Heterogeneous and monoclonal helper T cells induce similar anti-(4-hydroxy-3-nitrophenyl)acetyl (NP) antibody populations in the primary adoptive response. I. Isotype distribution

In the response to NP-lipopolysaccharide or NP-Ficoll predominantly anti-NP antibodies of the IgM class are produced in mice with lower amounts of IgG3 and IgG2b but little or no IgG1 and IgG2a. In contrast, in the primary T-dependent response to NP-keyhole limpet hemocyanin (KLH) or NP-chicken gamma globulin high amounts of all IgG isotypes are induced. To investigate whether isotype-specific T cells are responsible for these differences we carried out cell transfer experiments using carrier-specific T cell lines. Two such lines were established and one of the two could be cloned. Upon activation by antigen the T cell lines induced unprimed syngeneic splenic B cells to proliferate and differentiate into antibody-secreting cells in vitro in an antigen-nonspecific way. Antigen-specific activation of unprimed B cells in a cell transfer system in vivo showed that high concentrations of hapten-specific antibodies of all IgG isotypes are induced through both carrier-specific T helper lines. The isotypic pattern of these antibodies is similar to that produced via heterogeneous splenic T cells in the cell transfer system, or in normal animals on immunization with the same antigen. These results suggest that isotype-specific T cells are not required for the production of IgG isotypes in a primary anti-NP response and thus not responsible for the differences seen in isotypic patterns between T-dependent and T-independent responses.     

Effects of detraining following short term resistance training on eccentric and concentric muscle strength.

Healthy males were examined before and after 12 weeks of accommodated resistance training (three week-1) and after 12 weeks of detraining. Training consisted of four to five sets of six coupled maximum voluntary bilateral concentric and eccentric (Grp ECCON; n = 10) or 12 concentric (Grp CON; n = 8) quadriceps muscle actions. Concentric and eccentric peak torque at various constant angular velocities and three repetition maximum half-squat and vertical jump height were measured. Grp ECCON showed greater (P less than 0.05) overall increase in peak torque after training and detraining than Grp CON. Thus, concentric peak torque (0.52 rad s-1) increased more (P less than 0.05) over the experimental period in Grp ECCON and increases in eccentric peak torque were preserved in Grp ECCON only. Increases in peak torque in response to training were greater (P less than 0.05) at 0.52 than at 2.62 rad s-1. Alterations in the torque-velocity patterns induced by training remained after detraining in Grp ECCON but not in Grp CON. The retained increases (P less than 0.05) in half-squat were 12 and 18% in Grps CON and ECCON, respectively. Neither group showed increased vertical jump height after detraining. This study showed greater preservation of concentric and eccentric peak torque after detraining following coupled concentric and eccentric than concentric resistance training. Only the former regime induced a change in the shape of torque-velocity curves that was manifest after detraining.(ABSTRACT TRUNCATED AT 250 WORDS)     

Epstein-Barr virus-transformed B cells can present acetylcholine receptor to autologous autoreactive T cells

Epstein-Barr virus- (EBV-)transformed B cells were obtained from a patient with myasthenia gravis, who was also the donor of a T cell line specific for acetylcholine receptor (AChR). After three months of culture, the EBV-transformed B cells could effectively present native membrane-bound AChR to autologous AChR-specific T cells.     

Muscle hypertrophy following 5-week resistance training using a non-gravity-dependent exercise system

AIM: The efficacy of a mechanical, gravity-independent resistance exercise (RE) system to induce strength gains and muscle hypertrophy was validated. Designed for space crew in orbit, this technique offers resistance during coupled concentric and eccentric actions by utilizing the inertia of a rotating flywheel(s), set in motion by the trainee. METHODS: Ten middle-aged (30-53 years) men and women performed four sets of seven maximal, unilateral (left limb) knee extensions two or three times weekly for 5 weeks. Knee extensor force and electromyographic (EMG) activity of the three superficial quadriceps muscles were measured before and after this intervention. In addition, with the use of magnetic resonance imaging (MRI), volume of individual knee extensor and ankle plantar flexor muscles was assessed. RESULTS: Over the 12 training sessions, the average concentric (CON) and eccentric (ECC) force generated during exercise increased by 11% (P < 0.05). Likewise, maximal isometric strength (maximal voluntary contraction, MVC) at 90 and 120 degrees knee angle increased by (P < 0.05) 11 and 12% respectively, after training. Neither individual quadriceps muscle showed a change (P > 0.05) in maximal integrated EMG (iEMG) activity. Quadriceps muscle volume increased by 6.1% (P < 0.05). Although the magnitude of response varied, all individual quadriceps muscles showed increased (P < 0.05) volume after training. As expected, ankle plantar flexor volume of the trained limb was unchanged (P > 0.05). Likewise, MVC, CON and ECC force, iEMG and knee extensor and plantar flexor muscle volume were unaltered (P > 0.05) in the right, non-trained limb. CONCLUSION: The results of this study show that the present RE regimen produces marked muscle hypertrophy and important increases in maximal voluntary strength and appears equally effective as RE paradigms using gravity-dependent weights, in this regard.     

CD44-mediated neutrophil apoptosis in the rat

BACKGROUND: Apoptosis is an important mechanism by which neutrophils are removed from sites of inflammation, including the kidney. This study investigated whether ligation of the cell-surface adhesion molecule, CD44, can trigger neutrophil apoptosis. METHODS: The anti-rat CD44 antibody OX-50 was used to induce apoptosis of cultured blood neutrophils, as determined by flow cytometry using annexin V staining and by transmission electron microscopy. The functional consequences of OX-50-mediated neutrophil depletion were examined in a rat model of accelerated antiglomerular basement membrane glomerulonephritis. RESULTS: Flow cytometric analysis using the OX-50 antibody, which recognizes the common amino terminal domain of CD44, showed that rat blood neutrophils express very high levels of CD44. The addition of OX-50, but not control antibodies, rapidly induced neutrophil apoptosis in cultured rat blood leukocytes, as demonstrated by annexin V staining and by electron microscopy. Cross-linking of CD44 was essential since F(ab) fragments of the OX-50 antibody failed to induce neutrophil apoptosis. The CD44 ligand hyaluronan and an antibody to the CD44v6 isoform failed to induce neutrophil apoptosis, indicating that OX-50 antibody-mediated neutrophil apoptosis is epitope specific. This effect was specific to neutrophils since the OX-50 antibody did not induce apoptosis in other CD44-expressing cell types (lymphocytes, mesangial cells, or tubular epithelial cells). An injection of OX-50 antibody into normal rats caused a rapid and profound neutropenia, and apoptotic neutrophils could be seen in the blood by electron microscopy. Furthermore, the administration of OX-50 antibody abrogated neutrophil-dependent glomerular injury (proteinuria) on day 1 of rat antiglomerular basement membrane glomerulonephritis, whereas injury on day 10 of the disease (neutrophil independent) was largely unaffected. CONCLUSIONS: The cross-linking of specific epitopes of the CD44 molecule can rapidly induce neutrophil apoptosis in vitro and inhibit neutrophil-dependent renal injury in vivo. This finding suggests that physiological ligands of the CD44 molecule may play an important role in eliminating neutrophils from sites of inflammation, including inflammatory kidney disease.     

Treatment of advanced Hodgkin's disease with COPP/ABV/IMEP versus COPP/ABVD and consolidating radiotherapy: final results of the German Hodgkin's Lymphoma Study Group HD6 trial.

BACKGROUND: The purpose of this study was to compare the efficacy of the hybrid chemotherapeutic regimen COPP/ABV/IMEP (cyclophosphamide-vincristine-procarbazine-prednisone-doxorubicin-bleomycin-vinblastine-ifosfamide-methotrexate-etoposide) (CAI) with that of the standard regimen COPP/ABVD (COPP/ABV, dacarbacine) (CA) in the treatment of advanced-stage Hodgkin's disease (HD). PATIENTS AND METHODS: Between January 1988 and January 1993, 588 eligible patients with HD in stages IIIB and IV were randomly assigned to a treatment or control group. The treatment group received four cycles of CAI over a complete cycle duration of 43 days. The control group received four cycles of CA over 57 days. Both groups then received consolidating radiotherapy. RESULTS: Five hundred and eighty-four patients were suitable for arm comparison. Patients in each group were similar in age, sex, histological subtype and clinical risk factors. Complete remission rates, overall survival and freedom from treatment failure at 7 years were similar for the two groups: 77% versus 78%, 73% versus 73% and 54% versus 56% for CAI and CA, respectively. Differences in acute chemotherapy-related toxicity were significant, however. Prognostic factor analysis confirmed the relevance of the International Prognostic Index and revealed that stage IVB, low hemoglobin, low lymphocyte count, high age and male gender were associated with a poor prognosis CONCLUSION: The rapidly alternating hybrid CAI did not give superior results when compared with the standard regimen CA in advanced-stage HD.