Role Of Host Factors Research Articles

The role of host factors for the chemotherapy of BCG infection in inbred strains of mice.

Host factors have previously been considered to play a role in the efficacy of "incomplete" antituberculous chemotherapy. We investigated this aspect using a model of intravenous infection with M. bovis-BCG in three inbred strains of mice. Viable splenic counts of bacilli (CFU) were monitored following a three week regimen of rifampicin (R) and isoniazid (H) given either immediately or from three weeks after infection. At the end of the immediate (0-3 weeks) therapy the spleens of all mice were sterile and only a minority of animals had demonstrable CFU's at 23 weeks after infection. However, following the delayed-onset (3-6 weeks) therapy we found a pronounced relapse of BCG growth which was about 10 times higher in CBA/Ca and BALB/C than in C57B1/6 mice. These results indicated that host immunity which developed during the first three weeks after infection may have aggravated the relapse of bacterial growth following chemotherapy. This interpretation was corroborated by the finding that the immunosuppressive drug cyclosporin given concurrently with R/H reduced the splenic viable counts of BCG.

The role of host factors in an outbreak of necrotizing enterocolitis.

During an outbreak investigation of necrotizing enterocolitis (NEC) in a neonatal intensive care unit, we identified nine definite and six suspected cases of NEC on the basis of histopathologic, clinical, and roentgenographic findings. Neonates of low birth weight (less than 1,250 g) had the highest incidence of NEC, supporting a role for prematurity in this disease. Patients with definite NEC and those with severe clinical features had significantly lower birth weights and postconception ages (gestational age at birth plus postnatal age at onset of NEC) than the patients with suspected NEC. In a case-control study using birth weight-matched control subjects, maternal toxemia was identified as a possible protective factor for NEC. To our knowledge, this is the first report of the relationship between NEC disease severity and postconception age. These findings also suggest that toxemia may be an important protective factor in NEC and should be examined in subsequent studies.

Host Factors in the Formation of Abscesses

The role of host factors in the formation of subcutaneous abscesses due to Bacteroides fragilis or Staphylococcus aureus was investigated in athymic nude mice, mice deficient in the fifth component of complement (C5D), and mice pretreated with cobra venom factor (CVF). CVF-treated mice, inoculated with B. fragilis, had abscesses 62% larger than those of control mice at day 4 (P < 0.01), but no significant difference was observed when S. aureus was used. Athymic nude mice had significantly smaller abscesses than control animals at both days 4 and 7 after inoculation with either organism. There were no differences in abscess size or in the accumulation of neutrophils at day 4 when C5D mice were compared with control animals for either organism. The results suggested that the activity of the alternative complement pathway may influence abscess size and that chemotactic factors other than the fifth component of complement can supervene in C5D mice to produce encapsulated abscesses. The absence of thymic factors did not prevent containment of abscesses.

Influence of γ Irradiation on the Development of Neoplastic Disease in Mice: I. Reticular Tissue Tumors

The influence of ${}^{137}{\rm Cs} \gamma $ irradiation on the development of reticular tissue neoplasms was investiged using male and female RFM/Un mice. The relationship between radiation dose and incidence of thymic lymphoma for females was complex, and no simple model described the relationship over the entire dose range. Over the range 0 to 25 rad linearity could be rejected and a dose-squared model described the data, while over the range 50 to 300 rad the response was linear. Males were less sensitive to induction of thymic lymphoma than females and their dose-response relationship was less complex with a linear response predominating. Males were more sensitive than females to induction of myeloid leukemia, with the age-adjusted incidence at 300 rad reaching 20% in males but only 5% in females. The response was linear for both sexes. The age-adjusted incidence of reticulum cell sarcoma decreased with dose in both male and female mice. The role of host factors in determining the type of neoplasm as...

Role of host factors in the pathogenesis of Salmonella-associated arthritis in rats.

To evaluate the roles of the infectious agent and the host in the pathogensis of Salmonella-associated arthritis (SAA), 1O(3) to 10(6) heat-killed Salmonella enteritidis were injected directly into involved carpal joints in normal and actively immunized rats and in hosts adoptively immunized by the intravenous transfer of spleen cells from syngeneic donors with ongoing SAA. As many as 10(6) living Salmonellae invariably failed to generate more than a transient inflammatory response in normal rats. The regression of acute joint swelling was accelerated in both types of immunized hosts. The intensity and duration of acute inflammation evoked in normal rats by 10(6) and 10(9) heat-killed Salmonellae did not exceed the response elicited by 10(3) living organisms. In sharply contrasting results, however, a chronic arthritis became established in a significant number of actively and adoptively sensitized rats after the intra-articular injection of 10(9) heat-killed organisms. No Salmonellae were recovered from these adoptively sensitized rats although small numbers of organisms has been present among the spleen cells in the transfer inocula. Taken together, these results indicate the obligatory involvement of host factors in the mediation of this chronic arthritis and virtually eliminate any likelihood that joint damage in SAA is due to the directly destructive effects of intra-articular infection.

Experimental pneumococcal meningitis: III. Chemotactic activity in cerebrospinal fluid.

Chemotactic activity was assayed in CSF of rabbits with pneumococcal meningitis to further characterize the inflammatory response in this infection. CSF chemotactic activity was detected in increasing levels for 72 hr after infection. Activity was stable at 56 degrees and was inactivated by agents which denature proteins. Gel filtration demonstrated two chemotactically active fractions in infected CSF with mol wts of approximately 3000 and 11,000. Bacterial products appear to account for a portion of the observed CSF chemotactic activity, but the role of host factors remains to be clarified.

The role of host factors in mouse trophoblastic tissue growth

By means of 800 r whole-body x-irradiation, host defensive and immunologic responses were heavily suppressed. Fertilized ova from C57BL/6J, A/HeJ, and white albino mice were transplanted to the kidneys of x-irradiated mice from the same or different strains. At the time of peak growth the number of living trophoblastic cells in irradiated animals was higher than in nonirradiated animals. No malignant changes in trophoblastic cells were observed. This suggests that environmental factors related to the immunologic and defensi ve state of the host plays a significant role in the degree of growth, prolifera tion, and life-span of trophoblastic cells.

Tumor Autograft Responses in Patients with Glioblastoma Multiforme

T HE role of host factors in mal ignant disease has long intrigued cancer investigators. More recently, emphasis has again been placed on immunologic factors of the host. Much of the work on this aspect of the disease was carried out in experimental aninmls using t ransplantable tumors and a vas t amoun t of l i terature has been accunmlated on the subject. The interested reader is referred to the excellent reviews of Gofer, 9 Snell, 27 and Hauschka . ~6 These are quite comprehensive and present three fairly distinctive viewpoints. F rom this work on animals, a great deal has been learned about the genetic and immunologic factors involved in rejection of t ransplants . For example, abrogat ion of the immune mechanism m a y accelerate the appearance, growth and metastas is of a malignant tumor . In addition, some degree of resistance against t ransplantable tumors in animals m a y be obtained by act ive and passive immunizat ion procedures. In the human, there is both direct and indirect evidence tha t host factors play a role in the progress of a mal ignant disease. The most d ramat ic examples are found in those cases of authent ic , spontaneous regressions of mal ignant neoplasms. 5,15,2~ Other evidence is suggested by the following: (1) Prolonged survival of pa t ients af ter incomplete removal of their cancer or the sudden appearance of widespread metas tases m a n y years following apparen t ly successful t r ea tmen t of the primary lesion, s (2) Regression of proven