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We have previously shown that monoclonal antibodies specific for a 280-kd protein (gp280) concentrated within the coated pits of renal and yolk sac brush border-induced fetal malformations, whereas antibodies specific for gp330, another coated pit protein with a similar distribution, had no deleterious effect on embryonic development. In this study, we show that gp280 and gp330 are closely related proteins, as indicated by: 1) similarities in peptide maps obtained after cyanogen bromide cleavage, 2) immunological cross-reactivity related to a minor contingent of antibodies that do not have teratogenic activity, and 3) asynchronous but related expressions during ontogenesis. During the early stages of development, the expression of the two glycoproteins was limited to (gp330) or predominant in (gp280) the clathrin-coated pits and intermicrovillar areas. In the pre-implantation embryo, gp330 was expressed by trophectodermal cells, which became negative in day-6 embryos trapped in endometrial infoldings. At this stage, gp280 and gp330 were both simultaneously detectable at the apical pole of the first entoblastic cells and remained expressed by the brush border of visceral yolk sac epithelial cells until the end of pregnancy. In addition, gp330 was expressed by amniotic cells and neurectodermal structures. During nephrogenesis, in contrast, the expression of gp280 and gp330 by the intermicrovillar areas of the proximal tubule cell was the result of a complex maturation process. gp280 and gp330 were diffusely distributed in S-shaped bodies in the presumptive areas of the glomerulus, proximal tubule, and distal tubule (gp330). During development of the nephron, the pattern of expression became progressively restricted to the proximal tubule and glomerulus (gp330), and selective localization in the intermicrovillar areas was only achieved in filtrating nephrons.

Fetal malformations constitute a major problem of public health. Unfortunately the known causes do not account for more than 50% of the cases observed. The potential role of immune mechanisms is suggested by experimental studies in the rat indicating that antibodies reactive with the yolk sac induce fetal malformations. In this study we show that these antibodies are specific for a 280 kDa protein expressed only in the kidney and the yolk sac by cell structures associated with the formation of endocytic vesicles. We further show that a similar protein is expressed in man by the yolk sac, the kidney and the trophoblasts. The possible role in pathology of antibodies against the human protein is discussed.

Experimental studies performed in the rat over the last three decades have shown that antibodies raised against kidney or yolk sac, which, in the rat, surrounds the embryo and serves as a placenta during the major part of pregnancy, induced fetal resorptions or malformations. It is generally considered that the teratogenic antibodies decrease internalization and degradation of maternal proteins by yolk sac epithelial cells leading to an inadequate supply of nutriments to the embryo. These observations demonstrating the pathogenic role of antibodies to fetal envelopes are of great potential interest in clinical pathology since most cases of fetal malformations in humans are of unknown cause. The authors have recently shown that the key teratogenic antibodies in the murine system were directed against a 280 kDa-coated pit protein (gp280) specific for the brush border of epithelial cells lining the renal proximal tubule and the yolk sac. This observation allows for the unique opportunity to search for a similar system in humans. In this study, the presence in humans of a protein closely related to murine gp280 is shown, as indicated by extensive immunologic crossreactivity, close apparent molecular weights, strong homology of bidimensional peptide maps, and restricted distribution at the organ and subcellular level. In addition to kidney and yolk sac, human gp280 was also detected within the coated pits of the placental syncytiotrophoblastic cells. When introduced in an in vitro rat embryo culture system, antibodies to human gp280-induced developmental anomalies in a dose-dependent manner. These observations indicate that the antigenic component of the murine model is present in humans and can give rise to heterologous antibodies that cause developmental anomalies, suggesting that the experimental model might be of significance in human pathology.

Eosinophils immunopositive for bombesin tetradecapeptide were detected by means of light and electron microscopy in human and rat gastrointestinal tract and pulmonary tissue. This immunoreaction was only evidenced after the use of acetic acid-containing fixative such as Bouin's fluid. The dependence of this immunostaining on fixatives and time course were extensively studied. This immunoreaction promotes mainly one epitope probably associated with the C-terminal sequence. This epitope seems also to be present in other neuropeptides such as substance P (SP) and, to a lesser extent in chemotactic factors like formyl peptide (fMLP) or eosinophil chemotactic factor of anaphylaxis (ECF-A). At the electron microscopic level, the immunopositivity was associated with eosinophil membranes.

The detection and typing of human papillomaviruses on cervical smears were performed by means of a new application of the polymerase chain reaction allowing easier and faster detection of the amplification product. This application consisted of a combination of two series of amplifications and the use of primers labelled with biotin and with 125 iodine on a reporter group for the second amplification. The final amplification product was detected by counting the radioactivity after incubation of the media in avidin-coated tubes. This test was compared with conventional methods of detection by electrophoresis and Southern blot and its specificity was confirmed. The study of a series of 52 patients demonstrated a higher prevalence of type 16 in relation to type 6/11 and 18 and a correlation between the degree of dysplasia and the frequency of oncogenic types 16 and 18. This new application could facilitate studies of the prevalence of HPV in large series of cervical smears.

Immune glomerulonephritis (GN) progresses in three phases. Induction corresponding to the development of immune response; transduction characterized by the appearance of immunological reactants in the glomerulus, and mediation responsible for glomerular lesions and proteinuria. Studies of experimental models have resulted in significant advances in our understanding of these phases. The most striking acquisitions concern the genetic control of GN and its link with the major histocompatibility system; the identification of target antigens involved in Goodpasture's syndrome and in experimental epimembranous GN; the re-evaluation of the role played by circulating immune complexes in the in situ formation of immune complexes in the glomerular capillary wall; the identification of numerous mediatory systems (notably cytokines) which play an important part in glomerular inflammation and in the development of fibrosis. These advances may lead, in the short- or medium-term, to interesting therapeutic novelties.

We have previously reported the production of monoclonal antibody (MAb) 1BE12, which recognizes a glycoprotein in breast-cancer cells. In the present work, 1BE12 reactivity was tested by immunohistochemistry in bladder carcinoma (92 cases) and in non-tumoral bladder samples (15 cases). In 71% of bladder tumors, more than 30% of cells were intensely stained by 1BE12. The percentage of reactive cells was higher in cancers invading the muscle than in more superficial tumors (p = 0.039). In non-tumoral bladder, immuno-staining, when present, was usually confined to the superficial layers with a low number of cells stained (less than 30%) in 13/15 cases. Slot blots, performed on urine samples from 43 bladder-cancer patients and 21 healthy controls, were quantified by densitometry scanning. We found higher optical density (OD) values in urine from muscle-invasive-cancer patients than in urine from more superficial tumors and healthy controls, with a significantly different distribution (p = 0.005). The urinary antigen was detected by immunoblotting with 1BE12 as high-molecular-weight species (greater than 150 kDa). The reactive glycoprotein could thus be purified by immunoaffinity and FPLC filtration from the perchloric-acid-soluble fraction of urine from patients with invasive bladder carcinoma. The availability of purified antigen will allow us to quantitate our assay, in order to evaluate its potential use as a prognostic indicator in bladder-cancer patients.

An immunoultrastructural study has been undertaken for analysis of the extrarenal localization of two brush border (BB) glycoproteins of 90 kd and 330 kd expressed by glomeruli. In previous studies on renal tissue, it has been shown that gp 330 is restricted to coated pits and BB intermicrovillar invaginations, whereas gp 90 is diffusely distributed on epithelial cell membranes and in addition expressed on glomerular endothelial cells. At variance from observations made in the kidney, gp 330 and gp 90 are mainly expressed on different epithelial cell types: gp 330 is found on the coated pits of the epithelium lining the epididymis and on the entire surface of the microvilli of Type II pneumocytes, whereas gp 90 is detected on the gut brush border and the biliary pole of hepatocytes; gp 90 is also found on endothelia lining all distal capillary beds studied in heart, lung, liver, and spleen. These observations thus indicate that gp 90 is expressed by a wide variety of cell types, all associated with high membrane turnover. Conversely, gp 330 has a restricted distribution at the organ, cellular and subcellular level and may be related with a defined system of receptor-mediated endocytosis.

Blood and bone marrow abnormalities accompanying cancers have been known for a while, without yet being understood. The study of 89 patients having lung cancers leads to the following observations: thrombocytosis is frequent and should be considered as a diagnostic criterion; anemia is often associated and we have noticed a correlation between the two. The bone marrow abnormalities shown on biopsy are also frequent, presenting mainly (54/104) as irritative type. This histological pattern becomes a criterion of prognosis, since one should interpret it as a bone marrow reaction to the implantation of cancerous cells. Lastly, no relationship has been found between the blood count and the bone marrow pattern.

After a clinical and pathological study of 55 cases of granulomatous hepatitis, the authors are trying to understand the data so that they can predict the etiology of the granulomas. The authors must insist on the necessity of homogeneity in clinical data, histological findings and ethnic origins.

The bronchogenic small cell carcinoma has histological characteristics. They concern the nucleus, the cytoplasm and the cytoplasmic membrane. An ultrastructural study reveals a great diversity in aspect and cellular components.

The authors have previously reported the production of monoclonal anti-brush border antibodies defining two glycoprotein (gp) antigens of 90 and 330 kd which are also expressed on glomerular cells and may thus be of significance for in situ formation of immune complexes. The 330-kd antigen is involved in Heymann's nephritis, whereas the 90-kd antigen induces transient glomerular immune deposits. In this report, the authors describe the renal ultrastructural localization of the two antigens, which are both detectable on brush border and glomerular epithelial cells but assume contrasting patterns: gp 90 is diffusely present on the cell membranes, whereas gp 330 is concentrated in the intermicrovillar region and within the coated pits. Their localization within proximal tubular cells, on the membrane of intracytoplasmic vesicles, suggests that they are involved in endocytosis. In addition, gp 90 is expressed on endothelial cells lining glomerular capillaries. These observations may help us to understand the formation and different kinetics of immune glomerular deposits.

Four cases of hepatic granulomatosis with positive Yersinia serologic tests are reported. In one case, the Wright serodiagnostic tests were also positive. In the three other cases, no other likely etiology was demonstrated. The authors recall the main causes of hepatic granulomatosis, diagnostic criteria of Yersiniosis infections, and the possible occurrence of simultaneous positive serodiagnostic tests for Yersinia enterocolitica type 9 and Brucella abortus.

Over eight years the authors recorded 46 cases of hepatic tuberculosis. Most cases occurred in patients from black Africa. Forty-five patients had at least one extrahepatic tuberculous localization. Moderate cholestasis, without jaundice, found in 75% of patients, was the main biologic disorder. Upon histologic examination, five different types of granulomas were found. Each one has a specific predictive value concerning the outcome of the tuberculous infection.

In order to analyze the initial steps involved in the formation of subepithelial electron-dense immune deposits, the authors induced passive Heymann's nephritis in rats by intravenous injection of monoclonal or polyclonal antibodies to the relevant antigen, a 330,000-dalton brush border protein also expressed within coated pits of glomerular epithelial cells. Whereas both mono- and polyclonal antibodies induced deposits detectable by indirect immunofluorescence, electron-dense deposits were only found in glomerular capillary walls of rats injected with polyclonal antibodies. Immunoultrastructural analysis confirmed the subepithelial location of heterologous IgG: monoclonal antibodies were essentially confined to the coated pits of glomerular epithelial cells, whereas polyclonal antibodies were detected in coated pits and in the subepithelial electron-dense deposits. In the face of an excess of circulating antibody, gp 330 was not detectable in the deposits, but a striking increase in the number of endoplasmic reticula positive for gp 330 was found. The results indicate that highly cross-linked immune complexes formed by polyvalent antibodies on the epithelial cell surface are necessary for the induction of subepithelial electron-dense deposits.

This study of 96 bone biopsies carried out in 84 patients with various malignant solid tumours showed 27 normal bone marrows, 21 hypoplastic marrows, 34 irritant marrows and 14 metastatic marrows. All the patients in the last group and 75% of those with signs of irritation already had other metastases. Tolerance to chemotherapy was better in the normal marrows than in the other cases. There was a significant relationship between the irritant or metastatic or metastatic aspect and the existence of peripheral leucoerythroblastosis (metastatic marrows) or increased platelets (irritant appearances). A significant difference existed during the first five months of survival between these cases with a metastatic marrow and those with an iritant marrow. Bone biopsy should, in our opinion, form part of the routine investigation of cancer patients. It may identify metasine investigation of cancer patients. It may identify metastases where radiography and bone scans have failed.

The steps in the ultrastructural changes that occur in new cilia formation in tubal epithelium have been well demonstrated in animals. In women, it is difficult to show cilia growing again and some authors deny that new growth occurs. Transmission electron microscopy studies on 32 specimens have shown that human new growth of cilia does occur. It arises in the midst of a cellular population which has as its characteristic a cytoplasm that is more clear than those of the neighbouring cells. Different ultrastructural aspects can be described. They resemble those that have been demonstrated in different animal species. On the other hand no mitoses have been shown. We will study the correlations between plasma hormone levels, the numbers of tissue receptors and the appearance of these clear cells in another article.

A patient with Hodgkins disease developed successively, a thrombocytopenic purpura, a polyneuristis and a pneumopathy, during a period of remission, and over a period of time lasting 3 months. The authors discuss the possibility of cytomegalovirus being the causative agent.

A microsurgical technique was used to transplant the tube and the ovary in the rat. 49 autografts were carried out (in a pure line of Lewis strain) to study histologically the results of cold ischaemia and the functional future of the graft in the form of pregnancies. 40 hybrid allografts Lewis-DA were transplanted in Lewis or DA rats. 19 animals that were not treated allowed us to study the phenomena of rejection histologically. 21 further rats were treated with Cyclosporin A to study their fertility. The histological results of temporary cold ischaemia are minimal and come down to atresia of the active antral follicles of the cohort. None of the histological structures of the tube seemed to suffer from cold ischaemia that lasted 20 minutes. The average size of the litter for the autografts was 6.4 baby rats with an index of implantation of 0.65. Where no treatment was given, allografts were very quickly rejected. Giving Cyclosporin A allowed the allografts to be tolerated in 60% of cases. 5.6 baby rats per litter were obtained with an index of implantation of 0.65. Cyclosporin A in an immunosuppressive drug which is not teratogenic in animals and is not cytostatic. It inhibits immune responses at the cellular level as well as the production of lymphocyte T dependent antibodies. This study shows again the value of transplants for treating tubo-ovarian sterility.

Although membranous glomerulonephritis (MGN) has been long considered as a prototype of glomerulonephritis (GN) due to the deposition of circulating immune complexes (CIC), a growing body of evidence indicates that immune deposits can also be formed in situ and implicate antigens expressed by glomerular epithelial cells (GEC). Some of these antigens have recently been identified. The first one, gp330 - a 330-kd glycoprotein restricted to the coated pits of GEC and renal brush border (BB) - is responsible for Heymann nephritis, a rat model of MGN. However, it is absent in the human glomerulus and is therefore probably not involved in human cases of MGN, at least in those due to in situ formation of CIC. In addition, by raising monoclonal antibodies against rat and rabbit BB, we have isolated two other BB proteins also expressed on GEC. The latter, respectively identified as dipeptidyl peptidase IV (90 kd) and enkephalinase (85 kd), can serve as targets for the formation of short-lived immune deposits. Since they are also detected on human GEC, they might play a role in the pathogenesis of MGN in man.

During autopsies a few number of cases with coronary involvement by specific lesions of Horton's disease are found. It is very unusual that they may be responsible of death. In this case a white woman 79 years old present all symptoms and findings of temporal arteritis. Temporal artery biopsy proved affection. After prednisone therapy was started a tong necrosis appears and a myocardial infarction happens with collapse and death. Autopsy examination showed giant cell arteritis involving a coronary branch near myocardial fresh infarction. Four other cases of literature are summarized. In four times corticosteroide were started but coronary involvement was not stopped and coronary specific lesions responsible of death.

Between January 1981 and December 1983, a prospective therapeutic trial of detorubicin (14-diethoxyacetoxy-daunorubicin [DTR]) was conducted in 40 patients with histologically proven malignant mesothelioma (MM). DTR was given intravenously at 40 mg/m2 on days 1, 2, and 3 for five 21-day cycles, then 40 mg/m2 once every 21 days. Thirty-five patients (32 with pleural MM, 3 with peritoneal MM) were eligible. The overall median survival from onset of chemotherapy was 17 months. Complete relief from chest pain was observed in 8 of 15 cases (53%). Of 21 patients with measurable disease, there were 2 complete responses (10%) and 7 partial responses (33%). Median duration of response was 30 weeks. Congestive cardiac failure developed in two patients after 1100 and 1600 mg/m2 of DTR, respectively. Hematologic toxicity was moderate. This study demonstrates that DTR is effective against MM.

The authors report two studies : 1) Retrospective : study of liver biopsies in 44 Africans : 22 were HBs Ag positive and 22 HBs Ag negative ; 10 of the HBs Ag positive subjects were found to have chronic persistent hepatitis (CPH), 4 chronic active hepatitis (CAH) and 3 cirrhosis ; 2 of the HBs Ag negative subjects were found to have CPH and 3 CAH ; as far a biological findings are concerned, only the CAH and cirrhosis groups differed from the control group, with higher prothrombin times, transaminase levels and gammaglobulin levels. 2) Prospective : study of the incidence of HBs Ag carriage in 168 Africans ; 17.8 % of them were found to be carriers ; no correlation was found between HBs Ag carriage and S. haematobium schistosomiasis or hemoglobinopathies.