Protective immunity induced in mice by detoxified salmonella lipopolysaccharide.

C3H/HeNMTV mice were immunised intraperitoneally (i.p.) with lipopolysaccharide (LPS) or detoxified LPS (D-LPS) derived from Salmonella typhimurium strain SR-11. In both cases, effective protection was achieved against a challenge dose of greater than 2 x 10(2) LD50 of the same organism given by i.p. injection. However, by comparison with LPS, approximately 6- to 10-fold more of D-LPS by weight was needed to protect mice to an equivalent degree. Histopathological studies showed that the initial lesions in infected mice protected with either LPS or D-LPS were composed of self-limiting abscesses which transformed into granulomas as the animals recovered. It is suggested that D-LPS may be modified to become a highly effective, non-toxic salmonella vaccine.

Intracellular destruction of salmonellae in genetically resistant mice.

Virulent Salmonella typhimurium, 2000 LD50, were injected intraperitoneally into inbred male A/J mice, genetically resistant to salmonella infection. Peritoneal exudate cells were harvested between 5 and 54 h after infection and examined by electronmicroscopy. Polymorphs were seen ingesting as well as digesting the pathogens as early as 5 h after infection. Macrophages were equally active in destroying the phagocytosed organisms throughout this period. In the meantime, the proliferation of salmonellae appeared to occur extracellularly in the peritoneal cavity as evidenced by their division.

Electronmicroscopic studies on the location of salmonella proliferation in the murine spleen.

Highly susceptible inbred male C57BL/6 mice were infected intraperitoneally with 2 x 10(7) cfu of a virulent Salmonella typhimurium strain. Tissue sections were taken from the spleen 2 and 3 days after infection for examination by electronmicroscopy. Rapid infiltration of polymorphs and macrophages was evident at the site of infection. These inflammatory phagocytes displayed avid destructive action against ingested bacteria. Bacterial multiplication occurred primarily in extracellular locations within sinusoids or in lesions containing disintegrating host cells.

Electron microscopic studies on the location of bacterial proliferation in the liver in murine salmonellosis.

Highly susceptible inbred male C57BL/6 mice were infected with 2 X 10(7) virulent Salmonella typhimurium by intraperitoneal inoculation. Samples of the liver were removed 2 or 3 days post-infection for examination by electron microscopy. Rapid infiltration of polymorphs and macrophages was observed in the site of infection. Visual evidence is presented to confirm the destruction of salmonellae within these inflammatory phagocytes as previously reported. The proliferation of the pathogens occurred in the extracellular locations of sinusoids and early lesions, and within hepatocytes.

Electronmicroscopy studies on the opsonic role of antiserum and the subsequent destruction of Salmonellae within murine inflammatory leukocytes.

Inbred female C3H mice were given, by intraperitoneal injection, 4 X 10(7) virulent Salmonella typhimurium organisms opsonised with specific antiserum. Peritoneal washings were obtained between 1.5 and 24 h after injection and examined by electronmicroscopy. Opsonised salmonellae were ingested rapidly by peritoneal exudate cells and were digested rapidly. The presence of antibody facilitated the phagocytic efficiency of the host cells. Destruction of ingested bacteria appeared to be an innate capacity of the host phagocytes independent of the presence of antibody.

Electronmicroscopy studies on the bactericidal action of inflammatory leukocytes in murine salmonellosis.

Inbred female C3H mice were given 2 X 10(7) cfu virulent Salmonella typhimurium by intraperitoneal injection. Peritoneal washings were harvested between 3 h and 72 h after infection and examined by electronmicroscopy. There was evidence of intracellular killing by polymorphs and macrophages. The degeneration of intracellular salmonellae was seen initially as enlarging central electron-lucent areas in the cytoplasm and peripheral condensation of cytoplasmic granules, followed by disruption of the bacterial envelope and disintegration of cellular structure. Alternatively, the initial injury appeared as an irregular and discontinuous bacterial envelope with compression of the bacterium and diffuse condensation of cytoplasmic granules. It was also evident that virulent salmonellae multiplied extracellularly in the peritoneal cavity of the infected mice.

Histopathological evidence for protective immunity induced by sonicated Salmonella vaccine.

The highly susceptible inbred C3H/HeNMTV mice were vaccinated with fragments derived from sonicated Salmonella typhimurium and then infected with the pathogen. All of the vaccinated mice survived an otherwise rapidly fatal challenge of 10(5) organisms, i.e., greater than 10(3) x mean lethal dose (LD50). The vaccine also protected two-thirds of the mice infected with 10(6) bacteria and extended the survival time of the remainder in their fatal disease. Histopathological findings showed that, like the control mice, the vaccinated and infected mice developed abscesses with infiltration of polymorphonuclear leukocytes in the organs of the reticuloendothelial system during the early stage of the infection. However, unlike the primary lesions in the control mice, the lesions of the vaccinated mice tended to be discrete and self-limiting. They began to transform into granulomas after the first week of infection. Recovery and regeneration of tissues were evident 3 weeks after the infection.

Short rib-polydactyly syndrome type II (Majewski syndrome): a case report.

The Majewski type of Short Rib-Polydactyly syndrome is a rare lethal dwarfism syndrome that has recently been recognized as a distinct entity. The full range of associated anomalies remains to be described. This case report details the clinical and autopsy findings in this condition and reviews the differential diagnosis of polydactylous dwarfing syndromes.

Histopathological study of protective immunity against murine salmonellosis induced by killed vaccine.

Swiss-Webster mice were vaccinated with heat-killed salmonellae and then were infected with virulent Salmonella typhimurium. Only 1 of the 18 vaccinated mice died from a challenge of 10(4) X the 50% lethal dose, and about 70% of them survived a challenge of 10(5) X the 50% lethal dose. Histopathological examinations of the lesions developed in these vaccinated mice showed that they followed the characteristic features of a primary lesion in murine salmonellosis. There was an early necrosis with infiltration of polymorphonuclear leukocytes and abscess formation within the first 6 to 7 days after infection. However, these abscesses remained small and discrete. By days 7 to 10, the lesions began to transform into granulomas, first with the appearance of peripheral mononuclear cells and then by the replacement of polymorphs. By the third week of the infection, minute and discrete granulomas were seen scattered in the spleen, liver, and lymph nodes. Beyond this stage, healing and tissue regeneration followed. Thus, the characteristics of infectious lesions developed in mice vaccinated with heat-killed salmonellae are distinctly different from those developed in mice protected by the avirulent vaccine.

The role of delayed hypersensitivity in the enhancement of host resistance to infection.

Swiss-Webster mice were vaccinated by the intraperitoneal route (i.p.) with Mycobacterium tuberculosis BCG and challenged i.p. 4-10 weeks later with 10(4) virulent Salmonella typhimurium in the presence or absence of purified derivative (PPD) of tuberculin. Normal control mice were similarly challenged. Such an infection was fatal to the normal mice within 12 days. BCG vaccination prolonged the survival time and protected about 36% of the salmonella-infected mice from death. In contrast, tuberculin sensitivity, elicited in the BCG-vaccinated mice, significantly increased the survival time and protected about 70% of the mice against an otherwise fatal challenge. When these experiments were repeated using an infective dose of 10(6) organisms, the protective effect of the tuberculin reaction became substantially reduced, but there remained a statistically significant improvement in the survival distribution of the challenged mice as compared with that among the BCG-vaccinated mice. The examination of peritoneal washings obtained from BCG-vaccinated mice stimulated with PPD showed that the enhanced resistance to salmonella infection was directly associated with a quantitatively increased influx of phagocytic leukocytes accumulating at the site of infection as a result of the elicitation of tuberculin sensitivity.

Pathologic findings in mucopolysaccharidosis type IIIB (Sanfilippo's sydnrome B).

The pathologic changes in a rare case of mucopolysaccharidosis (MPS) type IIIB or Sanfilippo's syndrome B (absence of alpha-N-acetylglucosaminidase) are presented, along with the biochemical findings. Comparisons were made with other reported cases of MPS III subtypes and related storage disorders in terms of clinical, light microscopic, electron microscopic, and chemical findings, and a correlation of the ultrastructural changes made with the severe neurological dysfunction noted in this disorder. At present, MPS III subtypes cannot be separated from one another by morphological means because the same expression and distribution of lesions may be encountered among differing subtypes.

The comparative histopathology of primary and secondary lesions in murine salmonellosis.

In a primary infection, Swiss-Webster mice were injected i.p. with 10(2) or 10(3) virulent Salmonella typhimurium. Multiple microscopic acute abscesses with predominantly polymorphonuclear leucocytes (PMNs) were seen in the liver and the spleen beginning on the 4th day after infection. By the 7th day, these lesions had become enlarged and were gradually transformed into granulomas with central necrosis and peripheral mononuclear cells. The animals usually died within 12 days with massive systemic infection and degeneration of the tissues. In contrast, it was necessary to inoculate 10(6) virulent salmonella i.v. into mice immunized with avirulent S. thphimurium in order to initiate microscopically observable lesions in the liver and the spleen. These secondary lesions were characterized by the early appearance of minute granulomas composed almost entirely of histiocytic cells. They remained small and isolated, usually without central necrosis. Subsequent regression of the lesions and regeneration of normal tissue occurred after the 2nd week following infection. The animals usually survived such a challenge infection.

Multiple vascular malformation in the "blue rubber bleb naevus" syndrome: a case with aneurysm of vein of Galen and vascular lesions suggesting a link to the Weber-Osler-Rendu syndrome.

A case of Bean's syndrome is reported in which a wide variety of vascular malformations are illustrated. Among these were multiple arterio-venous malformations including a so-called vein of Galen aneurysm. A comparison of this case with those in the literature suggests that the pathology in patients with Bean's syndrome may be more varied than heretofore recognized, and that an overlap between this syndrome and the Osler-Weber-Rendu syndrome may exist.