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T P Jacobs

Publications and source records attributed to T P Jacobs.

63 records · Page 4Linked to original sources
PubMed1978

Response of 1alpha,25-dihydroxyvitamin D3 to hypocalcemia in human subjects.

We determined the response of 1alpha,25-dihydroxyvitamin D3 after mithramycin-induced hypocalcemia in eight subjects with polyostotic Paget's disease of bone. Thirty-six hours after infusion of mithramycin (25 microgram per kilogram), the average calcium declined from 9.9 +/- 0.14 (S.E.M.) to 8.0 +/- 0.19 mg per deciliter (P less than 0.005). Serum parathyroid hormone increased from 122 +/- 6 to 226 +/- 36 microliter eq per milliliter (P less than 0.05), serum phosphate decreased from 3.8 +/- 0.11 to 2.9 +/- 0.14 mg per deciliter (P less than 0.005), and urinary cyclic 3,5'-adenosine monophosphate increased from 4.6 +/- 0.35 to 7.5 +/- 0.80 mumol per gram of creatinine (P less than 0.005). Serum 1alpha25-dihydroxyvitamin D3 rose from 98 +/- 12 to 332 +/- 61 pM (P less than 0.05), the increase following the changes in parathyroid hormone and phosphate by 12 to 24 hours. When this lag period was taken into account, there was a significant relation (P less than 0.01) between the increase in 1alpha,25-dihydroxyvitamin D3 and changes in parathyroid hormone (correlation coefficient, r = +0.91) and phosphate (r = -0.96). The relatively rapid response of 1alpha,25-dihydroxyvitamin D3 to hypocalcemia occurs with a time course consistent with regulation by parathyroid hormone and phosphate.

Aged↗
PubMed1978

Epinephrine and dopamine beta-hydroxylase secretion from bovine adrenal.

The perfusate of the isolated, acetylcholine-stimulated bovine adrenal was studied for epinephrine (E) concentration and dopamine beta-hydroxylase (DBH) activity. Analysis of single stimuli showed that DBH disappeared from the perfusate with a t1/2 of 19.1-29.0 min. whereas E disappeared with a t1/2 of 0.78-1.0 min. Stimulation every 5 min over 105 min caused a gradual decline in E concentration to 36% of its initial value, whereas DBH activity reached a plateau after the second stimulus and thereafter remained unchanged. The decline in E was not influenced by addition of catecholamine precursors and biosynthetic cofactors to the medium and was not accompanied by a shift in the ratios of E and norepinephrine (NE) in the perfusate. Inhibitors of DBH activity were not detected in the perfusate and nonexocytotic leakage of DBH into the perfusate did not occur. These results document the temporal dissociation of the appearance and disappearance of DBH and E after a single stimulus and the progressive dissociation of DBH and E secretion under conditions of prolonged perfusion with rapid and repetitive stimulation. Possible explanations of these observations are offered.

Acetylcholine↗
PubMed1977

Plasma norepinephrine responses of man in cold water.

The hypothermic stress of immersion in cold water stimulates release of norepinephrine from the sympathetic nervous system. The speed and pattern of this response was studied in six healthy men by serial measurements of plasma norepinephrine concentrations before, during, and after 60 min of immersion in 10 degrees C water. After immersion for 2 min, the mean norepinephrine concentration was increased from 359+/-32 (basal) to 642+/-138 pg/ml and rose gradually to a maximum of 1.171+/-226 pg/ml after 45 min of immersion. Metabolic rate increased approximately threefold during the immersion period. After rewarming in warm water (40 degrees C), the subjects showed a transient peak in plasma norepinephrine followed by a rapid decrease to basal levels after 30 min. The fall in plasma norepinephrine after approximately 8 min of rewarming occurred despite persistent depression of the core temperature and coincided with a sudden decrease in metabolic rate and cessation of body shivering. These results suggest that the sympathetic nervous response to cold can be activated or suppressed very quickly and is dependent on the skin temperature.

Adult↗
PubMedDate not supplied

Neuropeptides in spinal cord injury: comparative experimental models.

The possible role of endogenous opioids in the pathophysiology of spinal cord injury was evaluated utilizing a variety of experimental models and species. In the cat, we have shown that beta-endorphin-like immunoreactivity was increased in plasma following traumatic spinal injury; such injury was associated with a decrease in spinal cord blood flow (SCBF) which was reversed by the opiate receptor antagonist naloxone. Naloxone treatment also significantly improved functional neurological recovery after severe injury. Thyrotropin-releasing hormone (TRH), possibly through its "anti-endorphin" actions, was even more effective than naloxone in improving functional recovery in the cat. In a rat model, utilizing a similar trauma method, TRH proved superior to naloxone in improving SCBF after injury. In addition, naloxone at high doses attenuated the hindlimb paralysis produced by temporary aortic occlusion in the rabbit. The high doses of naloxone required to improve neurological function after spinal injury suggest that naloxone's actions, if opiate receptor mediated, may be mediated by non-mu receptors. Dynorphin, an endogenous opioid with a high affinity for the kappa receptor, produced hindlimb paralysis following intrathecal administration in rats. Taken together, these findings suggest that endogenous opioids, possibly acting at kappa receptors in the spinal cord, may serve as pathophysiological factors in spinal cord injury.

Animals↗
PubMedDate not supplied

Deteriorating stroke model: histopathology, edema, and eicosanoid changes following spinal cord ischemia in rabbits.

Secondary motor dysfunction is often observed following ischemic episodes in the central nervous system. To study potential mechanisms of postischemic motor deterioration, we developed a rabbit spinal cord ischemia model that has characteristics similar to the clinical condition termed deteriorating stroke. In this model, 70% of the rabbits regained substantial motor function by 4 hours after complete hindlimb paralysis during lumbar spinal cord ischemia; however, over the next 20 hours motor function steadily declined to the point where only 30% of the rabbits had minimal hopping function. The role of eicosanoids in spinal cord ischemia was studied by radioimmunoassay of several prostaglandins (6-keto-PGF1 alpha, PGE2, and TxB2) in the spinal cord. After 5 minutes of reperfusion, TxB2 levels were markedly elevated (p less than 0.05) while 6-keto-PGF1 alpha levels did not change. The TxB2:6-keto-PGF1 alpha ratio was also significantly increased. After 30 minutes of reperfusion, PGE2 levels were also elevated (p less than 0.05). Tissue edema measured by microgravimetry was also increased after 30 minutes of reperfusion in both gray and white matter. By 4 hours of reperfusion, rabbits regained near-normal hindlimb motor function while PGE2, 6-keto-PGF1 alpha, TxB2, and tissue water content were back to normal. However, by 18 hours of reperfusion, when hindlimb function was deteriorating, TxB2 levels were elevated again, and edema in gray and white matter was increased as was the number of necrotic neurons observed by light microscopy. These results suggest that the secondary deterioration of motor neurologic function was due to the excess formation of TxA2 primarily in the late reperfusion phase. However, further studies are necessary to elucidate the relation of TxA2 with ischemic neural injury.

Animals↗
PubMedDate not supplied

Effect of systemic platelet-activating factor (PAF) on the rabbit spinal cord microcirculation.

Platelet-activating factor (PAF) is an endogenous phospholipid mediator with pro-inflammatory and vasoactive properties. Since PAF has been implicated in ischemic neuroinjury, we determined its effects on rabbit spinal cord microcirculation (SCM). Using laser-Doppler flow measurements, we monitored mean arterial pressure and SCM continuously on-line during and after i.v. infusion (1 min) of 0.5 nmol/kg of PAF (n = 20) and measured thromboxane B2 (TXB2) and 6-keto-prostaglandin F1 alpha (6-keto-PGF1 alpha) in arterial blood 1.5 min after the infusion. Responses were compared to those after indometacin pretreatment (4 mg/kg, n = 11). During the infusion, spinal cord blood flow (SCBF) decreased by 14 +/- 5% (P less than 0.05) paralleling the systemic hypotensive changes (17 +/- 5%, P less than 0.01) with no changes in vascular resistance (SCVR). However, immediately after termination of PAF infusion, SCVR decreased by 17 +/- 5% (P less than 0.01) while SCBF rapidly recovered. Plasma levels of both TXB2 and 6-keto-PGF1 alpha were significantly elevated. TXB2 release was correlated with the degree of hypotension during the PAF infusion (r greater than 0.72; P less than 0.05) while 6-keto-PGF1 alpha release correlated well with the decrease in SCVR during the infusion period (r greater than 0.64; P less than 0.05). Indomethacin blocked both the hemodynamic events and the eicosanoid release induced by PAF. Our data suggest that PAF modulates SCM through eicosanoid-mediated mechanism.

Animals↗