AIDS, Portugal, and Africa.
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Acquired Immunodeficiency Syndrome↗
Biomedical subjects
A D Webster
Publications and source records attributed to A D Webster.
Isolation of retroviruses from two patients with "common variable" hypogammaglobulinaemia.
Retroviruses related to human T-lymphotropic virus III/lymphadenopathy-associated virus (HTLV-III/LAV) have been isolated from peripheral-blood mononuclear cells of two patients with "common variable" hypogammaglobulinaemia who were being treated with intravenous gammaglobulin. One has had three different opportunistic infections. In both patients hypogammaglobulinaemia developed within 6 years of a longlasting undiagnosed viral-like illness in adolescence, and it is suggested that the virus causing that illness also gave rise to the hypogammaglobulinaemia. However, iatrogenic infection from intravenous gammaglobulin cannot be ruled out.
Adolescent↗
Acquired immunodeficiency with disseminated cryptococcosis.
A 9 year old Portuguese boy presented with severe wasting and a disseminated cryptococcal infection that resolved after massive doses of intrathecal and parenteral antifungal agents. Clinical and laboratory findings were consistent with AIDS. Apart from neonatal blood transfusions, there were no identified risk factors for HTLV III infection.
Acquired Immunodeficiency Syndrome↗
Non-adherent, low-density cells from human peripheral blood contain dendritic cells and monocytes, both with veiled morphology.
Dendritic cells (DC) from human peripheral blood, known to adhere transiently and to become non-adherent by 16 hr, can be separated in the low-density interface on hypertonic Metrizamide gradients. Many more low-density cells (5.8% of the mononuclear cells separated on Ficoll) were obtained from the population that was non-adherent after only 90 min. Over 95% of these low-density cells had veiled morphology. A proportion were monocytes by phenotypic and phagocytic properties. One-third of the cells (on average) were DC on the basis of lack of monocyte phenotype and of potency as stimulators in the mixed lymphocyte reaction. Including both the 16 hr and 90 min non-adherent cells, over 2% of the mononuclear cells isolated from human peripheral blood may be DC.
5'-Nucleotidase↗
Uptake of free adenosine and adenosine from adenosine monophosphate by human peripheral blood lymphocytes: possible kinetic role for ecto-5'-nucleotidase in the regulation of intracellular adenosine.
The role of 5'-nucleotidase in the uptake of adenosine from AMP was investigated in lymphocytes from normal subjects and patients with common variable hypogammaglobulinaemia (CVH) and chronic lymphatic leukaemia (CLL). At physiological pH, the Km values for the uptake of adenosine and of adenosine from AMP by intact cells were one order of magnitude higher than the Km values for 5'-nucleotidase. The Vmax values for the hydrolysis of AMP by 5'-nucleotidase were two orders of magnitude greater than for the uptake of adenosine itself or the uptake of adenosine from AMP by normal lymphocytes. 5'-Nucleotidase activity is clearly not rate-limiting in normal lymphocytes for uptake of adenosine from AMP in steady state conditions. Patients with common variable hypogammaglobulinaemia showed a low Vmax for 5'-nucleotidase assayed at pH 7.4 in intact cells as compared to values from control subjects. Michaelis constants (Km) for the uptake of free adenosine and adenosine from AMP as well as 5'-nucleotidase were similar compared to those obtained for controls. The uptake of adenosine moiety from AMP in CLL lymphocytes with a low Vmax for 5'-nucleotidase was also reduced, although not to the same extent as the reduction in 5'-nucleotidase activity. One CLL patient with supranormal levels of 5'-nucleotidase activity showed elevated uptake of adenosine moiety from AMP and of free adenosine. These results suggest that 5'-nucleotidase can influence the salvage of purine by lymphocytes from extracellular nucleotides but only when the enzyme activity is greatly reduced.
5'-Nucleotidase↗
B cells in patients with X-linked and 'common variable' hypogammaglobulinaemia.
E- cells from three patients with X-linked and three patients with non-familial 'common variable' hypogammaglobulinaemia were stained by indirect immunofluorescence with a panel of B cell specific monoclonal antibodies (anti-Bp95, Bp35 and Bp135). The number of B cells detected with the pan-B cell antibodies was variable between patients. One patient in each group was found to have near normal numbers of circulating B cells although those of the X-linked patient were clearly immature.
Adolescent↗
Impaired lymphokine-activated killer-cell activity in patients with hypogammaglobulinaemia.
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Agammaglobulinemia↗
Non-A, non-B hepatitis after intravenous gammaglobulin.
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Alanine Transaminase↗
Prospective study of cancer in patients with hypogammaglobulinaemia.
Among 377 patients with primary hypogammaglobulinaemia, mainly common variable immunodeficiency (CVID), 316 patients survived the first 2 years after diagnosis and were the subject of a study of cancer incidence. Among the 220 patients with CVID, there was a 5-fold increase of cancer due mainly to large excesses of stomach cancer (47-fold) and lymphomas (30-fold). The excess of stomach cancer is probably related to the high frequency of achlorhydria in CVID. 3 of the 7 patients with stomach cancer and CVID survived for 5 years or longer.
Adolescent↗
Serum factors for opsonisation of non-typable Haemophilus influenzae.
Neutrophil chemiluminescence was used to assess the opsonins required for phagocytosis of non-typable Haemophilus influenzae isolated from sputum samples of patients with hypogammaglobulinaemia. Immunoglobulin was the major opsonin, whereas complement was relatively unimportant. Evidence was found for a heat-labile opsonin other than complement that enhanced phagocytosis of these organisms. Tuftsin was shown to aid phagocytosis of H. influenzae without triggering chemiluminesence.
Agammaglobulinemia↗
Investigations of host defence in patients with sickle cell disease.
Parameters of host defence were investigated in 30 patients with sickle cell disease (SCD). A newly devised perfusion system was used to study the kinetics in whole blood of leucocyte adherence, phagocytosis, killing and solubilization of a mixture of Staph. aureus and Str. pneumoniae, and secretion of lactoferrin. A skin window technique was used to examine the accumulation of leucocytes at inflammatory foci and their subsequent rate of movement through a filter. Serum concentrations of C3, C4, total haemolytic complement and immunoglobulins were also measured. The rate of neutrophil migration into filters was slightly reduced in patients with SCD. The proportion of monocytes that emigrated from the skin windows and their rate of migration were markedly diminished. The adhesion of neutrophils and their ability to kill staphylococci were also reduced, particularly in patients of the haemoglobin (Hb) SS and Hb S-beta-thalassaemia genotypes. Neutrophil function was mostly impaired in patients with the greatest frequency of bacterial infection. The rate of clearance of pneumococci was related to the concentration of type specific immunoglobulin G but not M. Serum concentrations of immunoglobulins and complement were normal. We were unable to define a defect of host defence of sufficient magnitude to explain the susceptibility of these patients to severe infection.
Anemia, Sickle Cell↗
Reference ranges for IgG subclasses in preschool children.
A normal range for IgG1, IgG2, and IgG3 subclasses has been established for children aged 6 months to 5 years using commercially available monoclonal antisera. Of particular interest were the very low concentrations of IgG2 in some healthy children, a finding which casts doubt on the importance of IgG2 deficiency reported in some patients with otherwise unexplained infections. It was not possible to construct a normal range for IgG4 values probably because these segregate into two populations in normal subjects.
Aging↗
Microbial and metabolic profile of achlorhydric stomach: comparison of pernicious anaemia and hypogammaglobulinaemia.
The microbial flora and some of its metabolites and enzymes in the stomach were compared in patients with achlorhydria, pernicious anaemia, and primary hypogammaglobulinaemia and in patients with dyspepsia with normal gastric acidity. Detailed analysis of the flora of the gastric juice and of the mucosa from the antrum, body, and fundus in six patients with hypogammaglobulinaemia (mean pH 8.2), seven patients with pernicious anaemia (mean pH 7.3), and five patients with dyspepsia (mean pH 1.9) yielded 22 different genera of bacteria, mainly from the patients with achlorhydria, the most common being streptococci, micrococci, staphylococci, veillonella, and lactobacilli. A similar flora was found associated with the mucosa at all three sites. Various metabolites were also looked for. beta Glucoronidase and C14 lipase were found in patients with hypogammaglobulinaemia but not in those with pernicious anaemia or dyspepsia. Volatile fatty acids were not found. Relatively high concentrations of ethanol were found in the patients with hypogammaglobulinaemia compared with those with pernicious anaemia (p = 0.02). Similar concentrations of dimethylamine were found in all three groups, but the concentrations of trimethylamine were much higher in patients with pernicious anaemia and hypogammaglobulinaemia. The high concentrations of some microbial enzymes and ethanol differentiated the group with hypogammaglobulinaemia from the rest, and these may bear some relation to the high incidence of gastric cancer in patients with hypogammaglobulinaemia.
Achlorhydria↗
Ureaplasma urealyticum causing persistent urethritis in a patient with hypogammaglobulinaemia.
Ureaplasma urealyticum organisms (ureaplasmas) were isolated in large numbers (up to 10(8) colour changing units (ccu)/ml) over a period of four years from the urethra of a man with hypogammaglobulinaemia and non-gonococcal urethritis. Elimination of Mycoplasma hominis by antibiotic treatment early in the course of the urethritis did not diminish the severity of his condition, which indicated that this mycoplasma was not a cause. Courses of treatment with tetracyclines, spectinomycin, erythromycin, rosaramicin, and clindamycin on each occasion reduced the numbers of ureaplasma isolated from the urethra and the severity of disease. The organisms were not eliminated, however, sometimes due to the development of antibiotic resistance, and the urethritis recurred. Though netilmicin was not particularly effective in vitro, it was effective clinically, the disease resolving and the organisms disappearing for five months. Recurrence of urethritis, accompanied by epididymitis, was associated this time with the recovery of a different (tetracycline sensitive) ureaplasma strain; the urethritis and epididymitis were treated successfully with a combination of netilmicin and doxycycline. The administration of ureaplasma antiserum did not seem to be instrumental in eradicating the ureaplasmas. The various antibiotics had a greater influence on the mycoplasmas in the urethra than on those in the throat and joints, perhaps because the antibiotics were concentrated in the urogenital tract. The close association between the occurrence of urethritis and the ureaplasmas suggests strongly that they were responsible for it.
Adult↗
Defective low-density cells of dendritic morphology from the blood of patients with common variable hypogammaglobulinaemia: low immunoglobulin production on stimulation of normal B cells.
Low-density cells (LDC) of dendritic morphology from the blood of patients with common variable (late-onset) hypogammaglobulinaemia (CVH) did not induce allogeneic immunoglobulin production by normal B cells unlike LDC from normal blood. When LDC from patients were treated with pokeweed mitogen (PWM), a lower allogeneic secretion of IgM and IgG was induced in normal B cells than that induced by allogeneic normal LDC treated with PWM. B cells from hypogammaglobulinaemic patients were non-responsive to both normal and patient LDC treated with PWM under all conditions tested.
Agammaglobulinemia↗
ATP, ADP and AMP in plasma from peripheral venous blood.
ATP, ADP and AMP in concentrations at least 1 mumol/l have been found by high pressure liquid chromatography (HPLC) in plasma from peripheral venous blood. Total adenine nucleotide concentrations of about 15-20 mumol/l can be found in some conventional clinical samples of blood using EDTA as an anticoagulant. EDTA prevented adenine nucleotide conversion to inosine in plasma. In order to estimate concentrations in vivo, the contribution derived from the cell breakage inherent even in careful venous blood sampling has been estimated by extrapolation to zero 'haemoglobin' concentration in plasma and minimum values in samples of small volume. Available results appear to be consistent with the release of small amounts of ATP in or near the peripheral circulation at the time of venepuncture. In CSF, ATP, ADP and AMP concentrations were less than 0.05 mumol/l suggesting that membrane activity in the central nervous system is not associated with non-specific leakage. The high Km variant of lymphocyte ecto-5'-nucleotidase was not associated with a significantly higher concentration of its substrate AMP in plasma. However, this enzyme may function on the lymphocyte in the thymus and spleen.
5'-Nucleotidase↗
Non-A, non-B hepatitis occurring in agammaglobulinaemic patients after intravenous immunoglobulin.
Acute non-A, non-B hepatitis developed in twelve patients with primary hypogammaglobulinaemia during treatment with intravenous gammaglobulin prepared by Cohn fractionation of pooled plasma. The illness was clinically and histologically identical to the short-incubation non-A, non-B, hepatitis observed in haemophilic patients receiving factor VIII concentrates. Most of the patients were symptomless, but 10 months after onset ten of the twelve still had abnormal liver function. The occurrence of non-A, non-B hepatitis in agammaglobulinaemics indicates that humoral mechanisms are not essential for production of hepatocyte necrosis in this infection. This outbreak emphasises the need for a screening test to identify the agent in blood products, and shows that Cohn fractionation of plasma does not always inactivate the agent. Furthermore, the finding that the virus can be transmitted in IgG concentrates suggests either that the general population has a very low level of antibodies to the putative virus or that such antibodies are not virus-neutralising.
Agammaglobulinemia↗
Intravenous gammaglobulin treatment in patients with hypogammaglobulinaemia.
Intravenous gammaglobulin was compared with the standard British intramuscular preparation in patients with hypogammaglobulinaemia and chronic bronchitis. Five patients were given six months' treatment with the weekly intramuscular preparation and six months' treatment with intravenous gammaglobulin given once every 18 days. During the trial they recorded symptoms of infection, absence from work, and sputum volume; lung function tests were performed during the intravenous treatment. The half life of the intravenous IgG and changes in serum IgG and C1q concentrations were also measured in seven other patients who received intravenous gammaglobulin every two weeks for 12 weeks. IgG concentrations, sputum volume, and infection scores were significantly better during intravenous treatment and there were no adverse effects from the intravenous gammaglobulin. These five patients were significantly more healthy when they received an intravenous gammaglobulin preparation, probably because the intravenous preparation increased serum IgG concentrations. Although longer studies are needed, intravenous gammaglobulin should be considered for patients with severe chest disease and those who cannot tolerate intramuscular injections.
Agammaglobulinemia↗