How dolphins use their blubber to avoid heat stress during encounters with warm water.

Dolphins have been observed swimming in inshore tropical waters as warm as 36-38 degrees C. A simple protocol that mimicked the thermal conditions encountered by a dolphin moving from cool pelagic to warm inshore water was used to determine how dolphins avoid hyperthermia in water temperatures (Tw) at and above their normal core temperature (Tc). Tw (2 sites), rectal temperature (Tre; 3 depths), and skin temperature (Tsk; 7 sites) and rate of heat flow (4-5 sites) between the skin and the environment were measured while the dolphin rested in a chamber during a 30-min baseline and 40-60 min while water was warmed at approximately 0.43 degrees C/min until temperatures of 34-36 degrees C were attained. Instead of the expected increase, Tre consistently showed declines during the warming ramp, sometimes by amounts that were remarkable both in their magnitude (1.35 degrees C) and rapidity (8-15 min). The reduction in Tre occurred even while heat loss to the environment was prevented by continued controlled warming of the water that kept Tw slightly above Tsk and while metabolic heat production alone should have added 1.6-2 degrees C/h to the Tc. This reduction in Tc could only be due to a massive redistribution of heat from the core to the blubber layer.

Neuropeptide Y and Y1-receptor agonists increase blood flow through arteriovenous anastomoses in rat tail.

The purpose of this study was to characterize neuropeptide Y (NPY)-induced vasodilation in the rat tail. Sterile surgical technique was used (with pentobarbital sodium anesthesia) to equip rats with a jugular catheter and a blind-ended thermocouple reentrant tube next to the carotid artery. Tail skin and core temperature were measured with thermocouples during experiments. Tail skin blood flow was monitored with a laser Doppler flowmeter, and tail total blood flow and volume were measured with plethysmography. After baseline data were collected, saline, NPY (16, 32, 64, and 128 microg/kg), [Leu31 Pro34]NPY (63.25 microg/kg), or NPY[13-36] (44.7 microg/kg) was administered intravenously. Tail total blood flow, volume, and tail skin temperature increased, whereas tail skin blood flow and core temperature decreased in response to both NPY- and the Y1-receptor agonist [Leu31 Pro34]NPY but not in response to saline or NPY[13-36]. Studies conducted with the use of color microspheres demonstrated that arteriovenous anastomoses are involved in this NPY-induced vasodilation.

High-voltage pulsed galvanic stimulation: effects of frequency of current on blood flow in the human calf muscle.

1. Twelve healthy subjects received high-voltage pulsed galvanic stimulation (115-475 V d.c.) delivered in separate treatments of 2, 32 and 128 pulses/s for 10 min at the subject's maximum tolerable voltage while calf muscle blood flow was measured by non-invasive Whitney strain-gauge venous occlusion plethysmography. 2. The high-voltage pulsed galvanic stimulation was administered with negative polarity by an intermittent mode of 30 s on, 30 s off. Measurements of calf muscle blood flow were made during each 30 s period when the stimulus was off. The effect of one 30 s maximum isometric contraction of the calf muscles on blood flow was used as a standard for evaluating the effectiveness of high-voltage pulsed galvanic stimulation on calf muscle blood flow. 3. Significant (paired t-tests; P less than 0.05) increases in calf muscle blood flow over the preceding baseline levels occurred for the isometric contraction (322%) and for frequencies of 2 pulses/s (33.5%) and 128 pulses/s (13.36%), but not for a frequency of 32 pulses at which calf muscle blood flow increased in only six of 12 subjects. The mean increases in calf muscle blood flow at 2 and 128 pulses/s represented 11.63% and 4.0%, respectively, of that resulting from the isometric contraction. 4. A clear positive correlation between voltage level and the magnitude of increase in calf muscle blood flow was demonstrated but differed for each frequency used.(ABSTRACT TRUNCATED AT 250 WORDS)

The cold face test (diving reflex) in clinical autonomic assessment: methodological considerations and repeatability of responses.

1. Cold stimulus applied to the face causes bradycardia and peripheral vasoconstriction (i.e. the diving reflex), and has been suggested as a test of the autonomic pathways involved. The purpose of this study was to define standard procedures for conducting the test and analysing the responses to the cold face test, to evaluate variability in responses between subjects and within subjects when the same test is repeated, and to examine its usefulness in clinical autonomic assessment. 2. Sixteen (nine female, seven male) healthy adult (21-35 years old) subjects were used. Cold stimulus was applied with gel-filled compresses. Forehead temperature under the compress as an indication of stimulus magnitude, heart rate, blood flow in the finger, toe and calf by venous occlusion plethysmography, and systolic and diastolic blood pressure were monitored. Three protocols were carried out in which the temperature (0, 5, 10, 15 degrees C), placement (whole face, unilateral, forehead) and duration (20, 40, 60, 120 s) of the cold compress application were varied. 3. The data indicate that 0 degrees C compresses applied bilaterally for 40 s produced the maximum bradycardia and peripheral vasoconstriction. No subject found this test to be obnoxious, but a 120 s application was objectionable to some subjects. This cold face test resulted in 22%, 72%, 59% and 44% reductions in heart rate and blood flow to the finger, toe and calf, respectively. There was significant between-subject variability, but good consistency in responses to tests repeated in the same subject on different days, at different times of day and in different seasons.(ABSTRACT TRUNCATED AT 250 WORDS)

Proliferation of resting B cells is modulated by CR2 and CR1.

Absence of the third component of complement, C3, is associated with impaired ability to synthesize antibody, particularly in the presence of limiting antigen [1-9]. The mature B lymphocyte bearing the surface immunoglobulin receptor transduces signals for proliferation and differentiation upon binding of specific antigen. This mature B cell also bears two related membrane proteins, CR2 (the C3d/Epstein-Barr virus receptor) (CD35) [15], which can mediate the binding of ligands to which appropriate cleavage fragments of C3 have become attached [16]. It has been suggested that these receptors play a direct role(s) in B cell activation [17-25]. In light of previous in vivo observations we decided to assess the function of CR2 and CR1 in relation to B cell activation through the membrane IgM receptor. Highly purified splenic B cells were prepared. No contaminating T cells or macrophages were detected by flow cytometric analysis and no proliferative activity was present upon PHA or ConA stimulation of the purified cells. The B cells were separated into low (activated), medium (preactivated) and high density (resting) fractions by Percoll gradient density centrifugation [26]. The responses of the B cell subpopulations to various concentrations of anti mu (DA4.4 monoclonal antibody) [27] were examined for proliferation at 72 h and for IgM/IgG production at 7 days. Low density B cells were maximally stimulated and no concentration of anti-mu was effective in enhancing their responses. High density B cells proliferated to anti-mu in a concentration dependent manner. When substimulatory concentrations of anti-mu were employed, concomitant crosslinking of CR2 (with either of 2 distinct monoclonal antibodies HB-5 [28] or OKB7 [17]) resulted in a 45% enhancement of B cell proliferation above that observed by crosslinking of SIgM alone. In these studies, total IgM and IgG did not increase in the absence of T cells or T cell factors, indicating that terminal differentiation did not occur. In contrast, when a monoclonal antibody to CR1(44D) [29] was employed in an identical experiment, B cell proliferation was completely inhibited. Antibodies to CR2 or CR1 either alone or in crosslinked form did not enhance B cell proliferation. Immune complexes may crosslink the B cell surface in a manner analogous to our model when the immunoglobulin receptor and CR2 are simultaneously engaged. This activation signal may be particularly important in eliciting antibody responses when the quantity of specific antigen or the affinity for antigen is low. The marked inhibition of proliferation induced by CR1 suggests an alternate role for this receptor in modulation of B cell responses.

Effects of rearing temperature and level of food intake on organ size and tissue composition in piglets.

Piglets are particularly susceptible to cold and nutritional stress because of their poor insulation and low body fat. The purpose of this study was to examine how ambient temperature and level of food intake affect development in piglets. Thirty-two piglets were reared individually from 14 to 56 days of age in either a cold (10 degrees C) or a warm (35 degrees C) environment. Two feeding regimens, restricted and ad libitum, were used to assess the effect of food intake on organ mass. The ad libitum fed pigs in both environments gained weight at the same rate. Paired t-tests of organ weights of ad libitum fed pigs revealed that the mass of the heart, liver, kidneys, stomach, and small intestine, and total nitrogen and the length of the small intestine were greater in cold-reared than in warm-reared littermates of the same body weight. The skin mass and total fat mass, the lengths of the body, extremities, and individual long bones, and the total surface area were greater in warm-reared than in cold-reared individuals. A regression analysis showed body weight was the most important determinant of size for all tissues measured except fat mass, which was affected slightly more by rearing temperature. Of the organs and tissue components that differed in size in warm- and cold-reared pigs, heart, kidney, stomach, skin, nitrogen, and fat mass, and small intestine length and surface area were generally affected more by rearing temperature than by level of food intake. Liver and small intestine mass and femur length were affected more by level of food intake.(ABSTRACT TRUNCATED AT 250 WORDS)

Non-cutaneous peripheral thermosensitivity in the goat (Capra hircus).

1. A 0.2 m2 area of the trunk skin was denervated and its center was externally cooled or warmed, when central body temperature was lowered. 2. When the denervated skin was cooled, the central body temperature, at which shivering occurred, was significantly higher than with warming of the denervated skin. 3. It is concluded that the difference was caused by temperature signals originating from thermoreceptors in tissue layers underneath the denervated skin.

Thermosensitivity of the goat's brain.

1. Experiments were done in conscious goats to estimate the gain of brain temperature sensors and to evaluate that fraction of the thermosensitivity of the entire brain which can be determined by a thermode located in the hypothalamus. 2. The animals were implanted with local thermodes, carotid loops and intravascular heat exchangers permitting independent control of hypothalamic temperature, extrahypothalamic brain temperature and trunk core temperature. 3. Small and slow ramp-like displacements of hypothalamic temperature generated continuously increasing thermoregulatory responses without any dead band, if a negative feed-back from extrahypothalamic sources was suppressed. 4. The hypothalamic sensitivity determined by the metabolic response to slow ramp-like cooling of the thermode amounted to -1.4 W/(kg degrees C) and equalled approximately 30% of what had been found for total body core sensitivity in another series of experiments. 5. Total brain thermosensitivity was -1.6 W/(kg degrees C), which implies that a large thermode centred in the hypothalamus can detect approximately 85% of the thermosensitivity of the entire brain.

Effects of selective cutaneous denervation on hypothalamic thermosensitivity in rats.

The effect of altering input from cutaneous thermoreceptors of the face and trunk on the relationship between hypothalamic temperature (Thy) and heat production (HP) was studied in three rats. The signal from cutaneous receptors was altered in two ways: by altering skin temperature (Tsk) and by sectioning nerves supplying cutaneous receptors. It was found that when Tsk was lowered in normal rats Thy threshold for thermoregulatory HP was elevated, but the slope of the relationship between Thy and HP was not significantly altered. After the spinal nerves serving the trunk skin were sectioned, the slope was reduced and the threshold was elevated markedly at both test ambient temperatures (Ta), but Ta had essentially the same effect on the Thy vs. HP relationship after cutaneous denervation as before. Clearly, eliminating input from trunk cutaneous thermoreceptors has a different effect than does lowering or raising Tsk, but thermoregulation is being achieved by the same basic mechanism before and after cutaneous denervation. After the cranial nerves supplying the skin of the face were also sectioned, there was a further elevation in the Thy threshold for HP at Ta = 25 degrees C but no change at Ta = 15 degrees C. It is concluded that cutaneous denervation does not substantially interfere with the rat's ability to regulate its body temperature, and that the reduced Thy sensitivity and increased Thy threshold exhibited after cutaneous denervation is the result of input from intact warm- and cold-thermoreceptors located in the core and in tissues intermediate to core and skin.

Effects of skin temperature on cold defense after cutaneous denervation of the trunk.

In intact goats the core temperature threshold below which heat production increases with falling core temperature, is inversely related to the temperature of the water bath in which they stand and is therefore assumed to be indicative of the central integration of signals from skin and core temperature receptors. The present study shows that a difference in core temperature thresholds for bath temperatures of 35 degrees C and 40 degrees C persisted after denervation of about two-thirds of the skin of the trunk and limbs. Also, for a given combination of skin and core temperatures, heat production was as great or greater after cutaneous denervation as before. It is concluded that, following denervation of the trunk and upper limbs, intact temperature receptors in the non-denervated skin of the legs and tail, and/or also in tissues between the skin and core, provide important and significant inputs to the temperature regulating system. But these inputs cannot explain fully the thermoregulatory responses observed unless it is assumed that the thermosensitivity of these tissues increased.

Oxygen binding functions of blood and hemoglobin from the Chinese pangolin, Manis pentadactyla: possible implications of burrowing and low body temperature.

We measured O2 equilibria of adult blood and of 'stripped' (cofactor-free) hemolysates from adult and newborn Manis pentadactyla, in order to assess the implications of the burrowing habit and the low deep-core temperature in pangolins, and to discern the mechanisms for maternal-fetal O2 transfer. At pH 7.4 and body temperature (33 degrees C) the blood O2 affinity was significantly higher than in similarly sized non-burrowing, 'normothermic' mammals (P50 = 21 and 33 mm Hg, respectively) indicating an adaptation to hypoxic burrow conditions. This difference is not attributable to a higher intrinsic O2 affinity in the pangolin Hb or to significant differences in its sensitivity to temperature and erythrocytic 2,3 diphosphoglycerate (DPG), but tallies with lower DPG/Hb ratios than generally found in mammals. Stripped adult and newborn hemolysates show similar O2 affinities and pH and DPG sensitivities, but reveal a specific adult Hb that develops after birth, in sharp contrast with the ontogenetic changes in other mammals where specific fetal Hbs are lost after birth.

Body temperature and rate of O2 consumption in Chinese pangolins.

Body temperatures and rates of O2 consumption and CO2 production were measured in four Chinese pangolins (Manis pentadactyla) during short-term exposures (2-4 h) to ambient temperatures (Ta) of 10-34 degrees C. At Ta less than 27 degrees C the pangolins curled into a sphere. At Ta greater than 28 degrees C the animals laid on their backs with their soft abdominal skin exposed. Rectal temperatures between 33.4 and 35.5 degrees C were recorded from animals exposed to Ta of 10-32 degrees C. At Ta greater than or equal to 32 degrees C the animals appeared to be markedly heat stressed, rate of breathing was elevated, and core temperature rose somewhat. Resting metabolic rates averaged 3.06 ml O2 X kg-1 X min-1. This is significantly lower than would be predicted from the relationship between body mass and metabolic rate established by Kleiber (The Fire of Life: an Introduction to Animal Energetics. New York: Wiley, 1975) for other eutherian mammals. The magnitude of the metabolic response to Ta below the lower critical temperature was inversely correlated to the mass of the pangolin, the slope being greatest for the smallest animals. Respiratory quotients of 0.85-1.0 were observed.

Defective complement activity in chronic lymphocytic leukemia.

Patients with chronic lymphocytic leukemia (CLL) are at an increased risk for infections with bacteria which require complement for osponization. We explored the possibility that patients with CLL have a defect in binding the potent opsonin C3b to bacteria. Bacteria selected for these experiments included Streptococcus pneumoniae type 3, which binds C3 by activating the classical complement pathway (CCP), type 25, which can bind normal amounts of C3b by the alternative complement pathway (ACP), type 14, which can activate both the CCP and ACP, and Staphylococcus aureus and Escherichia coli, both of which activate the CCP. Bacteria were treated with normal serum or serum from 15 patients with CLL, and the bound C3b was quantified spectrophotofluorometrically. Despite normal serum concentrations of C3, C4, Factor B, C-reactive protein, and total hemolytic complement activity, all 15 CLL sera bound reduced amounts of C3b to at least one bacterial species; 9 to S pneumoniae type 3, 8 to types 14 and 25, 11 to S aureus, and 13 to E coli. Mixing normal serum with CLL serum restored C3b binding to all bacteria, suggesting a deficiency rather than an inhibitor of activity. Serum from ten hypogammaglobulinemic CLL patients bound less C3b (62.7 +/- 5% of normal) (means +/- SEM) than those with normal immunoglobulin levels (81.9 +/- 5%) (p less than .005). Nevertheless, the addition of specific antibacterial antibodies to CLL serum did not enhance C3b binding to any of the bacteria. Serum from patients with a history of a bacterial infection bound less C3b (62.3 +/- 5%) than those without a history of infections (76.1 +/- 6%) (p less than .05). Thus, there is a defect in either the activation or activity of C3 in CLL serum which may contribute to the increased incidence of infections in these patients.

Effect of cutaneous denervation of face and trunk on thermoregulatory responses to cold in rats.

The effect of eliminating afferent input from cutaneous thermoreceptors of the face and trunk on the ability of rats to regulate body temperature in cool environments was studied. Thermoregulatory ability in a cool environment was assessed first in a 25 degrees C environment and then during slow (20 min) and rapid (5 min) reductions of ambient temperature (Ta) to 15 degrees C by monitoring rate of heat production, rectal temperature, and skin temperature on the back, ear, and tail. These measurements were made in four rats while they were intact and during the 2 wk after cutaneous denervation. Rats were found to regulate body temperature well even after the cutaneous nerves of the trunk and face were sectioned. In eight rats the metabolic curve was determined before and 7-10 days after cutaneous denervation. Although the minimal resting metabolic rates did not differ in the two conditions, the lower critical temperature was significantly elevated from 26.8 to 28.9 degrees C and the rate of rise in metabolic rate per degrees celsius decrease in Ta was also significantly higher after cutaneous denervation. It appears that the higher rate of heat production is in compensation for an increase in the rate of heat loss in denervated rats.

Defective binding of the third component of complement (C3) to Streptococcus pneumoniae in multiple myeloma.

Patients with multiple myeloma (MM) are at an increased risk for infections with bacteria that require opsonization with complement. Because Streptococcus pneumoniae is the most frequently encountered pathogen in these patients, we investigated the ability of serum from patients with MM to mediate the binding of C3b, the major opsonin of the complement system, to S. pneumoniae. S. pneumoniae types 3, 14, and 25 were chosen for study, since S. pneumoniae type 3 activates primarily the classical complement pathway (CCP), type 25 primarily the alternative complement pathway (ACP), and type 14 both pathways. S. pneumoniae were treated with normal serum or serum from 17 patients with MM, and the bound C3b was quantified with fluorescein-conjugated anti-C3 in a spectrophotofluorometric assay. Despite normal or elevated serum concentrations of C3, total hemolytic complement, and C-reactive protein in all of the MM sera, factor B in 16/17 such sera, and C4 in 14/17 MM sera studied, all 17 sera demonstrated a defect in C3b binding to type 3 (32.7% +/- 6% of normal). In addition, serum from 15/17 patients bound decreased amounts of C3b to types 14 (39.6% +/- 8%) and 25 (52.2% +/- 8%). Mixing normal serum with MM serum restored MM C3b binding activity to all three S. pneumoniae types, suggesting that the defect was related to a deficiency rather than an inhibitor of C3 activation. Although MM patients are unable to produce specific antibodies to bacterial antigens, the addition of anti-S. pneumoniae antibodies to MM serum did not enhance C3b binding to any of the S. pneumoniae types. However, when S. pneumoniae were opsonized in a mixture of MM serum and C3-depleted normal serum, C3b binding was restored to all three S. pneumoniae types, demonstrating that MM C3 functions normally in the presence of other normal serum factors. In the present studies, the MM C3b binding defect appeared to correlate with the incidence of S. pneumoniae infections. Serum from patients with a history of an S. pneumoniae infection bound significantly less C3 (20.5% +/- 4%) than those study patients without a history of an S. pneumoniae infection (55.8% +/- 8%) (p less than 0.0025). Thus, MM serum has a defect in the activation of C3, and this may contribute to the increased susceptibility of MM patients to S. pneumoniae infections.

The effects of rearing-temperature on body conformation and organ size in young pigs.

Piglets were weaned at 14 days of age and subsequently reared for 23, 35, 42 or 59 days in a cold (10 degrees C) or a warm (35 degrees C) environment. They were fed to grow at the same rate by feeding cold-reared pigs more than warm-reared pigs. The external surface area, the surface area of the nasal cavity and the length of extremities were greater in warm- than in cold-reared pigs. Likewise, the mass of the skin with subcutaneous fat was greater in warm-reared pigs. The mass of the heart, liver, kidneys, stomach and small intestines was greater in cold- than in warm-reared pigs. There was no difference in the mass of the muscle, spleen, lungs, and large intestine between the two groups.

The effects of rearing-temperature on body composition in young pigs.

Pigs were reared for 23, 35, 42, or 59 days in a cold (10 degrees C) or a warm (35 degrees C) environment. They were fed to grow at the same rate. The total amount of fat was greater in warm-reared than in cold-reared pigs and fat was distributed differently in the two groups. Warm-reared pigs had more fat in the subcutaneous layer while cold-reared pigs had more fat in their abdominal tissues and skeletal muscle. The total amount of nitrogen was greater in cold-reared than in warm-reared pigs and no difference was found in its distribution.