Uptake of 18fluorodeoxyglucose in the cystic fibrosis lung: a measure of lung inflammation?

Positron emission tomography is a three-dimensional imaging technique that measures physiological effects, including metabolism. 18Fluorodeoxyglucose has been extensively used as a tracer of cellular energy metabolism in the brain and in tumour detection. As neutrophils utilise glucose as an energy source during their respiratory burst, it was hypothesised that 18fluorodeoxyglucose uptake, by these cells, could be interpreted as a measure of neutrophil activation in cystic fibrosis (CF). Ten adult CF patients were given a bolus intravenous injection of 18fluorodeoxyglucose, followed by a 90-min dynamic mid-lung acquisition scan. Right-lung 18fluorodeoxyglucose uptake was assessed using a Patlak plot and values were converted to glucose utilisation. Three clinically inactive pulmonary sarcoidosis patients served as controls. From the 10 CF patients with baseline sputum neutrophils of 14 x 10(6) cells x mL(-1) who were investigated, seven were found to have sputum at a normal or slightly depressed glucose utilisation rate (mean 1.33 micromol x g(-1) x h(-1)) compared with a mean of 2.82 micromol x g(-1) x h(-1) for the sarcoidosis patients. In eight patients, receiving inhaled tobramycin therapy, no change in lung glucose utilisation or sputum neutrophil counts were found. Despite high-sputum neutrophil levels, lung glucose utilisation was not elevated in patients with cystic fibrosis.     

Quantification of tissue plasma volume in the rat by contrast-enhanced magnetic resonance imaging

Magnetic resonance imaging enhanced with a macromolecular contrast medium (MMCM), albumin-Gd-DTPA, was used to estimate the plasma volume in vivo in the myocardium, lung, liver, and skeletal muscle of 10 normal rats. The plasma volumes of the same tissues in a parallel group of six rats were estimated in vitro by a conventional radioisotopic technique (¹¹¹In-transferrin). Plasma volumes of myocardium, lung, liver, and skeletal muscle estimated by the MR technique (μl plas. ia cc-¹ of tissue) were 101,109,163, and 11.0, respectively, while plasma volumes measured by the In-transferrin radioisotope technique (mg plasma g-¹ of tissue) were 78.6, 215,143, and 11-2, respectively. Assuming a ratio of densities of aerated lung to blood of 0.45 and of other tissues to blood of 1.0, correlation between the methods was excellent (R² = 0.99) indicating that MR imaging enhanced with MMCM permits reliable in vivo estimation of tissue plasma volume in the rat.     

Effect of incubation temperature on mitogen responses of lymphocytes from adult peripheral blood and from cord blood

Lymphocytes from normal adults, when cultured with phytohaemagglutinin (PHA) or Concanavalin A (Con A) at 39°C, showed an enhancement and earlier onset of ³H-thymidine incorporation compared with cultures incubated at 37°C. In contrast, the peak responses of cord blood lymphocytes incubated at either 35°C or 39°C did not differ significantly from those incubated at 37°C. Cultures of adult lymphocytes showed an exponential rise and fall in ³H-thymidine incorporation, which was much more rapid at 39°C than at 37°C. However, the kinetics of thymidine incorporation into mitogen-stimulated cord blood lymphocytes incubated at 39°C were similar to those at 37°C. The following results suggested that temperature acted predominantly on the proliferative phase of the transformation response. Firstly, by inhibiting binding of Con A using methyl-α-D-mannopyranoside, it was found that activation of adult lymphocytes took place within the same time period at both 39°C and 37°C. Secondly, cultures incubated at 37°C for 3 days, and labelled for 4 hr at either 37°C or 39°C showed no significant difference in ³H-thymidine uptake, whereas cultures incubated at 39°C for 3 days, and labelled for 4 hr at 37°C showed significantly higher responses than those both incubated and labelled at 37°C. Thirdly, the major increase in thymidine uptake occurred after incubation at 39°C for the second and third days of culture. These findings were consistent with a shortening of the cell cycle at the higher temperature. Thus, the failure of cord blood lymphocytes to show increased thymidine uptake after incubation at 39°C apparently reflects an insensitivity to temperature of certain of the metabolic pathways involved in cell replication in the neonate.     

Vidarabine versus acyclovir therapy in herpes simplex encephalitis

We randomly assigned 208 patients who underwent brain biopsy for presumptive herpes simplex encephalitis to receive either vidarabine (15 mg per kilogram of body weight per day) or acyclovir (30 mg per kilogram per day) for 10 days. Sixty-nine patients (33 percent) had biopsy-proved disease; 37 received vidarabine, and 32 acyclovir. The mortality in the vidarabine recipients was 54 percent, as compared with 28 percent in the acyclovir recipients (P = 0.008). Six-month mortality varied according to the Glasgow coma score at the onset of therapy. For scores of greater than 10, 7 to 10, and less than or equal to 6, mortality was 42, 46, and 67 percent in the patients treated with vidarabine, as compared with 0, 25, and 25 percent in those treated with acyclovir. A six-month morbidity assessment using an adapted scoring system revealed that 5 of 37 patients receiving vidarabine (14 percent) as compared with 12 of 32 receiving acyclovir (38 percent) were functioning normally (P = 0.021). Eight vidarabine-treated patients (22 percent) and three acyclovir-treated patients (9 percent) had moderate debility. Patients under 30 years of age and with a Glasgow coma score above 10 had the best outcome with acyclovir treatment. We conclude that acyclovir is currently the treatment of choice for biopsy-proved herpes simplex encephalitis.     

A novel glycoprotein for detection of herpes simplex virus type 1-specific antibodies

A novel herpes simplex virus type 1 (HSV-1)-specific glycoprotein reactive with monoclonal antibody H1379 was purified by affinity chromatography. This glycoprotein, provisionally designated as gG-1, forms two sets of bands with molecular weights of 40-44,000 and 60-88,000. When used in an immunodot enzymatic assay, gG-1 reacted strongly with rabbit antisera to HSV-1, but not with sera hyperimmune to HSV-2. Specificity of the assay was further established by the lack of reactivity of convalescent sera collected from 20 patients with primary genital HSV-2 infections, and from 100 sero-negative individuals. In contrast, antibodies to gG-1 were detected in 9 of 10 patients with primary HSV-1 infection, and in 63/67 patients with culture-positive, recurrent oral or genital HSV-1 infection. Reproducibility of the gG-1 immunodot assay for HSV-1 antibody detection was 96%. Serological assay with purified gG-1, done in parallel with the assay using purified gG-2 described in an earlier report, provides simple and reliable methods to detect type-specific HSV-1 and HSV-2 antibodies for seroepidemiological studies.     

Poly(Glu60Ala30Tyr10) (GAT)-induced IgG monoclonal antibodies cross-react with various self and non-self antigens through the complementarity determining regions. Comparison with IgM monoclonal polyreactive natural antibodies

Previous studies have shown that the antibodies of the preimmune repertoire are able to bind to various auto- and xenoantigens including chemical haptens. Sequence analysis of two such murine monoclonal IgM natural autoantibodies showed that they are encoded by unmutated germ-line variable regions of the light and heavy chain (V alpha and VH) genes which were also found in various murine immune responses, like phenyl-oxazolone, dinitrophenyl, arsonate, phosphorylcholine and influenza virus hemagglutinin. These data raised the question as to whether induced antibodies possessing germ-line sequence are also able to react with autoantigens. To study this problem, anti-poly(Glu60Ala30Tyr10) (GAT) and anti-alprenolol (Alp) monoclonal antibodies, carrying similar VH and V alpha genes and the same IgG1 isotype, were examined for their capacity to react with several self and non-self antigens. The results showed that: (a) the anti-GAT antibodies tested reacted with different autoantigens, such as murine tubulin, actin and myosin as well as trinitrophenyl (TNP) and bovine serum albumin. Similarly, one of the anti-Alp showed weak reactivities for myosin, DNA, actin and TNP; (b) in contrast two other anti-Alp antibodies did not react with any of the tested antigens. Since the major differences between the oligoreactive anti-GAT and the monoreactive anti-Alp antibodies are in the complementarity determining regions (CDR) our results suggest that the observed cross-reactions are mediated by hypervariable loops. Sequence comparison of these antibodies indicate a possible correlation between cross-reactivity and the presence of aromatic and charged amino acids in the CDR.