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Biomedical subjects

M A French

Publications and source records attributed to M A French.

At least 73 records · Page 4Linked to original sources
PubMed1990

Central MHC genes, IgA deficiency and autoimmune disease.

IgA deficiency is a common immunological disorder that is sometimes associated with an immunodeficiency syndrome, allergic disease, autoimmune disease and gluten enteropathy. Many subjects with this deficiency, however, are healthy, at least for many decades. Analysis of the immunological and genetic abnormalities found in IgA deficiency and in some of the associated disorders has led to the postulate that a genetically determined defect of immunoregulation underlies all of these diseases. Here, Martyn French and Roger Dawkins propose that the products of genes located within the central region of the major histocompatibility complex (MHC) regulate B cells and/or antibody production. Particular MHC ancestral haplotypes contain specific alleles and arrangements of these genes, thereby explaining associations with either increased or decreased production of immunoglobulin isotypes by B cells.

Agammaglobulinemia↗
PubMed1990

Major histocompatibility complex genes influence the outcome of HIV infection. Ancestral haplotypes with C4 null alleles explain diverse HLA associations.

Several alleles at multiple HLA loci have been found to be associated with infection with human immunodeficiency virus (HIV): HLA A1; B8, B35; Cw7, Cw4; DR1, DR3 and DQ1, are associated with particular disease manifestations and/or disease progression. Furthermore, in a pilot study we have shown an increase in the frequency of C4 null alleles and suggested that all the reported HLA alleles could reflect association with a limited number of ancestral haplotypes (AHs). On this occasion, we studied 122 Caucasoid patients classified according to Centers for Disease Control (CDC) criteria. The control group consisted of 67 seronegative homosexual or bisexual males at risk of developing HIV infection. C4 null alleles were unequivocally present in 58% of patients in CDC IV compared with 33% of the seronegative subjects (chi 2 = 5.65, p less than 0.05). Furthermore, C4 null alleles could be excluded in only 8% and 16% of CDC III and IV, respectively, but in 30% of the seronegative subjects. An increased frequency of three AHs largely accounted for the increases in C4 null and HLA alleles. To examine the role of specific AHs we undertook a longitudinal analysis of a subgroup of 26 patients who seroconverted under observation. Seventeen of these patients were followed for 32 to 63 months. All seven patients with the 8.1 AH (A1, CW7, B8, BfS, C4AQ0, C4B1, DR3, DQ2) developed low CD4 lymphocyte counts (less than 450 x 10(6)/l) compared with only 2 of 10 patients without this haplotype (p less than 0.002). All three deaths occurred in patients with the 8.1 AH. The acquired immunodeficiency syndrome developed in three further cases with either 8.1- or B35-bearing (35.x) haplotypes. Sequential CD4/8 ratios showed an early and progressive decline in individuals with 8.1 or 35.x. Since the 8.1 and 35.x AHs contain deletions of the central major histocompatibility complex (MHC) genes, we suggest that the genes affecting HIV infection and progression are within the central MHC region.

Alleles↗
PubMed1990

Multiple pneumatocoeles and bilateral tension pneumothoraces complicating pneumocystis pneumonia in AIDS.

Pneumatocoele and pneumothorax are uncommon complications of Pneumocystis carinii pneumonia. We report a patient with the Acquired Immune Deficiency Syndrome who developed multiple bilateral pneumatocoeles which we demonstrate to have ruptured leading to the subsequent bilateral tension pneumothoraces and to death. The computerised tomographic appearances, and histopathology of these unusual complications are presented. The literature on these manifestations is reviewed and management discussed.

Acquired Immunodeficiency Syndrome↗
PubMed1988

Chain shortening of palmitic acid in human subjects.

Chain shortening of palmitic acid was examined in vivo by comparing oxidation rates of [1-13C]palmitate vs [16-13C]palmitate fed to four male subjects consuming a high-fat diet. For 9 d subjects were fed a diet of normal foods providing an energy intake equal to their estimated requirements. The diet provided (as energy) approximately 14% protein, 46% carbohydrate, and 40% fat at a P:S ratio of 0.25. Analysis of breath 13CO2 enrichment on day 3 permitted analysis of background 13C contribution from the test diet alone. On days 4 and 7 either [1-13C]palmitic acid or [16-13C]palmitic acid (9-13.5 mg/kg body wt) was fed with the breakfast meal. The whole-body rate of oxidation of [1-13C]palmitic acid was significantly greater than that observed for [16-13C]palmitic acid. These results suggest that up to 34% of dietary palmitic acid consumed may be subjected to extramitochondrial chain shortening.

Adult↗
PubMed1988

Protein-losing enteropathy in systemic lupus erythematosus.

Two patients with systemic lupus erythematosus (SLE) presented with anasarca, pleural effusions and severe hypoalbuminema. Both were demonstrated to have protein-losing enteropathy, a rare complication of SLE. Other causes of gastrointestinal protein loss were excluded. There were marked similarities in both cases including circulating ANF with speckled staining, anti-(U1)RNP antibodies and low serum complement levels. Complete remission was achieved in both with prednisolone. Anti-(U1)RNP may be a marker for a subset of SLE in which protein-losing enteropathy is a major manifestation.

Adult↗
PubMed1987

Platelet monoamine oxidase: low activity in cigarette smokers.

Platelet monoamine oxidase (MAO) activity and plasma thiocyanate concentration (an index of smoking behavior) were measured in 109 normal male and female volunteers. MAO activity was significantly lower and plasma thiocyanate concentration significantly higher in smoking volunteers than in nonsmoking volunteers. A significant negative correlation between MAO activity and thiocyanate concentration was observed in female smokers (rs = 0.43, n = 36) but not for male smokers (rs = 0.02, n = 31). In nine smokers who gave up smoking, mean (+/- SD) platelet MAO activity increased significantly (17.5 +/- 4.1 nmole/mg/hour to 24.6 +/- 4.2 nmole/mg/hour). At the same time, mean (+/- SD) plasma thiocyanate concentrations decreased significantly (144 +/- 41 microM to 50 +/- 12 microM). These data suggest that smoking directly or indirectly reduced platelet MAO activity.

Adolescent↗
PubMed1987

Platelet monoamine oxidase activity in patients with Huntington's disease.

1. Platelet monoamine oxidase (MAO) activity was investigated in 30 patients with Huntington's disease and compared with the activity in a control group. 2. Significantly elevated activity was found in the patients (P less than 0.05; t-test) when same sex contrasts were carried out to account for the well known influence of sex on MAO activity. 3. The mean MAO activity in male patients was 23.5 +/- 6.0 nmol/mg protein per h and female patients was 29.5 +/- 8.9 nmol/mg protein per h using tyramine as the substrate. 4. The possible influence of environmental factors on the results is discussed.

Adolescent↗
PubMed1987

Serum IgG subclasses in patients with an increased susceptibility to respiratory tract infections.

Serum IgG subclass concentrations were assayed in 45 patients with chronic respiratory tract infections and 16 patients with recurrent acute respiratory tract infections. Eleven of these 61 patients, all but one with recurrent acute infections, were IgA-deficient but the remainder had normal or high serum immunoglobulin concentrations. Only 4% of patients with chronic infections were IgG2-deficient. The prevalence of IgG2 deficiency amongst patients with recurrent acute infections was greater (31%), but in most cases this appeared to be due to an association with IgA deficiency. Owing to the limits of assay sensitivity it was not possible to determine whether any patient was IgG4-deficient, but the number of sera with undetectable IgG4 was greater in patients with recurrent acute infections than in controls (37.5% vs 10%, p less than 0.01), although such patients were mainly those with IgA and IgG2 deficiency. None of the patients had IgG1 or IgG3 deficiency; in fact IgG3 concentrations were higher than those of controls in both groups of patients (p less than 0.001) and IgG1 concentrations were higher than those of controls in patients with recurrent infections (p less than 0.01). Thus, unequivocal IgG subclass deficiency is uncommon in non-IgA-deficient patients, but those with IgG2 deficiency may have an immune defect requiring further investigation.

Adult↗
PubMed1987

Immunoglobulin G subclass distribution of autoantibodies in systemic sclerosis, primary biliary cirrhosis, and overlap syndromes.

The IgG subclass reactivities of six anticellular antibodies were measured by indirect immunofluorescence on HEp2 cells using murine monoclonal antibodies to the four human IgG subclasses. Patients with scleroderma, primary biliary cirrhosis (PBC), systemic lupus erythematosus, and mixed connective tissue disease were studied. Anticentromere antibody (ACA) was virtually all IgG1 and 3; antibody to multiple nuclear dots (NSpI) was IgG1, 2, and 3; antimitochondrial antibody was mainly IgG2 and 3; nucleolar staining was varied in subclass reactivity but most often IgG4; the diffusely grainy staining associated with Scl-70 antibody was chiefly IgG1; and the speckled pattern associated with anti-RNP antibody was always IgG1 and 4, with IgG2 and 3 in some cases. These data fail to support the hypothesis that the various patterns of autoimmune disease reflect differences in the biological properties of the associated antibodies. The prominence of IgG2 in antibodies associated with PBC suggests the possibility of an immune response independent of T cells in that condition. Differential subclass staining showed an unexpectedly high frequency of antibody to multiple nuclear dots in ACA positive sera, and such patients (all with CREST syndrome) could be at increased risk of developing PBC later.

Antibodies, Antinuclear↗
PubMed1987

Antibody responses to tetanus toxoid in patients with primary biliary cirrhosis.

The primary and secondary antibody responses to tetanus toxoid were measured in 18 patients with primary biliary cirrhosis and compared with those in age and sex matched controls. Although the primary antibody response in the two groups was similar, the secondary IgM antibody response in primary biliary cirrhosis was significantly higher than that in control subjects. There seems to be a correlation between secondary IgM antibody titre and total serum IgM concentration, although this fails to reach significance (p = 0.069). These results show that in primary biliary cirrhosis there is a failure to switch from IgM to IgG antibody synthesis in response to foreign antigens, and this may account for the increased serum IgM concentrations that are usually found in this disease.

Adult↗
PubMed1987

Glomerulonephritis and IgA deficiency.

A mild self-limiting mesangial proliferative glomerulonephritis is described in 3 patients with selective IgA deficiency (less than 0.05 g/l). In all cases there was irregular thickening of peripheral glomerular capillary loops and paramesangial deposits. Arteriolar hyalinosis was present in two of the three cases. By direct immunofluorescence, and immunoperoxidase techniques in one case, IgM was present in the glomeruli and C3 was present in blood vessel walls. Secretory component was not detected in the glomeruli of any of the patients. The polyethylene glycol (PEG) precipitation immune complex assay was positive for IgM and IgG immune complexes in one patient and weakly positive for IgM immune complexes alone in another. The serum of one patient contained milk precipitins. All three patients had suffered from recurrent upper respiratory tract infections. It is suggested that the glomerular IgM immune complex deposition is related to the IgA deficiency and that, although the immune complexes may be a consequence of antibodies to dietary bovine proteins, this could be due to recurrent upper respiratory tract infections. This type of glomerulonephritis appears to resemble IgM associated glomerulonephritis in some aspects. Careful appraisal is required to establish if this association constitute a specific entity.

Adult↗
PubMed1986

An investigation into the effect of the IgG antibody system on the susceptibility of IgA-deficient patients to respiratory tract infections.

Serum IgG subclass concentrations and IgG-tetanus toxoid antibody (IgG-TTab) responses were measured in IgA-deficient patients with severe respiratory tract infections (n = 11), mild respiratory tract infections (n = 5) or no increased susceptibility to respiratory tract infections (n = 15). The severe infection group had lower IgG2 concentrations than the patients without infections (P less than 0.02) and was the only group with IgG2-deficient patients (36%). The number of sera in which IgG4 was not detected was higher in patients with severe infections than in both normal controls (45% vs 10%, P less than 0.01) and the other IgA-deficient patients (45% vs 20%), in part explained by a strong association with IgG2 deficiency. Subnormal IgG-TTab responses were demonstrated in 45% of patients with severe infections but in only one patient from each of the other two groups. Five patients with IgG2 deficiency and/or subnormal IgG-TTab responses were treated with gammaglobulin and apparently improved. There was a high serum concentration of IgG1 in 35% and IgG3 in 19% of the 31 patients, predominantly in those without severe infections. Thus a proportion of IgA-deficient patients have additional defects of IgG; IgG1 and IgG3 antibody responses may compensate for the IgA deficiency in asymptomatic patients.

Adolescent↗
PubMed1985

Serum immune complexes in systemic sclerosis: relationship with precipitating nuclear antibodies.

In a comparative study of antinuclear antibodies (ANA) and immune complexes in the serum of 43 patients with systemic sclerosis (SS) ANA were detected by indirect immunofluorescence on Hep 2 cells and/or double immunodiffusion in 90% of patients, while immune complex assays were positive in 32% of patients. The immune complex assays were positive only in sera containing antibodies to Scl 70, n-RNP, Ro, and La. The presence of immune complexes in SS sera is therefore related to ANA specificity. This might explain the variable findings of several previous studies of immune complexes in SS.

Adult↗
PubMed1985

Antibody-dependent cellular cytotoxicity of human vascular endothelium in systemic lupus erythematosus.

Sera from 35 patients with systemic lupus erythematosus were examined for a cytotoxic effect on human umbilical vein endothelium. Although none of these sera produced direct cytotoxicity of 51Cr-labelled endothelial cells, even with added complement, 3 sera regularly produced increased 51Cr release when co-cultured with endothelial cells and normal human peripheral blood mononuclear cells. The effector cells involved in this cytotoxicity possessed Fc-receptors but were non-T and non-adherent while fractionation studies indicated that the responsible serum factor(s) was IgG, probably in the form of immune complexes of small size. Control studies, using sera from both 27 normal controls and 19 patients with either diabetes or extensive atherosclerotic vascular disease failed to reveal any similar cytotoxicity. Two of the 3 patients, whose sera produced this antibody-dependent cellular cytotoxicity, had had clinical episodes of major vascular thrombosis, raising the possibility that the cytotoxicity might provide an additional pathogenic mechanism in certain patients with systemic lupus erythematosus.

Adult↗
PubMed1985

The IgG4 subclass is associated with a low affinity antibody response to tetanus toxoid in man.

The amount and relative affinity of antibodies to tetanus toxoid were measured, following immunization, in patients with chronic or recurrent acute chest infections and in healthy controls. The responding patients and controls produced similar amounts of antibody and, although antibody affinity was higher in the controls compared to the patients, the differences were not significant. Most individuals (65%) produced antibody of the IgG1 subclass with little or no IgG4 antibody, but in the remainder antibody was either predominantly IgG4 (29%) or equally distributed between the IgG1 and IgG4 subclasses (6%). Antibody affinity was significantly lower in both patients and controls producing IgG4 antibodies compared to those with a predominantly IgG1 response, and antibody affinity increased with the amount of IgG1 antibody present. These results provide preliminary evidence of an association between low antibody affinity and the IgG4 subclass in man.

Acute Disease↗
PubMed1984

Lymphadenopathy and selective IgA deficiency.

Four men presented with unexplained lymphadenopathy. Three had a history of recurrent respiratory infections for several years, and two had lymph node or hepatic granulomas. None was noted to have symptoms of immunodeficiency at the time of presentation. In one patient routine direct immunofluorescence study failed to detect IgA, and immunological investigations were therefore conducted in the rest. In all patients the findings were similar and characterised by a severe deficiency of IgA. In the absence of a more serious cause selective IgA deficiency may be enough to explain "idiopathic" lymphadenopathy.

Adult↗