Rejection nephropathy before and after therapeutic administration of cyclosporin A

During 1983 to 1986 41 patients were treated with Cyclosporin A (CyA) following kidney allotransplantation (TPL). 31 received the first (29 extra- and 2 intrafamilial) graft; in 10 there was second TPL, in 9 cases under high-risk conditions, where the first graft had been destroyed by (hyper)acute rejection or by rapidly progressive rejection with early vascular lesion. 21 needle biopsies and 5 excised grafts which had been collected 5 days to 18 months after TPL were examined by light microscopy and in addition 6 of the former also underwent electron and immunofluorescence microscopic study. The glomeruli showed discrete, inconstant segmental lesions but the ultrastructure also revealed severe general endothelial swelling. The tubular system had nonspecific degenerative changes of varying extent. In 11 patients focal cytoplasmic microvacuoles appeared in proximal tubular epithelia; there were also inconstant hyaline droplets, microcalcifications, and intratubular crystals. Electron microscopy revealed multiple round dense intramitochondrial inclusions in proximal tubules. The ultrastructure of the microvacuoles resembled that of "osmotic nephropathy". The rejection infiltrate and interstitial fibrosis of various degree did not essentially differ from those of conventionally treated grafts. In 7 patients cortical arterioles and small arteries exhibited a stenosing lesion (toxic?). In 3 cases metachromatic "mucoid" thickening of intima was prominent. Ultrastructure studies showed swollen endothelial cells with numerous globular dense bodies and a severe defect in the leiomyofibrils of muscle cells of the media. Hyperplasia of juxtaglomerular apparatus was apparent in 7 patients. Immunofluorescent microscopy of two biopsies from subsequently excised grafts visualized IgM, C3, and fibrinogen in small arteries and some glomerular capillary loops. Three early nephrectomies were caused by infarct-like necrosis. The discussion deals with differences between CyA- and conventionally treated grafts, diagnostic features, interpretation of findings, and measures following biopsy. In our patients with continual CyA-treatment no case of clinically and morphologically typical obliterative arterio-arteriolopathy (OA) and rapidly progressive irreversible rejection has as yet been noted.     

Influence of preexistent pyelonephritis on the development and manifestations of acute fatal glomerulonephritis

In a 39-year-old woman suffering for five years from chronic pyelonephritis with a stationary course, a sudden lethal renal failure occurred after an intercurrent febrile respiratory disease. The autopsy revealed scarred pyelonephritic kidneys with swollen hypertrophic areas. Microscopically, in sclerotic segments the glomeruli either were preserved or exhibited only various stages of vascular atrophy. Outside the pyelonephritic areas, however, massive subacute extra-intracapillary glomerulonephritis with typical crescents was apparent. — The role played by preexistent renal lesion in the pathogenesis of glomerulonephritis, and some problems involved in the diagnosis of coexistent glomerulo- and pyelonephritis, are discussed.     

Vascular lesions in human allotransplantated kidneys

Summary Sixteen patients with allotransplanted kidneys were examined by biopsy or autopsy during the last four years. In 5 patients there was conspicuous stenosis or occlusion of the cortical arteries and arterioles; in 4, the major interlobar muscular arteries were also involved. The vascular lumen was stenosed by hyaline deposits and edematous intimal thickening containing abundant erythrocytes, foam cells, and various mononuclear cells. In contrast, no striking thrombosis was present and fibrinoid deposits were scarce. The ultrastructure showed signs of a severe degeneration of both muscular and endothelial cells and an accumulation of cell fragments and debris but no fibrin or preserved blood platelets. In major muscular arteries there were dystrophic changes in the deep intima and media; in the subendothelial region muscular cells (newly formed?) preponderated. In the remaining eleven patients the arteries were normal or showed moderate hyaline and fibroelastic arterio-arteriolosclerosis.A severe obliterating arterio(lo) pathy (OA) means a grave prognosis, pointing to manifest or imminent renal insufficiency and forecasting the necessity of transplantectomy within a few months. The patients free of OA constitute a clinico-functionally nonhomogenous group, biopsies being performed for various reasons at various posttransplantation intervals; the average prognosis, however, is considerably more favourable. The pathogenesis of OA remains unclear as yet; the lesion offers, however, a rather striking morphological picture different from those of common arteriosclerotic and arteritic lesions.

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Zusammenfassung Im hiesigen Transplantationszentrum wurden in den letzten 4 Jahren 16 nierenallotransplantierte Patienten biopisch und/oder nekroptisch untersucht. In 5 Fällen fand sich eine schwere Stenose mit teilweiser Obliteration von corticalen Arterien und Arteriolen, der gleiche Befund in 4 Fällen auch an größeren interlobären Muskelarterien. Das Lumen der alterierten Gefäße zeigt jeweils eine hyalin und ödematös verquollene, von Erythrocyten, Schaumzellen und mononukleären Zellen durchsetzte Intimaschicht. Eine Thrombose oder Fibrinoidablagerungen werden selten oder gar nicht nachweisbar. Mikroskopisch finden sich schwere Endothel- und Muskelzelldegenerationen sowie eine Anhäufung von Zellfragmenten und Trümmerzonen. Dagegen werden Fibrin und intakte Blutplättchen vermißt. Größere Muskelarterien weisen eine schwere Dystrophie ihrer tiefen Intima- und Mediaschichten auf, im subendothelialen Raum überwiegen neugebildete Muskelzellen. — Die Nierenarterien und -arteriolen der übrigen 11 Patienten waren im wesentlichen gut erhalten. Sie zeigten lediglich eine diskrete bis mittelschwere hyaline bzw. fibroelastische Arterio-Arteriolosklerose.

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Dedicated to the 70th birthday of Prof. Dr. Antonín Fingerland, DrSc., Hradec Králové, Czechoslovakia.     

Identifying the Field of Health Communication

This empirical investigation addresses four paradigmatically framed research questions to illuminate the epistemological status of the field of health communication, systematically addressing the limitations of existing disciplinary introspections. A content analysis of published health communication research indicated that the millennium marked a new stage of health communication research with a visible shift onto macro-level communication of health information among nonhealth professionals. The analysis also revealed the emergence of a paradigm around this particular topic area, with its contributing scholars predominantly sharing postpositivistic thought traditions and cross-sectional survey-analytic methodologies. More interdisciplinary collaborations and meta-theoretical assessments are needed to facilitate a continued growth of this evolving paradigm, which may advance health communication scholars in their search for a disciplinary identity.     

BBK07 immunodominant peptides as serodiagnostic markers of Lyme disease

Lyme disease (LD) is a tick-borne infection caused by the bacterial pathogen Borrelia burgdorferi. Current diagnostic tests mostly use borrelial lysates or select antigens to detect serum antibodies against B. burgdorferi. These immunoassays are not entirely effective, especially for detection of early infection. We have recently characterized an in vivo-induced antigen, BBK07, as a serodiagnostic marker for LD. We now report that in a line blot assay, recombinant BBK07 protein-based detection is 90% sensitive and nearly 100% specific against B. burgdorferi infection in humans. Using an overlapping peptide library of 23 peptides encompassing full-length BBK07, we identified the immunodominant epitopes of BBK07 during human infection. We show that a select combination of amino-terminal peptides significantly enhanced BBK07-based diagnostic accuracy compared to that with the full-length protein. Although in enzyme-linked immunosorbent assay (ELISA) studies BBK07 peptides had overall lower sensitivity than established serodiagnostic peptides, such as the VlsE peptide C6 and OspC peptide pepC10, for the detection of early human LD, a subset of serum samples that failed to recognize either VlsE or OspC peptides were preferentially reactive to BBK07 peptides. These results highlight the fact that BBK07 peptides could be useful to complement the efficacy of VlsE and OspC peptide-based serodiagnostic assays. Finally, using a panel of canine sera, we show that BBK07 peptide is also effective for LD diagnosis in infected dogs. Together, our data show that peptides from the B. burgdorferi surface protein BBK07 are highly specific and sensitive serodiagnostic markers, and we suggest their future use in LD diagnostic assays.     

Achalasie bei HIV/HCV-Koinfektion

Esophageal involvement in the context of opportunistic infections in human immunodeficiency virus (HIV) positive patients is a frequent phenomenon. However, worldwide esophageal achalasia has been described only twice in HIV-infected patients. We report the case of a 44-year-old Caucasian patient with HIV and Hepatitis?C virus (HIV/HCV) coinfection who, within 2.5 years, displayed a progressive symptomatology with dysphagia, retrosternal pain, regurgitation as well as a considerable loss of weight before achalasia was finally diagnosed. Treatment was performed primarily surgically by means of laparoscopic Heller myotomy with an anterior 180° semifundoplication according to Dor. Histopathology of the specimens taken from the lower esophageal sphincter high-pressure zone proved alterations with abundant connective tissue and only scarce parts of the smooth muscular system without inflammatory infiltrations. In addition, the ganglia cells of the myenteric plexus as well as the interstitial cells of Cajal were significantly reduced. Interestingly, specific gene sequences of the hepatitis C virus could be detected in the esophageal tissue specimen. In contrast, analysis of specific HIV-gene sequences in the same tissue revealed a negative result. The possible but previously unknown relationship between esophageal achalasia and coinfection with HIV and HCV, also described as neurotropic viruses, will be discussed.     

Oral administration of Parabacteroides distasonis antigens attenuates experimental murine colitis through modulation of immunity and microbiota composition

Commensal bacteria have been shown to modulate the host mucosal immune system. Here, we report that oral treatment of BALB/c mice with components from the commensal, Parabacteroides distasonis, significantly reduces the severity of intestinal inflammation in murine models of acute and chronic colitis induced by dextran sulphate sodium (DSS). The membranous fraction of P. distasonis (mPd) prevented DSS-induced increases in several proinflammatory cytokines, increased mPd-specific serum antibodies and stabilized the intestinal microbial ecology. The anti-colitic effect of oral mPd was not observed in severe combined immunodeficient mice and probably involved induction of specific antibody responses and stabilization of the intestinal microbiota. Our results suggest that specific bacterial components derived from the commensal bacterium, P. distasonis, may be useful in the development of new therapeutic strategies for chronic inflammatory disorders such as inflammatory bowel disease.     

Borrelia burgdorferi complement regulator-acquiring surface protein 1 of the Lyme disease spirochetes is expressed in humans and induces antibody responses restricted to nondenatured structural determinants

Borrelia burgdorferi complement regulator-acquiring surface protein 1 (CRASP-1), the dominant factor H and FHL-1-binding protein of the Lyme disease spirochete B. burgdorferi, is implicated in pathogen persistence and was recently reported to be nonimmunogenic in humans. Here we show that serum samples from Lyme disease patients contain antibodies with exclusive specificity for nondenatured structural determinants of CRASP-1.