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Biomedical subjects

J R Flynn

Publications and source records attributed to J R Flynn.

At least 19 recordsLinked to original sources
PubMed2001

Heritability estimates versus large environmental effects: the IQ paradox resolved.

Some argue that the high heritability of IQ renders purely environmental explanations for large IQ differences between groups implausible. Yet, large environmentally induced IQ gains between generations suggest an important role for environment in shaping IQ. The authors present a formal model of the process determining IQ in which people's IQs are affected by both environment and genes, but in which their environments are matched to their IQs. The authors show how such a model allows very large effects for environment, even incorporating the highest estimates of heritability. Besides resolving the paradox, the authors show that the model can account for a number of other phenomena, some of which are anomalous when viewed from the standard perspective.

Adult↗
PubMed2000

IQ gains, WISC subtests and fluid g: g theory and the relevance of Spearman's hypothesis to race.

IQ gains over time were calculated for each WISC (Wechsler Intelligence Scale for Children) subtest and the subtests ranked by size of gain. Verbal similarities led at 20 points per generation--larger than gains on Raven's Progressive Matrices. Similarities measures on-the-spot problem-solving (something akin to fluid g); verbal subtests that do not measure this show low rates of gain. WISC subtests were also ranked by their correlations with Raven's, the latter being used as a marker for fluid g. The r between the two hierarchies was calculated to approximate a correlation between IQ gains and fluid g. The result of 0.50 contrasts with the negative correlation between IQ gains and the g generated by factor analysing the WISC battery itself, which is generally viewed as predominately a crystallized g. In sum, it appears that human groups can make massive fluid g gains in a period too short to accommodate radical change in the speed and efficiency of neural processes. Moreover, once gains in intelligent behaviour over historical time are seen to be independent of brain physiology, does g really provide a criterion for assessing their significance? Finally, not only a measure of fluid g (which is highly heritable) but also inbreeding depression are shown to be correlated with IQ gains--gains overwhelmingly environmental in origin. Therefore, correlations between such genetically influenced factors and the size of the black/white IQ gap do not show that the gap has a genetic component.

Brain↗
PubMed1994

Aberrant thyroglossal cyst.

A case is presented of a laterally occurring thyroglossal cyst. In conventional teaching, thyroglossal duct remnants occupy the midline, or a position adjacent to the midline, and are found in a line marking the descent of the thyroid anlage and move upwards on protruding the tongue. Laterally presenting thyroglossal duct remnants are unusual.

Humans↗
PubMed1994

Laparoscopic cholecystectomy: potential for missed pathology.

The performance of a general exploratory laparotomy immediately after opening the abdominal cavity has long been a foundation of surgical practice. Since the introduction of laparoscopy, this procedure has been modified. This may result in certain intra-abdominal pathologies being overlooked, especially in areas that are hard to observe with the laparoscope. In this paper we describe two patients who presented with carcinomas after uneventful laparoscopic procedures, one of the lower oesophagus and the other of the pancreas. This raises questions about the extent of preoperative investigation before the performance of laparoscopic procedures.

Cholecystectomy, Laparoscopic↗
PubMed1993

The increasing incidence of infantile hypertrophic pyloric stenosis.

Several reports have suggested that there is an increasing incidence of infantile hypertrophic pyloric stenosis (IHPS). We examined the incidence of IHPS in a stable population in the West of Ireland over a ten year period (1981-1990). During the 10 years of the study the number of live births per year did not alter significantly. The incidence of IHPS increased significantly from 0.87/1000 live births in 1981 to 5.10/1000 in 1990 (p < 0.001, Student's test), peaking in 1989 at 6.8/1000. There was no statistical correlation between the increasing incidence and feeding habits, birth rank, family history or gender distribution. The reason(s) for this increase remain unclear.

Female↗
PubMed1991

Structure-activity studies on a potent antagonist to organophosphate-induced toxicity.

Molecular modifications have been made on a highly potent, active antagonist to organophosphate-induced toxicity, 4,4'-bis[1,3-dioxan-2-ylmethyl)methylamino]acetyl]biphenyl dimethobromide (1). Stepwise removal of the oxygen atoms from the dioxane rings, as well as changing the position of attachment of substituents on the 1,3-dioxane rings and decreasing the ring size from six-membered to five-membered caused drastic or complete loss of pharmacological effect. Partial structures of 1 were all inactive. Thus, the structure of 1 seems to be remarkably specific. Additional pharmacological data are reported for 1.

Animals↗
PubMed1991

Dopaminergic structure-activity relationships of 2-aminoindans and cardiovascular action and dopaminergic activity of 4-hydroxy, 5-methyl, 2-di-n-propylaminoindan (RD-211).

Dopaminergic structure-activity relationships of 2-aminoindans were evaluated for their ability to inhibit responses to stimulation of cardioaccelerator nerves in cats. The major observations were as follows: 1) Unsubstituted di-n-propyl- and diethyl 2-aminoindan derivatives do not inhibit responses to stimulation of cardioaccelerator nerve, although previous studies identified stimulation of DA2-receptors. 2) 4-Hydroxy, 4,7-dimethoxy and 4-hydroxy, 5-CH3, -CH2OH or -H substitutions on selected indan derivatives produce dopaminergic activity in the cardioaccelerator nerve preparation. 3) 4-Hydroxy-2-di-n-propylaminoindan is stereoselective with the R-isomer being more potent than the S-isomer. One derivative, 4-hydroxy-5-methyl-di-n-propyl-2-aminoindan (RD-211) produced dose-dependent decreases in heart rate and mean arterial pressure. Larger doses also inhibited cardiac responses to stimulation of cardioaccelerator nerve in vivo and in isolated right atria of cats. All of the above responses were significantly inhibited by the dopamine-receptor antagonist sulpiride and not by the alpha 2-adrenoceptor antagonist yohimbine. RD-211 also possesses high affinity for 5-hydroxytryptamine1A receptors as revealed by radioligand binding studies. Results suggest that RD-211 stimulates dopamine DA2-receptors and may also activate 5-hydroxytryptamine1A receptors, but is inactive at alpha 2-adrenoceptors. RD-211 appears not to require metabolic activation even though it has the same chemical moiety as the aminotetralin homolog, which is a dopaminergic prodrug (5-hydroxy-6-methyl-2-di-n-propylaminotetralin).

Animals↗
PubMed1990

Hemicholinium-3 congeners as potential antagonists to organophosphate-induced toxicity.

A series of congeners of hemicholinium-3, in which the 1,4-oxazinium rings of hemicholinium are replaced by pyrrolidine, piperidine, 1,3-dioxane, or 1,4-oxazine rings, is described. Several of the target compounds produced blockade of neuromuscular transmission in the rabbit, and three heterocyclic derivatives, 10, 11, and 13, significantly antagonized paraoxon-induced lethality in mice. 1,3-Dioxane derivative 11 was an extremely potent antagonist of paraoxon-induced toxicity in mice, compared with prototypical protective agents physostigmine and pyridostigmine. Compound 11 exhibited a much more favorable therapeutic ratio than the reference drugs. The mechanism of action of 11 has not been elucidated, although it is concluded that it differs from that of hemicholinium-3 (inhibition of high-affinity, sodium-dependent uptake of choline into nerve terminals).

Animals↗
PubMed1990

Monomethyl ether derivatives of 7,8-dihydroxy- and 8,9-dihydroxy-4-n-propyl-1,2,3,4,4a,5,6,10b-octahydrobenzo[f]quinolines as possible products of metabolism by catechol-O-methyltransferase.

In order to facilitate identification of possible metabolites arising from in vitro action of catechol-O-methyltransferase upon 7,8-dihydroxy- and 8,9-dihydroxy-4-n-propyl-1,2,3,4,4a,5,6,10b-octahydrobenzo[f]quinolines (11, 12), all four possible monomethyl ether derivatives have been synthesized. Incubation of 11 and 12 with the enzyme revealed that the 8,9-dihydroxy positional isomer 12 (which contains the dopamine moiety held in the beta conformation) but not the 7,8-dihydroxy isomer 11 (which holds the dopamine moiety in the alpha conformation) was a substrate for the enzyme. The sole detectable product of 12 was 8-hydroxy-9-methoxy derivative 15 in which the "meta" hydroxy group of the dopamine moiety is etherified.

Animals↗
PubMed1989

Introduction of a putative dopaminergic prodrug moiety into a 6,7-substitution pattern characteristic of certain 2-aminotetralin dopaminergic agonists.

On the basis of the premise that the dopaminergic agonist profile of 2-(di-n-propylamino)-5-hydroxy-6-methyltetralin (1a) is due to in vivo oxidation of the 6-methyl moiety and that 1a may represent a novel prodrug strategy, the vicinal methyl-hydroxyl substitution pattern was incorporated into the 6- and 7-positions of 2-(di-n-propylamino)tetralin to give the 6-methyl-7-hydroxy and 6-hydroxy-7-methyl isomers 8 and 9, respectively. A multistep synthetic approach was devised which permitted preparation of target molecules 8 and 9. Pharmacological data revealed that both target compounds exhibit modest dopamine-like effects in the cardioaccelerator nerve assay in the cat, but neither appeared to be metabolically activated as was the case with 1a. The effects of 9 (but not of 8) were antagonized by pretreatment with haloperidol. Thus, the 5-hydroxy-6-methyl substitution pattern in the 2-aminotetralins remains unique as a dopaminergic agonist prodrug structure.

Animals↗
PubMed1988

(R)-(-)-10-methyl-11-hydroxyaporphine: a highly selective serotonergic agonist.

Prior work in these laboratories identified (+/-)-5-hydroxy-6-methyl-2- (di-n-propylamino)tetralin as a dopaminergic agonist prodrug. The ortho methyl hydroxy aromatic substitution pattern in this molecule has now been incorporated into the aporphine ring system to give a congener of the dopaminergic agonist apomorphine in which the position 10 OH group has been replaced by methyl. Preparation of the target compound involved acid-catalyzed rearrangement of the 3-(1-phenyltetrazolyl) ether of morphine and subsequent molecular modification of the product, the 10-(1-phenyltetrazolyl) ether of (R)-(-)-apomorphine. Surprisingly, the target compound elicited no responses in any assays for effects at dopamine receptors, but rather it displayed pharmacological properties consistent with its being a serotonergic agonist with a high degree of selectivity for 5-HT1A receptors similar to the serotonergic agonist 8-hydroxy-2-(di-n-propylamino)tetralin.

Animals↗
PubMed1988

Structure-activity relationship studies of hemicholinium (HC-3) congeners.

In a continuing investigation of structural requirements for hemicholinium-like activity (inhibition of neuromuscular transmission due to inhibition of uptake of choline into nerve terminals), some additional molecular modifications of hemicholinium ("HC-3"; structure 1) were made. The target compounds were prepared by standard one- or two-step sequences. Noncyclic acetal moieties in general permitted retention of pharmacological activity, as did concomitant replacement of the central biphenyl "spacer" by other bulky cyclic groupings and replacement of the oxazinium rings by piperidine or 4-methylpiperidine. However, these modifications generally produced compounds of a lower potency. Replacement of the biphenyl moiety of HC-3 with polyakylene chains permitted retention of a considerable degree of activity. In these target compounds, the two quaternary nitrogens can exist the same distance apart (approximately 14 A) as in the hemicholinium molecule. The ditertiary amino congener of a pharmacologically active bis-quaternary oxazinium compound was almost completely inactive. To date, only one tertiary amine has been found which displays a significant degree of hemicholinium-like activity.

Animals↗
PubMed1988

Alterations in acetylcholine metabolism in rat striatal slices by a 4-methyl piperidine analog of hemicholinium-3.

The in vitro effects of a tertiary amine, 4-methyl piperidine analog of hemicholinium-3 (A-4), were investigated on acetylcholine (ACh) metabolism in rat striatal slices. Rat striatal slices were incubated in the presence of 1.0 microM [3H]-choline in the presence or absence of 0.1 mM A-4. High pressure liquid chromatography with electrochemical detection was utilized to separate and measure total and [3H]-labeled ACh and choline. The effects of A-4 on [3H]-choline uptake, ACh and choline content, ACh release, and specific activity of ACh and choline tissue pools were investigated. Results indicated that A-4 inhibited the uptake of [3H]-choline into the striatal slices. Addition of 0.1 mM A-4 also produced a significant reduction in ACh content and ACh release and reduced the specific activity of the tissue choline and ACh pools. The effects of A-4 were more prominent upon immediate incubation than after a 60-min preincubation. These studies demonstrate that the pharmacological effects exhibited by A-4 are consistent with inhibition of choline uptake, with subsequent reduction in ACh synthesis and release.

Acetylcholine↗
PubMed1988

Stereoisomers of quaternary and tertiary 4-methyl piperidine analogs of hemicholinium-3.

Previous studies have shown that quaternary and tertiary 4-methyl piperidine derivatives of hemicholinium-3 (A-5 and A-4, respectively) are potent inhibitors of choline uptake. The d-, l-, and mesostereoisomers of A-5 and A-4 were separated and the potency and reversibility were compared. Isomeric forms of each compound were found to be approximately equipotent inhibitors in the following preparations: inhibition of rabbit neuromuscular transmission using the sciatic nerve-gastrocnemius muscle preparation, reductions in acetylcholine content in rat caudate tissue slices and inhibition of choline uptake in neuroblastoma cells, line NB41A3. Because these results show no difference in potency or reversibility for the stereoisomers of A-5 or A-4, these studies indicate that hydroxyl substitutions in these agents do not play a role in their biologic activity. Perhaps only 2-point attachment is required for inhibition of choline transport by hemicholinium-like compounds.

Acetylcholine↗
PubMed1987

A-4, a bis tertiary amine derivative of hemicholinium-3 produces in vivo reduction of acetylcholine in rat brain regions.

The pharmacological effects of A-4, a bis 4-methylpiperidine tertiary amine derivative of hemicholinium-3, were investigated. Systemic administration (i.p.) of this compound produced a dose-dependent reduction in acetylcholine content of several brain regions. A dose of 40 mg/kg of A-4 produced a 40% reduction in acetylcholine content in the corpus striatum and this reduction was maintained for over 4 hr. Increased choline content was found concurrent with the reduction in acetylcholine content. Reversal of the A-4-induced reductions in acetylcholine content was seen with eserine and oxotremorine but not with choline chloride. Acute treatment with A-4 appeared selective for cholinergic neurons as no significant changes were seen in norepinephrine or serotonin parameters of any of the brain regions assayed. Dopamine turnover was increased in the striatum. The neurochemical changes produced by A-4 were not seen with the bis 4-methylpiperidine quaternary amine, A-5, or hemicholinium-3 after systemic administration of doses which produced pronounced behavioral and toxic effects. Intraventricular administration of A-5 or hemicholinium-3 produced a selective reduction in acetylcholine content. No changes were seen in dopamine, norepinephrine or serotonin parameters. Thus, A-4 represents a novel hemicholinium-3 analog in its ability to act centrally after systemic administration and may be potentially useful as a pharmacological tool in understanding cholinergic mechanisms in the central nervous system.

3,4-Dihydroxyphenylacetic Acid↗