Malarial immunity in pregnant mice, in relation to total and unbound plasma corticosterone

A pregnancy dependent loss of malarial immunity is accompanied by an (excessive) increase of total as well as free plasma corticosterone. This loss of immunity was largely prevented by adrenalectomy. Moreover, malarial immunity was more sensitive to dexamethasone immunosuppression during pregnancy. Primary infections are more virulent during pregnancy and like in recrudescent mice, cause excessive total and free plasma corticosterone levels. Corticosterone may be considered an immuno-regulatory serum factor during pregnancy, the endocrine regulation of which is disturbed in pregnant, infected mice.     

Corticosterone regulation of the effector function of malarial immunity during pregnancy.

In the experimental Plasmodium berghei mouse model, as in human malaria, reduced maternal responsiveness and even loss of immunity were observed during pregnancy. Loss of immunity in the second half of pregnancy occurred during a period of elevated plasma corticoid levels. Further analysis showed that plasma corticoid levels were significantly higher in immunodepressed mice than in mice that remained immune throughout pregnancy. Plasma corticosterone levels differed increasingly from those in mice with persistent immunity towards recrudescence. In nonimmune infected controls, however, only a slight increase in plasma corticosterone, already present during the subpatent period, was measured. Blocking the maternal corticoid production by adrenalectomy delayed the increase of plasma corticosterone (fetoplacental origin) and reduced the number of mice that lost immunity during pregnancy considerably. The role of various plasma corticoid levels in the regulation of effector function of immunity during pregnancy is discussed.     

Synthesis and antitumor activity of cyclophosphamide analogs. 1. Benzo annulated cyclophosphamide and related systems.

Synthesis of 2-[bis(2-chloroethyl)amino]-3,4-dihydro-2H-1,3,2-benzoxazaphosphorin 2-oxide (2), which is a benzo annulated analog of cyclophosphamide [2-bis(2-chloroethyl)aminotetrahydro-2H-1,3,2-oxazaphosphorin 2-oxide (1)], was carried out in order to test for possible increased antitumor activity relative to 1 due to the presence of an oxidatively reactive C-4 benzylic site in 2. A structural isomer of 2, 2-[bis(2-chloroethyl)amino]-1,4-dihydro-2H-3,1,2-benzoxazaphosphorin 2-oxide (3), and cognate systems 2-[bis(2-chloroethyl)amino]-1,2,3,4-tetrahydro-1,3,2-benzodiazaphosphorin 2-oxide (4) and 2-[bis(2-chloroethyl)amino]-4H-1,3,2-benzodioxaphosphorin 2-oxide (5) were also prepared for comparative purposes. In vivo antitumor evaluation in mice against L1210 lymphoid leukemia indicated no significant activity for compound 2. Compounds 3 and 4 were likewise found to be inactive and only marginal activity was exhibited by 5.     

Biochemical characteristics and water exchange in the surface layer of human joint cartilage

We compared the contents of collagen, glycosaminoglycans, and various forms of water in the surface layer and whole tissue of joint cartilages of different localization. It was found that the surface layer is characterized by reduced content of glycosaminoglycans compared to the whole tissue and higher water-holding capacity due high content of bound water.     

The zebrafish spi1 promoter drives myeloid-specific expression in stable transgenic fish

The spi1 (pu.1) gene has recently been identified as a useful marker of early myeloid cells in zebrafish. To enhance the versatility of this organism as a model for studying myeloid development, the promoter of this gene has been isolated and characterized. Transient transgenesis revealed that a 5.3 kilobase promoter fragment immediately upstream of the spi1 coding sequence was sufficient to drive expression of enhanced green fluorescent protein (EGFP) in injected embryos in a manner that largely recapitulated the native spi1 gene expression pattern. This fragment was successfully used to produce a germ line transgenic line of zebrafish with EGFP-expressing myeloid cells. These TG(spi1:EGFP)pA301 transgenic zebrafish represent a valuable tool for further studies of myeloid development and its perturbation.     

Haematologic manifestations of the human immune deficiency virus (HIV)

A variety of haematologic abnormalities are associated with infection by HIV, the human retrovirus that is the primary aetiologic agent of the acquired immunodeficiency syndrome (AIDS). We have reviewed the haematologic findings in well-characterized cohorts of patients with AIDS, AIDS-related complex (ARC) and asymptomatic homosexual men at risk for this retrovirus. Anaemia, granulocytopenia and thrombocytopenia were found in increasing prevalence according to the severity of clinical disease associated with retroviral infection. Bone marrow aspirations and biopsies revealed frequent hypercellularity, dysplasia, plasmacytosis and lymphoid infiltrates. These marrow morphologic findings were strongly associated with anaemia and granulocytopenia. Review of transfusion records of patients with HIV antibodies revealed a 21% prevalence of a positive direct antiglobulin test. The pathophysiology of the observed haematologic abnormalities may involve direct retroviral infection of bone marrow progenitors, abnormal regulation of haematopoiesis and/or autoimmune phenomena.