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PubMedDate not supplied

Pathological and laboratory findings in LEC/Otk rats that spontaneously develop hepatic injury.

The LEC strain of rats that spontaneously develops hepatic injury has been introduced into specific pathogen-free (SPF) conditions (SPF-LEC/Otk). The present communication describes the clinical and pathological features of the SPF-LEC/Otk rats. The characteristic features of these animals are as follows: (i) Jaundice develops in almost all rats with increase in the P-GPT level; (ii) The animals show episodes of jaundice, a high P-GPT level and liver cell necrosis, but only slight inflammatory cell infiltration; (iii) The liver cells show characteristic microvesicular fatty changes; (iv) The P-GPT level shows increases, first at 18 weeks and then at 25 weeks of age; (v) The rats show immunological disorders, such as deficiency of immunoglobulins, especially IgG1, and of helper T cells; (vi) Infectious agents such as viruses do not seem to be involved, although this possibility cannot be absolutely excluded; (vii) The immunological disorders are not directly associated with the occurrence of liver cell necrosis; and (viii) The pattern of inheritance (autosomal single-recessive trait) of the disease strongly suggests that it is due to a genetic metabolic disorder.

Alanine Transaminase↗

PubMedDate not supplied

Partial review of immunotherapeutic pharmacology in stem cell transplantation.

In two separate lymphoma populations, we examined immune reconstitution following high dose chemotherapy (HDT) and bone marrow transplantation (BMT). In the first study we followed immune reconstitution for one year after HDT and BMT. In the second study we examined the ability of the orally active immunomodulator, Bestatin to augment immune reconstitution following HDT and BMT. The studies on immune reconstitution following HDT and BMT were undertaken in a cohort of non-Hodgkin's lymphoma (NHL) patients (n = 35) and examined the peripheral blood (PB) leukocyte subsets and their in vitro functions. Our results demonstrate that monocyte and natural killer (NK) cell engraftment occurred more rapidly then did T cell reconstitution. We also observed a significant decrease in the CD4:CD8 ratio post-transplantation as compared to normal PB donors due to a decrease in CD4+ cells. In addition, following HDT and BMT, measures of T cell function (phytohemagglutinin [PHA] mitogenesis) and T helper cell activity (pokeweed mitogen [PWM] mitogenesis) were consistently depressed as compared to cells from normal PB. Further, we demonstrate a correlation between the loss of T cell function and the frequency of circulating monocytes, suggesting a cause-effect relationship. Despite the dysfunction in T cells following HDT and BMT, immune-modulating agents can still augment the immune function. One such drug is Bestatin (ubenimex), an inhibitor of aminopeptidase (AP) that binds to CD13 on macrophage/monocytes. To examine its immune modulatory activity after HDT and BMT, a dose finding (10, 30, 90 and 180 mg/day) phase Ib trial was conducted with 30 Hodgkin's disease (HD) and NHL patients who received no drug (control), or Bestatin daily for 60 days following BMT. In these studies, Bestatin administration was initiated when the absolute neutrophil count was greater than 250/mm3 on two consecutive days. These studies revealed that Bestatin significantly increased the PHA and PWM responses in a dose-dependent manner. Flow cytometric analysis revealed a significant increase in NK cells (CD56+), B cells (CD19+), as well as the CD4:CD8 cell ratio. The latter observation was associated largely with a depression in the percent of CD8+ T cells as opposed to an increase in CD4+ T cells. We conclude that despite the peripheral tolerance observed following HDT and BMT, Bestatin could significantly increase some, but not all, immune surrogates.

Adjuvants, Immunologic↗