Twenty-nine patients with a positive antimitochondrial antibody titer greater than or equal to 1/40, who were detected during screening for other autoimmune disease, are described who had a normal serum bilirubin, alkaline phosphatase and transaminase and who had no symptoms of liver disease at presentation. Liver biopsies in 12 of the 29 fulfilled diagnostic criteria for primary biliary cirrhosis; a further 12 were consistent with primary biliary cirrhosis, but only 2 were normal. There was a high incidence of other autoantibodies and autoimmune diseases, especially thyroid antibodies and disorders. Sixteen of these patients have been followed for over 4 years since diagnosis (mean = 6 years, range = 4 to 9 years) and for a mean of 8.7 years since initial detection of the antimitochondrial antibody (range = 4 to 13). Five of 16 developed symptoms suggestive of primary biliary cirrhosis, and 11 of 16 developed elevation of alkaline phosphatase. The antimitochondrial antibody activity in these patients was in the same IgG subclasses (predominantly IgG1 and IgG3) as that seen in a group of 23 patients with clinically, biochemically and histologically advanced primary biliary cirrhosis. All showed the same abnormalities on quantitative estimation of the total IgG subclasses in serum; relative excess of IgG3 and, to a lesser extent, IgG2 was exhibited. It is concluded that, in this study, the finding of an antimitochondrial antibody titer greater than or equal to 1/40 is strongly suggestive of primary biliary cirrhosis even in the absence of symptoms and the presence of a normal alkaline phosphatase.

Bronchial responsiveness to inhaled methacholine was measured four to six days before fibreoptic bronchoscopy in 22 asthmatic patients (10 smokers) and 20 control subjects (12 smokers).The asthmatic patients had a baseline FEV, greater than 60% predicted and a PD20FEV, (provocative dose of methacholine causing a 20% fall in FEV,) of 0 006-3-7 mg. The 20 control subjects had normal pulmonary function and a PD20FEV, above the maximum cumulative dose of methacholine of 6-4 mg. Bronchoalveolar lavage of a middle lobe segment (lingula in four subjects) was performed with three sequential 60 ml aliquots of sterile saline. Cellular metabolic activity was stimulated with latex in aliquots of resuspended cells, and measured by means of luminol enhanced chemiluminescence to assess neutrophil activity and lucigenin enhanced chemiluminescence to assess macrophage activity. Mean absolute total cell counts were similar in the asthmatic and control groups but there were differences in differential cell counts, with a significant increase in eosinophil (p < 0 05) and lymphocyte (p < 0 05) counts in asthma. PD20FEV, was negatively correlated with percentage neutrophil counts (p < 0005). Luminol enhanced chemiluminescence/1000 neutrophils was increased about twofold in asthmatic subjects (p < 0 001), but was not correlated with PD20FEV1. Lucigenin enhanced chemiluminescence/1000 macrophages was increased nearly fourfold in asthmatic patients (p < 0-001) and showed a negative correlation with PD20FEV, (p < 0-01). The macrophage count was increased twofold in current smokers in both groups, but other cell numbers were not altered significantly. Smoking did not affect cellular metabolic activity in either group. This study supports the idea that an inflammatory process is present in the airways of those with asthma, and suggests a relation between bronchial responsiveness and both neutrophil numbers and macrophage activity.

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The functional capacity of human neonatal B lymphocytes has been investigated by in vitro methods using T lymphocyte-dependent (pokeweek mitogen, PWM) and -independent (Epstein-Barr virus, EBV) polyclonal B cell activators. B cell activation of single cells was detected by class-specific immunoglobulin (Ig) secretion using a reversed hemolytic plaque assay. It was found that neonatal B cells were triggered to secretion of IgM by EBV, with a magnitude comparable to adult levels, but that, in contrast to B cells from adults, they did not secret IgG. Cord lymphocytes did not secret Ig although they displayed a sizable DNA synthetic response to PWM. Using cell separation and culture experiments, it was shown that (allogeneic) adult T lymphocytes could restore cord B cell responsiveness to PWM and that cord T lymphocytes could not cooperate with adult B cells. In addition to this immaturity of cord T helper function for antibody synthesis, we found cells in the cord T cell-enriched fraction which inhibited the polyclonal response of adult lymphocytes to both PWM and EBV. These lymphocytes suppressed adult B lymphocytes directly but appeared ineffective against neonatal B lymphocytes themselves. The nature of these suppressing cells and their possible role in the fetal/maternal relationship are a matter of speculation.