We report here a factor (B cell growth factor) found in induced supernatants of the mouse thymoma EL4 that co-stimulates with anti-IgM antibodies in short-term cultures of purified B lymphocytes to induce polyclonal B cell proliferation but not antibody-forming cell production. The factor is not mitogenic for resting B cells and interacts with anti-IgM-activated B cells in a non-H-2-restricted manner. Absorption studies and molecular weight analysis reveal the factor is distinct from interleukin 2. This factor synergises with antigen, interleukin 2, and an interleukin 2-free, B cell growth factor-free T cell supernatant that contains T cell-replacing factor to produce erythrocyte-specific plaque-forming cells in cultures of highly purified B cells.

Near-infrared spectroscopy (NIRS) was initiated in 1977 by Jobsis as a simple, noninvasive method for measuring the presence of oxygen in muscle and other tissues in vivo. This review honoring Jobsis highlights the progress that has been made in developing and adapting NIRS and NIR imaging (NIRI) technologies for evaluating skeletal muscle O(2) dynamics and oxidative energy metabolism. Development of NIRS/NIRI technologies has included novel approaches to quantification of the signal, as well as the addition of multiple source detector pairs for imaging. Adaptation of NIRS technology has focused on the validity and reliability of NIRS measurements. NIRS measurements have been extended to resting, ischemic, localized exercise, and whole body exercise conditions. In addition, NIRS technology has been applied to the study of a number of chronic health conditions, including patients with chronic heart failure, peripheral vascular disease, chronic obstructive pulmonary disease, varying muscle diseases, spinal cord injury, and renal failure. As NIRS technology continues to evolve, the study of skeletal muscle function with NIRS first illuminated by Jobsis continues to be bright.

The purpose of this study was to determine whether the initial rate of hemoglobin and myoglobin deoxygenation during immediate postexercise ischemia, a reflection of muscle O2 consumption (VO2mus), can be a quantitative measure of muscle oxidative metabolism. The finger flexor muscles of five healthy men (aged 25-31 yr) were monitored by 31P-magnetic resonance spectroscopy for changes in phosphocreatine (PCr), Pi, and pH. Tests were conducted during 15 min of cuff ischemia and during 5 min of submaximal isotonic grip exercise at 10, 20, 30, and 40% of maximal voluntary contraction, one contraction every 4 s. The VO2mus changes were also monitored by near-infrared spectroscopy with continuous wave. The VO2mus during exercise was expressed relative to the resting value. The resting metabolic rate, calculated from the PCr breakdown rate after complete O2 depletion, was 0.0010 (SD) mM ATP/s. During submaximal exercise (pH > 6.9), the VO2mus increased with a rise in intensity (0.036 +/- 0.011, 0.054 +/- 0.016, 0.062 +/- 0.012, and 0.067 +/- 0.020 mM ATP/s during 10, 20, 30, and 40% maximal voluntary contraction, respectively) and showed significant correlation with changes in both calculated ADP and PCr values (r2 = 0.98 and r2 = 0.99, respectively). In conclusion, because of the significant correlation with regulatory metabolites (ADP and PCr) of oxidative phosphorylation, O2 decline rate in immediate postexercise ischemia determined by near-infrared spectroscopy with continuous wave can be utilized for the quantitative evaluation of localized muscle oxidative metabolism.

A new panel of mAbs was prepared to a stromal cell line known to support lymphocytes in Whitlock-Witte type long-term bone marrow cultures. These antibodies were then screened with a cell adhesion assay and four were selected that inhibited the binding of B lineage cells to stromal cell monolayers. Immunofluorescent and biochemical analyses revealed that these new antibodies detected epitopes of the previously described Pgp-1/CD44 antigen complex. Addition of Pgp-1/CD44 antibodies to Dexter-type long-term bone marrow cultures completely prevented emergence of myeloid cells and they also blocked lymphocyte growth in Whitlock-Witte type cultures. mAbs MEL-14, LFA-1, and CD45R did not inhibit under the same conditions and there was no apparent relationship to Ig isotype. Adherent layers in treated cultures were not unusual in terms of morphology and the antibodies did not affect factor-dependent replication of lymphoid or myeloid progenitor cells. Therefore, the mechanism of inhibition may not involve direct toxicity to precursors or microenvironmental elements. Previous studies in humans and mice have implicated Pgp-1/CD44-related glycoproteins in the migration of peripheral lymphoid cells, as well as interactions of cells with the extracellular matrix. These findings suggest that they may also be critical for formation of lymphoid and myeloid cells within bone marrow.

Background : Extracellular signal-regulated kinase 2 (ERK2) has been implicated in cell proliferation, differentiation, and survival. However, its role in vivo remains to be determined.

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IL-12 and IL-18 synergistically enhance IFN-γ mRNA transcription by activating STAT4 and AP-1, respectively. However, it is still unknown how STAT4/AP-1 elicit IFN-γ promoter activation. Using an IL-12/IL-18-responsive T cell clone, we investigated the mechanisms underlying synergistic enhancement of IFN-γ mRNA expression induced by these two cytokines. Synergy was observed in a reporter gene assay using an IFN-γ promoter fragment that binds AP-1, but not STAT4. An increase in c-Jun, a component of AP-1, in the nuclear compartment was elicited by stimulation with either IL-12 or IL-18, but accumulation of serine-phosphorylated c-Jun was induced only by IL-18 capable of activating c-Jun N-terminal kinase. The binding of AP-1 to the relevant promoter sequence depended on the presence of STAT4. STAT4 bound with c-Jun, and a phosphorylated c-Jun-STAT4 complex most efficiently interacted with the AP-1-relevant promoter sequence. Enhanced cobinding of STAT4 and c-Jun to the AP-1 sequence was also observed when activated lymph node T cells were exposed to IL-12 plus IL-18. These results show that STAT4 up-regulates AP-1-mediated IFN-γ promoter activation without directly binding to the promoter sequence, providing a mechanistic explanation for IL-12/IL-18-induced synergistic enhancement of IFN-γ gene expression.

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