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Biomedical subjects

R H Jackson

Publications and source records attributed to R H Jackson.

At least 55 records · Page 3Linked to original sources

Effects of fenfluramine on eight outpatients with the syndrome of autism.

Fenfluramine was administered to eight autistic outpatients in a double-blind study to determine its effects on symptomatic behavior, developmental scores, blood serotonin levels and platelet counts. Two children benefited substantially according to academic and cognitive tests, parental and teacher reports and the principal investigator's clinical impressions. They also manifested behavioral and mood swings. The remaining six children showed varying degrees of response; one was withdrawn during the study by his parents. The greatest improvement occurred in children with an IQ above 40; the more severely retarded improved little, and primarily in the motor sphere.

Adolescent↗

Vanishing earrings.

Four children who presented with impacted earrings are described. We suggest that the insertion of earrings in children under 10 years has hazards and recommend the use of sterling silver or 9 ct gold if the procedure is to be done in young children.

Child↗

Cholinergic stimulation of the hypothalamus and natriuresis in rats: role of the renal nerves.

The role of the renal nerves in the natriuresis seen after cholinergic stimulation of the hypothalamus was studied in anesthetized rats treated with injection into the lateral hypothalamus (LH) of 1 microgram of carbamylcholine chloride (carbachol) in 1 microliter of 0.15 M NaCl or NaCl alone. Injection of carbachol exhibited diuresis and natriuresis both in acutely denervated kidneys (P less than 0.01) and in contralateral innervated kidneys (P less than 0.01) without changes in glomerular filtration rate (GFR) or renal plasma flow (RPF) (n = 10). Salt and water excretion was unchanged in 10 rats after injection of NaCl. Micropuncture studies in denervated kidneys showed that, after carbachol injection, tubular fluid-to-plasma inulin concentration ratio [(F/P)In] in the late proximal tubule fell from 1.86 +/- 0.08 to 1.64 +/- 0.07 (P less than 0.01) without changes in single-nephron GFR. In nine other carbachol-treated rats in which renal perfusion pressure was maintained low and constant, diuresis and natriuresis, although attenuated, were again observed both in denervated (P less than 0.01) and in contralateral innervated kidneys (P less than 0.05). In another group of 11 animals, efferent renal nerve activity (ERNA) was recorded before and after LH injection of carbachol and isotonic saline. ERNA was significantly depressed for 30 min, only after carbachol injection. Our results suggest that the renal nerves, although involved, are not essential for the natriuretic response after cholinergic stimulation of LH. By exclusion, other factors, presumably hormones, must contribute to the response.

Animals↗

Study of sodium and potassium excretion after renal denervation and cholinergic stimulation of the lateral hypothalamic area of the rat.

Studies were undertaken to characterize the renal responses to acute unilateral renal denervation and chronic bilateral denervated kidneys after cholinergic stimulation of the anterior part of the lateral hypothalamus. Denervation was produced in anesthetized and conscious nondiuretic rats by application of phenol to the renal artery. Studies were also performed in sham denervated rats. Whole kidney function in anesthetized animals showed a significant increase of fractional sodium excretion (0.7 +/- 0.1 to 1.7 +/- 0.4%, P less than 0.01) both in the denervated and in the innervated kidney (0.09 +/- 0.02 to 1.1 +/- 0.2%, P less than 0.005) after carbachol injection into the LHA, whereas the percentage of filtered potassium excreted increased only in the innervated kidney (11.4 +/- 1.3 to 16.3 +/- 1.1%, P less than 0.01). Similarly, in conscious rats, fractional sodium excretion increased after cholinergic stimulation in animals having denervated kidneys (2.1 +/- 0.1 vs 3.6 +/- 0.2%, P less than 0.005). Fractional potassium excretion also increased both in rats with sham-denervated and denervated kidney. There was an acute elevation in mean arterial blood pressure and glomerular filtration rate (GFR) during the first 20-min after carbachol injection. Sodium excretion was statistically significant during the three 20-min collections of the experimental period. This suggests that the natriuresis is not associated with increased arterial pressure, GFR or renal plasma flow. Our results indicate that natriuresis occurs even in the absence of the renal nerves.

Animals↗

Changing pattern of poisoning in children in Newcastle, 1974-81.

All children aged under 15 years admitted to hospital in Newcastle upon Tyne between 1974 and 1981 with a diagnosis of poisoning were studied. After the introduction in 1976 of child resistant containers for salicylates and paracetamol, salicylate poisonings fell dramatically. The other most important medicines to cause poisoning in young children were tricyclic antidepressants, benzodiazapines, Lomotil (diphenoxylate and atropine), and iron preparations; these should also be packaged in child resistant containers by regulation. Few children had symptoms after poisoning with household products, but bleach, turpentine, and paraffin might also be packaged in child resistant containers. The numbers of adolescent girls admitted after deliberate self poisoning and of teenage boys admitted after ingestion of alcohol increased over the study period.

Acetaminophen↗

Inactivation of the 2-ketoglutarate and pyruvate dehydrogenase complexes of beef heart by branched chain keto acids.

Incubation of 2-ketoglutarate dehydrogenase complex with 2-ketoisovalerate, 2-keto-4-methylvalerate, or 2-keto-3-methylvalerate leads to the appearance of a lag phase and of a progressive loss of activity in subsequent measurements of the initial rate of oxidation of 2-ketoglutarate. In the case of 2-ketoisovalerate these effects are shown to be due to the formation of an isobutyryllipoate derivative of the enzyme, as a result of the very slow oxidation of 2-ketoisovalerate by the enzyme complex (Vmax congruent to 0.15% of that for 2-ketoglutarate). Incubation of the enzyme complex with 2-keto[14C]isovalerate or 2-keto[14C]glutarate results in comparable incorporation of radioactivity, amounting to 3.5 to 5.3 nmol of isobutyryl or succinyl residues per mg of protein in the complex. Isobutyryl residues are also incorporated in the enzyme during the simultaneous oxidation of both of these substrates. During the early phase of incubation of the complex with 2-ketoisovalerate the incorporation of isobutyryl residues is much faster than the loss of enzyme activity. This observation seems to support the suggestion that each 2-ketoglutarate decarboxylase subunit of the complex may catalyze the succinylation of more than one lipoate succinyltransferase subunit. Results are also presented showing the inactivation of pyruvate dehydrogenase complex on preincubation with 2-ketoisovalerate and of 2-ketoglutarate dehydrogenase complex with methylenecyclopropylpyruvate, the keto acid corresponding to the toxic amino acid hypoglycin. The relevance of covalent modifications of the two keto acid dehydrogenase complexes to the pathological manifestations of maple syrup urine disease are discussed.

Animals↗

Factors causing natriuresis after hypothalamic injection of a cholinergic drug in rats.

We investigated possible mechanisms for the natriuresis seen after injection of the cholinergic drug carbamylcholine chloride (carbachol) into the lateral hypothalamus of conscious rats. In unrestrained rats injection of 1 microgram of carbachol in 1 microliter of 0.15 M NaCl solution through a permanently implanted cannula produced a significant natriuresis and kaliuresis. Injection of vehicle produced no changes. The same animals were then subjected to bilateral renal denervation (n = 13) or sham denervation (n = 13) and injected with the same solutions 1 wk later. Carbachol injection produced a natriuresis (P less than 0.0001) and a kaliuresis (P less than 0.01) in all animals studied. Both responses were of a magnitude similar to the responses seen before denervation. We studied other rats while awake but restrained, which permitted the performance of clearance studies and blood pressure measurements. Injection of carbachol produced diuresis, natriuresis, and kaliuresis in all rats, with no change in p-aminohippurate clearance and only transient change in inulin clearance. An increase in blood pressure occurred in some but not all rats. The response in rats with bilaterally denervated kidneys (n = 7) was similar to that of rats with innervated kidneys (n = 5). The natriuresis seen after cholinergic stimulation of the hypothalamus in conscious rats is not primarily mediated by inhibition of renal nerve activity and can be dissociated from changes in blood pressure, glomerular filtration rate, and renal plasma flow.

Animals↗

The spectrum of human lung cancer cells in culture: a potential model for studying molecular determinants of tumor progression and metastasis.

We have reviewed the behavior of human lung cancer cells in culture. We have considered the implications of cell biology and biochemistry studies of the cultured cells for the in vivo behavior of lung neoplasms, including the metastatic potential of the different tumor types. Among the human lung cancers, SCC, which grows in culture as suspended aggregates of adherent cells, metastasizes earlier in the life cycle of the tumor and more widely than the major types of non-SCC lung cancers. These latter tumors grow as anchorage-dependent cells in culture. We have pointed out that ultrastructural studies of cultured human lung cancer cells reveal dramatic changes in cell surface membrane morphology coincident with progressive loss of SCC features and intercellular adhesion. We have stressed the potential value of these cultures of human lung cancer cells for studying the molecular determinants of intercellular adhesion and their importance to the process of metastasis. In this context, we have stressed that a different cell surface protein phenotype exists between SCC and non-SCC lung cancer cells in culture and that some of these proteins could be intimately involved in the different growth behavior patterns of these tumor cells. Finally, we have pointed out the need to construct models in which the growth characteristics and biochemical properties of cultured lung cancer cells can be directly compared in vivo with their metastatic potential.

Carcinoma, Small Cell↗

Electron-spin-resonance studies of the NADH-dependent nitrite reductase from Escherichia coli K12.

The NADH-dependent nitrite reductase of Escherichia coli, which contains sirohaem, flavin, non-haem iron and labile sulphide, was examined by low-temperature e.s.r. spectroscopy. The enzyme, stored in the presence of nitrite and ascorbate, gave the spectrum of a nitrosyl derivative, with hyperfine splitting due to the nitrosyl nitrogen. On removal of these reagents, a series of signals centred around g = 6 was observed, typical of high-spin ferric haem. Cyanide converted this into a low-spin form. On reduction of the enzyme with NADH, an axial spectrum at g = 1.92, 2.01 was observed. The temperature-dependence of this signal is indicative of a [2Fe-2S] iron-sulphur cluster. The midpoint potential of this cluster was estimated to be -230 +/- 15 mV by two independent methods. Reduction of the enzyme with dithionite yielded further signals, which are at present unidentified, at g = 2.1-2.28. No signals were observed that could be assigned to a [4Fe-4S] cluster, such as is found in other sulphite reductases and nitrite reductases that contain sirohaem.

Electron Spin Resonance Spectroscopy↗

The steady state kinetics of the NADH-dependent nitrite reductase from Escherichia coli K12. The reduction of single-electron acceptors.

The kinetic characteristics of the diaphorase activities associated with the NADH-dependent nitrite reductase (EC 1.6.6.4) from Escherichia coli have been determined. The values of the apparent maximum velocity are similar for the reduction of Fe(CN)6(3)-and mammalian cytochrome c by NADH. These reactions may therefore have the same rate-limiting step. NAD+ activates NADH-dependent reduction of cytochrome c, and the apparent maximum velocity for this substrate increases more sharply with the concentration of NAD+ than for hydroxylamine. The simplest explanation is that NAD+ activation of hydroxylamine reduction derives solely from activation of steps involved in the reduction of cytochrome c, a flavin-mediated reaction, but these steps are only partly rate-limiting for the reduction of hydroxylamine. At 0.5 mM-NAD+, the apparent maximum velocity was 2.3 times higher for 0.1 mM-cytochrome c as substrate than for 100 mM-hydroxylamine, suggesting that the rate-limiting step during hydroxylamine reduction is a step that is not involved in cytochrome c reduction. A scheme is proposed that can account for the pattern of variation with [NAD+] of the Michaelis-Menten parameters for hydroxylamine and for NADH with hydroxylamine or cytochrome c as oxidized substrate.

Cytochrome c Group↗