Suppression of anti-mouse immunoglobulin antibodies in subhuman primates receiving murine monoclonal antibodies against T cell antigens

Murine monoclonal antibodies stimulate the production of human anti-mouse immunoglobulin antibodies (AMIA) when administered to patients. This limits their long-term usefulness as therapeutic and diagnostic agents. We report the use of three maneuvers to suppress AMIA against T cell-specific monoclonal antibodies in cynomolgus monkeys. Twelve monkeys received daily i.v. infusions of 1 mg each of anti-Leu-2a, -3a, and -5 on days 1 through 10. One group (control) received no suppressive regimen. The second group received cyclosporine, 12.5 mg/kg daily on days -7 to +14. The third group (PI) were passively immunized with 0.4 ml of hyperimmune monkey AMIA serum on days -7, -1, 2, 4, 6, and 8. The fourth group (TLI) received 1700 rad fractionated total lymphoid irradiation ending on day -1. The animals treated with TLI were markedly delayed in the onset of AMIA, which was suppressed to less than 1% of the control group. The AMIA specific for the constant region of animals receiving PI was also suppressed to one-third of control. The majority of the AMIA in all the animals was anti-idiotypic and wholly anti-idiotypic in the TLI animals.     

9,10-Anthraquinone Reduces the Photosynthetic Efficiency of Oscillatoria perornata and Modifies Cellular Inclusions

The natural compound 9,10-anthraquinone was found to inhibit the growth of the musty odor-producing cyanobacterium Oscillatoria perornata at a low concentration (1 μM) in previous laboratory studies. In this study, the mode of action of 9,10-anthraquinone was investigated by observing ultrastructural changes in O. perornata and by monitoring chlorophyll fluorescence as an indicator of photosynthetic efficiency. Results indicate that 9,10-anthraquinone inhibits photosynthetic electron transport, probably at PSII, and thereby affects growth. Moreover, 9,10-anthraquinone treatment caused thylakoid disorganization and reduced the number of ribosomes in O. perornata. The thylakoid disorganization is identical to reported modification in a cyanobacterium treated with simazine, a PSII inhibitor.     

Global transcriptional response to mammalian temperature provides new insight into <Emphasis Type="Italic">Francisella tularensis</Emphasis> pathogenesis

Background  

After infecting a mammalian host, the facultative intracellular bacterium,Francisella tularensis, encounters an elevated environmental temperature. We hypothesized that this temperature change may regulate genes essential for infection.     

Effect of pH on the Kinetic Parameters of NADP-Malic Enzyme from a C(4)Flaveria (Asteraceae) Species

We have used the pH variation in the kinetic parameters with respect to malate of NADP-malic enzyme purified from the C₄ species, Flaveria trinervia, to compare the pK values of its functional groups with those for the pigeon liver NADP-malic enzyme (MI Schimerlik, WW Cleland [1977] Biochemistry 16: 576-583) and the plant NAD-malic enzyme (KO Willeford, RT Wedding [1987] Plant Physiol 84: 1084-1087). Like the other enzymes, the C₄ enzyme has a group with a pK of about 6.0 (6.6 for the C₄ enzyme), as indicated from plots of the log V_max/K_m (V_max = maximum rate of catalysis) versus pH, which must lose a proton for malate binding and subsequent catalysis. The optimum ionization for the C₄ enzyme-NADP-Mg²⁺ complex occurs at pH 7.1 to 7.5. From pH 7.5 to 8.4, the K_m increases, but V_max remains constant. The log V_max/K_m plot in this pH range indicates a group with a pK of about 7.7. The other malic enzymes exhibit a similar pK. Above pH 8.4, deprotonation leads to a marked increase in K_m and a decrease in V_max for the C₄ enzyme. As in the case of the animal enzyme, the log V_max/K_m plot for the C₄ enzyme appears to approach a slope of two. The curve suggests an average pK of 8.4 for the groups involved, while the animal enzyme exhibits an average pK of 9.0. The NAD-malic enzyme does not exhibit any pK values at these high pK values. We hypothesize that the putative groups with the high pK values may be at least partially responsible for the ability of the C₄ NADP-malic enzyme to maintain high activity at pH 8.0 in illuminated chloroplasts.     

Evaluation of Propionibacterium acnes Isolates Using Contour-clamped Homogeneous Electric Field Gel Electrophoresis

Contour-clamped homogeneous electric field electrophoresis was performed to compare strains ofPropionibacterium acnes isolated from patients with chronic postoperative endophthalmitis. Propionibacterium acnes isolates were obtained from the vitreous humor of nine patients with chronic postoperative endophthalmitis following cataract surgery. In two of the patients, P. acnes isolates were also obtained from the aqueous humor as well as from the vitreous humor. Bacterial DNA was digested using Not I and Spe I restriction endonucleases. The DNA fragments were then subjected to contour-clamped homogeneous electric field electrophoresis and the DNA banding patterns were analysed. Eight nonidentical banding patterns were identified among the nine vitreous isolates of P. acnes. In each of the two cases from which aqueous and vitreous isolates were recovered from the same eye, the banding patterns were identical. Contour-clamped homogeneous electric field electrophoresis is a powerful method to distinguish P. acnes isolates based on DNA banding patterns and could be used in the epidemiological study of clinical processes caused by this organism.     

Retrospective analysis of the management of 78 cases of postpartum metritis in the cow

Case records of post partum metritis in cows were obtained from Auburn University (42 cases) and Tuskegee University (36 cases) Large Animal Hospital files. Dairy cows (n=68) comprised 87.2% of the cases and beef (n=10) 12.8%. Age did not differ between the types, but the number of postpartum days at admission (mean +/- 1 SD) differed significantly (P=0.02) between dairy (7.3 +/- 4.27) and beef (3.7 +/- 4.06) cows. Older cows and those with hyperthermia were less likely to recover from puerperal metritis (P=0.07 and 0.03, respectively). Type of treatment had no significant association with survival. The number of days of hospitalization was associated with institution (P<0.001), number of postpartum days at admission (P=0.001), history of predisposing factors (P=0.0006), hyperthermia (P=0.006), and length of various treatments (P<0.001). However, the type of treatment had no significant association with length of hospitalization. This study suggests that the necessity for or type of therapy has little effect on the outcome of postpartum metritis.     

Special feature for the Olympics: effects of exercise on the immune system: exercise-induced modulation of macrophage function

Macrophages are important effector cells involved in phagocytosis, microbial killing and antitumour activity. Macrophages also display accessory cell function, in that they can present antigen to foster the development of T lymphocyte-mediated immunity. Recent work, including studies from this group, has demonstrated that acute and chronic exercise can affect many facets of macrophage biology. Manifestation of these effects depends on exercise intensity and duration, the function measured, the timing of measurement in relation to exercise and the concentration of the macrophage-activating stimulus. Exercise has potent stimulatory effects on phagocytosis, antitumour activity, reactive oxygen and nitrogen metabolism, and chemotaxis. Indeed, it has been shown that exercise training can increase macrophage antitumour activity in mice of different ages. However, not all functions are enhanced by exercise. Exercise-induced reductions in macrophage MHC II expression and antigen-presentation capacity have been documented. These findings bring up the possibility that exercise, and perhaps other stressors, activate macrophages for effector functions while downregulating accessory cell functions. To a large extent, the mechanisms responsible for the exercise-induced changes in macrophage function remain unknown, but may depend on exercise-induced changes in neuroendocrine factors. Future studies need to explore the effects in a mechanistic way and provide documentation as to their physiological significance.