Aferhods: 24 fonnalin-fixed nonnal placentas (6th-40th week) and four hydatid moles (6th-10th week) were investigated. A double labelling method combined irnmunoperoxidase staining for the detection of proliferation antigens with monoclonal antibody ivllB 1 (Ki-67), and alkaline phospatase staining for the identification of macropha'ges using mab HAlI.156. The percentage of proliferating versus non-proliferating ~crophages in placental chorionic villous stroma was evaluated by two observers counting several hundred to thousand cells. Results: Proliferating macrophages were detected in nonnal placentas as well as in hydatid moles. There was an even di­stribution of proliferating macrophages in normal placentas. Prolifera­tion rate deJ::reases during gestation starting with 23% in the 6th week of gestation and ending with 1 % in the 40th week. In hydatid moles less proliferating as well as resting macrophages were present showing an irregular distribution. Conclusion: The ability of placental macrophages to undergo mitotic division was observed by Hofbauer in 1903 and by many later investigators. The double labelling technique presented here provides a simple semi-quantitative means to demonstrate the relative proportion of macrophages in different placentas. High proportion of proliferating macrophages in first trimester placentas as well as the presence of proliferating macropha­ges in hydatid moles suggests that these cells can also originate from the chorionic mesenchyme.

Arbeitsgemeinschaft Kinderpathologie, Freie Themen Working Group Pa~dopathology, Miscellaneous Topics

248 Intrauterine Death by Maternal Nicotine Abuse

Horn, L.-C., Emmrich, P., Rosch, A.; Leipzig

Smoking during pregnancy is associated with reduced birth weight and intrauterine retardation.

We report an intrauterine death in the 38. weeks of gestation. The fetal weight and length was under the 10th percentile. The 27 year old, healthy mother smoked 30 cigarettes during the whole pregnancy.

At autopsy were no fetal malformations and no inflammation. The placental sectional surface showed a pale component which takes 58,4 % of the whole organ. The microscopic slides of this part presented immature chorionic villies. The vessels of the stem villies showed a marked endangiopathia obliterans, sometimes with a plug-like occlusion of the lumen. Most of the peripher villies were avascular with a marked stromal fibrosis. The syncytiotrophoblast showed hypoxic alterations. The other non-pale part of the organ presented a compensatoric angiomatosis of the villous stroma. During pregnancy occured no gestosis or eclampia, no incompatibility and no viral in­fections. We assume that the intrauterine death is caused by ~xcessive maternal nicotine abuse with consecutive placental insuffi­cience, done by the mentioned placental mor­phology.

Abstracts· 291

249 STRUCfURAL AND CELLULAR COMPOSTION OF

SPIRAL ARTERIES IN NORMAL PREGNANCY AND

PREECLAMPSIA

T. Stallmach (a.G.), P. Orban (a.G.), S. Hassam (a.G.), J. Briner Institut fiir klinische Pathologie des Universitiitsspitals ZUrich

For a few decades it has been known that in preeclampsia major alterations can be found at the level of the placental bed; the spiral arteries remain with a narrow lumen and a muscular coat, furthennore degenerative changes can be seen. Spiral arteries in born placentae and placental bed biopsies were examined to analyse the physiological changes of spiral arteries during gestation and the pathological alterations with preeclampsia. Therefore the different cell types within and around the vessel wall were analysed using immunohistochemistry plus interphase cytogenetics in order to determine the fetal or maternal origin of all cell types detected. . It could be demonstrated that the physiological changes which make spiral arteries wide are correlated to the presence of fetal trophoblastic cells with complete destruction of muscular components, collagen type IV remains as the mayor non-cellular vessel wall component. Narrow spiral arteries in preeclamptic cases do not contain fetal cells but are infiltrated by maternal macrophages, the muscular coat is not completely destructed but obscured by deposition of hyaline material.

250 Gyral development of the fetal brain. A sonographic-anatomic study

D.Jacobs (a.G.)", D.Hofmann (a.G.)", J.H.Lu (a.G.)"·, S.Kowalewski (a.G.)', H.J.FOdisch"

Abteilung flir Neonatologie des Zentrums flir Kinderheil­kunde (Dir. : Prof. Dr.S.Kowalewski) Institut flir Kinderpathologie (Dir. :Prof.Dr.H.J .FOdisch) und Yang-Ming Medical College, Taipei (Taiwan)

The convolutional patterns of cerebral cortex are reliable criteria of brain maturation (Larroche, J. Neuroradiol. .8:93-108,1981). Correlation between post mortem sonography and neuroanatomy is established (Lu et aI., Pediatr. Radiol. 19:281, 1989). Methods: In a prospective study we processed 59 brains of fetuses, prematures, and newborns (20-40 weeks of gestation) and attempted to evaluate the cortical development of sulci and gyri. Comparison was made between sonograms of intact cerebral cortex post mortem and corresponding brain sections in 6 coronal and midsagittal planes. The chronologic changes of 56 different fissures, sulci, and gyri were evaluated by computer tabulated analysis. Results: Sonographic identification of most primary sulci lag definitely 2 weeks behind their macroscopic visuabilty due to localization, depth of the sulci and sensitivity of the method. Conclusion: Using schematic drawings and a scoring system, which consists of 4 primary sulci, 3 secondary sulci and 2 measured parameters, seem to fit clinical routine usage.

292 . Abstracts

251 The range of endomyocardial changes in childhood. Anette Musil (a.G.), H.-J. Holzhausen (a.G.), F. W. Rath Institute of Pathology, Martin-Luther-University Halle-Wittenberg Halle/Saale

Diseases of the endomyocardium in childhood are rare. Mor­phologically perceptible changes in this area, obtained through autopsy or bioptic investigations, are designed to ascertain a still unclarified or to confirm an assumed cardiac disease. Frequently these findings are accidental.

Pathologic changes of the endomyocardium may occur in all age groups of childhood and have been observed even in the fetal period in individual cases. They are to be expected in connection with metabolic diseases, in structural myocardial changes on a cel­lular level or as a consequence of primary lesions of coronary ar­teries and of inflammation. Primary tumours of the heart are exep­tionally rare.

The authors report on findings obtained from routine autopsies with morphologically detectable pathologic lesions of the endo­myocardium, partially employing electron microscopy. The spe­cific features of endomyocardial fibroses and the role of diseases of the small intramural arteries are dealt with in detail.

252 Aortic-left ventricular tunnel. Clinical (pre- and postnatal) and patbo-morphologic findings

G.Kn6pfle·, R.Bald (a.GT, Tr.Phi Le (a.G.)""·, D.Hofmann (a.G.)", H.J.F6disch·

Institut fUr Kinderpathologie (Dir.:Prof.Dr.H.J.FMisch) Ahteilung fUr Priinatale Diagnostik und Therapie der Frauenklinik (Leiter: Prof. Dr.M. Hansmann) und Ahteilung fUr Piidiatrische Kardiologie des Zentrums fUr Kinderheilkunde (Leiter: Prof. Dr. D. Redel) der U niversitat Bonn

Aortic-left ventricular tunnel, first puhlished hy Levy et al. in 1963 is a rare congenital cardiac malformation, defined as an ahnormal channel heginning in the ascending aorta above the right coronary orifice and ending in the left ventricular chamher below the right aortic cusp. We present the spectrum of primary and secondary patho-morphologic cardiac findings in two own ohservations and in 20 additional cases of aortic-left ventricular tunnel reported in literature. Furthermore special attention is given to the pre- and postnatal Doppler echocardiographic findings in a male neonate of 38 weeks' gestation (tirst own case) with regard to the possibility of antenatal diagnosis of the anomaly. Severe excentric left heart hypertrophy in a stillhorn fetus of 25 weeks' gestation (second own case) indicates the hemodynamic effectiveness of the ahnormal aortic-left ventricular connection even in early fetal life.

253 MYOGENIC FETAL ARTHROGRYPOSIS IN FOUR OFF­SPRINGS OF TWO UNRELATED TURKISH FAMILIES H. Keppl, N. Behm Pediatric Pathology Section, Institute of Pathology, University of Freiburg.

Four cases of fetal arthrogryposis, offsprings of two unrelated Turkish families, each with consanguinity between the parents, were investigated by radiography, autopsy, histology, histochemi­stry and immunohistology. The two female siblings, 18 and 22 weeks e.g. a., of family one both revealed multiple pterygia and hydrops. Histologically the skeletal muscles were dystrophic with marked evidence of muscle fiber degeneration and resorptive inflammation. The diaphragm was least involved. The two male siblings, 32 and 36 weeks e.g.a., of family two both revealed the Pena Shokeir phenotype. HistolO­gically only single fiber necroses were found in the skeletal mus­cles, while the diaphragm was most severely involved showing marked loss of muscle fibers and advanced fibrosis. Brain and spinal cord were found to be normal in all four cases. We thus diagnosed fetal arthrogryposis caused by akinesia/dyski­nesia of myogenic (myodystrophic) origin in all four cases. Exter­nal phenotype, onset of intrauterine manifestation, and histomor­phology of skeletal muscle involvement appear to be strikingly similar within the two siblings of each family, but are markedly different, when the offsprings of the two families are compared. These findings suggest that we are dealing in the two Turkish families with two different types of fetal myodystrophy, both of which appear to be inherited in an autosomal recessive mode, since there are besides the probands healthy siblings of equal sex in each family.

254 A NEW TYPE OF PERIGLOMERULAR NEPHROBLASTOMA­TOSIS IN PRUNE-BELLY-SYNDROME H. Schafer*, H. Altrogge (a.G.)**, J. Stahl schmidt (a.G.)*, H. Kabisch (a.G.)** *Institut fUr Pathologie und **Kinderklinik, Universitat Hamburg

In a 12 years old boy with Prune-Belly-syndrome bilateral nephrectomy was performed in advance of renal transplantation. This was planned because of chronic renal failure attributed to chronic pyelonephritis due to megaureters and hydronephrosis pre­viously treated by bilateral ureterocutaneostomia. In addition to muscular hypoplasia of ureters and abdominal wall, Prune-Belly­syndrome was represented by bilateral cryptorchism.

Surprisingly, histologic examination of both hydronephrotic kid­neys revealed a special type of panlobular multi focal nephroblasto­matosis selectively involving the periglomerularregions. Nephro­blastomatosis was extensive and ring-like around well-preserved glomerula with sometimes augmented capillary loops. Proliferated undifferentiated cuboid epithelia apparently were derived from epi­thelia of Bowman capsules forming papillary, tubular resp. glo­meruloid structures partly obliterating lumen of Bowman capsules. Electron microscopy and immunocytochemical marker pattern of proliferating epithelial cells corresponded to normal capsule epithelia except additional expression of vimentin and a high pro­liferation rate as shown by markedly increased Ki67-antigene posi­tivity. Other parts of the kidneys only showed some tubular cysts, slight deformation and budding of otherwise well-differentiated tubules and nephrocalcinosis due to previously operated tertiary hyperparathyroidism.

It is concluded that the presented, to our knowledge yet unde­scribed type of glomerulum-associated nephroblastomatosis may be explained by an arrest of maturation of Bowman capsule epithelia

with persistant formation of abortive capsular and glomeruloid structures. Pathogenesis and possible risc for development of nephroblastoma is discussed in view of the cytogenetical status of kidney tissue of the patient presently under investigation.

255 Focal and segmental glomerulosclerosis in sudden infant death- immunohistological and quantitative studies. G. Molz and W. Bar. Inst. of Legal Medicine ZUrich Focal and segmental glomerulosclerosis is characterized by focal sclerosis and hyalinization in scattered glome­rul i. In infants who died the sudden infant death (SID) increased numbers of sclerotic glomeruli are reported. As yet no reports are available regarding the nature of glomerulosclerosis in SID-infants we approached the hi­stopathology of the le~ions by employing immunohistolo­gical methods. Investigations were carried out on the renal cortex of 43 SID- infants and of 14 controls. For each child the relative number of sclerosed glomeruli was demonstrated in four microscopic fields of six sections, stained im­munohistologically and in two additional sections stain­ed with the v.Gieson-elastica method. The immunoglobu­lins demonstrated were IgM, IgA and IgG. Immunohistologically the incidence of sclerosed glomeru­li in infants up to the age of 26 weeks was about 5% for each of the immunoglobulins in SID-infants and about 7% in the controls resepctively. During the second half of the 1st year the incidences remarkable decreased. IgM, IgA or IgG deposits were presented in the sclerosed glo­meruli of·the SID-infants and of the controls in the first half of the 1st year only. The deposits of IgM were the scantist and those of IgA the most common, in quantities varying from 2.9% to 14.8% respectively. The incidence of sclerosed qlomeruli in sections stain­ed with the v. Gieson-elastIca stain was higher as com­pared with those stained immunohistilogically; the dOl'in­ward trend noted during the second half of the 1st year was present in the SID-infants only. The present results do not give any evidence suggesting that glomeruloscle­rosis plays a decisive role in the pathogenesis of sud­den infant death.

256 Tennstedt. Cornelia (a.G.)*. Bollmann. R. (a.G.). Chaoui . R. (a.G.)** * institut fiir Pathologie, ** Frauenklinik, "Abteilung Priinatale Diagnostik und Therapie", Medizinische Fakultiit der Humboldt­Universitiit zu Berlin (Charitel. Deutschland

A case of bilateral congenital cystic adenomatoid malformation (CCAM) of the lung Type Ill: Prenatal diagnosis and pathological fmdings

The prenatal diagnosis of a bilateral Type III CCAM is reported.

The pregnant women was referred in the 17th week of gestation because of a non-immunological hydrops fetalis (NIHF) with severe ascites and oligohydramnios. The chromosomal finding was normal (46, XV) at amniocentesis. The prenatal sonographic diagnosis was completed by color-doppler-sonography. With 19 weeks the termination of pregnancy was performed. The fetus was post­mortem examined.

Prenatal color-doppler-sonography showed dilated pulmonal veins and a small heart nestling among the large homogeneous mass of the lungs. The placenta was hydropic. The prenatal findings were confirmed by the post-mortem examination and no additional malformation detected. Microscopically, the small cysts were less

Abstracts· 293

than 0.5 cm in diameter and irregularly shaped. Small "pseudoglands" were lined by non ciliated cuboidal epithelium and separated from each other by a loose vascular stroma. The bronchiole-like structures were composed of ciliated cuboidal epithelium overlying a thin wall of smooth muscle fibers and elastic tissue.

Congenital cystic adenomatoid malformation may sometimes be visualised in utero during routine second trimester fetal ultrasonography or as part of the differential diagnosis in NlHF. Type III CCAM produces mediastinal shift associated clinically with severe respiratory distress and carries a poor prognosis.

257 Value of modern radiological techniques for pediatric pathology

U.Runge (a.G.)", D.Hofmann (a.G.)", L.Solymosi (a.G.)", H.Sittek (a.G.)", H,J.FOdisch·

lnstitut fiir Kinderpathologie (DiT. : Prof. Dr.H.J . Fodisch) und Radiologische Klinik (DiT.: Prof. Dr. M .Reiser) der U niversitiit Bonn

The performance of conventional radiographs for detection and/or documentation of skeletal disorders or abnormal calcifications of soft tissue has been part of routine diagnostic in fetal and perinatal autopsy for a long time. A further analysis of soft tissue structures on the contrary is not possible with this method and anomalies of internal organs and soft tissue, especially vascular malformations could only be exposed during. dissection. The aim of our study is to demonstrate which additional information could be obtained by new radiologic techniques such as MRI, CT, and angiography that could be helpful for the subsequent autopsy. We performed angiography and/or MRI and CT on several fetuses, prematures, and newborns with clinical and pathological suspect of cardio­vascular disorders, conjoint twins, chorangiopagus parasiticus twins, rare malformation of the spine, and tumours. Our results suggest that especially with angiography additional information could be obtained that on one hand permids specific preparation during subsequent autopsy, and on the other hand an excellent documentation of non bone malformations.

258 Morphological investigations in so-called asphyxial infiltrates in human placenta

P.Emmrich,H.Dalitz Institut fur Pathologie Univ. Leipzig 561 placentas of consecutive deliveries are investigated histologically in respect to aequivalents of asphyxial infiltrates. They arise from 520 newborn at term, 26 preterm and 15 postterm deliveries. In 88 of these cases we have found cellular infiltrates of different quanti~in the subchorial area as well as infiltrates around the great vessels, in the vessel wall of the umbilical cord and in the chorionic membrane. Diffuse leucocytic infiltration of the fetal membranes was seen in 5 cases. Vie have tried to find out any correlations between these morphological findings and the clinical intrauterine and neonatal

294 . Abstracts

symptoms. Clinical signs of neonatal! int~auterine asphyxia (e.g.acidosis) were present in in 39 cases (44,4 %) of these 88 placentas with cellular infiltrates. 34 cases are without pathological clinical changes both ante - or postnatal as well as durirlg labor. According to this results we believe, that there is no connection between antenatal, intranata l or postnatal asphyxia and these so-c alled asphyxial infil t r ates in toe human placenta.

Symposium V Modelle menschlicher Erkrankungen Experimental Models of Human Diseases

259 Abstract not received

260 GENETIC MODIFICATION OF CELLS BY RECEPTOR­MEDIATED GENE DELIVERY K Zatloukal (a.G.)*, E. Wagner (a G.), M. Cotten (a. G.), W Schmidt (a. G.), M. Berger (a.G.), M .L Birnstiel (a. G.), Research Institute of Molecular Pathology, Vienna, Austria, *present address, Institute of Pathology, University of Graz, Austria.

We have developed)'( gene transfer system which uses the receptor-mediated endocytosis route to deliver gene constructs into cells by binding the DNA to polylysine-modified transferrin and to polylysine-modified, replication defective adenovirus. In this context, the virus serves only as an endosome-disruption agent to ensure the intracellular release of the endocytosed DNA. T ransfections performed with this technique generate in a variety of cell lines and primary cells such as fibroblasts, endOIhelial cells and hepato~ytes high levels of gene expression. A major difference of this technique to conventional viral vectofs (retroviral and adenoviral) is that the gene construct is not a part of the viral genome so that replication defective and chemically inactivated virus is used. Moreover it is possible to deliver large genes (up to 48kb) and no interference between sequences of the virus and the gene construct are encountered.

This allows, for instance, the expression of the full length human factor VIII or a B-domain deleted factor VIII . Transplantation of transfected primary fibroblasts into the spleen of mice led to the generation of therapeutic piasma concentrations of human factor VIII in the treated animals .

Another possible application of this technique is to genetically modifY cancer cells so that they produce immunostimulatory factors. Mice which had been immunized with interleukin-2-transfected, irradiated cancer cells generated a sytemic immune response which protected them from tumor development at the implantation site of highly tumorigenic doses of cancer cells.

261 VIRUS INDUCED AUTOIMMUNITY: AN ANIMAL MODEL FOR DIABETES MELLITUS TYPE I H. Hengartner Institut fUr Exp. Immunologie UniversiUitsspital ZUrich CH-809l Ziirich

For some time various viruses have been suspected to be somehow involved in triggering of autoantibodies and autoimmune diseases. This however is difficult to proof, since it is almost impossible to molecularly demonstrate immunologically crossreactive antivirallantiself specificities as a consequence of breaking of tolerance which then leads to autoreactive inflammatory processes.

We developed a Tcr transgenic mouse which at the same time expresses exclusively on pancreatic P cells, also transgenically encoded, the viral antigen recognized by this Tcr. Upon virus infection of such healthy animals we were able to study autoreactive inflammatory processes leading to diabetes mellitus. In contrast to spontaneously developing autoimmune diseases the disease inducing autoreactive specificitiy could be elucidated as a viral nonapeptide presented by a MHC class I antigen. This allowed us to develop immunization protocols against diabetes mellitus by the use of peptides in these transgenic animals.

262 Transgenic Mouse Models for Human Retroviral Diseases

Adriano Aguzzi (a.G.)

Institute of Neuropathology, Department of Pathology University Hospital ofZiirich, Sternwartstrasse 2, CH- 8091 Ziirich Tel. (+41-1-) 255 2869, FAX: (+41-1-) 255 4402

The family of foamy viruses designates a group of retroviruses which share a specific morphology and provoke characteristic cytopathic effects in cultured cells. Like HTL V and HIV, foamy viruses are complex viruses encoding a number of ancillary genes in addition to gag, pol and env, including a transcriptional transactivator, bel-I. Foamy viruses are endemic in various primate species, and a human foamy virus (HFV) has been isolated from patients with neoplastic and degenerative diseases. Despite a growing body of hints to the pathogenicity of foamy viruses, until today it has not been possible to identify a disease specifically caused by foamy virus infection in primates and in humans. I will focus on the neuropathogenic properties of HFV in transgenic mouse systems. HFV trans genes encompassing the bel region exhibit a striking neurotropism. They are transcribed in a biphasic pattern during development and adulthood, and the adult phase of expression is associated with a progressive degenerative disease of the central nervous system and of striated muscle. These findings provide the first evidence of a pathology induced by HFV gene expression in a mammalian host and suggest that HFV might also acJ as a human pathogen in neurological diseases. HFV is capable of trans-activating HIV in vitro and in double transgenic mice, and HFV transgenic mice develop accumulations of syncytial giant cells in their brains similar to those of patients with HIV -associated encephalopathy. The relevance of these findings for human neuropathology will be discussed.