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Biomedical subjects

L S Harris

Publications and source records attributed to L S Harris.

At least 127 records · Page 7Linked to original sources
PubMed1977

A cannabinoid with cardiovascular activity but no overt behavioral effects.

Abnormal-delta8-tetrahydrocannabinol (ABN-delta8-THC) failed to elicit central nervous system and cardiovascular effects in laboratory animals. Abnormal-cannabidiol (ABN-CBD) was also devoid of overt behavioral effects but produced marked hypotension with only slight bradycardia in anesthesized dogs.

Animals↗
PubMed1977

Acetylated methylmannose polysaccharide of Streptomyces.

A polysaccharide composed of 3-O-methyl-D-mannose and D-mannose in a molar ratio of approximately 10:1 and containing 3 to 4 esterified acetyl residues has been isolated from Streptomyces griseus. This acetylated methylmannose polysaccharide (AMMP) is similar to the methylmannose polysaccharide (MMP) of Mycobacterium smegmatis (Gray, G. R., and Ballou, C. E. (1971) J. Biol. Chem. 246, 6835-6842) in its size and composition, the absence of acidic or basic groups, and the lack of a reducing end. It is different, however, in its content of esterified acetyl residues, and it is slightly different in its structure and in its gel filtration properties. The structure of AMMP has been established by proton magnetic resonance spectroscopy, and by combinations of methylation analysis and Smith degradation utilizing non-radioactively labeled polysaccharide and [3H]methyl-labeled polysaccharide obtained from cells grown in the presence of L-[methyl-3H]methionine. It is concluded that AMMP is a linear, nonreducing, neutral polysaccharide composed of a terminal D-mannose residue linked alpha(1 leads to 4) to a chain of 10 consecutive alpha(1 leads to 4)-linked 3-O-methyl-D-mannose residues. The reducing terminal 3-O-methyl-D-mannose residue exists, at least in part, as its alpha-methyl glycoside. The positions of attachment of the ester residues have not been established.

Acetylation↗
PubMed1977

Monoamine metabolism in human brain.

Norepinephrine (NE), dopamine (DA), tyrosine hydroxylase (TH), catechol-O-methyltransferase (COMT) and monoamine oxidase (MAO) levels were measured in human brain tissue obtained at autopsy from a series of 39 patients dying of various medical and accidental causes. The nine following brain areas were studied: globus pallidus, thalamus, hypothalamus, hippocampus, substantia nigra, floor of the fourth ventricle, orbital cortex, caudate nucleus, and mammillary bodies. Enzyme activity correlated positively with age in all brain areas for MAO (with both benzylamine and tryptamine substrates) but no consistent pattern of correlation was found for COMT and TH. Mean MAO activity was significantly higher in women than men. There is increased brain MAO activity during late childhood and adolescence. These data are consistent with previous evidence suggesting that age and sex are important determinants of amine metabolism in the human central nervous system.

Adolescent↗
PubMed1977

Synthesis and pharmacological activity of some N-alkyl-substituted 9alpha-ethyl-2'-hydroxy-5-methyl-6,7-benzomorphans.

A series of N-substituted 9alpha-ethyl-2'-hydroxy-5-methyl-6,7-benzomorphans was synthesized and evaluated for their narcotic analgesic and antagonistic activities. Compounds 2a and 22 were as potent as morphine in the writhing (PPQ) and hot-plate tests, while a number of compounds demonstrated antagonistic activities greater than nalorphine. Generally, the compounds in this series show activities somewhat greater than the comparable compounds in the 5,9alpha-dimethyl-6,7-benzomorphan series for analgesic effect and similar or slightly less antagonistic potency.

Analgesics, Opioid↗
PubMed1977

Parasympatholytic (anticholinergic) esters of the isomeric 2-tropanols. 1. Glycolates.

The 38 esters in Table I were prepared from the four isomeric 2-tropanols and a variety of racemic glycolic acids and their optical isomers. Anticholinergic activity in mice was measured in the peripheral nervous system (mydriasis) and in the central nervous system (anti-tremorine) and compared with that of atropine, scopolamine, and racemic 2-quinuclidinyl benzilate. The results (Table III) showed that several esters (such as 8, 12, 14, and 21) had significantly greater activity in both the peripheral and central nervous systems than did the reference compounds. Esters of (+)-2alpha-tropanol were more potent than those of either its epimer (-)-2beta-tropanol or its optical isomer(-)-2alpha-tropanol. Esters derived from (-)-glycolic acids were uniformly more potent than those from the (+)-glycolic acids. Esters of (+)-2alpha-notropanol and five of its N-substituted derivatives had markedly decreased activity. Peripheral/central activity ratios and time-activity profiles for five active compounds are discussed and compared with those of the reference compounds.

Animals↗
PubMed1977

Enhanced susceptibility of mice to combinations of delta 9-tetrahydrocannabinol and live or killed gram-negative bacteria.

Combinations of delta 9-tetrahydrocannabinol (delta 9-THC) and bacterial endotoxin were shown to be hyperadditively toxic for mice. A variety of purified lipopolysaccharide (LPS) preparations elicted enhanced mortality in combination with delta 9-THC. Escherichia coli O26:B6 LPS (Boivin preparation) at an essentially nonlethal dose of 2.5 mg/kg reduced the dose of delta 9-THC required to kill 50% of the treated mice from ca. 350 to 150 mg/kg. Inbred BALB, DBA, and C3H/HeCr mice, noninbred ICR mice, and hybrid CDF1 and BDF1 mice were hyperreactive to combinations of delta 9-THC and LPS. Moreover, a variety of heat-killed intestinal and gram-negative bacteria, live E. coli, and complexes of lipid A with a variety of proteins substituted for LPS in the synergistic toxicity of LPS and delta 9-THC. Extracts of marijuana also elicited hyperreactivity to LPS. The hyperadditive lethality of combinations of delta 9-THC and LPS was markedly less in mice rendered refractory to LPS or delta 9-THC by repeated administration of LPS or delta 9-THC, respectively.

Animals↗
PubMed1977

The effects of naloxone and nalorphine during the development of morphine dependence in rhesus monkeys.

A randomized and blind experimental design was used to study the effects of naloxone and nalorphine on the development of morphine dependence in monkeys. The results suggest: (a) that significant dose-related differences existed for combined numbers of withdrawal symptoms times frequency of occurrences; (b) that naloxone and nalorphine were qualitatively similar; (c) antagonists are more effective as dependence develops; (d) naloxone is approximately 10 times more potent than nalorphine, and (e) vomiting was the only withdrawal sign with which ED50s could be calculated. Dependence on morphine still increases up to 9 months after the commonly accepted 90-day stabilization period as measured by the ED50 for vomiting for naloxone.

Animals↗
PubMed1977

Inhibition of cortiocosteroidogenesis by delta-9-tetrahydrocannabinol.

ACTH, cholera toxin, cyclic AMP but not pregnenolone-induced steroidogenesis in Y-1 functional mouse adrenal tumor cells was significantly inhibited by delta-9-tetrahydrocannabinol, cannabidiol, and cannabinol. The inhibition of steroidogenesis could not be correlated with a general depression in cell function or viability. The data suggest that cannabinoids inhibit corticosteroidogenesis at a site between the synthesis of cAMP and of pregnenolone.

20-alpha-Dihydroprogesterone↗
PubMed1977

9-nor-9beta-hydroxyhexahydrocannabinol, a cannabinoid with potent antinociceptive activity: comparisons with morphine.

The effects of (+/-)9-nor-9beta-hydroxyhexahydrocannabinol (beta-HHC) on tail-flick test activity and the accumulation of newly synthesized dopamine and norepinephrine were studied in the male albino mouse. The same parameters were also studied in naloxone-pretreated and morphine-tolerant mice. beta-HHC was about equipotent with morphine in the mouse tail-flick (ED50 = 7.12 mg/kg). The cannabinoid also produced dose-dependent increases in the accumulation of newly synthesized DA and NE. Pretreatment with 2 mg/kg of naloxone antagonized both the tail-flick activity and blocked the increases in catecholamine synthesis produced by beta-HHC. Cross-tolerance between beta-HHC and morphine did not exist in regard to either tail-flick activity or increased catecholamine synthesis. These studies suggest that beta-HHC may share some properties with the narcotic analgesics but that significant differences exist. Furthermore, these studies offer further evidence for the involvement of catecholamine containing neurons in the central mediation of the tail-flick response.

Analgesics↗
PubMed1977

Abdominal injuries in automobile accidents: review of care of fatally injured patients.

Hypovolemia continues to be an important cause of death in patients who die as a result of vehicular trauma. Diagnosis and treatment of a series of 127 patients who died with blunt abdominal trauma from automobile accidents during 1969-1974 in Vermont are reported. The most frequent errors in the cases reviewed were failure to recognize and adequately treat hypovolemia, and to appreciate the urgent need for surgery. Death on the X-ray table while allowing persistence of hypovolemia was the common denominator in four of the five victims who died of ruptured spleens in the emergency departments, after having arrived alive following vehicular trauma. Forty-seven per cent of all reported deaths in automobile accidents had blunt abdominal trauma. Of those with blunt abdominal trauma who arrived alive, 26% might have survived with appropriate treatment which should have been available.

Abdominal Injuries↗
PubMed1977

3H-delta9-tetrahydrocannabinol distribution in pregnant dogs and their fetuses.

Pregnant dogs were administered intravenously 0.5 mg/kg of 3H-delta9-tetrahydrocannabinol and sacrificed at 30 minutes, the time of peak behavioral effects. The distribution of radioactivity in mothers and fetuses was quantified in many peripheral tissues and in major brain areas by sample combustion and liquid scintillation spectrometry. Brains were subfractionated by differential centrifugation in order to compare the subcellular localization of radioactivity in maternal and fetal brains. Although the level of radioactivity in maternal brain was three times higher than that in fetal brain, the distribution of radioactivity in the major brain areas was similar in mothers and fetuses. However, the subcellular distribution of radioactivity in whole brain homogenate of fetal dogs was markedly different from that in whole brain homogenates from mothers and appeared to be related directly to differing phospholipid content.

Animals↗
PubMed1976

Derivatives of apomorphine and of other N-substituted norapomorphines.

Derivatives of apomorphine and of N-n-propylnorapomorphine were prepared to obtain modified pharmacological activity and enhanced chemical stability. Mouse profile and dog emesis screens were performed, and the activity of various N-substituted derivatives and their esters was evaluated and compared to the parent compounds. The N-n-propyl diacetate derivative and N-methyl and N-n-propyl ascorbate salts were remarkably stable to air: apomorphine etherate was no more stable than the free base. The dimers, the major products formed during the acid-catalyzed rearrangement of morphines to apomorphines, were all potent emetics. Additionally, two showed a significant antagonism to morphine in mice and dogs.

Animals↗
PubMed1976

Drugs derived from cannabinoids. 1. Nitrogen analogs, benzopyranopyridines and benzopyranopyrroles.

Various nitrogen analogs of delta6a,10a-tetrahydrocannabinol were synthesized by a general procedure described in an earlier communication. Minimum effective doses (MED50's) and lethal doses (LD50's) were determined by a modified Irwin mouse screen after iv administration of compounds in PEG 200. The most potent compounds were the propargyl (5t), allyl (5m), and chloroallyl (5o-q) derivatives. Overt behavioral effects (CNS depression, static ataxia, and hypersensitivity) of 5t and Roger Adams' carbocyclic analog (III) were found to be similar in the mouse, cat, dog, and monkey. Dichloroisoproterenol prevented and reversed many of the depressant effects of both III and 5t but had no effect on the ataxia produced by these compounds. In antinociceptive tests, 5t was active in the phenylquinone and Eddy hot-plate tests but was inactive in the tail-flick test.

Animals↗