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Biomedical subjects

R T Jones

Publications and source records attributed to R T Jones.

At least 253 records · Page 14Linked to original sources
PubMed1980

Tolerance and disposition of tetrahydrocannabinol in man.

The hypothesis was tested that the development of tolerance in man to the pharmacological effects of delta 9-tetrahydrocannabinol (THC) is due in part to changes in metabolism and disposition. Tolerance developed in six subjects following p.o. administration of 30 mg of THC every 4 hr for 10 to 12 days. Evaluation of THC pharmacokinetics was based on plasma levels of unchanged THC following i.v. administration of [14C] THC before and after the chronic p.o. THC. Development of tolerance was paralleled by pharmacokinetic changes: 1) average total metabolic clearance and the initial apparent volume of distribution increased from 605 to 977 ml/min and from 2.6 to 6.4 liters, respectively; 2) steady-state volume of distribution, averaging 684 liters, was unaltered; 3) the majority of model-dependent pharmacokinetic parameters as well as the time course of total metabolites in plasma were unchanged; 4) the percent dose excreted in urine decreased from 23.2 to 17.5%, but total elimination (urine plus feces) was not significantly changed; and 5) metabolites were rapidly formed (t 1/2 = 2.8-4.4 min), but slowly eliminated (t 1/2 = 49-53 hours) because of extensive protein binding. Renal clearance values of total metabolites were surprisingly low (maximum of 18-20 ml/min) and decreased with time (approximately 1 ml/min after 4-5 days), indicating the accumulation of highly bound metabolites. We conclude that such pharmacokinetic and metabolic changes cannot account for the development of tolerance to the cardiovascular, psychological and skin hypothermic effects of THC.

Adult↗
PubMed1980

Effects of pharmacological interventions on the rat liver following hypovolemic shock.

In order to determine if pharmacological intervention would modify the morphological alterations that we previously observed in the human liver in a rat hypovolemic shock model, male Sprague-Dawley rats were bled to a mean arterial pressure of 40 torr for 30 minutes. Following the shock period, animals were injected with either dopamine-HCl (30 micrograms/kg/min), glucagon (50 micrograms/kg/min) or methylprednisolone sodium succinate (30 mg/kg/min) over a 30-minute period. Following treatment, the shed blood was returned. Animals were killed at either 1 or 48 hours, a wedge biopsy of the liver was taken for morphological study, and a blood sample was taken for the determination of serum glutamic oxaloacetic transaminase (SGOT) and serum glutamic pyruvic transaminase (SGPT). Alterations in the untreated shock controls were consistent with those seen in the human liver by ultrastructural study in cases of mild to moderate shock. The most prominent alteration in the rat liver was the formation of autophagic vacuoles at 1 hour, while at 48 hours there was an increase in residual bodies with a decrease in autophagic vacuoles in both glucagon treated and in untreated controls. While dopamine and methylprednisolone significantly reduced the number of autophagic vacuoles and residual bodies in the animals studied, SGOT levels were increased in the glucagon and methylprednisolone treated animals at 48 hours and SGPT levels were increased only in the glucagon-treated animals at the same time period. Results suggest that methylprednisolone or dopamine prevent sublethal alterations in the rat liver in moderate hypovolemic shock.

Alanine Transaminase↗
PubMed1980

Hemoglobin Ohio (beta 142 Ala replaced by): a new abnormal hemoglobin with high oxygen affinity and erythrocytosis.

Hemoglobin Ohio [beta 142 (H20) Ala replaced by Asp] was found in three members of a white family, all of whom showed erythrocytosis. The variant hemoglobin has a high oxygen affinity, a reduced Bohr effect, and diminished cooperativity. The functional abnormalities of Hb Ohio are explained by the proximity of the substituent beta 142 residue, both to beta 143 His, which is involved in the DPG binding site of hemoglobin, and to the critical C terminal region of the beta chain, which participates in the stabilization of the deoxy (T) conformation.

Adult↗
PubMed1979

Dissociation of autonomic and cognitive effects of THC in man.

Intravenous THC, 30--44.8 microgram/kg, was administered to four subjects. Each received THC on four occasions preceded by either i.v. saline, 0.04 mg/kg atropine sulfate, 0.2 mg/kg propranolol, or both drugs together. Heart rates, subjective intoxication and symptom ratings, time productions, and EEG activity were measured. In the absence of autonomic blocking drugs, THC produced characteristic tachycardia, subjective intoxication, and EEG effects. After combined autonomic blockade, THC had no effect on heart rate, while subjective and EEG changes remained as intense. These findings argue against the hypothesis that the subjective and EEG effects of THC are mediated by autonomic receptors or by interoception of peripheral autonomic actions of THC.

Adult↗
PubMed1979

Cardiovascular effects of intravenous delta-9-tetrahydrocannabinol: autonomic nervous mechanisms.

The contribution of autonomic nervous system activity to the cardiovascular effects of delta-9-tetrahydrocannabinol (THC) was evaluated in 4 normal subjects. The peak heart rate rise after THC was attenuated by atropine and by propranolol, and nearly abolished by atropine-propranolol pretreatment. Blocking drugs also attenuated THC-induced changes in forearm blood flow and vascular resistance but did not affect changes in fingertip temperature. The data suggest that THC acts to induce sympathetic stimulation and parasympathetic inhibition of cardiovascular control pathways. Cardiovascular responses in an additional subject who developed hypertension after either intravenous or smoked marijuana are described.

Adult↗
PubMed1979

Changes in human event related potentials with prolonged delta-9-tetrahydrocannabinol (THC) use.

Auditory event related potentials and contingent negative variation (CNV) were recorded in a series of behavioral tasks from 27 hospitalized human volunteers before, early during (1--3 days), late during (10--14 days) and after chronic THC intoxication at two dose levels (70--90 mg/day or 180--210 mg/day in divided doses). Twelve additional hospitalized volunteers served as a control group. The N1 component of the auditory event related potential in all tasks was depressed when tested early during 180--210 mg/day THC administration. No N1 changes were seen for the subjects receiving 70--90 mg/day or the control subjects. Ten to 14 days during the chronic THC perioe CNV was depressed in all tasks except the control task for both doses at the early THC testing. Only at the most difficult task at the higher of the doses was the CNV depressed at the test late in the THC period. The changes seen in the N1 and the CNV may be indicative of different aspects of a common attentional alteration during stimulus processing. The results on our more difficult tasks suggest the alteration may continue in complex stimulus processing tasks in heavy marijuana users.

Attention↗
PubMed1979

Hemoglobin Cowtown (beta 146 HC3 His-Leu): a mutant with high oxygen affinity and erythrocytosis.

A new mutant, hemoglobin Cowtown, has been found in a white man and his father, both of whom have erythrocytosis. The father had previously been treated with 32P for polycythemia vera. The abnormal hemoglobin is not detectable on electrophoresis in alkaline buffers, but it resolves distinctively on electrophoresis in citrate agar, pH 6.0; similarly, the abnormal beta-globin chain does not separate from beta-A in urea 2-mercaptoethanol buffers of pH 8.9, but it moves anodically to beta-A at pH 6.0. Peptide chromatography and amino acid analysis of the beta chain reveal that the C-terminal histidine residue (beta 146) has been replaced by leucine. Like several other hemoglobins substituted at this residue, Hb Cowtown has a high oxygen affinity and a diminished Bohr effect.

Adult↗
PubMed1979

Enzymic profiles of bovine pancreatic ductal and acinar tissues.

The plasma membrane enzymes, alkaline phosphatase, bicarbonate-dependent adenosine triphosphatase, 5'-nucleotidase, and carbonate dehydratase, were measured in ductal and acinar preparations of bovine pancreas. Epithelial cells were scraped from the main duct and a piece of acinar tissue was dissected from the whole pancreas for homogenization. All enzymes studied demonstrated higher levels in the duct per milligram protein than in the acinus: bicarbonate-dependent adenosine triphosphatase was 2.8 times higher; 5'-nucleotidase, 4.1 times higher; carbonate dehydratase, 16.9 times higher, while alkaline phosphatase showed only a slight increase in the duct compared to acini.

Adenosine Triphosphatases↗
PubMed1979

The quantitative measurement of electrolyte elements in nuclei of maturing erythrocytes of chick embryo using electron-probe X-ray microanalysis.

Na, K and Cl measurements have been made on frozen sections of chick red blood cells throughout embryonic development, using electron-probe microanalysis. There is an apparent fluctuation in the levels of these elements during maturation, although the Na/K ratio remains fairly constant. The nuclear Na concentration resembles that of the cytoplasm, rather than that of the medium, at all stages. Inhibitor studies indicate that when cytoplasmic Na, K and Cl levels are altered, their corresponding nuclear levels are similarly affected. Additionally, the measurements in nuclei isolated in anhydrous media from lyophilized cells have shown artefactual accumulation of high Na, K, Ca and Mg.

Animals↗
PubMed1979

Tyrptic peptide compositions of hemoglobins from mink (Mustela vison) and hyena (Hyaenae hyaenae) and the alpha-chain of coatimundi (Nasua nasua).

The amino acid composition of the tryptic peptides from hyena hemoglobin, two hemoglobins of the mink and the alpha-chain of coatimundi have been determined, allowing comparison with data previously obtained from other carnivores. The two hemoglobins of mink differ at only one amino acid residue, alpha 15, which is glycyl in one hemoblobin and aspartyl in the other.

Amino Acids↗
PubMed1979

Induction and properties of aryl hydrocarbon hydroxylase in bovine pancreatic ducts.

Inducibility and characteristics of aryl hydrocarbon hydroxylase (AHH) in cultured bovine pancreatic ducts were studied by the fluorometric method. AHH was present and inducible in all the pancreatic ducts studied when they were exposed to 20 microgram benz[a]anthracene (BA)/ml medium. AHH activity in the control tissue ranged from 1.0 to 3.0 U/mg DNA, whereas the activity in the BA-treated tissue was 4.2--28.5 U/mg DNA, which resulted in the induction of 5- to 18-fold activity. At 12 hours of BA exposure, AHH activity in the treated tissue was 12-fold that in the control tissue and continued to increase to 15-, 19-, and 31-fold that in the control tissue at 24, 48, and 72 hours, respectively. The BA-induced AHH activity had a broad pH optimum between 7.1 and 7.7, and the maximum activity was found at pH 7.4. The AHH activity was linear with respect to the incubation time up to 30 minutes. The effect of the benzo[a]pyrene concentration on AHH activity was studied on the BA-induced enzyme. The apparent Michaelis constant for the substrate was 0.5 microM, and the maximum velocity was 8.6 U/mg DNA. BA-induced AHH activity was inhibited 65% by 100 microM 7,8-benzoflavone, whereas the control enzyme activity was stimulated 100% by the same concentration of 7,8-benzoflavone.

Animals↗
PubMed1979

The subcellular pathology of shock in trauma patients: studies using the immediate autopsy.

In summary, our immediate autopsy program provides a new tool for investigating the pathophysiologic effects of shock and trauma at the cellular and subcellular levels. By minimizing the time delay between death and tissue sampling with this technique, we have demonstrated the feasibility of validly applying the refinements of electron microscopy, histochemistry and analytical biochemistry to human tissue. Qualitative, semi-quantitative and quantitative data with these techniques have been integrated with clinical, physiologic and chemical studies on these patients during life. Cell injury produces an altered steady state of metabolism within the cell, evidence of which is seen in altered ultrastructure. If the injury is too severe, the cell will pass the "point-of-no-return," at which time the changes in the cell are no longer compatible with life and the cell dies and undergoes necrosis. Although the initiating injury and the patterns of the altered steady state may vary, once the cell has passed the "point-of-no-return," the patterns of cell injury regardless of the initial insult, are similar. We believe that the cellular patterns seen in patients dying from shock and trauma are remarkably similar to those produced by hypoxic tissue injury in experimental systems. Tissue from control patients in whom ischemic injury due to episodes of hypotension did not occur show good morphologic preservation with normal mitochondria and other cell organelles. Tissue from patients who have experienced acute shock consisting of a period of hypotensive ischemia show changes in the mitochondria and ER compatible with the experimental picture of hypoxia: i.e., dilated ER, with loss of ribosomes, swelling of mitochondria and the appearance of flocculent densities in the mitochondria. Tissues taken from the patients who had experienced repeated episodes of shock, whom we designated as those in "chronic shock," showed changes paralleling the acute changes, but also showed much evidence of autophagocytosis as a) the cells attempted to achieve a lower metabolic requirement in order to survive, and b) they attempted to "clean-up" and remove altered and damaged organelles and debris from previous bouts with sublethal ischemic injury. We hope that the increased knowledge of tissue and cellular injury obtained by the immediate autopsy will provide a means of integration, hypothesis formation and testing of the vast knowledge of cell biology and pathology, and the opportunity for developing in the human the potential for testing new hypotheses in model systems resulting in immediate and innovative feedback for the patient in terms of diagnosis, functional monitoring and treatment.

Adult↗