Clinical and laboratory characteristics of HIV-1 infection in Zimbabwe.

To define the impact of human immunodeficiency virus (HIV) infection in Africa, clinical and laboratory investigations were conducted on 265 HIV-seropositive outpatients in Zimbabwe. Twenty-four of the study subjects were asymptomatic (ASX), 124 had persistent generalized lymphadenopathy (PGL), and 117 had AIDS-related complex (ARC). HIV infection was assessed by commercial ELISA, Western blots, synthetic peptide ELISA, and measurement of p24 antigen. Serum immunoglobulins, lymphocyte mitogen responses, and CD4+ cell numbers were obtained in 54 sequential patients. Compared to seronegative subjects, mean CD4+ cell numbers were decreased and serum immunoglobulins, particularly IgM and IgG, were increased in all groups of seropositive subjects. Lymphocyte proliferative responses to phytohemagglutinin and concanavalin A decreased progressively in ASX, PGL, and ARC patients and were significantly lower in PGL and ARC patients compared to seronegative controls. Generalized lymphadenopathy was present in 234/265 (88%) of patients. Lymph node biopsies in 100 patients demonstrated follicular hyperplasia in 97 and Mycobacterium tuberculosis in 3. Of 165 patients followed for a median of 6 months, 5 developed the acquired immune deficiency syndrome (AIDS). Symptoms of ARC, low CD4+ cell number, and p24 antigen were predictive of the development of AIDS in Zimbabwe.

Clinical and laboratory characteristics of HIV-1 infection in Zimbabwe

To define the impact of human immunolodeficiency virus (HIV) infection in Africa; clinical and laboratory investigations were conducted on 265 HIV-seropositive outpatients in Zimbabwe. Twenty-four of the study subjects were asymptomatic (ASX); 124 had persistent generalized lympademopathy (PGL); and 117 had AIDS-related complex (ARC). HIV infection was assessed by commercial ELISA; Western blots; synthetic peptide ELISA; and measurement of p24 antigen. Serum immunoglobulins; lympocyte mitogen responses; and CD4+ cell numbers were obrtained in 54 sequential patients. Compared to seronegative subjects meab CD4+ cell numbers were decreased and serum immunoglobulins; particularly IgM and IgG; were increased in all groups of seropositive subjects. [abstract terminated]

Clearance and organ localization of particles and soluble complexes in mice with circulating complexes.

The clearance and organ localization of a number of substances cleared by either Fc-dependent or -independent mechanisms was studied in normal mice and in mice with endogenously produced persistent circulating complexes. Clearance of covalent dimers of mouse IgG, chicken IgG and ovalbumin were no different between the two groups of mice. By contrast, hepatic and splenic uptake of dimeric mouse IgG (but not of chicken IgG or ovalbumin dimer) was impaired in the mice with persisting complexes. Surprisingly the rate of clearance of sheep red blood cells (SRBC) was increased in mice with persisting complexes as was hepatic uptake of polyvinyl pyrrolidone. It is suggested that the mononuclear phagocytes of mice with persistent circulating complexes are non-specifically stimulated while their ability to take up soluble complexes by Fc-dependent attachment is selectively impaired.

Preparation of covalent IgG complexes of defined size and their clearance from the circulation of mice.

Covalent complexes of various sizes were made by coupling the photosensitive hapten, NAP (4-azido-2-nitrophenyl), to rabbit IgG and reacting the conjugates with rabbit anti-NAP antibodies. The resultant oligomers were stable, being eluted as the same discrete peaks after chromatography on gels both before and after injection into mice. Tests of their biological properties showed they fixed guinea pig complement in vitro in a size-dependent manner. Normal mice and mice with chronic endogenous circulating complexes cleared the oligomers according to size in a manner best described by a two-component exponential curve. There was no difference in the clearance rates between the two groups of mice. The advantages of these model complexes for examining the effect of circulating complexes on the mononuclear phagocyte system are discussed.

Clearance and localization of immunoglobulin oligomers in mice with chronic circulating endogenous complexes.

The ability of mice with circulating endogenous antigen-antibody complexes to clear and localize heat-aggregated rabbit IgG and a covalently linked tetramer of rabbit IgG anti-IgG was compared with that of normal mice. Although the clearance rates of both probes were unchanged their localization was altered. Hepatic localization in all mice with endogenous complexes was reduced. In some mice, splenic localization was also reduced whereas the amounts in the kidney were increased. These changes could not be attributed to alterations in the blood content of these organs as this was the same as that of normal mice. It is suggested that the observed differences result from saturation of a section of the mononuclear phagocyte system (MPS) with accelerated handling of complexes by mesangial cells in the kidney.

Continuous production of anti-host IgG antibodies contained in circulating IgG-anti-IgG complexes.

Weekly injection with antibody-coated pertussis led to the chronic production of serum complexes in mice. Mice bearing one allotype. Iga, received spleen cells from a congenic strain bearing another allotype, Igb, and weekly injections with Iga-coated pertussis. The serum complexes from these mice and from those receiving challenges alone were separated by ultracentrifugation at neutral and acid pH on sucrose density gradients and their fractions tested for their anti-Iga and Iga content. This revealed the presence of anti-host (Iga) allotype antibodies in fractions from mice that had received Igb cells but not from mice given Iga-coated pertussis alone. Iga allotype was detected in fractions from both groups. It is considered that anti-host allotype antibodies are continuously produced but that they cannot be detected in unfractionated serum because the antibody forms complexes with Iga. These findings are discussed in relation to rheumatoid disease in humans.

Evolutionary significance of the renal excretion of transferrin half-molecule fragments.

It is generally thought that the duplicated structure of serum transferrin in vertebrates arose by gene duplication and fusion from a small ancestral protein. We have found that the isolated domains of transferrin are rapidly lost from the bloodstream via the kidneys. Therefore we suggest that the ancestral transferrin was not a serum protein or, alternatively, that it was not as small as the half-molecule.

Production of antibodies to host IgG after transfer of histocompatible cells primed to host allotype.

A method is described to bring about endogenous production of antibodies to the Fc region of IgG. Mice of one allotype (Igb) were immunized against immunoglobulin from a congenic strain of mice bearing another allotype (Iga). The Iga-primed cells were transferred to congenic recipients bearing the Iga allotype and the production of anti-host allotype antibodies by the donor cells measured. Low levels of anti-host allotype antibodies were found in the sera of normal recipients but much greater amounts in recipients pretreated with cyclophosphamide. On ultracentrifugation some of these IgG antibodies sedimented at more than 7S probably because they were complexed with the IgG antigen. It is considered that thismodel may be of use in testing the effect of anti-Fc antibodies on joint inflammation.

Sodium, potassium and water metabolism in the rabbit: the effect of sodium depletion and repletion.

1. Dietary sodium depletion and subsequent repletion was studied in rabbits. Potassium intake was maintained constant. 2. during sodium depletion and repletion blood pressure, packed cell volume, food consumption and body weight remained at control values. 3. Decreased sodium excretion was observed in both urine and faeces during sodium depletion and the physiological control of these changes is discussed in relation to the renin-angiotensin-aldosterone system. 4. Potassium excretion during sodium depletion initially fell as a result of reduced urine volume and gradually returned to normal. Urine potassium concentration remained constant. 5. Faecal excretion of potassium rose by 63% during sodium depletion and there was a rise from a control value of 17-25% in the proportion of total potassium excretion accounted for by the faecal component. 6. Water consumption and urine volume both decreased in the initial phase of sodium depletion and then returned to control levels. 7. It is important to consider both urinary and faecal excretion of sodium and potassium when calculating balance status for either ion. Faecal excretion, as well as kidney function, shows important physiological adaptations.

Plasma active and inactive renin in the rabbit: effect of dietary sodium depletion and repletion.

1. Active and acid-activatable (inactive) renins were measured in rabbit plasma under control conditions and during sodium depletion with subsequent repletion. 2. Active renin increased by 97% during sodium depletion and returned to control levels on repletion. Both changes were complete within 1 day of changing the diet. 3. During dietary sodium depletion inactive renin levels initially fell to zero and then increased until, after 13 days, inactive renin was again 10% of total renin levels, a proportion comparable to the control values. 4. Sodium repletion caused plasma inactive renin to return to control levels over about 13 days, a quite different time course to active renin. Therefore, in the first phase of repletion the proportion of total renin in the inactive form rose to 19%. 5. These changes are discussed in relation to concurrent changes in sodium, potassium and water metabolism.

Inactive renin in rabbit plasma: effect of haemorrhage.

1. Renin activity in rabbit plasma increases after acidification (pH 3.3), probably due to activation of an inactive form of renin. 2. Both active and inactive renin in plasma increase after haemorrhage. This stimulus does not change the relative proportions of the two forms. 3. After ligation of the renal blood vessels neither form of renin increases in response to haemorrhage. 4. One day after bilateral nephrectomy no inactive renin could be demonstrated in plasma. 5. In the rabbit, therefore, the kidney is a major source of the inactive renin in plasma.