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Biomedical subjects

E Lengyel

Publications and source records attributed to E Lengyel.

At least 37 records · Page 2Linked to original sources
PubMed1998

In vitro modulation of human melanoma cell invasion and proliferation by all-trans-retinoic acid.

Invasive growth and formation of metastases involve complex interactions between tumour cells, host cells and components of the extracellular matrix. Retinoids, a group of vitamin A derivatives, modulate cell growth and differentiation and have been found to suppress tumour cell invasion in vitro and formation of metastases in vivo. The aim of our study was to investigate changes in proliferation and invasion through membrane barriers in vitro of seven human melanoma cell lines, established from human primary melanomas or metastases, in response to treatment with retinoic acid (RA). These changes were compared with the expression regulation of molecules that have been identified as targets of RA-mediated signal pathways. Invasiveness in vitro was correlated with the origin of the cell lines and was significantly higher in the lines derived from metastases. In all the cell lines proliferation and chemotaxis were inhibited by 10(-5) M RA, but the cell lines established from metastases were significantly more sensitive with respect to inhibition of invasion by RA. The specific expression patterns of MMP-1 and TIMP-2 were detected and regulated by RA in almost all cell lines, whereas expression of MMP-2 and TIMP-1 was not influenced by RA treatment. The most striking difference between the cell lines was a strong downregulation of transforming growth factor-beta (TGF-beta) expression in cell lines derived from metastases when treated with RA in contrast to cell lines from primary melanomas. These data provide evidence that RA modulates growth, chemotaxis and invasion in a broad panel of melanoma cell lines derived both from primary non-metastasized melanomas and metastases. However, distinct molecular mechanisms are involved in mediating these effects.

Antineoplastic Agents↗
PubMed1997

Elevated urokinase-type plasminogen activator receptor expression in a colon cancer cell line is due to a constitutively activated extracellular signal-regulated kinase-1-dependent signaling cascade.

The urokinase-type plasminogen activator receptor (u-PAR) facilitates extracellular matrix degradation in part by accelerating plasmin formation at the cell surface. We previously reported that u-PAR expression is elevated in colon cancer cell lines characterized by their in vitro invasive capacity. Since, u-PAR expression is increased by a variety of growth factors, which signal through the extracellular signal-regulated kinases 1 and 2 (ERK1/ERK2), we determined if these mitogen-activated protein kinases (MAPKs) regulate u-PAR expression in two cultured colon cancer cell lines. An in-gel kinase assay showed that ERK1 activity was considerably higher in RKO cells, which display > or = 10(5) receptors/cell, than the GEO cells which have approximately 10(4) urokinase receptors per cell. The expression of either an ERK-inactivating phosphatase (CL100), or a kinase-defective ERK1, decreased the activity of a u-PAR promoter-driven CAT reporter in RKO cells. Immune complex kinase assays indicated that the constitutive ERK1 activity in RKO cells was largely a result of an activated MEK1. Further, treatment of RKO cells with a specific inhibitor (PD 098059) of MEK1 activation, which diminished ERK1 activity, reduced the amount of urokinase specifically bound to the cell surface and this was associated with reduced laminin degradation. The expression of a dominant negative c-Raf-1 also reduced u-PAR promoter activity suggesting that MEK1 activation involved an activator at, or upstream, of this serine-threonine kinase. Transfection of the u-PAR-deficient GEO cells with a constitutively activated MEK1 expression construct up-regulated u-PAR promoter activity. Similarly treatment of GEO cells with a phosphatase inhibitor (sodium vanadate) caused a dose-dependent increase in ERK1 activity which paralleled increased cell surface binding of urokinase. Taken together, these data suggest that elevated u-PAR expression, in at least a sub-population of colon cancer, is partly a consequence of a constitutively activated ERK-1-dependent signaling cascade.

Calcium-Calmodulin-Dependent Protein Kinases↗
PubMed1997

Regulation of 92 kDa type IV collagenase expression by the jun aminoterminal kinase- and the extracellular signal-regulated kinase-dependent signaling cascades.

The 92 kDa type IV collagenase (MMP-9), which degrades type IV collagen, has been implicated in tissue remodeling. The purpose of the current study was to determine the role of Jun amino-terminal kinase (JNK)- and extracellular signal-regulated kinase- (ERK)-dependent signaling cascades in the regulation of MMP-9 expression. Towards this end, we first determined the transcriptional requirements for MMP-9 promoter activity in a cell line (UM-SCC-1) which is an avid secretor of this collagenase. Transfection of these cells with a CAT reporter driven by progressive 5' deleted fragments of the MMP-9 promoter indicated the requirement of a region spanning -144 to -73 for optimal promoter activity. DNase I footprinting revealed a protected region of the promoter spanning nucleotides -91 to -68 and containing a consensus AP-1 motif at -79. Mutation of this AP-1 motif practically abolished the activity of the MMP-9 promoter-driven CAT reporter. Mobility shift assays indicated c-Fos and Jun-D bound to this motif and transfection of the cells with a mutated c-Jun, which quenches the function of endogenous Jun and Fos proteins, decreased MMP-9 promoter activity by 80%. UM-SCC-1 cells contained a constitutively activated JNK and the expression of a kinase-deficient JNK1 reduced the activity of a CAT reporter driven either by the MMP-9 promoter or by three tandem AP-1 repeats upstream of a thymidine kinase minimal promoter. Conditioned medium collected from UM-SCC-1 cells transfected with the dominant negative JNK1 expression vector diminished 92 kDa gelatinolysis. Similarly, interfering with MEKK, which lies upstream of JNK1, using a dominant negative expression vector reduced MMP-9 promoter activity over the same concentration range which repressed the AP-1-thymidine kinase CAT reporter construct. UM-SCC-1 cells also contained a constitutively activated ERK1. MMP-9 expression, as determined by CAT assays and by zymography, was reduced by the co-expression of a kinase-deficient ERK1. Interfering with MEK1, which is an upstream activator of ERK1, either with PD 098059, which prevents the activation of MEK1, or with a dominant negative expression construct, reduced 92 kDa gelatinolysis and MMP-9 promoter activity respectively. c-Raf-1 is an upstream activator of MEK1 and a kinase-deficient c-Raf-1 expression construct decreased the activity of a promoter driven by either the MMP-9 promoter or three tandem AP-1 repeats. Conversely, treatment of UM-SCC-1 cells with PMA, which activates c-Raf-1, increased 92 kDa gelatinolysis. These data suggest that MMP-9 expression in UM-SCC-1 cells, is regulated by JNK- and ERK-dependent signaling pathways.

Binding Sites↗
PubMed1996

Requirement of an upstream AP-1 motif for the constitutive and phorbol ester-inducible expression of the urokinase-type plasminogen activator receptor gene.

The urokinase-type plasminogen activator receptor (u-PAR) facilitates extracellular matrix proteolysis by accelerating plasmin formation at the cell surface. The present study was undertaken to identify elements in the u-PAR promoter required for the elevated expression of this binding site. Toward this end, we used two cultured colon cancer cell lines; one (RKO) has a transcriptionally activated u-PAR gene, and the other (GEO) overexpresses the receptor only after phorbol ester treatment. A chloramphenicol acetyltransferase (CAT) reporter driven by 398 nucleotides of 5' regulatory sequence of the u-PAR gene was strongly activated in the RKO cells, which displays approximately 3 x 10(5) receptors/cell. A region of this promoter between -197 and -8 was required for optimal expression, as indicated using a CAT reporter driven by 5' deleted fragments. DNase I footprinting revealed three protected regions (I, -190 to -171; II, -148 to -124; and III, -99 to -70) in this part of the promoter. Mutation of an AP-1 binding site at -184 within region I reduced activation of the promoter by 85%. Deletion of either region II or III also reduced promoter activity by over 60%. An oligonucleotide spanning the AP-1 motif at -184 bound, specifically, nuclear factors from RKO cells, and antibodies specific for Jun-D, c-Jun, or Fra-1 proteins supershifted the complex indicating the presence of these proteins. The amount of these factors was reduced in GEO cells in which the u-PAR gene is only weakly transcriptionally activated. Expression of a vector encoding a wild-type Jun-D cDNA increased u-PAR promoter activity in GEO cells. Conversely, transfection of RKO cells with a transactivation domain-lacking Jun-D expression construct resulted in a dose-dependent decrease in u-PAR promoter activity. Treatment of GEO cells with phorbol ester increased u-PAR mRNA and the activity of a CAT reporter driven by the wild-type but not the AP-1 (-184)-mutated u-PAR promoter, and this was associated with a strong induction in the amount of Jun-D, c-Jun, and c-Fos. Methylation interference studies using a fragment of the u-PAR promoter (spanning -201 to -150) bound with nuclear extracted proteins from RKO cells, and phorbol 12-myristate 13-acetate-treated and -untreated GEO cells showed that the contact points corresponded to the AP-1 binding site at -184. Thus, the elevated expression of u-PAR in RKO cells, which constitutively produces this binding site, as well as in phorbol 12-myristate 13-acetate-stimulated GEO cells requires an AP-1 motif located 184 bp upstream of the transcriptional start site.

Base Sequence↗
PubMed1996

Regulation of urokinase-type plasminogen activator expression by an ERK1-dependent signaling pathway in a squamous cell carcinoma cell line.

The urokinase-type plasminogen activator contributes to tissue remodeling by controlling the synthesis of the extracellular matrix-degrading plasmin. We undertook a study to determine the role of the extracellular signal-regulated kinases (ERKs) in the regulation of urokinase-type plasminogen activator expression in a squamous cell carcinoma cell line (UM-SCC-1) that contains a transcriptionally activated urokinase-type plasminogen activator gene. Transient transfection studies using a CAT reporter driven by the urokinase-type plasminogen activator promoter, which had progressive 5' deletions or which had been point-mutated, indicated the requirement of binding sites for AP-1 (-1967) and PEA3 (-1973) for its maximal activation. Expression of a mutant jun protein, which lacks the transactivation domain, caused a dose-dependent repression of a CAT reporter driven by either the urokinase-type plasminogen activator promoter or three tandem AP-1 repeats upstream of a thymidine kinase minimal promoter indicating the importance of AP-1-binding transcription factor(s) in the regulation of urokinase-type plasminogen activator synthesis. Mobility shift assays with UM-SCC-1 nuclear extract revealed binding of fos and junD proteins to an oligonucleotide spanning the AP-1 site at -1967. In-gel kinase assays indicated the constitutive activation of ERK1, which regulates fos synthesis via phosphorylation of p62TCF, but not ERK2, in UM-SCC-1 cells. Moreover, the expression of a dominant-negative ERK1, but not ERK2, repressed urokinase-type plasminogen activator promoter activity. Similarly, interfering with the function of the c-raf serine-threonine kinase, which lies upstream of ERK1, by the expression of a kinase-inactive c-raf repressed the activity of a CAT reporter driven by either the urokinase-type plasminogen activator promotor or tandem AP-1 repeats. These data suggest that urokinase-type plasminogen activator expression in UM-SCC-1 cells is regulated partly by an ERK1, but not ERK2, -dependent signaling pathway.

Blotting, Western↗
PubMed1996

Stimulation of 92-kDa gelatinase B promoter activity by ras is mitogen-activated protein kinase kinase 1-independent and requires multiple transcription factor binding sites including closely spaced PEA3/ets and AP-1 sequences.

The 92-kDa type IV collagenase (92-kDa gelatinase B also referred to as MMP-9), which plays a critical role in extracellular matrix degradation, is regulated by growth factors that mediate their effects through the ras proto-oncogene. The current study was undertaken to determine the transcriptional requirements for the induction of 92-kDa gelatinase B expression by an activated ras oncogene. Transfection of OVCAR-3 cells with an expression vector encoding an activated Ha-ras increased 92-kDa gelatinolytic activity and stimulated (over 10-fold) the activity of a CAT reporter driven by 670 nucleotides of 5' flanking sequence of the 92-kDa gelatinase B gene. Transient assays using a CAT reporter driven by 5' deleted fragments of the 92-kDa gelatinase B promoter indicated that a region spanning -634 to -531 was required for optimal induction of the promoter. The individual deletion, or mutation, of a PEA3/ets (-540) motif, AP-1 sites (-533, -79), a NF-kappa B (-600) consensus sequence, and a GT box (-52) substantially reduced the activation of the promoter by ras. An expression vector encoding the PEA3 transcription factor caused a 3-fold stimulation of the wild type but not the PEA3/ets-deleted 92-kDa gelatinase B promoter. Coexpression of a dominant negative c-jun antagonized the ras-dependent stimulation of the 92-kDa gelatinase B promoter-driven CAT reporter. The signaling pathway mediating the induction of 92-kDa gelatinase B promoter activity by ras was examined. The expression of a phosphatase (CL100) which inactivates multiple mitogen-activate protein kinase members abrogated the stimulation of 92-kDa gelatinase B promoter activity by ras. However, the expression of a kinase-deficient mitogen-activated protein kinase kinase 1 (MEK1) did not prevent activation of the 92-kDa gelatinase B promoter by ras and a constitutively activated c-raf expression vector was insufficient for 92-kDa gelatinase B promoter activation. Thus, the stimulation of the 92-kDa gelatinase B promoter by ras requires multiple elements including closely spaced PEA3/est and AP-1 sites and is MEK1-independent.

Base Sequence↗
PubMed1996

Elevated keratin 18 protein expression indicates a favorable prognosis in patients with breast cancer.

This study was performed to determine if keratin 18 (K18) has prognostic significance in breast cancer cell lines and patients with breast carcinoma. Paraffin sections of primary breast carcinoma tumors and human breast carcinoma cell lines were examined for K18 expression by immunohistochemical staining with the monoclonal antibody CK2. K18 protein expression was low in highly metastatic cell lines and, conversely, high in weakly metastatic cell lines, suggesting that it may function as a prognostic indicator. K18 expression was consequently examined in 134 patients with breast cancer. The staining intensity was compared with clinicopathological variables and follow-up data spanning 8 years. A definitive positive staining was observed in 22 (16.4%) women. The mortality rate was 4. 5% in the K18-positive group and 44.6% in the K18-negative group. Multivariate analysis found K18 expression to be an independent and significant predictor for overall survival.

Adult↗
PubMed1995

Involvement of a mitogen-activated protein kinase signaling pathway in the regulation of urokinase promoter activity by c-Ha-ras.

The expression of the urokinase-type plasminogen activator, which plays a crucial role in tissue remodeling by controlling the synthesis of the broadly acting plasmin serine protease, is regulated by several tyrosine kinases. Since the actions of these tyrosine kinases is dependent on the activation of ras proteins, we undertook a study to identify signaling events downstream of ras responsible for the stimulation of urokinase promoter activity. Transient expression of an activated c-Ha-ras in OVCAR-3 cells, which do not harbor the mutated oncogene, led to a dose-dependent trans-activation of the urokinase promoter. A sequence residing between -2109 and -1964 was critical for the stimulation of the urokinase promoter by c-Ha-ras. Mutation of an AP-1 and a PEA3 site at -1967 and -1973, respectively, or the co-expression of a transactivation domain-lacking c-jun substantially impaired the ability of c-Ha-ras to stimulate urokinase promoter activity. The induction of the urokinase promoter by ras was completely blocked by expression of a dominant negative c-raf expression vector and substantially reduced in cells made to co-express a catalytically inactive mitogen-activated protein kinase kinase. Further, the expression of an ERK1/ERK2-inactivating phosphatase (CL100) abrogated the stimulation of the urokinase promoter by c-Ha-ras. These data argue for a role of a mitogen-activated protein kinase-dependent signaling pathway in the regulation of urokinase promoter activity by ras.

Adenocarcinoma↗
PubMed1995

Stimulation of urokinase expression by TNF-alpha requires the activation of binding sites for the AP-1 and PEA3 transcription factors.

The urokinase-type plasminogen activator plays a central role in tissue remodeling by controlling the synthesis of the extracellular matrix-degrading plasmin. Urokinase expression is transcriptionally regulated by a variety of cytokines including TNF-alpha. The present study was undertaken to identify key transcription factor binding sites in the urokinase promoter necessary for the TNF-alpha-dependent induction of urokinase expression. TNF-alpha treatment of a squamous cell carcinoma cell line, UM-SCC-1, which produces no detectable TNF-alpha, led to a dose-dependent increase in urokinase secretion, thus reflecting a more abundant mRNA. Transient transfections of UM-SCC-1 cells with a CAT reporter driven by 5' deletion fragments of the urokinase promoter indicated that a sequence spanning -2109 to -1870, which contained binding sites for AP-1 and PEA3 was required for the stimulation by TNF-alpha. Mutation of an AP-1 binding site at -1967 and a PEA3 motif at -1973 completely abrogated the inductive effect of TNF-alpha on urokinase promoter activity. Mobility shift assays indicated the presence of a jun-containing factor(s) which bound specifically to the AP-1 sequence present in the urokinase promoter. The amount and/or activity of this factor(s) was greatly enhanced by TNF-alpha treatment. UM-SCC-1 cells transiently transfected with a CAT reporter driven by 3 tandem AP-1 binding sites demonstrated increased CAT activity following TNF-alpha treatment. Thus, the induction of urokinase expression by TNF-alpha is likely to involve the altered expression and/or activity of transcription factors which bind to the AP-1 and PEA3 target sequences in the urokinase promoter.

Base Sequence↗
PubMed1995

Induction of M(r) 92,000 type IV collagenase expression in a squamous cell carcinoma cell line by fibroblasts.

A previous investigation (Matsumoto et al., J. Oral Pathol. Med., 18: 498-501, 1989) has shown that the in vitro invasion of a collagen gel by squamous cell carcinoma can be substantially augmented in the presence of fibroblasts. Therefore, we undertook a study to determine if the production of collagenase(s) by a squamous cell carcinoma cell line, UM-SCC-1, was up-regulated by fibroblasts. Cocultivation of UM-SCC-1 cells with MDA-TU-138 fibroblasts, both established from the oral cavity, resulted in a dose-dependent increase in the activity of a M(r) 92,000 gelatinase as shown by zymography. Augmented M(r) 92,000 gelatinase activity was a consequence of the stimulation of the UM-SCC-1 cells by a soluble, fibroblast-derived factor since this effect could be reproduced with fibroblast-conditioned medium but not with glutaraldehyde-fixed fibroblasts. The increased M(r) 92,000 gelatinolytic activity could be accounted for by an increase in M(r) 92,000 type IV collagenase (MMP-9) protein, as demonstrated by Western blotting for this metalloproteinase. Trypsin treatment of the fibroblast-conditioned medium abolished its ability to increase MMP-9 secretion by UM-SCC-1 cells. Furthermore, fractionation of the fibroblast-conditioned medium revealed a M(r) 3,000-10,000 soluble factor(s) which was responsible for the augmented production of MMP-9 by UM-SCC-1 cells. To determine if the increased production of MMP-9, in response to the fibroblasts, was a consequence of increased promoter activity, UM-SCC-1 cells were transiently transfected with a chloramphenicol acetyltransferase reporter driven by the MMP-9 promoter and plated on plastic or on a monolayer of MDA-TU-138 fibroblasts. A 4-5-fold stimulation of MMP-9 promoter activity was observed with UM-SCC-1 cells plated with the MDA-TU-138 fibroblasts, when compared with similarly transfected cells recultured on plastic. In conclusion, we have demonstrated that MMP-9 expression in a squamous cell carcinoma cell line is augmented by a fibroblast-derived protein(s). This finding indicates a role for stromal cells in the regulation of MMP-9 expression in squamous cell carcinoma. The ability of fibroblasts to regulate MMP-9 expression in tumor cells in vitro may explain the observation that the amount of M(r) 92,000 type IV collagenase mRNA in tumor cells is highest at the tumor:stromal interface of resected squamous cell carcinoma.

Carcinoma, Squamous Cell↗
PubMed1994

Coronary arteriopathy after lymphatic blockade: an experimental study in dogs.

The effects of lymph stasis on the histological and biochemical properties of the coronary arterial wall and on the coronary circulation were studied in 72 dogs. Cardiac lymph stasis was produced in 52 dogs by cardiac lymphatic blockade whereas in 20 dogs only a sham operation was performed. Blockade of cardiac lymph drainage promoted characteristic injury to the coronary arteries including subendothelial edema with plasma inbibition, interstitial and intracellular edema in the tunica media with degeneration in the smooth muscle layer, swelling of the adventitial space with dilated lymph vessels and, later, fibrosis. The biochemical properties of the coronary arterial wall also were adversely affected by cardiac lymph stasis. Thus, the collagen and hexosamine content of the coronary arteries increased and the metabolism of the coronary wall shifted in an anaerobic direction. Whereas coronary blood flow was slightly decreased with lymph blockade, the coronary circulatory reserve capacity and the adaptability of the coronary vascular system was markedly reduced. The histological changes were most apparent in the smaller coronary arteries. The coronary microvasculature was also pathologically altered with the development of numerous coronary arteriovenous microshunts. These findings in conjunction with other experimental and clinical information suggest that impaired cardiac lymph drainage contributes to the pathogenesis and progression of coronary artery disease.

Animals↗
PubMed1993

Keratin expression reveals mosaic differentiation in vaginal epithelium.

OBJECTIVE: Analyzing the expression of keratins has proved to be valuable for identifying of pathways of epithelial differentiation. In stratified epithelia K10 and K13 are representative for either the keratinizing (epidermal-type) or the nonkeratinizing pathway. STUDY DESIGN: We have investigated keratin expression in "normal" vaginal epithelium from 30 women, applying two-color immunofluorescence with monoclonal antibodies to K10 and K13 on cryostat sections and cell smears. RESULTS: A differential expression pattern of vaginal cells dependent on their localization within the epithelium was found. In cells of the first suprabasal layers differentiation began and became identifiable by a weak expression of K13. The adjacent layers displayed cells that concurrently expressed K10 and K13. In contrast, cells within the superficial strata expressed exclusively either one of the two keratins. CONCLUSION: Thus vaginal epithelium appears to be mosaic in differentiation, showing simultaneous expression of keratins K10 and K13, thought to be representative for distinct routes of differentiation.

Adult↗
PubMed1993

Physiological age-related changes: cross-sectional and longitudinal studies.

Physiological age-related changes were investigated by cross-sectional and longitudinal studies. The data of the study were derived from volunteers admitted to the Gerontology Center in Budapest. In the follow-up study 864 subjects took part, and in the cross-sectional study 2,281 individuals. The 20-year longitudinal study and the cross-sectional examination showed that from a clinical standpoint the most important observation is that several biochemical data do not change with age. No changes were found in the values in erythrocyte sedimentation, hemoglobin, hematocrit, serum total protein, albumin, liver function, glucose, creatinine, triglyceride, and HDL-cholesterol levels. Changes were observed in the levels of HDL-cholesterol, immunoglobulins, rheumatoid factors, antinuclear factors, morphology of lymphocytes, serum TSH and T3 concentration, and systolic blood pressures.

Aged↗
PubMed1991

Lymphatic arteriopathy: damage to the wall of the canine femoral artery after lymphatic blockade.

The effect of lymph stasis on the histological, biochemical, and elastic properties of the femoral artery were studied after regional lymphatic blockade in 36 dogs. Dogs were sacrificed 4-21 days after operation. Histologic changes of the femoral arterial wall (interstitial edema, degeneration in the muscle layer or media, thickened adventitia with dilated lymph vessels, and fibrosis) developed after regional lymphatic blockade. Characteristic metabolic alterations of the arterial wall (anaerobic catabolism of carbohydrate, increased lactate and glycosamine content) accompanied the morphological changes. Distensibility of the femoral artery decreased and greater elastic stiffness developed after regional lymphatic blockade. These results in conjunction with other experimental and clinical data support the concept that insufficient lymphatic transport within the blood vessel wall may contribute to the genesis and progression of arteriopathies.

Animals↗
PubMed1985

Occurrence of anti-low density lipoprotein antibodies and circulating immune complexes in aged subjects.

The incidence of circulating immune complexes, anti-low density lipoprotein (LDL) autoantibodies and the anti-LDL activity of immune complexes was studied in healthy young and aged controls and in patients with vascular diseases. Circulating immune complexes (CIC) frequently occurred both in the young or old patient groups and in the aged healthy control groups, whereas they could not be found in the young controls. Marked differences were found in the incidence of anti-LDL antibodies between the groups tested. In both young and aged control groups such antibodies were very rarely observed (4-5%). In contrast anti-LDL antibodies were present in 35-45% in the aged, or young patients. Similarly, no anti-LDL activity was found in CIC of the controls, whereas in the patients with vascular diseases a significant CIC-associated anti-LDL activity was detected. These results suggest that the presence of anti-LDL antibodies are associated with the arteriosclerotic manifestations, while that of circulating immune complexes is connected by the ageing process itself.

Adult↗
PubMed1984

Antibody and immunoglobulin levels in aged humans.

IgM and IgG type antibody titers and levels of serum IgG, IgA and IgM were determined in healthy young and aged subjects. The proportion of subjects of low antibacterial agglutinin titers progressively increased during the 7th and 8th decades of life. Anti-streptolysin-O titers were also shifted to the lower values in aged subjects, at least until the 8th decade of life, although subnormal values compared to the young control range were less frequent than in the case of IgM type antibodies. Anti-streptokinase values did not seem affected by age. In contrast to antibody levels, serum IgM was similar or slightly higher in old compared to young subjects. Evidence is presented that the proportion of 7 S IgM drops with aging. Both IgA and IgG levels increased through the 7th, 8th and 9th decades of life. Different class immunoglobulin levels seemed to be considerably correlated and a tendency to correlate was found between IgG type antibody and serum IgG levels. Complex investigations including quantitation of antibodies to extrinsic and intrinsic antigens and serum immunoglobulins are proposed to define the humoral immune status of aged subjects and to understand the causes as well as the diagnostic and prognostic significance of old age 'imbalances'.

Adult↗