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Showing papers by "St Bartholomew's Hospital published in 1971"



Journal ArticleDOI
TL;DR: A radioimmunoassay of plasma ACTH, useful for several mammalian species, has been adapted for the rat and binding studies showed that the antibody bound most effectively with the 1–24 fragment and nearly as effectively withThe 1–39 native human and porcine molecules.
Abstract: A radioimmunoassay of plasma ACTH, useful for several mammalian species, has been adapted for the rat. The antibody permitting this versatility was produced in the rabbit by immunization with the species-common, steroidogenic 1–24 amino acid sequence of ACTH. Binding studies, using polypeptide fragments of ACTH, showed that the antibody bound most effectively with the 1–24 fragment and nearly as effectively with the 1–39 native human and porcine molecules. The antibody failed to react significantly with αMSH, βP-MSH or with synthetic 1–16 amide or αp 17–39 fragments of ACTH. A close similarity was found between bioactivity and immunoreactivity in 3 tested specimens of rat plasma. Physiological validation of the method was obtained from the following studies. The immunoreactive plasma ACTH concentration at 9 AM in “resting” male rats was 23±4 pg/ml (mean±SE), when the plasma corticosterone concentration was 4 ± 0.4 μg/100 ml. At 4:30 PM, plasma ACTH was 63 ± 9 pg/ml and plasma corticosterone was 13 ± 2 μg/...

422 citations


Journal ArticleDOI
TL;DR: Clinical estimates of improvement and continued remission in azathioprine-treated patients of groups I and II were confirmed by " disease-activity scores " compiled from clinical and laboratory data.

271 citations


Journal ArticleDOI
TL;DR: It is suggested that, in the absence of pituitary or hypothalamic disease, the response of serum T.R.S.H.H., or synthetic thyrotrophin-releasing hormone, provides a simple, safe, sensitive, and reliable test of thyroid function.

250 citations


Journal ArticleDOI
10 Dec 1971-Nature
TL;DR: OXYTOCIN, a potent stimulant of myometrial activity, is used extensively in clinical practice for the induction of labour and the role of endogenous oxytocin, however, has been disputed.
Abstract: OXYTOCIN, a potent stimulant of myometrial activity, is used extensively in clinical practice for the induction of labour. The fact that in animals circulating concentrations of this peptide are increased during labour and maximal at the time of delivery1,2 suggests that oxytocin released by the maternal posterior pituitary may play an important part in spontaneous labour. The role of endogenous oxytocin, however, has been disputed. Bioassays suggest that the circulating concentrations are increased to 100 µU/ml. or more3,4, while indirect evidence suggests that there is no more than 10 µU/ml., and perhaps much less5.

218 citations



Journal ArticleDOI
TL;DR: It is concluded that Lipid peroxidation, by controlling membrane integrity, may exert a regulating effect on the oxidative metabolism and carbohydrate metabolism of the endoplasmic reticulum in vivo.
Abstract: 1. Induction of the formation of lipid peroxide in suspensions of liver microsomal preparations by incubation with ascorbate or NADPH, or by treatment with ionizing radiation, leads to a marked decrease of the activity of glucose 6-phosphatase. 2. The effect of peroxidation can be imitated by treating microsomal suspensions with detergents such as deoxycholate or with phospholipases. 3. The substrate, glucose 6-phosphate, protects the glucose 6-phosphatase activity of microsomal preparations against peroxidation or detergents. 4. The loss of glucose 6-phosphatase activity is not due to the formation of hydroperoxide or formation of malonaldehyde or other breakdown products of peroxidation, all of which are not toxic to the enzyme. 5. All experiments lead to the conclusion that the loss of activity of glucose 6-phosphatase resulting from peroxidation is a consequence of loss of membrane structure essential for the activity of the enzyme. 6. In addition to glucose 6-phosphatase, oxidative demethylation of aminopyrine or p-chloro-N-methylaniline, hydroxylation of aniline, NADPH oxidation and menadione-dependent NADPH oxidation are also strongly inhibited by peroxidation. However, another group of enzymes separated with the microsomal fraction, including NAD+/NADP+ glycohydrolase, adenosine triphosphatase, esterase and NADH–cytochrome c reductase are not inactivated by peroxidation. This group is not readily inactivated by treatment with detergents. 7. Lipid peroxidation, by controlling membrane integrity, may exert a regulating effect on the oxidative metabolism and carbohydrate metabolism of the endoplasmic reticulum in vivo.

164 citations




Journal ArticleDOI
TL;DR: Food in eight hospitals, eleven canteens, and two schools has been examined for the presence of Escherichia coli, Pseudomonas œruginosa, Klebsiella spp.

111 citations


Journal ArticleDOI
TL;DR: It is suggested that the poly ADP-ribose polymerase is more likely involved in the control of DNA synthesis than in NAD synthesis, because it cannot explain the different effects that nicotinamide and 5-methyl Nicotinamide have on hepatic NAD synthesis.

Journal ArticleDOI
TL;DR: The range of plasma levels of human chorionic somatomammotrophin in the third trimester of pregnancy has been established in 100 normal subjects and a relationship was found between mean circulating levels of the peptide and fetal weight.

Journal ArticleDOI
15 Jan 1971-Nature
TL;DR: The enzyme L-asparaginase, which breaks down asparagine, causes certain tumours to regress, and this property has been put to use in the treatment of malignant disease in man.
Abstract: The enzyme L-asparaginase, which breaks down asparagine, causes certain tumours to regress. This property has been put to use in the treatment of malignant disease in man.


Journal ArticleDOI
30 Apr 1971-Nature
TL;DR: A ONCE popular view among anthropologists was that many of the morphological features common to man and the living apes could be attributed to a shared evolutionary phase of brachiating locomotion.
Abstract: A ONCE popular view among anthropologists was that many of the morphological features common to man and the living apes (especially the gorilla and chimpanzee) could be attributed to a shared evolutionary phase of brachiating locomotion. It was further plausibly suggested that such arboreal suspensory activity could have provided an excellent apprenticeship for the adoption of erect bipedal posture by the early terrestrial hominids.

Journal ArticleDOI
TL;DR: It is supported that this phenomenon, as well as the raised liability to haemorrhage of group-O persons among those suffering from duodenal ulcers, is related to the higher average level of antihaemophilic globulin in A than in O persons.

Journal ArticleDOI
TL;DR: Dothiepin was superior to amitriptyline at the 5% significance level in terms of its antidepressant activity and was better tolerated in relation to its side effects than amitripyline.
Abstract: Fifty out-patients took part in a double-blind controlled comparison of two antidepressants dothiepin and amitriptyline. The subjects' psychiatric state was assessed by both self-rating and clinician-rated scales. Patients were followed up for a period of about three months.

Journal ArticleDOI
TL;DR: A rapid radioimmunoassay for human chorionic somatomammotrophin has been developed which permits an individual plasma determination to be completed in one hour, based on the use of high concentrations of antibody and labelled hormone.

Journal ArticleDOI
TL;DR: It is concluded that the seminiferous tubules of rat testes possess a steroidogenic capacity distinct from that of the interstitium and suggested that the Sertoli cells are the most likely source of the androgens and perhaps also of the C21 compounds.
Abstract: The seminiferous tubules of rat testes were separated from the adjacent interstitial tissue by dissection and incubated with [7$\alpha $-$^{3}$H]pregnenolone and [4-$^{14}$C]progesterone in an oxygenrich, Krebs-Ringer bicarbonate medium at 33 degrees C for a maximum period of 6 h. Samples of the incubation medium were taken at various time intervals throughout the experiment to provide a kinetic study of the metabolic processes occurring, and the radioactive steroid products were identified and estimated. There was conversion of the labelled substrates to androgens and to a series of hydroxylated and/or reduced C$_{21}$ compounds, namely 20$\alpha $-hydroxypregn-4-en-3-one, 5$\alpha $-pregnane-3$\beta $,20$\alpha $-diol, 5$\alpha $-pregnane-3$\beta $-ol-20-one, 5$\alpha $-pregnane-3$\alpha $-ol-20-one, and 5$\alpha $-pregnane-3,20-dione. The preferred pathway of androgen synthesis was via $\Delta ^{4}$ intermediates. Thus the two series of compounds originated from the common precursor, progesterone, and then diverged along separate pathways. A comparison with parallel studies carried out previously on isolated interstitial tissue shows that there are definite differences in the steroidogenic activity of the two main components of the testis which cannot be accounted for by contamination. Hence it is concluded that the tubules possess a steroidogenic capacity distinct from that of the interstitium. It is suggested that the Sertoli cells are the most likely source of the androgens and perhaps also of the C$_{21}$ compounds. On this basis, and evidence which suggests that a significant proportion of the labelled metabolites were retained by the tubules (e.g. by selective binding), the possibility is considered that the capacity of the Sertoli cells to elaborate steroids in vitro may be at least equal to that of the Leydig cells.

Journal ArticleDOI
TL;DR: The antibiotic sensitivity and ability to transfer resistance has been determined for strains of Escherichia coli isolated from animals, meat, hospital food, the faeces of hospital patients, and the faes of normal people.

Journal ArticleDOI
TL;DR: After sleep deprivation, detection performance was significantly impaired and was reflected in a fall of d′, whereas β was not significantly altered, which revealed a decrement in % signals detected and d′.
Abstract: Twelve subjects performed a high signal rate vigilance task, once after a night's sleep, and once after a night without sleep. Raw scores were transformed into the signal detection parameters, d′ and β. After sleep deprivation, detection performance was significantly impaired. This was reflected in a fall of d′, whereas β was not significantly altered. Analysing the control data alone for comparison with other vigilance studies revealed a decrement in % signals detected and d′, and an increase in β from the first to the second half of the test. Now at St. Bartholomew's Hospital, London. Senior author.

Journal ArticleDOI
TL;DR: It was concluded that nicotine may be concentrated within neurones, and that such intracellular accumulation may be augmented during depolarization induced by nicotine.
Abstract: 1. Uptake of (3)H-nicotine by isolated rat superior cervical sympathetic (SCG) and nodose (NG) ganglia was measured in vitro. Depolarization of the ganglia by nicotine was measured electrically.2. Nicotine depolarized the SCG but not the NG. The mean ED50 for depolarization was 5.3 x 10(-6)M.3. Both ganglia accumulated nicotine when incubated in 3.1 x 10(-5)M(3)H-nicotine: after 30 min incubation the ratios of tissue to medium concentrations were (mean +/- S.E. of mean): SCG, 3.49 +/- 0.13; NG, 2.50 +/- 0.09.4. Total water contents, estimated by drying to constant weight, were: SCG, 83.8 +/- 0.12%; NG, 80.1 +/- 0.21%. Extracellular spaces, measured as (3)H-mannitol space, were: SCG, 38.8 +/- 1.3; NG, 40.3 +/- 0.8% wet weight. These values were not significantly altered by nicotine.5. Correction for tissue fluid spaces indicated that the ratio of the mean intracellular fluid concentration to the extracellular fluid concentration for (3)H-nicotine at 3.1 x 10(-5)M were: SCG, 7.4; NG, 5.6. The ratios were not altered in any consistent manner on varying the nicotine concentration between 3.1 x 10(-7) and 1.6 x 10(-4)M.6. When the nicotine concentration was sufficiently great (6.2 x 10(-6)M or more) to evoke large SCG depolarizations, hexamethonium (2.5 x 10(-3)M) reduced (3)H-nicotine uptake by the SCG by up to 19% without affecting uptake by the NG, and thereby reduced the uptake difference between the two ganglia. With nicotine concentrations <6.2 x 10(-6)M, hexamethonium did not modify uptake by either ganglion.7. It was concluded that nicotine may be concentrated within neurones, and that such intracellular accumulation may be augmented during depolarization induced by nicotine.

Journal ArticleDOI
TL;DR: It is concluded that the low concentrations of nicotinamide nucleotides in rapidly dividing tissues are the result of competition between NAD synthesis and nucleic acid synthesis for common precursor and cofactors.
Abstract: 1 The concentrations and total content of the nicotinamide nucleotides were measured in the livers of rats at various times after partial hepatectomy and laparotomy (sham hepatectomy) and correlated with other events in the regeneration process 2 The NAD content and concentration in rat liver were relatively unaffected by laparotomy, but fell to a minimum, 25 and 33% below control values respectively, 24h after partial hepatectomy NADP content and concentration were affected similarly by both laparotomy and partial hepatectomy, falling rapidly and remaining depressed for up to 48h 3 The effect of injecting various doses of nicotinamide on the liver DNA and NAD 18h after partial hepatectomy was studied and revealed an inverse correlation between NAD content and DNA content 4 Injections of nicotinamide at various times after partial hepatectomy revealed that the ability to synthesize NAD from nicotinamide was impaired during the first 12h, rose to a peak at 26h and fell again by 48h after partial hepatectomy 5 The total liver activity of NAD pyrophosphorylase (EC 2771) remained at or slightly above the initial value for 12h after partial hepatectomy and then rose continuously until 48h after operation The activity of NMN pyrophosphorylase (EC 24212) showed a similar pattern of change after partial hepatectomy, but was at no time greater than 5% of the activity of NAD pyrophosphorylase 6 The results are discussed with reference to the control of NAD synthesis in rapidly dividing tissue It is suggested that the availability of cofactors and substrates for NAD synthesis is more important as a controlling factor than the maximum enzyme activities It is concluded that the low concentrations of nicotinamide nucleotides in rapidly dividing tissues are the result of competition between NAD synthesis and nucleic acid synthesis for common precursor and cofactors

Journal ArticleDOI
TL;DR: A new approach to treatment for alcoholism is based on the principle that social anxiety is the central feature of this disorder and when the patient has become anxiety-free in all normal social situations, using systematic desensitization, he no longer needs to drink to excess and yet can continue drinking socially.
Abstract: A new approach to treatment for alcoholism is based on the principle that social anxiety is the central feature of this disorder. When the patient has become anxiety-free in all normal social situa...

Journal ArticleDOI
15 Sep 1971-Nature
TL;DR: There is now not only geometrical congruence but also identical matching of atomic species in GABA and bicuculline.
Abstract: CURTIS et al.1,2 have described evidence suggesting that the alkaloid bicuculline is a specific antagonist to the action of γ-aminobutyric acid (GABA), a possible inhibitory transmitter in the mammalian brain3,4. By considering structural models, they suggested3 as a stereochemical basis for this antagonism a geometrical configuration in which the N and Ol=C1—O2 of GABA is isosteric with the N and C2—Cl—Ol in bicuculline (Fig. 1a and b). An alternative configuration of GABA, which would give a greater degree of stereochemical similarity to bicuculline, is depicted in Fig. 1c. In both molecules the N is now seen to be isosterically related to Ol=Cl—O2 and located at an angle of about 40° to the plane of the O=Cl—O group viewed towards C2 (Fig. 2). In contrast to Curtis's suggestion, there is now not only geometrical congruence but also identical matching of atomic species.




Journal ArticleDOI
TL;DR: It is suggested that polycythaemia in this case was caused by the production of erythropoietin and not by an indirect pressure effect from the tumour.
Abstract: Summary. A case is described of a woman with polycythaemia secondary to a uterine fibromyoma. The polycythaemia disappeared after the removal of the tumour. The tumour tissue and also fluid from cysts within the tumour showed erythropoietic activity when estimated by the polycythaemic mouse assay employing two dose levels and a standard related to the WHO erythropoietin standard. It is suggested that polycythaemia in this case was caused by the production of erythropoietin and not by an indirect pressure effect from the tumour.

Journal ArticleDOI
TL;DR: Using HCO3−-containing solutions, absorption of water, Na+ and Cl− takes place at an initial pH of 7.6 in the ileum, though it is negligible (water and Na+), or reduced (Cl−) at initial pH's of 6.6.