Research into the complex humoral and neurophysiological events of pyrogen-induced fever has proceeded rapidly to establish the thermal and non-thermal components of the fever syndrome. The major breakthroughs derive from the elucidation of the identity of the endogenous pyrogen interleukin 1 with the humoral factors responsible for the acute phase reaction and for the activation of lymphocytic, cellular, and immunological defence as host responses to infections. As a consequence, fever research is no longer concerned primarily with the changes in temperature regulation responsible for the febrile alteration of temperature regulation, but aims at the elucidation of the contributions that are made by both the thermal and non-thermal components of the fever syndrome to the defence of the host against the microbial intruder responsible for this syndrome.
In order to account for this development in these introductory remarks to the current issues of fever research, this review has tried to pay particular attention to the following points:
1) The role of humoral factors in the generation of febrile hyperthermia, including endogenous pyrogens as well as mediators acting on the thermoregulatory center.
2) The "fever syndrome" with special consideration of its regulation and of the significance of its components from the viewpoint of fever as a host-defence reaction.
3) The assessment of the role of PG's in the generation of the fever syndrome, both as putative central mediators and as systemically released agents, with special consideration of the inhibitory action of the established antipyretic drugs on PG synthesis.

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In urethane-anesthetized and vagotomized rabbits, electrical stimulation of the afferent renal nerve (RN) elicited reflex changes in renal nerve activity (RNA) and arterial pressure (AP). The responses were attributable mostly to excitation of nonmyelinated afferent fibers, although in about 30% of the animals, they were contributed slightly by myelinated afferents. In about 70% of rabbits, the peristimulus time histogram (PTH) of RNA following stimulation of the RN consisted of a long-lasting inhibitory (I) component occasionally accompanied, during its recovery phase, by a transient excitatory (E) component. In these animals, tetanic stimulation of the RN resulted in a depressor response, either alone or, if an E component was present in the PTH, followed by a slight pressor response. In the remaining rabbits, the PTH was composed exclusively of an E component and tetanic stimulation caused a pressor response. Stimulation of the RN evoked reflex changes in cardiac sympathetic discharges comparable to that of RNA, whereas the change in cervical sympathetic discharges was much smaller. The sympathetic response remained intact after a total transection of the rostral medulla near the ponto-medullary junction; the I component was even augmented. However, it usually disappeared following a transection at the high cervical cord. Bilateral lesions of the nucl. tractus solitarius (NTS) near the obex failed to appreciably affect the response. Among chemical and mechanical stimuli examined, nociceptive stimulation of the kidney elicited a sympathetic response comparable to that following nerve stimulation In conclusion, the renal-sympathetic reflex in rabbits (1) originates predominantly from nonmyelinated afferent renal fibers activated effectively by nociceptive stimulation applied to the kidney; (2) depends critically on medullary structures other than the NTS; and (3) evokes changes of the same temporal pattern but of nonuniform magnitude in sympathetic discharges to different organs.

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In an effort to locate medullary structures that mediate the renal-sympathetic reflex, the effect, on the excitatory (E) and inhibitory (I) components of that reflex, of certain drugs applied to the ventral surface of the medulla was investigated in urethane-anesthetized and vagotomized rabbits. Application of bicuculline, a GABA receptor antagonist, selectively abolished the I component of the renal-sympathetic reflex as well as the sympathoinhibition elicited by stimulation of the aortic nerve. The E component, on the other hand, was specifically eliminated by kynurenic acid, a glutamate receptor antagonist. Strychnine or atropine sulfate did not affect either reflex appreciably. Subsequently, within the region of the ventrolateral medulla (VLM) subjacent to the site of drug applications, we searched for neurons which responded to stimulation of the renal nerve and/or the aortic nerve. Of 68 responsive VLM neurons found, 50 (73.5%) responded to stimulation of both nerves. Of the 50 neurons, 40 were tested for their antidromic activation to stimulation of the spinal cord. Twenty-four neurons (60%) were antidromically activated. Responses of these reticulospinal neurons to stimulation of the renal nerve preceded that of renal nerve activity (RNA) by about 100ms. All the antidromically activated, VLM neurons which responded to stimulation of the renal nerve also responded to stimulation of the aortic nerve. In conclusion, the renal-sympathetic reflex appears to be mediated by the same pool of bulbospinal neurons in the ventrolateral medulla that mediates the arterial baroreceptor reflex, and the E and I components of that reflex can be selectively abolished by pharmacological intervention of the subjacent ventral surface of the medulla.

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Three hundred thirty-four healthy male non-smokers and 300 healthy male smokers of the age range 20-60 years were investigated for their spirometric lung functions by the method and technique recommended by American Thoracic Society. It was found that FVC, FEV₁, FEV₁%, FEF_{200-1, 200}, FEF_25-75%, FEF_75-85%, MVV, and PEFR were significantly lower in smokers. When the subjects were blocked into several half decades these differences persisted. These functions deteriorated with age both in smokers and non-smokers, but in the former group the functions were reduced to a greater extent. Significant negative correlation was obtained between lung functions and smoking histories. Separate multiple regression equations were developed separately for non-smokers and smokers. The sensitivity of the tests was determined. The FEF_25-75% and FEV₁ were found to be most sensitive in detecting early airway obstruction. When comparison of lung function wasmade among American, European, Jordanian, Negro, and Pakistani subjects, it was found that the former three groups are superior to the remaining. Negroes and Pakistanis are comparable to Indians in respect to their lung function. These differences in these functions between the nations of developed countries and the underdeveloped or developing countries might be attributable to the differences in their life-style, physical activity status, nutritional status, environmental condition, and race and ethnicity. The spirometric functions of Indians in the Eastern region of India are comparable to North-West Indians and superior to Southern Indians.

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We examined the effects of porcine gastrin-releasing peptide (GRP) on exocrine secretion from dispersed rat pancreatic acini using a perifusion system. GRP stimulated amylase secretion, in a dose-dependent manner in the range of 10^-10-10^-5M. The submaximum response was observed at 10^-8M. Stimulation with 10^-8M GRP caused a biphasic release of amylase. Amylase secretion by GRP stimulation was not affected by the addition of carbachol, dibutyryl cyclic GMP, or atropine. W-7, a calmodulin antagonist, inhibited the amylase secretion induced by GRP. The addition of isobutylmethylxanthine or secretin increased amylase secretion caused by GRP stimulation. These observations suggest that GRP facilitates enzyme secretion by a direct action on pancreatic acini and not through muscarinic and cholecystokinin receptors. The interaction by the Ca²⁺-calmodulin complex was suggested.

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Temporal differences in the onset of inspiratory activities between the efferent vagal (superior laryngeal, Xsl) or hypoglossal (XII) and phrenic (Phr) nerves were measured at various levels of chemical stimuli in the halothane-anesthetized, vagotomized, and artificially ventilated rat. The onset of Xsl (XII) inspiratory activities always preceded the abrupt start of the Phr discharge. Hyperoxic hypocapnia due to hyperventilation delayed the start of inspiratory activity (reduction in respiratory frequency) and shortened the difference in onset time between the cranial (Xsl, XII) and Phr nerve discharges (T_d). During respiratory stimulation due to asphyxia (progressive hypoxia and hypercapnia), the start of Xsl (XII) inspiratory activity became progressively earlier than that of Phr discharge, which extremely prolonged the T_d. Severe asphyxia, however, retarded the start of inspiratory activities with accompanying long T_d and slow respiratory frequency. The early but gradually augmenting inspiratory activity of the Xsl (XII) nerve was always followed by large bursts synchronized with Phr discharges during altered chemical stimuli. The termination of inspiratory activity, which occurred simultaneously in the three respiratory nerves, was not significantly affected by changes in chemical stimuli except for extreme hypocapnia. The results indicate that changes in chemical stimuli not only alter the start of inspiratory activity but also influence the transition from the initial slow onset to the final synchronized inspiratory activity in the Xsl (XII) nerve. The apparent dissociation of the onset time between the Xsl (XII) and Phr nerve discharges shows that the temporal aspect of the brain stem process(es) for starting inspiratory activities may not be determined from the trajectory of Phr discharges only.

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Ventilatory response during external dead space (tube) breathing and CO₂ inhalation for given increase in PET_CO2 were compared at different levels of PET_O2 (hyperoxia, normoxia, and hypoxia) in human subjects. At all the PET_O2 levels studied, magnitude of increment in minute ventilation (VE) and tidal volume were larger in the dead space breathing than in the CO₂ inhalation. The slope of CO₂-ventilation response line was significantly steeper in the dead space breathing only in the hypoxic condition. There was no significant difference in frequency response to CO₂ between the two methods. These results suggested that augmented ventilatory response to CO₂ in the dead space breathing occurs in the condition of peripheral chemoreceptor activation.

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The circular muscle strips were isolated from rat uterus 10-60h after parturition, and the electrical and mechanical responses were investigated. The muscle strips exhibited a variety of contractile activity ranging from frequent spontaneous contractions generated on an elevated muscle tone to a sustained contracture, when incubated with Mg-free Krebs solution. The muscle tone was lowered, and phasic contractions were abolished when the external Ca was removed. Muscle tone was also lowered by addition of 1.2mM Mg, 1mM spermidine, or 1mM tetracaine. The membrane potential was about -25mV in a muscle which exhibited a contracture, and the membrane was hyperpolarized by 20-25mV by the application of 1.2mM Mg or 1mM spermidine. Addition of indomethacin (1.5-4.5×10^-5M) caused a gradual decrease in muscle tone, and the membrane was hyperpolarized. In view of the above results, it is hypothesized that Ca-influx was increased, for which prostaglandin(s) was probably responsible, in the circular muscle of postpartum rat uterus, thereby elevating the muscle tone in Mg-free solution.

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Effects of physostigmine and of beating rate on the negative chronotropic and inotropic responses to tonic intramural parasympathetic nerve stimulation at a frequency of 5Hz for 2min were investigated, using the isolated, blood-perfused dog atrium which was pretreated with propranolol. The responses to stimulation reached a maximum, and then "faded" back toward the control levels during stimulation. Before physostigmine, the fade of the inotropic response was consistently observed but the fade of the chronotropic response was minimal. Both the maximum effect and the fade of the chronotropic response were augmented dose-dependently by physostigmine in spontaneously beating atria. Physostigmine increased the maximum chronotropic response to infusion of acetylcholine (ACh) but did not potentiate the fade response. These results suggest that the potentiation of the fade of the chronotropic response to stimulation after physostigmine is due to decreases in the amount of ACh at the neuroeffector junction.The maximum negative inotropic responses were dose-dependently potentiated similarly by physostigmine in isolated spontaneously beating or paced atria. The fade of the inotropic response in spontaneously beating atria was decreased along with reduction of the rate by physostigmine, whereas the fades in paced atria at 2 and 3Hz were not changed, showing that decreases in rate during stimulation influenced the reduction of the fade. Increases in contractile force induced by infusion of CaCl₂ did not alter the maximum and fade responses to stimulation in 2Hz paced atria. The blood flow into an isolated atrium was not changed detectably during stimulation. These results suggest that the fade of the inotropic response to parasympathetic nerve stimulation is related subsidiarily to acetylcholinesterase or washout of ACh at the neuroeffector junction in isolated perfused atria.

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Neurohormonal, mechanical, and muscle exercise effects on tendon blood flow were studied in thirty-five rabbits. After anesthesia by urethane, experiments were performed on in situ preparation of the hindlimb under stable state in systemic blood pressure. Tendon and muscle blood flow were measured simultaneously by the hydrogen gas clearance method, and their temperature and P_O2 were continuously observed by thermocouple and oxygen sensor, respectively. The resting blood flow in the denervated tendon tibialis anterior, gastrocnemius, and soleus (ml/(100g•min)) was 39.0±4.0, 34.5±8.2, and 30.2±4.3, respectively, whereas in their muscles it was 17.8±1.5, 17.1±2.1, and 12.6±1.1, respectively. The tendon tissue temperature and P_O2 increased gradually until 15-20min after cutting the sciatic nerve, and the increasing rate depended upon the initial control level before denervation. Intravenous injection of noradrenaline in the dose of 1-9.9μg/kg produced a marked decrease in the tendon tissue temperature of the tibialis anterior, but a mild one in the muscle. The longitudinal tension force produced a decrease in the tendon tissue temperature of the tibialis anterior, but no change in the muscle. During muscle exercise, tendon blood flow and temperature tended to decrease, whereas the muscle blood flow and temperature increased markedly from the beginning of muscle exercise. There was no evidence to demonstrate the existence of exercise hyperemia in the tendon tissue. These data suggest that tendon blood circulation can be modified by many factors, and that mechanical and exercise effects may play a role in regulation of tendon blood flow channels and fluid transfer for the lubrication of tendon fiber movements.

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Ventilation (VE), cardiac output (Q), oxygen consumption (V_O2), carbon dioxide production (V_CO2) and end tidal gas tensions (PET_O2 and PET_CO2) were measured in four healthy men during stepwise, steady state increases in work rate on a bicycle ergometer (25, 50, 75, 100, 125, and 150W). Both the ventilation equivalent (VE/V_CO2) and the cardiac equivalent (Q/V_CO2) for carbon dioxide, fell during a steady state exercise at 150W to 2/3 and to 1/3 of the initial levels, respectively. This stepwise reduction in the carbon dioxide production with increasing work rate was compatible with a non-chemical stimulus increasing in proportion to work rate, and governing both ventilation and circulation. These observations do not support the cardio-dynamic hypothesis.

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The ductus arteriosus (DA), connecting the aorta with the pulmonary artery in the fetus, which normally closes up just after birth in terrestrial mammals, has been claimed not to close, but to remain open in normal, adult cetaceans, just as in the adult lungfish. We have examined the hearts from two Pilot Whales. In those we found no persisting DA, but an almost totally obliterated lumen. Blood flow through the ductus of these two whales could be excluded. Instead of an anatomical shunt mammals may use a functional pulmonary shunt. To the extent diving mammals can empty their alveoli for air at depth through reinforced bronchiole, and their very compliant thorax, they block alveolar gas exchange, and thus avoid decompression sickness, nitrogen narcosis and pulmonary squeeze.

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Effect of cold acclimation on gangliosides as well as triglyceride and glycogen in brown adipose tissue was studied in rats. Ganglioside GM₃ level per unit fresh weight and per unit fat-free-dry-matter was significantly higher in cold-acclimated rats (CA) than in warm controls, while the tissue triglyceride and glycogen levels were lower in CA. GM₃ may be involved in cold-induced proliferation and differentiation of brown adipose tissue.

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