The genetic control of antibody affinity in mice.

Random-bred TO mice have been selectively bred into two lines on the basis of the relative affinity (KR) of antibody produced to protein antigens, one line producing high and the other low KR antibody. After four generations of selective breeding the difference in KR between the two lines was highly significant (P less than 0-001). The selection on the basis of KR did not result in a corresponding selection for antibody levels (Abt), which were not significantly different in the two lines. These results indicate that antibody affinity is a genetically controlled parameter of the immune response. Furthermore, this control appears to be expressed by a mechanism which is independent of the amount of antibody produced.


Organ distribution of sheep red blood cells in ALS-treated rats.

The inter-organ distribution of radioactivity in rats injected with 51Cr-labelled SRBC is altered after treatment with ALS absorbed with this antigen. The alteration is due to the presence of soluble SRBC antigens in the serum and subsequent immunization of the tested animals. The 51Cr distribution does not correspond to the uptake of antigenic material in immunized rats.


Computer simulation of immunochemical interactions.

A computer model for simulation of the interactions between a macromolecular antigen and its corresponding IgG has been developed. The model takes all possible immune complexes into account, and it calculates the most probable immune complex distribution patterns on the basis of basic thermodynamic principles from the valences and initial concentrations of antigen and antibody, respectively, together with an association constant assumed to be common to all mutual interactions. In antigen excess small antigen-rich complexes are predicted. At or near equivalence a rich variety of relatively small complexes is predicted, while in antibody excess complexes of the type AgAbn are found to be the most probable. By further assuming that the precipitate consists of antibody excess complexes, a precipitin curve can be calculated. The agreement between calculated results and experimentally obtained data is found to be good. It is of special interest that this theory implies that the outcome of immunochemical interactions depend equally well on the concentrations of antigen and of antibody.


Characterization of the temperature-dependent inactivating factor of the thermostable direct hemolysin in Vibrio parahaemolyticus.

The termostable direct hemolysin of Vibrio parahaemolyticus is inactivated by heating at around 55 C with an inactivating factor isolated from culture filtrates of V. parahaemolyticus. The characteristics of the temperature-dependent inactivating factor were studied by using polyacrylamide gel disc electrophoresis. It was found that when heated with the hemolysin, the inactivating factor destroyed the hemolysin and thus inactivated the hemolytic activity, suggesting that the inactivating factor has proteolytic activity. It was also demonstrated that the inactivating factor itself is heat labile, losing its activity on heating with the hemolysin at 95 C for 15 min. The inactivating factor was stimulated by the presence of NaCl or MgCl2 and showed maximal activity at around pH 8.0. The results support our previous hypothesis that the Arrhenius effect observed with crude hemolysin of V. parahaemolyticus is due to the presence of a temperature-dependent inactivating factor. The fact that the factor is activated on heating at 50 to 60 C but is inactivated on heating at 70 to 100 C explains the Arrheius effect of crude hemolysin of V. parahaemolyticus.


Experimental in utero infection of fetal pigs with a porcine parvovirus.

In utero infection of fetuses of six specific-pathogen-free large white sows at 35, 48, 55, 72, 99, and 105 days was studied. The fetuses were infected by direct inoculation of porcine parvovirus into the amniotic sac. The inoculation consisted of 0.25 ml of tissue culture fluid containing 10(5.5) mean tissue culture infective doses per ml of porcine parvovirus strain G10/1. Fetuses of one uterus horn were infected, whereas fetuses in the opposite horn were given 0.25 ml of noninfected cell culture material. No clinical signs of infection were observed; however, all sows developed antibodies 7 to 9 days postinfection. A total of 24 virus-inoculated fetuses and 20 control fetuses were studied. Fetuses infected at 35, 48, and 55 days of gestation died between about 5 and 22 days after infection. Virus was isolated from their organs and fetal blood. Virus spread to control fetuses but did not cause death and mummification or stimulate antibody production. Fetuses from sows infected at 72, 99, and 105 days of gestation survived. They developed high antibody titer in utero. Control piglets remained antibody free.


Binding of cholera toxin by various tissues.

Under certain conditions, it is possible to confirm the observation by Peterson (1974) that the cholera toxin-binding capacities of tissues from brain and colon mucosa, and from liver and small intestine mucosa, are comparable. Binding of toxin by all tissues except brain is very variable, but is roughtly proportional to their content of the toxin-binding ganglioside galactosyl-N-acetylgalactosaminyl (sialosyl) lactosyl ceramide. It appears that some toxin-binding sites of the mucosa of the small intestin and colon may be masked. It has also been confirmed that there may be some solubilization of toxin-binding material from brain on standing a few days at 4 C, but this is comparatively slight. Some disadvantages of measuring toxin binding by adding small amounts of radioactive toxin to compartively large amounts of tissue are discussed.


Oxygen consumption by trachea organ cultures infected with Mycoplasma pneumoniae.

Hamster trachea organ cultres were shown to consume measurable amounts of oxygen when incubated in a closed micro-chamber. Several simple and complex media were evaluated, and the optimal system involved incubating 2 to 4 mg of tracheal tissue in Tyrodes balanced salt solution at 37 C for 60 min, with oxygen activity measured with a Clark electrode. Tracheas infected with Mycoplasma pneumoniae showed a significantly lower oxygen utilitzation than did uninfected controls. The effect was dose dependent when levels of 105 to 107 colony-forming units per ml were used to infect the tracheal rings. Virulent mycoplasmas caused significant decreases in relative ciliary activity and oxygen utilization, whereas attenuated mycoplasmas reduced ciliary activity and oxygen utilization levels to a lesser extent.


Cell-mediated immunity in guinea pigs to subunits derived from hepatitis B surface antigen.

Guinea pigs immunized wit- hepatitis B surface antigen (HBSAg), types adw and ayw, and with two polypeptides (400,000 and 24,000 molecular weight) developed cell-mediated immunity (CMI), as determined by radioimmunoassay. Peritoneal exudate (PE) cells from guinea pigs immunized with the 40,000-molecular-weight polypeptide migrated poorly (30 to 88% inhibition) after challenge with the immunizing subunit or with purified HBSAg, type gdw or ayw. Response of the same PE cells to the 24,000-molecular-weight subunit was significantly reduced. Similar but less striking evidence for CMI was observed was PE cells derived from guinea pigs inoculated with purified type-specific HBSAg or with the 24,000-molecular-weight polypeptide. Humoral responses were predictable and showed a reasonable degree of correlation with the CMI response. PE cells from control animals inoculated with normal human serum or polyacrylamide gel were not inhibited after challenge with purified preparations of HBSAg or with the 400,000-molecular-weight polypeptide, but did show CMI with their respective immunogens. In addition, PE cells from guinea pigs inoculated with normal human serum were inhibited from migrating after challenge with the 24,000-molecular-weight subunit, suggesting that the latter may contain an antigenic determinant related to a human serum protein.


Effect of cyclophosphamide on the growth of Rickettsia sennetsu in experimentally infected mice.

The growth rate of Rickettsia sennetsu, the etiological agent of sennetsu rickettsiosis, a special type of infectious mononucleosis found in western Japan, is very low when the ordinary experimental methods used for other members of the rickettsiae are employed. Attempts have been made to increase its growth the rickettsiae are employed. Attempts have been made to increase its growth rate in cells and animals. By treating mice with cyclophosphamide, considerable enhancement of growth of the rickettsia was observed. In the drug-treated mice, infective titers expressed as mean lethal dose in the spleens reached 10(8,5) in animals treated by the intraperitoneal route three times at 5-day intervals with 0.33 mg/g (body weight). Infective titers in drug-treated mice were more than 100-fold above those of the infected non-drug-treated mice. In peritoneal cells of drug-treated mice rickettsial particles were observed in great abundance. The numbers of cells containing rickettsiae almost paralleled the infective titers of the spleens in each group in mice. Lymph nodes and spleens of the drug-treated mice diminished in size during infection.


A comparison of the diuretic effects of prostaglandin A1, sodium ethacrynate, and placebo.

The comparative diuretic activity of prostaglandin A1 (PGA1), sodium ethacrynate, and placebo was assessed in healthy volunteers. Known active dosages of the various agents were administered as intravenous infusions. In the first four hours after the start of the infusion, the ratio of urine output to liquid intake was higher for sodium ethacrynate than either PGA1 or placebo. Sodium ethacrynate was the only treatment which significantly changed urinary electrolyte excretion. At the doses administered in this study, sodium ethacrynate was more effective as a diuretic than either PGA1 or placebo. PGA1 and placebo exerted nearly identical effects upon the variables studied. This study suggests that PGA1 may be effective only in the presence of altered distribution of blood flow in renal disturbances where tubular functions are involved in maintaining electrolyte excretion.


Changing world patterns of drug abuse, 1945-1974.

New patterns of drug abuse have rapidly appeared in the Western world since the Second World War. These patterns are characterized by the rapid introduction and spread of manufactured substances adopted from medicine. Interest has been sustained among illicit users by the search for new mood altering drugs. Both recreational use and multiple drug patterns are becoming increasingly predominant. Western youth has taken the forefront in the new patterns, especially in the rise of marijuana. Sex differentials are rapidly decreasing as more females are smoking. In the United States, hallucinogens have also been abused in large amounts. This reveals an important difference from Europe, where hallucinogen abuse has been low, but amphetamine abuse has been as high or higher than in the United States. Spread has been rapid throughout the populations studied, both from the colleges to the secondary schools, and from country to country, based on current rapid methods of communication and transportation. These data are important in formulating hypotheses for study and control of both epidemic and endemic drug abuse.


Studies on the CNS-availability of amphetamine from amphetaminil.

The biotransformation of amphetaminil to amphetamine was confirmed using 3H- and 14C-labelled ampehtaminil. The metabolites were isolated, identified and quantified from blood, brain, adipose tissue and urine. These studies showed that the intact molecule of amphetaminil passes into the circulation only to a very small extent. The time spent by the amphetaminil in the alimentary canal does not appear to be a critical factor in the stability and degradation of this substance. The proportion of unchanged amphetaminil represents no more than 2% of the total radioactivity in the blood. The amphetamine, which results from the cleavage of amphetaminil, enters the CNS and is excreted in the urine after hydroxylation and glucuronidation. The other cleavage product, benzaldehyde, seems to be rapidly converted into hippuric acid, which is excreted. Amphetaminil is enriched in adipose tissue, especially after i.p. injection; but this fraction will be cleaved upon re-entering the blood, and it can only enter the brain as amphetamine.


Toxicity of marijuana and tobacco smoking in the beagle.

Four cigarettes of marijuana or tobacco in the form of smoke inhaled into the trachea were administered to dogs daily over a period of nine months. Marijuana caused a slowing of body weight gain. Food consumption increased at first and was accompanied by diarrhea; then it decreased. This suggests a malabsorption of food or a more fundamental metabolic disturbance. The tobacco smoking group consumed much less food without showing any significant change in body weight gain in 3 and 6 months, but it did in 9 months only. In marijuana smoking dog, blood pressure remained unchanged. The resting heart rate was increased (by 32% at 3, 30% at 6, and 15% at 9 months). Alpha1-globulin, eosinophils and lymphocyte count were significantly decreased. A decrease in serum triglycerides was noted. In addition, a behavioral study permitted us to note a general perturbation in the behaviour of the marijuana smoking dogs. The dogs showed impairment of learning, probably due to these behavioral perturbations.


L-dopa, growth hormone and adipokinesis in the lean and the obese.

Fourteen human volunteers (5 lean of both sexes, 4 grossly obese male, 4 grossly obese female, and one patient suffering from hypopituitarism) were given 500 mg of L-dopa orally, and growth hormone (HGH), cortisol, prolactin (hPRL), insulin, FSH, LH, free fatty acids (FFA) and blood glucose were determined up to 300 minutes following the drug. The lean group showed a uniformly marked increase in HGH followed by a significant FFA rise. The obese females exhibited blunted HGH and a somewhat reduced FFA response. In the obese male, there were no HGH und FFA increments. Unstimulated levels of HGH were lower and FFA markedly higher in both obese male and female vs the lean group. The patient with hypopituitarism showed no significant HGH and FFA response. In all groups, hPRL decreased, while Cortisol, LH, FSH, and blood glucose levels remained uninfluenced.


The acute effect of 2-bromo-a-ergocryptine (CB-154) on anterior pituitary hormones and free fatty acids in man.

CB-154 was administered to six healthy subjects in three different single doses - 1 mg, 2,5 mg, and 3 mg. Growth hormone, prolactin, follicle stimulating hormone, luteinizing hormone, cortisol, blood sugar and free fatty acids were determined. 2.5 and 3 mg doses of CB-154 induced a significant rise in growth hormone and free fatty acids, while prolactin decreased. In addition, CB-154 prevented the circadian fall of plasma cortisol. There were no changes in follicle stimulating hormone, luteinizing hormone or blood sugar levels.


Effects of chronic administration of delta 9-transtetrahydrocannabinol (delta9-THC) in guinea-pigs.

The guinea-pigs were divided into three groups: (1) absolute control, (2) solvent control (tween 4%), and (3) delta9-THC group (3 mg/kg). The selected dose of delta9-THC corresponds to the minim amount producing physiological effects in acute administration and was given for six months at the rate of five injections/week. The results showed that THC produced no changes on these parameters: serum glucose, urea nitrogen, total proteins, Mg, Ca, Na, and K. However, the fatty acids and alpha1 globulin were significantly decreased. There was a significant increase in gamma globulin. The body weight gain of delta9-THC treated animals was lower than of the two controls. Delta9-THC decreased the relative weight of liver and spleen; however, it did not significantly affect the relative weight of heart, adrenals, and kidneys. Similarly, the morphological examinations showed no alteration in these tissues, except in the liver tissue, where a perturbation of the autodigestion of glycogen was noted. These observations suggest that the toxic effect of the drug is caused by its accumulation in the liver, which provokes an inhibition of certain liver enzymatic systems.


Phenacetin abuse and renal pelvic carcinoma.

This work is a review of 62 patients with abuse of phenacetin containing drugs and uroepithelial tumours of the renal pelvis, all of them carcinomas. Most of the patients had a pre-existing nephropathy with papillary necrosis as a prominent feature. Renal impairment contributed to the poor prognosis. On the basis of present knowledge of urinary tract carcinogens and phenacetin metabolites, it is assumed that phenacetin is the crucial factor for development of the tumours.


Problems and solutions to single-dose testing of analgesics: comparison of propoxyphene, codeine, and fenoprofen.

Discrepancies exist between reports arising from single-dose and multiple-dose studies intended to compare the efficacy of oral analgesics. D Differences in the pharmacokinetic characteristics of these drugs account for much of the discord. Codeine and fenoprofen rapidly achieve their ultimate plasma equilibrium levels (on a q. 6h. schedule), whereas, propoxyphene requires a longer period, doubtless due to its longer half-life and proportionately smaller maintenance dose. If the drugs are not to be compared during the steady state, then administration of appropriate loading doses permits satisfactory single dose comparisons at steady-state concentrations.


Recent progress in the long-term pharmacological research on cannabis.

Rapid increase in our knowledge of acute biological effects of cannabis and its biologically active components is contrasted with the slow rate of progress achieved in the area of effects of long-term use of cannabis in man. Such studies belong to the difficult category of long-term clinical pharmacological studies, that are time-consuming, require large population samples, and considerable expertise of staff. Recently published epidemiological studies on effects of long-term cannabis use, although still not yet conclusive, supply increasing evidence of harmful effects of such use. Recently, the World Health Organization has sponsored several research projects of this nature in countries with easy access to long-term heavy cannabis users.


Pharmacological approaches to the treatment of morphine-type dependence.

Of the two pharmacologically different possibilities of interfering with the processes of either tolerance or dependence of the morphine type, the so-called maintenance method commonly using methadone is predominantly a matter of tolerance, whereas the blockade with specific opiate antagonists such as cyclazocine intervenes in processes underlying dependence and withdrawal. The experimental evidence for these mechanisms is described.


The danger of fixed drug combinations.

After the second world war a number of pharmaceutical firms which were not able to create new therapeutic substances by their own research, put a great number of fixed drug combinations on the market. Their number quickly increased, as the efficiency of these compounds required no legal proof and as, with appropriate propaganda, large profits could be earned. The number of firms doing this sort of production also increased, and in West Germany, for instance, more than 3/4 of all drugs on the official list are now fixed combinations. Our task is, therefore, to ask for regulations which limit fixed combinations to such preparation the efficiency of which has been shown and whose advantages more than outweigh their disadvantages. The advantages of these preparations are convenience to the patient, avoidance of potential mistakes made possible by too many drugs given on the same day and, perhaps, lower prices. The disadvantages are: 1. The individual optimum dose for a patient cannot be achieved, because in case of a change of dosis all components are changed. 2. Different components may have different duration of action. 3. Different components may have a different bioavailability. 4. Different components may interact. 5. Some components may create tolerance, others not. In many cases fixed combinations have been used to make drugs with poor efficiency financially viable by combining them with very efficient drugs. The existence of thousands of fixed combinations makes the drug market indiscernible and useless. They obscure the relatively few essential drugs and make it difficult for the doctor to find his way amongst the mass of offered medicaments. Few fixed combinations are justifiable. These are well known and they should be permitted as before. All others should be banned until it has been shown that their advantages are greater than their disadvantages.


A study of practolol elimination in all grades of chronic renal failure.

Plasma and renal elimination of practolol have been studied in 12 patients with varying degrees of stable chronic renal failure and 14 normal volunteers. Each individual received 200 mg of oral practolol. The mean time to peak plasma level in the group of patients with renal failure was later than in the normal group, the difference between the two being significant. There were significant correlations between plasma practolol clearance and creatinine clearance, and also between renal practolol clearance and creatinine clearance. Total clearance of practolol from plasma was slightly higher than its renal clearance, the difference being significant, which suggested a small non-renal component to elimination. Renal practolol clearances tended to exceed creatinine clearances, the difference being significant, suggesting some renal tubular secretion of the drug. It is suggested that--in patients with chronic renal failure--the maintenance dose of practolol be reduced roughly in proportion to the reduction in creatinine clearance from normal. If effective plasma practolol concentrations are required quickly, the need for giving a loading dose becomes important under such circumstances.


Tritiated digoxin metabolism after prior treatment with propranolol or diphenylhydantoin sodium.

Digitalis-induced arrhythmias can be suppressed by intravenous potassium, diphenylhydantoin sodium and propranolol. As it is known that hyperkalemia can interfere with the myocardial uptake of digoxin, this study was performed to determine whether diphenylhydantoin sodium or propranolol could exert any antiarrhythmic effect by altering the metabolism of 3H-digoxin and, in particular, the accumulation of the glycoside by cardiac muscle. Three groups of anesthetized dogs were given 6 muCi 3H-digoxin per kilogram intravenously, and in two groups 15 mg/kg diphenylhydantoin sodium or 3 mg/kg propranolol were injected intravenously 15 minutes prior to the glycoside. The concentration of labelled digoxin was measured in plasma up to one hour, and then tissues were removed and analyzed for digoxin content. Diphenylhydantoin sodium did not influence myocardial uptake of digoxin. It is considered its suppressant action on digitalis-induced arrhythmias is not due to any effect on the cardiac accumulation of digoxin. Propranolol did reduce the myocardial uptake of digoxin, but this was not considered of sufficient magnitude to be the main factor in suppressing arrhythmias induced by digitalis. These studies provide evidence that both diphenylhydantoin sodium and propranolol do not have a suppressant effect on digitalis-induced arrhythmias by virtue of any significant interference with the uptake of digoxin by myocardial tissue.


The changing distribution of disease in Regionville.

This survey is a partial replication study of a community with the fictitious name of Regionville which was first studied by Koos in the period 1946-50 (1). In the present paper, we are concerned only with that part having to do with the distribution of disease. Though differences in methods do not allow for a true replication, the indications are that social classes are much more similar in their reported experience of disability now than they were a generation ago. Sources of bias are examined, and it is suggested that differential perceptions of appropriate sick role behaviour may contaminate the findings. Moreover, the sample probably did not include a large enough number of the poverty-stricken population--which is a rather small proportion of the total population--to discover such differences as might in fact exist. It is concluded, however, that the findings do represent a real change in the distribution of disability in the population of Regionville.


Model of transition between causes of death.

This paper describes an attempt to estimate the probabilities of transition between various major causes of death during the period 1954-1962. The regression coefficients have been estimated from French département death rates for ten main or typical causes of death, assessed by sex for the age group 45-64 years.


Rheumatoid arthritis in the Pima Indians of Arizona: an assessment of the clinical components of the New York criteria.

When a prevalence study of Rheumatoid Arthritis (RA) was made in the adult Pima Indian population living on the Gila River Reservation, a high prevalence was found using the New York criteria (5-9 per cent). This was mainly due to the high frequency of limitation of motion which brought in many undesirable subjects. After excluding it as a component of New York criteria we found a prevalence for RA of 3 per cent with a predominance among the females (3-8 as against 2-0 per cent in males). The group so defined fulfilled the requirements of the Rome criteria, showed a higher concordance with serological or radiological evidence of RA, and appeared to identify subjects in whom the experienced clinical rheumatologist would more often agree with the diagnosis.


Serum HI antibody and protection against influenza: a follow-up survey at community level of three epidemics caused by different H3N2-variants.

Serial blood specimens from Rh-negative pregnant women sent to laboratory for Rh antibody testing were stored and used for influenza investigations. The study period covered three epidemics, each caused by a different variant of influenza A (H3N2) virus. The relationship between pre-epidemic haemagglutination inhibiting (HI) antibody level against the epidemic virus and serological evidence of infection was analysed. Titre associated with protection was very similar in the three epidemics. In 1973-74 the influenza A epidemic had an exceptional course characterized by prolonged duration. The study revealed data on the rate of infection in one age and sex category that are difficult to obtain using standard indicators of influenza epidemiology.


Sequelae of Venezuelan equine encephalitis in humans: a four year follow-up.

The purpose of this study was the identification of possible sequelae of the infection of human individuals with Virus of Venezuelan Equine Encephalitis (VEE). Special emphasis was laid on exploring neurological, psychological and behavioural aspects and particularly on the search for a possible association of the disease with epileptic phenomena, brain damage and/or mental deficiency. A four-year period of observation was conducted on a sample of children from El Carmelo (Colombia) where an epidemic of VEE took place in 1967. A group of seven children who presented the encephalitic type of the illness and were hospitalized with symptoms of CNS involvement and a confirmed diagnosis of VEE constituted the index group. This group was compared with four control groups of children with matched demographic characteristics but separated according to whether they were ill at the time of the epidemic and whether they presented serological evidence of having been infected with VEE Virus. Evaluations were conducted at three points in time during the follow-up period and they included the following procedures: (1) Survey on personal background and behaviour (through a standard questionnaire dealing with all areas of functioning); (2) Complete paediatric examination, including a careful neurological check-up; (3) Psychological examination using intelligence tests; (4) Electro-encephalographic examination according to standard techniques, with the patient awake, asleep and under photic stimulation; (5) Bi-weekly home visits to keep a record on intercurrent illness throughout the observation period. Statistical analysis of results shows significant differences between the groups in regard to the distribution of abnormalities.


Aggregated physiological measures of individual and group health status.

Two health status indices applicable to individuals and groups are presented for research and health programme evaluation purposes. Both indices are functions of distances from cultural or group norms of the healthy state on a number of physiological dimensions that are theoretically or empirically related to health. Ways of deriving group norms are briefly discussed.


An epidemiological model of the natural history of a disease within a multilevel care system.

Detailed epidemiological data on the entire course and treatment of illnesses requiring a variety of forms of management and various levels of institutionalization are scarce, probably due to the difficulty of assembling such data from a multiplicity of sources, particularly within complex and fragmented health care delivery systems. This paper described several analytic approaches to, and applications of, such a body of data, taken from a retrospective cohort study of 552 fractured hip cases incident in one year in an upstate New York county. Examples of six analytic applications of the data are presented, and emphasis is placed on the potential for practical use of some of the results.


Upake of plasma lipids by extrahepatic tissues of vitamin A fed rats.

The uptake of newly synthesized plasma lipids from intraportally injected palmitate 1(-14)C by heart, kidney and adipose tissues of rats fed 33 mg retinol for 2 days have been studied. The uptake of plasma lipids by adipose tissues and heart was decreased and that by kidney increased in rats fed retinol as compared to the controls.


RNA synthesis in liver nuclei of young rats fed varying amounts of vitamin A.

Twenty five days old male rats were feed 5000, 20000 and 40000 I.U. of vitamin A for two days and its effects studied on RNA contents and its synthesis from orotic acid-6(-14)C in liver and its nuclear and mitochondrial fractions. RNA contents and its synthesis from orotic acid-6(-14)C in liver, its nuclear and mitochondrial fractions was not affected in rats 5000 I.U. of vitamin A, but these were reduced in rats fed 20000 and 40000 I.U. of vitamin A. The turnover rate of nuclear RNA was significantly greater in rats fed 5000 I.U. of vitamin A as compared to the controls.


Effect of Ovral, a combination type oral contraceptive agent, on vitamin A metabolism in rats.

When a typical combination-type oral contraceptive agent (Ovral, which contains 0.5 mg norgestrel and 0.05 mg ethinyl estradiol per tablet), is given to young female rats at 50 x the human dosage for an extended period, plasma vitamin A levels are elevated about 50%. The increase is mainly due to a higher steadystate level of retinol binding protein, and not to the presence of more lipoprotein-bound retinyl ester. In Ovral treated rats, the depletion of vitamin A from the liver, calculated as a linear rate, as a linear rate per unit body weight, or as a half-life, tends to be greater, although the differences are only marginally significant. The absorption, storage and short-term excretion patterns of a dose of radioactive vitamin A are not demonstrably affected by Ovral treatment.


[Effect of prolonged ingestion of tannic acid, potassium metabisulfite and ethanol, administered alone or in combination, on the liver vitamin A concentration in the rat].

Young male rats were alloted to 23 factorial arrangement to dietary treatments. The eight dietary treatments were: 1) standard semi-synthetic diet (R); 2) stand diet with 1 p. 100 potassium bisulfite (S); 3) standard diet with 3,2 p. 100 tannic acid (T); 4) standard diet with sulfite and tannic acid (ST); 5) standard diet in which ethanol took place of 30 p. 100 of the carbohydrate calories (E); 6) standard diet with sulfite and ethanol (SE); 7) standard diet with tannic and ethanol (TE); 8) standard diet with sulfite, tannic acid and ethanol (STE). After two and six months, the hepatic levels of vitamin A were determined. Factorial analysis of variance was employed in evaluating main effects of the three compounds and their interactions. Tannic acid, alone or associated with sulfite and/or ethanol caused a marked decrease of the concentration of vitamin A after two months, and still more important after six months. The influence of tannic acid on the absorption of vitamin A is discussed. An interaction between sulfite and tannic acid is observed: without tannic acid, sulfite caused a slight but significative increase of vitamin A, but with tannic acid sulfite caused a non-significative decrease of vitamin A. Ethanol had no effect on the store of hepatic vitamin A, but a slight and significative main effect in increasing the concentration.


Thiamine absorption in the rat. III. Effect of ethyl alcohol on active absorption of thiamine in-vitro.

The effect of ethanol on active thiamine absorption in-vitro was studied in everted sacs of rat small intestines. Non-adapted, normally fed rats were used which had not previously been treated with alcohol. It was found that ethanol at 1% final concentration significantly increased active transport of thiamine to approximately fourfold. It is suggested that increased permeability of the intestinal wall plays a major role in phenomenon.


Effects of pyridoxal phosphate N-oxide and 2'-hydroxy pyridoxal phosphate on L-aspartate beta-decarboxylase.

Pyridoxal phosphate N-oxide and 2'-hydroxypyridoxal phosphate served as the coenzyme for aspartate beta-decarboxylase (EC 4.1.1.12) from Pseudomonas dacunhae. Reconstituted enzymes with those pyridoxal phosphate analogues exhibited an absorption band near 370 nm. Close to 1 mole of vitamin B6 derivative is bound per minimal catalytic unit with high affinity. The decarboxylase, desulfinase, and transaminase activites of the both pyridoxal phosphate derivate-enzymes are relatively low. But the Km values for aspartate and cysteine sulfinate are not affected.


[Urinary excretion of pantothenic acid as a measurement of nutritional requirements].

Several groups of male Wistar-Rats were fed for 15 month with a purified diet containing different amounts of pantothenic acid. The groups received 150, 100, 25 and 0% pantothenic acid of the requirement respectively. A further group was fed without pantothenic acid in the diet but administered with the antagonist omega-methyl-pantothenic acid. The excretion of pantothenic acid in the urine was measured at different times, and a groups specific level of excretion could be established for the different groups. Differences to the controls were highly significant in the test groups after 2-18 weeks. Studies of this type were conducted in order to obtain basic informations for later experiments in human beings.


Mechanisms of reversed flavonoid action on blood cells: significance in thromboembolism.

An investigation was conducted on reversal of flavonoid action on erythrocyte aggregation and sedimentation (ESR) in blood from hospitalized patients. Nine compounds were tested. The flavonoids inhibited the ESR in some patients, showed no effect in others and accelerated the ESR in still other patients. With normal ratios of plasma proteins and packed cell volumes (PCV) of 40 vol % or lower the flavonoids inhibited the ESR, but they reversed their action and accelerated the ESR with increased PCV, alteration of plasma proteins, increased calcium and decreased phosphorus; conditions which apparently decreased intercellular distance enabling flavonoids to bridge between erythrocytes similar to antibodies and increase aggregation and sedimentation. The PCV of 156 patients, 60 males and 96 females, average 42 vol % for males and 39 vol % for females. Among these patients 27 had PCV's above 45 vol % and 63.9% of this group (ac PCV 49.5) had experiencedrecent thrombotic episodes compared to only 3.4% for patients with PCV's below 45 vol % (av PCV 41.0). These data point to hazards of PCV's that are considerably above the range of maximum oxygen transport of 40 to 42 vol %. Since the liver and spleen remove clumped cells from the circulation, present evidence indicates flavonoids via their aggregating action at high PCV's may function as regulators acting to maintain tissue perfusion via their antiadhesive action on blood cells and adjustment of ratio of cells to fluid volume of the blood.


[Serum and plasma insulin levels in zinc-deficient rats following glucose stimulation].

In three experiments male Sprague-Dawley rats depleted in zinc (2 ppm dietary zinc) for 30 to 35 days had greatly reduced serum insulin levels when compared to ad libitum-fed control animals (100 ppm dietary zinc) but in only one of the experiments when compared to pair-fed control animals (100 ppm dietary zinc) which also had reduced insulin levels. Similarly, in a following study the plasma insulin levels of zinc-deficient animals depleted for 20 days were not different from those of pair-weight control animals (100 ppm dietary zinc). Fifteen minutes after one i.m. glucose injection and 15 minutes after two glucose injections, two hours apart, the zinc-deficient rats showed a higher blood glucose level than the pair-weight controls. The plasma insulin contents also increased after the glucose stimulation but were not significantly different between the zinc-deficient and the zinc-supplemented groups. It is assumed that zinc deficiency lowers the physiological potency of insulin and thereby effects a reduced glucose homeostasis of zinc-deficient rats. This could also be demonstrated by additional studies with zinc-deficient rats which secreted 76 per cent more insulin after a Rastinon injection than control animals though they showed about the same bloodglucose levels.


[Influence of protein-enriched food on tissue vitamin content in pregnant and lactating rats].

Two groups of female rats were fed, during gestation and until weaning of their pups, diets containing respectively 18% (normal protein diet) and 27% (high protein diet) by weight of casein. Two control groups of female rats were fed the same diet. Thiamin, riboflavin and vitamin B6 contents were measured in: - liver and carcass of the mothers before and immediately after delivery or at weaning (21st day), - whole body of the new born rats or in liver and carcass of 21 days old pups. - liver and carcass of the control animals. The high protein diet, as compared to the normal diet, gives the following results: 1) There is no variation of the thiamin content in control animals, female rats at delivery, new born rats. However, at weaning, carcasses of mothers and pups (mainly liver) are enriched in thiamin. 2) On the other hand, riboflavin content in tissues increases in control animals (liver and carcass), in mothers before and after delivery (carcass) but particularly in mothers at the end of lactation (liver and carcass) and it is also the case with pups at weaning (carcass). Only in new born rats do both diets have the same effect. 3)The influence of the high protein diet on vitamin B6 content in tissues is complex. The content is not modified in control animals, in mothers at delivery and in new born rats. At the end of lactation (mothers) and at weaning (pups), the vitamin B6 content increases in liver but strongly decreases in carcass.


Effect of feeding diets lacking various essential amino acids on body composition of rats.

The effect of amino acid deficiency on the change of body composition in adult rats has been investigated. Six experimentaldiets, lysine-, methionine-, threonine-, tryptophan-, and protein-free, as well as the lactalbumin diet were prepared. The rats fed the lysine-free diet lost the least body weight while the rats fed threonine-, or protein-free diets lost body weight very rapidly. Themean weight loss in the methionine-, or tryptophan-free rats was between that of the lysine-, and threonine-free rats. The water contents in rats adequately reflected the weight loss. The rats that lost the least body weight showed the lowest water contents in their bodies and vice versa. Total body nitrogen contents in rats fed diets devoid of lysine, methionine, or tryptophan were not significantly different from the group fed the lactalbumin diet, whereas total body nitrogen contents in the group fed a threonine-, or protein-free diet were the lowest. Deficiency of lysine resulted in an accumulation of larger amounts of fat in the body as well as in the liver of the rats.


Effect of oral administration of large quantities of ascorbic acid on blood levels and urinary excretion of ascorbic acid in healthy men.

The influence of the daily ingestion of 1, 2, 3, and 5 grams of ascorbic acid on whole blood and plasma ascorbic acid levels and on the urinary excretion of ascorbic acid has been investigated. The ingestion of one gram of ascorbic acid per day for one week significantly increases plasma and whole blood levels over presupplementation levels, but larger amounts of ascorbic acid do not further increase plasma and whole blood ascorbic acid levels. Urinary excretion increases with intake, up to intakes of 3 grams per day but does not increase further when 5 grams of ascorbic acid is ingested per day. Upon discontinuing ascorbic acid supplementation the plasma and whole blood levels decline rapidly and the urinary excretion of ascorbic acid falls to presupplementation values within a few days. The results suggest that there is need for a detailed study of the routes of excretion of ascorbic acid at high levels of intake and that the safety of ingesting large quantities of ascorbic acid may be questioned.


Prevalence of hepatitis B antigen among army inductees.

Eighteen thousand eight hundred and thirty-three consecutive army inductees from the Tel Aviv and Central Districts in Israel were examined for hepatitis B surface antigen (HBsAG) by the counterelectrophoresis technique. The overall prevalence was 1.36%, with a higher rate for males (1.84%) than for females (0.78%). The highest rates were observed among Jews of North African and Yemenite origin (4.14 and 3.97%, respectively) and the lowest rates was found among Jews of European origin (0.31%). There was a negative correlation between the prevalence of HBsAg and the level of education. If we assume that the prevalence of HBsAg in a population reflects the rate of infection with hepatitis B virus interacting with host factors, the results of this study support the hypothesis that infections with type B hepatitis in Israel occur mainly during childhood, more frequently among the lower socioeconomic classes, and with a predilection of either the infection or of the chronic carrier state for males and certain ethnic groups.


Polyamine excretion in the urine of cancer patients.

In the human body, the production of three polyamines--putrescine, spermidine and spermine--is largely associated with tissue growth, while that of a fourth--cadaverine--seems to be the result of bacterial action. In 37 (88%) of 42 cancer patients and in 24 (44%) of 54 patients with various nonmalignant diseases, increased amounts of polyamines were found in the urine. In the nonmalignant group, which served as a control group, the increased polyamine excretion was especially evident in patients with infections. There were, however, differences in the excretion patterns of the cancer and control groups: combinations of elevated levels of putrescine, spermidine and spermine were seen exclusively in the cancer patients; spermine was not found in the urine of women in the control group. The determination of urinary polyamines appears to hold promise as an aid in the diagnosis of malignant disease and in following up the results of therapy.


Maple syrup urine disease. Two cases in Israel.

The first two patients in Israel in whom the diagnosis of maple syrup urine disease was confirmed are reported. The clinical course of the disease and therapeutic procedures during the first months of life are described. The age on onset and the severity of neurological symptomatology were different in the two patients. In the first, blood leucine levels were extremely high, and drastic procedures, such as peritoneal dialysis, were employed in addition to dietary treatment to lower the leucine levels to normal and to improve the patient's clinical condition. In the second infant, blood leucine levels were moderately elevated and the disease was controlled by dietary treatment alone. Neither of the patients responded to thiamine hydrochloride treatment. The two infants probably represent examples of different genotypes of the classic form of maple syrup urine disease.


Drug hoarding in a rural community in Israel. Results of a pilot epidemiologic investigation.

The total quantity of drugs hoarded in a rural village in Israel was established as a result of a comprehensive house-to-house search. In 43 of the 44 houses in the village, hoarded drugs were found. The average number of different drugs found per household was 15.5 and the median number, 9.5. Analgesic and antipyretic drugs, topical skin preparations and antibiotics were found most frequently among a total of 166 identifiable medicines. The drugs found included 5,998 tablets and capsules, 3,327 ml of liquid preparations, 1,290 g of creams and powders and 369 suppositories and pessaries. These findings are discussed in relation to the drug expenditure of the largest Israel health insurance fund, the serious health hazards which they present, and their possible relevance to the total Israel population. The possibility of a "hoarding-prone" personality is raised.


Acute transient monocular disequilibrium (Halpern's syndrome).

An acute transient form of monocular disequilibrium (Halpern's syndrome) was found in two patients. Misjudgement of verticality and motion was induced by looking with one eye and was alleviated by use of the fellow eye. This symptomatology is discussed in the light of recent concepts of oculovestibulocerebellar integration.


Obstructive jaundice associated with carcinoma of the prostate.

An unusual case of prostatic carcinoma presenting as severe obstructive jaundice is reported. After treatment with stilbestrol and bilateral orchidectomy, liver function tests became normal and lung metastases disappeared. During a second episode of jaundice due to serum hepatitis, liver function deteriorated following stilbestrol administration, and the drug was temporarily discontinued. The patient has been followed up for three years and liver function tests remain normal.


[Vitality evaluation of malignant melanoma metastases following endolymphatic radionuclide therapy using the Falck-Hillarp method].

A case of malignant melanoma involving the regional lymphnodes was treated by endolymphatic isotope therapy. Because of the great diameter the radiation of some metastases was not completely sufficient. Fluorescent and living cells of malignant melanoma between damaged cells could be seen in the center of these metastases. Melanophages surrounded concentrically the central part of the metastases enclosing the melanoma cells. It is shown that in the search and identification for pigment producing melanoma cells the fluorescent histochemical method of Falck-Hillarp is superior to usual light microscopical methods. Beyond of this, the phenomenon of fluorescence in malignant melanoma cells probably is an indication for the vitality of these cells.


Granuloma inguinale in Vietnam: successful therapy with ampicillin and lincomycin.

Thirty-six patients having granuloma inguinale were treated at the 483 USAF Hospital, Cam Ranh Bay, Republic of South Vietnam between October 1970 and September 1971. In 24 cases biopsy of the genital ulcerations revealed Donovan bodies pathognomonic for the disorder. The lesions generally did not heal during tetracycline therapy. All but 2 of the 31 cases treated primarily with ampicillin responded with complete healing of the local lesions which occurred primarily on the penis or in the groin. Of the remaining 2 patients, one responded to a second course of ampicillin and the other patient responded to a two week course of lincomycin after dorsal slit had been performed for partial phimosis and balanoposthitis. The 5 patients who were allergic to penicillin were treated primarily with lincomycin and all responded with complete healing. No previous reference could be found in the literature for the successful use of lincomycin in patients with granuloma inguinale. Further clinical trials with this medication are indicated.


Plate fixation of iliac shaft fractures in the dog.

In a series of 20 dogs, 23 fractured ilia were reduced and stabilized with a variety of bone plates. The results indicated that fixation was rigid enough for fracture healing and for  the patient to be ambulatory soon after surgery. Plate fixation can therefore be recommended as a reliable method of repair in selected fractures of the canine ilium.


Familial canine diabetes mellitus.

A 10-year-old male Miniature Poodle was found to have clinical diabetes mellitus. The patient's dam had died from diabetes. Two 4-year-old dogs, produced from a mating between the patient and its dam, were examined and an oral glucose tolerance test was performed on each. One dog had striking glucose intolerance and was considered to be prediabetic.


Grisorixin, an ionophorous antibiotic of the nigericin group. II. Chemical and structural study of grisorixin and some derivatives.

Grisorixin, a polycyclic polyether antibiotic of the nigericin group, showed ionophorous properties. The conformations of crystallized grisorixin and its metallic salts are very similar and are compared in this paper. The physico-chemical properties of the salts are described. The chemical oxidation of grisorixin methyl ester allowed us to isolate several oxidation products whose structures are described.


A new antibiotic victomycin (XK 49-1-B-2). I. Taxonomy and production of the producing organism.

A new antibiotic designated as victomycin which belongs to the phleomycin-bleomycin group antibiotics was isolated from a sporangia-forming actinomycete. From taxonomic studies, the producing strain was classified as Streptosporangium violaceochromogenes nov., sp. Kawamoto et Nara 1974. Fermentative production of antibiotic complex XK 49 is described.


A new antibiotic victomycin (XK 49-1-B-2). II. Isolation, purification and physicochemical and biological properties.

A new antibiotic, victomycin, is active against a variety of Gram-positive and Gram-negative bacteria, and also has in vivo activity against solid Sarcoma 180 and Ehrlich ascites carcinoma. It belongs to the phleomycin-bleomycin group of antibiotics and has been differentiated from all known phleomycins and bleomycins by its physicochemical properties and thin-layer chromatograms.


Time course of termination of the glucose transport action of insulin in adipocytes.

Rapid sequence measures of changes in the rate of 14CO2 production from [14C]glucose bathing the cells was abruptly reduced from 20 to 4 microunits/ml. Interpretation of the data in terms of glucose transport was based on calibration experiments that described the time course of change in 14CO2 production when [14C]glucose entry  into adipocytes was slowed by reducing the specific activity of [14C]glucose in the incubation medium. All experiments were performed at 37 degrees in Krebs-Ringer bicarbonate buffer at pH 7.4. Termination of the glucose transport action of insulin (which includes insulin-receptor disassociation and all other steps leading to decelerated glucose entry) began within 2 min and was complete within 30 min. The transition from one steady state rate of glucose transport to the other could be approximated by an exponential process occurring with a half-time of 14 min. For comparison, the time course of initiation of the glucose transport action of insulin was measured under the same conditions. The transition curve was virtually identical.


Thermodynamical studies of oxygen equilibrium of hemoglobin. Nonuniform heats and entropy changes for the individual oxygenation steps and enthalpy-entropy compensation.

Precise oxygen equilibrium curves of human adult hemoglobin were determined by the automatic recording method at several temperatures in the presence and absence of 2,3-diphosphoglycerate (DPG) or inositol hexaphosphate (IHP) with 0.05 M 2,2-bis(hydroxymethyl)-2,2',2''-nitrolotriethanol (bis-tris) buffers (pH 7.4) containing 0.1 M Cl-. The equilibrium data were analyzed according to the Adair scheme, and the heats, deltaHi (i = 1,2,3,4) and the entropy changes, deltaSi (i = 1,2,3,4), for the individual oxygenation steps were obtained. The shape of the equilibrium curve varies on temperature changes whether DPG or IHP is present or absent. In consequence, the deltaHi value depends on i and on the presence of DPG and IHP. Behavior of deltaSi is similar to that of deltaHi. The similar behavior of deltaHi and deltaSi resulted in a compensation phenomenon. The contribution of T cdeltaSi to the free energy change is compensated by the contribution of deltaHi at the first three oxygenation steps but not at the fourth step, and for i = 1,2, and 3 changes of T cdeltaSi value upon the addition of DPG and IHP are compensated by accompanied changes of deltaHi value, where T c (= 260 K) is the compensation temperature. A major part of both the enthalpy-entropy compensation and nonuniformity of deltaHi and deltaSi appears to be attributable to contributions of the oxygen-linked binding of Cl-, DPG and IHP, by hemoglobin. The present results do not necessarily support the earlier idea of Wyman that the cooperative oxygenbinding is essentially an entropy effect.


X-ray crystallographic study of boronic acid adducts with subtilisin BPN' (Novo). A model for the catalytic transition state.

We have studied the structures of adducts formed between subtilisin BPN' and both benzeneboronic acid and 2-phenylethaneboronic acid by x-ray diffraction techniques. Electron density and difference maps at 2.5 A resolution were computed with phases calculated from a partially refined structure of the native enzyme (R = 0.23 at 2.0 A). Both adducts contain a covalent bond between Ogamma of the catalytic Ser-221 and the inhibitor boron atom. The boron atom is coordinated tetrahedrally, with one of the two additional boronic acid oxygen atoms lying in the "oxyanion hole" and the other at the leaving group site identified in previous studies (ROBERTUS, J.D., Kraut, J. ALDEN, R.A., and BIRKTOFT, J.J. (1972) Biochemistry 11, 4293-4303). Moreover, the previously postulated structure of the tetrahedral intermediate for substrate hydrolysis is isosteric with these boronic acid adducts, which can therefore be considered good models for the transition state complex (KOEHLER, K.K., and LIENHARD, G.E. (1972) Biochemistry 10, 2477-2483). These observations further support the suggestion that an important contribution to stabilization of this transition state complex, relative to both the Michaelis complex and the acyl intermediate, occurs as a consequence of hydrogen bond donation to the substrate carbonyl oxygen atom from the side chain amido group of Asn-155 and from the backbone amido group of Ser-221.


A possible involvement of sulfhydryl groups in the conversion of lysine monooxygenase to an oxidase.

Lysine monooxygenase catalyzes the oxygenation of lysine and arginine, and produces delta-amino-n-valeramide and gamma-guanidinobutyramide, respectively, concomitant with decarboxylation. In a preliminary communication, treatment of the native enzyme with p-chloromercuribenzoate was shown to inactivate the oxygenase and to induce an oxidase activity. The modified enzyme catalyzed predominantly the oxidative deamination of lysine and arginine resulting in the formation of the corresponding alpha-keto acid, ammonia, and hydrogen peroxide (YAMAUCHI, T., YAMAMOTO, S., and HAYAISHI, O.(1973) J. Biol. Chem. 2j8, 3750-3752). Paper electrophoresis, cellulose thin layer chromatography, and chemical degradation of the reaction products from lysine and arginine, provided further evidence for their identity with alpha-keto-epsilon-aminocaproate and alpha-keto-delta-guanidinovalerate, respectively. Further studies were carried out to establish the involvement of sulfhydryl groups in this conversion of the enzyme activities. Various sulfhydryl reagents including certain mercurials, alkylating, and oxidizing reagents, showed essentially identical effects on the enzyme. Dithiothreitol treatment reversed the conversion produced by various mercurials; the oxidase activity disappeared and the oxygenase activity was recovered. When p-chloromercuribenzoate was added to the enzyme and the increase in the absorbance at 250 nm was followed, 3.6 of the 6.5 half-cystine residues present per enzyme-bound FAD were readily titrated within 3 to 4 min. The inactivation of the oxygenase and the induction of the oxidase activity were almost maximal with 4 to 5 mol of p-chloromercuribenzoate/mol of enzyme, and these effects occurred within 3 to 4 min. These results together with other properties of the modified enzyme provided evidence for a possible involvement of these reactive sulfhydryl groups during the conversion of the oxygenase to an oxidase.


Isolation and characterization of protein A24, a "histone-like" non-histone chromosomal protein.

In earlier studies, the nucleolar levels of protein A24 were found to be markedly decreased in the nucleolar hypertrophy induced by thioacetamide or during liver regeneration (Ballal, N.R., Goldknopf, I.L., Goldberg, D.A., and Busch, H. (1974) Life Sci. 14, 1835-1845; Ballal, N.R., Kang, Y.-J., Olson, M.O.-J., and Busch, H.J. Biol. Chem. 250, 5921-5925). To determine the role of protein A24, methods were developed for its isolation in highly purified form. Milligram quantities of highly purified protein A24 were isolated from the 0.4 N H2SO4-soluble proteins of calf thymus chromatin by exclusion chromatography on Sephadex G-100, followed by preparative polyacrylamide gel electrophoresis. Protein A24 was highly purified as shown by its migration as a single spot on two-dimensional polyacrylamide gel electrophoresis, its single NH2-terminal amino acid, methionine, and the production of approximately 50 peptides by tryptic digestion. Like histones 2A, 2B, 3, and 4. A24 was extractable from chromatin with 0.4 N H2SO4 or 3 M NaCl/7 M urea, but unlike most non-histone proteins or histone 1, protein A24 was not extracted with 0.35 M NaCl, 0.5 M HClO4, or 0.6 M NaCl. Protein A24 was present in only 1.9% of the total amount of histones 2A, 2B, 3 and 4; its molecular weight is 27,000.


On the role of substrate and GTP in the regulation of argininosuccinase activity.

As determined by equilibrium dialysis, bovine liver argininosuccinase of molecular weight 202,000 binds 4 mol of argininosuccinate or arginine/mol of enzyme. Negative homotropic interactions occur in the binding of both ligands at 0.15 ionic strength in the presence of phosphate. Argininosuccinate binds to two sites (Kdiss 1.6 times 10(-5) M) and four sites (Kdiss 2.9 times 10(-4) M) at low and high substrate concentration. Similarly, arginine binds to two sites (Kdiss 4.9 times 10(-4) M), and four sites (Kdiss 1.6 times 10(-3) M). At 0.05 ionic strength in Tris-HCl buffer, the four enzyme sites bind argininosuccinate independently and arginine binding remains negatively cooperative. Kinetic analysis gave double reciprocal plots that showed negative cooperatively also. The changes in Km were analogous to changes in Kdiss, thus indicating that the substrate binding sites correspond to catalytic sites. Since the catalytically active enzyme is a tetramer composed of four identical or closely similar subunits (Lusty, C.J., and Ratner, S. (1972) J. Biol. Chem. 247, 7010-7022), the present results show that each subunit contains one catalytic site. Ionic strength, phosphate ions, and GTP have each been found to influence negative cooperatively through a change in the affinity for argininosuccinate. The significance of the negative homotropic interactions and of the specific stimulation of activity by GTP is discussed with respect to different conformational forms of the enzyme and the in vivo regulation of argininosuccinase activity.


Evidence for specific binding sites for guanine nucleotides in adipocyte and hepatocyte plasma membranes. A difference in fate of GTP and guanosine 5'-(beta, gamma-imino) triphosphate.

Binding and degradation of GTP and guanosine 5'-(beta, gamma-imino)triphosphate (Gpp(NH)p by plasma membranes from rat liver and fat cells were investigated. Gpp(NH)p is hydrolyzed predominantly by nucleotide pyrophosphohydrolases in the membranes, whereas GTP is hydrolyzed primarily by nucleotide phosphohydrolases. These enzymes are not specific for the guanine nucleotides since co-addition of the analogous adenine nucleotides spares their hydrolysis. Both Gpp(NH)p and GTP are taken up by the membranes at sites which, to the extent that high concentrations of the corresponding adenine nucleotides fail to inhibit uptake, appear to be specific for guanine nucleotides. Gpp(NH)p taken up at these sites remains essentially intact irrespective of the degree of hydrolysis of unbound Gpp(NH)p by nucleotide pyrophosphohydrolases, indicating that the binding siteis incapable of degrading Gpp(NH)p. GTP and GDP inhibit competitively the binding of Gpp(NH)p; the binding constants for the three nucleotides are similar (0.1 to 0.4 muM) and are in the same range required for their effects on adenylate cyclase activity. Binding of the nucleotides is inhibited by sulfhydryl agents, suggesting that a sulfhydryl group is involved in the binding process. In contrast to binding of Gpp(NH)p, uptake of GTP is accompanied by substantial hydrolysis, primarily to GDP, under incubation conditions (high [ATP] plus ATP regenerating system) in which [GTP] in the medium remains essentially constant. GDP bound to the membranes is progressively hydrolyzed to 5'-GMP. Thus, GTP and Gpp(NH)p, although binding to the same specific sites, are differentially susceptible to hydrolysis at their terminal phosphates when bound to these sites. These findings are discussed in terms of the markedly different potencies of GTP and Gpp(NH)p as activators of adenylate cyclase systems.


Elementary chain composition of guinea pig thyroglobulin.

Thyroglobulin obtained from guinea pigs was examined by Na dodecyl-SO4-polyacrylamide gel electrophoresis after reduction and alkylation. In contrast to thyroglobulin from other mammalian sources, only three groups of polypeptide chains accounted for 95% or more of the protein. Determinations of the molecular weights of these purified proteins by equilibrium centrifugation in 6 M guanidine HCl gave values of 295,000 (species A), 210,000 (species B), and 110,000 (species C). Molecular weights determined by gel filtration in 6 M guanidine HCl gave similar results. Due to the large size of the polypeptides, satisfactory molecular weights could not be obtained from Na dodecyl-SO4-polyacrylamide gel electrophoresis. Amino acid analysis of the three species was similar to that of whole thyroglobulin. Only slightly higher level of lysine and histidine and a lower level of glutamic acid were seen in species C. The iodine contents were found to range from 0.07 to 0.12 to 0.20% for species A, B, and C, respectively.


Characterization of cell-free synthesis of collagen by lung polysomes in a heterologous system.

In normal lung growth, post-pneumonectomy lung growth, and in possibly several lung disorders, there are marked alterations in the density of collagen and changes in the rate of synthesis of collagen relative to the synthesis of other lung proteins. To provide a technology to begin to understand these changes at the molecular level, polysomes were prepared from rabbit lung and translated in a heterologous cell-free system including rabbit reticulocyte 0.5 M KCl ribosomal wash fraction and liver tRNA. Collagen was shown in the cell-free product by collagenase sensitivity, hydroxylation of incorporated proline by peptidyl prolyl hydroxylase, agarose gel chromatography, and sodium dodecyl sulfate acrylamide gel electrophoresis. The cell-free system was optimized with respect to K+, Mg2+, amino acids, and ribosomal wash fraction and used under conditions where total protein synthesis and collagen synthesis are linear with respect to time and amount of polysomes. Under these conditions, collagen synthesis was directed almost entirely by polysomes derived from the endoplasmic reticulum. Polysomes isolated from late fetal lung directed collagen synthesis at twice the rate (per polysome) as those polysomes isolated from adult lung. Similar changes were seen if lung tRNA replaced liver tRNA and if lung ribosomal wash fraction replaced reticulocyte wash fraction. Although these changes in cell-free lung collagen synthesis with tissue explants, further studies will have to be carried out to determine whether, in fact, age-related alterations in control of lung collagen synthesis are truly explained by these findings.


On the "activation" of cytokinins.

A number of cytokinin analogs containing modifications in the heterocyclic moiety were prepared. These compounds were tested for activity as cytokinins and anticytokinins in the tabacco bioassay and the results were used to determine whether any position(s) of the heterocyclic nucleus of cytokinins may require derivatization as part of an over-all "activation" process. 3-substituted 4-alkylaminopyrazolo [3,4-d]pyrimidines and 4-alkylaminopyrrolo[2,3-d]pyrimidines, for example, have (substituted) carbon rather than nitrogen atoms at positions 3 and 5, respectively (analogous to position 7 in purines) and would be predicted to be metabolically stable at these positions. The finding that these compounds had cytokinin activity suggested that modification at the metabolically stable positions. The finding that these compounds had cytokinin activity suggested that modification at the metabolically stable position, and by extension at position 7 in cytokinin analogues which are purines, is not a prerequisite for the expression of cytokinin activity. Similar consideration of other heterocyclic analogs which have cytokinin activity suggests that the active form of a cytokinin can be the exogenous compound itself. Certain structural analogs of cytokinins were found to inhibit the growth of tobacco callus promoted by 6-(3-methyl-2-butenylamino)purine. These compounds were studied as potential cytokinin antagonists, i.e. having activity analogous to the 7-alkylamino-3-methylpyrazolo[4,3-d]pyrimidines (Hecht, S. M., 2068-2610; Skoog, F., Schmitz, R.Y., Hecht, S.M., and Bock, R. M. (1973) Phytochemistry 12, 25-37). The activity of these compounds is discussed and criteria are proposed to distinguish between those species which are specific anticytokinins and those which otherwise inhibit growth.


Interconversion of different molecular weight forms of human erythrocyte orotidylate decarboxylase.

Orotidylate decarboxylase has been purified approximately 300-fold from human erythrocytes. It was shown to exist in three molecular weight forms, a probable monomer of molecular weight 62,000, a dimer, and a tetramer. Conversion of the monomer to higher molecular weight forms was associated with increased stability to thermal inactivation and was promoted by a number of low molecular weight compounds, including orotic acid and competitive inhibitors of the enzyme. Orotic acid phosphoribosyltransferase co-purified with the decarboxylase but was much more susceptible to inactivation. The partially purified orotidylate decarboxylase showed a triphasic Lineweaver-Burk plot when examined over a wide range of substrate concentrations. The separated molecular weight forms gave linear double reciprocal plots with Km values corresponding to the three values obtained with the erythrocyte enzyme preparation. The values obtained were 25, 3, and 0.6 muM for the monomer, dimer, and tetramer forms, respectively.


Evidence for the lack of subunit exchange between aldolase tetramers in vivo.

The results of a double isotope experiment using 3H- and 14C-labeled leucine as precursors of protein synthesis demonstrated that the aldolase C to A subunit transition which is associated with chick skeletal muscle development involves the preferential synthesis of different aldolase isoenzymes. This developmental system was used to test for subunit exchange between aldolase tetramers in vivo. In a second double isotope experiment, it was found that the 14C:3H ratios of A and C subunits derived from the same heterotetramer were essentially identical, while the isotope ratios of the same subunit type derived from different isoenzymes were considerably different. Had subunit exchange between the isoenzymes occurred, A subunits of a given heterotetramer would have been expected to have higher isotope ratios than the corresponding C subunits. Therefore, these data suggest that subunit exchange between aldolase tetramers does not occur in vivo, at least not in skeletal muscle to an appreciable extent. The results of the present study suggest that all aldolase tetramers are constructed at the time of the initial assembly of newly synthesized subunits, that is, "new" tetramers would not be generated by subunit exchange between already constructed tetramers. In addition, the present work suggests that the degradation of all four subunits of an aldolase tetramer are coupled inasmuch as the subunits would not be reincorporated into other tetramers. Thus, in contrast to some other proteins, it appears that the subunits of the aldolase tetramer turn over coordinately.


Purified liver microsomal cytochrome P-450. Electron-accepting properties and oxidation-reduction potential.

The reduction of highly purified cytochrome P-450 from rabbit liver microsomes under anaerobic conditions requires 2 electrons per molecule. Similar results were obtained with dithionite, NADPH in the presence of NADPH-cytochrome P-450 reductase, or a photochemical system as the electron donor, with CO or other ligands, with substrate or phosphatidylcholine present, after denaturation to form cytochrome P-420, or with cytochrome P-450 partially purified from rat or mouse liver microsomes. The reduced cytochrome P-450 donates 2 electrons to dichlorophenolindophenol or to cytochrome c. Reoxidation of reduced cytochrome P-450 by molecular oxygen restores a state where 2 electrons from dithionite are required for re-reduction. Although these unexpected findings indicate the presence of an electron acceptor in addition to the heme iron atom, significant amounts of non-heme iron, other metals or cofactors, or disulfide bonds were not found, and free radicals were not detected by electron paramagnetic resonance spectrometry. Resolution of the cytochrome with acetone and acid yielded the apoenzyme, which did not accept electrons, and ferriprotoporphyrin IX, which accepted a single electron. A reconstituted hemoprotein preparation with the spectral characteristics of cytochrome P-420 accepted as much as 0.7 extra electron equivalent per heme. The midpoint oxidation-reduction potential of purified cytochrome P-450 from rabbit liver microsomes at pH 7.0 is -330 mv, and with CO present this value is changed to about -150 mv. The oxidation-reduction potential is unaffected by the presence of phosphatidylcholine or benzphetamine, a typical substrate. Laurate, aminopyrine, and benzphetamine undergo hydroxylation in the presence of chemically reduced cytochrome P-450 and molecular oxygen. Neither NADPH nor the reductase is required for substrate hydroxylation under these conditions.


The covalent structure of collagen. Amino acid sequence of alpha1-CB5 glycopeptide and alpha1-CB4 from chick skin collagen.

The amino acid sequences of chick skin alpha1-CB4 and alpha1-CB5 have been determined by automated Edman degradation of the intact peptides and of their tryptic and chymotryptic peptides. The two peptides contain 47 and 37 residues and comprise residues 56 to 102 and 103 to 139, respectively, of the alpha1(I) chain. In addition, alpha1-CB5 is the major hexose-containing peptide, previously reported to be active in mediating platelet aggregation. A comparison of the sequence with previously reported data on the homologous region of the rat skin alpha1(I) chain indicates that there are only three interspecies differences, or a sequence identity of 96%.


Separation of a protein factor necessary for the oxidative desaturation of fatty acids in the rat.

Microsomes from rat liver were extracted by low ionic strength solutions. Extracted microsomes lost most of the linoleic acid desaturation activity. The addition of the extract back into the extracted microsomes was necessary to restore full desaturation activity. The soluble fraction had no desaturation activity. The existence of a soluble factor loosely bound to the microsomes, stable to sonication, and unstable to heat and trypsin digestion was recognized. This protein could not be replaced by albumin. The factor was also essential for the oxidative desaturation of palmitic, stearic, linoleic, and gamma-linolenic acid. The present experiment suggests that the protein factor is not NADH-cytochrome b5 reductase, cytochrome b5, or the cyanide-sensitive factor.


Passive Ca2+ permeability of phospholipid vesicles and sarcoplasmic reticulum membranes.

During the excitation of muscle the estimated rate of Ca2+ release from sarcoplasmic reticulum may increase 10(3)- to 10(4)-fold compared with relaxed muscle or isolated sarcoplasmic reticulum in vitro, implying a major change in the calcium permeability of the sarcoplasmic reticulum membrane. As a first step in the assessment of the role of various membrane constituents in the regulation of calcium fluxes, the contribution of phospholipids to the definition of calcium permeability was studied in model systems. The rate of calcium release from vesicles prepared from pure phosphatidylcholine, phosphatidylethanolamine, phosphatidylserine, phosphatidylinositides, cardiolipin, and extracted microsomal lipids is in the range of 10(-15) to 10(18) mol of calcium/cm2/s. This rate is several orders of magnitude lower than the passive calcium outflux from isolated sarcoplasmic reticulum membranes. The permeability to Ca2+ is influenced by fatty acid composition and net charge and it is markedly increased with increasing temperature or after the addition of local anesthetics.


A comparison of the heme binding pocket in globins and cytochrome b5.

Of the 85 three-dimensionally characterized residues of cytochrome b5, 51 are found to be structurally and topologically equivalent to the globin fold. When these proteins have been superimposed, the heme irons are found to be less than 1.4 A separated and the heme normals are inclined by less than 9.5 degrees. The proximal histidine of the globins and two adjacent helices are equivalent to the sixth iron ligand and adjacent helices of cytochrome b5. Larger differences in structure are observed on the distal side of the heme, coincident with the most changeable part of the globin structures. The heme itself is rotated by 53 degrees about its normal but such a change is energetically minimal and conservative as the heme side groups are not directly involved in the function of the molecules. The beta-sheet of cytochrome b5 is inserted into a corresponding cavity of the globins forming an additional lining to the heme pocket. The roughly 50 residues missing at the carboxy end of the known cytochrome b5 fragment could correspond in part to the H helix in the globins. While it would seem probable that these similarities represent divergent evolution from a primordial heme-binding protein, the possibility of structural convergence to a functionally satisfactory protein cannot be excluded.


Isolation of lectins of different specificities on a single affinity adsorbent.

Affinity chromatography on Sepharose-fetuin columns was used in a single step procedure to isolate the lectins concanavalin A, Favin, phytohemagglutinin, wheat germ agglutinin, and Limulus hemagglutinin. New lectins with unknown binding specificities were also purified by the same procedure from extracts of small California white beans, Idaho red beans, and white pea beans. The purified lectins exhibited different cell surface mapping properties on erythrocytes, lymphocytes, and sperm cells. It was particularly striking that neither 131I-labeled concanavalin nor 125I-labeled wheat germ agglutinin had any effect on the binding of the other to mouse spleen cells. In accord with this observation, gel electrophoretic analysis of radiolabeled lymphocyte receptors for these two lecithins yielded different patterns. These results indicate that highly purified lectins prepared by affinity chromatography on the same adsorbent can possess strikingly different binding specificities for cell surface receptors.


Conformity and psychopathology: a comparative study of conformity behaviors in manic-depressive, paranoid schizophrenic and normal populations.

Several theorists have speculated that schizophrenia constitutes a disorder in which there is minimal motivation to conform to social pressures, while manic-depressive psychoses represent disorders in which there is maximal motivation to conform to social pressures. However, there have been few experimental tests of these speculations, and those that have been conducted generally have yielded conflicting results because of methodological inconsistencies and limitations. The present investigation examined conformity behavior of male and female manic-depressives (MD), paranoid schizophrenics (PS), and normals (N) on two conformity tasks: attitude change and perceptual judgment. It was hypothesized that manic depressives would conform more than normals, who would conform more than paranoid schizophrenics (MD less than N less than PS). Results indicated that manic-depressives and normals conformed significantly more than paranoid schizophrenics, but did not differ from each other on either of the conformity tasks. Thus, the hypothesis was supported only partially. The results do not support the view that manic-depressive psychoses constitute disorders in which there is maximal motivation to conform to social pressures; however, the results do support the view that schizophrenia represents a disorder in which there is minimum motivation to conform. The results are discussed in terms of their implication for the uses of interpersonal psychotherapy forms.


Sex differences as related to measurement of emotional arousal.

This study examined two categories of stress as a possible factor in previously mixed findings with regard to sex differences. Imagined physical stress and mental stress were induced by having Ss listen to tape-recorded descriptions of a car accident or taking a final exam. A self-report checklist was used to obtain ratings of anxiety, hostility and depression, and a Likert-type scale was employed to get Ss' estimates of their own emotional reactions. All Ss showed marked increase in emotionality scores after scene presentations. The results did not support the view that there are sex differences in responding due to different stressful conditions. However, females tended to express more emotionality than males to the stressful scenes. These differences were discussed in view of in vivo vs. in vitro presentation of stressful stimuli and the obtainment of sex differences as a function of where the measurement instrument falls on a subtle-obvious dimension.


The effects of vicarious reinforcement on modeling by schizophrenic hospital patients.

Adult male schizophrenic Ss were exposed to a peer model under conditions of positive vicarious reinforcement, negative vicarious reinforcement, and no vicarious reinforcement. The degree to which the Ss imitated the behaviors of the model was not affected by the vicarious reinforcement, although the Ss did emit significantly more of the dependent measure behaviors than did a group of control Ss who had seen no model. The failure of the Ss to respond to the vicarious reinforcement was seen in terms of the inability of schizophrenics to attend to relevant detail.


The relationship between self-actualization and psychosocial maturity.

Similarities were noted between Maslow's notion of self-actualization (SA) and Erikson's notion of psychosocial maturity. Previous research by Simmons has shown a significant relationship between identity achievement status and the degree of SA as measured by the Personal Orientation Inventory (POI). Results of the present study extend these findings to include one's total level of psychosocial maturity as measured by Constantinople's Inventory of Psychosocial Development (IPD). Highly significant positive correlations were obtained between one's overall score on the IPD and the two major dimensions of the POI. Implications of this relationship were discussed.


Parental factors as reported by patient groups.

A cluster analysis was performed on data collected from six different groups, one of controls and five of various patient groups. The analysis produced two clusters of items that differentiated groups at significant levels. The schizophrenic group, in particular, showed very high levels of significance when compared with all other groups on a factor that consisted of items that cover situations that involve consideration and respect for the rights of others. Schizophrenics reported their parents as significantly less concerned with these behaviors than all other groups. A second factor, which consisted of items related to sex, differentiated the depressive group from most others.


Introversion-extraversion and psychiatric diagnoses: a test of Eysenck's hypothesis.

Eysenck has stated that dysthymics were introverted and psychopaths were extraverted This study tested this hypothesis. The Ss were 28 male and 7 female inpatients from a state mental hospital. Twenty were diagnosed as neurotics, 15 as psychopaths. The sample was divided into extravert-introvert groups on the basis of scores on the Meyers-Briggs Type Indicator. Chi-square analysis revealed no significant differences in patient distribution by type and diagnosis. It was concluded that extraversion-introversion scores would not aid in the diagnosis of neurosis or psychopathy.


The relationship of aerobic physical fitness to selected personality traits.

The relationships between aerobic physical fitness and selected personality traits measured by the MMPI were investigated for college males engaged in an aerobic conditioning class. Results indicated that physical fitness scores and selected scales on the MMPI are related in college males and that changes in aerobic physical fitness are related to score changes on selected scales of the MMPI for college males who participated in an aerobic exercise program.


The relationships among the Hoffer-Osmond Diagnostic Test, the Minnesota Multiphasic Personality Inventory, and independent clinical diagnoses.

A study was conducted to determine the relationship between two tests in the detection of schizophrenia. One of the tests used was the Minnesota Multiphasic Personality Inventory (MMPI) and the other, a less familiar test, was the Hoffer-Osmond Diagnostic Test (HOD). Also investigated was the difference between the MMPI and the HOD when compared to independently made clinical diagnoses. Of 100 outpatients examined, 75 with valid test results were used. It was hypothesized that the correlation between HOD scores and the Schizophrenia and Paranoia t-scores on the MMPI would be significant. Also, no difference between the two tests and comparable clinical diagnoses was expected. The predicted effects were found. Possible preference for the HOD under certain circumstances was discussed.


Personality characteristics of long and short sleepers.

College students categorized as either long sleepers (mean = 9.25 hours per day) or short sleepers (mean = 6.2 hours per day) were administered a variety of personality tests. With a multiple regression analysis the patterns on the MMPI of higher MA and F with a lowered PD and CI (number of critical items) most significantly differentiated the short from the long sleepers. Also of relevance was the finding that long sleepers were more likely to score in the pathological direction on most of the MMPI clinical scales.


Cluster analysis of preference ratings of pictorial stimuli.

The present research attempted to utilize cluster analysis to develop a comprehensive array of objective pictorial scales that could be used to identify the distinguishing perceptual and personality characteristics of various medical and psychiatric hospital populations. A cluster analysis of individuals' preference ratings of a large number of picture stimuli was described.


The conceptual congruence inventory (CCI): an experimental tool for the investigation and measurement of 22 common affective concepts.

This paper describes a prototype of the Conceptual Congruence Inventory (CCI), designed to assess the degree of overinclusion and underinclusion of 22 of a person's affective concepts with respect to a standard group. The CCI, the text of which is 15 short descriptions of characters' behavior evaluated for certain "traits" by the testee, was standardized for scale means and SDs with a group of 125 college students. An additional sample of 20 students was used to establish test-retest reliability over a period of 6 months, the correlation coefficient of which was .899.


Level of education, diagnosis and race-related differences in MMPI performance.

MMPIs were obtained from eight groups of black and white, schizophrenic and nonschizophrenic, and highly educated and poorly educated psychiatric patients. Profiles were classified blindly by use of two rules (Sc greater than 70; Sc greater than PT). All but poorly educated blacks were classified correctly beyond a chance level. Almost half of the poorly educated black nonschizophrenics were misclassified as schizophrenic. Implications for diagnostic work were discussed.


Repression-sensitization and MMPI correlates of retrospective reports of parental child-rearing behaviors.

Relationships were sought between college students' retrospective reports of parental behavior and their R-S scores and MMPI profiles. In general, reports of greater parental rejection and greater covert parental control were found to be associated significantly with higher R-S scores and higher scores on a number of MMPI scales as well as greater overall elevation of MMPI profiles. Implications for clinical history taking were noted, and caution was urged in consideration of an individual's reports of past events and relationships.


Factor analysis of the MMPI-STAI.

Since MMPI measures of anxiety do not differentiate situational from chronic anxiety, an attempt was made to factor analyze the MMPI-STAI scores of 311 psychiatric inpatients. Four factors emerged that were labeled Adjustment, Passivity, Somatic Concern and Anxiety Proneness. The results were compared with other MMPI factor-analytic studies. Evidence supported Welsh's A as a measure of chronic anxiety.


Use of estimated CPI factor scores to formulate personality types.

CPI scale scores were correlated with specially-scored CPI factor scales, and the results indicated that such factor scores could be estimated reasonably by the standard scales. By the use of CPI scales as measures of the two major factors of that instrument, the incidence of profile types in a normal sample was tabulated. For both males and females, six types accounted for 80% of the protocols: the first three types accounted for over 50% of the individuals. It was suggested that this type of analysis might contribute to interpretation of CPI protocols.


Tangible reinforcement and feedback effects on the IQ scores of college students.

College students who retook an intelligence test under conditions that informed the student of each correct answer made significantly higher gains than a control group that retook the test under standard conditions. A group that retook the test under feedback and reward conditions did not differ significantly from the control group.


Comparison of Bender-Gestalt and WISC correlations for Puerto Rican, White and Negro children.

Correlations between Bender-Gestalt scores and WISC IQs were obtained for three ethnic groups of 123 Puerto Rican, 82 white, and 61 Negro children in the first grade. The Bender-Gestalt test did not show any significant relationship with the WISC scores of the Puerto Rican children. Significant correlations (p less than .01) between the Bender and all the WISC scores were found for the Negro group. For the white Ss, the WISC-Bender relationship was significant (p less than .01) only for the Performance and Full Scale scores. The absence of a significant correlation between the Bender and the WISC Verbal IQ in these children was attributed to the relative superiority of their Verbal scores.


WAIS performance differences of male and female psychiatric patients.

This study compared the WAIS IQ and subtest scores of 167 male and 112 female patients of a heterogeneous psychiatric population. Males obtained significantly higher Verbal, Performance, and Full Scale IQ scores than did females, and significantly more male than female patients obtained Full Scale scores above the Average classification of intelligence (IQ is greater than or equal to 110). These data suggest that relatively high intelligence levels and, in particular, IQ scores above the Average classification are more effective to reduce the observed incidence of behavioral disorders among females than among males, perhaps because differing societal demands result in less effective coping behaviors at given levels of intelligence for males than for females. This explanation also is consistent with the significant overrepresentation of males in this clinic sample relative to their proportion in the general population. Further work at other facilities would help to determine the generality of these findings and to clarify their interpretation.


What patients want from counseling and psychotherapy.

In order to determine why individuals apply for help to a university counseling center, a parallel-response questionnaire was administered to the patients and therapists of the Kent State University psychological clinic immediately after each intake interview. Analysis focused on the frequency, structure, and patient-therapist agreement of reported wants. Eight of the 14 surveyed wants were endorsed by over 80% of the 57 patients surveyed. The items most frequently endorsed by patients were: "Get help in talking about what is really troubling me" (95%) and "Have someone respond to me on a person-to person basis" (91%). Although patients exceed therapists in the frequency of endorsement of nearly all of the items, both were in high agreement about the underlying dimensions of patient wants. Three major themes predominated for both the patients and therapist samples: Self-exploration, Catharsis, and Encouragement. The results underscore the importance of clarifying patient wants in the initial interview.


Moral judgment and parental identification among children.

The relationship of moral judgment and parental identification was studied in 50 boys and 50 girls, all of whom were white, lower-middle-class children, aged 9 1/2 to 11 1/2 years. Two hypotheses were proposed: (1) that within each sex group, children with a higher-level parental identification attain a higher stage of moral judgment than children with a lower level of parental identification; and (2) that there are no sex differences in the stage of moral judgment attained by Ss from similar socioeconomic backgrounds. Ss were screened for socioeconomic status and age. Moral judgment was defined in terms of Piaget's "two moralities" of the child and measured by a structured interview that consisted of five subtests taken from Piaget. Parental identification was measured by means of a semantic space and differential technique, and Ss were grouped on the basis of low, medium and high levels of paternal and maternal identification. Results indicate that there are no significant sex differences in moral judgment. Within each sex group there is a clear positive relationship between high-level identification and a higher stage of moral judgment.


A scale for the measurement of client and therapist expressiveness.

In light of recent theoretical and empirical work that stresses the importance of both the client's and therapist's expressiveness for productive therapeutic process, an ordinal scale was developed and presented to assess levels of client and therapist expressiveness in the ongoing therapy interaction. Scale points were constructed on the basis of face validity and empirical findings with nominal classification systems for client and therapist expressiveness; they were defined in terms of stylistic features of language and voice quality. In addition to presenting reliability data that indicate that the scale can be used with considerable interrater agreement, a number of important questions were posed for future research on the client-therapist interaction.


Effect of induced locus of control on change in field independence.

Three groups, alike in Rod and Frame Test (RFT) scores on pretesting, were given different instructions for Rotter's Locus of Control scale. Thirty-two Ss were told to fake internal or external answers. Another 16 Ss were instructed to answer the scale according to their own actual beliefs. Analysis of RFT pretest-posttest changes revealed that in both experimental conditions initially field-dependent Ss changed in the direction of higher field independence, and field-independent Ss shifted toward higher field dependence. The total amount of change manifested by field-dependent Ss in both conditions was in excess of the change by field-independent Ss. Standard test-taking instructions raised the level of field independence for field-dependent and field-independent Ss, with the magnitude of change greater among field-independent Ss. When Ss given internal and external instructions filled out the Locus of Control scale again at the end of the experiment, field-independent Ss professed to hold significantly more beliefs than field-dependent Ss that were coincident with beliefs of their previously simulated role. The findings were discussed primarily in terms of the relationship between role-playing and development of identity.


The effects of hypnotic susceptibility on reducing smoking behavior treated by an hypnotic technique.

This study sought to obtain empirical data on the issue of whether susceptibility to hypnosis influences the outcome of an hypnotic therapy. At the first of two sessions, Ss had their susceptibility evaluated unobtrusively. At the second session, they learned Spiegel's self-hypnotic method to stop smoking. At the end of 3 months' follow-up 7 of 54 volunteers were completely abstinent (13%), while 31% had reduced smoking by 50% or more. Of the 7 totally abstaining Ss, 1 was high, 1 was low and 5 were medium susceptible, which is not unlike the distribution of hypnotic susceptibility in the general population. However, it was found that significantly more Ss of higher susceptibility reduced by 50% or more than did less susceptible Ss.


Repression-sensitization and response to the implicit cue requirements of a social situation.

It was hypothesized that in an experiment that used verbal recall of threatening statements, repressors would reproduce significantly more of the threatening statements than would sensitizers when the implicit social cue requirement implied the desirability of attending to such statements. SSs were 20 female repressors, as defined by scores on the Repression-Sensitization scale. Ss first heard and then reproduced from memory either a control paragraph or a paragraph intended to imply the desirability of attending to the threatening stimuli. Next, all Ss wer read 20 statements, half of which were intended to be threatening and half of which were nonthreatening. After the Ss had heard all 20 statements, they reproduced from memory as many as they could. Results indicated that when the implicit social cue requirements implied the desirability of attending to the threatening statements, male repressors reproduced more of the statements than did other Ss in accord with predictions. In contrast, female repressors who were exposed to the implicit social due requirements that implied the desirability of attending to the threatening statements reproduced fewer of the statements than did other Ss.


Therapy with eight schizophrenic and borderline patients: summary of a therapy approach that employs a semi-symbiotic bond between patient and therapist.

In conclusion, it appears to this therapist that working through a semi-symbiotic union is a useful and perhaps essential therapy technique with both schizophrenic and borderline patients. The essential ingredients of this technique include: (1) open expression of feelings by the therapist; (2) consistency and reliability by the therapist; (3) understanding and acceptance of schizophrenic jargon; (4) acceptance of the patient's ambivalent feelings about closeness and distance and allowing distancing tactics; (5) interpreting and working through distancing needs as an on-going process -- understanding that they generally indicate both fear of rejection and of incorporation; (6) acceptance of a long-term semi-symbiotic responsibility to the patient; (7) expression of the therapist's own legitimate limits and of his inability to meet all the patient's needs; (8) allowing and encouraging the patient the freedom to grow toward increasing independence with security.