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Biomedical subjects

J D Rose

Publications and source records attributed to J D Rose.

At least 73 records · Page 4Linked to original sources
PubMed1984

Joint and separate effects of estrogen and progesterone on responses of midbrain neurons to lordosis-controlling somatic stimuli in the female golden Syrian hamster.

Single midbrain neurons were examined for effects of ovarian hormone administration on responsiveness to an array of lordosis-controlling types of somatosensory stimuli in anesthetized, ovariectomized Syrian hamsters. Neuronal responses were recorded under four different hormonal treatment conditions: 1) estradiol benzoate (EB) followed by progesterone (P), 2) EB alone, 3) P alone, or 4) no hormone administration. Only the hamsters receiving both EB and P showed lordosis in a mating test immediately prior to preparation for recording. The joint administration of EB and P strongly facilitated unit responsiveness to lordosis-eliciting (e.g., lumbosacral tactile) forms of stimulation. The incidence of units showing sustained changes in firing of at least +/- 30% in response to these stimuli was highest in animals having received EB and P (69%) and lowest in those given P alone (37%), with the occurrence of responsive units significantly different across the four hormonal conditions. The magnitude of the median unit response to lordosis-trigger stimuli in hamsters given EB and P was significantly higher than unit responses in hamsters receiving either P alone or no hormone. Bilateral shoulders stimulation, a weak stimulus for lordosis elicitation, produced the most responses in units from animals given EB and P (42%) and the fewest in hamsters given EB alone (12%), with a significant difference in responsiveness across the hormonal conditions. The incidence of units responding exclusively to facial stimulation, which is strongly antagonistic to lordosis in behaving animals, was greatest in hamsters injected with P alone (22%) and least for cells from the animals given both EB and P (6%). The difference in unit responsiveness to this stimulus across the four hormone conditions was significant. Analysis of unit-response patterns by the multivariate technique of discriminant analysis revealed that neuronal responses to most stimuli, especially flanks, back, shoulders, and face, were differentially affected by the hormone treatments such that these response patterns could be used to identify the four hormonal conditions from which the neurons were sampled. In addition, the hormonal treatments were found to have influenced the incidence of accelerative or decelerative unit responses to somatic stimuli. Discriminant analysis of unit responses as a function of location of the cells within the midbrain showed that neurons in the tectum and central gray had response patterns highly distinguishable from each other as well as from those of cells in the central and ventromedial tegmental regions.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1983

Impairment or abolition of lordosis in the golden hamster by transection of spinal pathways.

Lumbosacral and thoracic tactile stimulation elicits lordosis in sexually-receptive female hamsters. Because of the major dorsal column involvement in transmission of tactile activity, transection of this pathway was examined for effects on somatosensory elicitation of lordosis and compared with effects of lateral column (unilateral or bilateral) transections. Interruption of either pathway completely eliminated lordosis on some tests. Dorsal column section at cervical or lumbar levels produced a unique effect, however, where lumbosacral stimuli elicited the tail, rump and hindlimb manifestations of lordosis without evoking the usual immobility of the forelimbs, head and vibrissae. In animals with lumbar transections, the rostral, but not caudal, motoric components of lordosis could still be elicited by thoracic stimuli. Lateral column transection did not consistently prevent complete, sustained lordosis responses, but the response posture was abnormal. These results show the integrity of the hamster's dorsal columns to be essential for elicitation of complete lordosis responses and suggest that the caudal and rostral motor components differ significantly in the nature of their control by spinal and supraspinal levels of the central nervous system.

Afferent Pathways↗
PubMed1983

1,2-Dihydropyrido[3,4-b]pyrazines: structure-activity relationships.

Certain derivatives containing the 1,2-dihydropyrido[3,4-b]pyrazine (1-deaza-7,8-dihydropteridine) ring system are active against experimental neoplasms in mice. The mechanism of action of these agents has been attributed to the accumulation of cells at mitosis. Identification of the structural features that are necessary for activity was accomplished by evaluation of modified 1-deazapteridines and ring and ring-opened analogues. Relative to ethyl 4-amino-1-deaza-7,8-dihydro-6-[(N-methylanilino)methyl]pteridine-2-carbamate (11) and the corresponding 6-phenyl compound (12), no antitumor activity was observed with 7,8-dihydropteridines, 3-deaza-7,8-dihydropteridines, and the corresponding heteroaromatic compounds. Also, activity was diminished or destroyed when 1-deaza-7,8-dihydropteridines were oxidized to 1-deazapteridines or reduced to 1-deaza-5,6,7,8-tetrahydropteridines. In addition, replacement of the 4-amino group with other substituents destroyed activity. The presence of a 6-substituent containing an aryl group appeared to be necessary for activity, which was increased when a methyl group was substituted at the 7-position.

Animals↗
PubMed1983

A prospective randomised controlled trial of diazepam (valium) vs emulsified diazepam (diazemuls) as a premedication for upper gastrointestinal endoscopy.

Two hundred and forty four patients were randomised to receive either diazepam or emulsified diazepam (diazemuls) intravenously prior to routine upper gastrointestinal endoscopy. The groups were comparable with regard to age, sex, medical condition, vein size, and amount of drug administered. A quantitative assessment of symptoms at the injection site during the ensuing week was made by analysing questionnaires on pain and tenderness, which the patients graded each day, on a scale 0-3. Twenty-one out of 82 patients who received diazepam (25.6%) and 22 out of 84 who received diazemuls (26.2%) had local symptoms. Although the mean symptom scores over 7 days for the two groups were not different (5.95 +/- 5.19 and 7.27 +/- 6.30 respectively), more patients who received diazepam reported induration (P = 0.033). In 112 patients, signs of thrombosis in the injected veins were looked for 3-7 weeks later without knowledge of the preparation given. Thrombosis was present in 13 (25%) patients who had received diazepam and two (3.6%) who had received diazemuls (P less than 0.002). Only eight (53%) patients with thrombosed veins had symptoms. Thrombosis after intravenous injection of diazepam or diazemuls may be symptomless, and is significantly less likely following diazemuls.

Adult↗
PubMed1983

Factors affecting successful endoscopic sclerotherapy for oesophageal varices.

Forty patients with bleeding oesophageal varices were studied during treatment by endoscopic sclerotherapy to discover what factors determine successful outcome. Large varices required more injections than small varices for obliteration, and rebleeding during treatment occurred only in patients with large varices. Radiological studies with sclerosant contrast mixture showed that in two groups of varices of comparable size, intravenous sclerosant was significantly more effective, leading to thrombosis in 8/10 as opposed to only 3/10 after paravasal injection (p less than 0.05). Intravenous contrast was rapidly cleared upwards, whereas paravasal contrast formed a rounded opacity alongside the vein that persisted for approximately 90 minutes, responsible for the complications of oesophageal ulceration and stenosis.

Adolescent↗
PubMed1983

Fibre endoscopic insertion of palliative oesophageal tubes with the Nottingham introducer.

Using the Nottingham introducer and diazepam sedation, 93 of 100 patients with oesophagogastric malignancy have been successfully intubated, 67 with Celestin tubes and 26 with Atkinson tubes. Their mean age was 72 years (range 36-91). Six of the failures were in patients with fundal adenocarcinoma. Sixty-nine patients were discharged from hospital after initial intubation (74%). Nine patients developed a perforation, 6 died and there were 5 deaths from aspiration. Nine patients are alive up to 11 months later. The mean survival after discharge was four months with a maximum of 18 months. Later 11 tubes obstructed and 12 Celestin tubes displaced upward. Endoscopic insertion of oesophageal prosthetic tubes provides satisfactory palliation for inoperable oesophagogastric malignancy. The development of the Atkinson tube with a distal flange has eliminated tube displacement upwards.

Adenocarcinoma↗
PubMed1982

Midbrain distribution of neurons with strong, sustained responses to lordosis trigger stimuli in the female golden hamster.

Midbrain single units in anesthetized female hamsters were examined for pronounced, sustained responses to types of somatic stimuli which control the display of lordosis during periods of sexual receptivity. Units showing strong responses to lordosis trigger stimuli were widely distributed, but tended to be most concentrated in th deep superior colliculus, ventromedial midbrain and central gray, brain regions previously implicated, by other methods, in the control of hamster lordosis.

Animals↗
PubMed1982

Synthesis of pseudo cofactor analogues as potential inhibitors of the folate enzymes.

Reaction of 5,6,7,8-tetrahydrofolic acid (THF,7) with phosgene, thiophosgene, and cyanogen bromide gave the bridged derivatives, 5,10-(CO)-THF (8), 5,10-(CS)-THF (9), and 5,10-(C = NH)-THF (11), respectively. Catalytic hydrogenation of 10-(chloroacetyl)folic acid (2) gave 5,10-(CH2CO)-THF (12). A similar reaction with 10-(3-chloropropionyl)folic acid (3) gave 10-(ClCH2CH2CO)-THF (14) rather than 5,10-(CH2CH2CO)-THF (13). In the catalytic hydrogenation of 10-ethoxalylfolic acid (5), the initial product 10-(EtO2CCO)-THF (22) rearranged readily to give 5-(EtO2CCO)-THF (21). Acylation of THF with chloroacetyl chloride gave a N5,N10-diacylated product (18 or 19), which could not be converted to 5,10-COCH2)-THF (17). Reductive alkylation of THF with glyoxylic acid and 5-hydroxypentanal, respectively, gave 5-(HO2CCH2)-THF (24) and 5-[HO(CH2)5]-THF (25). Reductive dialkylation of THF with formaldehyde gave 5,10-(CH3)2-THF (27), whereas glyoxal gave 5,10-CH2CH2)-THF (10). Also, both folic acid and 5-(CHO)-THF were reductively alkylated with formaldehyde to give 10-methylfolic acid (6) and 5-(CHO)-10-(CH3)-THF (28), respectively. These compounds were tested as inhibitors of the enzymes involved in folate metabolism and for activity against lymphocytic leukemia P388 in mice.

Animals↗
PubMed1982

New anticancer agents: synthesis of 1,2-dihydropyrido[3,4-b]pyrazines (1-deaza-7,8-dihydropteridines).

Reaction of alpha-aminoacetophenone oximes (2) with ethyl 6-amino-4-chloro-5-nitropyridine-2-carbamate (1) gave ethyl 6-amino-5-nitro-4-[(2-oxo-2-phenylethyl)amino]pyridine-2-carbamate oximes (3), which were hydrolyzed under acidic conditions to give the corresponding ketones (4). Related pyridines substituted with a keto side chain were prepared from 1 and 1,3-diaminopropanone oximes and by oxidation of the side-chain hydroxy group of ethyl 6-amino-4- [[3-(N-methyl-N-phenylamino)-2-hydroxypropyl]amino]-5-nitropyridine-7- carbamates (6). Catalytic hydrogenation of the nitro group of 4 over Raney nickel in a large volume of ethanol gave the 1-deaza-7,8-dihydropteridines (7). Several of the oximes 3 were successfully hydrogenated to give 7 directly. The resulting 1-deaza-7,8-dihydropteridines showed potent cytotoxicity against cultured L1210 cells and significant anticancer activity against lymphocytic leukemia P-388 in mice. These biological activities are attributed to the accumulation of cells at mitosis.

Animals↗
PubMed1981

New synthesis of N-[4-[[(2-amino-4(3H)-oxopyrido[3,2-d]pyrimidin-6-yl)methyl]amino]benzoyl]-L-glutamic acid (8-deazafolic acid) and the preparation of some 5,6,7,8-tetrahydro derivatives.

Previously, 8-deazafolic acid (17) was shown to be a potent inhibitor of the folate-dependent bacteria, Streptococcus faecium (ATCC 8043) and Lactobacillus casei (ATCC 7469), and to have activity against lymphoid leukemia L1210 in mice. To examine the 5,6,7,8-tetrahydro derivatives, a new synthesis of 17 was developed from 8-deaza-2,4-dichloro-6-methylpteridine. Treatment of the latter with aqueous base gave the corresponding pteridin-4(3H)-one, which was aminated with ammonia to give 8-deaza-6-methylpterin (9). Bromination of 9 gave mainly 8-deaza-6-(tribromomethyl)pterin, which on reaction with p-aminobenzoyl-L-glutamic acid resulted in the formation of the 9-oxo derivative of 17. In contrast, bromination of the 2-acetyl derivative of 9 gave mainly the corresponding 6-(bromomethyl)pterin, which was converted to 17 in 23% yield (from 9). Hydrogenation of 17 at atmospheric pressure and room temperature was unsuccessful either in a basic medium or formic acid. In trifluoroacetic acid, overreduction occurred to give a mixture containing 8-deaza-5,6,7,8-tetrahydro-6-methylpterin and the 5,6,7,8-tetrahydro derivative of 17. The latter was characterized by conversion to the methenyl analogue 21, which was also prepared by hydrogenation of the 10-formyl derivative of 17. Treatment of 21 with hydroxide gave 8-deaza-10-formyl-5,6,7,8-tetrahydrofolic acid. Compound 21 showed cytotoxicity to cultured H.Ep.-2 cells and was tested as an inhibitor of bovine dihydrofolic reductase. Lineweaver-Burk analysis indicated inhibition competitive with dihydrofolate.

Animals↗