[Heterogeneity of seminal vesicle amyloid. Immunohistochemical detection of lactoferrin and amyloid of the prealbumin-transthyretin type]. / Heterogenität des Samenblasenamyloids. Immunhistochemischer Nachweis von Lactoferrin und Amyloid vom Präalbumin-Transthyretin-Typ.

Localized depositions of amyloid in the seminal vesicles may occur in elderly men. Earlier immunohistochemical studies have failed to identify immunoreactivity of known amyloid material. In this autopsy study, all seminal vesicles of males older than 50 years were histologically examined to determine incidence and phenotype of seminal vesicle amyloidosis. Seven out of 50 patients (14%) showed depositions of amyloid in the seminal vesicles. These amyloid depositions as well as one additional case were characterized histochemically, immunohistochemically and electronmicroscopically. All but two of these patients (75%) showed simultaneously amyloid depositions in the heart. Lactoferrin immunoreactivity was found in 6 patients (75%). Lactoferrin is an iron-binding, bacteriostatic glycoprotein, which is produced in the seminal vesicles. Four patients with lactoferrin positive amyloid in seminal vesicle showed different amyloid depositions in the heart (immunoglobulin light chain amyloid AL-lambda). Two cases (25%) showed the same amyloid type in heart and seminal vesicles (prealbumin-transthyretin type amyloid). Our study shows that most amyloidoses of the seminal vesicles are organ-limited depositions of lactoferrin. These forms of localized amyloidosis have to be separated from senile systemic amyloidosis with seminal vesicle involvement.

Patterns of p53, erbB-2, and EGF-r expression in premalignant lesions of the urinary bladder.

Frequent recurrences and multicentricity of bladder cancer suggest that alterations of the urothelium distant from the tumor may be relevant to prognosis. In this study immunohistochemistry and fluorescence in situ hybridization (FISH) were used to examine expression of p53, erbB-2, and epidermal growth factor receptor (EGF-r), genomic aberrations, and tumor cell proliferation (Ki67 LI) in normal and dysplastic urothelium. Biopsy specimens examined included normal urothelium (n = 40), mild dysplasia (n = 34), moderate dysplasia (n = 18) and carcinoma in situ (CIS; n = 20). Several different oncogene expression patterns were found, only some of which were associated with dysplasia. EGF-r expression was equally frequent in normal and dysplastic urothelium and showed a strong association with Ki67 LI (P < .0001). A purely superficial erbB-2 positivity was present in both normal and dysplastic biopsies. However, diffuse erbB-2 positivity and p53 overexpression were both associated with advanced dysplasia (P < .0001 each). FISH analysis showed erbB-2 gene amplification and p53 deletions in selected CIS, as well as a marked chromosome 17 copy number heterogeneity in all six CIS examined. These findings indicate a considerable genomic instability in bladder CIS. They show that both erbB-2 and p53 are altered during malignant transformation. Detectable oncogene expression alone, however, is not diagnostic of malignancy in bladder urothelium.

Ciclosporin-associated arteriolopathy: the renin producing vascular smooth muscle cells are more sensitive to ciclosporin toxicity.

The pathogenesis of ciclosporin (Cs) induced renal vasoconstriction and CS-associated arteriolopathy (CAA) has not been fully explained. CAA affects the part of the afferent arteriole where renin is most abundant, and an effect by Cs on the renin producing smooth muscle cells leading to necrosis has been suggested. Forty transplant biopsies with CAA of different degrees were compared with 10 transplant biopsies from Cs treated patients without CAA, and with 10 "zero-hour" control biopsies (taken from the donor kidney at implantation). Immunoreactivity to renin by the ABC method was recorded in the arterioles. Compared to the control group there was a slight increase in the proportion of renin positive arterioles in the Cs treated group without CAA, but with increasing CAA there was a decrease in the proportion of renin positive arterioles. In the group of arterioles with CAA, we found that with increase in the severity of CAA, there was an increase in renin negative arterioles, indicating a loss of renin containing cells in these arterioles. This suggests that a large proportion of the necrotic cells in CAA has once been renin producing smooth muscle cells. Our findings support the possibility that Cs stimulates renin production, and that the renin producing cells are more sensitive to Cs toxicity.

p53 but not erbB-2 expression is associated with rapid tumor proliferation in urinary bladder cancer.

Tumor proliferation in bladder cancer is associated with tumor behavior. To assess the association between Ki-67 labeling index (LI), p53, and c-erbB-2 overexpression, formalin-fixed tissue samples of 160 patients with transitional cell carcinoma (TCC) of the urinary bladder were studied by immunohistochemistry. Ki-67 LI was strongly associated with tumor stage (P < .0001), tumor grade (P < .0001), and p53 status (P = .0014) but not with erbB-2 overexpression (P > .2). Ki-67 LI was higher in p53-positive tumors (19%) than in p53-negative tumors (14%) when all stages were compared. Ki-67 LI was independent of p53 expression in pTa tumors (p53-positive, 9%; p53-negative, 11%), showing that p53 overexpression alone is not sufficient to induce rapid tumor cell proliferation in pTa tumors. Ki-67 LI also was independent of p53 expression in pT2 to pT4 tumors (p53-positive, 20%; p53-negative, 23%), indicating that p53 expression is not necessary for rapid tumor cell proliferation in advanced stages. However, there was a striking difference in Ki-67 LI between p53-positive pT1 tumors (22.0% +/- 8.8 standard deviation [SD]; n = 20) and p53-negative pT1 tumors (9.7 +/- 8.3 SD; n = 22; P = .0001). These results suggest that increased proliferation in p53-positive pT1 tumors is caused by additional alterations that occur during tumor progression.

A new case of malignant mesothelioma of the tunica vaginalis testis. Immunohistochemistry in comparison with an adenomatoid tumor of the testis.

Malignant mesothelioma of the tunica vaginalis testis is an extremely rare tumor with 41 previously reported cases. The histological and immunohistological features of a new case in an 80-year-old patient are described and compared with an adenomatoid tumor of the tunica vaginalis testis, which is considered to be the benign variant of malignant mesothelioma. Both tumors revealed strong cytoplasmic staining for a panepithelial antibody (Lu-5) and membranous staining for BMA-120 (a mesothelial/endothelial cell marker) but yielded negative staining results with the endothelial cell markers QBend-10 (CD 34), Factor VIII-related antigen (vWF) and UEA-1. There was also negative staining for CEA, Ber-EP4, HEA-125 and Blood group related antigens A, B, H. An identical staining pattern was evident in normal and reactive mesothelial cells. Our data support a mesothelial rather than an endothelial derivation of the adenomatoid tumor studied.

The common pattern of cytokeratin alteration in alcoholic and cholestatic liver disease is different from that of hepatitic liver damage. A study with the panepithelial monoclonal antibody lu-5.

The patterns of cytokeratin as determined by murine monoclonal antikeratin antibody lu-5 (mAb lu-5) were quantitated in paraffin-embedded liver tissue from normal and diseased subjects. In tissue from healthy medical students, mAb lu-5 was found to decorate 2-4 periportal and 2-3 perivenular cell layers. Alcoholic liver disease was accompanied by a marked increase in intensity of mAb lu-5 antigen expression in zone I and III hepatocytes. Moreover, additional liver cells of both zones were progressively recruited, so that in advanced lesions all three lobular zones became positive. In mechanical as well as in drug-induced cholestasis, a similar increase of mAb lu-5 antigen expression was already observed in earlier stages of disease, including an earlier recruitment of zone II hepatocytes. In both alcoholic and cholestatic biopsies the intensity and extent of mAb lu-5 epitope expression increased with the duration and severity of disease. In primary biliary cirrhosis (PBC) and seemingly also in primary sclerosing cholangitis the increase and extent was more marked in zone I, the zone of assumed cholate accumulation. Changes in zone III, the territory of histologic cholestasis (bilirubinostasis), became evident only in late stages of PBC. Mallory bodies of alcoholic and cholestatic liver disease showed an identical mAB lu-5 antigen expression, thus giving rise to four different staining patterns. Changes of cytokeratin expression are similar in alcoholic and cholestatic liver diseases. In chronic viral hepatitis, however, cytokeratin alterations are discrete and restricted to precirrhotic/cirrhotic stages.

Immunocytochemistry in diagnostic cytology.

As the decision for immunocytochemistry is usually made on the basis of findings in Papanicolaou-stained smears and uncovering of the smears takes time, the immunocytochemical results are often reported with some delay. But they are of clinical interest only if reported within a short time. Therefore, immunocytochemistry on cytologic preparations must be carefully organized. The decision for immunocytochemistry must be made before the mounting medium has completely hardened to keep the time of uncovering short. The method of immunocytochemistry should fulfill the following prerequisites: 1. Cell sampling and fixation should be easy to handle for the clinician who sends the specimen to the laboratory. 2. Unspecific background staining, especially in cytologic preparations rich in blood and protein, should not occur. 3. The immunostaining method should be applicable to all kinds of cytologic material, fixed and stained smears included. 4. The nuclear structure of tumor cells should not be destroyed by the immunocytochemical procedure so that tumor cells after incubation are clearly distinguishable from normal cells showing a similar reaction as the tumor cells. There has hitherto been no such all-round method fulfilling all these prerequisites since the properties of the antigenic epitopes of the cells and of the antibodies recognizing them are too heterogeneous. Therefore several methods have to be considered and a variety of technical aspects such as fixation, storage of cytologic material, properties of tinctorial stains, of antibodies and of the antigenic epitopes must be studied to find out the two or three standard methods which meet the requirements in most cases. We recommend the ABC method for Papanicolaou-stained smears and the APAAP method for demonstration of lymphocyte markers. The indication of immunocytochemistry in diagnostic cytology is restricted by the limited number of specimens. Therefore, the following rules have to be observed: 1. The conventional light-microscopic examination must have priority over the immunocytochemical examination. 2. The cytologic specimens assigned for immunocytochemical examination must have been adequately fixed and stored. 3. As the number of smears is limited, the immunocytochemical examinations must be carefully planned and restricted to the absolutely necessary incubations. If possible, an informative smear has to be spared for documentation and future training of cytologists and cytotechnicians. 4. Immunocytochemical examinations in cytology are only justified if the diagnostic problem can be clearly defined. 5. The panel of antibodies should be selected carefully so that the results may give an answer to alternative questions. At least two antibodies should be applied.(ABSTRACT TRUNCATED AT 400 WORDS)

[Pathology of myxoid mitral valve degeneration: literature review and personal results]. / Pathologie der myxoiden Mitralklappendegeneration: Literaturübersicht und eigene Resultate.

Mitral prolapse is a parachute-like protrusion of the value into the left atrium. Almost always a myxoid degeneration of the valve is the base of such a prolapse. Myxoid degeneration is understood as dissolution of the collagenous fibrous layer and its replacement by acid glucosaminoglycans. An alteration of collagen is suspected as primary defect in this sometimes also inherited disorder. The electron microscope reveals fragmentation of collagen fibrils and elastic fibers and, within the myxoid material, free lysosomes, so called "matrix-vesicles". An isolated disturbance of collagen types I and III could not be detected by immunohistochemistry. Studies could also to date not demonstrate mutations in the genes coding for collagens.

Collagen type III glomerulopathy: a new idiopathic glomerular disease.

A new type of idiopathic glomerular disease is reported in a 49-year-old Italian woman who presented with uncharacteristic renal symptoms, i.e., hypertension and slight proteinuria. Clinical investigation excluded a familial renal disease and more specifically nail-patella syndrome. Diagnostic renal biopsy by light microscopy showed a picture similar to membranoproliferative glomerulonephritis. The enlarged glomeruli were lobulated, the peripheral basement membranes were thickened by the deposition of light-microscopically undefined material, cell proliferation was lacking. By electron microscopy, the material was nonhomogenous, partly granular partly fibrillar, containing typical collagen fibers. The latter were identified as collagen type III, to a lesser extent collagen type I. Review of the literature resulted in 12 similar or identical cases reported from Japan and one additional case reported in a white American female. Evidence of systemic disease is lacking. Etiology and pathogenesis are elusive. A progressive deterioration of renal function must be expected. Collagen type III glomerulopathy is suggested as term of this new type of idiopathic glomerular disease.

[Health education of adolescents against tobacco, alcohol and drug consumption. The Rapperswil Study (author's transl)]. / Gesundheitserziehung Jugendlicher gegen Tabak-, Alkohol- und Drogenkonsum. Wirksamkeit mittelfristiger Interventionen--Rapperswiler Studie.

In an 8-year longitudinal study, 368 pupils of the Jona-Rapperswil Vocational School aged between 15 and 17 years were subjected to a combined medical-educational half-yearly health education action against luxury articles and habit-forming substances in groups comprising the classes of each individual year. Before group session 34% were smokers, after the intensive instruction 23%. Before the session 62% drank, afterwards 34% took alcoholic drinks occasionally. No pupil had tried drugs during the six months instruction; the number of drug-takers remained constant at 3%. However, the desire to try a drug out of curiosity rose from 22% to 27%.