The cytoplasmic phosphorylation potential. Its possible role in the control of myocardial respiration and cardiac contractility.
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Biomedical subjects
Publications and source records attributed to C Gibbs.
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Recombinant human IL-2, produced by yeast cells, was tested in a number of in vitro responses with murine lymphocytes. The responses studied included proliferation of a cloned murine T lymphocyte line, generation of cytotoxic responses, recall of cytotoxic memory, and restoration of responses in spleen cells taken from cyclophosphamide-treated mice. In all cases, the recombinant human IL-2 had the same activity as purified murine IL-2. The recombinant material represents a source of IL-2 free of other lymphokines. The responses described in this work can therefore be ascribed to the direct effects of human IL-2, of known sequence, on the cells of interest.
The response of T lymphocytes to interleukin 2 (IL 2) is accurately described by a four-parameter logistic function. Both data generated by a theoretical model of IL 2-driven proliferation and experimental data conformed to this function for all doses of IL 2. Assays measuring either the rate of DNA synthesis or cellular metabolism were well described. The variance of response was not constant but increased in a predictable way. Weighting was therefore included in deriving a nonlinear curve-fitting program. The effects on response of cell density, time, and the T lymphocyte line used were examined. Assays gave reproducible estimates of potency when test preparations were compared with a standard preparation, but not otherwise. A model for IL 2 proliferation was derived on the basis of the two-state model of the cell cycle, with cells leaving a quiescent state randomly and then traversing the other stages of the cell cycle in a determinate way.
Experiments were carried out to investigate the changes which occur in the energy production of cross reinnervated fast and slow twitch skeletal muscles. Rat soleus (SOL) and extensor digitorum longus (EDL) muscles were used in myothermic experiments. It was found that the energy production of cross reinnervated skeletal muscle is largely determined by the source of the nervous innervation; as are the dynamic and histological properties of mammalian skeletal muscle. There was an increase in the energy production of crossed soleus muscle and a concomitant reduction in the energy production of crossed EDL. The changes observed correlated well with the measured changes in the force-velocity properties.
Two cases of histopathologically documented Creutzfeldt-Jakob disease were observed in the same area of the province of Siena in 1974-1975. The transmission of the disease was obtained through brain homogenates and lymphnodes in one of the two cases. This confirms that the agent is present in other tissues besides the brain and underlines further the analogies between Creutzfeld-Jakob disease and scrapie.
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The clinical features, radiographic findings, management and outcome in 13 cases of traumatic fracture of the hock joint are reported. The principal fracture sites were the distal tibial malleoli (5 cases), the fibular tarsal bone (4 cases), the tibial tarsal bone (3 cases) and the proximal end of metatarsal IV (one case). An additional small chip fracture of the central tarsal was noted in 2 cases. Three horses were destroyed immediately after diagnosis, 2 failed to recover following surgical intervention and one remained lame and was destroyed after 3 months' rest. Seven horses recovered completely and returned to work following periods of rest ranging from 3 to 9 months. The fracture involved the lateral or medial malleolus in 5 of these cases and the fibular tarsal in the other 2.
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Prostaglandin D2 (PGD2) is a powerful antiaggregatory agent and contracts various types of smooth muscle preparations, including isolated canine and bovine pulmonary vessels. Pulmonary vascular responses of anesthetized fetal and adult goats and newborn lambs to PGD2 were evaluated in situ by means of an isolated perfused lower left lobe preparation. These experiments indicate that PGD2 is a pulmonary vasodilator in fetal goats, both a pulmonary vasodilator and vasoconstrictor in newborn lambs depending on the dose used, and a pulmonary vasoconstrictor in adult goats. Evidence is presented of an age-related change in pulmonary vascular response to prostaglandins. The responses of the pulmonary vasculature are dose dependent; however, there is not a significant dose-dependent relationship for systemic arterial pressure or heart rate with intrapulmonary infusions of PGD2. The inhibition of prostaglandin synthesis potentiates the pulmonary response to PGD2 in fetal goats. In contrast with other prostaglandins, PGI2, PGE2, and PGE1, which dilate both the fetal pulmonary and systemic circulations, PGD2 has minimal action on the systemic circulation over a wide range of doses.
Murine Interleukin 2 (IL2) was denatured with sodium dodecyl sulfate (SDS) with or without concomitant reduction of disulfide bonds. Between 50 and 100% of the activity was recovered upon removal of SDS. When SDS-denatured IL2 was chromatographed on a calibrated gel filtration column in the presence of SDS, it eluted with proteins of m.w. 16,000. This value is supported by sedimentation velocity studies in SDS-containing glycerol gradients. Three activities previously associated with IL2, namely the obligatory role in thymocyte mitogenesis, helper activity in the generation of cytotoxic T lymphocytes, and T cell growth factor activity, co-purified after SDS denaturation. These results indicate that the essential component of murine IL2 is a peptide of m.w. about 16,000. The 3 species of Interleukin 2 studied so far--rat, human, and murine--thus can all exist as polypeptide chains of 15,000 to 16,000 m.w. The murine factor is normally isolated as a larger entity, of about twice this m.w.
The effects of prostacyclin (PGI2) and its metabolite, 6-keto-PGF1 alpha, on pulmonary and systemic circulations of anesthetized, unventilated fetal goats and sheep were evaluated in situ using an isolated perfused lower left lobe preparation. Results from infusions of PGI2 into the left pulmonary artery suggested dose-dependent decreases in pulmonary vascular resistance (PVR) and mean systemic arterial pressure (SAP). Two-minute infusions produced more pronounced reductions in PVR than 1-minute infusions, and fetal goats exhibited greater depressor responses to PGI2 (2-minute infusions) than fetal lambs. For every 10% decrease in mean pulmonary arterial pressure (PAP), SAP decreased by 3% in sheep receiving 1-minute infusions of PGI2. Systemic hypotensive responses and increases in heart rate were similar in both species. PGI2 appears to be a more powerful dilator of the fetal pulmonary circulation than PGE1 or PGE2; also, intrapulmonary infusions of PGI2 resulted in greater and more sustained systemic hypotensive effects than similar infusions of PGE1 and PGE2. The stable metabolite of PGI2, 6-keto-PGF1 alpha, produced attenuated pulmonary vasodilation. Since PGI2 may produce systemic hypotension, the use of this agent in treatment of persistent pulmonary hypertension should be considered with caution.
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Lack of penile erection was diagnosed in nine bulls (Poll Hereford three; Aberdeen Angus two; Friesian two; horned Hereford; Sussex). Five had previously served successfully but four had proved impotent when first put to use. In each bull, the dorsal longitudinal canal of the corpus cavernosum penis (ccp) was occluded by fibrous tissue and this was considered to be the immediate cause of impotence. The ventral canals were also occluded in four bulls. In every case, the lesions were so extensive that treatment would not have been likely to succeed. In two bulls the dorsal canal and the tunica albuginea were ruptured proximal to the sigmoid flexure. Radiography of the cavernous spaces and veins during life, and anatomical injections of post mortem specimens, showed that in four bulls the ccp was drained by the dorsal venous system at or distal to the sigmoid flexure. The aetiology and the diagnosis are discussed and the possible physiological implications of occlusions of the canals are considered in terms of the functional anatomy of the ccp.
Six young bulls (two Friesian, two Charolais, one polled Devon and one North Devon) that had never served successfully, showed good libido but lacked penile erection. In five of these bulls, the short flaccid organ was not protruded during attempted service. Radiography of the cavernous bodies and veins of the penis in the living animal demonstrated major venous drainage of the corpus cavernosum penis (ccp) by the dorsal venous system in all cases. This was not seen in normal bulls. Radiography and anatomical preparations of post mortem specimens showed that the ccp was drained by the dorsal venous system throughout the length of the organ. Proximally, the cavernous spaces of the ccp anastomosed with those of the corpus spongiosum penis (csp) and were drained by numerous small veins. Distally, a system of larger veins, not seen in normal bulls, drained into left and right sides of the dorsal venous system. No microscopical abnormalities of spermatozoa or of testes were found, but there was a marked lack of spermatozoa in the caudae epididymides. The evidence suggests that abnormal venous drainage of the ccp may have been the immediate cause of impotence in these bulls.