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A G Nerlich

Publications and source records attributed to A G Nerlich.

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

[Value of basement membrane imaging in diagnosis of invasive carcinomas].

The destruction of the epithelial basement membrane is widely regarded as a clear criterion for invasive malignant tumor growth. Since, however, defects in the basement membrane may also occur in non-invasive conditions, such as inflammatory and proliferative lesions, and since it has been shown that particularly in highly differentiated squamous cell carcinomas a continuous basement membrane is mimicked by the presence of isolated components, this criterion seems to be of minor value for the diagnosis of malignancy. Despite these drawbacks, the immunolocalization of basement membrane material may still be of differential diagnostic significance in certain situations. This holds particularly true for invasive (ductal) breast carcinomas, which usually completely lack a basement membrane. Accordingly, sclerosing adenosis can be distinguished from invasive carcinoma, as a distinction can be made between neoplastic (malignant) tubular formations and reactive lesions.

Basement Membrane↗
PubMed1998

Immunolocalization of major interstitial collagen types in human lumbar intervertebral discs of various ages.

We used complete transverse sections through 65 samples of human lumbar intervertebral discs for immunolocalization of the major interstitial collagen types I, II, III, V, VI and IX. The samples were selected from 47 patients ranging in age from 0 (fetuses) to 86 years. The results were compared with the histological findings in disc tissue degeneration and/or reparative alterations as indicated by tear and cleft formation, chondrocyte proliferation, mucous degeneration, granular matrix changes and fibrocartilage fibrillation. We observed a typical pattern for each antibody and each anatomical structure, with, however, remarkable inter- and intraindividual variability, which could be monitored only by use of the complete transverse sections. Accordingly, collagen I was seen in the normal annulus fibrosus and in the degeneratively altered nucleus pulposus, but not within the end-plate, regardless of degenerative changes. Collagens II and IX were found in the normal nucleus pulposus, the inner annulus fibrosus and the end-plate. The collagen II (and IX) staining seemed to be enhanced in areas of minor degenerative lesions, but reduced in advanced lesions and in the degenerated end-plate. Collagens III and VI were significantly increased in areas of minor to advanced degeneration in all anatomical settings, while collagen V showed only minor changes in its staining pattern. In general, histological signs of tissue degeneration coincided with significant quantitative, but also with certain qualitative, changes in the composition of the collagenous disc matrix. These observations indicate the association of degenerative and/or reparative alterations of the intervertebral disc and changes in the collagenous matrix, but document the variability in the extent of the abnormalities observed.

Adolescent↗
PubMed1998

Defective basement membrane in laryngeal carcinomas with heterogeneous loss of distinct components.

In this study, we evaluated immunohistochemically the composition of the tumor-associated epithelial basement membrane (BM) in a series of 66 laryngeal squamous cell carcinomas (SCC) and compared these results with those from 10 cases with laryngeal dysplasia and five cases with normal mucosa (controls). The major BM components collagen IV and VII, laminin-1, perlecan (heparan sulfate proteoglycan), and fibronectin were evaluated. The extent of the retained BM material was quantified by semiautomated morphometry. A subsequent statistical analysis correlated the immunohistochemical findings with the histopathologically evaluated degree of tumor cell differentiation. In our series, we observed a distinct correlation between the degree of tumor cell differentiation and the amount of retained BM material. The loss of BM affected the various components differently, with a more extensive loss of collagen VII even in highly differentiated tumors and a progressive loss of collagen IV immunostaining with decreasing tumor cell differentiation. With respect to the other BM components, a stepwise loss of BM material also was seen with decreasing degree of the tumor cell differentiation. This loss, however was not at a statistically significant level, so these parameters did not show further statistically relevant data. In dysplastic lesions (regardless of the degree of dysplasia), focal BM disruptions were seen that affected the various BM components to a very similar extent. Our observations provide evidence that laryngeal carcinomas show a progressive loss of BM material along with decreasing tumor cell differentiation. This loss of BM, however, affects the various BM components differently. This indicates a dysregulation of the BM, either induced by uncoordinated neosynthesis or selectively enhanced degradation by proteases or both. Finally, the BM analysis may provide information on the biological course of the tumors. The loss of collagen VII may serve as a marker for "early" invasive tumor growth, whereas the amount of collagen IV provides significant information on the loss of tumor cell differentiation.

Adult↗
PubMed1998

In situ apoptotic and proliferation index in laryngeal squamous cell carcinomas.

The rate of cellular growth is mainly influenced by the balance between cell proliferation and cellular decay. Since to our knowledge, no study so far has analysed the rate of proliferation and apoptosis in the normal laryngeal mucosa and in invasive laryngeal carcinomas, we performed a morphological analysis on both parameters in biopsies from 30 patients with laryngeal carcinoma. We applied the TUNEL end labelling technique for the investigation of apoptosis and immunohistochemistry (Ki-67 antigen) for the determination of the cell proliferation. In our study we demonstrated that invasive tumour growth of the larynx coincides with an increase of both cellular proliferation and apoptosis. Both parameters, however, affected various tumour areas differently. While there was a preferential expression of the Ki-67 antigen at the tumour-stroma interface, apoptotic figures could be found randomly distributed in the tumour. This indicates that the replication of tumour cells and tumour cell decay are differently distributed and possibly independently regulated. Since we observed a particularly strong increase of cell proliferation at the tumour-stroma interface which outnumbered the corresponding rate of apoptosis by far, the enhanced cell proliferation at the tumour border seems to be a main factor for tumour growth. A statistical evaluation revealed significant correlation between the apoptotic index and the degree of tumour cell differentiation, indicating that a high rate of apoptosis coincides with a high level of tumour cell differentiation. There was, however, no statistically significant correlation between prognostic clinical parameters and the rate of apoptosis or that of proliferation.

Adult↗
PubMed1998

Expression of glutamine:fructose-6-phosphate amidotransferase in human tissues: evidence for high variability and distinct regulation in diabetes.

Recent in vitro and in vivo studies suggested that the increased flux of glucose through the hexosamine biosynthetic pathway may contribute to glucose-induced insulin resistance and to the induction of the synthesis of growth factors. Because glutamine:fructose-6-phosphate amidotransferase (GFAT) catalyzes the first and rate-limiting step in the formation of hexosamine products, this enzyme is the key regulator in this pathway and is therefore possibly also involved in the alterations occurring in preclinical or manifest diabetic patients. To study the expression of GFAT in human tissues, we produced and characterized a peptic antiserum specifically recognizing GFAT protein and a riboprobe for the detection of GFAT mRNA. Immunohistochemical and nonradioactive in situ hybridization analysis revealed high levels of expression of GFAT protein and mRNA in adipocytes and skeletal muscle. Furthermore, a marked GFAT expression was found in vascular smooth muscle cells with unexpectedly high variability and lower levels in other cells, e.g., peripheral nerve sheath cells or endocrine-active cells, including the pancreatic islet cell. GFAT protein expression was below detection level in endothelium, osteocytes, lymphocytes, granulocytes, and in most quiescent fibroblasts. In renal tissue, GFAT was expressed in tubular epithelial cells, while glomerular cells remained essentially unstained. Renal sections obtained from patients with diabetic nephropathy showed significant GFAT expression in some glomerular epithelial and mesangial cells, indicating that GFAT expression may be induced by manifest diabetes. Our data indicate that GFAT is expressed in most tissues involved in the development of diabetic late complications. Furthermore, the results suggest that GFAT gene expression is highly regulated.

Adipocytes↗
PubMed1997

1997 Volvo Award winner in basic science studies. Immunohistologic markers for age-related changes of human lumbar intervertebral discs.

STUDY DESIGN: The authors performed a correlative macroscopic, histologic, and immunohistochemical investigation on human lumbar intervertebral discs using complete motion segment slices, including all age groups and stages of degeneration. OBJECTIVES: To identify markers for age-related changes of human lumbar intervertebral discs. In particular, to investigate changes in the distribution pattern of collagen Types I, II, III, IV, V, VI, IX, and X. In addition, to study posttranslational protein modification by the immunolocalization of N-(carboxylmethyl)lysine (CML), which is regarded as a biomarker for oxidative stress. SUMMARY OF BACKGROUND DATA: Data on a correlation of age-related changes in disc morphology and disc matrix composition is sparse. So far, no comprehensive analysis considered a correlation of macroscopic, histologic, and biochemical age-related alterations using complete sections of intervertebral discs (i.e., including nucleus pulposus, anulus fibrosus, endplates, and vertebral bodies). In addition, there is need for specific markers for these disc changes to allow for a better correlation with disc function. METHODS: After photodocumentation of the macroscopic appearance, 229 sagittal lumbar motion segments obtained from 47 individuals (fetal to 86 years) during routine autopsy were processed for histologic and immunohistochemical analysis. All slices were investigated for histologic alterations of disc degeneration. A randomly selected subset of these specimens (n = 45) was used for a correlative analysis of interstitial collagens and molecular modifications of matrix proteins. RESULTS: The presence of CML-modification of extracellular matrix proteins, mainly collagen, was observed first in the nucleus pulposus of a 13-year-old individual and increased significantly with age. In elderly people, both the nucleus pulposus and the anulus fibrosus showed extensive CML deposition. This CML deposition was accentuated in areas of macroscopic and histologic disc degeneration. After the occurrence of CML in the nucleus pulposus, we found a change in the collagen type pattern. An initial increase in nuclear collagen Types II, III, and VI staining was followed by a loss of collagen Type II, the occurrence of collagen Type I, and the persistence of high collagen Type III and VI levels, which were finally decreased again. The nuclear chondrocytes revealed significant changes in their immediate pericellular matrix, indicating phenotypic changes. Thus, exclusively in the nucleus pulposus of adolescents and young adults a significant proportion of cells positively stained for the basement membrane collagen Type IV. Collagen Type X was expressed by nuclear chondrocytes at a higher age and was associated with advanced degenerative disc alterations. CONCLUSIONS: The authors present the first study in which age-related changes are correlated on a macroscopic, histologic, and molecular level using complete sections of lumbar motion segments. They reconfirm the notion that disc degeneration starts as early as in the second decade of life. Therefore, only early prevention of disc damage may inhibit disc degeneration and its sequelae. Phenotypic alterations of nuclear chondrocytes as monitored by collagen Type IV in young adults with minor lesions and collagen Type X in advanced lesions indicate distinct cellular reactions, possibly as a reaction to enhanced oxidative stress. The degree of this oxidative stress is reflected by the CML-staining pattern which, in turn, indicates that the disc undergoes an accumulative stress, possibly leading to altered properties of the collagen fibrils and, thereby, tissue destruction. The deposition of CML proved to be the best marker for ongoing age-related changes in the intervertebral disc.

Adolescent↗
PubMed1997

Increased accumulation of the glycoxidation product N(epsilon)-(carboxymethyl)lysine in human tissues in diabetes and aging.

N(epsilon)-(Carboxymethyl)lysine (CML), a major product of oxidative modification of glycated proteins, has been suggested to represent a general marker of oxidative stress and long-term damage to proteins in aging, atherosclerosis, and diabetes. To investigate the occurrence and distribution of CML in humans an antiserum specifically recognizing protein-bound CML was generated. The oxidative formation of CML from glycated proteins was reduced by lipoic acid, aminoguanidine, superoxide dismutase, catalase, and particularly vitamin E and desferrioxamine. Immunolocalization of CML in skin, lung, heart, kidney, intestine, intervertebral discs, and particularly in arteries provided evidence for an age-dependent increase in CML accumulation in distinct locations, and acceleration of this process in diabetes. Intense staining of the arterial wall and particularly the elastic membrane was found. High levels of CML modification were observed within atherosclerotic plaques and in foam cells. The preferential location of CML immunoreactivity in lesions may indicate the contribution of glycoxidation to the processes occurring in diabetes and aging. Additionally, we found increased CML content in serum proteins in diabetic patients. The strong dependence of CML formation on oxidative conditions together with the increased occurrence of CML in diabetic serum and tissue proteins suggest a role for CML as endogenous biomarker for oxidative damage.

Adult↗
PubMed1997

Immunolocalization of type X collagen in human lumbar intervertebral discs during ageing and degeneration.

Type X collagen has so far not been reported to occur in human intervertebral discs. The objective of this study was therefore to investigate the occurrence of type X collagen in human lumbar intervertebral discs during ageing and degeneration. Ninety intervertebral discs with adjacent endplates were excised in toto from individuals (0-86 years) without known spinal disease and were processed for routine decalcified histology. Appropriate slices of each disc were processed for immunohistochemistry using a type-specific, monoclonal antibody raised against human type X collagen. Each intervertebral disc was examined for macroscopic and histomorphological features of disc degeneration. Immunohistochemically, a positive specific type X staining was observed in the hypertrophic zone of the growth plate and only in the interstitial matrix of juvenile (<2 years) nucleus pulposus. In adult discs, type X collagen could be localized in conjunction with advanced disc degeneration and first occurred in the disc matrix (i.e., pericellular region) of a 47-year-old specimen. Positive type X staining of the disc matrix was more frequently found in senile (>70 years) discs with end stages of disc degeneration. This study provides the first evidence for the occurrence of type X collagen in human lumbar intervertebral discs and it appears that type X collagen is re-expressed in late stages of disc degeneration.

Adolescent↗
PubMed1996

Radiological and histological variants of thanatophoric dysplasia are associated with common mutations in FGFR-3.

We describe two fetuses of the 21st week of gestation that share some macroscopic, radiologic, and histologic findings of thanatophoric dysplasia (TD), but also show distinct differences from the usual subtypes of TD. These differences mainly comprise the lack of facial abnormality, only mild reduction of chondrocyte proliferation and hypertrophy, and the lack of fibrous tissue interposition between cartilage and periosteal bone. Thus, these two cases may represent a distinct variant of thanatophoric dysplasia. The molecular analysis of the FGF-R-3 gene demonstrated in both cases mutations which were not significantly different from those of other cases of TD. Thus, the phenotypic modulation within the subtypes of TD may be influenced by additional and yet unknown factors.

Adult↗
PubMed1996

Distribution of basement membrane components in normal adipose tissue and in benign and malignant tumors of lipomatous origin.

Normal adipose tissue as well as 13 benign and 17 malignant lipomatous tumors (lipomas, hibernomas, lipoblastomas, and liposarcomas) were immunohistochemically analyzed for their expression of the basement membrane components collagen IV, laminin, heparan sulfate proteoglycan, and fibronectin. Monovacuolar cells in normal white fat tissue and in lipomas generally exhibited a distinctive pericellular basement membrane composed of collagen IV and laminin, whereas heparan sulfate proteoglycan and fibronectin were almost completely missing. In brown fat tissue and hibernomas the characteristic multivacuolated cells differed from the monovacuolated white fat cells by the additional content of heparan sulfate proteoglycan and fibronectin and the more intensive staining for the other components tested. In contrast, multi-/monovacuolated cells in lipoblastomas exhibited no characteristic immunohistochemical feature because they reacted irregularly and only faintly for collagen IV, laminin, and heparan sulfate proteoglycan. Spindle cell areas in benign lipomatous tumors displayed more fibronectin than laminin and heparan sulfate proteoglycan indicating a "preadipose" fibroblast-like cellular differentiation. In liposarcomas, only well-differentiated lipoma-like neoplasms revealed a basement membrane pattern resembling that of white fat tissue. Otherwise, in nonlipoma-like liposarcomas, a marked decrease particularly of collagen IV staining was evident. Poorly differentiated liposarcomas mostly failed to express any of the basement membrane components, but showed a relative increase of fibronectin. Our results provide evidence that the staining pattern of basement membrane components parallels the histogenetic derivation of benign lipomatous tumors from either brown or white adipose tissue and, additionally, may reflect such a derivation in liposarcomas.

Adipose Tissue↗
PubMed1995

Collagen types in the middle ear mucosa.

The distribution of various collagen types--in particular that of type II as the major collagen in cartilage--in normal auricular structures is discussed with reference to a 1994 report by Ovesen describing the presence of collagen type II in normal middle ear mucosa. In contrast to this report, no collagen type II is normally found in the normal mucosa of the middle ear, while multiple structures of the normal middle and inner ear (which mostly consist of cartilage or have at least a cartilaginous origin) contain this unique collagen type. This indicates that the collagen type II staining previously observed in the normal middle ear mucosa is most likely an artifact. Of the at least 18 collagen types now known, interstitial and ubiquitously present types I, III and V can be found in the normal middle ear. The minor cartilage collagen types IX and XI have been found in cartilage of the middle (and inner) ear. The basement membrane collagen type IV is normally present in different microanatomical settings, particularly in the epithelial and endothelial basement membranes. In general, an exclusive morphometric estimation of area changes for collagens, particularly for collagen type IV, regardless of any tissue localization seems to be of minor value, since no attribution can be drawn to any of the histoanatomical structures present in the ear. The presence of further collagen types has not yet been tested in normal auricular structures.

Basement Membrane↗
PubMed1995

Extensive pulmonary haemorrhage in an Egyptian mummy.

We report on the morphological and trace element findings of several internal organs from an Egyptian mummy approximately dating from the year 950 B.C. according to 14C-analysis. By use of a multidisciplinary approach we succeeded in discovering evidence for severe and presumably recurrent pulmonary bleeding during life. This was suggested by the finding of massive haemosiderin deposits in the lung and a selectively and markedly elevated level of iron in trace element analysis of the lung tissue. Furthermore, we observed an enhanced deposition of birefringent particles in the lung tissue, without significant fibrosis. The histological analysis of liver, stomach and intestine confirmed the macroscopic organ diagnoses without evidence of any major pathological processes. In addition, analysis for various drugs revealed a significant deposition of tetrahydrocannabinol (THC), nicotine and cocaine in several organs of the mummy. The concentration profiles additionally provide evidence for a preferential inhalation of THC, while nicotine and cocaine containing drugs seem to have been consumed orally.

Adult↗
PubMed1995

Localization of extracellular matrix components in congenital nephrotic syndromes.

While renal tissue from one fetus and a newborn with congenital nephrotic syndrome, Finnish type (FCNS), showed a normal basement membrane (BM) localization and composition, in another type of congenital nephrotic syndrome, diffuse mesangial sclerosis (DMS), most glomeruli demonstrated a completely disorganized matrix. In the latter, hyalinized glomerular segments were composed of irregular deposits of interstitial collagens I, III, V, and extensive deposits of heparin sulphate proteoglycan (HSPG), while collagen IV and laminin were completely absent in those areas. Apart from these sclerosed glomerular areas, normal capillarly loops revealed a matrix composition that was comparable to normal glomeruli. The additional immunolocalization of various extracellular matrix components during the development of normal human glomeruli revealed some significant age-dependent changes both in the localization of interstitial collagens and BM components: interstitial collagens I and III disappeared after the first S-shaped indentations appeared, while the interstitial collagen V remained along the glomerular BM and within the mesangium. The BM components showed no significant qualitative changes, but quantitative changes, with a post-natal relative decrease in the collagen IV and laminin content when compared with the level of BM-associated HSPG. Our results provide circumstantial evidence that the composition of the extracellular matrix (and in particular of the BM) shows age-dependent quantitative changes which may be associated with functional adaptation processes of the developing kidney. The observed matrix composition in the two different congenital nephrotic syndromes suggests various pathomechanisms which may be located either in the molecular structure of the negatively charged molecules (e.g. abnormal sulphatation of HSPG in FCNS) or in the dysregulated synthesis of various matrix components (DMS).

Adult↗
PubMed1994

Pathomorphological and biochemical alterations in Ehlers-Danlos-syndrome type IV.

We are reporting the morphological and biochemical data of a patient with the characteristic features of the Ehlers-Danlos-Syndrome Type IV (Sack-Barabas Type) who died acutely after an episode of recurrent ruptures of the bowel with subsequent septic peritonitis. Morphologically, the connective tissue of the vessel walls, the dermis and the connective tissue of internal organs, particularly that of liver and lung, showed a distinct hypoplasia of the collagenous scaffold. Collagen fibers were irregularly arranged which was also corroborated by ultrastructural examination of the collagen fibrils of the dermis and of intervertebral disc material. Immunohistochemically, a loss in the staining intensity for collagen III could be observed in all locations. In contrast, the localization of collagen I, IV, V and VI appeared normal, although with some reduced staining intensity which particularly held true for collagen I in the dermis and vessel wall. The biochemical content of collagen III in lung and liver tissue was significantly reduced when compared to control tissues. Accordingly, in the pool of newly synthesized collagen from skin fibroblasts, only minute amounts of collagen III could be found which was normally secreted and had a normal electrophoretic migration.

Cells, Cultured↗
PubMed1994

Immunohistochemical localization of collagen VI in diabetic glomeruli.

Late stage diabetic nephropathy is histologically characterized by either diffuse or nodular expansion of the glomerular matrix. This is presumed to represent the morphological correlate for the functional impairment of the kidney. The exact matrix composition of the nodular glomerulosclerosis lesion of end-stage diabetic nephropathy is not known. Biochemical studies have provided evidence that the microfibrillar collagen type VI is increased in diabetic nephropathy. Consequently, this immunohistochemical study was designed to evaluate the extent and exact morphologic location of increased collagen VI deposition at various stages of diabetic glomerulosclerosis (GS). An irregular, sometimes spot-like staining of collagen VI was observed in diffuse GS in the mesangial portion. The uninterrupted staining which was evident along the glomerular basement membrane in normal glomeruli was discontinuous in diffusely sclerotic glomeruli. In nodular GS, the markedly increased deposition of collagen VI appeared to be evenly distributed throughout the entire nodular lesion. At the same time, mesangial staining for collagen IV was reduced in nodular GS, suggesting that in the expanded mesangial matrix collagen IV is progressively substituted by collagen VI during the transition from diffuse to nodular GS. The colocalization of PAS staining with collagen VI deposition in nodular GS suggests that the typical Kimmelstiel-Wilson lesions at least in part consist of collagen VI. Biochemical analysis confirmed the increased collagen VI deposition in glomeruli extracted from diabetic patients with nodular GS. Application of two antisera, recognizing primarily the alpha 1(VI)- and alpha 2(VI)-chains and the N-terminal part of alpha 3(VI)-chain, respectively, revealed no difference in staining pattern.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1993

Immunohistochemical localization of interstitial collagens in bone tissue from patients with various forms of osteogenesis imperfecta.

Immunohistochemical studies of bone from individuals with osteogenesis imperfecta (OI) type II, OI type III, or OI type IV demonstrate a similar pattern, but varying extent, of the abnormal presence of interstitial collagens in bone matrix. OI type II bone had nests of cartilage with type II collagen, and significant type III collagen in the bone matrix. In OI types III and IV, type II collagen was present only in epiphyseal cartilage but bone still contained type III collagen. These findings resembled those in developing fetal bone indicating the "immature" nature of OI bone.

Adult↗