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Biomedical subjects

J K Morris

Publications and source records attributed to J K Morris.

67 records · Page 4Linked to original sources
PubMed1993

Hormone induction of luteinization and prostaglandin endoperoxide synthase-2 involves multiple cellular signaling pathways.

To determine the cellular signaling pathways involved in granulosa cell luteinization, known activators of protein kinase-A (LH and FSH) and protein kinase-C [GnRH and phorbol 12-myristate 13-acetate (PMA)] as well as inhibitors of tyrosine kinases (AG18 and genistein) were tested in an in vitro system using specific markers of luteinization (cell hypertrophy, side-chain cleavage cytochrome P450, and progesterone) and ovulation [prostaglandin endoperoxide synthase-2 (PGS-2)]. When preovulatory follicles were incubated in the presence of an ovulatory (500 ng/ml) dose of LH or high GnRH (1 microM), the granulosa cells harvested from these follicles assumed and maintained a stable luteal cell phenotype in vitro. Granulosa cells harvested from follicles incubated in subovulatory doses of LH (5 and 50 ng/ml), lower doses of GnRH (5, 50, and 500 nM), or PMA alone were unable to form a stable luteal cell phenotype. When PMA was combined with subovulatory doses of LH, granulosa cells luteinized, and PGS-2 protein was induced. AG18 (or genistein) blocked agonist induction of luteinization and of PGS-2 mRNA and protein when present during the first 2 h (0-2 h) of follicle incubation, but failed to block these events if added for the last 2 h (5-7 h of incubation). Combined, these results provide evidence to support a primary role for cAMP and protein kinase-A, a supportive but essential role for protein kinase-C, and an obligatory role for tyrosine kinases acting at an early stage in the cascade of events required for luteinization and ovulation.

Animals↗
PubMed1993

Medicinal chemistry of imidazoquinolinone dopamine receptor agonists.

(R)-5-(Dipropylamino)-5,6-dihydro-4H-imidazo[4,5,1-ij]-quinolin-2( 1H)-on e (1a, U-86170), a potent high intrinsic activity dopamine (D2) agonist, has been prepared in eleven steps from quinoline. In several tests, the compound showed dopamine autoreceptor agonist activity at low doses. It showed postsynaptic agonist activity at somewhat higher doses, reversing the effects of reserpine in mice and increasing striatal acetylcholine levels. The compound showed some serotonergic (5HT1A) activity, but was inactive at other receptors. The related monopropylamine 2 (U-91356), also showed good dopaminergic agonist activity, and had improved metabolic stability and oral bioavailability in the rat and monkey when compared to 1a. Compounds 1a and 2 have been prepared in tritiated form, and [3H]1a (69 Ci/mmol) has found use as a D2 agonist radioligand in binding assays. The dopaminergic (D2) and serotonergic (5HT1A) activities of a series of compounds related to 1a have been evaluated using this ligand, [3H]raclopride, and [3H]8-OH DPAT.

Aminoquinolines↗
PubMed1992

Dopaminergic and serotonergic activities of imidazoquinolinones and related compounds.

The synthesis of 5-(dipropylamino)-5,6-dihydro-4H-imidazo[4,5,1-ij] quinolin-2(1H)-one (5), a potent dopamine D2 agonist showing high dopamine/serotonin (5HT1A) selectivity, is described. Dopaminergic activity is associated with the (R)-enantiomer of 5; the (S)-enantiomer shows no dopaminergic activity. A series of analogues where the imidazolone ring was modified to various 5- or 6-membered heterocyclic rings were prepared. Some of these compounds showed a combination of dopaminergic and serotonergic activity, while one compound, 6-(dipropylamino)-1,2,6,7-tetrahydro-3H,5H-pyrido[3,2,1- ij]quinazolin-3-one (24), was a selective serotonergic agonist. Various analogues of 5 where the dipropylamine substituent was modified were prepared. Most of these showed reduced dopaminergic activity, while several were as potent as 5 at the serotonin 5HT1A receptor. Orientations for the new compounds at dopamine and serotonin receptors are proposed and compared with those of other tricyclic ligands known to have high affinity at these receptors.

Aminoquinolines↗
PubMed1992

Non-employment and changes in smoking, drinking, and body weight.

OBJECTIVE: To assess the effect of unemployment and early retirement on cigarette smoking, alcohol consumption, and body weight in middle aged British men. DESIGN: Prospective cohort study (British regional heart study). SETTING: One general practice in 24 towns in Britain. SUBJECTS: 6057 men aged 40-59 who had been continuously employed for five years before the initial screening. Five years after screening 4412 men had been continuously employed and 1645 had experienced some unemployment or retired. MAIN OUTCOME MEASURES: Numbers of cigarettes smoked and units of alcohol consumed per week and body mass index (kg/m2). RESULTS: An initial screening significantly higher percentages of men who subsequently experienced non-employment smoked or had high alcohol consumption than of men who remained continuously employed: 43.0% versus 37.0% continuously employed for cigarette smoking (95% confidence interval for difference 3.2% to 9.0%) and 12.1% versus 9.0% for heavy drinking (1.3% to 5.1%). There was no evidence that men increased their smoking or drinking on becoming non-employed. Men non-employed through illness were significantly more likely to reduce their smoking and drinking than men who remained continuously employed. Men who experienced non-employment were significantly more likely to gain over 10% in weight than men who remained continuously employed: 7.5% versus 5.0% continuously employed (0.9% to 4.0%). CONCLUSIONS: Loss of employment was not associated with increased smoking or drinking but was associated with an increased likelihood of gaining weight. The long term effects of the higher levels of smoking and alcohol consumption before nonemployment should be taken into account when comparing mortality and morbidity in groups of unemployed and employed people.

Adult↗
PubMed1992

In vivo T1 values from guinea pig brain depend on body temperature.

T1 and T2 values were calculated from guinea pig brain in vivo at 0.5 T. T1 values showed significant dependence on body temperature, but the effect varied significantly from animal to animal and from one tissue type to another. Mean dependencies were 8.2 ms/degrees C for corpus callosum, 14.7 ms/degrees C for gray matter, and 21.5 ms/degrees C for hemispheric white matter (1.7, 2.6, and 4.5%/degrees C, respectively), all with respect to core temperature. These findings suggest that body temperature monitoring and control may be needed when sensitive measurements of T1 are being made. There was evidence for regulation of brain temperature within the hyperthermic range of body temperature.

Animals↗
PubMed1992

Use of general practice by intravenous heroin users on a methadone programme.

Users of intravenous heroin represent a major challenge for general practice. A study was undertaken in a general practice in central London in 1990 to investigate the use of general practice made by intravenous heroin users who were on a methadone programme. Using information recorded in the patients' notes, 29 intravenous heroin users on a methadone programme were identified; 58 non-drug users (two controls per case) were matched for age, sex and general practitioner. A study of the number of routine consultations, missed appointments, emergency appointments and prescribed items showed that during the study period, those on a methadone programme made a larger number of routine consultations than the control subjects (median number of consultations 14 versus 0). When consultations at which only a prescription was issued were excluded this difference disappeared. Appointments were missed by 14 drug abusers (48%) but by none of the control group (P < 0.001). Emergency appointments were made by seven drug abusers (24%) compared with only two controls (3%) (P < 0.01). Even after prescriptions for methadone hydrochloride had been excluded from the analysis, patients on the methadone programme were prescribed significantly more items than patients in the control group (P < 0.001). This research has shown that intravenous heroin users on a methadone programme used general practice to a greater extent than non-drug users, according to the criteria used in the study. The implications that this may have in discouraging budget holding practices from running such schemes are discussed.

Adult↗
PubMed1992

Non-consulters and high consulters in general practice: cardio-respiratory health and risk factors.

The 1990 General Practitioner contract requires that health promotion and illness prevention services should be provided to all patients aged 16-74 years. Consultation rates over a period of three years were examined in 7010 middle-aged men in Great Britain to compare the cardio-respiratory health and risk factor status of non-consulters (men who did not consult in three years) with those of average consulters (men who consulted 3-5 times in three years) and high consulters (men who consulted 24 or more times in three years) to assess their relative need for health promotion and illness prevention services. The non-consulters (n = 1025) were remarkably similar to the average consulters (n = 1585) in health and lifestyle characteristics. The high consulters (n = 306) had a greater burden of ill-health and a less healthy lifestyle. Chest pain on exertion, chronic bronchitis, breathlessness or wheeze were present in 23 per cent of non-consulters, 27 per cent of average consulters and over 50 per cent of high consulters. Similarly, 48 per cent of the non-consulters smoked, drank heavily or were obese compared with 47 per cent of the average consulters and 61 per cent of the high consulters. The prevalence of recall of high blood pressure which had been diagnosed by a doctor rose from 6 per cent in non-consulters and 10 per cent in average consulters to 29 per cent in high consulters.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1991

Sources of T1 variance in normal human white matter.

The major factors contributing to T1 variance at 0.5 T in white matter were studied in healthy people. Anatomical location of the white matter sampled and differences between individuals contributed 74% of the total variance in serial measurements of the same subjects. There was also significant change over time within an individual subject that could not be attributed to machine drift. This information permitted estimates to be made concerning adequate sample size in future studies that examine for pathological white matter T1 change.

Adolescent↗
PubMed1991

Cholinergic activity of acetylenic imidazoles and related compounds.

A series of acetylenic imidazoles related to oxotremorine (1a) were prepared and evaluated as cholinergic agents with in vitro binding assays and in vivo pharmacological tests in mice. 1-[4-(1H-Imidazol-1-yl)-2-butynyl]-2-pyrrolidinone (1b) was a cholinergic agonist with one-half the potency of oxotremorine. Analogues of 1b with a 5- or 2-methyl substituent in the imidazole ring (compounds 1c and 1g) were cholinergic partial agonists. Analogues of 1b with a methyl substituent at the 5-position in the pyrrolidinone ring (7b) or at the alpha-position in the acetylenic chain (8b) were antagonists. Various analogues of these imidazole acetylenes where the pyrrolidinone ring was replaced by an amide, carbamate, or urea residue were prepared. Several compounds which contained 5-methylimidazole as the amine substituent were partial agonists. The activities of the imidazole compounds are compared with those of the related pyrrolidine and dimethylamine analogues. Agonist and antagonist conformations for these compounds at muscarinic receptors are proposed.

Acetylene↗
PubMed1991

A critical review of the effect of factory closures on health.

The dramatic rise in unemployment in the 1970s and 1980s has led to an increase in research into the possible effects of unemployment on health. Studies of the effects of job loss are difficult to interpret because of the difficulty in ruling out selection effects--for example, the least fit may be more likely to be made redundant. The study of factory closures is appealing since all employees are made redundant and all the studies of factory closure recorded in the Index Medicus since 1980 are reviewed. None of the studies fulfil all the criteria for an ideal study, and most fail on several counts. The small sample sizes are often unavoidable, but the lack of awareness of possible selection effects often results in a biased control group of only those people who are economically active. Also, the short duration of follow up restricts the detection of possible long term effects on health. Thus the conclusions that can be drawn about the health effects of factory closures are limited. Whereas there is evidence of short term effects on mental health and of increased use of primary health care, no long term effects have been studied and objective data on physical health are almost non-existent.

Adult↗
PubMed1990

Consultation rates among middle aged men in general practice over three years.

OBJECTIVE: To provide data on consultation rates in general practice for middle aged men over three years according to their age and social class. DESIGN: Prospective study of men over eight years. Data on consultation rates during years 6-8 were collected retrospectively from practice records. SETTING: Over 1000 general practices in Great Britain by year 8. Initially (in 1978-80) the men had been selected at random from one practice in each of 24 towns. SUBJECTS: 7013 Men aged 46-65 in the sixth year of follow up. MAIN OUTCOME MEASURE: Number of consultations a year over three years. RESULTS: The mean annual consultation rate over the three years rose steadily with age (7.0 at age 46-50 to 9.7 at age 61-65) and with social class (6.4 in class I to 10.0 in class V) but was potentially misleading as the distribution was skew: 10.5% of men (736) did not consult over the three years and 17.2% (1209) consulted only once or twice, whereas 11.4% (798) of men were seen more than 18 times. The percentage of men who did not consult over three years fell only slightly with age and was unrelated to social class, with roughly a tenth of all age and social class groups not consulting. Two thirds of non-consulters in year 6 (1598/2334) consulted in year 7 or 8. CONCLUSIONS: The mean is not an appropriate summary measure of consultation rates and may conceal important differences among practices or other groups. The new general practitioner contract stipulates that all patients aged 16-74 must be provided with information to promote health and prevent illness at least once every three years. Most practices will have to approach a tenth of their men aged 46-65 specially to provide this service even if one consultation in three years is regarded as sufficient to allow a service to be provided.

Age Factors↗
PubMed1990

Effect of storage temperature, cooling rates and two different semen extenders on canine spermatozoal motility.

Ejaculates were collected form three mixed-breed male dogs daily for 3 d. The semen was diluted in either a nonfat dried milk solid-glucose (NFDMS-G) or egg yolk citrate (EYC) extender at a concentration of 25 x 10(6) sperm/ml. The diluted samples were exposed to three different storage temperatures (35, 22 and 4 degrees C). Three cooling rates (-1.0, -0.3 and -0.1 degrees C/min) were also investigated at the lowest storage temperature (4 degrees C). The semen was evaluated for total motility, progressive motility and velocity at 0, 6, 12, 24, 48, 72, 96 and 120 h after collection by two independent observers. Interactions between extenders, temperatures and time after collection were found for each of the variables. Nonfat dried milk solid-glucose diluent was superior to EYC (P<0.05) in preservating sperm motility parameters that were evaluated for most of the observations. The evaluated sperm motility parameters were also significantly superior (P<0.05) in semen stored at 4 degrees C than at 35 or 22 degrees C for most of the observations. The progressive motility and velocity of sperm in semen cooled at 4 degrees C in NFDMS-G were higher (P<0.05) at the fast and medium cooling rates (-1.0 and -0.3 degrees C) than at the slow cooling rate (-0.1 degrees C/min) at 24 and 72 h, and at 48 h, respectively. In conclusion, the present study suggests that canine spermatozoal motility is well preserved when a NFDMS-glucose extender is added to the semen and the semen is cooled at a medium or fast rate to a storage temperature of 4 degrees C. Additional studies are needed to evaluate the fertility of semen stored in this manner.

Journal Article↗