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IN a recent paper1, Leo Szilard has shown that a system consisting of an enzyme, an enzyme-forming apparatus and a repressor may be able to exist in two stable states, provided the combining energies between the various components of this system lie within certain ranges of magnitude. The two stable states which can exist contain either high or low concentrations of the enzyme. If the concentration of the enzyme or the repressor is changed by external manipulation, the system returns to one or the other of the stable states. Such a system was termed ‘para-constitutive’ by Szilard, and its possible biological significance in differentiation and antibody formation2 was suggested by him.

Rats or mice developed centrolobular hepatic necrosis within 24 h after an intraperitoneal injection of 14C-bromobenzene or other radiolabeled halogenated aromatic hydrocarbons. The hepatic

During some experiments performed with tetraethylthiuram disulfide (antabus®) in the laboratory, Dr. Jens Hald and one of us (E. J.) discovered that persons who have ingested this substance showed symptoms after consumption of alcohol which differed quantitatively and qualitatively from the common picture of alcoholic intoxication. The discomfort after alcohol consumption in persons treated with tetraethylthiuram disulfide was so intense that we decided to submit this drug to trial as a remedy for alcoholism. The clinical experiments were conducted by one of us (O. M.-L.). The present report includes a short review of the results obtained in the investigations on the biochemical mechanism of this effect and of the clinical results on 100 persons with alcoholism who were treated for six to twelve months. PHARMACOLOGIC CONSIDERATIONS Tetraethylthiuram disulfide is a white, or slightly yellow, powder which is insoluble in water. It is relatively nontoxic. The fatal dose is 2 to

OUR studies on two strains of rats with opposite genetic predisposition to hypertension showed that their adrenal steroid production differed significantly1,2. This suggested a theory concerning the role of mineralocorticoids in the initiation of hypertension. The two strains of rats3–9 were separated genetically on the basis of their disparate blood pressure responses to salt (NaCl). The members of one strain (sensitive or S) rapidly develop fatal hypertension from salt intakes to which members of the other strain (resistant or R) respond only mildly, if at all. These same effects were shown when five other techniques were used to induce experimental hypertension (deoxycorticosterone acetate plus NaCl; unilateral renal artery compression without NaCl; cortisone without NaCl; adrenal regeneration with NaCl; uninephrectomy without (or with—unpublished observations) NaCl). Since the genetic influence seems critical in determining the effectiveness of a variety of stimuli known to induce experimental hypertension, we have suggested that a similar situation prevails in human hypertension6,9. Breeding experiments have shown that the control of these dramatic blood pressure differences between S and R rats is due to the expressions of two to four genes8. Our objective was to identify the biochemical mechanism controlled by each gene.

Studies with cell fre systems of protein synthesis have shown that mRNAs are not translated uniformly by ribosomes. In particular the existence of mRNA specific initiation factors which stimulate or inhibit the translation of individual cistrons is now well recognized. We originally reported that E. coli initiation factor IF3 activity can be separated into subfractions differing in their activity toward MS2 and T4 mRNA. Our recent work, however, indicates that the specificity of IF3 for mRNAs actually results from its combination with "interference" protein factors. These proteins act in the presence of IF3 to stimulate the translation of certain cistrons while inhibiting that of others. We have isolated three interference factors from E. coli and characterized some of their cistron specificities on MS2 RNA, T4 and T7 early and late mRNAs. These factors can explain the heterogeneity of IF3 toward various mRNA. In vivo variations in the activity of ribosomes can result from changes either in IF3 or in an interference factor. We have also recently purified a mRNA-specific initiation factor from mammalian cells. This factor isolated from the ribosomal wash of rabbit reticulocytes stimulates haemoglobin mRNA translation but not that of Mengo virus RNA, in a crude extract from Krebs ascites cells. This factor stimulates a globin synthesis. Ribosome activity may be, therefore, regulated both quantitatively and qualitatively by such factors.

1. Die O2-Aufnahme und ATP-Synthese der Gehirnzellen wird durch Largactil, Phenergan, Multergan und Parsidol wesentlich in gleicher Weise und in gleichem Mase beeinflust. Alle vier genannten Praparate haben eine ausgesprochene Nervenzellen-Spezifitat; zur gleichen Hemmung des Leberzellstoffwechsels ist eine 6–8 mal hohere Konzentration notwendig. 2. Der energiereiche Phosphatgehalt des Gehirns nimmt in vivo nach Largactilbehandlung zu, obwohl Largactil die Atmungskettenphosphorylierung in vitro entkoppelt. 3. Von den vier untersuchten Phenothiazinderivaten hemmt nur Largactil die Gehirn-ATP-aseaktivitat, am starksten in der Groshirnrinde und in der Regio hypothalamica. Diese Hemmung beruht wahrscheinlich auf einer Beeinflussung der „wahren“, hydrolytischen ATP-ase: die Phosphatubertragung von ATP auf CoA wird durch Largactil nicht gehemmt, eher etwas gesteigert. Parsidol und Phenergan haben keinen Einflus auf die ATP-aseaktivitat, wahrend Multergan diese steigert. 4. Aus den Versuchen wird der Schlus gezogen, das die narkobiotische Wirkung der Phenothiazinderivate mit der Hemmung der oxydativen Phosphorylierung in befriedigender Weise erklart werden kann, wahrend fur das Zustandekommen einer zentralnervosen pharmakologischen Wirkung — innerhalb dieser Reide — die Hemmung der Energieproduktion allein nicht genugt. Hierfur mus wahrscheinlich auch der Energieverbrauch der Nervenzellen gehemmt werden.

A precise understanding of the genomic and epigenomic features of chronic lymphocytic leukemia (CLL) may benefit the study of the disease’s staging and treatment. While recent reports have shed some light on these aspects, several challenges need to be addressed before translating this research into clinical practice. Thus, even the best candidate driver genes display low mutational rates compared to other tumors. This means that a large percentage of cases do not display clear tumor-driving point mutations, or show candidate driving point mutations with no obvious biochemical relationship to the more frequently mutated genes. This genomic landscape probably reflects either an unknown underlying biochemical mechanism playing a key role in CLL or multiple biochemical pathways independently driving the development of this tumor. The elucidation of either scenario will have important consequences on the clinical management of CLL. Herein, we review the recent advances in the definition of the genomic landscape of CLL and the ongoing research to characterize the underlying biochemical events that drive this disease.

In recent years, studies on mineralized tissues are becoming increasingly popular not only due to the diverse mechanophysical properties of such materials but also because of the growing need to understand the intricate mechanism involved in their assembly and formation. The biochemical mechanism that results in the formation of such hierarchical structures through a well-coordinated accumulation of inorganic and organic components is termed biomineralization. Some prime examples of such tissues in the human body are teeth and bones. Our current study is an attempt to dissect the compositional details of the inorganic and organic components in four major types of human teeth using mass spectrometry-based approaches. We quantified inorganic materials using inductively coupled plasma resonance mass spectrometry (ICP-MS). Differential level of ten different elements, Iron (Fe), Cadmium (Cd), Potassium (K), Sulphur (S), Cobalt (Co), Magnesium (Mg), Manganese (Mn), Zinc (Zn), Aluminum (Al), and Copper (Cu) were quantified across different teeth types. The qualitative and quantitative details of their respective proteomic milieu revealed compositional differences. We found 152 proteins in total tooth protein extract. Differential abundance of proteins in different teeth types were also noted. Further, we were able to find out some significant protein-protein interaction (PPI) backbone through the STRING database. Since this is the first study analyzing the differential details of inorganic and organic counterparts within teeth, this report will pave new directions to the compositional understanding and development of novel in-vitro repair strategies for such biological materials.

Stereotypies in animals and man are viewed as behavioural reminiscences of past developmental stages, when the movements in question may have been solutions to motor problems, such as position and motion control of the body and its extremities. For reasons yet unknown, which may be linked with psychodynamic factors such as trauma or stress, psychotic individuals may continue to perform these movements after passing the respective developmental stage when the movements are known to be performed by normal children (Thelen, 1979). Nine different stereotypies in autistic children were described from video-recordings and analysed at a macro-level. The video-recordings were made of an experimental situation in which a group of four psychotic children played for 15 minutes in a play-room equipped with large toy vehicles. A fifth child then entered the room to play simultaneously with the four children for another period of 15 minutes. It is suggested that four of the described stereotypic movements may serve as a means of non-verbal communication. In contradistinction to the case of normal motor development and skill development, where a progressive simplification of the movements can be seen (often referred to as “automatisation” or “habituation”), there is, in the case of behavioural stereotypy, no such “falling-off” effect in the behaviour pattern after it has been shaped by the first trials. A hypothesis, shared by students of animal stereotypy, maintains that the initial act or behaviour pattern becomes fixated by some, not yet known, biochemical mechanism. This, according to the view put forward here, prevents the progressive simplification (and eventual total elimination) of the apparently superfluous and non-functional, stereotypic movements. This hypothesis seems in agreement with recent discoveries of. the differences between “non-established” and “established” stereotypies in animals (Odberg, 1978).

Male rats treated with clofibrate, tibric acid, or Wy-14,643 show an 11- to 18-fold increase in the capacity of their livers to oxidize palmitoyl-coenzyme A. This provides a plausible biochemical mechanism for the action of these hypolipidemic drugs in reducing lipid concentrations in the serum.

Accumulation of long-chain acylcarnitines in the cytoplasm of ischemic myocardium has been associated with a changed ion transport resulting in a decline of contractile force and an increased susceptibility to arrhythmias (Katz & Messineo, 1981). To elucidate the underlying biochemical mechanism for the impaired calcium availability, we studied the influence of acylcarnitines on

KOE and Weissman have demonstrated that p-chlorophenylalanine (pCPA) depletes serotonin in the brain of mammals1. pCPA induces a variety of behaviour changes in rat, cat and other animals2,3, presumably because of the depletion of serotonin in the brain. The biochemical mechanism of the depletion remains, however, to be elucidated, although it has been proposed that pCPA might inactivate tryptophan hydroxylase in the brain4. We demonstrate here that pCPA does not inactivate tryptophan hydroxylase in rat pineal, although pCPA depletes the serotonin level in the pineal.

Hydrolytische Deaminierung der Purinbasen ist eine mogliche Erklarung der beobachteten Mutation. Jene lasst sichin vitro durch HNO2 oder durch Ultraviolettlicht in Gegenwart von Alkali erzielen. Die entstehenden Hydroxy-Purinbasen kann man durch Ammoniak in Gegenwart von Amino-Purinbasen reaminieren. Eine Theorie zur Erklarung des beobachteten Phanomens wird vorgeschlagen und genetische Folgen werden besprochen.

The course of bacteriolysis as determinated by the oxygen consumption of the bacteria is different during bacteriolysis produced by the phagesT1,3,5,7 as compared with that produced by phagesT2,4,6. With phagesT1,3,5,7, the bacteriolysis occurs, rapidly, but incompletely after a latent period. With the phagesT2,4,6 bacteriolysis occurs slowly and the course of the respiration shows a « plateau » but goes to completion. The biochemical mechanism of the bacteriolysis therefore seems to differ in both cases.

EFFORTS aimed at establishing a biochemical mechanism for carcinogenic action have included studies of the inhibition of unsaturated lipid oxidation by carcinogenic compounds1. The haematin compounds, particularly haemoglobin, myoglobin and cytochrome c, appear to be the main catalysts of unsaturated lipid oxidation occurring in animal tissues. This reaction has been postulated to be of prime importance in many types of pathological unsaturated fat oxidation in vivo2. This report presents results of studies undertaken in an attempt to demonstrate what, if any, effects were induced by the presence of certain carcinogenic compounds in in vitro haematin-catalysed unsaturated fat oxidation systems.

Molecular structures can serve to either validate or rule out existing hypotheses, and they can also spawn new, deeper proposals about biochemical mechanism. In this issue of Structure , Schonegge et al. use single-particle cryo-electron microscopy and flexible docking to examine the function of human tripeptidyl peptidase II, including the role of conformational changes in enzyme activation.

THE life spans of various mammalian species differ but the biochemical mechanism of this regularity is unknown. In our opinion there is a sufficient amount of experimental data to solve this problem. We refer to the data presented in twelve investigations by different authors collated into one table (Table 1), and the data of the two works collated in another (Table 2)1. In these, the data on the protein plasma turnover for various species of mammals is presented. We have added a column on the maximum life span of the species2 into each table.

The scientific revelations of 1967 regarding the relationship between glycogen and exercise endurance set in motion two decades of research mostly oriented toward the practical application of those early findings. It is surprising that, in spite of the considerable time that has elapsed between those initial studies and the wealth of knowledge accumulated since, we still do not know the biochemical mechanism that explains why carbohydrate is essential to the ability of the muscle fiber to maintain high force outputs. It may be that the discoveries of 1967 were so widely accepted and so essentially unchallenged that we narrowed our vision as to the potential mechanisms responsible for the observations reported. The time has come for us to lay this issue to rest and answer the question: Why is glycogen availability necessary to perform prolonged, heavy-intensity exercise?

Excerpt Erythropoietic protoporphyria (EPP), an inborn error of metabolism transmitted as a mendelian dominant trait, is characterized by increased erythrocyte protoporphyrin (EP) concentrations, s...

The second volume of this overdue series continues to follow the high standards of Volume 1. The publication begins with a review of the status and recent advancements made by pharmacology in India, China, and Europe. The remainder of the volume reviews in detail major advances made in various sections of pharmacology. The 2 general areas of pharmacology, biochemical and physiological, seem to be well balanced. This balanced presentation is evidenced by the following topics: biochemical mechanism, drug absorption and excretion, comparative pharmacology, chemotherapy, hormones, central nervous system, cardiorenal, anesthesia, toxicology, and advances in biochemical assay techniques. This volume is highly recommended for the physician in practice or research. Reviews of this type offer an excellent opportunity to keep abreast with this rapidly developing basic science.