Search PubMed⌕ Search

Biomedical subjects

A Nerlich

Publications and source records attributed to A Nerlich.

At least 127 records · Page 7Linked to original sources

Low diacylglycerol values in colonic adenomas and colorectal cancer.

The biochemical events that make colonic epithelial cells proceed along the adenoma-carcinoma sequence are not well understood. The phosphoinositol signal transduction pathway is involved in the regulation of cell growth and differentiation. To determine its role in colonic neoplasias we performed mass measurements of its second messenger sn-1,2-diacylglycerol in biopsy specimens from normal mucosa and neoplasias of the colon. Normal colonic mucosa was also investigated in patients without colonic abnormalities (n = 10). Compared with pooled diacylglycerol values from five colonic sites (100%), values in patients with a normal colon were highest in the ascending colon (120 (5)%, p less than 0.05) and lowest in the rectum (81 (5)%, p less than 0.01). Absolute diacylglycerol values in patients with normal colons (2.62 (0.16) nmol/mg protein) were not significantly different from those found in the normal mucosa of patients with colorectal neoplasias (2.45 (0.17) nmol/mg protein). Both colonic adenomas (n = 15) and colorectal carcinomas (n = 14) showed significantly decreased diacylglycerol values compared with the adjacent normal mucosa of each patient (72 (4)%, p less than 0.001, and 71 (4)%, p less than 0.001 respectively). The appreciable decrease in mass diacylglycerol values clearly distinguishes adenomas and carcinomas of the colon from the surrounding normal mucosa. This finding suggests that profound metabolic changes of the phosphoinositol signal transduction pathway occur early in the adenoma-carcinoma sequence and may be important in colonic carcinogenesis.

Adenocarcinoma↗

[Molecular biological demonstration of parvovirus infection in fetal tissue].

We report on the morphological findings in 16 fetuses with serologically confirmed maternal parvovirus B19 infection. Typical routine morphological findings of the hydropic fetuses were the presence of abnormal erythroblasts with typical nuclear inclusions. These infected cells positively stained immunohistochemically with antibodies against a recombinant virus protein, as well as they ultrastructurally contained virus particles. Using in-situ hybridization techniques, we were able to demonstrate the presence of parvovirus B19 genome in the infected cells, while no other cell type was shown to contain virus genome. According to our results the differential diagnosis of fetal parvovirus B19 infection should be considered in each case with hydrops fetalis of unknown origin. The careful routine microscopic examination of fetal tissue may provide evidence for parvovirus infection which should be confirmed by in-situ hybridization analysis.

Bone Marrow↗

Parvovirus B19 infection in pregnancy.

Parvovirus B19 infection in pregnancy can cause hydrops fetalis resulting in fetal loss. Acute B19 infection was serologically confirmed in 80 pregnant women by ELISA. Of 80 pregnancies, 4 were terminated. Of the remaining 76 pregnancies, no fetal complications were observed in 36 (47.4%), hydrops fetalis occurred in 18 (23.7%) and no further information was available in 22 (28.9%). 15 of 18 (83.3%) fetuses with hydrops died. Intrauterine transfusion was performed in the remaining three fetuses and pregnancy continued without further complications. B19 infected fetal erythroblasts can be detected by standard histological staining methods and in situ hybridisation using a digoxigenin-labelled B19 DNA probe. Non-immune pregnant females working in kindergartens or schools should be suspended during an epidemic outbreak of B19 in such institutions.

Enzyme-Linked Immunosorbent Assay↗

[Interstitial and intramural pregnancy--definition and sonographic references].

Two cases of atypical implantation are presented in order to illustrate the difference between interstitial and intramural pregnancy. Ultrasonography can provide a method of early diagnosis of heterotypic sitting before the occurrence of clinical symptoms. In cases where complications already occurred, sonography can be used to confirm the clinical diagnosis.

Adult↗

[Sonographic diagnosis of a case of type 1 achondrogenesis in the 2d trimester].

The authors report on a prenatal ultrasonic diagnosis of lethal osteochondrodysplasia achondrogenesis type I (Parenti-Fraccaro) in the 17th week of pregnancy. The prenatal findings were confirmed by necropsy after termination of the pregnancy. The possibility to recognize lethal skeletal disorders early in pregnancy is discussed as well as the patho-anatomical criteria and possible patho-physiological mechanisms of achondrogenesis.

Abortion, Induced↗

Osteogenesis imperfecta: insufficient collagen synthesis in early childhood as evidenced by analysis of compact bone and fibroblast cultures.

We analysed the composition of compact bone from 30 patients suffering from various forms of osteogenesis imperfecta (OI). Collagen and total protein content per cell of controls increased with the age of the donors, but were generally low in OI. In fibroblast cultures controls had a maximum of collagen synthesis between 2 and 9 years of age, an observation which was not seen in OI cells. In bone collagen both OI type II patients showed overhydroxylation of lysyl residues as did some patients with OI type III (25%) and OI type IV (33%). The collagen of OI type I patients was never found to be overmodified. In controls, collagen III was found exclusively during fetal time while it was present in significant amounts in bone tissue of all types of OI. The proportion of collagen V was somewhat higher in OI bones (about twice) than in controls. Our data suggest that the normal increase of collagen synthesis is defective in patients with OI. Perhaps some of these changes are due to specific molecular defects in collagen while others may be due to defective regulation of the maturation process.

Adolescent↗

Pena-Shokeir phenotype with major CNS-malformations: clinicopathological report of two siblings.

Clinical and pathological features of two siblings of opposite sex with the Pena-Shokeir phenotype are reported. A detailed account of the prenatal and dysmorphological findings is given in one case. A broad range of deformations regarded as secondary to fetal hypokinesia was present, including a number of yet unreported findings. One case showed additional endocrine hyperplasia and left lung trilobation. Both siblings displayed extensive, highly similar CNS-abnormalities. The type and convergence of these malformations differ from previously reported cases and characterize a new familial subtype of the Pena-Shokeir phenotype.

Abnormalities, Multiple↗

Biochemical analysis of callus tissue in osteogenesis imperfecta type IV. Evidence for transient overmodification in collagen types I and III.

We analyzed tissue and cells from a stationary and a rapidly growing hyperplastic callus from a patient with osteogenesis imperfecta (OI) type IV and compared the results with those of compact bone and skin fibroblasts of an age-matched control. Collagen and protein contents per cell were low in the callus tissues and collagen I and III were overmodified as evidenced by an elevated level of hydroxylysine. The degree of lysyl hydroxylation was highest in those regions that appeared most immature by histological examination. Lysyl hydroxylation approached normal levels in collagen from the stationary callus and from the center of the growing callus. Overmodification of collagen was not seen in compact bone or cell cultures (neither skin fibroblasts nor callus cells) from the patient. Elevation of hydroxylysine in collagen from OI patients is generally attributed to mutations that delay triple helix formation. Our observations suggest that the varying degree of collagen modifications may occur in consequence of regulatory mechanisms during bone development and tissue repair. These mechanisms may be defective in some patients with OI as seen in this case with hyperplastic callus formation.

Adolescent↗

Isolation, characterization and immunological determination of basement membrane-associated heparan sulfate proteoglycan.

Basement membrane-associated heparan sulfate proteoglycan (HSPG) was extracted from isolated porcine glomerular basement membranes and purified by ion-exchange chromatography. The proteogycan was characterized by specific enzymatic digestions, by amino-acid analysis, by SDS-polyacrylamide gel electrophoresis and by density gradient centrifugation. Polyclonal antibodies were raised against the purified HSPG in rabbits. Antibodies were characterized by enzyme immunoassays, immunoprecipitation and immunohistological methods. They were shown to recognize specifically the core protein of HSPG from porcine, human and rat glomerular basement membrane but did not recognize HSPG from guinea pig or rabbit kidney. The affinity-purified antibodies did not cross-react with other basement membrane proteins like laminin, fibronectin or collagen type IV nor with chondroitin sulfate-rich or keratan sulfate-rich proteoglycans from human or bovine tissue. Using these antibodies an enzyme immunoassay was developed for determination of HSPG in the range of 1-100 ng/ml. Studies with cultured porcine endothelial cells showed that subendothelial basement membrane-associated HSPG may be determined with the enzyme immunoassay.

Amino Acids↗

[Immunohistochemical localization of various components of the basal membrane and interstitial collagen in diabetic nephropathy].

We analyzed the composition of the extracellular matrix in the glomeruli from 31 cases with different degrees of diabetic nephropathy by immunohistochemical means. While the enlarged mesangial matrix in diffuse glomerulosclerosis showed an increased staining reaction for the basement membrane components collagen IV and V, laminin and fibronectin, the staining pattern of the basement membrane associated heparan sulfate proteoglycan (HSPG) was markedly reduced. Early, small nodular lesions in diabetic glomeruli were similarly positive for most of the basement membrane (BM)-components, while HSPG remained absent. With an increase in the diameter of the noduli, however, the staining reaction for the BM-components diminished, while interstitial collagens V and III were present in these noduli in substantial amounts. Our findings provide evidence that the changes in the glomerular matrix in diabetic nephropathy may be divided into distinct and progressing stages of lesions. The reduced amount of HSPG even in slight, early lesions may represent the morphological correlate to the impaired filter function of the glomerular BM, while the occurrence of interstitial collagens within the glomeruli in late nodular stages may be regarded as the result of an altered pattern of expression of the mesangial cells.

Basement Membrane↗

Pathobiochemical aspects of diabetic nephropathy.

Diabetic nephropathy develops in many diabetic patients as consequence of glomerulosclerosis. On the basis of a series of recent observations it is suggested that a combination of metabolic and hemodynamic changes is responsible for the pathogenesis of diabetic nephropathy. Since the glomerular filtration unit has been characterized to consist of collagen type IV and minor components like laminin, fibronectin and heparan sulfate proteoglycan, influence of diabetes on basement membrane (BM) components has been studied. Biochemical alterations of glomerular BM consist of an increased nonenzymatic glucosylation of type IV collagen leading to unphysiological crosslinking. This, in turn, may result in alteration of the size selective properties of the glomerular filtration unit. Changes in composition of glomerular BM have recently been described. An increased synthesis of type IV collagen with concomitant decrease of heparan sulfate proteoglycan may lead to alteration of the charge selective barrier and consequently to increased permeability of the glomerular BM. Permanently unbalanced synthesis of BM components finally results in obliteration of the capillary lumen. In late state nephropathy intrinsic basement membrane components are no longer produced. Instead, massive accumulation of PAS positive material occurs.

Animals↗

[The significance of collagen in determining the age of a wound].

The aim of the present study was to find out whether the quantitative and/or qualitative analysis of collagen can be useful in the determination of the age of healing skin wounds in various body regions of patients of different ages and sex. The quantitative measurement of total wound collagen revealed no clear time-dependent changes. Immunohistochemical staining for collagen types I and III demonstrated the presence of type III as early as 2 days after injury. Procollagen type I was found in wounds beginning from 4 days on, while type I collagen was not present before 6 days after the injury. Immunohistochemical analysis of specific basement membrane proteins, collagen type IV and laminin, showed a reconstruction of the epithelial basement membrane beginning from on day 5, while a completely rebuilt basement membrane was found in most cases after more than 14 days, depending on the dimension of the wound and its treatment.

Adolescent↗

[Amniotic band syndrome associated with an acardiac malformation in a twin pregnancy. Apropos of a case].

We report herein a case of a twin pregnancy with one fetus showing an amniotic band syndrome, the other being an acardiac monster. This is, to our knowledge, the first case of this unusual combination. Both fetuses showed multiple severe malformations. According to the classification of Napolitani, one fetus had to be classified as "acardius anceps". The malformations of both bodies and the anomalies of both umbilical cords suggest a similar defect of the germinal disc, possibly occurring very early during the pregnancy.

Abnormalities, Multiple↗