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All organs within the body are composed of cells of several different types which together perform the various functions of that organ. It is obvious that if the organ is to function normally, then the activities of the different cell types must be co-ordinated and the most logical way in which this could be achieved is by direct communication between the various cell types. In this context, the idea that the Sertoli cells should communicate with the Leydig cells within the testis is therefore far from unique, and yet this pathway has been all but ignored by the majority of workers engaged on research into testicular function. This neglect is all the more remarkable when it is considered that fertility is critically dependent on the link between Sertoli and Leydig cells, in that spermatogenesis is regulated by the Sertoli cell only under the driving influence of testosterone from the Leydig cells (Hansson et al., 1978; Ritzen et al., 1981). Because of this dependence it seems essential that the Sertoli cells should have some means of communicating with the Leydig cells to ensure the optimum supply of testos- terone for maintenance of spermatogenesis. This paper assesses the possible factors that might be involved in this communication and gives particular attention to the possibil- ity that the Sertoli cells may locally regulate testosterone production by the Leydig cells via secretion of a luteinizing hormone-releasing hormone (LHRH)-like peptide.

This paper presents a rationale for the use of biomarkers in detecting early stages of environmental stress and describes the greater responsiveness of biomarkers to varied and multiple stressors. A set of biomarkers from different biological levels is much more desirable than a single measure. Examples of multivariate approaches for data reduction and analysis of sets of biomarkers are suggested.

Treatment of the rat uterus with estradiol results in many morphological and biochemical changes. In order to examine the biochemical mechanisms of these changes, we are interested in finding a protein which can be used as an end-point indicator or marker. Estradiol administration results in the increased synthesis and release of a 115,000 and 65,000 dalton protein into the incubation media. In this paper, we demonstrate that these proteins are actually subunits of a larger protein having a molecular weight of 180,000 daltons. This protein appears to be specific to the uterus and may be produced mainly or solely by the epithelial cells. In the normal estrous cycle, maximal production is seen at estrus with essentially no production at diestrus. In the immature rat, synthesis of the 180K dalton protein is blocked by the interaction of progesterone and estradiol. However, unlike some uterine responses, the 180K protein is increased by treatment with several antiestrogens. This protein is also present in sufficient quantities to allow for the production of monoclonal antibodies. Thus this protein has many attributes of an excellent “marker protein” and will be of value in future studies aimed at elucidating the molecular mechanism(s) of steroid hormone action in the uterus.

Evidence is accumulating rapidly to support the concept that specific receptors for certain neuropeptides on lymphocytes may provide a means through which neurophysiological signals can influence immunological processes. Human lymphoid cells have been reported to have receptors for beta-endorphin (1), somatostatin (2), substance P (3), and vasoactive intestinal peptide (4), and a variety of investigations suggest that each of these neuropeptides can affect the behaviour of human lymphocytes in vitro. It has also been proposed that neurophysiological factors could have an important impact on the immune system in vivo by regulating the migration of lymphocytes through lymphoid tissue (5,6). This paper concerns experiments that were performed to test the hypothesis that receptors for the neuropeptide vasoactive intestinal peptide (VIP) influence the migration of T cells.

Absorption spectrophotometry in the ultraviolet, visible, and near-infrared spectral regions has become an extremely important analytical tool in the last two decades, its progress having been greatly accelerated by the development of commercially available recording spectrophotometers. This paper briefly discusses its history, describes laboratory techniques, and cites many practical applications from the chemical literature. It is intended both to introduce the novice to the field and to acquaint the specialist with the versatility of these techniques.

A synthetic retina design, consisting of three layers of active parallel-processing optoelectronic elements which are coupled by two synaptic fields, has been described.* This system attempted to duplicate functionally the four-image feature-extracting processes found by Lettvin and coworkers in the frog retina.† Since then we have significantly expanded and improved the model. The new model is more general. It is based on majority logic, attempts to provide realistic receptive fields and provides for duplication of all the time dependences reported in a later paper by Maturana and coworkers.‡ We have also extrapolated image-processing functions to include those which might have biological counterparts in subcortical and cortical activity. A crude eight-stage model for visual pathways in the human brain has been worked out.

The Goodyear Tire & Rubber Company has been using an ADL arc imaging furnace* for research purposes for the past two years. This paper discusses two applications for which we have found the arc imaging furnace to be well suited. These are (1) study of ablative insulation and (2) polymer identification. The work concerning ablative insulation will be presented first.

The mounting evidence of the biological effects of magnetic fields, reviewed in the other papers in this volume, and in particular the effects observed by our colleagues on the respiration of tumor and normal embryonic cells1 (see also Part III, Ch. 1), made us wonder if the metabolic effects could directly involve enzymes. Since studies on the denaturation of trypsin by ultraviolet irradiation were under way in our laboratory, we decided to compare the results with the behavior of trypsin in a magnetic field.

The subject of algae culturing is one so large that even a book would not exhaust our knowledge about the results so far reached. Therefore, I shall point out certain modern developments which either have not received a satisfactory answer, or are still creating some confusion. Among such problems are: the estimation of growth or yield; different methods of purification to obtain bacteria- free cultures; the influence and the size of the inoculum on the growth of the culture; more or less pure cultures of algae used as indicators for ecological water properties or value of the water supply at all; algae considered as purifiers of industrial wastes and sewage; and algae and pollution control in general.

The amount of a steroid produced per day is usually evaluated by methods which measure the disposition of an isotopically labeled tracer of the hormone (injected intravenously) by following the decline in the specific activity of the hormone in blood [1] or by determining the cumulative specific activity of a urinary metabolite of the hormone [2,3,4]. In the application of these methods it has been assumed that they provide a measure of the dilution of the tracer by the endogenously secreted hormone. In this article, situations will be described in which the measurement of the dilution of the injected tracer of the hormone would not be sufficient to evaluate its rate of secretion. Such situations may arise when the hormone is produced not only by secretion but also by peripheral conversion from other precursors, or when the produced hormone does not mix completely with the injected tracer and does not have the same metabolic fate. In these situations it is convenient to correlate the fate of the administered isotope with that of the endogenously secreted hormone by considering models consisting of interrelated “compartments” or “pools.” A pool is defined by both a compound and the space in which it is distributed. A compound or a tracer entering a pool is assumed to mix immediately with the entire pool. The calculation of rates of entry of material into each pool or rates of transfer from one pool to another is dependent on the chosen models. Some conclusions obtained from tracer analysis of open systems of multiple pools at the steady state are presented in this article where it will be shown that the simultaneous administration of more than one tracer can make possible the evaluation of the secretory rates of a hormone in situations in which. that information cannot be obtained by administering only one tracer of the hormone. The mathematical proofs of statements made in this article are given in a paper in the Journal of Clinical Endocrinology and Metabolism [5].

The rapid increase in the production and applications of liquid hydrogen has focused renewed interest on the catalysts for the ortho-parahydrogen conversion. Although the hydrous ferric oxide catalyst developed by Weitzel and co-workers [1–4] has been used in several large liquid-hydrogen plants, the activity of the catalyst has been found to be extremely sensitive to the method of preparation, composition, and technique of activation. This paper reports the results of an investigation into these factors and shows how the activity of the ferric oxide gel catalyst may be doubled over that previously reported by improvements in the method of activation.

The nuclear magnetic resonance in ND4C1 and ND4Br has been investigated previously by Chiba.1 His paper gives for these salts in powder form the room-temperature line widths of the deuteron magnetic resonance. Furthermore, the deuteron-quadrupole coupling constant in the [ND4]+ ion has been briefly discussed by Bersohn.2 He predicts this constant to be greater than 200 kcps. Chiba’s results indicate rapid reorientation of the [ND4]+ ions at room temperature. Therefore, line width transitions can be expected to occur at lower temperatures. The object of the present investigation was to determine these transition temperatures and, in the same connection, to find the principal origin of the line broadening above the transition temperatures.

It was recommended that this session might include one rather bread-and-butter paper, namely, a brief review of some of the contributions that genetics can make to the practice of medicine and surgery here and now, or at least in the reasonably foreseeable future. The first contribution I should like to mention is the help a knowledge of genetics can give in facilitating early diagnosis when this is important if effective treatment is to be instituted. Early diagnosis is important in a number of genetically determined conditions. A well-known example is multiple polyposis of the colon and rectum, a condition determined by a dominant gene.4 This is a pre-cancerous condition and early operation has saved many lives. Dr Dukes and his colleagues at St Mark’s Hospital have kept in touch with very many family groups, and as individuals of the younger generations grow up they are examined and, if polyposis is found, are operated on.

A rapid and reliable method for the analysis of urinary androsterone (A), etiocholanolone (E) and dehydroepiandrosterone (D) was required for a forward study designed to investigate the relationship between these steroids and subsequent breast cancer in 5,000 normal women (1). Gasliquid chromatography seemed most likely to be the method of choice and this paper describes investigations into a suitable method.

The ideal tool in human steroid chemistry would be one that would separate a conglomerate of steroids and render a quantitative answer for each with a minimum of time and effort. We have not expected GLC to do this alone. Our aim has been to utilize preliminary solvent partition extraction; column, paper, or TLC; and GLC for isolation and quantitation of urinary steroids. Our approach has been to analyze the steroids as the free alcohols or ketones rather than as acetates or ethers. We recognize the advantage of derivatives, but we are also concerned about incomplete conversion of the steroids to esters and ethers. This paper is a short presentation of our experience with GLC of adrenal steroids.

The medial telencephalic wall is composed of cortical and nuclear areas forming part of the rhinencephalic ring or limbic lobe of the cerebrum. This lobe includes the septum, the hippocampal formation, and the amygdala, the organization of which in the marsupial is quite simple but sets a pattern for higher mammalian forms. In the marsupial, this pattern remains relatively uncomplicated because the rostrocaudal extent of the dorsal portion of the ring is not interrupted by the corpus callosum. The present paper deals with the hippocampal formation of the opossum, Didelphis virginiana. This area, along with the amygdala and the septal area, is also under investigation in certain kangaroos and South American marsupials, with the findings to be presented at a later date.

This paper describes a set of experiments designed to illustrate the suitability of the laboratory animal as a model for (1) the screening of psychiatric and neurologic agents and (2) neurobiochemical studies of certain mechanisms intimately related to brain functions. Thus, this presentation will be divided into two sections, both of which deal with behavioral abnormalities induced by an aminonitrile, namely, β-β′-iminodipropionitrile.

In the seismo-acoustic method for studying stress and fracture in rock, we analyze changes in the character of elastic vibrations, either excited in the specimens by an external source or arising during the formation of fracture surfaces. The use of external excitation is based on the fact that the elastic moduli of rocks increase when the rocks are subjected to static loads [1]. By measurements of physical parameters related to the elastic moduli (i. e., velocity of elastic wave propagation, frequency of natural vibrations of shaped pieces of rock), we can thus estimate changes of stress in the rock [1–4]. The use of fracture-surface formation is based on the fact that the characteristics of elastic pulses accompanying fissure formation and growth change in a way which reflects the fracture dynamics [5–7], The present paper examines results of laboratory investigations of both types.

Previous studies have revealed that when polycrystalline AgCl is deformed in aqueous solutions containing complex ions of high negative charge, e.g., AgCl4 −3, Ag(SCN)4 −3, and Ag(S2O3)3 −5, the fracture mode changes from ductile and transcrystalline (as in air) to brittle and intercrystalline. In the present paper, it is demonstrated that: (1) embrittlement in chloride environments can be prevented by the presence, in solution, of inhibitor ions such as K+, Cs+, Zn+2, Cd+2, and Hg+2; (2) embrittlement can be induced by complex ions of high positive charge; and (3) monocrystals can be embrittled, providing they contain a pre-existing crack. Studies of monocrystal fracture surfaces have revealed that the fracture process is discontinuous. For this and other reasons discussed, it is concluded that embrittlement cannot be explained on the basis of a dissolution-dependent mechanism, but is more likely to be associated with the adsorption of complex ions of high charge in the vicinity of strained surface bonds. It is suggested that the charge on the complex induces a localized redistribution of the shared electrons constituting the bond, effectively reducing its strength and causing the bond to break at an abnormally low stress level.

The present paper represents the results of a morphologic study of the medial hemisphere wall of the forebrain of the tailless amphibians. In an earlier publication concerned with the telencephalon of anurans (Hoffmansc, 1963), the hippocampal and the septal formations were identified and some of their connections reported. This current study has provided the opportunity for a further elaboration of these cellular configurations and will afford a background for subsequent experimental investigations of such areas.

A few weeks ago a manuscript was accepted from our laboratory (Schnitzlein a. Crosby, in press) on the nuclei and the fiber systems of the telencephalon of the African lungfish, Protopterus. The present paper expands the material previously presented on the primordial amygdaloid complex in this lungfish.

The purpose of this paper is to describe an attempt to obtain a better understanding of the oxygen supply to the cells of the brain by examining all phases of the release, diffusion, and consumption processes in a mathematical model. Since the original investigations of August Krogh in 1919, the mechanisms by which molecular oxygen is transported from red blood cells while they are carried in blood flowing longitudinally through capillaries, into plasma, thence radially out to and through the capillary wall into the surrounding tissues for tissue cell respiration, have been a topic of major interest. During maximal good health, and during several states of special physiology and disease states or pathologic conditions, what specific factors, or summation of factors, limit in the mathematical sense of the term the rates of oxygen supply to individual tissue cells located in individual geometric positions in the living organs? As examples, what are the effects of inhaling air containing low concentrations of oxygen, such as at high altitudes, on the individual nerve cells surrounding and all along the lengths of brain capillaries? What are the specific effects of forcibly reducing the linear rates of flow of blood through capillaries on nerve cells along the lengths of, and at various positions between, capillaries? What are the specific effects on nerve cells so located produced by the inhalation of air containing excessively high concentrations of oxygen, or of pure oxygen, perhaps under pressure such as during hyperbaric conditions?

In 1955, Thompson and McConnell described an experiment in which flatworms were reported to be classically conditioned. Further studies on regeneration, initiated by McConnell, Jacobson and Kimble (1959), and the role of RNA on the retention of conditioned responses in regenerated planarians (e.g., Corning and John, 1961) have led to a great deal of research on a number of controversial issues. One of these is whether or not planarians are capable of being conditioned; whether they really learn or are instead demonstrating habituation, sensitization, pseudoconditioning, or something else, owing to improper control of experimental variables. A second question, assuming that planarians can be conditioned, is whether or not retention of the learned response survives regeneration. A third question is whether or not RNA is the means by which retention of the learned response survives regeneration. The present paper is concerned primarily with the first question, although some reference will be made to the other two.

The regular oestrous cycles of the sow are interrupted by two situations during its normal reproductive life, namely pregnancy and lactation. It is with the mechanisms underlying the second of these two anoestrous periods that this paper is concerned.

There is considerable interest at the present time in the use of hormones to produce temporary or permanent suppression of oestrus and ovulation. This paper deals with the effects of progestagens on the prepubertal ovary of the pig, a field which has received little attention until recently, and there are many unanswered questions concerning the response of the prepubertal ovary to hormone treatment.

In this paper I propose to discuss the major influences responsible for foetal and infant deaths and to assess the extent to which these deaths are potentially preventable. This undertaking poses three main difficulties. The first is that a considerable number of deaths are attributed either to ill-defined causes, or to pseudo-specific causes, such as immaturity— which only conceal our ignorance. A second difficulty arises because in some cases where death is associated with a well-recognized condition, such as toxaemia of pregnancy or a congenital malformation, little or nothing may be known about its aetiology. Finally, even where there is considerable knowledge of aetiology, as in the case of a post-natal infection, death cannot without reservation be considered invariably preventable. It is this uncertainty which has led to the use of the somewhat ambiguous term ‘potentially preventable’, which at least has the excuse that it does not claim too much.

Although the title of my paper refers to psychiatric disorders, I shall have occasion to speak of somatic ailments too, since the social factors I wish to discuss may influence the prevalence of both categories of illness in similar fashion.

Implantation is the first stage in the formation of the placenta when blastocysts are attached to the wall of the uterus in a sufficiently intimate manner to permit the exchange of nutrients and waste materials between the mother and the offspring. The extent to which changes occur in the uterus to allow this exchange varies considerably between species. In the pig, for example, the histological changes are minimal, whereas in rodents the implantation reaction in the uterus is considerable. The mouse provides a useful experimental animal for the study of these changes and this paper is largely concerned with the changes induced in the mouse uterus during implantation.

This paper will undertake a critical discussion of recently observed interactions of certain antidepressants with highly purified and partially characterized liver mitochondrial monoamine-oxidase (MAO) preparations (rabbit and pig) and their possible mechanisms of action.

This symposium contains a series of papers on the production, destruction and possible function of vasoactive polypeptides. Dr. Lewis and Dr. Greenbaum in their presentations were cautious about the role of kinins in inflammation and summarize the evidence which leads to the conclusion that bradykinin and related polypeptides may be involved as mediators of the inflammatory response. A more definitive statement cannot be made at this time because, although all tissues have the capacity for kinin production, the response of tissues to exogenously administered bradykinin does not correlate completely with the microvascular changes observed during an inflammatory response (see Cotran and Majno, Ann. N. Y. Acad. Sci. 116, 750, 1964). In addition, model systems used to investigate the mechanism of action of anti-inflammatory agents, particularly their modification of kinin formation and/or kinin action, have generally failed to give convincing evidence for or against the involvement of kinins as mediators of inflammation. This is the consequence of a poor correlation between anti-inflammatory properties and antagonistic effects in the model systems used.

In this paper we explore positive drug effects on the learning behavior of two classes of rats characterized by learning deficit—the aged rat and the young adult rat made deficient by a procedure involving the intraperitoneal injection of 10–20% body weight of 5.5% dextrose, originally developed by Darrow and Yannet [1]. This procedure lowers the electroconvulsive-shock threshold, while increasing brain intracellular water and sodium and decreasing total brain electrolytes [2]. Because of their lowered electroconvulsive-shock threshold, rats so treated have been used to evaluate anticonvulsant drugs [2]. That animals so treated also manifest a learning deficit represents a new finding of our laboratory. It will be specifically shown that these animals reflect aspects of the deficit that develops with aging, thereby constituting a limited model for this condition.

In the preceding papers many studies were reported regarding the release of insulin “in vivo” in animals and men, mainly under the aspects of gastrointestinal control of insulin secretion. I will take a slightly different position. I shall describe experiments performed in collaboration with Drs. Telib, Ammon, Hildebrandt, Raptis, Schroder, Veboah, Schwarz and Melani, in which 1) insulin secretion “in vitro” was studied in the presence of different sugars and amino acids, polypeptide hormones of gastrointestinal origin and sulfonylureas of different β-cytotropic activities, 2) the response of the pancreatic tissue of various species of animals including amphibians was examined 3) the relation between the extractable pancreatic insulin content and the amount of insulin released following stimulation was investigated as well as the conceivable incorporation of glucose and amino acids into the insulin molecule.

The existence of a stimulatory effect of glucagon on the adrenal medulla has been demonstrated on the isolated-perfused adrenal glands of the dog by SCIAN et al. (10) and on the adrenals in situ of the rat by LEFEBVRE and DRESSE (7). It has been confirmed in rats by DRESSE and LEFEBVRE (1), in dogs by SARCIONE et al. (8) and in man by SCHMID et al. (9) and von KUSCHKE et al. (12, 13) The interest of this phenomenon for the diagnosis of pheochromocytoma has been demonstrated by LAWRENCE and FORLAND (4), LAWRENCE (2, 3) and LEFEBVRE et al. (5). In the present paper we report the effects of pharmacological doses of glucagon on pulse rate, blood pressure and catecholamines blood level in normal man, in sujects suffering from hypertension of various origin and in two patients with documented pheochromocytoma. An extensive study on the mechanism of the stimulation by the glucagon of the adrenergic system in the rat will be reported elsewhere (6).

Hormone action under physiological conditions is a complex process of many stages, including biosynthesis of the hormone, release, transport and distribution, excretion, and metabolic process (inactivation and sometimes activation) as well as the interaction of the hormone with its tissue receptor and the processes triggered by this interaction. The relations between structure and biological activity of the peptide hormones and their synthetic analogues have been analysed mainly in terms of the interactions at the receptor. This paper will be concerned with some approaches to the metabolic phase of hormonal regulation involving the design of synthetic analogues of oxytocin and vasopressin directed specifically toward this end.

The development of immunoassays for the various peptide hormones has greatly enhanced our understanding of endocrine physiology. The present paper reports progress in the development of an immunoassay for the relatively small peptide hormone, oxytocin.

There are two main methods that have been used to study the movements of substances across cells; these are (1) the study of the electrical characteristics of the cell under various specified conditions and (2) the study of the movements of radioactive substances. The application of these two methods to the nervous system of the snail Helix aspersa will be described in the present paper.

This paper will review research on the menstrual cycle and on oral contraceptives currently in progress in the Department of Psychiatry at Stanford University. The psychological aspect of the work is oriented around two major purposes. The first is an attempt to develop a standard technique for the assessment of symptoms and change of symptoms throughout the menstrual cycle. The second involves the comparison of women on oral contraceptives with women not on oral contraceptives in terms of the symptom changes throughout their menstrual cycles.

This presentation will concern itself with the effects of estrogenic hormones, either administered or through increased production during pregnancy, on two protein systems: 1. liver enzymes involved in the metabolism of cortisol and 2. the elevation in plasma transcortin concentration and its relation to progesterone-cortisol interplay. Both of these parameters have been the subjects of separate reports from our laboratory (Sandberg, Rosenthal and Slaunwhite, 1966; Rosenthal, Slaunwhite and Sandberg, 1969) and this paper will endeavor to stress the salient points of these effects.

For functional integration methods in quantum mechanics there is a nice text book of Feynman and Hibbs1), in which Chapters 10–12 give introductions to statistical mechanics, variational method and other problems in probability. It is also very useful for people who are interested in probability theory (and its application to physical sciences) to refer to Kac’s book2). Since Feynman’s heuristic proposal of his path-integrals in non-relativistic quantum mechanics3) a number of papers have appeared treating related topics, some of which are included in reference4). Unfortunately, however, the study of the subject has not yet been developed in a completely satisfactory way and there are still many things left to be done.

Fifty years ago while writing my doctor’s thesis 1 was already strongly under the influence of Landau although I had never met him as yet. The fact was that in his correspondence he gave as well sharp criticism as warm encouragement which altered the contents considerably. Especially the period, in which I was fortunately enough to work with him at Gottingen, contributed beyond measure to my mathematical development. The present paper would perhaps never have been written without him, even if it diverges to a great extent from the method followed always by him in thought and intent. He preferred to devote his attention to special problems which were characteristic for extensive domains. Whenever as a pioneer he had found a solution for these problems, it was made easy for his followers to generalize the results. The opposite way is taken in this article in which the general question is treated whether and in which measure a given calculus can be extended. In view of the extensiveness of the subject 1 must restrict myself to some indication. The method developed herewith can be applied in many diversified branches, a.o. in the analytic theory of numbers and for this reason it may find a place in a volume dedicated to Edmund Landau. Had this publication appeared fourty years earlier he certainly would have read, accepted and applied it.

Mice of the AKR strain have a very high incidence of lymphocytic neoplasms which appear to be caused by a vertically transmitted virus (see reviews by Kaplan, 1967; Moloney, 1962; Furth et al., 1964; Gross, 1958 and 1961). Since this agent is vertically transmitted, it is expected that germfree mice would also develop leukemia, unless the presence of a microbial flora, or other horizontally transmitted viruses, contribute to its development. That this is indeed the case has been demonstrated by Pollard and his co-workers (Pollard et al., 1966; Pollard, 1967) who showed that germfree AKR mice do develop leukemia in high incidence. The purpose of this paper is to compare the incidence of leukemia in germfree AKR mice with their conventional counterparts. We will also describe some of the characteristics of the germfree AKR mouse which make it somewhat different from other germfree inbred strains.

There are a variety of methods for qualitative and quantitative determination of lipoproteins. Electrophoresis has found broad application as a routine method on account of simplicity as compared to ultracentrifu-gation. Thereby, serum lipoproteins are separated into various bands: alpha-, β-, pre-β-lipoproteins and chylomicrons and the relations of these bands to each other are visualized. In addition to the use of agar (URIEL and GRABAR, 1956; PEZOLD, 1957, 1958) and Reinagar (HOUTSMULLER et al., 1964) as supporting medium paper electrophoresis according to JEHCKS and DURRUM (1955) as modified by LEES and HATCH (1963) has been most commonly used, particularly since EREDRICKSON and LEES (1965) have recommended paper electrophoresis for differentiation of hyperlipidemia. Although paper electrophoresis permits demonstration of typical lipoprotein patterns for various types of hyperlipidemias, it is unsatisfactory with regard to the duration of 16 hours, and the frequent occurrence of poor separation particularly for pre-β- and β-lipoproteins.

I would also like to address myself to the people who have discussed or who gave, papers relating to schizophrenia. I think that anyone who works in this field of biological psychiatry has to be complimented, and if I were king, then my royal coffers would open wide, and they would have bounteous largesse.

In regard to Dr. Hsia’s interesting paper, he has shown us that mothers who have plasma phenylalanine levels above 20 milligrams per cent have children who are more markedly retarded.

Recent epidemiological studies (1,2) have shown that use of oral contraceptives of the combined progestin and estrogen type is associated with a considerably increased risk of venous thromboembolism and cerebral thrombosis, though an association between coronary thrombosis and contraceptive use has not yet been statistically proven. As the preparations used contain one of a wide variety of progestins combined with one of only two similar estrogens (ethynyl estradiol or mestranol), it is probable, if a causal relationship exists, that the harmful component is the estrogen. This conclusion is supported by reports that use of synthetic estrogens alone to suppress lactation (3) or in the treatment of carcinoma of the prostate (4) is associated with increased risk of venous thrombosis and pulmonary embolism. A wide range of both experimental and clinical studies have established the importance of blood platelets in both hemostasis and arterial thrombosis but, although there is considerable evidence for altered platelet function in venous thrombosis and in conditions predisposing thereto, platelets have often been ignored in this latter context. In an attempt to redress the balance this paper will be devoted mainly to an assessment of the possible roles for platelets in venous thrombosis and pulmonary embolism with particular emphasis on the effects of contraceptive steroids on platelet function.

The purpose of the present paper is to introduce the concept that with hyperphenylalanemia the retardation of mental development is an expression of the excessive levels of phenylalanine or its related metabolites rather than a manifestation of the specific disease entity which we call phenylketonuria. We shall present first three pieces of clinical evidence which support this concept and then report on a survey carried out to show the distribution of increased phenylalanine levels when ascertained by newborn screening.

Based on the present state of knowledge concerning the anatomy and physiology of the placenta, a theoretical analysis of the transport of oxygen from maternal to fetal blood is presented in this paper. Distributed parameter mathematical models are derived which describe the convection, diffusion and reaction processes involved in the oxygen exchange. Steady state simulations of placental oxygen transport are obtained by solving the mathematical models for two cases. Case 1 is a simulation of oxygen transport as if it occurred from maternal blood flowing concurrently to fetal blood in a straight capillary. Case 2 simulated the process as if it occurred in a multivillous flow pattern with concurrent flow characteristic of each exchange unit.

This paper reports a portion of the findings of a larger study concerned with the measurement and prediction of change in mental hospital patients [1,2]. As part of this study, a great deal of psychological and social history information had been obtained on a group of patients. The patients were divided into hallucinated (H) and non-hallucinated (NH) sub-groups on the basis of the reported presence or absence of hallucinations in the patient’s hospital chart. The aim was to identify distinguishing characteristics of patients with a history of hallucinations. The general hypothesis was that groups of patients differentiated on the basis of exhibiting hallucinations would also differ in other predictable ways.

Interest in the spontaneous or background activity of neural centers, which appeared at the dawn of electrophysiology, has continued throughout the modern period of neurophysiological research. One of the initiators of such research in the USSR is Livanov, whose work has been devoted to the experimental analysis of activity of the brain as a whole as reflected in the EEG, and of single unit activity of cortical neurons (Livanov, 1938, 1940, 1944a, 1965b). At the present time an analysis of the concrete principles governing integration of the activity of neural units is being conducted in Livanov’s laboratory. As a part of this analysis I have investigated a relatively simple preparation: the ventral nerve chain of the crayfish. The preliminary results of these investigations are described in this paper and an attempt is made to generalize the results of several authors studying the organization of spontaneous or background activity in neural structures.