomucoid and p-IgA (RCE unchanged). It probably accounted for the appearance in BAL of a characteristic peak of serum type dimeric IgA unbound to secretory component (SC), for the reduced percentage of free SC (5% versus 27% in control subjects), and for part of the increased percentage of m-IgA (52% versus 28% in control subjects). Contribution of local synthesis, presumably by cells infiltrating the alveolar tissue, was indirectly demonstrated for m-IgA and IgG, which were selectively secreted, more than 2-fold greater than albumin.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1985

Ontogenic changes in secretory component expression by villous and crypt cells of rat small intestine.

In order to determine whether the rat small intestine exhibits quantitative changes in the synthesis of the secretory component (SC) during growth, epithelial villus and crypt cells were isolated from jejunal segments at intervals after birth up to adulthood. SC concentration was measured in each cell fraction by immunoradiometric assay and compared to sucrase activity, an enzyme marker of the differentiated villus enterocyte. The following results were observed. (i) Adult rats showed a characteristic decreasing concentration gradient of SC from the crypts (mean concentration in crypt cells: 636 +/- 173 ng/mg protein) to the villus tip (mean concentration in villus cells: 152 +/- 17 ng/mg protein). This gradient was the reverse of that found for sucrase activity. (ii) In young sucklings (10 days old), SC was virtually absent in both villus and crypt cells, but its concentration progressively increased in weanling rats and reached adult levels by day 40 postpartum. (iii) The crypt to villus cell gradient of SC, absent in sucklings up to day 20, developed during the fourth postnatal week. (iv) Treatment of 10-day-old suckling pups with pharmacological doses of either corticosterone or L-thyroxine for 3 consecutive days failed to induce the precocious synthesis of SC by jejunal enterocytes, but produced significant (P less than 0.01) decreases in concentration. Under the same conditions, sucrase activity was markedly enhanced. In conclusion, major changes in the ability of the immature crypt cell to produce the specific receptor for transepithelial transport of polymeric immunoglobulins occur during the fourth week of rat life. The initiation of this ontogenic process is not triggered by the dietary and hormonal changes known to control the maturation of other functions linked to the differenciated villus cell, such as sucrase activity.

Animals↗
PubMed1985

Gall bladder: the predominant source of bile IgA in man?

The sedimentation profiles of IgA and Secretory Component (SC) and the concentrations of IgA, IgG, IgM, SC and albumin were evaluated after an overnight fast in gall bladder bile of six adult subjects without hepatobiliary disease. The sedimentation profiles differed from those previously obtained in hepatic bile in three ways: gall bladder bile contained a greater percentage of free-SC, a greater percentage of polymeric-IgA (p-IgA), and a major peak of 14 to 19 S p-IgA associated to SC. In contrast to hepatic bile in which IgG is the predominant Ig, IgA clearly was the predominant Ig in gall-bladder bile, its concentration averaging 92 micrograms/ml. Relative-to-albumin coefficients of excretion of proteins in gall bladder bile averaged 0.99 for IgG, 8.6 for monomeric IgA, 196 for p-IgA and 31 for IgM, indicating that there was a selective excretion of IgA and IgM into gall bladder bile. As compared to hepatic bile, the enrichment of gall bladder bile with IgA and IgM was respectively 6.5 and 11.5 times greater than with IgG. These results suggest that quite a significant amount of p-IgA could have been added to bile during its storage in the gall bladder which should therefore be regarded as the predominant source of bile IgA in humans.

Bile↗
PubMed1984

Typing of subclasses and light chains of human monoclonal immunoglobulins by particle counting immunoassay (PACIA).

The subclasses of monoclonal IgGs and IgAs were identified by particle-counting immunoassay. The principle of the test is the inhibition of the agglutinating activity of either specific antisera or monoclonal antibodies (for IgA only) on latex particles coated with a monoclonal IgG or IgA of known subclass. The feasibility of assay of polyclonal Ig subclasses was demonstrated. However, the anti-IgG2 antiserum cross-reacted with an allotype (nG4m(b)) of IgG4. The possibility of typing monoclonal Igs for light chains by the same technique was also demonstrated. Results are obtained in 30 min, and the method requires only small amounts of purified immunoglobulins (Igs) and antisera or monoclonal antibodies.

Agglutination Tests↗
PubMed1984

Study of IgA in the cerebrospinal fluid of neurological patients with special reference to size, subclass and local production.

IgA was assayed by particle counting immunoassay in cerebrospinal fluid (CSF) from non-neurological and neurological patients. Reference values had a logarithmic normal distribution with a mean of 1.54 mg/l and an upper limit of 5 mg/l. To estimate the possible intra-blood-brain barrier (BBB) production of IgA we have calculated an IgA index: CSF-IgA/serum-IgA: CSF-albumin/serum-albumin. Values higher than the upper reference limit of 0.41 were found in 12 out of 67 patients with multiple sclerosis (18%), in 5 out of 11 with aseptic meningitis, in 7 out of 8 with herpetic encephalitis, in 1 out of 8 with Guillain-Barré syndrome and in 2 cases of tuberculous meningitis. However, this index does not take into account the relative proportions of monomeric and polymeric IgA in CSF and serum. We therefore ultracentrifuged 17 paired CSF and serum samples and determined the relative proportions of monomeric and dimeric IgA and calculated the indices for monomeric and dimeric IgA. In controls the proportion of dimeric IgA in CSF was below 5% of total IgA whereas this proportion was increased up to 53.9% in the case of intra-BBB production of IgA, which is thus characterized by a very high dimeric IgA index. In all cases IgA1 remained the predominant subclass. These results had to be compared with those observed in cultures of peripheral blood lymphocytes, which secrete about equal proportions of monomeric and polymeric IgA pertaining to the IgA1 subclass.

Herpesviridae Infections↗
PubMed1984

Multiple gene deletions within the human immunoglobulin heavy-chain cluster.

Two subjects, of 11,000 healthy individuals screened, were found to be missing three and four immunoglobulin isotypes, respectively (IgA1, IgG2, and IgG4; IgA1, IgG2, IgG4, and IgE), and have been analyzed at the DNA level by means of Southern blotting and Ig heavy-chain-specific probes. A broad deletion within the heavy-chain constant region (C) gene cluster was found on chromosome 14 of both probands. Two different haplotypes are described: the first has lost the C alpha 1, C psi gamma, C gamma 2, C gamma 4, and C epsilon genes; the second lacks the C psi epsilon, C alpha 1, C psi gamma, C gamma 2, and C gamma 4 genes. These findings confirm the reciprocal order of the Ig heavy-chain genes as derived by molecular cloning. The inclusion of the C psi gamma gene within the deleted regions confirms its location between C alpha 1 and C gamma 2. From the observed frequency of the homozygous genotype, 1%-3% of healthy subjects from our population are expected to be heterozygous for multiple heavy-chain gene deletions. Cross-over between mispaired homologous regions seems to be the favored mechanism of multiple Ig gene deletions and duplications, and, generally, in the evolution of the human Ig heavy-chain gene family.

Alleles↗
PubMed1984

Immunohistochemical localization of secretory component in the liver of guinea pigs and dogs versus rats, rabbits, and mice.

Secretory component (SC) was localized in the liver of guinea pigs, dogs, rabbits, rats, and mice. In rabbits, rats, and mice SC localized predominantly in bile canaliculi and on hepatocyte sinusoidal membranes but was doubtful in cholangiocytes . In dogs and guinea pigs SC-staining was not detected in/on hepatocytes and canaliculi but was strong in/on cholangiocytes , as reported for humans. In guinea pigs IgA biliary output was small (0.23 mg/kg/day), as for dogs and humans, and below IgG output (1.4 mg), in contrast to rats, whose IgA biliary output (38 mg/kg/day) was much larger than IgG output (2mg). Biliary obstruction in guinea pigs induced only minor increases in serum IgA (+ 26% over 24 h), as reported for dogs and humans, in contrast to rats (+ 800% over 24h) and rabbits. Hepatocyte SC expression correlates with IgA hepatobiliary excretion, being low in guinea pigs, dogs, and humans but high in rats, rabbits, and mice.

Animals↗
PubMed1984

Role of dietary iron in maturation of rat small intestine at weaning.

The weanling process is characterized by the transition from a liquid diet poor in iron (rat milk) to a solid diet high in iron (chow pellets). To examine the effects of iron content of the weanling diet on terminal maturation of rat small intestine, suckling pups, nursed by iron-sufficient mothers, were weaned by day 16 onto a solid basal diet that was either deficient [low-iron diet (LID): 0.5 mg iron/100 g solid] or high [high-iron diet (HID) controls: 30 mg iron/100 g solid] in iron. The animals were studied during or at the end of the 4th postnatal wk. By day 17 rats weaned onto the LID exhibited an initial rise in jejunal sucrase activity as did their controls, but the activity plateau of the enzyme was reduced to a level 60% of the controls. On day 28 iron-deprived rats were anemic and showed significant decreases (P less than 0.01 compared with HID rats) in the activity of jejunal sucrase (-57%), neutral lactase (-83%), and maltase (-46%), whereas villus height, crypt depth, mucosal mass parameters, ileal acid beta-galactosidase activity, mucosal protein, and DNA synthesis rates were equivalent in LID and HID groups. The concentration of the secretory component, a glycoprotein synthesized by the intestinal crypt cell, was markedly depressed (P less than 0.01 vs. controls) in the jejunum (-54%) and ileum (-79%) of iron-deprived rats. When D-[1-14C]glucosamine was injected intraperitoneally, incorporation of the label into jejunal and ileal brush-border proteins was two to three times lower for iron-deficient rats than for controls.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1984

Secretion of immunoglobulins and plasma proteins from the jejunal mucosa. Transport rate and origin of polymeric immunoglobulin A.

Parameters of secretion of IgA and several other plasma proteins from the jejunal mucosa were investigated in 11 individuals who had a normal distribution of Ig-containing cells in the lamina propria and in one patient who was totally deficient in jejunal IgA and IgM plasmacytes. Jejunal samples were collected during segmental gut perfusion. The following results were obtained: (a) The secretion of polymeric IgA (p-IgA, mean equals 217 micrograms/40 cm per min) exceeded those of albumin (132 micrograms), IgG (35 micrograms), and monomeric IgA (m-IgA, 15 micrograms, or 6.4% of total IgA). About 35% of IgA was IgA2 in the jejunal secretion, compared with approximately 23% in serum. This closely corresponds to the 35 and 24% of IgA2 plasmocytes in jejunal mucosa and peripheral lymph nodes, respectively. (b) For each protein, a relative coefficient of excretion (RCE) was calculated (jejunum to serum concentration ratio expressed relative to that of albumin). RCEs of 1.41 for orosomucoid, 1.0 for albumin, 0.83 for IgG, and 0.74 for IgE and, in the deficient patient, of 0.64 for m-IgA and 0.016 for IgM were obtained. This was inversely related to the molecular weight of these proteins and indicated their predominantly passive transport into the jejunum. However, in normal individuals, the RCE of transferrin (approximately 1.11 greater than 1, P greater than 0.05), alpha 2-macro globulin (approximately 0.77), m-IgA (approximately 1.98), and p-IgA (approximately 218) exceeded the value expected from simple seepage from plasma, thus pointing to an additional role of either local gut synthesis and/or active transepithelial transport. (c) Approximately 98% of p-IgA, approximately 99% of IgM, and approximately 68% of m-IgA in jejunal secretions were derived from local production in the gut wall, as determined by 125I-p-IgA specific activities and/or by comparison between the RCE values of the deficient patient to the values of controls. Therefore, the jejunal production of p-IgA (approximately 312 mg/d per 40 cm vs. approximately 54 mg/d from bile) contributes the majority of upper intestinal IgA in humans. The active transport of plasma p-IgA across the intestinal mucosa (approximately 0.08 mg/40 cm per kg per d) contributes less than 2% of the total amount of p-IgA (4.5 mg/kg per d) that is cleared daily from plasma.

Adult↗
PubMed1984

Localization and serum concentration of secretory component during massive necrosis of human liver.

The serum concentration of secretory component was monitored in 9 patients with massive liver necrosis. During acute cytolysis, no increase in serum secretory component levels was observed. Later on, patients with fulminant evolution displayed minor elevations. Values as high as those usually found in acute hepatitis were only observed in cases with delayed liver failure. In these patients, levels were elevated before failure, dropped as liver failure developed, and rose again during recovery. This evolution of serum secretory component level cannot be accounted for by a defective liver clearance of circulating secretory component. It rather suggests a release into the blood of secretory component produced in the liver by cells other than damaged hepatocytes, possibly during liver regeneration. In 3 cases, secretory component localization in the liver was demonstrated by immunocytochemistry and was compared with that in normal liver and in obstructive jaundice. In normal liver, it was restricted to portal bile duct cells and lumens. In obstructive jaundice, additional secretory component staining was found in bile canaliculi. After fatal liver necrosis, secretory component was localized to portal ducts and to a variable proportion of the cholangiocytelike cells belonging to the numerous extraportal proliferating ducts. In these structures, 0.1%, 21%, and 4% of the cells were stained 3, 8, and 30 days after maximal cytolysis, respectively. Remaining hepatocytes and bile canaliculi or bile plugs were unstained. Therefore, portal cholangiocytes and extraportal cholangiocytelike cells are probably essential sources of secretory component in human liver. We propose that proliferation of extraportal cholangiocytelike cells, expression of secretory component synthesis by these cells, and their inability to secrete secretory component in a disorganized biliary tree result in the elevated serum concentration of secretory component observed after acute liver necrosis.

Acute Disease↗
PubMed1983

High proportion of polymeric IgA in young infants' sera and independence between IgA-size and IgA-subclass distributions.

The serum IgA in young infants (6-240 days old) comprised a much larger proportion (means = 36%; range, 7.5-72%) of polymeric IgA than in normal adults (means = 13%; range, 4.7-22%), but with a normal subclass distribution. In contrast, in IgA-deficient adult serum, there was a higher proportion (means = 34%; range, 16.3-38%) of IgA2 than in normal adult serum (means = 21%; range, 5-36%), with, however, a normal proportion of polymers. The distribution of IgA subclasses in the separated monomeric and polymeric IgA fractions was similar to that in unfractionated sera. The proportions of IgA polymers and IgA2 in serum are unlinked parameters, suggesting that both do not necessarily represent mucosal contributions to blood IgA.

Adult↗
PubMed1983

Changes in size, subclass, and metabolic properties of serum immunoglobulin A in liver diseases and in other diseases with high serum immunoglobulin A.

We have studied the relative contributions of monomeric (m-) and polymeric IgA (p-IgA) and of IgA1 and IgA2 to total serum IgA in healthy adults and patients with liver disease (LD) or with other diseases and high serum IgA. Serum concentration of total secretory component (SC) was also determined. In addition, fractional catabolic rates (FCR) and synthetic rates for both m- and p-IgA were measured in nine controls and nine cirrhotics. Our results support four main conclusions: (a) In healthy adults, intravascular p-IgA contributes to only 4-22% (mean 12%) of serum IgA, because its FCR and synthetic rate are approximately two times higher and four times smaller, respectively, than those of intravascular m-IgA. (b) in LD, biliary obstruction does not result in a significant increase in serum p-IgA unlike in rats and rabbits, indicating that in humans the SC-dependent biliary transport of p-IgA plays a much less significant role in selective removal of p-IgA from plasma than in rats and rabbits. (c) In contrast to biliary obstruction, parenchymal LD results in a significant and preferential increase in serum p-IgA, which in cirrhotics correlates with a selective reduction of the p-IgA-FCR. This supports a role for the human liver in selective removal of p-IgA from plasma, but another mechanism than the SC-dependent biliary transport should be considered. (d) Total SC, p-IgA, and IgA2 in serum are unlinked parameters, not necessarily reflecting mucosal events. A marked increase in serum SC occurs almost selectively in LD. Although a shift to IgA2 is suggested in Crohn's disease and alcoholic cirrhosis, a shift to IgA1 frequently associated to a shift to p-IgA occurs in chronic active LD, primary Sicca, and connective tissue diseases.

Adult↗
PubMed1983

IgA in alcoholic cirrhosis.

Circulating IgA in patients with alcoholic cirrhosis was quantitated and characterized to determine the proportion of monomer and dimer present. Polymeric (p) IgA formed a significantly greater proportion of the total serum IgA in cirrhosis, but these individuals showed significant elevations of serum levels of monomeric (m) as well as pIgA. Thus a selective disturbance of pIgA metabolism could not entirely account for the abnormal serum IgA levels. Studies on spontaneous IgA synthesis in vitro by peripheral blood lymphocytes showed that greater amounts of both mIgA and pIgA were formed by cells from patients with cirrhosis compared with control individuals.

Adult↗
PubMed1982

Non-proteic immunogenic impurity in proteins purified by preparative electrophoresis on Pevikon.

Purified IgA proteins, obtained by zonal electrophoresis on blocks of Pevikon, contained an uncharged, non-proteic, water-soluble macromolecular impurity. The contaminant, which precipitates in half-saturated ammonium sulfate, could be an unknown derivative of polyvinyl alcohol. It was discovered because it induced the synthesis of specific precipitating antibodies in a rabbit used for antibody production against the electrophoresed protein, generating spurious precipitin reactions during its immunochemical analysis. Thorough washing of the Pevikon will substantially reduce the amount of impurity and the danger of obtaining precipitating antibodies against it after injection into animals.

Animals↗
PubMed1982

High serum levels of secretory IgA in liver disease: possible liver origin of the circulating secretory component.

Patients with liver disease frequently display unexplained elevations of serum secretory IgA (sIgA). The sIgA levels in various liver diseases were compared to various biochemical or clinical parameters. Patients with primary biliary cirrhosis, biliary tract obstruction, or acute hepatitis displayed highest sIgA levels. In chronic parenchymal liver disease sIgA levels correlated strongly with serum alkaline phosphatase (r = 0.79), leucine aminopeptidase (r = 0.83), and direct bilirubin levels (r = 0.63), but not with prothrombin time, aminopyrine breath test, or presence of portacaval shunting. In acute hepatitis sIgA correlated best with serum glutamic oxaloacetic transaminase (r = 0.69) but not with bilirubin; in four patients with fulminant hepatitis, sIgA fell rapidly together with all liver enzymes and prothrombin time; it rose quickly again in one patient when parenchymal regeneration occurred. These results suggest a hepatobiliary origin of the serum sIgA in liver disease. In acute hepatitis the persistence of hepatocytes seems necessary for maintaining high serum sIgA levels, suggesting a possible hepatocyte origin of the secretory component.

Adolescent↗