B lymphocytes secreting IgG linked to latent transforming growth factor- beta prevent primary cytolytic T lymphocyte responses

B lymphocytes secreting IgG linked to latent transforming growth factor (TGF)-beta (IgG-TGF-beta) prevent cytolytic T lymphocyte (CTL) responses to unrelated antigens in mixed lymphocyte cultures (MLC) so long as resting resident macrophages and functional Fc receptors are present. This was shown using IgG-secreting plaque-forming cells (PFC) to sheep erythrocytes (SRBC) obtained from popliteal lymph nodes of mice injected repeatedly in foot pads with SRBC. Remarkably, as few as approximately 300 PFC prevented CTL responses of 5 x 10(5) normal syngeneic spleen cells in MLC. Supranatants of short-term cultures of PFC also prevented CTL responses, and suppression was prevented by eliminating or dissociating IgG and TGF-beta present in supranatants or by antibody against active TGF-beta. Furthermore, the latency- associated peptide of latent TGF-beta was detected in approximately 10% of foci of IgG captured from single PFC, indicating that at least some B lymphocytes secrete IgG-TGF-beta as a complex. Resting resident macrophages (which do not produce latent TGF-beta) and functional Fc receptors were required for suppression, consistent with idea that IgG- TGF-beta is taken up through Fc receptors for IgG and that active TGF- beta, cleaved from latent TGF-beta of the complex, is delivered directly to potentially responding CTL. If CTL responses in man are similarly regulated by B lymphocytes, then an ongoing B cell response in patients with chronic viral infections or bearing immunogenic cancers may prevent effective therapeutic vaccination.      

Effect of a Polymeric Additive on the Pore‐Size Distribution and Shrinking Process of a Hydrogel Network

A systematic comparison of the effect of architectural modifications to the network structure on the internal microstructure of N‐isopropylacrylamide (NIPA) based hydrogels showed that the addition of a second component to the network significantly increased the proportion of macropores in the network. The second components considered were short poly(N‐isopropylacrylamide) (PNIPAM) chains grafted to the network backbone, high‐molecular‐weight polyacrylamide (PAM) chains, or microsphere particles of PNIPAM. Structures are proposed for each of the modified gel networks taking into account the new structural information. Through a combination of the pore size and network structure data reported here, and with the shrinking data obtained previously, shrinking mechanisms are proposed for each of the modified network structures. In all cases, the enhanced shrinking rates were directly caused by the presence of the second component, which acted as nuclei for shrinking (graft‐PNIPAM and PNIPAM microspheres) or as water‐release channels (PAM gel), and indirectly caused by the second components via their affect on the network microstructure.

Proposed structures for the architecturally modified gels based on the pore‐size information. Graft‐PNIPAM gel. The freely mobile graft chains prevent chains from meeting resulting in larger pores.     

The effect of age on the fibrinolytic enzyme system

Components of the fibrinolytic enzyme system, FR-antigen and fibrinogen, were measured in 20 healthy volunteers aged 20-40 years and in 61 elderly subjects aged 66-96 years. Plasminogen activator levels did not significantly differ between the 20-40 and 66-75 age groups, but were higher in those over 75. Plasminogen showed no change with age except for a fall in those over 75. Fibrinogen, FR-antigen, alpha(1)-antitrypsin, and alpha(2)-macroglobulin all rose with age, but the mean fibrinogen concentration fell in the very elderly.     

Psychophysiological Correlates of Electrodermal Lability

This study of 75 college student subjects investigated the psychophysiological correlates of electrodermal lability. Resting-stabile and resting-labile subjects were defined as those who were respectively below and above the median of all same-sex subjects in frequency of nonspecific skin conductance responses during rest, whereas stimulus-stabile and stimulus-labile subjects were those respectively below and above the median in trials to habituation of the skin conductance orienting response. These two classification systems were found to be highly correlated with one another, but not entirely equivalent. With both lability measures, labiles had higher resting skin conductance levels than stabiles and also exhibited larger skin conductance orienting responses to both signal and nonsignal tones. Labiles produced orienting responses with shorter latencies, rise times, and half recovery-times. Resting-labiles also differed from resting-stabiles in the components of the triphasic heart rate response to the tones, having larger decelerative responses. The data are consistent with the view that labiles are better able than stabiles to allocate attentional capacity to environmental events and to respond to changing demands in an attentional situation.     

Arm Blood Flow and Oxygenation on the Transition from Arm to Combined Arm and Leg Exercise in Humans

The cardiovascular response to exercise with several groups of skeletal muscle implies that work with the legs may reduce arm blood flow. This study followed arm blood flow ( _arm) and oxygenation on the transition from arm cranking (A) to combined arm and leg exercise (A+L). Seven healthy male subjects performed A at ∼80 % of maximum work rate ( W _max) and A at ∼80 % W _max combined with L at ∼60 % W _max. A transition trial to volitional exhaustion was performed where L was added after 2 min of A. The _arm was determined by constant infusion thermodilution in the axillary vein and changes in biceps muscle oxygenation were measured with near-infrared spectroscopy. During A+L _arm was lowered by 0.38 ± 0.06 l min⁻¹ (10.4 ± 3.3 %,   P < 0.05  ) from 2.96 ± 1.54 l min⁻¹ during A. Total (HbT) and oxygenated haemoglobin (HbO₂) concentrations were also lower. During the transition from A to A+L _arm decreased by 0.22 ± 0.03 l min⁻¹ (7.9 ± 1.8 %,   P < 0.05  ) within 9.6 ± 0.2 s, while HbT and HbO₂ decreased similarly within 30 ± 2 s. At the same time mean arterial pressure and arm vascular conductance also decreased. The data demonstrate reduction in blood flow to active skeletal muscle during maximal whole body exercise to a degree that arm oxygen uptake and muscle tissue oxygenation are compromised.     

Correlation between the numbers of naive T cells infused with blood stem cell allografts and the counts of naive T cells after transplantation.

Naive T cells after allogeneic hematopoietic cell transplantation are thought to originate from the engrafted hematopoietic cells. In this report, we show that there is a correlation between the number of naive CD4 T cells infused with peripheral blood stem cell grafts and the absolute number of peripheral naive CD4 T cells on day 30 (R = 0.65; P <.001), day 80 (R = 0.63; P <.001), and day 180 (R = 0.66; P <.001) after transplantation. These results suggest that in the first 6 months after transplantation, most naive CD4 T cells are derived from the naive T cells infused with the graft.     

Static and dynamic response characteristics, receptive fields, and interaction with noxious input of midline medullary thermoresponsive neurons in the rat

Thermal clamping of deep-body temperature and 16 fields covering the total truncal skin surface enabled characterization of thermal transmission neurons distributed in a midline medullary location. The total data set comprised 136 neurons from 54 female rats. Relative abundance of neuronal types was 27 to 34 to 75 for cold-responsive, warm-responsive, and thermally unresponsive neurons. Response maxima of thermoresponsive neurons to static thermal stimulation of the total truncal surface were 55 +/- 4 ips (mean +/- SE) at 5 degrees C for cold-responsive neurons and 6.0 +/- 1.6 ips at 35 degrees C for warm-responsive neurons. Dynamic thermal stimulation of the total truncal surface at rates up to +/- 1.6 degrees C/s failed to reveal a clear dynamic thermosensitivity in either cold- or warm-responsive neuronal pools. Instead, the data suggest a preferential passing of the static response relative to the dynamic response. Cutaneous thermal receptive fields were diffuse, occupying most of the truncal surface. Subparts of these fields drove thermoresponsive neurons to variable extents, suggesting convergence from unequally represented multiple cutaneous sources. Noxious stimulation at widely distributed body sites consistently augmented activity in cold-responsive neurons. A thermoregulatory rather than somatesthetic role is proposed for the midline medullary neurons studied here.     

Precursor B-lymphoblastic transformation of grade I follicle center lymphoma

Part of the natural history of follicle center lymphoma (FCL) is transformation to a more aggressive neoplasm, almost always a diffuse large B-cell lymphoma. We describe a rare example of a precursor B-lymphoblastic transformation of grade I FCL occurring in a 45-year-old woman 12 years after initial presentation and 3 years after successful treatment for a diffuse large cell transformation. The lymphoblastic lymphoma shared the same immunoglobulin heavy chain gene rearrangement as the FCL as assessed by polymerase chain reaction amplification and direct sequencing, as well as identical kappa light chain gene rearrangements by Southern blot analysis. The immunoglobulin heavy chain variable gene sequences of both tumors showed numerous identical base substitutions compared with germline sequences and 3 additional mutations in the lymphoblastic lymphoma not present in the low-grade FCL. These results indicate origin of the lymphoblastic process from the mature follicle center B-cell clone, rather than divergent origin of the 2 tumors from a common immature B-cell precursor.     

Cardiac drift during prolonged exercise with echocardiographic evidence of reduced diastolic function of the heart

This study examined whether, in 16 male subjects, a continuous increase in heart rate (HR) during 4 h of ergometry cycling relates to cardiac fatigue or cardiomyocyte damage. Serum cardiac troponin T (cTnT) was determined and echocardiographic assessment was carried out prior to and after 2 h of exercise, within 15 min of completing exercise and after 24 h. Left ventricular contractile function (end-systolic blood pressure–volume relationship [SBP/ESV]) and diastolic filling (ratio of early to late peak left ventricular filling velocities [E:A]) were calculated. During exercise HR was 132±5 beats min^–1 after 2 h and increased to 141±5 beats min^–1 (mean ± SD; P<0.05), but there was no evidence of altered LV contractile function (SBP/ESV 39.0±5.1 mmHg cm^–1 to 36.5±5.2 mmHg cm^–1 and SBP/ESV was not correlated to maximal oxygen uptake (r²=0.363). In contrast, E:A decreased (1.82±0.32 to 1.48±0.30; P<0.05) and returned towards baseline after 24 h (1.78±0.28), and individual changes were correlated to maximal oxygen uptake (r²=0.61; P<0.05). Low levels of cTnT were detected in two subjects after 4 h of exercise that had normalised by 24 h of recovery. During prolonged exercise cardiovascular drift occurred with echocardiographic signs of a reduced diastolic function of the heart, especially in those subjects with a high maximal oxygen uptake.