The effectiveness of the random dot E stereotest as a preschool vision screening instrument. Sixty nursery-school children (ages 39--76 months) were screened with a modified-clinical method (visual acuity, retinoscopy, cover test, NPC) and with a relatively new vectographic test for stereopsis--the Random Dot E. Screening outcomes indicate that the RDE was as effective in identifying children for referral as was the modified clinical battery. Implications are discussed.


Helping patients to follow their treatment plans. The optometrist encounters patients who do not adhere or comply with his recommended treatment. This problem of non-adherence adversely affects both the optometrist and the patient. A general framework is presented which the optometrist can use to evaluate his effectiveness at improving adherence. This framework includes problem formulation, joint development of the treatment plan, extended responsibility, and systematic followup.


Visual acuity and the developing visual system. The objective measurement of visual acuity in infants is reviewed. Recent techniques have shown that visual acuity levels as early as four to six months after birth. This and other evidence indicates that the most sensitive period in the development of the visual system may be during the first six months of life. With this as a rationale, it is suggested that eye care practitioners consider eye examinations and correction of refractive errors during infancy as a means of prevention of future strabismus and amblyopia.


[Copper intra-uterine devices (I.U.D.) and pregnancy: a study of the metabolism of copper and of ceruloplasmin in the mother and in the products of conception (author's transl)]. The authors studied the variations in levels of copper and ceruloplasmin in the mother and in products of conception during the first trimester of pregnancy, during the 4th month of pregnancy and near term, having a series of 12 pregnancies with the copper I.U.D. in position. No change was observed between the levels of copper and ceruloplasmin in comparison with a control series.


[The concentration of fetal cells in maternal haematopoietic organs during pregnancy. An experimental study in mice (author's transl)]. We have been able to show that fetal cells are able to survive and multiply in the haematopoietic organs of the pregnant mouse. We have been able to label fetal cells with a chromosome marker (T6) which is clearly visible in the metaphase of mitosis. It is not only that there is a considerable concentration of fetal cells in the maternal spleen (3 to 6 per cent) but there are several factors that suggest that these fetal cells can multiply there. These are, the presence of mitoses, long survival, and a rise in numbers in the case of a new pregnancy. Thus pregnancy seems to bring about a physiological "microchimerism".


[Hormone receptors in gynaecology. Towards practical applications? (author's transl)]. A general review of hormone receptors in gynaecology describes the receptors of the membrane for polypeptide hormones and the receptors for steroids. The hormone stays intact in the case of the membrane receptor and activates by contact a second intra-cellular messenger which then induces protein biosynthesis. The constant of dissociation and the number of binding-sites in the human corpus luteum are established for HCG-LH during the cycle, during pregnancy or at the menopause. The working out of these receptors for levels of polypeptides by radio bio-assay gives biological specificity and radio-immunological exactness. Steroid receptors consist of a cytosol receptor which is activated and transferred to the nucleus to induce protein synthesis. They are well recognised for oestradiol and for progesterone in the endometrium and in pathological breast tissue. Variations in the cytosol receptors and the nucleus receptors are known for different phases of the menstrual cycle. Indications for hormone treatment in cancers of the endometrium and of the breast in human pathological conditions can be improved rapidly by recognition of these receptors.


[Prenatal diagnosis. A psychological study. II. Pregnancy after the age of 40 (author's transl)]. This article, which is the second installment of a study of the psychological aspects of antenatal diagnosis, presents the analysis of interviews with women (and with some of their partners) who were examined because of their age. The characteristics of these "late" pregnancies seem to be the following: 1. The question of a abnormality shifts the emphasis from the child to the pregnancy itself, which is often lived through as something abnormal; 2. knowing the sex of the child before its birth emphasizes the abnormality of the pregnancy and therefore draws attention to the problem of the age of the mother; 3. this last chance of pregnancy emphasizes the question, which is near in time for these women, of the menopause, of getting old and of death; 4. it also emphasizes in a most emphatic way the question of mourning, of loss, of the place of the future child in the history of the woman and in a more general way the question of the desire to have a baby.


[Gastro-duodenal ulcers with pregnancy. Condition of shock in labour due to intestinal haemorrhage from an ulcer (author's transl)]. We present the case of a multiparous woman of 32 years of age who, at term after a more or less normal pregnancy, went into severe shock in labour. The patient in this case was very difficult to diagnose. Her life was only saved after massive blood transfusions and after delivering a fresh stillborn infant. It was not a case of uterine rupture nor of retro-placental haemorrhage. The site of origin of the hypovolaemic shock was intestinal. The patient had an ulcer of the pylorus which was diagnosed after fibroscopy. Some authors state that it appears that the few ulcers that have been diagnosed before pregnancy go into remission during pregnancy. All the same it would appear that sometimes very serious complicated ulcers which have to be treated with great respect do occur, especially in toxaemic patients at the end of pregnancy, and these carry with them a significant mortality both for the mother and the fetus. Although medical treatment (resuscitation) is essential, surgery should be resorted to if necessary because it may save the mother and sometimes the infant and so improve the prognosis of complicated ulcers occurring in pregnancy.


[Neuropathology and pregnancy. 189 consecutive cases (1971--1976) (author's transl)]. The authors report 189 case histories of pregnant women who had a neurological disorder, which either existed before the pregnancy or were discovered during the pregnancy. The most frequent aetiological conditions were, epilepsy, psychoses, vascular accidents, tumours and disseminated sclerosis. Pregnancy and neuropathology are an association for which the prognosis as a whole is good and linked to the time in the pregnancy when the neurological condition, whether it is stable or not, is discovered. The combination is absolutely compatible with the normal progress of pregnancy so long as the appropriate treatment is continued during the pregnancy. Cerebral vascular accidents that occur in pregnancy make the prognosis very much worse. In these circumstances neurosurgery may give some hope. This applies also for cerebral tumours, among which pituitary adenoma is becoming more and more frequent. Psychopathies can be a very baffling chapter when they are combined with pregnancy. Finally disseminated sclerosis, once it has been stabilised, is perfectly compatible with the normal outcome for a pregnancy.


A primer on antitrust and hospital regulation. This paper begins with a comparison of the effects of regulation and antitrust litigation on general market dysfunction. The authors then describe the medical marketplace and the effects both regulation and antitrust efforts have had in this arena. They conclude that public policy probably will continue to be concerned with regulation, given that traditional forces do not, and apparently cannot be made to, operate in the health care market. However, through tax benefits, cost-sharing programs, etc., for other-than-traditional modes of care, regulation can be more an instrument for expanding the range of consumer choice than it historically has been.


Market power and resource misallocation in medicine: the case of neurosurgery. This article concludes that substantial excess neurosurgical capacity exists. Neurosurgery like other specialties has permitted almost free entry and as a result of such factors as high earnings and status, excess capacity has developed and because of insufficient competition it has not been eliminated. The costs of excess capacity include idle capacity and an alleged reduction in skill levels. The neurosurgery market's performance is evaluated and it is found that while relative income has declined, entry has continued at a high rate; excess capacity is therefore not being eliminated. Policy recommendations of a pro-competitive variety are suggested to improve the market's performance instead of regulation (whether governmental or by the profession itself).


Inheritance of yellow dun and blue dun in the Icelandic toelter horse. The coat colors of 161 progeny from matings between 10 yellow dun and 6 blue dun stallions and mares of 8 different colors are described. The results confirm the previous hypothesis that a dominant dilution gene, D, converts bay to yellow dun with dark mane and tail, chestnut to yellow dun and dun mane and tail, and black to blue dun (mouse, grullo). The palomino gene, c cr, on the other hand, is hypostatic to black and blue dun. In heterozygous form, c cr converts bay to buckskin, and chestnut and sorrel to palomino, and results in blue-eyed white when homozygous. No particular effect of D is known in the homozygous state. Altogether 12 progeny were obtained from matings where both parents carried D; all progeny carried D, and no abnormal colors occurred.


Genetic analysis of two enzyme polymorphisms in a malaria vector mosquito: octanol dehydrogenase and acid phosphatase in Anopheles culicifacies Giles. Genetic analysis was performed on two polymorphic enzyme systems in the malaria vector, Anopheles culicifacies Giles. The data indicate that both enzymes, octanol dehydrogenase and acid phosphatase, are controlled by autosomal loci but that these two loci are not linked. The three expected linkage groups in this mosquito have now been identified: linkage group I contains sex and rose-eye; linkage group II contains Odh; and linkage group III contains Acph.


Gene frequencies of an isolated population of Drosophila pseudoobscura. Allozyme and karyotype frequencies were determined for an isolated population of Drosophila pseudoobscura on San Miguel island off the California coast. This population was not very different from that of the mainland, and seems to indicate that isolation does not necessarily lead to genetic differentiation.


Linkage group III in the Syrian hamster: linkage between white band and long hair. A correction is made to the previously reported cross-over frequency between the genes Ba and l: the corrected value is 8.98 +/- 1.71.


Karyological analysis of the Horsfield's shrew from peninsular India. The chromosome complement of the Horsfield's shrew, Crocidura horsfieldi (Soricidae--Insectivora) was studied and the diploid number established to be 2n = 38. Comparisons were made with other species of the genera.


A correlative chemical and histochemical study of the O-acetylated sialic acids of human colonic epithelial glycoproteins in formalin fixed paraffin embedded tissues. Procedures are described for the isolation and identification of epithelial glycoproteins from formalin fixed, paraffin embedded specimens of human large intestine. The side chain O-acetylation patterns of the sialic acids of these glycoproteins were surprisingly similar to those of purified glycoproteins prepared from epithelial cells obtained from the same tissue before fixation. These results were consistent with those obtained by histochemical procedures performed on representative sections taken from the same tissue blocks. The methodology described permits a direct correlation of chemical and histochemical results obtained from the study of colonic epithelial glycoproteins of both normal and diseased tissues. It eliminates some of the difficulties associated with interpretation of the results by either discipline and may provide new information which would be unavailable by either chemistry or histochemistry alone.


Oxygen incineration and electron microscope x-ray microanalysis of mineral particles in biological tissues. Techniques employed for the recovery from biological tissues of noncombustible fine particles such as asbestos, talc, kaolin and diatomaceous material were assessed by electron microscope x-ray microanalysis. Recovery procedures which have been proven successful for lung tissue were found to be impracticable for more solid types of tissues. Digestion techniques employing acids, alkalis or enzymes and standard incineration procedures were found to be unsatisfactory for human adrenal, cervix, liver and ovarian tissues when the resultant residues were examined by electron microscope microanalysis. The recovered particles were often completely masked with residues which were shown to be composed of organic elements. The use of oxygen during the incineration process completely removed this contaminating material in nearly all cases studied. When such procedures were used, clearly defined particles were recovered from the tissue, thereby permitting x-ray analysis. A quantitative analysis could then be made to estimate the particle content in a variety of tissues.


Murine arylsulfatase B: regulation of As-1 expression in different tissues. The proportions of arylsulfatases A, B and B' differ markedly among various murine tissues. Although arylsulfatase B' may be a derivative of arylsulfatase B, their respective activities appeared to vary independently in the five murine tissues investigated. As-1, the apparent structural locus for murine arylsulfatase B, is expressed in brain, liver, kidney, lung, and spleen. Heat-stable arylsulfatase B is inherited as an autosomal incomplete dominant in most tissues. Current evidence suggests the existence of a regulatory element with cis-dominant effects that is situated near As-1 and is expressed in these tissues. However, control of liver arylsulfatase B is subject to more complex control and may involve participation of several genes, some of which are unlinked to As-1.


Genetics and pathology of hereditary adrenal hyperplasia in the rabbit: a model for congenital lipoid adrenal hyperplasia. One-hundred-twenty-nine cases of adrenal hyperplasia in the rabbit were shown to be associated with a fully penetrant autosomal recessive gene, symbolized ah. The mutant is viable prenatally, may be recognized by gross examination of the adrenal at least as early as 19 days of gestation, but dies soon after birth. There is an external feminizing effect of the gene and the model is similar to the feminizing congenital lipoid adrenal hyperplasia reported in man. This mutant is being maintained in strain IIIVO/ahJ.


Salmonella pollution of surface waters.

Salmonella pollution of surface waters. Surface waters in 14 selected sites were examined for the presence of salmonella using modified Moore's swabs. The sites included an upland impounding reservoir, 3 rivers and 10 streams within Lancashire and Cheshire, selected because of their accessibility to farm livestock. Salmonellas were isolated from 22 out of the 57 swabs examined representing 10 sites. The probable source of pollution was shown to be sewage or farm effluent and an examination of sites over a wider area may be expected to produce similar results. The significance of these findings is discussed in relation to the epidemiology of salmonella infections and the possible disinfection of effluent discharges.


Frequency of color genes in Faeroe Islands sheep. A color classification was made of 679 sheep, comprising 355 ewes and 324 lambs in two Faeroese flocks. The colors observed were: white without tan (124); white with tan (121); black mouflon (2); gray (134); gray-brown (5); black (251); and brown (42). Among the 434 nonwhite sheep, 210 had white markings. The color alleles found at three loci were as follows. The A locus: Awh(0.20), producing white or tan; Ag(0.14), producing gray; and a (0.66), resulting in self color when homozygous. The B locus: B (0.67), producing black pigment, and b (0.33), producing brown pigment. The S-locus: S (0.30), resulting in solid color, and s (0.70), resulting in spotted color in nonwhite sheep and absence of tan color in white sheep. A significant difference between generations with respect to frequency of colors was found, the lambs showing a significant deficiency of white and gray and a corresponding excess of black and brown. The gene frequency estimates are compared with estimates available for Soay, Corsican, Shetland, Orkney, and Icelandic sheep.


Inheritance of short coat and long coat in St. Bernard dogs. A popular belief among dog breeders is that long coat and short coat in certain dog breeds is controlled by a single pair of autosomal alleles, short coat being dominant to long coat. Data are presented for 221 litters and 1216 pups of the St. Bernard breed that support and verify this belief.


Cholera: possible infection from aircraft effluent. This paper presents the hypothesis that some cases of cholera might be due to effluent discharge from aircraft. The theoretical case is borne out by inspection of data on the physical conditions pertaining between high altitudes and ground level. A study of the distribution of isolated outbreaks and single cases of disease and their relation to major airline routes showed a reasonable correspondence. Sporadic outbreaks of cholera in Europe between 1970 and 1975 were found to lie within the flight paths of regular airline services from Calcutta, where cholera is endemic, to the Northern Hemisphere. Laboratory studies on the stability of Vibrio cholerae to conditions likely to be encountered in droplets falling from high altitude to the ground suggested that significant numbers of organisms might survive. It should be noted that in this study no account was taken of the effect of ultra-violet light on viability and it is known that at high altitides the ultraviolet light component of solar radiation is much higher than at ground level. Results of experiments where small numbers of organisms were inoculated into relatively poor media showed that rapid growth ensued and that sufficient organisms were produced to give an infective dose of Vibrio cholerae in 1-10 ml/fluid. It could be concluded that human infection could easily occur by ingestion of fluids such as milk or soup which had some time earlier received a fortuitous but slight contamination from the air. Investigation of one disinfectant (chloramine T) showed that it reacted rapidly and in a complex manner with peptone. One effect of this reaction was the elimination of bactericidal activity and it seems likely that, as at present employed, chloramine T is of doubtful value in aeroplane hygiene. One important conclusion that arises from this work is that if cholera can be spread, even only occasionally, by effluent from aircraft then close investigation should be made of the possibility of other bacteria and viruses being spread in a similar way.


Origin of the B/J, R/J, and Y/J strains of rabbits. The inbreeding of strains B/J, Y/J, and R/J, formerly designated ACCR(B), ACCR(Y), and ACCR(R), was started by full brother X sister inbreeding by C. Cohen to test the effect of inbreeding on the selective value of the different blood group genes.


Haemagglutination-inhibition test for the detection of rubella antibody. Between 1969 and 1972 three quality control studies were set up to investigate the variation in results that was occurring between and within laboratories performing routine tests for the diagnosis of rubella infection. No attempt was made to standardize the test in these studies, and a wide range in titres of sera was reported. The aims of the present studies were:(i) to investigate in greater detail whether results were more reproducible between laboratories if test sera were compared with control sera of known potency and the results given in international units of activity, and(ii) to ascertain whether results between laboratories would be more reproducible if a standard test procedure was used.Eleven laboratories participated in testing 38 sera on three separate occasions by a prescribed standard technique and by that used routinely in each laboratory. Eight of the 38 sera consisted of four pairs of duplicate samples.Analysis of results of the study showed that the reproducibility between laboratories was substantially improved when the test sera were compared with a control serum of known potency and when a standard test procedure was used.Variation in results between laboratories was least when a control serum of low rather than high potency was used. Variation within laboratories can be reduced by increasing the number of times the control and test sera are tested.Since the rubella antibody content of the British Standard anti-rubella serum is expressed in international units, the potency of the control and results of test sera should also be expressed in such units.


e-Antigen: a link between immune response and infectivity in hepatitis B? In a study of the distribution of e-antigen and anti-e in subjects whose blood was positive for hepatitis B surface antigen (HBsAg), patients with acute hepatitis B who were tested during the incubation period were all e-antigen-positive but after the onset of illness e-antigen was detected in only 11%. Persistence, and in some instances reappearance of e-antigen in those who became long-term carriers of HBsAg was associated with high titres of HBsAg. There was a high incidence of e-antigen in those conditions in which cell-mediated immunity may be depressed, including Down's syndrome and chronic renal failure. The majority of HBsAg carries identified as sources of infection were e-antigen-positive. A postive reaction for e-antigen is evidently associated with a defective immune response to hepatitis B virus infection which permits continued replication of virus in liver cells accompanied by high titres of HBsAg, numerous Dane particles and detectable DNA polymerase in the blood with consequently a greater likelihood of transmitting infection. Although it cannot be assumed that anti-e positive carriers of HBsAg are not infective, it may be necessary, in the assessment of passive or active immunization for the control of hepatitis B, to take into account the e-antigen/antibody status of possible sources of infection.


The development and use of a test to identify resistance to the anticoagulant difenacoum in the Norway rat (Rattus norvegicus). Feeding tests were carried out in the laboratory to obtain basic data on the susceptibility of wild Norway rats to difenacoum. The results were used to derive a standard test procedure for the identification of difenacoum resistance in warfarin-susceptible and resistant rats. Details are given of tests on rats from suspected difenacoum-resistant infestations on farms.


The evaluation of fabrics in relation to their use as protective garments in nursing and surgery. I. Physical measurements and bench tests. Eleven fabrics selected to provide a representative range of yarns and weaves have been examined microscopically and subjected to a series of tests. The observations were directed towards assessing the potential ability of each fabric to resist penetration by particles, such as skin scales, which might carry micro-organisms. The number, size and shape of pores penetrating through the material were estimated and the penetration of test dusts assessed in several ways. While, generally, the relative merits of the fabrics are similar whatever test or measurement is considered there are a number of significant exceptions which reflect peculiarities of the test system or of a fabric. Comparison with the results of dispersal experiments with volunteers wearing garments made of the fabrics is made in a following paper.


The evaluation of fabrics in relation to their use as protective garments in nursing and surgery. II. Dispersal of skin organisms in a test chamber. The effectiveness of a representative range of fabrics in restricting dispersal through them of dry skin-borne bacteria has been examined. The fabrics were tested made up into trousers which were worn by volunteers during standardized exercise in a test chamber operated within a unidirectional flow clean-air room. Under these conditions, with careful attention to sealing at ankles and waist, it was possible to estimate penetration as low as 0.3%. Penetrations as low as 1% were observed with some synthetic fabrics. These had a relatively high surface resistivity and developed significant electrostatic charges. When the observed values for penetration were compared with the results of a series of measurements and tests made on the fabrics it was clear that the correlation between these values and the other results was in every case very close for all the five woven cotton or cotton terylene fabrics but that no measurement or test was capable or predicting the behaviour of all the other materials in dispersal experiments. The inherent variability of dispersal experiments seems to be very great. With a standard deviation of the approximately log-normal distribution of the experimental values as high as  about 2 times the mean, it is necessary to carry out as many as 20 replicate experiments in order to differentiate with certainty between garments with a two-fold difference in penetration.


The dimensions of skin fragments dispersed into the air during activity. There was a 1000-fold difference between the highest and the lowest mean rate of dispersal of bacteria-carrying particles during exercise among a group of three male and three female subjects. Differences in the numbers of skin fragments dispersed and in the proportion of these carrying bacteria were almost equally responsible for this. Since there is little difference between individuals in the rate of skin replacement the differences in the rates of dispersal of skin fragments during exercise must reflect large variations in the amount of skin surface removed in  other ways. The skin fragments dispersed had a wide size range extending below 5 micrometer for the minimum projected diameter (MPD). The median MPD was about 20 micrometer with 7-10% less than 10 micrometer. Many of the particles could therefore pass freely through tightly woven fabrics with pores up to 10-15 micrometer which might seem to be impenetrable to whole corneocytes, typically larger than 30 X 40 micrometer in the hydrated state.


Variation in energy intake of aldolescent schoolgirls. Twenty-four 16 to 17 year-old grammar school girls completed daily dietary histories (for eight weeks), and recorded details of mood, appetite and menstrual cycle. Marked daily variation in energy intakes was noted: on average an individual's highest daily intake was nearly four times her lowest intake, one subject having a nearly tenfold difference. Fluctuations were not related to mood, suggesting that this has less influence on dietary patterns than is generally supposed. While sitting examinations, energy intake was reduced by an average of 11.85%. It was not significantly changed during a field trip or by menstruation. This study suggests that dietary patterns previously considered to be abnormal or unusual are exhibited by and firmly entrenched in normal school girls.


Guar gum--its acceptability to diabetic patients when incorporated into baked food products. Guar gum was incorporated into 10 g carbohydrate portions of cheese biscuits and 20 g carbohydrate portions of pizza and egg and bacon flan. Their acceptability to diabetic patients was assessed by means of a taste panel. The results were favourable. Other diabetic patients were asked to judge three cheese biscuits of varying guar gum content. The biscuit with the lowest content was most favoured.


Introducing dietetics into general practice. A dietetic clinic, initially monthly, now weekly, is held in a general medical practice with four partners. In one year 462 patients were seen (207 new and 255 repeat visits); 68% were on reducing diets and 8% were diabetics. Advice was given on a variety of therapeutic diets, ante-natal and infant feeding. The elderly were visited at home. Patients were pleased to have dietary advice available in general practice. Results of weight reductions have been encouraging. Prescriptions for appetite suppressants and laxatives have dropped.


alpha-N-acetyl-D-galactosaminyl- and alpha-D-galactosyltransferase activities in sera of cis AB blood group individuals. Thirteen cis AB persons from five families were examined for serum glycosyltransferase activities associated with the biosynthesis of A and B blood group characters. Their transferases were generally homogeneous within one family, except for A2/cis AB genotypes, whose A enzyme level was similar to the A2 normal sera, but they varied from one family to another. These activities differed quantitatively and qualitatively from A, B and AB normal sera. Studies of A transferase showed variations in the pH-dependent curve, the effect of cofactors and the capacity of conversion of O red cells into A-active cells. Moreover, A and B transferases behaved differently with respect to their relative levels than did AB heterozygous normal sera. The results were discussed and it was suggested that a mutation of a single enzyme transferring both galactose and N-acetyl-galactosamine could explain these properties.


The effects of enzymes on the blood factors associated with the FV system of bovine erythrocytes. Treatment of cattle red cells (CRC) with proteases and neuraminidase revealed at least one trypsin- or pronase-sensitive type and a protease-resistant type of sialoglycoprotein. The antigen F itself and the antigen IM in the F/F and F/V type of CRC were associated with the protease-resistant glycoprotein. Moreover, they were demonstrable in the agglutination test, but only after treatment with proteases. The antigen V, allelic to F, was, however, associated with a pronase-sensitive protein and the antigen IM in the V/V type of CRC with a trypsin- or pronase-sensitive glycoprotein. The antigen N' was inactivated by chymotrypsin or pronase, irrespective of whether it was transmitted with the F or with the V. While the antigens IM, N' and the antigen reacting with rabbit serum, in addition to the antigen F in the F/F type of CRC, showed no or only very weak (titre 1:2) reactions, these same antigens, in addition to the antigen V in the V/V type of CRC, all showed high titres (1:32 to 1:128) in the anti-globulin test.


Bile acid kinetics in relation to endogenous tryglyceride metabolism in various types of hyperlipoproteinemia. Bile acid and plasma endogenous triglyceride kinetics were determined under standardized dietary conditions in 47 hyperlipidemic subjects with the aid of [14C]cholic acid, [14C]chenodeoxycholic acid, and [3H]glycerol, respectively. On the basis of their lipoprotein pattern the patients were separated into three groups characterized by hyperlipoproteinemia (HLP) type IIa (n = 19), type IIb (n = 6), and type IV (n = 22). In keeping with previous reports from this laboratory the total bile acid formation reports from this laboratory the total bile acid formation in HLP type IV (19.5 +/- 2.2) mumol kg-1d-1, mean +/- SEM) exceeded that encountered in type IIa (10.7 +/- 0.9 mumol kg-1d-1, P less than 0.005). This difference was mainly due to an increased synthesis of cholic acid in type IV HLP (12.7 +/- 1.7 mumol kg-1d-1 vs. 6.1 +/- 0.5 mumol kg-1d-1, P less than 0.005). Bile acid formation in type IIb HLP was essentially within the limits recorded for type IIa. Apparent plasma triglyceride formation (as calculated from the 10-hr radioactivity decay curve) averaged 10.5 +/- 0.7 mumol kg-1hr-1 in type IIa HLP and was significantly higher in type IIb (20.7 +/- 1.9 mumol kg-1hr-1, P less than 0.001) and in type IV (22.1 +/- 1.4 mumol kg-1hr-1, P less than 0.001). The apparent fractional turnover rate of plasma triglyceride in type IV HLP (0.147 +/- 0.011 hr-1) was lower than that encountered in type IIa (0.188 +/- 0.008, P less than 0.01) and in type IIb (0.177 +/- 0.011 hr-1). The apparent production of plasma triglycerides and the formation of cholic acid correlated in type IIa (r = +0.69, P less than 0.001) and in type IV HLP (r = +0.70, P less than 0.001). A similar pattern was seen for total bile acid formation, while chenodeoxycholic acid showed a correlation to apparent triglyceride synthesis only in type IV HLP. It is suggested that an increased formation of plasma triglycerides--monitoring very low density lipoprotein synthesis--is linked to an enhanced degradation of cholesterol to bile acids and that there is an integrated regulation of the metabolism of these two parameters.


Effects of cholestyramine and chenodeoxycholic acid on the metabolism of endogenous triglyceride in hyperlipoproteinemia. Previous studies conducted under basal conditions have suggested a linkage between the formation of plasma triglyceride and the degradation of cholesterol to bile acids. To further examine this relationship, plasma endogenous triglyceride kinetics were determined using [(3)H]glycerol in 26 hyperlipidemic subjects before and during stimulated (cholestyramine treatment) and inhibited (chenodeoxycholic acid treatment) bile acid synthesis. All patients with hyperlipoproteinemia (HLP) type II (n = 9) treated with cholestyramine (12 g daily for 2-4 months) displayed increased apparent biosynthesis (12.8 +/- 1.5 vs. 9.7 +/- 1.2 micro mol kg(-1)hr(-1), mean +/- SEM, P < 0.005) and an elevated apparent fractional turnover rate (0.230 +/- 0.017 vs. 0.176 +/- 0.014 hr(-1), P < 0.001) as determined over a 10-hr period, in spite of essentially unchanged plasma triglyceride concentrations. No consistent effect of this therapy was encountered in the five patients studied with type IV HLP. Chenodeoxycholic acid feeding (1.9 mmol daily for 3-4 months) resulted in a reduced apparent synthesis of plasma triglycerides both in type IIa (n = 5, 7.9 +/- 0.5 vs. 13.1 +/- 1.2 micro mol kg(-1)hr(-1), P < 0.01) and type IV HLP (n = 7, 15.5 +/- 1.8 vs. 23.6 +/- 3.7 micro mol kg(-1)hr(-1), P < 0.02). Furthermore, a 20-25% reduction of the apparent fractional turnover rate was seen, and the plasma concentration of triglycerides was reduced by about 15%. It is concluded that the present experimental conditions that primarily influence cholesterol and bile acid biosynthesis also affect the metabolism of plasma triglycerides-and presumably that of very low density lipoprotein-in a regulatory manner. Hypothetically, this may be achieved via a hepatic pool of newly synthesized cholesterol.


Antilipolytic effects of chlorophenoxyisobutyrate and warfarin in adipocytes. This study was designed to examine whether displacement of free fatty acids (FFA) from albumin (BSA) can explain the antilipolytic effect of chlorophenoxyisobutyrate (CPIB). Warfarin, which binds to albumin with equal affinity, was used to test the generality of this mechanism. The procedure was to measure the concentration of free drug needed to inhibit hormone-stimulated lipolysis in isolated rat epididymal fat cells, and the effect on this process of albumin, which binds both FFA ligand and drug. The free drug concentration was initially obtained by ultrafiltration studies with albumin and 14C-labeled CPIB or 14C-labeled warfarin in the absence of cells. When epinephrine-activated lipolysis was measured, inclusion of 0.3 mM albumin decreased the free CPIB concentration required for 50% inhibition from 1.8 mM (-BSA) to 0.08 mM. Warfarin also inhibited lipolysis more effectively in the presence of albumin, with 50% inhibition at 0.06 mM (+BSA) vs. 0.7 mM (-BSA). Both drugs showed a similar high-affinity binding constant to albumin of n = 1, k = 2--4 X 10(5) M-1, and both competitively displaced [14C]stearate, provided that a hydrophobic trap was present. The results are consistent with the possibility that the antilipolytic effect of CPIB and warfarin is mediated by way of a competitive displacement of FFA from albumin, or an analogous cellular binding site, with subsequent feedback inhibition of lipolysis.


Purification of pancreatic lipase via its affinity for bile salts and apolar surfaces. An improved method for the purification of pancreatic lipase in milligram amounts is described. Only one batch step and one chromatographic step are required to produce a lipase-colipase complex and a lipase largely free of colipase. Both species are lipid free; physical and kinetic data indicate that the predominant lipase species is lipase B.


A simplified method for the measurement of gamma-butyrobetaine hydroxylase activity. A method for the assay of gamma-butyrobetaine hydroxylase activity is described. The procedure is based on the measurement of 3H2O formed from [2,3-3H]gamma-butyrobetaine. The formation of 3H2O was essentially linear with time of incubation and enzyme concentration. Despite a significant isotope effect that causes the extent of hydroxylation to be underestimated, an appropriately determined correction factor permits one to relate quantitatively the degree of detritiation to the amount of carnitine formed. The assay is simple, rapid, specific, accurate, highly reproducible, and relatively sensitive. Its reliability and convenience represent an improvement over existing methods based on the tedious and time-consuming enzymatic radioisotopic determination of the carnitine formed or on the coupled decarboxylation of [1-14C]alpha-ketoglutarate, a method that cannot be used in crude extracts.


Procedure for determination of free and total cholesterol in micro- or nanogram amounts suitable for studies with cultured cells. Procedures for the determination of free and total cholesterol in lipid extracts or sonicates of 10(4) cultured human skin fibroblasts are described. The method for free cholesterol employs cholesterol oxidase to generate H2O2 and peroxidase to catalyze the reaction of H2O2 with p-hydroxyphenylacetic acid to yield a stable fluorescent product. Cholesterol ester hydrolase is included for determination of total cholesterol. When samples of sonified cell suspensions are used directly, the extraction of lipids is avoided, permitting one person to carry out analyses of 30 or more subcultures in one day.


7-Hydroxylation of 3-oxygenated C27-, C28-, and C29-steroids in rat liver 18,000 g supernate. Structurally closely related steroids have been tested as substrates for the NADPH-dependent cholesterol-and cholestanol-7 alpha-hydroxylase(s) considered to be the rate-limiting enzyme(s) in bile acid biosynthesis. Of the steroids tested, 5-cholesten-3 alpha-0l, 5 alpha-cholestan-3 alpha-ol, 5 beta-cholestan-3 alpha-ol, 5 beta-cholestan-3 beta-ol, 4-cholesten-3 alpha-ol, 4-cholesten-3 beta-ol, 5 alpha-cholestan-3-one, 5 beta-cholestan-3-one, 24 alpha-methylcholesterol and the 24 alpha-ethyl derivatives of cholestanol, 5 beta-cholestan-3 alpha-ol, 5 beta-cholestan-3 beta-ol, and 4-cholesten-3-one, only 4-cholesten-3 beta-ol was 7 alpha-hydroxylated to a significant extent (approximately 1/5 of the conversion of exogenous cholesterol). This suggests that the 7 alpha-hydroxylase(s) is sensitive to the structure of the side chain, and that it requires a rather flat steroid nucleus (delta4-, delta5-, or 5 alpha-steroid) and an equatorial or quasiequatorial hydroxyl group at C3. The nature of the 7 alpha-hydroxylation is discussed and the importance of the beta-side of the steroid molecule is emphasized. Minute amounts of the 7 beta-hydroxy derivatives were formed from 4-cholesten-3 beta-ol, 5 beta-cholestan-3 alpha-ol, 24 alpha-ethyl-5 beta-cholestan-3 alpha-ol and, probably, from 5 beta-cholestan-3 beta-ol and 24 alpha-ethyl-5 beta-cholestan-3 beta-ol.


Critical tables for calculating the cholesterol saturation of native bile. A simple method for the rigorous derivation of lithogenic index or percent cholesterol saturation, embodying both relative and total lipid concentrations, is described. We recently demonstrated that under physiological conditions only two key physical-chemical variables, the bile salt-lecithin ratio and the total lipid (bile salts + lecithin + cholesterol) concentration determine the equilibrium cholesterol solubility of bile. Of relevance to gallstone formation and dissolution in man is that the influence of variations in total lipid concentration on cholesterol solubility is quantitatively more important but has essentially been ignored. Using model biliary lipid systems, we experimentally determined a family of cholesterol solubility curves to encompass a wide range of bile salt-lecithin ratios for physiological variations in total lipid concentration (0.3--30 g/dl) at 37 degrees C (pH 7.0, 0.15 M NaCl) and accurately fitted these with fifth degree polynomial equations. We have now solved these equations for moles percent cholesterol, i.e., [cholesterol] X 100/[bile salt] + [lecithin] + [cholesterol] employing physiological values (0.085--0.425) for molar [lecithini]/[bile salt] + [lecithin] ratios. The resulting tables provide precise values for the maximal amount of cholesterol that would be soluble in bile at any total lipid concentration and bile salt-lecithin ratio and allow for rapid and accurate calculation of lithogenic index or percent cholesterol saturation from the moles percent cholesterol actually present in hepatic, gallbladder, and duodenal biles.


Gas-liquid chromatography-mass spectrometry of trimethylsilyl ethers of bile alcohols. This report describes the gas-liquid chromatography-mass spectrometry (GLC-MS) of the trimethylsilyl ethers of 5 beta-cholestane-3 alpha, 7 alpha, 12 alpha-triol with mono- or dihydroxy substitution in the side chain. Compounds with 24- and 25-unsaturation in the side chain were also studied. The gas-liquid chromatographic separation of the different bile alcohols was carried out using 3% QF-1 and 1% HI-EFF 8BP as column packings. Both columns were useful in that the retention times of the trimethyl-silyl ethers of the various 5 beta-cholestanetetrols varied linearly with the position of the side-chain trimethylsiloxyl substituent. The major fragmentations in the GLC-MS of all bile alcohols tested were due to the trimethylsiloxyl side-chain substituent(s). A trimethylsiloxyl group at C-22 was the most effective in promoting side-chain fragmentation, followed, in order of decreasing effectiveness, by substituents at carbons 25, 23, 24, and 26. The side-chain fragments generally gave rise to one or two intense mass peaks and a series of weaker peaks, 90 mass units apart, owing to the loss of successive molecules of trimethylsilanol. Most 5 beta-cholestane-triols, -tetrols, and -pentols can be unequivocally identified by their strong side-chain fragmentation peaks, except for 5 beta-cholestane-3 alpha, 7 alpha, 12 alpha, 26-tetrol, the trimethylsilyl ether of which exhibited very low intensity side-chain fragments.


Evaluation of a continuous isotope feeding method for measurement of cholesterol absorption in man. A new method has been developed for measurement of cholesterol absorption. Seven patients were fed [14C]cholesterol together with [3H]-beta-sitosterol three times daily for 10 days. Stools were collected on days 3--10. The ratio of isotopes in stools became essentially constant after the first 3 days of isotope administration. Percentage absorption of cholesterol was calculated from the difference between the dietary and fecal isotope ratios. Percentage absorption of cholesterol in these seven patients ranged from 47 to 65% (mean 54%). The coefficient of variation on individual samples for all the patients ranged from 3.2 to 15.0% (mean 7.8%). This method was evaluated in five additional patients by comparison with a standard sterol balance method (Method II, see Quintao, E., S. M. Grundy, and E. H. Ahrens. 1971. J. Lipid Res. 12: 221--232). The results obtained by the two methods were essentially identical. The new method offers the advantages of simplicity of administration of isotope, ease of analysis of stool samples, and daily repeatability of analysis.


Influence of cholestyramine on synthesis of cholesterol and bile acids in germfree rats. The present investigation describes the influence of partial, pharmacologic interruption of bile acid enterohepatic circulation on cholesterol and bile acid synthesis in germfree rats. Seven rats received a basal, semisynthetic diet and five rats received the basal diet supplemented with 5% cholestyramine. After 6 weeks, feces were collected in one 3- and one 4-day pool for analysis of bile acids and cholesterol. When the sampling period was concluded, the rats were killed and the liver microsomal fractions were isolated. The activities of HMG CoA reductase and 7alpha-hydroxylase were determined. The main fecal bile acids in the untreated rats were cholic acid and beta-muricholic acid. During cholestyramine treatment cholic acid increased from 4.4 +/- 0.7 to 39.5 +/- 5.6 mg/kg body weight/day and beta-muricholic acid from 4.5 +/- 0.6 to 7.7 +/- 0.9 mg/kg body weight/day. Chenodeoxycholic acid became a major bile acid averaging 10.4 +/- 1.6 mg/kg body weight/day. The total amount of bile acids increased about 6-7 times and the percentage of cholic acid increased from 49.4 +/- 2.0 to 68.6 +/- 1.1%. The 7alpha-hydroxylase activity increased 4-5 times. During cholestyramine treatment the fecal excretion of cholesterol was increased from 12.0 +/- 1.4 to 68.0 +/- 5.0 mg/kg body weight/day. The endogenous formation of cholesterol was increased 6 times and the HMG CoA reductase activity was increased about 20 times. In conclusion, germfree rats, like conventional rats, have the ability to increase the endogenous formation of bile acids and cholesterol during interruption of the enterohepatic circulation of bile acids, which is also reflected in a stimulation of the activities of the rate-determining enzymes.


Studies of bile acid secretion by isolated rat hepatocytes. Bile acid secretion was studied in isolated rat hepatocytes cultured in medium supplemented with cofactors and succinate. Succinate as a respiratory substrate was found to be essential for bile acid synthesis. Feedback mechanism was demonstrated with different inhibitory potency of different bile acids on bile acid synthesis in isolated hepatocytes.


A fully coupled transient excited state model for the sodium channel. I. Conductance in the voltage clamped case. The behavior under voltage clamp conditions of a coupled kinetic scheme for the sodium channel is examined. The scheme is given diagrammatically by: Numerical simulations are presented which show that this model fits the voltage clamp data which are well described by the Hodgkin-Huxley equations, but also gives the sorts of behavior anomalous to the Hodgkin-Huxley model which have been seen experimentally. Further, straightforward changes in parameter values are shown to be capable of mimicking the ways in which some axonal preparations differ from others. Detailed, but admittedly heuristic, arguments are presented for the propositions that: 1) the model is minimal; i.e. no simpler kinetic model will fit the array of data simulated, and: 2) the transient excited state is necessary; i.e. no model of comparable simplicity with pure voltage dependent kinetics will fit the array of data simulated.


Molecular model for sodium conductance and calcium transport in the squid axon. A molecular and biochemically plausible model for the excitation process of the sodium pore is suggested. From basic arguments it is concluded that the sodium pore exists in at least three states: the resting state, the sodium conducting state, and the refractory state. They are connected to form a cyclic process. A specification of the different states is given. It is suggested that inactivation of the sodium pore results from a conformational change, which is caused by the transport of a calcium ion through the membrane. The transport carrier is the sodium pore. This assumption can explain the observed calcium influx during stimulation, and the effect of Ca on the rate of inactivation and on the rate, at which sodium conductance shuts off upon repolarization. It cannot give a quantitative explanation for the effect of Ca on the rate of rise, peak sodium conductance, and steady state inactivation. These asects are successfully described by the surface potential hypothesis, which has been published recently. It is concluded, that a combination of both theories gives a rather complete description of the sodium pore. The Ca transport model is discussed quantitatively and in great detail.


Periodic metabolic systems: oscillations in multiple-loop negative feedback biochemical control networks. For a general multiple loop feedback inhibition system in which the end product can inhibit any or all of the intermediate reactions it is shown that biologically significant behaviour is always confined to a bounded region of reaction space containing a unique equilibrium. By explicit construction of a Liapunov function for the general n dimensional differential equation it is shown that some values of reaction parameters cause the concentration vector to approach the equilibrium asymptotically for all physically realizable initial conditions. As the parameter values change, periodic solutions can appear within the bounded region. Some information about these periodic solutions can be obtained from the Hopf bifurcation theorem. Alternatively, if specific parameter values are known a numerical method can be used to find periodic solutions and determine their stability by locating a zero of the displacement map. The single loop Goodwin oscillator is analysed in detail. The methods are then used to treat an oscillator with two feedback loops and it is found that oscillations are possible even if both Hill coefficients are equal to one.


Hormonal regulation of 5alpha-reductase activity in rat epididymis. The specific activity of epididymal 5alpha-reductase (pmol 5alpha-reduced products mg protein-1 h-1) decreased by 17, 44, 58 and 83% of the initial value and its total activity (nmol 5alpha-reduced products organ-1 h-1) decreased by 66, 85, 94 and 98% 2, 4, 8 and 14 days respectively, after castration. The loss of total activity always exceeded the decrease in organ weight and protein content. The decline in enzymic activity could be prevented by implantation of testosterone at the time of castration. Administration of testosterone propionate (200 microgram/day) for 12 days starting 1 month after castration was associated with the weights of the accessory organs returning to the control values and although the specific activity of 5alpha-reductase was almost completely restored by this treatment, the total activity of the nuclear fraction remained at 49% of the control value. Recombination experiments demonstrated that the effect of androgens is not mediated by a factor present in the soluble fraction and the concomitant administration of androgen and either cycloheximide or actinomycin D blocked the effect of androgen. These data suggest that androgens stimulate the synthesis of epididymal 5alpha-reductase.


Secretion of progesterone during gestation in the rat. The concentrations of progesterone and 5alpha-pregnane-3,20-dione in ovarian and uterine venous plasma and in the systemic circulation were measured during gestation in the rat. The steroids were quantified by radioimmunoassay after separation on silicic acid micro-columns with the solvent system hexane : ethyl acetate (5 : 2, v/v). The concentration of progesterone in the systemic circulation was highest on days 3--4 and 13--17 of pregnancy; throughout gestation, the concentration of 5alpha-pregnane-3,20-dione was low in relation to that of progesterone and showed no marked changes as gestation proceeded. The level of progesterone in ovarian venous effluent was 10--20 times higher than that in the uterine vein and 20--50 times greater than that in the systemic circulation. The rate of secretion of progesterone by the ovary was highest during days 13--17 of gestation and ovariectomy during this period markedly reduced the levels of progesterone in the peripheral circulation. The concentration of progesterone in the uterine venous effluent was raised compared with the concentration in plasma from the abdominal aorta, especially on days 7 and 9 of pregnancy. These results suggest that, in vivo, the rat placenta synthesizes small amounts of progesterone and secretes it into the maternal circulation. The ovary is the primary source of progesterone during pregnancy and the placental contribution is of secondary importance. Although 4-ene-5alpha-reductase enzyme(s) is present in the ovary and placenta, significant quantities of the reduced progestin 5alpha-pregnane-3,20-dione are not secreted into the systemic circulation during gestation in the rat.


Transfer of milk prolactin to the plasma of neonatal rats by intestinal absorption. Prolactin passes from the systemic circulation of lactating rats into the milk where it can be consumed by the young rats during suckling. 131I-Labelled rat prolactin was detected in the plasma of 9- to 14-day-old rats after being nursed by mothers previously injected with 131I-labelled rat prolactin and after the pups had received 131I-labelled rat prolactin by gastric intubation. It was estimated that 16% of the 131I-labelled rat prolactin given by gastric intubation subsequently appeared in the plasma of the neonate. Gastric administration of 10.5 or 21.0 microgram B-1 rat prolactin significantly raised the level of prolactin in the plasma of 13-day-old pups, but a similar increase was not observed when 27-day-old rats were given 46.2 microgram B-1 prolactin by gastric intubation. The concentration of prolactin in the plasma of 13- to 14-day-old rats rose to 55 ng/ml 30 min after the onset of nursing by mothers whose mammary glands were full of milk, whereas the concentration in the plasma of offspring suckled by mothers with empty mammary glands remained at basal values. It is concluded that the intestine of the newborn rat is permeable to prolactin and that milk may constitute an exogenous source of prolactin for the suckled offspring.


Changes in the concentration of uterine cytoplasmic oestrogen receptors induced by doxorubicin and methotrexate. The effects of doxorubicin and methotrexate on the oestradiol-induced depletion, replenishment and subsequent increase beyond the normal value (overshoot) in the number of uterine cytoplasmic oestrogen receptors were investigated in intact rats. Injection of doxorubicin (0.5 mg/kg, i.v.) or methotrexate (1mg/kg, i.m.) 5 min after a single i.p. injection of 10 ng oestradiol-17beta (which is able to induce a 50% depletion in the number of oestrogen receptors) caused a significant increase in the oestradiol-induced depletion. Both drugs inhibited the replenishment and the overshoot phases until 48 h after treatment, although the effect was more marked with doxorubicin. Experiments in vitro showed that both methotrexate and doxorubicin affected the capacity of oestradiol-17beta to bind to specific cytoplasmic receptors, inducing an increase in binding when used at low concentrations and a decrease at higher concentrations. The effects of doxorubicin and methotrexate on the depletion, replenishment and overshoot of oestrogen receptors seemed to be partly dependent on the inhibition of protein synthesis and partly due to direct action on the binding of oestradiol-17beta to its receptors.


Specific interaction of corticosteroids with binding sites in the plasma membranes of the rat anterior pituitary gland. The binding of glucocorticoids to a crude fraction of rat pituitary plasma membranes and to solubilized membrane proteins was measured. The binding characteristics were similar to those exhibited by transcortin: radioactive corticosterone was bound to a greater extent than radioactive dexamethasone and labelled corticosterone, but not labelled dexamethasone, was displaced by unlabelled corticosterone, deoxycorticosterone and progesterone. A Scatchard plot of the binding data revealed the presence of a binding material with a dissociation constant of about 3.2 nmol/l, which sedimented at 4S after sucrose density-gradient centrifugation. It was found that the number of binding sites was inversely related to the concentration of corticosterone in the circulation and was increased after long-term adrenalectomy. These data suggest that a material similar to transcortin is complexed to the plasma membrane of rat pituitary cells.


Effects of a long-acting progestin on reproductive function in female mice. The duration of activity of a long-acting progestin, medroxyprogesterone acetate, was compared using three tests for progestational activity: the induction of stromal mitosis in the endometrium, implantation of blastocysts and inhibition of ovulation. The duration of activity was similar in each test and was longer when higher doses were given.


Effects of dietary cyclopropene fatty acids on the mixed function oxidase system of the rainbow trout (Salmo gairdneri). Dietary cyclopropene fatty acids (CPFA) in rainbow trout (Salmo gairdneri) decreased cytochrome P-450 and b5 content and NADPH-cytochrome c reductase activity 67.8 percent, 22.0 percent, and 38.4 percent respectively compared to control-fed trout after 22 days. Dietary CPFA induced benzo(alpha)pyrene aryl hydrocarbon hydroxylase 37.5 percent over controls for the same time period. Microsomal protein levels were consistently lower in CPFA-fed trout. This pattern remained established in CPFA-fed trout for the duration of the experiment (74 days). The data suggest a possible mechanism by which dietary CPFA act as co-carcinogens.


Comparative effects of aminotriazole on normal and acatalasemic mice. Some pharmacological and toxicological effects of dietary 3-amino-1,2,4-triazole (AT), a known catalase inhibitor, antithyroid agent, and carcinogen, have been examined, using acatalasemic (Csb) and normal catalase, "wild-type" (Csa) substrains of highly inbred C3H and C57BL mice. It was found that (a) the acatalasemic substrains are more resistant to weight loss and death on the AT diet than are their normal catalase counterparts; (b) Csb and Csa substrains of C57BL mice are more resistant to weight loss and death on the AT diet than are the Csb and Csa substrains of the C3H mouse; (c) the liver catalase, as well as the whole body catalase, of the two C57BL substrains is less inhibited by the AT diet than is that of the C3H substrains; (d) mice consuming the same quantity of either normal or AT-containing diet gain much more weight on the normal diet; (e) temporary consumption of the AT diet causes a considerable increase in thyroid weight, with an extremely slow, and only partial, return toward normal weight; and (f) the C3H/Csa mouse on an AT diet develops a scaly, necrotic tail very similar in appearance to the so-called rodent ringtail; this lesion is never observed in the acatalasemic mouse on the same diet.


Pancreatic carcinogenesis and naturally occurring pancreatic neoplasms of rats and mice in the NCI carcinogenesis testing program. Over two hundred chemicals were examined in a two year rodent bioassay system for possible carcinogenicity. Of these, only nitrofen significantly increased the incidence of neoplasms of the exocrine pancreas of rats or mice (female Osborne-Mendel rats); azinphosmethyl was the only agent tested which significantly increased the incidence of islet-cell tumors of rats or mice (male Osborne-Mendel rats). The use of the rat (Osborne-Mendel or Fischer 344) and mouse (B6C3F1) as models for the detection of chemically-induced pancreatic neoplasms also was investigated. The incidences of specific neoplasms of the exocrine or endocrine pancreas produced by all chemicals tested were combined and compared with the combined incidences of similar neoplasms in control animals in order to increase the sensitivity of the test. The data obtained through this procedure suggests that the male rat may be a good, sensitive model for the detection of islet-cell tumors.


Hexachlorobenzene I. Uptake, distribution and excretion of hexachlorobenzene (HCB) in growing lambs. The uptake, distribution, and excretion of hexachlorobenzene (HCB) was studied in young male (castrated) lambs. Lambs were exposed for 90 days at a dietary concentration of 0, 0.01, 0.1 and 1.0 ppm. Tissue concentration of HCB were monitored by periodic omental biopsy and by post-slaughter collection of tissues at 90 and at 300 days. Blood samples were collected by venipuncture each time that biopsies or sacrifice occurred. Findings of the 300 days duration study were: (1) the growth rate of the exposed lambs was unaffected by the exposure to the dietary HCB, (2) adipose tissue concentrations reached a level approximately ten times that in the diet at the end of the 90-day exposure period, (3) HCB concentration was higher in the omental fat than in the perirenal fat at 90 days but not at 300 days, (4) a good portion of the apparent decresae in HCB in the fat following cessation of exposure is due to dilution (by increasing carcass fat), (5) the apparent half-life of HCB was approximately 90 days and was not dose-dependent at the exposure rates studied, and (6) the highest HCB concentrations in other tissues were in the brain and liver. The study demonstrated that the omental biopsy provides an excellent means of estimating body fat burden of this lipid soluble pesticide, although it tends to provide an overestimate during actual dietary exposure. The finding that the bioconcentration of and the depletion from the adipose tissues were independent of dose enables prediction of the degree to which food animals might become contaminated if allowed to feed on HCB-contaminated pastures or feed stuffs, and of the time which will be required for such residues to decrease to negligible levels. This predictive ability is of obvious benefit to both the food animal producer and the consumer. Since the HCB is apparently much more stable in the body than is indicated by the depletion half-life of 90 days in these growing lambs, it follows that environmental contamination of grazing lands or animal feeds is of far greater consequence for adult animals which would not be likely to experience the growth dilution of carcass residues.


Chronic effects of three crude oils on oysters suspended in estuarine ponds. Gross and histological observations obtained from the study of oysters chronically exposed to single, low level (4 ppm) quantities of Empire Mix, Saudi Arabian, and Nigerian crude oils in estuarine ponds indicate a reduced intake and/or assimilation of food by the test animals. The tissues of many of the test animals, especially from the Saudi Arabian and Nigerian oil-treated ponds, were clear, watery, and emaciated in appearance, which was not the normal condition of oysters from the Gulf during the period of the samplings. Histologically, there were serious alterations in the connective tissues associated with the body wall, mantle, and food groove. The muscle and connective tissue fibers in these areas of many of the surviving oysters were swollen, translucent, homogeneous, structureless masses. These masses most nearly resembled the condition classically described as hyaline degeneration. In addition, there was a reduction in the development of the germinal epithelial tissues, indicating reduced reproductive potential.


Zinc protoporphyrin in blood as a biological indicator of chronic lead intoxication. Traditionally, the diagnosis of lead intoxication has relied upon blood lead and urine lead determinations. However, metabolic changes in the biosynthetic pathway of heme as well as damage in other organ systems may occur at blood lead levels hitherto regarded as "safe." Lead intoxication leads to elevated zinc protoporphyrin (ZPP) levels in the blood which can be measured quickly, inexpensively and conveniently on a drop of unprocessed whole blood by means of a dedicated front face fluorometer, called a hematofluorometer. In the present study, ZPP showed a strong correlation with the lead-in-blood level, as well as with signs and symptoms of lead-related disease. It is concluded that zinc protoporphyrin determination offers a preferred primary screening test for lead-exposed populations.


[Enzymic determination of acetoacetate and D(--)-3-hydroxybutyrate in urine (author's transl)]. The enzymic methods for the quantitative determination of acetoacetate and D(--)-3-hydroxybutyrate in blood were modified for the routine determination of these compounds in urine for clinical purposes. Preliminary normal values are reported for children.


Hexachlorobenzene II. Effects on growing lambs of prolonged low-level oral exposure to hexachlorobenzene (HCB). Fifty growing male (castrated) lambs were exposed to hexachlorobenzene in the diet at levels of 0, 0.01, 0.1 and 1.0 ppm for 90 days. They were then moved to clean quarters and the study continued for an additional 210 days. Growth rates, certain plasma enzyme activities and hepatic microsomal enzyme activities were studied to detect subclinical effects related to the exposure. A 19-day acute exposure at 100 ppm was done and the same parameters except for growth rate, measured. Hematocrit and plasma protein concentrations were also monitored. No significant changes were seen in the growth rates (90 days exposure), in the plasma enzymes alkaline phosphatase, glutamic oxaloacetic transaminase, glucose 6-phosphate dehydrogenase or succinic dehydrogenase, or in the hematocrit or plasma protein concentrations after either the 90-day or 19-day exposures. However, in vivo metabolism of antipyrine was increased in both the 1.0 ppm (90-day) and the 100 ppm (19-day), but was significantly increased (p less than 0.01) in only the 100-ppm exposure. Additionally, hepatic microsomal N-demethylase was increased significantly by the 90-day exposure at 1.0 ppm and the 19-day exposure at 100 ppm, but the hepatic microsomal O-demethylase was significantly increased only after the 1.0-ppm exposure. Histopathologic examination of tissues (brain, lung, myocardium, large and small intestines, liver, kidneys, adrenals, mesenteric lymph nodes) collected from animals sacrificed at 90 days and at the termination of the study (300 days) revealed no lesions suggestive of harmful HCB exposure.


[Adaptation of an entirely enzymatic triglyceride assay to the GSA II Greiner. Application to the study of the stability of triglycerides, and factors causing interference in the analysis (author's transl)]. The assay of triglycerides by an entirely enzymatic pathway was adapted for use on the GSA II Greiner. The method requires only 20 microliters of biological material. The reaction time is short: 8 min at 37 degrees C. The coefficient of variation does not exceed 6% over a period of one month. Linearity of the measurements was verified up to a level of 4 mmol/l. It was shown that the free glycerol level should be systematically measured and deducted from that of the total glycerol to assure accurate results. The stability of the plasma triglycerides was investigated as a function of the length and temperature of storage (+4 degrees C and -196 degrees C). The free glycerol increases as a function of time, whereas the level of triglycerides stays constant. Haemoglobin and various medicaments, in particular, hypolipemiants and hypoglycemiants, did not interfere.


Hemodynamic effects of long term feeding of sympathomimetic amines to swine. The hemodynamic effects of long term feeding of sympathomimetic amines (SPMA) to swine were studied. Three groups of female swine (N = 20 for each group) were fed either aminorex fumarate, d-amphetamine sulfate, or dextrose (control) for as long as 8 months in dosages up to 15 mg/kg/day. After 4 months of this feeding regiment, the weight gain of the pigs fed either aminorex or amphetamine was significantly less than the control animals. Hemodynamic measurements on awake swine indicated no elevation of pulmonary arterial blood pressure in the pigs fed SPMA. Measurement of systemic hemodynamics revealed that cardiac index was lower in the treated pigs than in control animals, but that heart rate and systemic arterial blood pressure were not altered by the drugs. In addition to baseline measurements of hemodynamic variables, the animals were exposed to acute hypoxia (12 percent O2 in N2) for 5 minutes. Although pulmonary arterial blood pressure increased similarly in the 3 groups of pigs, total pulmonary resistance increased to a greater extent in the pigs fed SPMA, indicating perhaps an enhancement of the hypoxic pulmonary pressor response after chronic ingestion of either amphetamine or aminorex. In a limited number of pigs, SPMA were fed for a period of 8 months, of which the last 3 months were during pregnancy. Hemodynamic measurements on sedated (metomidate, IV) swine revealed no difference in pulmonary arterial blood pressures between treated and control animals. We conclude that chronic ingestion of large doses of aminorex or amphetamine in swine does not lead to pulmonary arterial hypertension, but that slight reductions in cardiac output and subtle alterations in the pulmonary pressor response to acute hypoxia may occur.


Combined batchwise and continuous flow mechanization of solid-phase radioimmunoassays. A new modification of the "coated-tube"-technique for the radioimmunoassay of human placental lactogen is described. Polyvinylchloride capillaries are used as reaction-vessels. Most working steps of the test procedure are mechanized. The possibilities and limitations of the new technique are discussed. The reliability of the method was shown by a recovery test, dilution tests, reproducibility and a comparison of the results for 71 sera, ranging from the 6th to the 42nd week of pregnancy, with those obtained by a conventional assay procedure.


When does a response error become a judgmental bias? Commentary on "Judged Frequency of Lethal Events". The study of Lichtenstein, Slovic, Fischhoff, Layman, and Combs reports several types of errors in subjects' frequency judgments of lethal events. These errors are interpreted as reflecting the operation of two types of judgment biases. In this research, the objective or actual frequency of lethal events served as a standard of comparison; any deviation from this standard was defined as a bias. Thus, the research strategy used is apparently modeled after that of a psychophysicist using illusions to study basic perceptual processes. There is one key difference, however. In the case of illusions, the subject is directly exposed to the physical stimulus object. In the present study, however, subjects were never exposed to actual stimuli. Since subjects were asked to make judgments about things they had not directly experienced, it is not surprising that they would be inaccurate. But unlike the study of illusions, such inaccuracies have not been shown to have any necessary connection to psychological mechanisms. Therefore, it seems somewhat tenuous to offer psychological interpretations of judgmental biases when the origins of those biases have not yet been identified.


Rod sensitivity and visual pigment concentration in Xenopus. Xenopus larvae were raised on a vitamin A-free diet under constant illumination until their visual pigment content had decreased to between 8% of normal and an undetectably low level. After the intramuscular injection of 2.1 X 10(13-2.1 X 10(16) molecules of [3H]vitamin A, ocular tissue showed a rapid rate of uptake of label which reached a maximum level of incorporation by 48 h. Light-microscopic autoradiography revealed that the retinal uptake of label was concentrated within the receptor outer segments. Spectral transmissivity measurements at various times after injection were made upon intact retinas and upon digitonin extracts. They showed that visual pigment with a lambdamax of 504 nm was formed in the retina and that the amount formed was a function of incubation time and the magnitude of the dose administered. Electrophysiological measures of photoreceptor light responses were obtained from the PIII component of the electroretinogram, isolated with aspartate. The quantal flux required to elicit a criterion response was determined and related to the fraction of visual pigment present. The results showed that rod sensitivity varied linearly with the probability of quantal absorption.


Formation, conversion, and utilization of isorhodopsin, rhodopsin, and porphyropsin by rod photoreceptors in the Xenopus retina. The visual pigment content of rod photoreceptors in Xenopus larvae was reduced greater than 90% through a combination of vitamin A-deficient diet and constant light. Thereafter, a dose of either all-trans-retinol or 9-cis-retinal was injected intramuscularly, leading to the formation of a rhodopsin (lambdamax 504 nm) or isorhodopsin (lambdamax 487-493 nm) pigment, respectively. Electrophysiological measurements were made of the threshold and spectral sensitivity of the aspartate-isolated PIII (photoreceptoral) component of the electroretinogram. These measures established that either rhodopsin or isorhodopsin subserved visual transduction with the same efficiency as the 519 nm porphyropsin pigment encountered normally. When animals with rhodopsin or isorhodopsin were kept in darkness or placed on a cyclical lighting regimen for 8 days, retinal densitometry showed that either pigment was being converted to porphyropsin; significantly more porphyropsin was formed as a result of cyclical lighting than after complete darkness.


Nonsymmetrical bifurcations in arterial branching. The results of optimality studies of the branching angles of arterial bifurcations are extended to nonsymmetrical bifurcations. Predicted nonsymmetrical bifurcations are found to be not unlike those observed in the cardiovascular system.


Analysis of sodium and potassium redistribution during sustained permeability increases at the innervated face of Electrophorus electroplaques. Cholinergic agonists cause an increase in the membrane permeability of Na and K at the innervated face of Electrophorus electroplaques. Therefore, sustained exposure to agonist reduces Na and K concentration gradients. There gradients are monitored with voltage-clamp sequences and pharmacological treatments that selectively measure the Nernst potentials for individual ions. EK is normally near--90 mV but moves toward zero during bath application of agonist. Depolarizations by bath-applied agonist measure primarily this shift of EK, not short-circuiting of EK by the agonist-induced conductance. After a rapid jump of agonist concentration, there is a fast (millisecond) depolarization due to the conductance increase, followed by a much slower additional "creep" due to the shift in EK. Sodium replaces the lost intracellular potassium: ENa, normally very positive, also moves toward zero. The shifts in EK and ENa are normally reversible but become permanent after blockade of the Na-K pump. In the presence of agonist, the shifts can be driven further by passing current of the appropriate polarity. Similar ion redistribution occurs with other drugs, such as batrachotoxin and nystatin, which induce prolonged increases in Na permeability. The redistributions cause little net change in the reversal potential of the neurally evoked postsynaptic current.


Initial conditions and the kinetics of the sodium conductance in Myxicola giant axons. I. effects on the time-course of the sodium conductance. The effects of conditioning polarizations, ranging from--150 to 0 mV and of durations from 50 mus to 30 ms, on the time-course of GNa during test steps in potential were studied in Myxicola giant axons. Beyond the effects of conditioning polarizations on the amplitude of GNa, the only effect was to produce a translation of GNa(t) along the time axis without a change in shape. For depolarizing conditioning potentials, Hodgkin-Huxley kinetics predict time shifts about threefold greater than found experimentally, whereas the predictions of the coupled model of Goldman (1975. Biophys. J. 15:119--136) were in approximate agreement with our experiments. The time shifts developed over an exponential time-course as the conditioning pulse duration was increased. The time constant of development of the time shift was considerably faster than, and showed the opposite dependency on potential from, the values predicted by both models. It had a mean Q10 of 1/2.50. This fast activation process cannot account for the observed rise time behavior of GNa, suggesting that there is an additional activation process. All results are consistent with the idea that the gating structure displays more than three states, with state intermediate between rest and conducting.


Initial conditions and the kinetics of the sodium conductance in Myxicola giant axons. II. Relaxation experiments. The time-course of the decay of INa on resetting the membrane potential to various levels after test steps in potential was studied. The effects of different initial conditions on these Na tail currents were also studied. For postpulse potentials at or negative to -35 mV, these currents may be attributed nearly entirely to the shutdown of the activation process, inactivation being little involved. Several relaxations may be detected in the tail currents. The slower two are well defined exponentials with time constants of approximately 1 ms and 100 mus in the hyperpolarizing potential range. The fastest relaxation is only poorly resolved. Different initial conditions could alter the relative weighting factors on the various exponential terms, but did not affect any of the individual time constants. The activation of the sodium conductance cannot be attributed to any number of independent and identical two-state subunits with first order transitions. The results of this and the previous paper are discussed in terms of the minimum kinetic scheme consistent with the data. Evidence is also presented suggesting that there may exist a small subpopulation of channels with different kinetics and a faster rate of recovery from TTX block than the rest of the population.


Genetic recombination in Streptomyces fradiae by protoplast fusion and cell regeneration. Conditions for highly efficient genetic recombination in Streptomyces by protoplast fusion are described. Protoplasts of S. fradiae and S. griseofuscus were formed by a modification of the glycine-lysozyme-lytic enzyme method (Okanishi, Suzuki & Umezawa, 1974). Regeneration of cells from protoplasts was monitored throughout the growth cycle and was most efficient when cells of either S. fradiae or S. griseofuscus were taken from the transition phase between the exponential and stationary growth phases. Fusion of protoplasts carrying different auxotrophic or chromosomal drug-resistance markers was achieved by treatment with polyethylene glycol, and high frequencies of stable genetic recombinants were obtained.


'Viscotaxis', a new behavioural response of Leptospira interrogans (biflexa) strain B16. When in a non-viscous environment and confronted with a viscous one, Leptospira interrogans (biflexa) strain B16 preferentially selected the latter. We have designated this positive response to a viscosity gradient as 'viscotaxis'. Using an originally designed experimental chamber, a pool of leptospires were faced with capillary tubes containing either polyvinylpyrrolidone (PVP) or N-2-hydroxyethylpiperazine-N'-2-ethanesulphonic acid (HEPES). Leptospires suspended in HEPES responded positively to 2% (w/v) PVP in capillaries, and migrated into them in large numbers in 1 h. No response was observed when the chamber and capillary tubes contained solutions of the same viscosity. As the viscosity of PVP was increased, a proportionally larger number of leptospires migrated into it. This newly observed aspect of leptospiral behaviour may have ecological significance.


Thermosensitive antibiotic resistance plasmids in enterobacteria. Of 775 conjugative plasmids found in enterobacteria mediating antibiotic resistance, 24 (3.1%) were thermosensitive (ts); they were most common in Klebsiella pneumoniae. Ts plasmids were also found in all the samples of sewage and river water examined. Over half of 73 ts plasmids from unrelated sources mediated resistance to chloramphenicol in addition to several other antibiotics. Many of them mediated resistance to mercury (53.4%), arsenite (38.4%) and tellurite (79.5%) but not to copper, cobalt and silver. Fifty-eight belonged to incompatibility group H2 and 12 belonged to the H1 group. Resistance to mercury, arsenite and tellurite was common in strains containing H2 plasmids but not in H1 plasmids. The 73 plasmids transferred at high rates at 22 and 28 degrees C and at lower rates at 15 degrees C; they transferred at very low rates or not at all at 37 degrees C. They could be divided into two sets according to whether they transferred at a high or at a low rate at 33 degrees C. Unlike the prototype plasmid, Rts 1, they were solely or mainly ts for transfer and not for replication and only one of them brought about a marked reduction in growth rate of its host organism at 42 degrees C. None of the 73 plasmids mediated colicin or haemolysin production. Three plasmids, all from K. pneumoniae, mediated utilization of lactose, two of sucrose and raffinose and three, all belonging to group H1, of citrate. None of the plasmids increased the pathogenicity of Salmonella typhimurium for chicks or Escherichia coli K12 for mice.


Some bits and pieces of the genus Nocardia: N. carnea, N. vaccinii, N. transvalensis, N. orientalis and N. aerocolonigenes. Since 1951 when our taxonomic study of the genus Nocardia began, only eight strains of N. carnea (Rossi-Doria) Castellani & Chalmers, four strains of N. vaccinii Demaree & Smith, five of N. transvalensis Pijper & Pullinger, 21 or N. orientalis (Pittenger & Brigham) Pridham and 14 of N. aerocolonigenes (Shinobu & Kawato) Pridham have been found. These five groups of strains are described and are compared with strains of nine accepted species of Nocardia. With the possible exception of N. orientalis, more strains of these five taxa must be assembled and examined to establish the reliability of our descriptions and identifications.


Effect of ethanol during hepatitis B virus infection in chimpanzees. To determine whether the use of ethyl alcohol (ethanol, C2H5OH) may increase the liver damage caused by hepatitis B virus infection, ethanol was infused into four chimpanzees on one or two occasions during the course of natural or experimentally induced hepatitis B virus infections. A fifth chimpanzee, without active hepatitis B virus infection, served as a control. Moderate elevations of serum aspartate or alanine aminotransferases occurred in four of the five chimpanzees, including the control chimpanzee, in direct association with ethanol infusion; pre-existing enzyme elevations persisted in a fifth chimpanzee. No alteration occurred in the titers of hepatitis B surface antigen or of antibody to hepatitis B core antigen in three of the four infected chimpanzees. There was no significant alteration in the course of hepatitis B virus infection by ethanol infusion in these chimpanzees.


Subacute encephalitis and hydrocephalus in hamsters caused by measles virus from persistently infected cell cultures. Newborn hamsters were inoculated intracerebrally with measles virus materials from Lu 106 and Vero carrier cell lines. Extracellular and cell-associated materials from cultures incubated at 37 degrees C and at 33 degrees C were used. The lower temperature allows accentuated virus replication. No animals contracted acute encephalitis, but 8 animals developed advanced neurological disease (unsteady gait, serial myoclonic jerks, hypoactivity) 79 to 212 days after injection. Seven out of these 8 animals belonged to a group of 50 animals, which had been inoculated with cell-associated material from cultures incubated at 33 degrees C. Viral antigen and nucleocapsids were found in neurons and glial cells from diseased animals, which showed degenerative changes and inflammation, particularly in the mesencephalon. Some of these animals also had hydrocephalus, which, however, also occurred in many apparently healthy animals. Also this pathological alteration occurred most frequently (5 out of 11 animals examined 9--10 months after inoculation) in hamsters receiving cell-associated material from carrier cutlures incubated at 33 degrees C. Possible mechanisms for the appearance of hydrocephalus are discussed.


CNS disease following dissemination of SSPE measles virus from intraperitoneal inoculation of suckling hamsters. Acute encephalitis was observed in suckling Golden Syrian hamsters following intraperitoneal (ip) inoculation of a hamster brain adapted strain of subacute sclerosing panencephalitis (SSPE) measles virus (HBS). Virus was isolated from the brains of all encephalitic animals by cocultivation of tissue with Vero cells. The histopathology of the encephalitis was characterized by perivascular mononuclear infiltrates, necrosis, eosinophilic inclusion bodies, and rare giant cells. Association of encephalitis with systemic viral infection was observed with virus present in lung and a kidney-spleen pool in addition to brain. Viral dissemination in asymptomatic animals was documented with virus being isolated from multiple non-neural tissues (spleen, lung, liver) of animals having no recoverable virus in their brains and no signs of encephalitis. Treatment of animals with cyclophosphamide prior to ip virus inoculation did not increase dissemination to brain. Absence of encephalitis in asymptomatic animals with proven viral dissemination to parenchymal organs indicates that neither viremia alone, nor viremia in conjunction with dissemination are sufficient conditions to establish central nervous system disease. The association of encephalitis with systemic viral infection and the dissemination to brain establish this model's potential value for the study of the pathogenesis of measles encephalitis.


Antibodies to single-stranded DNA: an aid in diagnosis of viral hepatitis. In clinical and subclinical viral hepatitis a significant increase of antibodies to single-stranded DNA revealed by the prepatent stage of the disease before any elevation of serum transaminases. In type A hepatitis, a rise in anti-DNA titers was detectable one to two weeks before onset of clinical and biochemical signs; in type B hepatitis, the rise of anti-DNA coincided with or preceded the appearance of HBSAg, several weeks before the onset of clinical illness. In both hepatitis types anti-DNA titers reached a peak (640--2,560) at onset and dropped shortly after serum transaminases returned to normal at the end of acute illness. The anti-DNA response in non-A/non-B hepatitis was of similar magnitude. Anti-DNA elevation was the only positive sign found in most silent infections of either type that later showed specific seroconversion. Anti-DNA levels in noninfected contacts were in the same range as those found in a group of health individuals. The anti-DNA test is useful for early diagnosis of viral hepatitis and should be a valuable addition to current epidemiological and clinical procedures.


Rapid detection of hepatitis B surface antigen by double antibody radioimmunoassay. HBsAg and anti-HBs can be detected by double-antibody radioimmunoassay in a reliable routine overnight assay of sensitivity approaching that of solid-phase immunoradiometric assay. The test requires careful standardisation and regular preparation of I125-HBsAg of appropriate quality, but otherwise uses only small quantities of commercially available reagents. In this paper, the reaction kinetics of the first incubation (test sample + limiting amount of rabbit anti-HBs), second incubation (reaction mixture + I125 -HBsAg) and precipitation reaction (reaction mixture + antirabbit globulin) were examined, to determine the minimum time required for the assay compatible with adequate sensitivity and user convenience; in addition, in order to reduce the time of radioactive counting, the maximum amount of I125-HBsAg per test compatible with a satisfactory assay was examined. It was concluded that, by terminating each reaction before equilibrium was reached, results could be obtained in 2--3 hours with a detection limit similar to the standard overnight procedure. To allow routine examination of large numbers of samples, the possibilities of complete automation of this liquid-phase type of assay were discussed.


Detection of HBeAg and anti-HBe in acute hepatitis B by a sensitive radioimmunoassay. A solid-phase radioimmunoassay using anti-HBe-coated polysterence beads and iodine-125-labeled anti-HBe of human origin was developed for the detection of HBeAg. Anti-HBe could be determined by a blocking test. Both assays were about 500-fold more sensitive than immunodiffusion. Few nonspecific positive results for HBeAg could be recognized in the anti-HBe test by increase in cpm over that of the negative control. HBeAg was not found in acute hepatitis A and non A-non B hepatitis or in a control group of accident patients. On admission to the hospital 12 of 48 (25%) acute hepatitis B patients from Greece and 17 of 20 (85%) acute hepatitis B patients from Germany were HBeAg-positive. All 39 initially HBeAg negative sera were already anti-HBe positive. Tests of the acute stage and follow-up sera of the 20 German patients indicated that HBeAg is regularly present in the incubation period and early acute phase of hepatitis B. After onset of disease the antigen is cleared from the serum very rapidly in uncomplicated cases and is usually followed by the appearance of anti-HBe. Like anti-HBc, anti-HBe can serve as a tool for the diagnosis of hepatitis B after the disappearance of HBsAg.


Diagnosis of hepatitis B by Dane particle associated DNA polymerase assay. We have studied prospectively 478 subjects exposed to hepatitis B virus and 20 pregnant women who developed HBs antigen during the last trimester of pregnancy. The results suggest that the DNA polymerase assay might be useful for the diagnosis of hepatitis B infection and that in confirmed cases of hepatitis, the enzyme might be detected in the absence of HBs antigen. HBe antigen appeared in 19% of those subjects who developed HBs and a positive correlation between HBe antigen and DNA polymerase was found in 40% of the cases positive for this antigen. The data presented also suggest that HBe antigenemia in pregnant women is not consistently associated with HBs infection in the babies born to them. However the children born to HBe positive mothers are at higher risk than those born to HBe negative mothers.


The role of the hepatitis B virus infection in patients with chronic hepatitis in Argentina. Over a seven-year period, we monitored 221 patients with chronic hepatitis from two medical centers. By using the counterlectrophoresis (CEP) test to detect the presence of HBsAg and anti-HBc, or both, we established that 87.7% of them had hepatitis B infection. Serum specimens originally found negative for HBsAg by CEP were further tested by reversed passive hemagglutination (RPH), and those originally found negative for anti-HBc by CEP were further tested by radioimmunoassay (RIA). Five patients were anti-HBc-positive and HBs-Ag-negative. No sex predominance was observed, but HBsAg incidence increased with increasing age. The HBeAg antigen was detected in 46.8% of the 161 cases tested for it; the most frequent subtype found was adw (63.7%). The present findings indicate that HBV infection largely contributes to the development of chronic hepatitis in Argentinian patients.


The IgM antibody responses to the core antigen of hepatitis B virus. Little is known about the immunoglobulin class of antibodies to HBcAg. In the present study sera containing anti-HBc were fractionated by surcose density-gradient centrifugation, and all serum fractions were tested against HBcAg by immunoelectro-osmophoresis. In addition selected fractions were examined by complement fixation test, immune adherence hemagglutination and immune electron microscopy. Anti-HBc activity in IgG serum fractions was demonstrated by all four techniques used, but HBcAg-specific IgM was detected only by immunoelectro-osmophoresis and by immune electron microscopy. In acute hepatitis B, HBcAg-specific IgM was detected for up to eight weeks after the onset of jaundice. It was also found transiently in two patients who developed chronic hepatitis B without an icteric episode and in one out of thirteen patients with HBsAg-positive chronic liver disease, but in none of eight healthy HBsAg carriers. The results suggested that HBcAg-specific IgM is formed transiently in response to primary HBV infection but is generally undetectable in established HBsAg carriers.


Memory effects and sensory integration: an examination of sensory modality translation models of intersensory functioning. The sensory modality of a task and the modality of a retroactive interfering activity were systematically covaried in order to test Connolly and Jones' and Pick's translation models of intersensory functioning. Forty 10-year-old boys and girls were asked to recall distance and location cues of length under intrasensory and intersensory task conditions (visual and kinesthetic). Visual and kinesthetic interpolated activities were used in an attempt to provide modality specific interference with the recall of length under the various sensory task conditions. Results of the data analyses provided no support for the Connolly and Jones model of modality specific storage with translation. Rather, the findings of the study were interpreted as supportive of Pick's hypothesis which emphasizes the coding of stimulus information (regardless of modality of input) into a form specific to whatever modality is specialized for detection of the information.


Developmental stages in children's representation of regular solid figures. Styles of representing regular three-dimensional figures were studied in a sample of 80 Jamaican boys and girls 7- to 15-years-old. Each child drew five common solids under short and long exposure conditions. Inspection of children's drawings of four of the solids suggested a developmental sequence of four stages (plane schematic, solid schematic, prerealistic, and realistic) corresponding closely to previously obtained stages for children's spontaneous drawings. The sequence of stages was validated through several considerations, including a clear age progression and a high reliability of a total score over eight drawings. Discussion focuses on the possible ways in which the geometrical characteristics of a regular solid might influence the rate of development of the corresponding representational schema.


Effects of task difficulty on state-trait anxiety in emotionally disturbed children. In order to investigate the effects of a difficult vs. easier task on state-trait anxiety in emotionally disturbed children (N = 30 boys and girls), older (mean age 12.81) and younger (mean age 9.89) groups were exposed to two lists of nonsense syllables, varying on meaningfulness (0% vs. 100%) with measures of A-State and A-Trait anxiety being obtained during a no-stress period and immediately after each list. The results indicated that the younger group did not show any difference in A-State following the two lists, while the older group showed significantly more A-State increase following the difficult list. Results were discussed in terms of previous research, and in terms of possible explanations for the differences between the reactions of the older and younger children.


Family socialization and adolescent personality and their association with adolescent use of marijuana. This study examines family socialization practices and adolescent personality/attitudinal characteristics, their interrelation, and association with adolescent use of marijuana. Two hundred and eighty-four adolescents and their mothers served as Ss. As hypothesized, parental socialization factors and adolescent personality/attitudinal attributes each had an independent effect on adolescent use of marijuana and each comprised its own set of sufficient conditions for adolescent marijuana use.


The effect of haloperidol, spiperone and pimozide on the flexor reflex of the hind limb of the spinal rat. It was found that spiperone and pimozide in doses which themselves do not influence the flexor reflex of the hind limb of the spinal rat inhibit stimulation of this reflex induced by serotoninomimetic drugs (LSD and fenfluramine). Higher doses of spiperone depress the flexor reflex and inhibit the stimulating effect of clonidine. Pimozide has no such effect. Haloperidol in doses which do not influence the action of LSD and fenfluramine produces a depression of the flexor reflex and antagonizes the action of clonidine. Our findings indicate that, irrespective of their antidopamine action, spiperone has a central antiserotonin effect and an antinoradrenaline one, pimozide--an antiserotonin one and haloperidol--an antinoradrenaline one.


Plasma serotonin contents in cerebrovascular disease. The plasma serotonin contents of fourty-three cerebrovascular patients were examined. 1. Abnormal serotonin contents were found in 72 per cent of fourty-three cerebrovascular patients. 2. In cerebral hemorrhage, serotonin contents were significantly low in the acute period. 3. Serotonin contents in cerebral hemorrhage and subarachnoid hemorrhage, had an increasing tendency from the fourth week to the eigth week, but after the eighth week, they returned to normal.