Rapid cytotoxicity of human B lymphocytes induced by VH4-34 (VH4.21) gene-encoded monoclonal antibodies, II

We have previously described complement-independent killing of human B lymphocytes by two IgM MoAbs derived from the VH4-34 (VH4.21) gene. Analysis of 17 independently derived VH4-34-encoded MoAbs shows that B cell toxicity is not limited to the two described MoAbs, but is a general property shared by a subset of MoAbs derived from the VH4-34 gene. As observed by two independent microscopy techniques, giant membrane pores were formed on target B cells within 10–15 min of exposure to cytotoxic VH4-34-derived MoAbs. Toxicity by individual MoAb correlated directly to its B cell binding intensity measured by FACS, i.e. stronger the binding greater the killing. Sequence analysis showed that V_H region in germ-line or in near germ-line configuration was necessary but not sufficient for B cell binding. In addition, a particular sequence motif enriched in basic amino acids in the CDR3 may be required to supplement the reactivity mediated by the V_H region of the MoAb molecule. VH4-34-encoded antibodies that fulfil the above sequence requirements have cold agglutinin activity towards the i antigen of cord erythrocytes. In vivo, such anti-i/anti-B cell antibodies are rarely detected in healthy adults, but serum levels are dramatically elevated in selective pathological conditions, such as systemic lupus erythematosus and infectious mononucleosis. This strict regulation may be related to the novel and rapid mechanism of human B cell toxicity demonstrated by antibodies encoded by a single human V_H gene.     

Effects of chlorpromazine on hypothalamic aminergic neurons and stress responses in moderate cold

Summary Guinea-pigs were treated with chlorpromazine or 0.9% NaCl and exposed to +4° C or +23° C for 2 h. Hypothalamic noradrenaline (NA), dopamine (DA), 5-hydroxytryptamine (5HT), 3-methoxy-4-hydroxyphenylethylene-glycol (MHPG), homovanillinic acid (HVA) and 5-hydroxyindoleacetic acid (5-HIAA) were determined by high-performance liquid chromatography. Serum and urinary catecholamines, muscle and liver glycogen and blood glucose were also measured. Chlorpromazine caused deep hypothermia at this moderately cold temperature and slight hypothermia at room temperature. Cold increased the activity of noradrenergic and serotonergic neurons, as indicated by the increase in hypothalamic MHPG and 5-HIAA and also the MHPG∶NA and 5-HIAA∶5-HT ratios. A tendency towards drug-induced inhibition of hypothalamic serotonergic neurons was seen, although this was not significant. A drug-induced inhibition of noradrenergic neurons could not be ruled out. Increased drug-induced turnover of DA was observed in the cold, and a tendency in the same direction was seen at room temperature. Excretion of DA into the urine was induced by chlorpromazine. The hypothermic guinea-pigs had low serum catecholamines, indicating diminished sympathetic activity, but high urinary catechols, a sign of cold stress.     

Gross efficiency of muscular work during step exercise at -15°C and 21 °C

In an effort to assess the effect of ambient temperature on the gross efficiency (Eff_g) of step exercise 12 subjects performed a modified step test either at —15 °C or 21°C ascending to three different heights (corresponding to light, moderate and heavy work), for 20 min each with a frequency of 18 steps min^-1. Heart rate (HR), rectal temperature, skin temperatures and heat flux from skin were continuously measured. Oxygen consumption was measured during the last 5 min of each step height and perceptions of thermal sensation were recorded. The results indicate that, while using conventional clothing adequate in these temperatures, Eff_g is altered in a contradictory manner. At —15°C Eff_g increased with increasing work load, whereas at 21°C it decreased when the work load increased. The highest Eff_g (heavy work at —15°C and light work at 21°C) values are reflected as rather similar rectal temperatures (37.4–37.7°C) and identical mean skin temperatures (32.8 °C) as well as the same (slightly warm) thermal sensation of the legs. At — 15 °C the lowest Eff_g in light work was probably hue to the need to warm up the muscles. At 21°C, on the contrary, the activation of heat dissipation systems was probably responsible for the lowest Eff_g in heavy work.     

Cardiac responses to pressor challenges in congenital central hypoventilation syndrome

Summary Question of the Study   Congenital central hypoventilation syndrome (CCHS) subjects exhibit diminished respiratory-related heart rate variation in addition to defining characteristics of CO₂ insensitivity and reduced ventilatory drive during sleep. Loss of cardiovascular and breathing coupling may diminish blood pressure influences on breathing; such influences may be determined by evaluating cardiorespiratory responses to different pressor challenges.
Patients and Methods   Ten children with CCHS and 10 age- and gender-matched controls were subjected to a forehead cold pressor challenge and to Valsalva maneuvers. Heart and respiratory rates and variability during 30-s baseline and 120-s challenge periods were assessed with scatterplot displays and by analysis of variance procedures.
Results   Cold pressor challenges enhanced breathing efforts and increased respiratory-related heart rate variation in controls but not in CCHS patients, while lower frequency heart rate variability increased in both controls and CCHS subjects. Heart rate variation resulting from voluntary expiratory efforts was present but slightly reduced in CCHS. Respiratory and cardiac rate trends differed in control and CCHS cases.
Conclusions   More-rapidly changing heart rate variation from spontaneous or reflexively-induced sources is diminished in CCHS but remains intact from voluntary expiratory ­efforts, as does slower variation. Loss of reflexive influences on breathing from blood pressure changes may attenuate a source of respiratory drive.     

Hostility and sex differences in the magnitude, duration, and determinants of heart rate response to forehead cold pressor: Parasympathetic aspects of risk

Recent models hypothesize that hostility confers increased risk of CHD through weaker parasympathetic dampening of cardiovascular reactivity (CVR). We tested this possibility using the forehead cold pressor task, a common maneuver which elicits the “dive reflex” characterized by a reflexive decrease in HR presumably through cardiac-parasympathetic stimulation. Participants were initially chosen from the outer quartiles of a sample of 670 undergraduates screened using the hostility subscale of the Aggression Questionnaire ([Buss, A.H., Perry, M., 1992. The Aggression Questionnaire. Journal of Personality and Social Psychology, 63, 452-459.]). The final sample of 80 participants was evenly divided between men and women and high and low hostility. Following a 10-min baseline, participants underwent a 3-min forehead cold pressor task. The task evoked a significant HR deceleration that was mediated by PNS activation, as assessed by respiratory sinus arrhythmia (RSA). Replicating prior research, men displayed greater decrease in HR. More important, low hostiles maintained larger HR deceleration over time compared to high hostiles although the autonomic basis for this effect was unclear. The findings broaden understanding of hostility and sex-related cardiovascular functioning and support the task as a method for evoking PNS-cardiac stimulation.     

Supra-maximal cycling efficiency assessed in humans by using a new protocol

This study proposed a non-invasive method to determine the gross (GE, no baseline correction), net (NE, resting metabolism as the baseline correction) and work (WE, unloaded cycling as the baseline correction) efficiencies during cycling at an intensity higher than the maximal aerobic power (MAP). Twelve male subjects performed two exercises consisting of 4 min at 50% MAP followed either by 8 min at 63% MAP or by 8 sequences of 60 s divided into 10 s at 130% MAP and 50 s at 50% MAP (i.e., 63% MAP on average). Oxygen uptake was continuously measured to calculate GE, NE and WE at 50%, 63% and 130% MAP, and the data presented as the means and standard deviations. The GE values were 18.2%, 19.1%, 22.7%, the NE values were 22.4%, 22.8%, 24.3% and the WE values were 34.2%, 31.4% and 27.2% at 50%, 63% and 130% MAP, respectively. The GE and NE increased (P<0.001) whereas the WE decreased (P<0.001) with each increment in power output. The GE was lower than the NE (P<0.001) at 50% and 63% MAP and than the WE (P<0.001) at all intensities. The NE was lower (P<0.001) than the WE at 50% and 63% MAP. These results showed that (1) efficiency index values obtained during supra-maximal exercise were consistent with previous proposals and (2) the efficiency-power output relationships were not limited to sub-maximal intensity levels but were confirmed at higher power output.     

Effect of ligands of opiate receptors on morphofunctional state of the sympathoadrenal system and electrical stability of the heart in acute cold exposure

Acute cold exposure (−20°C, 4 h) induces a transient decrease in the ventricular fibrillation threshold without morphological and radionuclide signs of irreversible damage to cardiomyocytes. The agonist of μ-receptors DAGO, which reduces adrenoreactivity of the myocardium, prevents the decrease in the ventricular fibrillation threshold induced by acute cold exposure. Translated fromByulleten’ Eksperimental’noi Biologii i Meditsiny, Vol. 123, No. 2, pp. 154–157, February, 1997     

Isolation of rhinoviruses and coronaviruses from 38 colds in adults

Nasal washings were collected from 27 normal adults during 38 naturally acquired colds. The washings were exhaustively tested using tissue cultures, organ cultures and electron microscopy. Washings yielding no identifiable agent were inoculated into human volunteers, and further specimens obtained from the latter were examined by the same techniques in vitro. Viruses were identified in association with 25 of the original 38 colds (65.7%). Fifteen were rhinoviruses (39.5%), seven coronaviruses (18.4%), two were para-influenza viruses, and one was influenza virus. Use of organ cultures and of volunteers significantly increased the isolation rate. No agent was cultivated from the remaining 13 specimens, although tests in volunteers showed that cold-producing agents were present in five of them (13%). Three specimens gave doubtful results in volunteers, and five others, all collected within a period of six weeks in December and January, apparently contained no infectious agent.     

Thermoregulatory responses to intermittent exercise are influenced by knit structure of underwear

Summary The purpose of this study was to evaluate the role of knit structure in underwear on thermoregulatory responses. Underwear manufactured from 100% polypropylene fibres in five different knit structures (1-by-1 rib, fleece, fishnet, interlock, double-layer rib) was evaluated. All five underwear prototypes were tested as part of a prototype clothing system. Measured on a thermal manikin these clothing systems had total thermal resistances of 0.243, 0.268, 0.256, 0.248 and 0.250 m² · K · W^–1, respectively (including a value for the thermal resistance of the ambient environment of 0.104 m² · K · W^–1). Human testing was done on eight male subjects and took place at ambient temperature (T _a)=5°C, dew point temperature (T _dp)=–3.5° C and air velocity (V _a)=0.32 m · s^–1. The test comprised a repeated bout of 40-min cycle exercise (315 W · m^–2; 52%, SD 4.9% maximal oxygen uptake) followed by 20 min of rest (62 W · m^–2). The oxygen uptake, heart rate, oesophageal temperature, skin temperature,T _a,T _dp at the skin and in the ambient air, onset of sweating, evaporation rate, non-evaporated sweat accumulated in the clothing and total evaporative loss of mass were measured. Skin wettedness was calculated. The differences in knit structure of the underwear in the clothing systems resulted in significant differences in mean skin temperature, local and average skin wettedness, non-evaporated and evaporated sweat during the course of the intermittent exercise test. No differences were observed over this period in the core temperature measurements.The views, opinions and/or findings in this report are those of the authors and should not be construed as an official Department of the Army position, policy, or decision, unless so designated by other official documentation