Endotoxin and nanobacteria in polycystic kidney disease.

BACKGROUND: Microbes have been suspected as provocateurs of polycystic kidney disease (PKD), but attempts to isolate viable organisms have failed. Bacterial endotoxin is the most often reported microbial product found in PKD fluids. We assessed potential microbial origins of endotoxin in cyst fluids from 13 PKD patients and urines of PKD and control individuals. METHODS: Fluids were probed for endotoxin and nanobacteria, a new bacterium, by the differential Limulus Amebocyte Lysate assay (dLAL), genus-specific antilipopolysaccharide (LPS) antibodies, monoclonal antibodies to nanobacteria, and hyperimmune serum to Bartonella henselae (HS-Bh). Selected specimens were also assessed by transmission electron microscopy (TEM) and nanobacterial culture methods. RESULTS: LPS or its antigenic metabolites were found in more than 75% of cyst fluids tested. Nanobacteria were cultured from 11 of 13 PKD kidneys, visualized in 8 of 8 kidneys by TEM, and immunodetected in all 13 PKD kidneys. By immunodetection, nanobacterial antigens were found in urine from 7 of 7 PKD males, 1 of 7 PKD females, 3 of 10 normal males, and 1 of 10 normal females. "Nanobacterium sanguineum" was dLAL positive and cross-reactive with antichlamydial LPS and HS-Bh. Some cyst fluids were also positive for LPS antigens from Escherichia coli, Bacteroides fragilis and/or Chlamydia, and HS-Bh, as were liver cyst fluids from one patient. Tetracycline and citrate inhibited nanobacterial growth in vitro. CONCLUSION: Nanobacteria or its antigens were present in PKD kidney, liver, and urine. The identification of candidate microbial pathogens is the first step in ascertaining their contribution, if any, to human disease.

On the possible origin of extra-epithelial enterochromaffin cells by budding from the crypts of Lieberkuhn.

This study was undertaken to test Pierre Masson's still unconfirmed theory that extra-epithelial enterochromaffin cells in the gut arise in adult life by budding from the crypts of Lieberkuhn under conditions of low grade inflammation. Appendices (900) were reviewed and 19 were selected for serial section study because in random sections they showed lateral fusion of the crypts, one of the key features described by Masson. Ten specimens without crypt fusion served as controls. Sixteen of the 19 study specimens and one of the control specimens showed budding, averaging one bud in every 88 sections. Most buds were in direct contact with Schwann cells in the adjacent lamina propria and 45 per cent of them contained enterochromaffin cells. There was also histologic evidence linking buds and lateral crypt fusion to low grade inflammation. Masson's ideas are, therefore, confirmed insofar as the existence of buds and their relationship to enterochromaffin cells, Schwann cells, and inflammation is concerned. The actual separation of buds from the crypts to form extra-epithelial enterochromaffin cells has yet to be proved.

Extraepithelial enterochromaffin cells and Schwann cells in the human appendix.

To test earlier theories on the subject, extraepithelial enterochromaffin (EEEC) cells were sought in the mucosa of 500 appendixes and in the solid axial cores of 283 others whose lumina were obliterated over part or all of their lengths. The EEEC cells were lying free in the lamina propria of 53% of the specimens with intact lumina and in the axial cores of 49% of the obliterated specimens. In both locations they were invariably accompanied by Schwann cells and neurites, which were often present in markedly increased numbers. Therefore, because they occur so frequently in nonepithelial locations, enterochromaffin cells can no longer be considered as exclusively epithelial. Their close association with Schwann cells and neurites suggests that they may have some sort of neural function.

Epitheloid germinal centers: an acquired immunologic deficit?

The histologic structure of lymphoid tissue in cases of fatal infection was reviewed, and epithelioid germinal centers, completely devoid of the usual dark zone of rapidly dividing blast cells, were found in 16 infants and children, one of whom also had Reye's syndrome. Epithelioid change has been previously reported to occur in various childhood infections and in the sudden infant death syndrome. All reported cases have been fatal. In four additional cases there was toxic follicle alteration, or massive necrosis of germinal center cells. Toxic follicle alteration and epithelioid change have been found in childhood infections and sudden infant death syndrome, and some evidence of a pathogenetic relationship between the two was found in this study. It is concluded that epithelioid change represents a definite pathologic alteration of germinal centers associated with total destruction of a whole population of cells. It probably represents an acutely acquired immunologic deficit and therefore may well contribute to the thus far uniformly fatal outcome of the associated diseases.