The restricted penetration of iodinated rat FSH and LH into the seminiferous tubules of the rat testis. The penetration of 125I-iodinated rat follicle-stimulating hormone (FSH; labelled by three different techniques) and luteinizing hormone (LH) through the walls of the seminiferous tubules of the rat testis has been studied by injecting the labelled hormone into rats with the efferent ducts of one testis ligated 16 h before the collection of samples of blood and tissues. The concentration of trichloracetic acid-precipitable and immunoprecipitable radioactivity was measured in blood plasma and rete testis fluid and calculated for the total secreted fluid retained in the testis by the ligature, and for the additional tubular fluid from the ligated testis, separated by centrifugation after decapsulating the testis and dispersing the cells. Very little intact hormone penetrated into the testicular fluids, even 16 h after injection of the labelled hormone, and the volume of distribution in the unligated testis of the trichloracetic acid-precipitable radioactivity was only slightly greater than that for markers known to be confined to the extracellular interstitial fluid. This suggests that the labelled hormones do not penetrate readily through the walls of the semiferous tubules into their lumina. Injected inorganic iodiide and trichloracetic acid-soluble 125I-circulating after the injection of iodinated hormones penetrated more rapidly into the tubules, but had not reached equilibrium between the testicular fluids and blood plasma 16 h after injection. Labelled FSH was reasonably stable in the circulation after injection, but 80% of the 125I was not protein-bound 16 h after injection of labelled LH.


Relative sensitivity of the corpus luteum of different days of pregnancy to LH-deprivation in the rat and hamster. Deprivation of endogenous LH by LH antiserum (LH A/S) in 6-day pregnant rats did not affect the luteal or serum progesterone within 24 h. LH A/S treatment on day 7 or 8 of pregnancy, however, caused a 70 and 92% reduction in luteal progesterone, respectively, within 24 h. Serum levels of progesterone showed a similar reduction. In the case of pregnant hamster, unlike the rat, there was a significant decrease in progesterone in the serum, luteal and non-luteal compartments whether the A/S was administered on day 4, 5 or 6. There was more than a 10-fold increase in the luteal cholesterol esters within 24 h whether the A/S was given on day 6, 7 or 8 of pregnancy in the rat. Rat corpora lutea of days 6 and 8 of pregnancy reacted in a like manner to LH-deprivation, showing an increased utilization of [U-14C]glucose to form 14CO2 in vitro. In the rat, LH (25 mug NIH-S19) administration in vivo either on day 6 or day 8 of pregnancy, caused within 2 h an increase in serum and non-luteal progesterone, but luteal progesterone was unchanged. On the other hand, LH administration to hamsters on day 8 of pregnancy caused an increase in progesterone levels in serum, luteal and non-luteal tissue. Incubation of corpora lutea isolated from untreated 6- and 8-day pregnant rats with LH brought about an increase in progesterone secretion into the medium in both cases. The results show that, even though LH-deprivation does not apparently affect progesterone concentration in the corpus luteum of 6-day pregnant rats, it does affect other metabolic parameters such as glucose utilization and cholesterol turnover, suggesting that the corpus luteum of early pregnancy exhibits a continuous dependency on LH for the maintainence of metabolic functions.


Cytochrome P-450 and the aromatization of 16alpha-hydroxytestosterone and androstenedione by human placental microsomes. When measured in vitro using human placental microsomal preparations, the aromatization of 16alpha-hydroxytestosterone to estriol and androstenedione to estrone and estradiol proceeds at almost identical initial rates. Important differences between 16alpha-hydroxytestosterone and adrostenedione aromatization are evident, however. While substantial findings have implicated cytochrome P-450 in placental aromatization, the aromatizaiton of androstenedione is insensitive to CO although it is competitively inhibited by metyrapone. 16alpha-Hydroxytestosterone aromatization, in contrast, is inhibited 50-60% by CO and is strongly inhibited by metyrapone. 16alpha-hydroxytestosterone aromatization is strongly inhibited in a competitive manner by androstenedione, while 16alpha-hydroxytestosterone has essentially no effect on androstenedione aromatization, althogh at very high 16alpha-hydroxytestosterone concentrations (65 muM) and subsaturating androstenedione concentrations, 16alpha-hydroxytestosterone appears to noncomptitively inhibit androstenedione aromatization. The apparent Km for the aromatization of androstenedione is 95 nM and for 16alpha-hydroxytestosterone, 7 muM. Both androstenedione and 16alpha-hydroxytestosterone cause type I spectral perturbations associated with binding to cytochrome P-450 when added to placental microsomes; however, the deltaA390-420 is twice as great in response to saturating amounts of androstenedione than in response to 16alpha-hydroxytestosterone. If androstenedione is added to 16alpha-hydroxytestosterone, the same spectral change as that caused by androstenedione alone is expressed. The apparent spectral dissociation constant for androstenedione is 93 nM while for 16alpha-hydroxytestosterone it is 11muM; both essentially the same as the comparable apparent Kms for aromatization. The evidence suggests the presence of two aromatase P-450's in human placenta.


Site at which FSH regulates estradiol-17beta biosynthesis in Sertoli cell preparations in culture. Sertoli cells were isolated from testes of 20-day-old rats and were maintained in primary culture. The ability of these cells to synthesise estradiol-17beta from a variety of exogenous substrates, progesterone, testosterone,androstenedione, 19-hydroxyandrostenedione and 19-hydroxytestosterone in the presence and absence of follicle-stimulating hormone (FSH) was examined. In the presence of each of the substrates alone for 24 h the rate of estradiol-17beta synthesis was very low. FSH (NIH-FSH-S11, 5 mug/ml) stimulated estradiol-17beta synthesis 75-fold when added to medium containing testosterone (5 X 10(-7)M) but caused only marginal stimulation when added to medium containing progesterone (5 X 10(-7) M). Both FSH and dibutyryl cyclic AMP (bu2cAMP) stimulated the conversion of each of the substrates, androstenedione, 19-hydroxyandrostenedione and 19-hydroxytestosterone to estradiol-17beta, and the effects were similar to those observed in the presence of testosterone. These data indicate that, under the culture conditions employed, progesterone is not an effective substrate for conversion to estradiol-17beta by Sertoli cells. Estradiol-17beta synthesis was stimulated by FSH in the presence of the C19 steluences the conversion of androgens to estrogens, either directly or indirectly, at the aromatisation step (i.e. the conversion of 19-hydroxylated androgens to estrogens).


Estrogen-induced changes of ribonucleic acid in the rat uterus. The incorporation of [3H]uridine into uterine RNA of immature rats was studied up to 6 h after a single injection of estradiol. Under these experimental conditions, estradiol progressively increased the incorporation of the radioactive precursor into the total RNA. This increase could not be explained by variations in the uptake of [3H]uridine by the tissue. The total RNA and the fractions obtained by differential thermal extraction were analysed by gel electrophoresis. One hour after hormone treatment, a similar increase of incorporation of the labelled precursor in the different RNA species was observed. After a long period of time, [3H]uridine was preferentially incorporated into rRNA as compared to HnRNA and to heterogenous cytoplasmic RNA. Experiments which involved the use of low doses of actinomycin D sufficient to inhibit any rRNA synthesis, confirmed the relatively slight increase in precursor incorporation into non-ribosomal RNA. The distribution of the radioactivity incorporated into the 3 fractions of RNA, obtained by thermal extraction (2 nuclear fractions and 1 cytoplasmic), suggested an increase in the rate of transcription and transport of the RNA during hormonal treatment. The polyA-containing uterine RNA was isolated on a column of oligo(dT)-cellulose and subsequently studied by electrophoresis. There is no preferential incorporation of precursor into the polyA-containing RNA when compared with the total RNA. However, the polyA-containing RNA constitutes the only part of the non-ribosomal RNA whose synthesis continues to increase throughout the period of hormone treatment.


Clostridium oedematiens: observations on potency assaying. The United States has established a Standard Requirement for the potency testing of biological products containing Clostridium oedematiens belonging to two types: type B (Cl. novyi) and type D (Cl. haemolyticum). Guinea pig testing has provided widely varying results depending on the origin of the animals. The tests reported are intended to determine the efficacity of the vaccines (Cl. novyi and Cl. haemolyticum) depending on the animal tested: guinea pigs, sheep and bovines; they further establish a parallelism between the antitoxin titer and the immunity of the animal.


Potency testing of Clostridium septicum bacterins in sheep and laboratory animals. The immunogenic potency of bacterins containing Clostridium septicum was evaluated in mice, hamsters, guinea pigs, rabbits and sheep to establish potency requirements for these bacterins. Two subcutaneous injections of Cl. septicum bacterins were shown to provide resistance against intramuscular spore challenge. Protection in mice, hamsters and guinea pigs was generally at low levels, in the range of 1 to 5 LD50. Efficacy estimates, at these levels of challenge, indicated that a degree of relationship existed between the response of rabbits and the response of sheep. This relationship was confirmed at higher levels of spore challenge, at greater than 5 to 500 LD50. Undiluted bacterins were classed as good or poor based on percent survival responses in sheep. Bacterins providing 90 to 100% survival were classed as good; those providing 30 to 57% survival were classed as poor. In rabbits, this classification was less evident with the undiluted bacterins. Dilution of bacterins to 1:32 provided a discriminatory level with 7 of 8 bacterins examined and represented correlation of the sheep and rabbits responses. A similar relationship was demonstrated between protection in sheep against spore challenge and the antitoxin response in rabbits to undiluted bacterins. Antitoxin responses, when obtained, were generally higher in rabbits than those obtained in sheep. Further evaluation of a good and a poor bacterin in rabbits indicated that no direct relationship existed between antitoxin titer in rabbits and resistance to spore challenge, when compared at the same dilutions of bacterins. Evaluation of serum agglutination responses to types I and II somatic antigens indicated a poor relationship between agglutination response and resistance to spore challenge in both sheep and rabbits. Cl. septicum toxoids were shown to provide resistance to spore challenge in rabbits.


Preparation and evaluation to Clostridium septicum toxoid. Clostridium septicum was grown under controlled conditions to produce high levels of alpha toxin. The toxin was toxoided and concentrated by ultrafiltration. The toxoided alpha toxin retained immunizing properties. The concentrated toxoid, when formulated on Total Combining Power, in monovalent or multivalent clostridial products, provided protection to rabbits against direct challenge with Cl. septicum spores. The toxoided alpha toxin produced antitoxin levels which exceeded current minima.


Some observations on the quality control testing of Clostridium chauvoei vaccines. Agglutination tests are not suitable for the estimation of the protective antibody level in the sera of vaccinated animals and should not be used for the quality control testing of blackleg vaccines. Some highly virulent strains of Cl. chauvoei are only effectively protected against by vaccines containing cells with a heat labile protective antigen in addition to the heat stable antigen common to all cells of Cl. chauvoei. As these highly virulent strains may be encountered in the field it is important that such strains should be selected for the challenge of vaccinated animals in the quality control testing of blackleg vaccines. It would be useful if an international center could be responsible for the collection and distribution of such strains.


Some problems concerning the assay of Clostridium chauvoei vaccine in laboratory animals. The potency test prescribed for Cl. chauvoei vaccines in the British Veterinary Codex requires the complete survival of a group of immunized guinea pigs and death of all unvaccinated controls. Problems arising from the influence of extraneous factors such as animal strain, diet and seasonal variation on the outcome of this test are discussed together with alternative methods that might permit the use of a standard preparation.


[Failure of anti-symptomatic vaccination and the methods of vaccine activity control]. Blackleg (Clostridium chauvoei) infection in Charollais cattle appears to have undergone some etiological and pathogenic changes which are reflected in the apparent failure of vaccination. Two methods have been used to determine the quality of the vaccines in order to meet the different requirements specified by pharmacopeias. The two methods differ in the vaccination schedules of the guinea pigs and the test strain used which may be either a virulent culture or a suspension of spore in calcium chloride. Both methods appear to be efficient in selecting vaccines which provide good protection. It follows, therefore, that the vaccination failures would appear to be the result of intensive selection of beef cattle with reduced immunological response. If this is the case, the remedy for these vaccination failures might lie in an adaptation of the vaccination schedule to the early developing breeds of cattle obtained by intensive selective breeding.


Potency testing of Cl. sordellii bacterin-toxoids by means of a mouse protection test. A potency assay method involving mouse protection against spore challenge has been developed and used, since 1967, for the potency testing of the Cl. sordellii component of several multivalent clostridial bacterins. The mouse test results obtained with several experimental bacterin formulations are presented along with other test data concerning the relationship of alpha antitoxin response and protection in guinea pigs and cattle.


The assay of clostridial vaccines in mice. The proposed establishment of a multicomponent clostridial standard vaccine inevitably raises the question of how such a preparation might be used in the standardization of batches of vaccine. Traditional multipoint parallel line assays based on the antitoxin responses of rabbits and guinea pigs are likely to prove prohibitively costly, whilst simpler methods based on single dose levels of either vaccine fail to quantitate the relationship between test vaccine and standard.


[Determination and the trial of a polyvalent anatoxin against clostridiosis of the sheep]. Description of the preparation and composition of a new type of polyvalent vaccine against bradsot, infectious enterotoxemia and malignant edema (necrotic hepatitis) of sheep as well as dysentery of lambs. This vaccine is a formolized polyanatoxin obtained after centrifugation, purification and concentration of the toxins followed by formolization and adsorption on aluminum hydroxyde. The serum antibody titers are much higher than after utilizing the usual vaccines and the period of immunity in the sheep is considerably extended.


The relative potency of an oily adjuvant multicomponent vaccine in laboratory animals and sheep. Oil emulsion vaccines differ considerably from conventional alum precipitated vaccines both in their method of application and immunological response. It is questionable whether the existing statutory tests provide meaningful evaluation of such vaccines. Attempts were therefore made to determine how far antigenicity tests of an oil emulsion vaccine in laboratory animals reflects the potency of this vaccine in the target species - sheep. The results that were obtained are presented and discussed and comparisons are made with similar results obtained with a multicomponent alum precipitated vaccine.


The development of the EEG in the rat.

The development of the EEG in the rat. The development of the electroencephalogram (EEG) and, especially, behavioral state-specific EEG patterns was studied in white and black hooded rats of the Lister strain, aged 9-30 days. Movements of the rat were recorded and the behavioral state was monitored by means of a push-button device. The EEG was collected when the rat was in State 1 (regular respiration, absence of movements, and, after the 14th day when the rat eye opens, eyes closed), State 2 (irregular respiration, continual occurrence of twitches, and, after the 14th day, eyes closed), and in State 4 (irregular respiration, presence of gross body movements, and, after the 14th day, eyes opened). The EEG of rats on the 9th and 10th day did not reveal behavioral state-specific patterns. The amplitudes of the EEG were low and only low frequencies occurred. Between the 10th and 13th day an EEG pattern specific for State 1 containing high amplitudes developed. From the 14th day onwards spindles (frequencies from 14-18 Hz) occurred in the EEG during State 1. From the 14th day onwards, the EEG from the visual cortex during State 2 showed a regular and continually occurring 5-Hz rhythm. Bursts with 5-Hz waves were recorded from the visual cortex only intermittently during State 4. The EEG frequencies during the bursts varied between 5 and 7 Hz from the 17th day onwards. Computer analysis of the amplitude distributions showed a considerable increase in the power after the 10th day. The analysis of the frequency spectra indicated that the power increase occurs expecially in the higher frequencies of the EEG signal. Visual analysis as well as computer analysis of the EEG did not reveal systematic changes in the EEG after the 18th day when the EEG was similar to that recorded at older ages.


Reaction time and the psychological refractory period in children and adults. The psychological refractory period-the prolonged reaction time (RT) to the second of 2 closely-spaced stimuli-was investigated in groups of 13 children and 13 adults. Subjects responded as fast as possible to the 2nd of 2 loud clicks that were presented after a soft click which served as a ready signal. The inter-stimulus interval (ISI), or time between loud clicks, was investigated as an independent variable. The results for ISI's of 50, 100, 250, and 500 msec confirmed the existence of an inverse relationship between RT and ISI. In accordance with the hypothesis investigated, RT was more prolonged in children than in adults as ISI decreased. Findings were consistent with the view that refractory period (RP) of an information-processing element in the central processor is longer in children than in adults. A single-channel model of information processing was proposed which could explain the inverse relationship between RT and ISI; could account for the slope differences between the RT vs ISI curves from children and adults; and could account, in part, for the overall longer RT's of children than of adults.


Undernutrition in early life: lasting effects on activity and social behavior of male and female rats. The growth-retarded offspring of mother rats undernourished throughout pregnancy and lactation were fed ad libitum from weaning. Males were tested at 100 days of age, and ovariectomized females at 150 days. After 2 weeks of isolation, pairs of males consisting of 1 control (C) and 1 previously undernourished (PU) rat were observed for 10 min on each of 9 consecutive days. Similarly paired and treated female rats were tested a total of 8 times, the first 3 tests being separated from the last 5 by a 10-day interval. The PU rats, whether male or female, performed more rearing responses and PU male rats ambulated more in the social situation than C rats. The PU males also performed more of the social responses allogroom, walk over, and mount than C males. Similarly, PU females performed more allogroom and crawl under than C females. In general, PU rats were more active than C rats and more socially responsive.


A longitudinal study of bioelectric activity in the pre- and post-hatch chick. A technique for embryonic implantation and the subsequent recording of electrocortical, neck muscle, and ocular activity continously from the 20th day of incubation through hatching and the first few days thereafter is demonstrated. The embryonic maturation of the EEG, with a characteristic muscle burst pattern heralding hatching was found, supporting previous reports obtained with acute preparations. The technique for injection into the chorioallantoic membrane (CAM) vessels or direct deposition onto the CAM is also described. The usefulness of the embryonic neurophysiological implantation coupled with the injection at specific stages of development is discusses as an approach to the understanding of the parameters of the maturation of the sleep-wakefulness cycle, neurochemistry, and behavior.


Short exposures to enriched environments can increase genetic variability of behavior in mice. Previous work indicates that mice of different genotypes reared in enriched environments show differential increases in performance on a food-seeking task. In this study 2 experiments examined the effects in selected mice strains of short exposures to such enrichment. Experiment 1 indicated that 48 hr of exposure to enriched cages was sufficient to produce results found previously when subjects were reared from birth in enriched cages. Experiment 2 indicated that as little as 6 hr of exposure to an enriched cage was sufficient to produce almost maximal enrichment effects in C57BL/10J mice.


Effects of cyclophosphamide treatment of newborn mice on the development of swimming and reflex behavior and on adult behavioral performance. Cyclophosphamide (CP), an antineoplastic agent, was administered subcutaneously to Swiss-Webster mice on the day of birth and the mice were later tested for developmental or adult behavioral abnormalities. The CP dosages of 20, 30, or 45 mg/kg of body weight retarded maturation of swimming ability and 45 mg/kg retarded maturation of the righting reflex. At 7 weeks of age mice treated neonatally with 30 or 45 mg/kg of CP had reduced locomotor activity and were more emotionally reactive than controls in an open field. Mice treated with 30 but not 20 mg/kg of CP tended to avoid shock less than controls and those treated with 20 mg/kg fell more frequently when crossing a rotating rod for food. Rotorod performance was improved by treatment with 45 but not 30 mg/kg of CP. All dosages examined decreased body weight gains but only 30 or 45 mg/kg resulted in gross body malformations. The results indicate that CP can functionally impair the development of mice and that some of these impairments are independent of gross body malformations.


The effects of tactile and kinesthetic stimulation on neonatal development in the premature infant. The effects of tactile and kinesthetic stimulation on the neonatal development of 12 premature infants were investigated. Experimental infants received four 15-min periods of tactile and kinesthetic stimulation daily for 10 days. The control infants received only standard, routine nursery care. Data were collected daily on 8 dependent measures: weight, number of feedings, amount of formula intake, body temperature, respiration, heart rate, frequency of voiding, and frequency of stooling. The data analyses revealed significant differences in amount of formula intake and in weight at the end of the treatment period in favor of the experimental infants. Additionally, the experimental infants required significantly fewer feedings during the stimulation period. All others dependent measures were nonsignificant.


Genetic and ontogenetic variations in locomotor activity following treatment with scopolamine or d-amphetamine. Highly inbred mice of 3 strains (A/J, DBA/2J, and C57BL/6J) were tested in an open field at 14, 21, or 28 days of age. Ten minutes prior to testing, mice received treatment of saline, scopolamine (.5 or 1.0 mg/kg of body weight), or d-amphetamine (.5, 1.0, or 5.0 mg/kg). The d-amphetamine (5.0 mg/kg) increased activity in all strains at 14 days and 28 days of age, and at 21 days significantly increased activity in all except the C5BL/6. In contrast, increased activity with the scopolamine treatment was seen in DBA/2 at 21 days, but not in A and C57BL/6 until 28 days postnatally. The data support a caudal-rostral gradient of brain development with the inhibitory cholinergic system developing more slowly than the excitatory catecholamine system. In addition, strain-specific differences in activity levels are discussed in relation to the differential rates of chloinergic maturation.


Neonatal and adult brain parameters in mice selected for adult brain weight. Several neonatal and adult parameters were determined in the Roderick-Wimer lines of mice selected for low (L) or for high (Hb and Hg) adult brain weight, and in the unselected control line (C). Neonatal cerebral weight, DNA (index of cell number), and protein were significantly higher in the H and C lines than in the L line. The ratios of cerebral DNA/weight (index of cell density), cerebral protein/weight, and cerebral protein/DNA (index of protein content per cell or cell size) were at birth practically the same in all lines. In the adult animals all the differences were amplified and, in addition, some of the differences in the above ratios were significant, for the cerebral cortex as well as for the cerebellum. These findings may be causally related to the reported superiority in behavioral performance of the H line.


On gluconeogenesis of human liver. Accelerated hepatic glucose formation induced by increased precursor supply. In 8 subjects in whom portal vein catheters had been inserted 5-6 days previously during cholecystectomy, arterial and portal concentrations of glucose, lactate, pyruvate, glycerol, alanine, free fatty acids, beta-hydroxybutyrate and acetoacetate revealed no significant differences. This provided the basis for the calculation of hepatic balances from arterio-hepatic venous substrate-differences in 17 healthy volunteers. In eight of them metabolic balances were determined during elevated hepatic lactate supply. Kinetics of the substrates throughout the whole test period in 9 controls showed no gross interference from the catheterization or infusion procedure. The elevated hepatic lactate concentration caused a doubling of hepatic glucose output, which could almost entirely be accounted for by a fivefold increase of hepatic lactate uptake. This acceleration of hepatic gluconeogenesis was accompanied by a significant increment of hepatic free fatty acid uptake, whereas hepatic ketone body production did not change. These data seem to support the view that hepatic energy requirements caused by an accelerated gluconeogenesis might be covered from enhanced free fatty acid oxidation.


Regulation of brittle diabetics by a pre-planned insulin infusion programme. Eleven brittle diabetics, mean duration 11.5 years, all treated with highly purified porcine NPH insulin twice daily, were placed on highly purified porcine regular insulin 4 times daily for 2 days. Thereafter pre-planned intravenous insulin infusion was started. Insulin in an amount corresponding to the daily insulin requirement was infused by a mobile electric infusion pump at precalculated rates between 30 and 7 ml/hour during 2 days. The patients were ambulatory. Capillary blood glucose was taken every 30 min after meals and every two hours during the night. After an equilibration period of 7 hours, blood glucose fluctuations were in the physiological range in nearly all patients during the infusion period. [Only 1.3% of the blood samples showed glucose levels lower than 2.5 mmol/l and 2.9% levels exceeding 10.0 mmol/l during the infusion days]. Mean blood glucose (MBG) was 6.0 +/- 0.9 mmol/l (mean +/- s.d.), the standard deviation of MBG was 1.8 +/- 0.5 mmol/l, the mean amplitude of blood glucose excursions (MAGE) 4.7 +/- 1.4 mmol/l, and glucosuria 3.1 +/- 3.9 g/day. All these data of glucose  homeostasis were significantly lower during the infusion days. The incidence of hypoglycaemic attacks was low (0.32/patient/day) and not significantly higher than during NPH treatment. It is concluded that near normal blood glucose fluctuations can be achieved in brittle diabetics by preplanned insulin infusion without blood glucose monitoring.


Arterial concentration and forearm extraction of glucose and insulin during the early phase of a glucose infusion. The concentrations of glucose and insulin were determined with high precision at half minute intervals in arterial and deep forearm vein blood after a bolus injection of glucose (4 g), followed by a constant i. v. infusion (200 mg/min), in four healthy subjects. The values for the deep vein were corrected for the transit time, which was determined by injection of Cardio-green. Arterial glucose peaked at the end of the bolus injection, venous glucose 1 1/2 min later. Arterial insulin reached its maximum later than glucose, after 2 1/2-4 min. The venous insulin reached its maximum later and was much lower than the arterial level, in two cases only around 50% of the arterial concentration. It is concluded that early after glucose administration there is a considerable extraction of both glucose and insulin by the forearm. Since the insulin extraction was quite variable venous insulin concentrations cannot be used for the assessment of early insulin response to glucose.


Biological properties of chemically modified insulins. I. Biological activity of proinsulin and insulin modified at A1-glycine and B29-lysine. Beef insulin, pork proinsulin and four derivatives of beef insulin modified at the A1-B29 site on the molecular surface have been studied. Three derivatives had a synthetic crosslink between the A and B chains. Previous studies with these materials [2, 3 and 5] had demonstrated in vivo bioactivities which were much higher than those displayed in vitro. This paper reports experiments which explain this discrepancy. The analogues were administered at equimolar rates to anaesthetised greyhounds by a priming-dose constant infusion technique and the plasma concentrations achieved were estimated by radioimmunoassay. Proinsulin and the modified insulins were metabolised more slowly than insulin. Biopotency values, which related fall in plasma glucose concentration to the total administered dose of analogue, agreed broadly with published results of conventional in vivo bioassays. On the other hand, calculation of potency in relation to the serum concentration of analogue actually achieved, yielded results which agreed more closely with in vitro assay data. We conclude that for these analogues, reported discrepancies between in vitro and in vivo biopotencies can be largely explained by the different rates at which these materials are metabolised.


Response of gastric inhibitory polypeptide (GIP) to test meal in chronic pancreatitis--relationship to endocrine and exocrine insufficiency. Twenty-nine patients with chronic pancreatitis had a significantly greater IR-GIP response to a test meal than 15 controls. This increased response was not related to the degree of steatorrhoea or glucose intolerance. It was most marked in a group of patients with moderately impaired IRI release and medium steatorrhoea. From this is concluded that the IR-GIP response to a test meal is determined by at least two factors: 1. feedback control via insulin secretion, 2. assimilation of fat. In chronic pancreatitis endocrine insufficiency may induce an exaggerated GIP response and severe exocrine insufficiency may prevent fat induced GIP release. Gastrin is not involved in the different GIP response in patients with chronic pancreatitis.


Plasma glucagon immunoreactivity in a totally pancreatectomized patient. Analysis of the plasma from a totally pancreatectomized patient, with antiserum 30 K, has demonstrated basal glucagon immunoreactivity (GIR) levels in the normal range (80-110 pg/ml). Neither i. v. arginine nor oral glucose affected these GIR values, thus indicating the absence of functioning pancreatic or gastrointestinal A-cells. Furthermore, filtration of whole plasma on Bio Gel P-30 showed no GIR in the 3500 MW elution volume. GIR was found to be distributed in two peaks. One peak eluted in the protein region, similarly to "big plasma glucagon" (BPG), and the second peak appeared after the glucagon-I125 marker. The protein-sized moiety was not absorbable by charcoal, and on Sephadex G-100 it eluted within the globulin region. When subjected to trypsin treatment, it yielded smaller GIR fractions. According to these criteria, it can be assumed that this component is identical to BPG. Therefore, an extrapancreatic source for BPG is suggested. On the other hand, the presence of fasting hyperglycaemia in this patient indicates that insulin deficiency by itself suffices to raise blood sugar to diabetic levels.


Effects of monosodium glutamate administration in the neonatal period on the diabetic syndrome in KK mice. Administration of monosodium glutamate (MSG) to KK mice during the neonatal period resulted in a syndrome of obesity, stunting and hypogonadism. In some animals the genetic predisposition to diabetes was unmasked with the development of marked hyperglycaemia and or hyperinsulinaemia. Food intake was not increased compared to controls. The elevated plasma glucose and insulin in fed MSG treated mice fell rapidly with food deprivation. Glucose disposal was comparable in MSG treated and control mice after IP glucose, but after oral glucose MSG treated mice showed impaired glucose tolerance. Insulin secretion was defective in MSG treated mice after IP but not after oral glucose.


C-peptide in children with juvenile diabetes. A preliminary report. Serum C-peptide, insulin-binding IgG and total insulin (IRI) were determined in 96 juvenile diabetics aged 4-21 years, with onset of diabetes at the age of 1-16 years and with 2-17 years' duration of diabetes. Thirty-four patients (35.4%) had detectable levels of C-peptide (greater than or equal to 0.04 pmol/ml). Compared to non-diabetic adults, 19 had values below the normal range, 12 showed values within the normal range (0.18-0.63 pmol/ml) and 3 rated above normal. There was a negative correlation between the fasting C-peptide concentration and the degree of ketonuria at the onset of diabetes and a positive correlation between C-peptide levels and the incidence of post-initial remission periods. Patients without detectable C-peptide had significantly higher levels of insulin antibodies than those who had detectable levels of C-peptide. The possibility of a relationship between the intensity of the initial treatment of diabetes and the preservation of the B-cell function is discussed, as well as the possibility of insulin antibodies being a cause of B-cell exhaustion.


Effect of N-methyl-N'-nitro-N-nitrosoguanidine on immune response in rats in stomach carcinogenesis. Subcutaneous injections of N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) at the dose of 50 mg/kg body weight for 10 days showed depressed production of hemolysin against sheep red blood cells (SRNC) in Wistar rats. On the other hand, oral administration at the dose of approximately 35 mg/kg body weight for 30 weeks scarcely suppressed antibody preduction to heterologous RBC and cell-mediated immune response to Walker-256 carcinosarcoma in Wistar rats during the experimental period of 55 weeks. The daily administration by way of oral route proved to be efficient for the induction of stomach cancer. The difference in immunosuppressive effect of MNNG by these two routes will be discussed in relation to the susceptibility of in vivo degradation of the carcinogen.


Effect of experimental immune atrophic gastritis on the induction of gastric carcinoma by X-irradiation in ICR mice. Divided doses of 6,000 or 8,000 rad of X-ray were given to the gastric region of ICR/JCL female mice with immune atrophic gastritis produced by the injection with allogenic stomach antigen. The carcinogenic effect of X-rays for inducing gastric carcinoma was significantly increased by this method. Two points can be presented as its reason. First, the pyloric gland mucosa regenerating from injuries by immunization was exposed to the divided dose of X-rays. Second, the marked requirement of gastrin secretion attributable to severe injuries of parietal cell mass by immunization and local X-irradiation acted as a promoting factor on the induction of gastric carcinoma by X-ray for a long time through the trophic effects on the pyloric gland.


Radioimmunoassay of carcinoembryonic antigen and clinical significance of its level in plasma. The level of carcinoembryonic antigen (CEA) in the plasma was measured in 258 patients, consisting of 198 patients with various cancers and 60 with various non-malignant diseases. As the normal control, the plasma CEA level was examined in 330 apparently healthy individuals and the value was 3.1 +/- 1.1 ng/ml on the average. If the level higher than 4.2 ng/ml could be assumed to be above the normal, 109 out of 198 (55%) patients with malignant diseases were considered to show abnormally elevated CEA values. Based on the above criterion, the CEA titer was abnormally elevated only in 11 out of 60 cases (18%) without cancers. Among cancerous patients, the ones with carcinomas of the digestive tract and the lung exhibited a positive titer of CEA higher than 10.1 ng/ml. When the relationship between the plasma CEA level and histological findings in patients with lung cancer was examined, cases with the adenocarcinoma had more elevated titers than those with any other types of lung cancer. It was also found, by the serial estimation of plasma CEA, that the titer dropped after a successful therapy but elevated again with the recurrence of cancer. Repeated estimation of Cea is thought to be valuable as an indicator for clinical phases of cancer patients.


Clinical value of protein-bound fucose in patients with carcinoma and other diseases. Protein-bound fucose content in sera from normal persons and patients with various malignant and non-malignant diseases was measured and statistically analyzed. Normal serum gave a mean value of 6.84 +/- 0.13 mg/100 ml, and rarely exceeded 9 mg/100 ml. Although no significant difference was found between sexes, there was a tendency of fucose content to decrease in older persons. It was noted that more than 90% of cancer-bearing patients have significantly higher level than critical value (9 mg/100 ml), while only 8.7% of patients with benign tumor showed positive result. These results were not limited to special organs but in common to all cases studied. The elevation of serum fucose content in malignant tumor was well correlated with its stages of progression, though the levels were less significant in early and in rather locally restricted breast and thyroid cancer. Serial postoperative follow-up study showed that the levels in serum fucose content was a useful parameter for judging the effectiveness of therapy and the prognosis of the patient. The fucose content in malignant tumor tissue and metastasized lymph node appeared to be significantly elevated than that in normal tissue. The practical usage and limitation of the fucose value in various diseases, together with a possible source of serum fucose were discussed.


Development of adenocarcinoma of the prostate in ICR mice locally irradiated with X-rays. The pelvic region of male ICR/JCL mice 5 approximately 7 weeks of age was irradiated with 1,000 rad of X-rays for a total of 8 exposures ot determine whether such irradiation would induce prostatic carcinoma. Prostatic adenocarcinoma was observed in 5 of 135 animals which survived more than 12 weeks after the first X-irradiation. Because spontaneous development of prostatic adenocarcinoma has not been reported in mice, development of this carcinoma in these animals can be considered to be attributable to X-irradiation.


Haptoglobin types in cancer patients in comparison with normal populations in the Eastern India. The distribution of haptoglobin (Hp) phenotypes in patients with different types of cancer was compared with those in the normal population, with the aid of vertical disc polyacrylamide gel electrophoresis. The Hp1 gene frequency (0.0647) of the normal population exhibited only a slight difference from that of the cancer patients, as against previous records. The only appreciable difference was in the range of mobility of the Hp2 bands from the origin in individuals with Hp 2-1 and 2-2 phenotypes.


Human breast cancer serially transplantable in nude mice in ascites form. Cell suspension of a human breast cancer cell line (Hattori line) was injected intraperitoneally into an athymic nude mouse to produce ascites form breast cancer (peritoneal carcinomatosis). Subsequent serail transfers of cancer cells in ascites were also successful in mice. All male and female nude mice injected 1 X 10(7) tumor cells died of accumulation of ascites after a latency period averaging 4 weeks, with one exception which died of a wasting disease. Multiple lung metastases were observed in some mice. The tumor cells retained cytological characteristics of the original cell line, and histology of the infiltrating tumor in the peritoneum and omentum was that of poorly differentiated adenocarcinoma. Differentiation not only toward acinar or duct lining cells but also toward myoepithelial cells was observed by histochemistry, immunohistochemistry, and electron microscopy.


Absence of vitamin B12-binding proteins in the histamine-containing gastric carcinoid in Praomys (Mastomys) natalensis. The transplantable argyrophilic gastric carcinoids producing histamine found in Praomys (Mastomys) natalensis contained no significant amount of vitamin B12-binding proteins. It was also demonstrated that the concentration of vitamin B12-binding proteins in glandular stomach of mastomys was much lower than those in the same tissues of the rat or mouse.


Recovery in Burkitt lymphoma cells after X-ray irradiation. The radiation response of cultured Burkitt lymphoma cell, known as a particular cell line of high radiosensitivity, was studied by the colony formation method. The values of n, Dq, and Do derived from the survival curve after a single dose X-irradiation resulted in small values as 1.1, 10 rad, and 125 rad. The maximum recovery of about 5% was observed 3 hr after the irradiation by a split-dose experiment. In the survival curve derived from a split-dose irradiation, n and Dq increased while Do remained unchanged. The reason for these increases in n and Dq may be attributed to the nonhomogeneous or mixed population response.


Cell population size dependency of therapeutic effect of divided dosage of 1-beta-D-arabinofuranosylcytosine. A total dose of 960 mg/kg body weight of 1-beta-D-arabinofuranosylcytosine (cytosine arabinoside) was given intraperitoneally to rats bearing Yoshida sarcoma, in a single or divided doses. Single-dose therapy gave an increased life span of about 1 day irrespective of cell population size in accord with the concept of constant percentage cell kill. Tumor cell reduction was estimated to be about 70%. Divded-dose therapy, however, brought about increased life span which was reciprocally proportional to the logarithm of population size. Estimated cell reduction was 87% when population size was 10(8) cells and 99.95% at 10(4) cells.


Enzymes and reproduction in natural populations of Drosophila euronotus. Populations of Drosophila euronotus, one from southern Louisiana )3 samples), and one from Missouri (2 samples), were classified for allele frequencies at alkaline phosphatase (APH) and acid phosphatase (ACPH) loci. The two populations differed consistently in allele frequencies at both loci. The APH locus is on the inversion-free X chromosome; the chromosomal locus of the autosomal ACPH is unknown, and could involve inversion polymorphism. Wild females from Missouri and Louisiana populations heterozygous at the APH locus carried more sperm at capture than did the corresponding homozygotes. This heterotic association was significant for the combined samples, and whether it was the result of heterosis at the enzyme locus studied, or due to geographically widespread close linkage with other heterotic loci, it should help to maintain heterozygosity at the APH locus. In a Louisiana collection which included large numbers of sperm-free females, simultaneous homozygosity at both enzyme loci was significantly associated with lack of sperm. It is suggested that the latter association is the result of young heterozygous females achieving sexual maturity earlier than do the double homozygotes. The average effective sperm load for 225 wild females was only 29.4, suggesting the necessity for frequent repeat-mating in nature to maintain female fertility. A comparison of the sex-linked APH genotypes of wild females with those of their daughters indicated that among 295 wild-inseminated females from five populations, 35% had mated more than once, and of this 35%, six females had mated at least three times. Because of ascertainment difficulties, it is clear that the true frequency of multiple-mating in nature must have been much higher than the observed 35%. Laboratory studies indicate that multiple-mating in this species does not involve sperm displacement, possibly due to the small number of sperms transmitted per mating, and the fact that the sperm receptacles are only partially filled by a given mating.


Hidden genetic variability within electromorphs in finite populations. The amount of hidden genetic variability within electromorphs in finite populations is studied by using the infinite site model and stepwise mutation model simultaneously. A formula is developed for the bivariate probability generating function for the number of codon differences and the number of electromorph state differences between two randomly chosen cistrons. Using this formula, the distribution as well as the mean and variance of the number of codon differences between two identical or nonidentical electromorphs are studied. The distribution of the number of codon differences between two randomly chosen identical electromorphs is similar to the geometric distribution but more leptokurtic. Studies are also made on the number of codon differences between two electromorphs chosen at random one from each of two populations which have been separated for an arbitrary number of generations. It is shown that the amount of hidden genetic variability is very large if the product of effective population size and mutation rate is large.


The Lewontin and Krakauer test on quantitative characters. It is shown that LEWONTIN and KRAKAUER's test could also be applied to quantitative characters that do not show important dominance and epistatic genetic variances. The design of experiments for this purpose and the error of the estimation of F are discussed.


Marker effects on reversion of T4rII mutants. The frequencies of 2-aminopurine- and 5-bromouracil-induced A:T leads to G:C transitions were compared at nonsense sites throughout the rII region of bacteriophage T4. These frequencies are influenced both by adjacent base pairs within the nonsense codons and by extracodonic factors. Following 2AP treatment, they are high in amber (UAG) and lower in opal (UGA) codons than in allelic ochre (UAA) codons. In general, 5BU-induced transitions are more frequent in both amber and opal codons than in the allelic ochre codons. 2AP- and 5BU-induced transition frequencies in the first and third positions of opal codons are correlated with those in the corresponding positions of the allelic ochre codons. Similarly, the frequencies of 2AP-induced transition in the first and second positions of amber codons and their ochre alleles are correlated. However, there is little correlation between the frequencies of 5BU-induced transitions in the first and second positions of allelic amber and ochre codons.


Mapping of the homothallic genes, HM alpha and HMa, in Saccharomyces yeasts. Two of the three homothallic genes, HM alpha and HMa, showed direct linkage to the mating-type locus at approximately 73 and 98 strans (57 and 65 centimorgans [cM], respectively, whereas, the other, HO, showed no linkage to 25 standard markers distributed over 17 chromosomes including the mating-type locus. To determine whether the HM alpha and HMa loci located on the left or right side of the mating-type locus, equations for three factor analysis of three linked genes were derived. Tetrad data were collected and were compared with expected values by chi 2 statistics. Calculations indicated that the HM alpha gene is probably located on the right arm at 95 strans (65 cM) from the centromere and the HMa locus at approximately 90 strans (64 cM) on the left arm of chromosome III.


Nonbehavioral selection for pawns, mutants of Paramecium aurelia with decreased excitability. The reversal response in Paramecium aurelia is mediated by calcium which carries the inward current during excitation. Electrophysiological studies indicate that strontium and barium can also carry the inward current. Exposure to high concentrations of barium rapidly paralyzes and later kills wild-type paramecia. Following mutagenesis with nitrosoguanidine, seven mutants which continued to swim in the ;high-barium' solution were selected. All of the mutants show decreased reversal behavior, with phenotypes ranging from extremely non-reversing (;extreme' pawns) to nearly wild-type reversal behavior (;partial' pawns). The mutations fall into three complementation groups, identical to the pwA, pwB, and pwC genes of Kunget al. (1975). All of the pwA and pwB mutants withstand longer exposure to barium, the pwB mutants surviving longer than the pwA mutants. Among mutants of each gene, survival is correlated with loss of reversal behavior. Double mutants (A-B, A-C, B-C), identified in the exautogamous progeny of crosses between ;partial' mutants, exhibited a more extreme non-reversing phenotype than either of their single-mutant (;partial' pawn) parents.---Inability to reverse could be expected from an alteration in the calcium-activated reversal mechanism or in excitation. A normal calcium-activated structure was demonstrated in all pawns by chlorpromazine treatment. In a separate report (Schein, Bennett and Katz 1976) the results of electrophysiological investigations directly demonstrate decreased excitability in all of the mutants, a decrease due to an altered calcium activation. The studies of the genetics, the survival in barium and the electro-physiology of the pawns demonstrate that the pwA and pwB genes have different effects on calcium activation.


Sulfhydryl compounds in melanocytes of yellow (Ay/a), nonagouti (a/a), and agouti (A/A) mice. CLEFFMANN (1953, 1963a,b) has reported that yellow but not black melanocytes of agouti (A/A) rabbits contained reducing sulfhydryl compounds. We have attempted to repeat CLEFFMANN's observations in mouse melanocytes of the lethal yellow (Ay/a), nonagouti (a/a) and agouti (A/A) genotypes. Our results contradict those of CLEFFMANN and reveal that yellow and black melanocytes, regardless of genotype, possess equivalent amounts of histochemically detectable sulfhydryl compounds. These results do not support the hypothesis that agouti-locus genes act by controlling the sulfhydryl metabolism of pigment cells.


Lack of genic similarity between two sibling species of drosophila as revealed by varied techniques. Acrylamide gel electrophoresis was performed on the enzyme xanthine dehydrogenase in sixty isochromosomal lines of Drosophila persimilis from three geographic populations. Sequential electrophoretic analysis using varied gel concentrations and buffers revealed twenty-three alleles in this species where only five had been described previously. These new electrophoretic techniques also detected a profound increase in divergence of gene frequencies at this locus between D. persimilis and its sibling species D. pseudoobscura. The implications of these results for questions of speciation and the maintenance of genetic variability are discussed.


Genetic heterogeneity within electrophoretic "alleles" of xanthine dehydrogenase in Drosophila pseudoobscura. An experimental plan for an exhaustive determination of genic variation at structural gene loci is presented. In the initial steps of this program, 146 isochromosomal lines from 12 geographic populations of D. pseudoobscura were examined for allelic variation of xanthine dehydrogenase by the serial use of 4 different electrophoretic conditions and a head stability test. The 5 criteria revealed a total of 37 allelic classes out of the 146 genomes examined where only 6 had been previously revealed by the usual method of gel electrophoresis. This immense increase in genic variation also showed previously unsuspected population differences between the main part of the species distribution and the isolated population of Bogotá population. The average heterozygosity at the Xdh locus is at least 72% in natural populations. This result, together with the very large number of alleles segregating and the pattern of allelic frequencies, has implications for theories of genetic polymorphism which are discussed.


Polymorphism in a cyclic parthenogenetic species: Simocephalus serrulatus. A survey of sixteen isozyme loci using electrophoretic techniques was conducted for three isolated natural populations and one laboratory population of the cyclic parthenogenetic species, Simocephalus serrulatus. The proportion of polymorphic loci (33%-60%) and the average number of heterozygous loci per individual (6%-23%) in the three natural populations were found to be comparable to those found in most sexually reproducing organisms. Detailed analyses were made for one of these populations using five polymorphic loci. The results indicated that (1) seasonal changes in genotypic frequencies took place, (2) apomicitic parthenogenesis does not lead to genetic homogeneity, and (3) marked gametic disequilibrium at these five loci was present in the population, indicating that selection acted on coadapted groups of genes.


Testing for selective neutrality of electrophoretically detectable protein polymorphisms. The statistical assessment of gene-frequency data on protein polymorphisms in natural populations remains a contentious issue. Here we formulate a test of whether polymorphisms detected by electrophoresis are in accordance with the stepwise, or charge-state, model of mutation in finite populations in the absence of selection. First, estimates of the model parameters are derived by minimizing chi-square deviations of the observed frequencies of genotypes with alleles (0,1,2...) units apart from their theoretical expected values. Then the remaining deviation is tested under the null hypothesis of neutrality. The procedure was found to be conservative for false rejections in simulation data. We applied the test to Ayala and Tracey 's data on 27 allozymic loci in six populations of Drosophila willistoni . About one-quarter of polymorphic loci showed significant departure from the neutral theory predictions in virtually all populations. A further quarter showed significant departure in some populations. The remaining data showed an acceptable fit to the charge state model. A predominating mode of selection was selection against alleles associated with extreme electrophoretic mobilities. The advantageous properties and the difficulties of the procedure are discussed.


[Lethal and mutagenic photodynamic effect of acridine orange on bacteriophage cd]. Both acridine-sensitized inactivation and mutagenesis in phage sd have been studied and compared with the effect of other mutagens. Inactivation curve was not stictly exponential, with a small shoulder at short light doses and deviation of survival lower than 10(-5). The lethal effect was not reactivated by multiplicity reactivation. Photodynamic damage in phage sd was accompanied by the increase of the rise (but not of the latent) period in the one-step curve of phage multiplication and increase of the burst size. Experiments were carried out at dye concentration of 1-10(-5) M or lower; a strong dark effect of the dye being observed under 2-fold increase of the dye concentration. Plaque-type mutants were formed up to the maximum approximately 1% at the survival approximately 2--10(-5); in comparison with other mutagens photo-sensitized mutagenesis in phage sd was lower. The significant increase in the number of plaque mutants was observed after the illumination of phage fraction surviving the pre-treatment with higher acridine orange concentration (greater than or equal to 2-10(-5)M).


[Genetic characteristics of the "EEC" syndrome (ectrodactyly, ectodermal dysplasis, cheilognathopalatoschisis)]. The analysis of the literature and author's observations of the "EEC" syndrome (ectrodactyly, ectodermal dysplasia and cleft lip/palate) revealed that this is a disorder with an autosomal-dominant type of inheritance with an incomplete penetrance and varying expressivity. Both sexes are affected with the same frequency. The complete form of the syndrome was mentioned in 27 cases only; all other patients had incomplete forms. The combination of two out of 3 main features is enough for the diagnosis of this syndrome. The most common trait of the "EEC" syndrome is ectrodactyly (73/77), clefts of lip or palate were observed in 53 patients out of 77, the ectodermal dysplasia was mentioned in 44 cases. There is an increase of mutation frequency in older parents.


[Mechanism of action of antimutagens. I. ionol modification of aberrations induced by different factors]. The capacity of decreasing the frequency of chromosome aberrations, spontaneous and induced by ionizing radiation (gamma-rays) and alkylating compounds (ethylene imine) was established to be inherent in ionole (2,6-di-tretbutyl-4-methylphenole). Crepis capillaris was used as the experimental material. Ionole was particularly efficient with respect to aberrations induced by ethylene imine. The decrease of the frequency of spontaneous and induced aberrations did not affect their spectrum.


[Mechanism of action of antimutagens. II. Relationship between the antimutagenic effect of ionol and the stage of the mitotic cycle of Crepis capillaris L]. When a synchronous population of Crepis capillaris L. cells was used as the experimental material, the repair of spontaneous and induced aberrations by antimutagens was established to take place at the G1 stage. A definite period within this stage when the repair proceeds is discovered.


[Mutagenic effect of different types of irradiation on the sex cells of male mice. IX. Duration of preservation of radiation-induced reciprocal translocations during the course of the reproductive period]. The rate of induction of reciprocal translocations by gamma-irradiation of mouse spermatogonia was studied by cytological examination of descendent spermatocytes. The CBA mice were given a total single acute dose of 300 r or 3 times per 300 r with 7 and 28 days intervals. The irradiated mice were killed within 3,7 and 12 month after the irradiation. The frequency of translocations in 3 and 7 month after the treatment was the same. A 25% decrease in the yield of reciprocal translocations was observed in 12 months after the irradiation. It suggests that the genetic risk from ionizing radiation remains high a year after the irradiation.


[Mutagenic effect of different types of irradiation on the sex cells of male mice. X. Frequency of recessive lethal mutations and reciprocal translocations in the spermatogonia of mice subjected to fractional gamma-irradiation]. The frequency of recessive lethal mutations and reciprocal translocations was investigated in spermatogonia of CBA male mice which were thrice gamma-irradiated at doses of 300 r with 28 days intervals. The rate of induced recessive lethals was estimated 1) by comparison of embryos survival between the irradiated and control groups in mating of the F1 males with their daughters, and 2) by estimation the frequency of males heterozygotes for recessive lethals in the first generation. In the first case the frequency of recessive lethals was 2,8 +/- 0,8-10(-4) per r per gamete (for the pre- and post-implantation death) and 1,6 +/- 0,1-10(-4) per r per gamete (for the pre- and post-implantation death) and 1,6 +/- 0,1-10(-4) per r per gamete in the second case. The frequency of heterozygotes for reciprocal translocations in the first generations of males was 3,1 +/- 0,9-10(-5) per r per gamete.


[Relationship between genetic differentiation of the thymus in mice of different strains and malignant growth. IV. Genetic analysis of the thymic index in mice]. Relative thymus weight was estimated in C3H/He, C57BL/6 mice, their F1 and backcross hybrids, as well as in the progeny of complete diallel crosses between the BALB/c, C3H/He, C57BL/6 and AKR/J strains. On the basis of the analysis of these measurements, a conclusion is drawn that this character is inherited with incomplete dominance of smaller relative weight. The genes determining greater thymus weight are concentrated in the genetic pool of AKR/J and C57BL/6 strains. These genes are characterized by some degree of recessivity with respect to the genes determining smaller thymus weight which are concentrated in the genetic pool of C3H/He and BALB/c strains. The highest concentration of the "plus" and "minus" genes is found in the genetic pools of AKR/J and C3H/He strains respectively.


[Substrate of a UV-induced repair system providing for W-reactivation of lambda phage]. Escherichia coli uvrA, polA and uvrD cells carrying non-UV-inducible prophage lambdac1857ind- were infected with 3H-thymidine labelled homoimmune phage lambdac1857, and the effect of UV-irradiation of super-infecting phage and lysogenic bacterial cells on the content of intracellular covalently-closed lambda DNA circles (cccDNA) and pyrimidine dimer content in lambda DNA are studied. UV-irradiation of host cells results in two-fold increase of relative content of cccDNA of UV-irradiated phage lambda in uvrD mutant, while there is no such an effect in uvrA and polA mutants. In UV-irradiated or intact uvrA lysogens cccDNA molecules, forming after the infection with UV-irradiated phage lambda, contain pyrimidine dimers, but in uvrD mutant cccDNA in free of dimers. The data indicate that the repair system induced by UV-irradiation of uvrA and polA cells acts exclusively on the DNA defects appearing after (or in the course) of phage genomes replication. UV-inducible repair system in uvrD mutant can operate also on some intermediates of abortive excision repair, possibly on long single straided excision gaps.


[Genetic study of bacteriophage phi81. I. Isolation, study of complementation and preliminary mapping of amber-mutants of bacteriophage phi81]. 123 Amber mutants of lambdoid bacteriophage phi81 are isolated and distributed into 19 complementation groups. Deletion mapping made possible to locate 5 gene groups on the genetic map of bacteriophage phi81 and to determine a region of possible location of mm' sticky ends on the prophage genetic map. A gene of phage phi81 is localized, which controls the adsorption specificity, and which functional similarity to a respective gene of phage phi80 is demonstrated.


When primary cancer spreads to the skin. The lesions usually are asymptomatic, rapidly growing nodules that seem to crop up overnight. In most patients, the site is not far away from the primary tumor. For example, the metastatic seeds from breast carcinoma--the most common cause of secondary skin cancer--have an affinity for the anterior chest wall. An exception to this tendency toward localization is the scalp, which holds an odd attraction for implants from distant as well as nearby tumors. A high index of suspicion and an adequate biopsy are essential to diagnosis. The skin lesions can be puzzling when the primary tumor is silent or unrecognized. Tumors that masquerade as benign growths can allow a covert malignancy to remain undetected for a long time unless histologic sections are examined. Most secondary skin lesions do not require treatment. The exceptions are inflammatory, painful, or ulcerating neoplasms and relatively slow-growing tumors that yield to simple measures--i.e., surgical excision and/or radiotherapy. The psychologic value of treating symptom-free but highly noticeable lesions should also be considered.


Biofeedback training to overcome poststroke foot-drop. The technique has exciting potential for elderly hemiplegic patients, even those who are confined to a nursing home. There are limiting factors, of course; the method is time-consuming and the initial outlay for equipment is high. But the rewards can be well worth the time, effort, and cost involved. The recovery potential of some geriatric patients after a cerebrovascular accident may seem bleak because of multiple disabilities, e.g., paralysis, delayed reflexes, aphasia. Fortunately, these disorders do not necessarily decree failure of biofeedback training. Neither does advanced age. The strongest component in success is motivation. A case in point is the 82 year old woman described here who had been hemiparetic for seven years. With biofeedback training, she gained--and maintained--muscle strength.


Oral signs of aging and their clinical significance. A look in the patient's mouth can give clues to his overall health. For instance, atrophic glossitis--or breakdown of the tongue's papillary structure--reveals that there may be incomplete absorption of vitamin B complex or some other nutritional deficiency. Tenderness and impaired motion in the jaw can mean any of a number of problems related to other joints of the body. Osteoarthritis is often to blame. Or the disablement may be due to rheumatoid arthritis or to sclerosis of joint surfaces. Atrophy of the alveolar bone, which progresses slowly during normal aging, is speeded up in persons with osteoporosis. Even after all teeth are gone, bone loss continues. It's likely to be excessive and uneven, and the resultant sharp ridges and spicules sometimes cause so much pain and irritation that the patient can't tolerate dentures.


Important factors in rehabilitating the psychiatric patient. Family conflicts, retirement, bereavement, and isolation often precipitate emotional and physical decompensation in the elderly. Such stresses can cause a precipitous regression, and as the ego tries to master the intense anxiety, massive denial, hypochondriasis, projection, introjection, and helplessness can take over. Evaluation of an emotionally distraught patient with behavioral changes should include comprehensive assessment of medical, psychologic, and social problems. The physician should not be concerned only with physical disorders and ignore psychosocial data; neither should the psychiatrist focus on the psyche and disregard obvious somatic disorders. Treatment must be realistic, prompt, and energetic. Undertreatment for fear of drug toxicity, overtreatment by plying the patient with multiple drugs, and delay in treatment are equally destructive. Appropriate medication and group psycho-therapy are extremely useful, but the most important element of treatment is a doctor-patient relationship that supports and sustains hope in the distressed patient.


A look at Gerovital--the "youth" drug.

A look at Gerovital--the "youth" drug. The FDA is permitting controlled studies of the drug's possible antidepressant effects--but hasn't approved its use to "reverse" aging.


Arterial blood gas tensions during upper gastrointestinal endoscopy. Arterial blood gas tensions were measured before and during upper gastrointestinal endoscopy, with (group I) and without (group 2) sedation with intravenous diazepam. There was a highly significant fall in the PaO2, which occurred in both groups and was therefore not attributable to diazepam. Measurement of FEV, and FVC before endoscopy had no predictive value for those patients whose PaO2 fell the most.


Coeliac disease and dermatitis herpetiformis: further studies of their relationship. Using diagnostic criteria which are currently accepted as most reliable we have found that 19% (9/47) of patients with dermatitis herpetiformis (DH) have no evidence of coeliac disease. The incidence of HL-A8 in the DH patients was 78%, which is considerably greater than that in healthy controls and no different from that reported in coeliac disease. Furthermore, the incidence of HL-A8 was just as much increased in those DH patients without evidence of coeliac disease suggesting that HL-A8 is associated with DH per se--that is, regardless of its association with coeliac disease.


Complement fixing hepatitis B core antigen immune complexes in the liver of patients with HBs antigen positive chronic disease. One hundred and fifty-two biopsies from serologically HBsAg positive and negative patients with liver disease were studied in immunofluorescence: for the presence of the surface (HBs) and the core (HBc) antigenic determinants foeterminants of the hepatitis B virus, of immunoglobulins and complement (C) deposits, and for the capacity to fix human C. Circumstantial evidence is presented suggesting that HBc immune-complexes are a relevant feature in the establishment and progression of chronic HBSAg liver disease. C fixation by liver cells was shown in all HBC positive patients with chronic hepatitis; an active form was present in every case, except two with a persistent hepatitis, an inverse ratio of HBc to C binding fluorescence being noted between active chronic hepatitis and cirrhotic patients. HBc without C fixation was observed in only three patients in the incubation phase of infectious hepatitis. IgG deposits were often found in HBc containing, C fixing nuclei. No C binding or IgG deposits were observed in acute self-limited type B hepatitis, in serologically positive patients with normal liver or minimal histological lesions, with and without HBs cytoplasmic fluorescence in their biopsy, or in serologically negative individuals.


Study of an epidemic of venoocclusive disease in India. Twenty-five cases of rapidly developing ascites occurring in an epidemic form were observed in a tribal district in Central India during August 1972-May 1973. Eleven of the patients died. Six patients were brought to hospital and studied for periods of two to 17 months. Necropsy was performed on one patient who died. The clinical features suggested an outflow tract obstruction such as a Budd-Chiari-like syndrome or venoocclusive disease. Radiographic and haemodynamic studies demonstrated a combination of post and perisinusoidal blocks. Liver dysfunction was indicated by the presence of a marked bromsulphthalein retention and mild to moderate hypoalbuminaemia. Histological examination of the liver biopsies showed changes that ranged from centrizonal haemorrhagic necrosis to an extensive centrilobular fibrosis associated with central vein occlusion. The disease was apparently caused by a food toxin, and the possible nature of this is discussed.


Effect of portal-systemic anastomosis on renal haemodynamics in cirrhosis. In 12 patients with portal hypertension and repeated bleedings from oesophageal varices the central haemodynamics, portal pressure, and mean renal blood flow (RBF) were investigated immediately before and two  to seven months after portal-systemic shunt. Cardiac output increased significantly, whereas arterial pressure was unchanged after operation. RBF, which was initially less than in controls, did not change. As portal pressure decreased significantly, a direct portal-renal, neural, or humoral reflex mechanism does not explain the subnormal RBF in cirrhosis. As plasma volume was large and unchanged after operation a "diminished circulating plasma volume" is an unlikely explanation. Therefore, on the basis of the present observations, previously postulated causes of renal hypoperfusion in cirrhosis need revision.


Sulphated and unsulphated bile acids in serum, bile, and urine of patients with cholestasis. Samples of serum, bile, and urine were collected simultaneously from patients with cholestasis of varying aetiology and from patients with cirrhosis; their bile acid composition was determined by gas/liquid chromatography and mass spectrometry. In cholestasis, the patterns in all three body fluids differed consistently and strikingly. In serum, cholic acid was the major bile acid and most bile acids (greater than 93%) were unsulphated, whereas, in urine, chenodeoxycholic was the major bile acid, and the majority of bile acids (greater than 60%) were sulphated. Secondary bile acids were virtually absent in bile, serum, and urine. The total amount of bile acids excreted for 24 hours correlated highly with the concentration of serum bile acids; in patients with complete obstruction, urinary excretion averaged 71-6 mg/24 h. In cirrhotic patients, serum bile acids were less raised, and chenodeoxycholic acid was the predominant acid. In healthy controls, serum bile acids were consistently richer in chenodeoxycholic acid than biliary bile acids, and no bile acids were present in urine. No unusual monohydroxy bile acids were present in patients with primary biliary cirrhosis, but, in several patients, there was a considerable amount of hyocholic acid present in the urinary bile acids. The analyses of individual bile acids in serum and urine did not appear to provide helpful information in the differential diagnosis of cholestasis. Thus, in cholestasis, conjugation of chenodeoxycholic acid with sulphate becomes a major biochemical pathway, urine becomes a major route of bile acid excretion, and abnormal bile acids are formed.


Analysis of the effects of food and of digestive secretions on the small intestine of the rat. 1. Mucosal morphology and epithelial replacement. A modified Roux-en-Y repositioning of rat small intestine was performed so that the proximal segment of bowel (A) received only bile and pancreastic secretions, the second (B) received food direct from the stomach, and these two segments drained into a third (C). Four to five weeks after operation, cell production was assessed by injection of vincristine into operated, sham-operated and unoperated rats, and counts of blocked metaphases were made on isolated microdissected crypts. Villus height, crypt depth, and the number of crypts per villus (crypt/villus ratio) were also measured. Most of segment A showed no significant differences from sham-operated intestine, although the normal proximo-distal gradient of villus height was abolished. At the distal end (near the anastomosis with segments B and C), crypt depth and cell production were increased. The villus height gradient in segment B was also abolished, although crypt depth and cell production were significantly increased, especially at the proximal end. Crypt/villus ratio was also increased. Segment C showed all the characteristics of small bowel promoted to a more proximal position: increased villus height, crypt depth and cell production. Increased crypt/villus ratio was also observed. These results are discussed in terms of the role of food and of digestive secretions in the control of mucosal morphology and epithelial replacement.


Endemic tropical sprue in Rhodesia.

Endemic tropical sprue in Rhodesia. The existence of tropical sprue in Africa is controversial. In this paper we present 31 cases seen in Rhodesia over a 15 month period. They have the clinical features, small intestinal morphology, malabsorption pattern, and treatment response of tropical sprue. Other causes of malabsorption, and primary malnutrition, have been excluded. The severity of the clinical state and intestinal malabsorption distinguish these patients from those we have described with tropical enteropathy. The previous work on tropical sprue in Africa is reviewed and it is apparent that, when it has been adequately looked for, it has been found. It is clear that the question of tropical sprue in Africa must be re-examined and that it existence may have hitherto been concealed by the assumption that primary malnutrition is responsible for the high prevalence of deficiency states.


Tropical enteropathy in Rhodesia.

Tropical enteropathy in Rhodesia. Tropical enteropathy, which may be related to tropical sprue, has been described in many developing countries including parts of Africa. The jejunal changes of enteropathy are seen in Rhodesians of all social and racial categories. Xylose excretion, however, is related to socioeconomic status, but not race. Upper socioeconomic Africans and Europeans excrete significantly more xylose than lower socioeconomic Africans. Vitamin B12 and fat absorption are normal, suggesting predominant involvement of the proximal small intestine. Tropical enteropathy in Rhodesia is similar to that seen in Nigeria but is associated with less malabsorption than is found in the Caribbean, the Indian subcontinent, and South East Asia. The possible aetiological factors are discussed. It is postulated that the lighter exposure of upper class Africans and Europeans to repeated gastrointestinal infections may accound for their superior xylose absorption compared with Africans of low socioeconomic circumstances. It is further suggested that the milder enteropathy seen in Africa may be explained by a lower prevalence of acute gastroenteritis than in experienced elsewhere in the tropics.


Effect of paracetamol (acetaminophen) on gastric ionic fluxes and potential difference in man. Paracetamol has replaced aspirin as the analgesic of choice in many situations. The major reason is the damaging effect of aspirin on gastric mucosa. Alterations in gastric ionic fluxes and potential difference provide measures of aspirin-induced structural damage. We studied the effect of large doses of paracetamol (acetaminophen 2-0 g) on gastric ionic fluxes in man. In addition, the effect of 2-0 g paracetamol on gastric potential difference was compared with that of 600 mg aspirin. In contrast with salicylates, paracetamol caused no significant alteration in movement of H+ and Na+ ions over control periods. Aspirin causes a significant fall in transmucosal potential difference (PD) across gastric mucosa of 15 mv, while paracetamol cuased no significant change. Paracetamol in a dose four times that recommended does not alter gastric ionic fluxes or potential difference. These studies support choice of paracetamol as analgesic over aspirin where damage to gastric mucosa may be critical.


Histocompatibility antigens in inflammatory bowel disease. Their clinical significance and their association with arthropathy with special reference to HLA-B27 (W27). Histocompatibility (HLA) antigen phenotypes have been studied in 100 patients with ulcerative colitis, 100 with Crohn's disease, and 283 normal controls. In addition the incidence of ankylosing spondylitis, sacroiliitis, and "enteropathic" peripheral arthropathy was determined in the patients with inflammatory bowel disease (IBD). There was no significant difference in antigen frequency between patients and controls. However, the incidence of HLA-B27 was increased in the patients complicated by ankylosing spondylitis and/or sacroiliitis in both ulcerative colitis and Crohn's disease. In contrast, none of the 29 IBD patients with "enteropathic" peripheral arthropathy had B27 antigen. Furthermore, ankylosing spondylitis was found more frequently in ulcerative colitis bearing HLA-B27 compared with non-B27 patients (P less than 0-01). The same was found in Crohn's disease, although this difference was not statistically significant. In addition, 12 of 14 ulcerative colitis patients and five out of six Crohn's patients with HLA-B27 had total colitis, compared with the frequency of total colitis in non-B27 patients (P less than 0-024 and less than 0-03 respectively). The data suggest that B27 histocompatibility antigen could be a pathogenetic discriminator between the  arthropathies in IBD and may be of prognostic significance with respect to extension and severity of the disease.


Steroid-protein binding: from circulating blood to target cell nucleus. The concept of protein binding of steroid hormones is traced from its origins through the period of confirmation and initial extension. Further considerations include cell surface recognition sites, subcellular sources of binding protein, and the new evidence that lysosomes participate in the translocation and intranuclear penetration of the hormone in steroid target cells. This short review thus aims to provide a link between current investigations and the ideas upon which they have been based.


An analysis of the mechanisms of egg transport in the ampulla of the rabbit oviduct. Ampullary transport of supravitally stained cumulus egg masses was studied in intact oviducts of anesthetized rabbits whose abdomens had been opened for observation. Following observations of normal transport, muscular activity of the ampulla was inhibited pharmacologically with Acepromazine, a preanesthetic tranquilizer. With muscle contractions blocked, egg transport continued but in a dramatically altered fashion; in the final two thirds of the ampulla the motion changed from rapid to-and-fro movements to a slow uniform prouterine movement which was attributed to ciliary activity. However, the net velocity of transport did not change when the smooth muscle was inhibited indicating that muscle contractions are at least unnecessary and perhaps ineffective for ampullary egg transport in the rabbit.


Induction of a labile chicken plasma coagulation factor by choline: dose-response relations, specificity, and effects of protein synthesis inhibitors. Minimum oral doses of 21.5 mg/kg choline chloride were required for induction of maximum plasma level of the choline-dependent component (pi-factor) of of the labile factor activity complex in chickens on a choline-deficient diet. Several derivatives and potential precursors of choline were inactive as substitutes for the free base. After intravenous injections of optimal doses of choline, an initial lag of about 8 min was followed by a linear increase in pi-factor level reaching the maximum level about 31 min after the injection. The response was blocked and arrested by simultaneous and delayed injections, respectively, of puromycin and cycloheximide. After intravenous injections of actinomycin D, the response of choline was unaffected by a delay of up to 40 min, but completely abolished by a further delay of 90 min or more. The data suggest that the plasma level of pi-factor is goverened by the supply of choline by regulation of a pre-translational step in the biosynthesis of pi-factor.


Sonography: a method for localization of hematomas in hemophiliacs. Sonography was used to visualize hematomas in hemophilic patients. The method is especially helpful for the diagnosis of psoas hematoma and retroperitoneal hematoma and allows the follow-up of hematomas of the cervical region and muscle hematomas. The method is simple, rapid, painless and has no known adverse effects.


Pretreatment with heparin in thrombolytic therapy with Urokinase. Heparin-urokinase therapy. Initially, we administered urokinase to five patients according to the following schedule: 500,000 CTA U during the first 10 min, then 250,000 CTA U/h for 12 h. Using this modality, we noted the appearance, during the first hours of treatment, of hypercoagulability. We then choose to modify the schedule by pretreatment with 7,500 U. i.v. of heparin, followed promptly by 250,000 CTA U/h of urokinase (without a loading dose). This obviate the appearance of hypercoagulability without reducing the fibrinolytic effect of treatment and without producing hemorrhagic complications.


Platelet-collagen interaction. The influence of native and modified collagen (Type I) on the aggregation of human platelets. Type I collagen from calf skin, collagen modified by pepsin treatment, methylation, succinylation or deamidation, as well as the alpha-chains and cyanogen bromide peptides of the alpha1-chain were investigated with respect to their capacity to induce aggregation of human platelets. These preparations permitted an evaluation of the efficacy of the amino acid sequence, triple conformation,and various fibrillar structures in platelet aggregation. All collagens in dissolved in dissolved form (collagen dissolved at acid pH, pepsin-treated, methylated, deamidated, and succinylated collagen) induced platelet aggregation only after fibril formation. The arrangement of molecules within fibrils is of secondary importance. Modification of the side chains of amino acid residues affects primarily the formation of fibrils. The effect of these side chains on platelet aggregation is masked by the overwhelming potency of the fibrillar forms.


Factor-VIII-related antigen and cold-insoluble globulin in leukemias and carcinomas. An elevated plasma level of the factor-VIII-related antigen is not specific for leukemias and malignancies but is also observed in inflammations and in rheumatic diseases. As a reason for this nonspecific change an increased tissue breakdown has to be considered as well as an impaired elimination of the protein, possibly in some cases in the course of a consumption coagulopathy. The plasma levels of the cold-insoluble globulin were reduced in chronic lymphatic leukemias and in acute inflammations, but elevated in rheumatic diseases. Production and liberation of the cold-insoluble globulin may not only be changed by malignant transformation of cells but also by inflammatory and infectious processes.


Rat liver macrophages will not phagocytose fibrin during disseminated intravascular coagulation. Disseminated intravascular coagulation was induced in rats by injection of a silver colloid suspension or thrombin. Ten min after the injection of colloid, fibrin deposits were observed light microscopically in all major organs. At 30 min, fibrin was no longer present. In rats treated with antifibrinolytics (epsilon-aminocaproic acid or Trasylol) fibrin was still present at 30 and 60 min. Interaction of fibrin with Kupffer cells was studied by electron microscopy. At 3, 10, and 20 min after the colloid injection, all fibrin occurred extracellularly, close to the surface of Kupffer cells. At 30 min, all fibrin had disappeared. In rats pretreated with antifibrinolytics, too, all fibrin was found extracellularly at 10, 30, and 60 min. Comparable results were obtained when thrombin was used to induce coagulation. It is concluded that removal of native fibrin from the circulation by Kupffer-cell phagocytosis is unlikely.


Binding of 14C-ADP by thrombasthenic platelet membranes. We have measured the binding of 14C-ADP to isolated human platelet membranes by a technique using 0.8-mum Millipore filters to separate unbound tracer from membrane-bound nucleotide. The binding was dependent on the time of incubation and on the nucleotide concentration in the medium. The affinity constant was found to be comprised between 0.35 x 10(6) and 0.55 x 10 (6) M-1. Platelet membranes prepared from different thrombasthenic patients bound 14C-ADP with the same kinetic parameters as those from normal subjects. The affinity constant as determined for two of these thrombasthenic platelet membrane preparations was in the normal range.


Dose-dependent influence of acetylsalicyclic acid on platelet functions and plasmatic coagulation factors. Lysine salt of acetylsalicylic acid (ASA) was given to ten patients by intravenous infusion. Blood samples taken at intervals during the infusion permitted the examination of the influence of the dose of ASA on platelet functions. Aggregation was significantly reduced when 50 mg ASA had entered circulation, while a diminution of PF3 and PF4 availability could only be demonstrated when the dose had reached 500 and 200 mg, respectively. In order to exclude a longer latency time for the diminution of PF3 and pf4 availability, a second series of ten patients received intravenous injections of 100 and 300 mg ASA, respectively. From these patients, blood was taken 1 h after the injection. The decrease of PF3 and PF4 availability in these cases was comparable to the results of the first group. In a third series of patients, a daily intravenous dose of 2,000 mg ASA was given. In these cases, a moderate decrease of factors II, VII, IX and X was observed. Since the appearance of a PIVKA effect could also be demonstrated, vitamin K antagonism was assumed when a high dose of AS


Combined administration of low dose heparin and aspirin as prophylaxis of deep vein thrombosis after hip joint surgery. The study was carried out on 75 patients undergoing hip joint surgery. The efficacy of a prophylaxis of deep vein thrombosis (DVT) by acetylsalicyclic lysine (ASL) and by a low dose heparin (LDH) combined with the ASL treatment was investigated using the 125I-fibrinogen test. DVT was not significantly decreased by the ASL application (53%) compared to the controls (60%). DVT occurred significantly less under the combined administration (27%) than in the other two groups.


Changes in coagulation factors following acute myocardial infarction in man. The whole blood clotting time, plasma fibrinogen and individual coagulation factors II, V, VII, VIII, IX, X, XI, and XII were serially measured in 14 patients over a 10-day period following acute myocardial infarction. A further six patients with similar symptoms but without evidence of myocardial infarction were also studied. The whole blood clotting time was significantly shorter within the first 24 h after infarction than on subsequent days. There were significant increases in the levels of fibrinogen and of factors VIII, IX, and XI and a significant decrease in factor XII in the patients who had sustained a myocardial infarction. The patients without myocardial infarction had no significant change in any of the coagulation factors measured.


Surgical treatment of fractures of the scapula in the dog and cat. As osteosynthesis of fractures ofthe scapula in the dog and cat have so far been almost completely ignored, personally observed cases are reported including 14 treated by osteosynthesis and one by ostectomy.


The quantitative analysis of glass by atomic absorption spectroscopy. An analytical procedure for the determination of manganese and magnesium in glass fragments of approximately 1 mg has been developed. The concentrations of these elements in glass are shown to have some potential value for classification and discrimination of glass.


Dilution of blood in fresh water drowning. Post-mortem determination of osmolarity and electrolytes in blood, cerebrospinal fluid and vitreous humor. In an attempt to detect signs of dilution of blood 38 autopsy cases of drowning in fresh water and 35 cases with other causes of death were investigated. Osmolarity and sodium and potassium concentrations were determined in serum from the right and left sides of the heart, cerebrospinal fluiid and vitreous humor...


[Use of seat belts by pregnant women].

[Use of seat belts by pregnant women]. There are almost no pregnant women who never use a motorcar. The safety in crashes is diminished by mistakes in contruction and handling of the safety-equipment. Only every fourth woman can be regarded as properly protected. It should be the task of the physician to instruct his pregnant patients in the use of the seat belt.


Notes on epidemiology of homicide in an urban area. Over the past 30 years, there was a slow but steady increase of the homicide rate in the United States. The increase was faster in the urban areas. In St. Louis, Missouri, the rate had increased from 7/100 000 in 1943 to 33/100 000 in 1973. The development of meaningful preventive measures depends upon repeated epidemiologic investigations to determine the changes in patterns of crime to see if our approach to the problem is still adequate to meet the need. The police records of 214 homicide victims in the city of St. Louis during 1973 were examined. Mean age of the victims was 35 years. Eighty-five per cent of them were men and 81% were black. There are 2 distinctly different profiles of homicide victims, "younger" under 30 years old, and "older" 30 years old and over. "Young" victims had a mean age of 21 years. They were more likely to be black, killed after an argument over money or property, or while committing a crime, and killed by a gun. There were more black victims killed by other blacks and the murderer was usually older (mean age 26 years). These homicides were less frequently victim-precipitated, killed by a relative or friend, or while drinking. "Older" victims had a mean age of 49 years. Among them there were more whites, more victim-precipitated and more victims drank prior to their death, while the murderer was usually younger (mean age 35 years).


[Alcohol and pregnancy. Negative and positive effects of acute and chronic effect of alcohol on the course and outcome of pregnancy]. The attitude towards alcohol is ambiguous and mainly depending upon the role attributed to it:as a stimulant, as a pharmacon or as a drug the person may be addicted to. Acute and chronic alcohol intoxication may be followed by psychic and somatic leasons. As far as pregnancy is concerned, leasons due to chronic alcohol consume have to be considered as maternal factors of high risk to the pregnancy. Acute alcohol intoxication may be harmful for the pregnancy as well as gametogenesis and gametes and embryo. Alcohol has been used in obstetrics as an analgetic during delivery, for premedication in obstetrical operations, for elimination of edema in toxicosis, as an abortifacient and as adjuvant in termination of lactation. Critical evaluation shows that these indications are only of historical value. Today more effective and specific compounds are available and as for the narcotic effect is concerned the dosage of the new narcotics of course is more exact. Alcohol recently has been proposed as a tocolytic agent. Although today other tocolytics are available, it should be kept in mind as a substitute if the use of beta-mimetic substances is not possible. The controversy about the value of alcohol in therapy or prevention of newborn hyperbilirubinaemie is not yet resolved, but should be clarified since this therapy--if of value--would constitute one of the rare possibilities to interfere with the fetal metabolism.


Statistical assessment of the value of numerical evidence. Statistical parameter V measuring the value of numerical evidence was introduced. It is a decisional parameter and it changes between 0 and 1. Its definition takes into account statistical properties of the general population and sources investigated, as well as the operating characteristic function of the test used. It was concluded that the value of evidence increases contrary to the value of the quotient of determinants of variance--covariance matrices of the source population and general population. A method was developed to choose attributes of the investigated material to satisfy best possible results of the identification.


[Course observation after intra-amniotic administration of lecithin in premature cesarean section]. A report of a 36 year old patient is given who was hospitalized because of an erythroblastosis. An indicated sectio caesarea resulted in an intraamnial application of lecithine for preventing a respiratory distress syndrome. It can be concluded by the measured lecithin-concentration that a high phospholipid-level in the amniotic fluid leads to an increased resorption by the fetus. Postpartal investigations showed a completely normal lung function in the newborne.


Isolated rat hepatocytes as an experimental tool in the study of cell injury. Effect of anoxia. Rat hepatocytes were isolated by liver perfusion in the presence of collagenase and hyaluronidase and incubated in the absence or presence of oxygen. As a result of anoxia, there was a gradual increase in plasma membrane permeability, noted as an increase in succinate-stimulated oxygen uptake, a decrease in trypan blue exclusion frequency, a leakage of cytosolic lactate dehydrogenase activity and an increased proportion of swollen and disrupted cells. After anaerobic incubation for 30 minutes--but not for 60 minutes--there were signs of recovery from anoxic cell injury upon re-oxygenation. The changes in plasma membrane permeability properties in anoxia seemed to be preceded by a marked decrease in cellular ATP level; aerobic incubation of hepatocytes in the presence of an uncoupler of phosphorylation from respiration led to a similar decrease in cellular ATP concentration followed by similar disturbances in plasma membrane permeability properties. It is suggested that a distrubed plasma membrane function caused by a decreased energy level is of primary importance for the initiation of cell death in anoxia.


[Psycho- and somatoneuroses in comparison : anxiety neurosis/phobia--bronchial asthma. Psychosomatic inquiry study]. In order to answer the question of whether an interrater's stable facts make it possible to differentiate between neurosis, 50 psychosomatics (asthamatics) were compared with 50 psychosomatics (asthmatics) were compared with 50 psychoneurotics including 25 cases of anxiety neurotics and 25 phobics. The age at the time the patient became ill, the age at the time of the scientific investigation, length of illness, psycho- and psychosomatic pre-illnesses, former hospitalizations, primordial and accompanying symptoms, social facts, types of the conflict situation which triggered the illness and the results of intelligent tests were correlated with the main variabilities: neurosis, sex, character structure and tests for statistical significance: psycho and psychosomatic neurosis as well as anxiety neurosis and phobia are different from one another in numberous variabilities.