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Zusammenfassung: Hintergrund: Die autologe Transplantation retinal er Pigmentepithelzellen (RPE) nach der Entfernung der choroidalen Neovaskularisationsmembran (CNV) im Rahmen der subretinalen Chirurgie ist eine zukunftsorientierte Behandlungsmethode der AMD. Ziel der vorliegenden Studie war die Untersuchung möglicher Zusammenhänge zwischen den Eigenschaften der entfernten Membranen und der postoperativen Entwicklung der Sehschärfe bei den behandelten Patienten. Material und Methoden: Untersucht wurden die Morphologie der CNV-Membranen und die präoperative Membrangröße bei 19 AMD-Patienten, die mittels subretinaler Chirurgie mit autologer RPE-Zell-Transplantation behandelt wurden. Alle Patientinnen zeigten postoperativ entweder eine Sehverbesserung oder eine stabilisierte Sehschärfe. Die Membranen wurden in Serienschnitten nach einem standardisierten Schema untersucht, im einzelnen wurde der Anteil an Matrix, das Ausmaß der Neovaskularisation und die Dichte des entzündlichen Infiltrates sowie der Anteil an RPE bestimmt und semiquantitativ gescort. Die Membrangröße wurde präoperativ mittels Fluoreszeinangiographie (FLA) gemessen. Die gewonnenen Daten wurden mit der postoperativen Visusentwicklung verglichen. Ergebnisse: Alle Membranen wurden in der präoperativen FLA als okkult bzw. prädominant okkult klassifiziert. Hinsichtlich des postoperativen Verlaufs ließen sich die Patientinnen in 2 Gruppen aufteilen. Gruppe I umfaßte 7 Patienten mit Visusverbesserung von ≥ 2 Zeilen, Gruppe II die restlichen 12 Patientinnen mit stabilisiertem Visus von ± 1 Zeile. Die mittlere Membrangröße betrug 6,19 ± 1,33 mm in Gruppe I bzw. 6,41 ± 1,87 mm in Gruppe II (nicht signifikant). Rezidive wurden nicht beobachtet. Histologische Untersuchung: Alle 19 Membranen zeigten einen hohen Anteil an extrazellulärer Matrix (2+/3+). Eine ausgeprägte Neovaskularisation mit hoher Mikrogefäßdichte (MGD) fand sich in 13/19 Biopsien; diese war in der Regel assoziiert mit einem mehr oder weniger dichten, überwiegend lymphozytären entzündlichen Infiltrat (14/19). Bei 6/19 Membranen handelte es sich um minimal vaskularisierte und weitgehend zellfreie Narben. 15/19 Fällen enthielten reichlich RPE-Zellen mit einer Prävalenz bei Patientinnen der Gruppe II. Klinischer Verlauf: Verglichen mit der postoperativen Visusentwicklung zeigten weder Membrangröße noch morphologische Parameter einen signifikanten Zusammenhang. Schlussfolgerung: Aus der vorliegenden Pilotstudie mit 19 Patientinnen ergibt sich, dass offensichtlich andere Faktoren als Größe und Morphologie von CNV-Membranen die postoperative Visusentwicklung bestimmen. Eine mögliche Prävalenz eines höheren Gehaltes von RPE-Zellen in der Gruppe jener Patientinnen, die postoperativ nur mit der Stabilisierung, aber nicht mit der Verbesserung der visuellen Funktionen reagiert haben, wird derzeit genauer untersucht. Summary: Purpose: We have recently described combined subretinal surgery and simultaneous autologous transplantation of RPE as a therapeutic option for the treatment of CNV in patients with advanced AMD. The purpose of the present study was to determine whether the size and morphology of the membranes were correlated with patient outcome. Methods: We selected 19 AMD patients, which underwent combined subretinal surgery and autologous transplantation of RPE. All patients had improved or stabilized visual acuity in follow-up after surgery. The membranes were prepared for conventional histology and evaluated for their morphological composition on serial sections applying a semiquantitative score of 0, 1+, 2+ and 3+ to the following parameters: amount of acellular matrix, neovascularization/ microvascular density (MVD), cellularity with special reference to inflammatory cells, and presence of RPE. These data including membrane size as determined preoperatively by fluorescein angiography (FLA) were correlated with postoperative visual acuity. Results: By preoperative FLA all lesions were classified as clinically predominantly occult. Regarding postoperative outcome we divided all patients in two groups. Group I with visual improvement of 2 and more lines comprised 7 patients, and group II with unchanged/stabilized visual acuity of ± 1 line the remaining 12 patients. Mean membrane size was 6.19 ± 1.33 mm in the group of patients with, and 6.41 ± 1.87 in the group without visual improvement, respectively. Recurrences did not occur. Histology: All 19 membranes contained a significant amount of acellular matrix (scores 2+/3+); a prominent neovascularization/high MVD was present in 13/19 specimens and was usually associated with a high degree of cellularity, i.e. a moderate or marked inflammatory component predominated by lymphocytes (14/19). 6/19 membranes presented as minimally vascularized and acellular scars. In 15/19 cases a significant amount of RPE cells was present in the excised membranes; this prevalence was especially high in the group II. Outcome: When compared to the development of visual acuity after therapy, neither FLA findings, nor histopathologic features of the membranes were predictive. Conclusion: In a pilot study of 19 patients with advanced AMD/CNV treated with combined subretinal surgery and autologous RPE transplantation features other than membrane morphology and membrane size seem to determine patient outcome. The tendency for a higher amount of RPE cells in the group of patients without improvement is currently under investigation.

Using the techniques of approximation and factorization of convolution operators we study the problem of irregular sampling of band-limited functions on a locally compact Abelian group G. The results of this paper relate to earlier work by Feichtinger and Gröchenig in a similar way as Kluvánek's work published in 1969 relates to the classical Shannon Sampling Theorem. Generally speaking we claim that reconstruction is possible as long as there is sufficient high sampling density. Moreover, the iterative reconstruction algorithms apply simultaneously to families of Banach spaces.

Abstract Heat shock proteins (HSPs) have been shown to represent potential target molecules for T‐cell‐mediated allograft rejection in heart and kidney transplants. In the present study, we therefore investigated the expression of HSP subtypes 60, 72, and 73 in normal kidneys and qualitative and/or quantitative changes in rejected renal allografts. Six normal kidney tissue specimens, three biopsies from patients with minimal change nephritis, as well as 37 biopsies and eight transplant nephrectomy specimens of patients with renal allograft rejection were studied. Type and severity of rejection were assessed according to the Banff classification. Immuno‐histochemical demonstration of HSP expression was performed using specific monoclonal antibodies after wet autoclave antigen retrieval on sections from either Carnoy‐fixed (biopsies) or formalin‐fixed (transplant nephrectomies) and paraffin‐embedded tissue. The expression was scored in a semiquantitative manner. All three subtypes were found to be constitutively expressed in normal kidney tissue and in non‐inflammatory minimal change nephritis, albeit with a characteristic compartmental and cellular distribution. Rejection resulted in a higher immunohistochemical scoring for all three HSP subtypes in compartments in which they were normally present; in addition, a de novo expression of HSP60 was found in the vascular compartment and, moreover, infiltrating mononuclear cells were strongly immunoreactive for HSP60 and HSP73. Only quantitative differences were observed for HSP72 immunoreactivity. These results indicate that rejection episodes are paralleled by an increased but differential expression of HSPs in the glomerular, tubular, and vascular compartments of the kidney. This enhancement as well as the de novo appearance of HSP60 on vascular endothelial cells might explain the presence of HSP‐reactive T lymphocytes in rejected allografts.

Es wird über den experimentellen Stand der retinalen Transplantation, den Hintergrund, Problematik der Abstoßungsreaktion und die Entwicklung einer eigenen Technik der autologen RPR-Transplantation berichtet. In this article we report about the rationale, experimental background, the problem of immune reaction and the development of a technique to transplant autologous RPE cells into the subretinal space.

In the study of Weyl–Heisenberg frames the assumption of having a finite frame upper bound appears recurrently. In this article it is shown that it actually depends critically on the time–frequency lattice used. Indeed, for any irrational α>0 we can construct a smooth g∈ L2(R) such that for any two rationals a >0 and b >0 the collection (gna, mb)n, m∈ Zof time–frequency translates of ghas a finite frame upper bound, while for any β>0 and any rational c> 0 the collection (gncα, mβ)n, m∈ Zhas no such bound. It follows from a theorem of I. Daubechies, as well as from the general atomic theory developed by Feichtinger and Gro¨chenig, that for any nonzero g∈ L2(R) which is sufficiently well behaved, there exist ac>0, bc>0 such that (gn a, m b)n, m∈ Zis a frame whenever 0 < a < ac, 0 < b < bc. We present two examples of a nonzero g∈ L2(R), bounded and supported by (0, 1), for which such numbers ac, bcdo not exist. In the first one of these examples, the frame bound equals 0 for all a >0, b >0, b <1. In the second example, the frame lower bound equals 0 for all aof the form l· 3− kwith l, k∈ N and all b, 0 < b <1, while the frame lower bound is at least 1 for all aof the form (2 m)− 1with m∈ N and all b, 0 < b <1.

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Two cases of infantile liver cirrhosis of unknown origin occurred in a circumscribed rural area of Northern Germany. Both children had increased dietary copper exposure. The search for additional cases of what appeared to be idiopathic copper toxicosis (ICT) revealed a cluster of affected infants in this region, raising questions about the relative importance of genetic and environmental factors that are considered to be etiologic. We gathered clinical and pathologic data concerning the patients, analyzed the pedigrees of affected families, and searched for possible environmental factors contributing to the pathologic process. We encountered 8 cases of infantile liver cirrhosis in 5 families in Emsland, a circumscribed and predominantly rural area of Northern Germany; ICT was definitely proven in 2 cases. Clinical presentation and liver pathology in 6 additional cases were consistent with the diagnosis of ICT. Pedigrees of affected families revealed complex relationships with occasional consanguinity of parents, suggesting autosomal recessive inheritance. The households were served by private wells with water of low pH flowing through copper pipes, suggesting the possibility of increased alimentary copper exposure. These findings support earlier conclusions that ICT develops when an infant with a genetic predisposition is exposed to a copper-enriched diet. (J Pediatr 1999;135:189-96)

Microvessel density was recently reported to be an independent correlate of tumour stage in whole mount prostatectomy specimens. This prompted an investigation of whether the quantitation of tumour microvessels could also be reliably applied to prostatic core biopsies, as a presurgical determinant of local tumour extension. The study was performed on a series of 46 unselected patients with prostatic adenocarcinomas undergoing radical prostatectomy. Intratumoural microvasculature was highlighted immunohistochemically using an antibody against CD31 and subsequently evaluated at ×400 magnification in both biopsies and corresponding prostatectomies. The highest microvessel count was reported for each case. Ten cases (22 per cent) had to be excluded because of insufficient measurable tumour areas in core biopsies. The remaining 36 cases (16 pT2; 20 pT3) showed a high degree of correlation between microvessel density in biopsies and prostatectomies (P<0·0001). Similarly, pre‐ and post‐operatively determined microvascular counts correlated well with tumour stage (P<0·0001). Furthermore, the median microvessel density in core biopsies and tumours, i.e., 34, distinguished well between organ‐confined and organ‐extending tumours (positive predictive value for pT3 tumours 94·4 per cent; sensitivity 85 per cent). These data indicate that the evaluation of microvessels in core biopsies, eventually combined with other parameters, could be a reliable method for the individual prediction of the post‐surgical tumour stage of prostatic adenocarcinoma. © 1997 John Wiley & Sons, Ltd.

Summary Recent studies have provided us with new insights into the natural history of female bladder cancer as well as the behaviour of the isolated urethra after cystectomy. Based on more than 16 years of experience with orthotopic lower urinary tract reconstruction to the urethra in men, a similar approach was attempted in women with transitional-cell cancer of the bladder. Refinements in the technique of cystectomy and subsequent intestinourethral anastomosis based on anatomical, histological, and clinical studies are described that should improve postoperative results in women undergoing anterior exenteration and creation of an orthotopic neobladder to the urethra. Our findings in a series of 11 patients are presented and compared with data from other institutions. Improved postoperative continence and micturition without compromise of the oncological outcome may be a result of preservation of the entire lateral vaginal walls, nerve-sparing dissection of the bladder neck and proximal urethra, removal of 1 cm of proximal urethra en bloc with the cystectomy specimen, and a J-omentum flap or an additional attachment of the anastomosed intestinal pouch to surrounding pelvic structures. Taken together, our average of 90% daytime and 73% nighttime continence, 90% spontaneous residual-free micturition, and 100% patient satisfaction without compromise of the surgical oncological outcome seems to justify the creation of an orthotopic neobladder in selected women with bladder cancer.

Great progress has been made in developing thermodynamic equations for high-nitrogen steels. Much of this work has centered on the effects of alloy composition on nitrogen concentration. Most of the currently produced high-nitrogen steels are formed by high-pressure melting. This joint U.S. Bureau of Mines, SRIM, and SIM study presents recent attempts to include the effects of pressure on the thermodynamic expressions used to determine the nitrogen concentration in Fe-Cr-Mn-Ni alloys.

The intermediate filament of mature human Sertoli cells is vimentin. A co-expression of vimentin together with cytokeratin has been demonstrated in Sertoli cells during embryonal development and under pathologic conditions in adult testes. We analysed the presence of vimentin, cytokeratin, and desmin in Sertoli cells of fetal testes (n=20), in seminiferous tubules of cryptorchid testes (n=10) and adjacent to testicular germ cell tumours (n=47) using specific monoclonal antibodies and single and double-labelling immunohistochemistry. During embryonal development prominent cytokeratin expression disappears after the 20th week of gestation. Interestingly, we also found desmin in immature intratubular Sertoli cells between weeks 11 and 14. In adult cryptorchid testes and in peritumour tubules, desmin was also prominently present in Sertoli cells in the vast majority of the cases investigated, as well as vimentin and cytokeratin co-expression. This first description of desmin immunoreactivity may shed some light on the ontogeny of human Sertoli cells and demonstrates that this cell type is able to express three types of intermediate filaments in a complex manner.

A 6-year-old girl with acquired immunodeficiency syndrome (AIDS) had extensive alveolar echinococcosis. Diagnosis was proved by needle biopsy of a specimen from affected liver tissue. The case was characterized by the unusually young age of the patient and more specifically by the absence of any detectable parasite-specific humoral and cellular immune response at diagnosis or later. Thus the present case indicates that a marked immunodeficiency caused by AIDS may substantially contribute to the rapid proliferation and early manifestation of the disease. In patients with pediatric AIDS and living in areas endemic for Echinococcus multilocularis , alveolar echinococcosis should be considered in intrahepatic tumorlike lesions even if the result of immunodiagnostic testing is negative. (J Pediatr 1997;130:320-3)

Carcinoid tumours (bronchial and intestinal) were analyzed by immunoblotting for the presence of chromogranin A, B and secretogranin II. In all tumours an antigen corresponding in electrophoretic behaviour to adrenal chromogranin A was present. Lung carcinoids (3 out of 5) contained a relatively high concentration of a proteoglycan form of this antigen in addition. Chromogranin B was found in all tumours. In one and two dimensional immunoblotting it appeared identical to the corresponding adrenal antigen. Secretogranin II was also present, however concentrations (especially in intestinal carcinoids) were low and variable. Furthermore, in intestinal tumours it differed from the adrenal antigen by having a slightly higher molecular size and a more alkaline pI. Immunohistochemistry revealed that the tumour tissues stained positively for all three antigens. For secretogranin II the staining in intestinal tumours was relatively weak and quite variable. These results should provide a defined basis for immunohistochemical screening of carcinoids for the chromogranin/secretogranin antigens.

Detailed investigation of cell growth and nucleolar organizer region associated argyrophilic proteins (Ag-NORs) is necessary to asses a possible impact of Ag-NOR quantification on the diagnosis and prognosis of tumours. In this study, cellular proliferation of the transitional-cell carcinoma cell line HOK-1 was modulated over a period of 11 days by starvation and subsequent medium addition. Proliferation was determined daily by DNA flow cytometric estimation of S-phase fraction (SPF) and mitotic index (MI) calculation. The number and area of interphase Ag-NORs were quantified by automated image analysis daily and the number of Ag-NOR bearing chromosomes in metaphase was counted. In interphase nuclei, Ag-NOR area showed a highly significant correlation with SPF (p<0.0001) whereas interphase Ag-NOR number showed significant correlation with MI (p<0.05). A positive relationship between the number of Ag-NOR bearing chromosomes in metaphases and cellular proliferation was also observed. There is variability in Ag-NOR quantity during interphase and metaphase depending on growth conditions in vitro. Correlations of the number of interphase Ag-NORs with the MI on one hand and Ag-NOR area with SPF on the other provide further evidence that distribution and quantity of Ag-NORs are strongly influenced by the cell cycle phase within the structural-functional unit of the nucleolus.

Abstract: Great progress has been made in developing thermodynamic equations for high-nitrogen steels. Much of this work has centered on the effects of alloy composition on nitrogen concentration. Most of the currently produced high-nitrogen steels are formed by high-pressure melting. This joint U.S. Bureau of Mines, SRIM, and SIM study presents recent attempts to include the effects of pressure on the thermodynamic expressions used to determine the nitrogen concentration in Fe-Cr-Mn-Ni alloys.

Summary In the present study methods are described for the analysis of the genomic structure of DNA isolated from tissues that have been stored up to several years as air-dried or stained bone marrow smears, bone marrow biopsies in “Histicon”, chromosomal preparations in fixative or as formalin fixed tissues embedded in paraffin. By application of the new techniques clonal B- and T-cell disorders, Philadelphia chromosome translocations and ras oncogene mutations in pancreatic carcinomas could be detected. Thus, these DNA extraction procedures may open new avenues to pathological archives and enable the analysis of samples when fresh material is not available.