Persistent vaginal cornification in mice treated with estrogen prenatally. Twelve of 14 female mice of the ICR strain which had received a single injection of 50 mug estradiol-17beta on day 17 of fetal life exhibited irreversible cornification or stratification of the vaginal epithelium which persisted after ovariectomy until sacrifice performed 42-48 days later. Eight of the 12 mice had corpora lutea in their ovaries removed at 3-5 months of age. A similar injection of estradiol on day 15 of fetal life induced irreversible cornification or stratification of the vaginal epithelium in 6 of 12 females and only one of the 6 had corpora lutea in its ovaries when removed at 3-5 months. Mice given the same dose of estradiol on the day of birth or at 3 days of postnatal age invariably had ovaries bearing follicles of varying sizes and hypertrophied interstitial tissue but no corpora lutea. Changes in the vaginal epithelium in these animals were less remarkable as compared to that in prenatally treated mice.


Boiling method for the extraction of gut glucagon-like immunoreactive materials. The boiling method deviced in accordance with the extraction procedure of secretin was applied to the extraction of gut glucagon-like immunoreactive material (GLI) and compared with the acid alcohol method of Kenny with respect to efficiency of the extraction and property of the extracted materials. GLI was extracted from minced porcine small intestine by each method. The total amount of GLI extracted by the boiling method was 14.45+/-2.07 mug/10g small intestine (mean+/-SE), showing a high yield as compared to 4.07+/-0.29 mug/10 g small intestine obtained by the acid alcohol method. The difference was statistically significant (p less than 0.005). The gel chromatogram of the acid alcohol extract was separated into two peaks; peak 1 appeared before the the insulin marker, while peak II was eluted with the glucagon marker. The chromatogram of the boiling extract has a main broad fraction including insulin marker and a minor second peak corresponding to peak II of the acid alcohol extract. Boiling of the acid alcohol extract did not cause any shift of peak I in chromatogram. GLI present in the first half of the main fraction of the boiling extract was different from that in the latter half, but identical to peak I of the acid alcohol extract with respect to the immunoreactivity against glucagon antibody. It is concluded that in the extraction of GLI not only high yield is achieved but one or more new components is picked up by the boiling procedure as compared to the acid alcohol method.


Effects of glucosamine on insulin and glucagon secretion in dogs and ducks. The effects of infusion of glucosamine on immunoreactive glucagon (IRG) and insulin (IRI) secretion were studied in dogs and ducks. During systemic infusion of glucosamine, hyperglycemia developed and insulin secretion was inhibited in both species. An immediate and sustained elevation of peripheral IRG levels was induced in ducks but a transient rise, detectable only in the pancreatic vein blood, was provoked in dogs. Suppression of insulin release and stimulation of glucagon release may be mediated by the inhibition of glucose utilization in beta- and alpha-cells. The very prompt response of IRG in ducks may imply that glucosamine has a specific stimulating effect on the alpha-cells of ducks. Intrapancreatic administration of glucosamine in dogs, however, failed to elicit the rise of IRG, although insulin secretion was inhibited. Thus, it is suggested that the systemic administration of glucosamine in dogs may stimulate IRG secretion by some indirect effect. In one dog, however, a sustained rise of the pancreatic vein IRG was observed. Thus, the possibility cannot be ruled out that the difference in IRG response to glucosamine in dogs and ducks is quantitative rather than qualitative. Glucagon release by glucosamine may provide an additional factor to the hyperglycemic effect of glucosamine, in addition to its effect to suppress insulin release as well as its direct inhibitory effect on glucose utilization in tissues.


Decidualization in rats given 5alpha-dihydrotestosterone or its propionate neonatally. In Experiment 1, female rats were given a single subcutaneous injection of 1.25 mg 5alpha-dihydrotestosterone (DHT) or its propionate (DHTP) on day 5 of postnatal life. All of them showed regular estrous cycles as adults like untreated control animals. At about 60 days of age, the rats were ovariectomized and given 7 daily injections of 2 mg progesterone (P) plus 0.2 mug estradiol-17beta (ED). Uterine trauma applied on the 4th day of P-ED injections resulted in well developed deciduomata in all animals by the day after the last injection. This made a sharp contrast to the failure of female rats receiving testosterone propionate (TP) neonatally to give a positive response under similar experimental conditions (Takewaki and Ohta, 1974). The mean weight of traumatized horns was significantly larger in DHTP-treated rats (but not in DHT-treated rats) than in controls. In Experiment 2, rats were ovariectomized on day 4 and given a dose of 1.25 mg DHT or DHTP on day 5. Controls were ovariectomized on day 4 but not given any steroid on the next day. A series of 7 daily injections of 2 mg P plus 0.2 mug ED was started at about 60 days of age, after the animals had received 3 daily injections of 0.2 mug ED or 30 daily injections of 0.1 mug ED. Incidence of deciduomata following uterine traumatization was markedly lowered only in animals treated with DHTP neonatally and given 0.1 mug ED for 30 days as adults, no significant differences being found in both incidence and size of deciduomata among the other groups. It was suggested that the effects of neonatal steroid administration on uterine responsiveness in adulthood are specific to the steroid. The previous conclusion that persistent estrus in androgen-sterilized rats plays a part in the reduction of uterine responsiveness was confirmed. An exposure of rats to estrogen for a prolonged postpuberal period was without effect, unless the animals had received enough androgen neonatally.


LH discharge induced by medial preoptic implantation of estrone or dopamine in the ovariectomized estradiol primed rat. Effect of implantation of estrogens or catecholamines into the medial preoptic area through chronically implanted double cannula on the release of LH was examined in the ovariectomized estradiol-primed rat. Implantation of estrone at 12:00 on the second or third day after subcutaneous injection of estradiol benzoate (20 mug) increased the serum concentration of LH at 18:00 compared with that in the non-implanted controls, whereas implantation of estradiol benzoate on the third day did not affect it. Dopamine implantation at 12:00 on the third day also induced a significant increase of LH concentration at 18:00, and, in contrast, norepinephrine implantation decreased the concentration at 18:00. It may be said that the medial preoptic area is responsive to estrone and can induce LH release, whereas it is not to estradiol. Furthermore, dopamine was effective for the activation of the medial preoptic area in relation to the inducement of LH release.


A hexapeptide angiotensin antagonist, Des-(Asp1, Arg2), Ile8)-angiotensin II. In the smallest biologically active fragment of angiotensin or a 3-8 hexapeptide the C-terminal was substituted by isoleucine residue. It proved to be the smallest potent antagonist of angiotensin II so far reported.


Insulin transport by thoracic duct of male rabbits with CCI4-induced liver cirrhosis. Insulin concentration in the peripheral blood and the thoracic duct lymph from male rabbits with CCl4-induced liver cirrhosis was measured using a radioimmunoassay technique. Although insulin concentration in the lymph was lower in the cirrhotic animals than in the control ones, the hourly transport of the hormone by the lymphatic vessel of the cirrhotic animals markedly increased in company with the higher flow rate of the lymph.


Suppression of serum growth hormone levels by glucagon in patients with active acromegaly. One mg of glucagon was given subcutaneously to eight patients with active acromegaly. Seven out of eight patients had a rapid decrease in serum growth hormone (GH) levels at 30 min after the glucagon injection. In two out of seven patients a rebound increase in serum GH following the early GH reduction was observed. On the other hand, oral administration of 50 g glucose which caused a comparable increase in blood glucose to that after the glucagon injection elicited no early suppression in serum GH levels in the same patients. These data suggest that the inhibition of GH release induced by glucagon could not be related to the increase in blood glucose by glucagon.


Nutrition and national development planning. We have argued that development strategies aimed at the reduction of all forms of deprivation, according to an explict statement of values and priorities, are necessary for the integration of nutrition planning into overall national development planning. We do not regard this as likely to lead to the neglect of the key issues of investment and production. Instead, we argue that consideration of investment and production strategies should be explicitly directed to their purpose, the reduction of deprivation, rather than, as in the past, treated as the necessary means to that purpose. Thus investment and production strategies would be aimed directly at relieving deprivation including, especially, nutritional deprivation, and their impact in this respect will need to be explicitly predicted and evaluated. We have argued that problems and potentials differ greatly at the area level and that planning must be an iterative process in which national and area-level strategies and programmes are brought to consistency through successive cycles of adjustment and reappraisal. A major role in planning, especially in detailed design and implementation, is assigned to area level. Planning must proceed from an identification of the deprivations under attack to the identification of intervention measures. Elsewhere we have argued the case for the 'functional classification" of malnutrition and the use of "typical profiles" in the understanding of "the ecology and etiology of malnutition". Where planning accepts the need for an integrated approach to the attack on all forms of deprivation, these analyses of nutritional deprivation would from part of a more comprehensive analysis of general deprivation. The existence of "functional classification" and "typical profiles" analysis with respect to malnutrition would provide an excellent base from which a more comprehensive view might be developed. The factors affecting the evolution of nutritional - and other - deprivation problems need to be understood in order that we can identify points in the system where intervention may control theri emergence. In any situation there will be alternative intervention points bearing either directly on the alleviation of symptoms (malnutrition) or, more or less indirectly, on the control of its causes. In general, mixed strategies will be called for. At this stage in our understanding no generalizations are possible about the nature of strategy choices. Our choice of intervention measures must be based upon an understanding of the overall system as it generates malnutrition, and of which forces exert the most powerful effects. One important element of this analysis will be an understanding of the behaviour of the malnourished. However, conventional planning approaches, in which ministries and departments concern themselves only with problems and measures which conform to the definition of their own spheres of responsibility, have failed to define these choices effectively...


The healing of myocardial infarcts in man. One hundred and fifty hearts of patients who died within 25 days of the onset of a clinically proven myocardial infarct were examined. Three morphologically distinct forms of myocardial necrosis were recognized. In the central and median zones of an infarct the muscle showed coagulation necrosis. Subsequently the dead tissue was obsorbed by macrophages with the preservation of sarcolemmal sheaths. Then fibroblastic collagenization of the preserved stroma occurred. Repair was not achieved by granulation tissue. Coagulative myocytolysis occurred in the outer zone of an infarct and in the non-infarcted myocardium. The dead cells were acidophilic and showed myofibrillary damage characterized by anomalous cytoplasmic band formation. Breakdown of the fibres was followed by macrophage absorption and healing as in the central area of coagulation necrosis. Colliquative myocytolysis was seen in big infarcts. It affected a narrow band of myocardial cells in the subendocardial zone or surrounding blood vessels. The fibres became oedematous and seemed to liquefy.


[Surgical treatment of cardiac abnormalities associated with corrected transposition of the great arteries (author's transl)]. Twelve patients with corrected transposition of the great arteries, who underwent surgical repair, are reported. In four cases a ventricular septal defect was present; in six cases, a ventricular septal defect and pulmonary stenosis and in two an incompetence of the systemic atrio-ventricular valve. The anatomic types of corrected transposition and the pertinent diagnostic characteristics were reviewed and discussed. The problems related to the surgical correction and the different approaches to the intracardiac lesions are considered and the difficulties of treating the obstruction of the venous ventricle successfully are emphasized.


[Recent advances in the hormonal treatment of sterility (author's transl)]. The present trends in the utilization of hormones in the treatment of sterility are reviewed, special reference being made to the utilization of gonadotrophins, hypothalamic hormones and gonadal hormones as well as other substances (clomiphene, epimestrol, cyclophenyl) that are also utilized in this type of treatments.


[Functional block in the His-Purkinje system (author's transl)]. In nine patients without clinical or laboratory evidence of heart disease, premature atrial depolarization (PAB) induced a complete block of conduction in the intraventricular conducting system. In these patients the functional refractory period AV (FRPav)) gave short and very similar results to the effective refractory period of the His-Purkinje system (ERPhp), and the effective refractory period AV (ERPAV) was found to be shorter than the ERPhp in all cases. A linear correlation between the ERPhp and the basic cycle length (BCL) was also observed. These special functional properties of the AV node justify the occurrence of intraventricular block after PAB. In fact, the stimulus, rapidly conducted through the AV node, finds a complete or incomplete refractoriness in the ventricular conducting system, and therefore bundle branch or complete intraventricular block occurs. The linear correlation between the ERPHP and the BCL explains why the atrial pacing is not always useful for pointing out intraventricular conducting defects.


Radioimmunoassay of norethindrone (17 alpha-ethynyl-17 beta-hydroxy-4-estren-3-one) and ethynyl-estradiol (17 alpha-ethynyl-1,3,5, (10)-estratien-3, 17 beta-diol). Application to human plasma determination of norethindrone after oral administration of this steroid. The experiment conditions for the evaluation of Norethindrone (17 alpha-Ethynyl-17 beta-hydroxy-4-estren-3-one, NET) and Ethynyl-estradiol (17 alpha-ethynyl-1, 3, 5 (10) estratrien-3, 17 beta-diol, EE) by radioimmunoassay are described. A minimal quantity of 25 pg of these two steroids could be evaluated using different reduced metabolites of NET, very little cross reaction is observed with 200 pg of these metabolites. No effect was observed with estradiol for the EE-antiserum. The NET-antiserum was used to evaluate this steroid and ethynodiol diacetate after oral administration to female volunteers. Maximal values in the plasma (2-3% of the administered dose) was found between 1-3 h after administration and at 24 h a concentration of 0.1-0.3% still remained in the plasma.


[Cytological changes in hypophysis of immatur rats after administration of anti-LH antibodies (author's transl)]. In the present work, cytological changes produced in rats' pars distalis were studied by administration of anti-LH antibodies. The anti-LH sera was obtained by active immunization of adult rabbits using bovine LH hormone with Freund's complete adjuvant. Newborn albino Wistar male and female rats were daily and subcutaneously inoculated with 0.1 ml. to 0.8 ml of anti-LH sera from the first 24 hr. on during 5 weeks. For controls, a similar schedule of inoculations with normal rabbit serum was used. At weekly intervals during the treatment, 5 lots of rats were sacrificed and the rest after a recovery period of 95 days. At the end of the 2nd week of immunization, both male and female animals showed degranulated gonadotroph cells in the central part of the pars distalis; at the 3rd week these cells were hypertrophied and presented developed Golgi complex. At the 4th week, the first large vacuoles of "castration" were seen in the gonadotroph cells of male pars distalis, besides in the females the degranulation of gonadotrophs continued. During the last week of treatment, the gonadotrophs of the male animals presented a highly dilated Golgi complex, more "castration-like cells" and numerous mitosis figures. The gonadotrophs of females pars distalis presented degranulation, but not vacuoles. After the recovery period the gonadotrophs of male rats were similar to those of the control hypophisis and did not show castration vacuoles in their cytoplasm. In female rats, the gonadotrophic cells showed "castration-like vacuoles" and a raised number of mitosis cells compared to control pituitaries. The significance of these findings will be discussed.


[Electronmicroscopical aspects of endometrial distrophy induced by oral contraceptives (author's transl)]. An electron-optical study on the endometrium of 5 controls and 25 patients subjected during 3-12 months to 0.25 mg norgestrel + 0.05 mg etinil-estradiol association treatment is performed. The most prominent electronmicroscopical features of endometrial changes are described, such as the asynchronical maturation of the epithelium and the stroma, the shorthening of the proliferative and secretory phases and the epithelial involution towards the last days of the cycle. Special emphasis is placed on the zonal distribution of these changes. An increase of the nostocitosis phenomena is reported and its significance as a complementary contraceptive mechanism is discussed.


[Short and long term prognosis of intraventricular conduction disturbances in myocardial infarction (author's transl)]. Intraventricular conduction disturbances (IVD) were found in 181 (21,9%) out of 828 patients with acute myocardial infarction. Isolated RBBB was present in 6,3% of cases; both RBBB and LAH or LPH in 3,4%; isolated LAH in 5,8%; LBBB in 3%; suspect blocks of the three brances [RBBB+LAH+first degree atrio-ventricular block (AVB), or LBBB+first degree AVB] in 2,9% of cases. The severe mortality (41%) during hospitalisation of patients with IVB seems to be due to the haemodynamic impairement: cardiogrnic shock was observed in 20% of these patiens and acute pulmonary oedema in 18%. Transient or permanent complete AVB occurred during hospitalisation in 24,3% of these patients. The occurrence of complete AVB was higher (54%) in patients in whom suspect block of three branches was present. It was found that the progression of IVD to complete AVB increased the mortality rate to 48%. The short term prognosis of patients with IVD does not seem to be improved by prophilactic electrical stimulation, but the rate of deaths for asystolia is reduced. The mortality rate after one year of patients discharged from hospital was 25%; suspect three branches IVD died suddenly and 2 progressed to complete AVB. In the author's opinion the implantation of permanent electrical stimulation is indicated in patients showing IVD of the three branches assessed using His bundle electrgram during the acute phase of myocardial infarction.


[Prognostic significance of the intraventricular blocks during acute myocardial infarction (author's transl)]. An intraventricular conduction defect complicated 39 out of 489 cases of acute myocardial infarctions. The defect, with the exception of one case, always developed in infarctions in the anterior wall of the heart. Compared with the other acute anterior myocardial infarctions in which the mortality in the Coronary Care Unit was 15%, infarctions complicated by intraventricular conduction defects have on the whole, presented a worse clinical course and a higher mortality rate (56%). It must be stressed that clinical course and mortality rate have been very different in the various conduction defects. The most innocuous conduction defects were the left anterior hemiblock, and, with some reservation, the right bundle branch block too, -- defects in which the clinical course and the mortality rate were not significantly different from those of the other anterior myocardial infarctions not complicated by intraventricular conduction troubles. On the contrary clinical course was more serious and mortality rate higher (50%) in the cases in which the two defects were associated. Myocardial infarctions complicated by left bundle branch block, right bundle branch block with left posterior hemiblock, alternating bundle branch block or 1 degrees and 2 degrees atrioventricular block and bundle branch block, presented an extremely serious clinical course and a very high mortality rate (83%). These differences in the clinical course and in the mortality rate of the various intraventricular conduction defects are explained by the fact that they are associated with myocardial damage of different degree, which is clarified by knowledge of the blood supply of the intraventricular conduction system.


[Phono-mechanographic aspects in parietal blocks of left ventricle (author's transl)]. 20 subjects with parietal ventricular block, detected by Frank vectoracardiogram, were submitted to phono-mechanographic examination. Prolongation of PEP was shown; the second period of electromechanical interval (A-C interval in apex-cardiogram) was given in detail. Isovolumetric contraction, systolic ejection time and diastolic period were normal. This pattern is quite typical for parietal block and completely differs from bundle blocks and cardiomyopathies. Therefore it may be useful in differntial diagnosis of these kinds of conduction disturbances as well.


[Electrophysiological bases of the antiarrhythmic activity of amiodarone (author's transl)]. The electrophysiological effects of orally administered Amiodarone (600 mg daily for 8 days) were evaluated using His bundle electrograms, the extrastimulus method and atrial pacing in 16 patients with proved ischemic heart disease. Our results show that Amiodarone: 1) does not affect sinus node activity; 2) considerably prolongs the refractory periods of the atrium; 3) slightly and inconsistently prolongs the refractory periods of the atrio-ventricular node and the intraventricular conduction system; 4) slightly decreases the atrio-ventricular conduction; 5) does not consistently depress the intraventricular conduction. These properties contribute to the explanation of the antiarrhythmic effects of the drug.


[Evaluation of cardiac performace in 222 patients with pulmonary sarcoidosis (author's transl)]. Electrocardiogram at rest, blood pressure, systolic intervals (PEP/LVET), cardiothoracic ratio and circulation time were evaluated in 222 sarcoidotic subjects without cardiac symptoms and with no past or present history of cardiac disease. Very few, slight alterations were observed and were probably not the result of sarcoidotic myocardial involvement. Abnormalities distribution according to stage on the basis of chest-x-rays findings and the duration of sarcoidosis did not appear significantly different. Prospective study is being undertaken to determine which of the observed abnormalities may represent precursors or symptoms of sarcoidotic cardiac involvemenet.


[Levocardia with spleen inversion, but without atrial transposition (author's transl)]. The case of a 14-year-old boy with levocardia is reported herein. By scintiphotography, a normal spleen was identified in the right upper quadrant of the abdomen. As angiographic and electrocardiographic considerations rule out the transposition of the atria, the patient must be a very rare case of levocardia with an inverted spleen, which is not associated with transposition of the atria.


[Corvisart's syndrome. report of a case diagnosed in a 64 year-old woman (author's transl)]. The case of a 64 year-old woman, hospitalized for cyanosis, clubbing of the fingers and probably cerebral embolism, in which the clinical and laboratory findings lead to a diagnosis of Tetralogy of Fallot of the Corvisart type, is presented. The possible reasons for benignity and long survival are discussed.


A transforming marker that produces merodiploids with high efficiency and stable transformants with low efficiency in Streptococcus. A mutation (ery-r8) conferring a high level of resistance to erythromycin in the Challis strain of Streptoccus sanguis can be transferred to wild-type erythromycin-sensitive recipients via single molecules of donor DNA. The transformants thus produced are of two types: (1) cells slightly more resistant to erythromycin than wild-type and capable of segregating (at a frequency of 2 X 10(-4)/bacterium/generation) either wild-type or highly-resistant cells like the original donor type; (2) cells phenotypically and genotypically identical to the original donor type. The unstable diploids (ery-r8/+) occur with a frequency equivalent to that obtained with high-efficiency (HE) markers, whereas the stable donor-type (ery-r8) transformants occur with about five hundred times lower frequency. Penetration of the wild-type recipient by more than one molecule of DNA bearing the ery-r8 marker increases by as much as seven times the incidence of stable transformants. UV-irradiation of molecules bearing the ery-r8 marker diminishes their ability to cooperate in producing a stable transformant, although the UV sensitivity of stable transformant production by a single DNA molecule is not different from that of diploid production. Hence, stable transformants do not appear to be produced by a process typical of low efficiency (LE) markers, which are generally highly sensitive to ultraviolet irradiation. Moreover, stable ery-r8 transformants are produced with equally low frequencies in strains of S. pneumoniae that discriminate (hex+) and fail to discriminate (hex--) between HE and LE markers. We postulate that all transformations by the ery-r8 marker result in ery-r8/+ diploids, and that segregation results in the infrequent stable transformants of the original donor type. This hypothesis is supported by the observations that rifampin treatment of ery-r8/+ populations increases the frequency of segregation and similar treatment of wild-type recipients under-going transformation by the ery-r8 marker increases the frequency of stable transformants.--In producing the ery-r8/+ transformant the r8 allele is integrated close to the site of its wild-type homolog, since single molecules of DNA from this transformant can be shown to carry both alleles. Segregation of either the ery-r8 or + allele is not detectably enhanced by acridine orange or thymidine deprivation.--The ery-r8 marker occurs close to a site of mutation (ery-r2) which confers erythromycin resistance upon ribosomes. When the r2 and r8 markers are jointly transferred, ery-r2-r8/+ genomes are produced in which the r2 marker is stably integrated but the r8 marker is unstably adjoined to its wild-type homolog. Thus, the duplicated region can be quite short. When the ery-r8 marker is stably integrated, the region of the marker is refractory to subsequent transformation. Markers with properties like ery-r8 are not particularly rare, being found with a frequency of about 4% among spontaneous mutations to erythromycin resistance.


Genetic analysis of copper resistance in Paramecium aurelia syngen 4. Measurement of the median tolerance limit to cupric ion of 28 wild stocks of Paramecium aurelia syngen 4 revealed a phenotypic polymorphism: two stocks showed a much greater resistance than the others. Genetic analysis showed the resistant phenotype was produced by a recessive allele, cur, identical in both resistant wild stocks. No modification of the phenotypic expression of this allele could be detected after backcrossing into different genetic backgrounds. The results are interpreted to support the importance of mutational adaptation in this inbreeding species. Possible patterns of internal genetic organization of species which rely on mutation for adaptation are discussed.


Temperature-sensitive mutants of a Chinese hamster cell line. I. Selection of clones with defective macromolecular biosynthesis. Temperature-sensitive clones have been selected from a mutagenized culture of Chinese hamster lung cells by a procedure involving bromodeoxyuridine (BrdU) incorporation and irradiation with black light. The selection procedure used in these studies was adapted from methods developed by others to yield mutants that cease DNA replication within a short time after they are transferred to nonpermissive temperature. After mutagenesis with ethyl methanosulfonate ten clones survived the selection procedure. Three of the clones (mutants) were temperature-sensitive as measured by growth properties. Two mutants ceased DNA synthesis within six hours of being shifted to 39degrees and the third mutant continued to synthesize DNA at nonpermissive temperature at a reduced rate for at least 24 hours. Thus, all three mutants survived the selection procedure for understandable reasons, since each was unable to incorporate sufficient BrdU at 39degrees to lethally protosensitize its DNA during the standard exposure period. The two mutants that cease DNA synthesis at high temperature (clones 115-47 and 115-53) also stop incorporating radioactive amino acids and uridine within six hours at 39degrees. Their complex phenotype, i.e. defective DNA, RNA and protein biosynthesis, is reversible. When these mutants were returned to 33 degrees after 8 hours at 39 degrees, both resumed DNA synthesis immediately (less than 1 hour). Reversal of defective DNA synthesis in both mutants were sensitive to drugs that inhibit protein biosynthesis specifically. Those same drugs, as well as toxic amino acids analogs, also effected a striking mutant phenocopy in wild-type cells. The phenocopy produced by amino acid analogs that are incorporated into mammalian proteins suggested that one or more proteins must be synthesized continuously to support mammalian cells engaged in programmed DNA replication.


Esterase gene frequency differences and linkage equilibrium in Drosophila virilis populations from different ecological habitats. In order to study the gene frequency and linkage equilibrium in natural populations, about 5740 chromosomes of Drosophila virilis flies from eight natural populations were analyzed by the null strain method for two linked esterase loci. The frequencies of these esterase genes appear to depend on habitat characteristics rather than on geographical distribution. The populations kept a high degree of linkage equilibrium among them (D-.005).


Conditions for the existence of clines.

Conditions for the existence of clines. A very general partial differential equation in space and time satisfied by the gene frequency in a monoecious population distributed continuously over an arbitrary habitat is derived. The treatment is restricted to a single diallelic locus in the absence of mutation and random drift, and it is supposed that time is continuous, births and deaths occur at random, and migration is independent of genotype. With the further assumptions that migration is isotropic and homogeneous, the population density is constant and uniform (as permitted by the population regulation mechanism included in the formulation), and Hardy-Weinberg proportions obtain locally, this partial differential equation reduces to the simplest multidimensional generalization of the classical Fisher-Haldane cline model. The efficacy of migration and selection in maintaining genetic variability at equilibrium in this model is investigated by deducing conditions for the existence of clines under various circumstances. The effects of the degree of dominance, a neutral belt between the regions where a particular allele is advantageous and deleterious, finiteness of the habitat, and habitat dimensionality are evaluated. Provided at least one of the alleles is favored only in a finite region, excluding the special case in which its total effective selective coefficient is zero, if conditions for supporting a cline are too unfavorable because migration is too strong, selection is too weak, or both, a cline cannot exist at all. Thus, unless there is overdominance, the population must be monomorphic. It is possible for a cline which can barely exist under the prevailing ecological circumstances to show a large amount of variation in gene frequency.


Limits to the advantage of recombination in increasing the rate of incorporation of favorable mutants. The advantage of recombination in increasing the rate of incorporation of favorable mutants is shown to disappear for large NU if substitution is occurring at only two loci. Recombination will, on the average, destroy all double favorable individuals in a haploid population until the product of the frequencies of the single favorable mutants exceeds 1/N. As NU increases there is an increasing probability of the occurrence of the double favorable my mutation alone. Recombination provides a significant advantage in the rate of incorporation of favorable mutants only if 2s/InN less than NU less than 2c when substitution is occurring at only two loci. If substitution is occurring at more than two loci the recombining population apparently has a substantial advantage for large NU.


Genetic loads in heterogeneous environments. A model of population structure in heterogeneous environments is described with attention focused on genetic variation at a single locus. The existence of equilibria at which there is no genetic load is examined.--The absolute fitness of any genotype is regarded as a function of location in the niche space and the population density at that location. It is assumed that each organism chooses to live in that habitat in which it is most fit ("optimal habitat selection").--Equilibria at which there is no segregation load ("loadless equilibria") may exist. Necessary and sufficient conditions for the existence of such equilibria are very weak. If there is a sufficient amount of dominance or area in which the alleles are selectively neutral, then there exist equilibria without segregational loads. In the N2p phase plane defined by population size, N, and gene frequency, p, these equilibria generally consist of a line segment which is parallel to the p axis. These equilibria are frequently stable.


The study of genic variation by electrophoretic and heat denaturation techniques at the octanol dehydrogenase locus in members of the Drosophila virilis group. Heat denaturation studies of three different electrophoretic allozymes of octanol dehydrogenase were performed from 10 species of the Drosophila virilis group. A total of 18 alleles were discovered, and in 3 species in which electrophoretic studies indicated that the locus was monomorphic, heat denaturation showed that the locus was polymorphic. We show that electrophoretic studies underestimate the number of alleles at this locus by a factor of 2.6 in these species. The results are discussed in the light of the continuing controversy over selection and neutral theories of genetic variation.


[Characteristics of somatic cell hybrids (mouse X Chinese hamster) with different ratios of parental species chromosome sets. IV. Electrophoretic analysis of several enzymes of the dehydrogenase class]. Electrophoretic mobilities in polyacrylamide gel of five dehydrogenases: NADP-dependent malate dehydrogenase (NADP-MDH), 6-phosphogluconate dehydrogenase (6PGD), alcohol dehydrogenase (ADH), glucose-6-phosphate dehydrogenase (G6PD) and glutamate dehydrogenase (GDH) were investigated in a series of mouse X Chinese hamster somatic cell hybrids. Seven hybrid lines with different ratio of chromosome sets of hamster and mouse: 1:1, 2:1, 3:1 and 1:2 respectively were studied. NADP-MDH and 6PGD of both parental species and intermediate hybrid bands were present in all hybrids except two lines. These lines had only hamster MDH due to the elimination of mouse chromosomes. A correlation was found between the gene dose and the intensity of the expression of the MDH bands. The mouse type ADH was detected in all hybrids. The hamster ADH was found in one of the hybrid lines that lost all mouse chromosomes during cultivation. It is suggested that hamster ADH activity was suppressed in hybrids by the mouse genome. The species origin of GDH and G6PD could not be established due to similarity of electrophoretic mobilities of respective enzymes in parental cells.


[Isolation and properties of several auxotrophic mutants of a highly virulent strain of the plague microbe]. 2432 stable auxotrophic mutants were selected from high virulent Yersinia pestis strain 20b after treatment with nitroso guanidine. They were deficient in amino acids (arginine, aspartic acid, citrulline, glycine, glutamic acid, histidine, isoleucine, serine, leucine, lysine, ornithine, proline, tryptophan, tyrosine, valine), pyrimidine and vitamins (riboflavin, thyamine, nicotinamide). Some mutants were two- and three-fold dependent. The leucine-, histidine-, purine-dependent mutants were isolated with the high frequency. All the mutants, like their original strain, grew in R-form; they were sensitive to diagnostic phages, had pesticine-fibrinolysin-coagulase system (fraction I) and were calcium-dependent. P+ cultures of auxotrophs were not virulent for laboratory animals.


[Processes of chromosome damage repair in unstimulated human peripheral blood lyphocytes by the method of fractional irradiation and temperature variation]. The fractionation experiments were carried out on resting lymphocytes. Non-stimulated lymphocytes were X-irradiated at the total dose of 200 r separated into two equal parts by either 5-hour or 20-hour intervals. The whole blood samples were kept during the intervals between the exposure at the temperature of 20 degrees centigrade or 37 degrees centigrade. All the cultures were made after the last radiation exposure at 37 degrees centigrade. Dicentrics and centric rings were scored. It is shown that a fractionation effect takes place in resting lymphocytes when the whole blood was kept for intervals between the half-dose at 37 degrees centigrade and is absent at the temperature of 20 degrees centigrade. It is suggested that there is the repair in lymphocytes at the stage G0, AT least, from the dose of 100 r.


[Genetic control of the substrate specificity of sheep plasma arylesterase]. By means of starch gel electrophoresis blood plasma esterases in sheep of different breeds were studied. It is shown that the esterase pattern is a poly-enzyme system consisting of at least three enzymes: arylesterase, carboxylesterase and choline esterase. Postnatal changes of esterase pattern in sheep blood plasma were also studied. Polymorphism on substrate specificities is described, which is expressed in the fact that different arylesterase variants have different affinity to alpha- and beta-isomers of carbone ethers of naphtol. The breeding test suggests that two allelic autosomal genes, reffered to as Es-1a and Es-1b, control the substrate specificity of arylesterase in sheep. The data are discussed in connection with Es-1a and Es-1b gene expression in heterozygous sheep, with the effect of (mosaic) dominance.


[Biochemical genetics of erythrocyte arylesterase in karakul sheep]. Three zones of esterase activity were established in zymograms of erythrocyte lysates in karakul sheep by means of starch gel electrophoresis. These zones were distinguished according to their substrate specificity and inhibition tests and desnguated as arylesterase (I), carbonic anhydrase (II) and aliesterase (III). The following phenotypes of erythrocyte arylesterase were distinguished in the two populations of karakul sheep studied: AEs - A, AEs - AB, AEs - AC, AEs - AD, AEs - B, AEs - BC, AEs - BD, AEs - C, AEs - CD, AEs - D. These phenotypes are controlled by 4 dominant alleles, VIZ. AEsA, AEsB, AEsC, AEsD. Gene frequencies vary from population to population: from 0.012 +/- 0.005 to 0.118 +/- 0.027, from 0.331 +/- 0.021 to 0.340 +/- 0.012, from 0.601 +/- 0.022 to 0.250 +/- 0.011 and from 0.056 +/- 0.003 to 0.292 +/- 0.011 for AEsA, AEsB, AEsC and AEsD respectively. The actually observed distribution of arylesterase phenotypes is in accordance with the theoretically expected values (p is less than 0.95).


[Effect of a magnetic field on the chromosome set and cell division]. An effect of stable magnetic field on karyotype and cell division of human lymphocytes from peripheral blood was studied in tissue culture. Comparative investigations were carried out with lymphocytes, which were treated with magnetic field of different tension (0,179; 0,391 and 0,600 Ts) and continuance (30 sec, 30 and 60 min). Lymphocytes, treated with stable magnetic field, were suspended in donor plasma and immediately cultivated after treatment. The stable magnetic field was found to have a distinct mutagenic effect on cultivated lymphocytes of human peripheral blood. The increase in structural impairements of chromosomes correlated with tension of magnetic field and continuance of its effect. In structural impairements of chromosomes the chromatid gaps and breaks were more often observed but chromosome ruptures and pericentric clearances occurred more rarely. The effect of stable magnetic field on lymphocytes proliferation was studied. Under weak and transient using of magnetic field the proliferated was stimulated, but in rigid conditions - mitosis and blastic transformation were decreased. Continuous effect of magnetic field with weak tension did not inhibite the blastic transformation but influenced on the survival rate of cells in tissue culture, enhancing their lethality.


[Cytogenetic analysis of the action of new bifunctional alkylating compounds]. The mutagenic activity of nitrogen mustard derivatives of aminovinylketones (NP-130, NP-161, NP-163), aminovinylphosphoric acid (RVS-445, RVS-446, RVS-448, RVS-398) and ethylene imine derivatives of ethane sulphonic acid (AR, RJ) was established for the first time in the experiments with Allium fistulosum L. The mutagenic activity of aminovinylketones (NP-130, NP-160) was established for the first time in the experiments with Crepis capillaris (L.) Wallr. The effect of the compounds studied on the seedlings characterized by the high level of natural mutability of chromosomes did not alter the spectrum of structural chromosome mutations. As it is shown by the results of the analysis, the compounds studied exert their action mainly at the S stage of the cell cycle. However, the initiation of potential changes at the G1 stage that are realized into actual breaks at the S stage is not excluded. In some experiments in which high concentrations of mutagens were used no delayed effect was observed which might be explained by the action of mutagens on cells at the G2 stage or at a still later stage.


[Biochemical-genetic mechanisms of learning. II. Selection for a higher and lower rate of motor conditioned reflex acquisition]. Using the model of feeding motor conditioned reflex, polymorphism for the rate of the formation of this response was found in a population of laboratory animals. Selection for high and low rate of the formation of this reflex resulted in significant differences in this character between two strains already in the second generation. These differences are maintained in subsequent generations. The existing henerogeneity for the rate of the formation of conditioned response in the population is shown to be genetically determined.


[Mutagenic effect of different types of radiation on the sex cells of male mice. VIII. Frequency of development of reciprocal translocations in the spermatogonia of mice subjected to chronic gamma radiation]. The frequency of reciprocal translocations in mice spermatogonia after the exposure to chronic gamma-irradiation at doses of 100, 200, 300, 600, 920 r, at the dose rate of 4,2 r/day was investigated. It was shown that the mutation frequency increased insignificantly with the increase of the radiation dose (y=0,8+0,0011x). The comparison of the data obtained with earlier results revealed no changes in the yeild of translocations at the reduction of the dose rate from 10 r/day to 4,2 r/day. The investigation of the genetic radiosensitivity of mice spermatogonia after a chronic gamma-irradiation showed a tendency to increase in their radioresistance.


The depressive character.

The depressive character. The depressive character is characterized by perpetual and unsuccessful efforts to maintain self-esteem and to avoid a sense of helplessness. Such individuals suffer from chronic depression which may or may not be masked, but which permeates their character. Although the condition is among the commonest seen in many of our clinics and practices, it remains without a generally accepted diagnostic form. It is suggested that the essential, clinical, dynamic, and structural features of the depressive character are: (1) consistently low self-esteem and a sense of helplessness, dependent object relations and chronic guilt; (2) self-directed aggression and masochism are frequent but not invariable; (3) extensive use of the mechanism of denial is as common as the previously described obsessional defenses seen in patients subject to psychotic depression; (4) often the depressive character suffers from intense oral envy; (5) depressive character traits may help to ward off any of the basic anxieties, namely, object loss, loss of love, castration anxiety, and superego anxiety (guilt) (6) the depressive character may be similar to a number of related disorders, namely, the obsessional character, hysterical characters with a large oral component, and depressive borderline states; (7) sensitivity to loss, sadness, and fragility of self-esteem makes the depressive character especially vulnerable to regression into overt depression; (8) the persistence of oral incorporative mechanisms, ambivalent, dependent object relations, ego versus superego tension with depressive affect, and sensitivity to loss are characteristic of the ego of the depressive character.


Comparative analysis of persistent dyskinesias of long-term usage with neuroleptics in France and in Japan. The prevalence of tardive dyskinesia was studied in two psychiatric hospitals, one in France (Hopital psychiatrique de Bassens) and the other in Japan (Inogashire Hospital). Twenty-four of 131 patients in Bassens exhibited this disorder, and 22 of 123 patients in Inogashira. No difference was observed between the prevalence of both hospitals. Higher incidence in older age and a marked coexistence of chronic brain disorders were common characteristics of the patients affected by this disorder in both hospitals. All cases in France and in Japan presented a typical oral dyskinesia, but in general the symptoms in France were less intermittent and more pronounced than those in Japan. There existed a considerable contrast of the psychotropic medications between the two hospitals, which seemed to be related not to the prevalence, but to the severity of the symptoms.


Effect of motor-response-deprivation on contingent negative variation (CNV). I: Normal adult data. CNV's were obtained in S1-S2-MR paradigm from 22 normal subjects between the ages of 19 and 67 years (the mean age, 33.5+/-12.5). And then the effect of the presence or absence of a motor response on the CNV was studied. Results were as follows; (1) In the control session (S1-S2-MR), the mean CNV amplitude was 14+/-5 muV, and the mean response time was 291+/-76 msec. There was no significant difference with age, but the mean CNV amplitude for female was significantly higher than that for male. (2) Under the nonresponse condition (S1-S2) where the subject was instructed to attend to S1-S2 without a motor response, CNV amplitude significantly reduced for all subjects (7+/-5 muV). The mean voltage of the attentive-to-stimuli group was significantly higher than that of the inattentive group, and sex difference was not significant for the attentive group. However, CNV of the inattentive male disappeared completely, while the CNV of the inattentive female was significantly higher (8+/-5 muV). (3) Under the response condition (S1-S2-MR), CNV recovered almost to the magnitude level of the control condition (14+/-3 muV), in spite of the fact that the mean response time was significantly shortened between the control and response sessions. (4) We speculate that CNV changes may be dependent upon the dynamic balance of the excitatory-inhibitory activity.


Cortical electrographic correlates of convulsive seizure development induced by daily electrical stimulation of the amygdala in rats and cats. Increasing complexity of neocortical AD morphology was associated with clinical seizure development of amygdaloid origin in both rats and cats. Chronological examination of cortical AD and IID patterns in cats suggests very early involvement of basal cortical areas. Delayed but progressive ictal participation of anterior neocortical areas with eventual development of IID was coincident with eventual development of IID was coincident with recruitment of ictal motor manifestations while neocortical asymmetry with contralateral "desynchronization" pattern persisted throughout seizure development. It is suggested that anterior neocortex participates in the clinical expression of seizure development while verticle ictal propagation into the brain stem is responsible for seizure generalization.


Narrow band noise audiometry: the effect of filter slope. Children with sharply sloping audiometric configurations were examined audiometrically using pure tones and narrow bands of noise with equivalent bandwidths but varying in filter slope. Thresholds were established at the octave frequencies from 500 to 5000 Hz. The results indicated more sensitive thresholds for narrow bands of noise with threshold sensitivity improving progressively as filter slope decreased. Clinical implications are discussed.


Unreliability of half-list discrimination tests. The present study was undertaken to investigate the reliability of the half-list forms of the CID W-22 and the NU no. 6 auditory discrimination tests with both normally hearing and sensorineurally impaired subjects. For each group of subjects, both the first half-lists and the whole-lists were scored. Analysis of the data indicated that the half-list forms of the tests were not as reliable as sometimes suggested in the literature. Further, the half-list form of the NU no. 6 was demonstrated to be not as reliable as the half-list form of the CID W-22 even before the correction coefficient was applied.


Performance of noise-induced hearing-impaired listeners on time-compressed consonant-nucleus-consonant monosyllables. The effects of time compression on the intelligibility of consonant-nucleus-consonant (CNC) monosyllables was investigated by presenting six conditions of a time-compressed versions of the Northwestern University Auditory Test no. 6; at four sensation levels, to nine subjects with noise-induced sensorineural hearing impairments. Results indicated that intelligibility gradually decreased as the ratio of time compression increased, with a dramatic breakdown at the highest ratio of time compression. A typical roll-over phenomenon was also found. Results are related to data on normal listeners.


Sickle cell anemia: audiological findings. The investigation was conducted to determine if there are any characteristic manifestations detectable in the auditory system having some connection with sickle cell anemia (SCA). Hearing loss is easily subjected to analysis and appeared to offer objectivity in probing for possible communicative complications affecting individuals with SCA symptomatology. Employing standardized procedures" the hearing acuity of 10 adult male subjects with sicke cell anemia was examined. Six subjects reported hemolytic crises and evenly separated into short and long period-to-period episodes. Upon comparison all threshold responses of subjects with 1-6-month recurrence rates were consistently poorer than those experiencing 12-36-month cycles. Because there seems to be more fluctuation with more frequent crises, sensorineural deficits in the high frequencies and high short increment sensitivity index (SISI) scores may quite possibly be related to cochlear thrombosis in microcirculations. Further experimentation should first identify those tests and testing patterns most sensitive to the suspected "crises" connected hearing impairment.


The use of visual stimuli during auditory assessment. Two groups of male subjects beyond 50 years of age were given audiometric tasks with and without visual stimulation to determine if visual stimuli changed auditory perception. The first group consisted of 10 subjects with normal auditory acuity; the second, 10 with sensorineural hearing losses greater than 30 decibels. The rate of presentation of the visual stimuli, consisting of photographic slides of various subjects, was determined in experiment I of the study. The subjects, while viewing the slides at their own rate, took an audiotry speech discrimination test. Advisedly they changed the slides at a speed which they felt facilitated attention while performing the auditory task. The mean rate of slide-changing behavior was used as the "optimum" visual stimulation rate in experiment II, which was designed to explore the interaction of the bisensory presentation of stimuli. Bekesy tracings and Rush Hughes recordings were administered without and with visual stimuli, the latter presented at the mean rate of slide changes found in experiment I. Analysis of data indicated that (1) no statistically significant difference exists between visual and nonvisual conditions during speech discrimination and Bekesy testing; and (2) subjects did not believe that visual stimuli as presented in this study helped them to listen more effectively. The experimenter concluded that the various auditory stimuli encountered in the auditory test situation may actually be a deterrent to boredom because of the variety of tasks required in a testing situation.


The effects of duration, frequency, and loudness upon the reproduction of temporal intervals. Subjects (five normal hearing graduate students in the Department of Audiology) were asked to reproduce temporal intervals of 1, 3, 5, 7, and 9 sec. The intervals were filled with pure tones at frequencies of 250, 500, 1000, 2000, and 4000 Hz and at loudness levels of 40, 50, 60, 70, and 80 phons. The reproductions were transformed into the ratio DT/T, where DT represents the difference-time between the stimulus duration and the duration of the reproduction, and T represents the stimulus duration. It was found that neither frequency nor loudness had any significant effect upon the ability to reproduce the durations. The only significant variable was duration. There were no significant interactions among the variables. On the average, the durations of 1 and 3 sec were overestimated and the durations of 7 and 9 sec were overestimated. The duration of 5 sec was neither overestimated nor underestimated, the indifference point falling at 4.90 sec.


A comparison of the effects of sedatives on the auditory evoked cortical response. Several sedatives were selected that were judged to be amenable for routine clinical use in electroencephalic response audiometry (ERA). These sedatives were investigated to determine which were most effective for ERA; the relationship between sleep stages and the auditory evoked cortical response (AECR), the reliability of the AECR in sleep, and whether either the early or late response was more consistent or detectable during sedation. The early response was evoked by tone pips with a 10-musec  rise-decay time and an acoustic duration of 5 msec. Tone pips were presented at a rate of 8 per sec and an averaged response was based upon 1500 stimulus presentations. The late response was evoked by tone bursts centered at 1000 Hz with a 10-msec rise-decay time and an acoustic duration of 150 msec. All tone pips and tone bursts were presented at 40 dB sensation level. Eleven normal hearing adults were selected as subjects who demonstrated clear and consistent eerly and late AECR's while awake and in natural sleep. Early and late responses were analyzed to determine the percentage of detectable responses, and amplitude and latency under all sedatives and different sleep stages. The results showed that nonbarbiturates and sleep stage 2 and 3 were more effective for ERA.


[Environmentally affected differentiation of dendrite spines of pyramidal neurons in rat hippocampus (CA 1)]. Three groups of newborn WISTAR-rats were exposed to different environmental influences. The first group was raised in darkness from birth onwards, the second was permanently subjected to noise immediately after birth, while the third group (controls) was reared under normal laboratory conditions. The animals of all three groups were killed on the 15th day after birth and handled by a modified Golgi-Kopsch method. Then the distribution of spines on apical dendrites of CA 1-neurons of the hippocampus was investigated. For apical dendrites of a comparable length the mean number of spines per 50 mum as well as the mean total of spines on the apical dendrite was evaluated. Rats reared in darkness show significantly less spines on the apical dendrites of CA 1-neurons in comparison with the control animals. Rats permanently subjected to noise, on the contrary, have significantly more spines in comparison with the controls (total number of spines on the apical dendrite is 89,8 +/- 10,2 in the control animals, 55,0 +/- 16,6 in the animals reared in darkness, and 125,8 +/- 29,4 in the animals subjected to noise). The changes involve the whole apical dendrite; extreme changes in the individual segments of the apical dendrite were not observed. The results suggest that environmental factors have an influence on the differentiation of central neurons, which is not restricted to the specific analyzer concerned.


[Morphological study of hippocampal development in cell and explant cultures]. Cell-and explantatcultures from hippocampal region of embryonal rats and newborn rats were cultivated up to 4 weeks. Pyramidal neurons, multiformed neurons and granule cells were observed in the explantatcultures. In the cellcultures were observed small and big Neurons after 4 weeks in vitro. Mantenance and differentiation of cellcultures are possible only by showing in at least 60 000 cells/ml. The Morphology of neurons in vitro was related to in vivo.


[Comparative quantitative study on brains of wild and laboratory rats. I. Comparison of volume of total brain and classical brain parts]. The intraspecific allometric relation between brain weight and body weight of wild Norway rats and laboratory rats was gained from sufficient material. The intraspecific allometry exponent a=0.25, being typical for mammals, also came out as a result for Norway and laboratory rats. But laboratory rats have 8.3% less brain substance at a comparable body weight. This decrease in brain size was interpreted as an adaption to the specific conditions of domestication and discussed accordingly. Futhermore the fresh volumes of the fundamental brain parts telencephalon, diencephalon, mesencephalon, cerebellum, medulla oblongata, neocortex, corpus striatum and allocortex were ascertained by means of serial sections of 8 Norway and 8 laboratory rats, and they were compared with each other by their average brain proporationing. Consequently, differently strong reduction intensities in the sizes of these brain parts from 1.6% (medulla oblongata) to 12.5% (neocortex) became evident. The high reduction values of corpus striatum (10.9%) and cerebellum (10.3%) were especially remarkable. They almost reached the same degree as the forebrain (10.6%). The size reduction of the measured brain parts of rats, caused by domestication were compared with the results of other domestic mammals and discussed accordingly.


[Comparative quantitative study on brains of wild and laboratory rats. II. Comparison of size of allocortical brain centers]. The size of allocortical regions in the telencephalon of 8 wild Norway rats and 8 laboratory rats of different body size were measured by means of serial sections at equal intervals. On the intraspecific allometric relation between brain size and body size differences in size of the measured structures between wild and domestic animals came out as a result. The olfactory regions of the allocortex in totality were 5.9% smaller in laboratory than in Norway rats. Included in this were, however, size increase of the structures bulbus olfactorius and tuberculum olfactorium as well as size decrease to a different degree of the other olfactory centers. Compared with this all limbic structures showed clearly decrease in size. In totally they were reduced to 9.6% from Norway to laboratory rats. The highest reduction values were found in the adjoining structures of the archicortex and the schizocortex. Equivalent reduction intensities of 10.2% could be established for the main centers of the hippocampus formation (cornuammonis; fascia dentata). The different rates of reduction intensity were interpreted as due to the special environmental changes caused by domestication. They seem to be related to behavioral changes.


[Primary visual centers in Protopterus dolloi Boulenger]. Modifications of the Nauta's method (Fink-Heimer, Ebbesson-Heimer) were used to study the optic centers and pathways of rotoperus dolloi following unilateral enucleation. After ablation, animals were kept at 25degrees C from 6 to 51 days. We saw optimum degenerescences from 10 to 13 days of postoperatory life. Retinofugal fibers are completely crossed. The projections to necleus preopticus and hypothalamus seem to be bi-lateral. The mean primary optic centers are: the thalamic neuropil which is may be homologous with the Bellonci's neuropil in Amphilbia; the pretectal and tectal neuropils; the neuropil of the basal optic root. Results obtained in Protopterus can be compared with our knowledges in Amphibia.


Contribution to the study of 150 cases of cerebral metastases. II. Neuropathological study. This study deals with the morphology of 150 cases of cerebral metastases. They are, for the most part, associated to other cases of metastases elsewhere in the body (96.7%). A histological study shows that the nervous parenchyma is more frequently invaded by expansion than infiltration; the majority of metastases settle in the grey matter or where the white matter meets the cortex. There is no predominance for one of the two hemispheres. The frequency of metastases in the various lobes is proportionate to their respective volumes. In 30% of the cases, there is only one single metastasis; these are then, very often, tumours from the digestive tract and from the breast. Usually they are large, and especially if they originate from the digestive tract. Single metastases are three times more frequent in the brain than in the cerebellum. In 10% of the cases, only the cerebellum is affected by metastases. Breast tumours are by far the most frequent kind of tumor to invade the dura. The widely accepted principle that the brain is invaded by means of the arteries is confirmed by our series, where no document shows an illustration in support of the venous theory. In most cases, the metastases are of the same histological type as the primary tumour. More or less deep necroses are found quite often. These disorders of vascular permeability explain fairly clearly the varying responses of the environing nervous tissue to the tumours invasion, particularly in the presence of hemorrhages. When they are voluminous, they may clinically have appeared in the form of an ictus. These hemorrhages occur preferably in the white matter. Necroses are sometimes cavitary, their centre being taken up by a necrosis of liquefaction, surrounded by a more or less continuous neoplastic border. The most frequent inflammatory reaction is lymphoplasmocytarian, particularly accentuated on the periphery of the metastasis and in the neighbouring meninges. Oedema predominates in the white matter. They nearly always lead to demyelinization, with its aftermath of granulofatty bodies or astrocytarian reactions. Fibrosis is also frequent, it is intra-metastatic and in direct relationship with the tumour's histological type; it is more rarely perimetastatic, developing from the vascular mesenchyma. The vascular changes constitute one of the most constant peri-metastatic parenchymatous alterations. They may appear in the form of vascular ectasia or neoformations of vessels, the most characteristic aspect of which is the formation of vascular glomerules. These undergo a very quick evolution and are indubitably linked to the degree of malignancy.


Intracranial pressure in adult non-tumoral hydrocephalus. Intracranial pressure (ICP) was monitored continuously for 48 hours in four patients with different types of non-tumoral adult hydrocephalus and classificated according to ICP recordings. It is emphasized that ICP monitoring is essential in the diagnosis of normal pressure hydrocephalus (NPH), since its possible to observe abnormal pressure recordings with morphological alterations which can be accompanied or not by periods of raised ICP. It is suggested that this method may help identify cases suitable for surgery.


Experimental induction of colonic carcinomas in rats. Analysis of factors influencing upon the incidence. A method to make a diverted segment of the colon keeping direct continuity to the main colonic lumen was introduced to study carcinogenesis in the colon of rats. This method was proved to be useful for analyzing several factors influencing upon cancerization in the colonic mucous membrane. Macroscopical colonic neoplasia were induced in nearly 80% of rats treated with N-methyl-N'-nitro-N-nitrosoguanidine introduced into the colonic lumen through the diverted segment. Neoplastic lesion of the mucous membrane developed mainly in the colonic segments which were in direct contact with intestinal content. The importance of intestinal content and colonic microflora was discussed and reviewed. One epithelial cell line was established from one intraperitoneal metastatic deposit of a huge colonic carcinoma induced by the carcinogen. This cell line has been maintained in tissue culture. The liver was susceptible to the carcinogen, and multiple cystic lesions were observed after intracolonic administration of the chemical.


Isolation and properties of a streptococcal hemolysin formed in the presence of colistin. The strains of beta-hemolytic streptococci capable of producing streptolysin S, Su and Blackmore, were found to be useful in acquiring CIH (colistin-induced hemolysin), while C203U strain, which produces only streptolysin O, was ineffective in this respect. In these experimental series, much amounts of coccal cells from exponential phase of culture were necessary for obtaining good results and for its reproducibility. Further experiments showed that an oligoribonucleotide, rich in guanylic residu, separated by DEAE-cellulose column chromatography could be favourably compared with RNase-core in production of CIH in the medium. Yield of this hemolysin was fully dependent upon the concentration of K+ (100 mM), Mg2+ (10 mM) ions and maltose (5 mM) contained in the reaction medium, respectively. When one of three components was omitted, CIH was not obtained, even though colistin and oligoribonucleotide were present. Additionally, crude preparation of CIH was fractionated on DEAE-cellulose column, resulting in isolation of two peaks (F-I and F-II) with hemolytic activity. Considering the response of two hemolytic fractions to various inhibitors and activators, F-II is likely to correspond to streptolysin S, while F-I may, at least, be a segment differed from the streptolysin, S and O.


Isolation of Friend leukemia virus resistant line from non-inbred mouse colony. Among a non-inbred ddY mouse colony, a small portion showed marked resistance to splenomegaly induction by Friend leukemia virus (FLV). The resistance to the virus appears to be governed by a single gene, and is dominant over the susceptibility. Thus, it was possible to breed two lines of mice, which are respectively resistant and susceptible to the virus. Resistant response to FLV of the resulting mice, which seemed to be homozygous for the dominant resistant gene, is similar to that of C57BL/6 and more rigid than that of BALB/c mice. Phenotype of F1, segregation ratio in F2 and BC1 hybrid progeny between resistant and susceptible lines were also compatible with the single gene model.


FV-4: a new gene affecting the splenomegaly induction by Friend leukemia virus. Analysis of offsprings from mating of a Friend leukemia virus (FLV) resistant new mouse line, G, and DBA/S mice confirmed the existence of a single dominant gene for the resistance of G to FLV. In these offsprings, no correlation between resistance to FLV and hair-color genes (b, d and c) were observed. In the progeny of ((G X BALB/c) X DBA/2) mating, the resistance gene seregated independently from Fv-1. The allele(s) on Fv-1 locus in G mice seemed to be permissive to N-tropic virus. Therefore, conconmitance of Fv-1b in G mice was excluded. These results indicated that the resistance gene in the new line mice differ from Fv-1 and Fv-2.


Further study on cerebral sphingolipids including gangliosides in two cases of juvenile amaurotic family idiocy (Spielmeyer-Vogt type) using a new analytical procedure of sphingolipids. Sphingolipids isolated from cerebral grey and white matter of two patients with Juvenile Amaurotic Idiocy (Spielmeyer-Vogt Type) were studied. A new analytical procedure was attempted for the determination of sphingolipids, i.e., cerebroside, sulfatide, sphingomyelin and gangliosides were subjected to ozonolysis and reduced with NaBH4. Fatty alcohols thus derived from the double bond-containing long chain bases of the sphingolipids were analyzed by GLC as their TMS-derivatives using an internal standard. The new procedure was suitable for the analysis of small amounts of sphingolipids and could determine the amounts of C18 and C20 sphingosines. It was found that all individual gangliosides in both cases gave lower proportions of C20 sphingosine to the total long chain bases. Sphingomyelin in normal human grey matter contained a small but significant amount of C20 sphingosine, while the sphingomyelin of the two patient brains indicated a much lower proportion of C20 sphingosine in comparison with those of age-matched controls. Thus, this disease seemed to be related to a genetical defect in the metabolic regulation of the long chain bases of gangliosides and grey matter sphingomyelin. On the other hand, it was noted that the ganglioside pattern of grey matter in case-1 was entirely different from that of case-2. The grey matter gangliosides in case-1 were composed of 1.78% of GM2, 81.19% of GM1 and 17.02% of GD1b by the amounts of long chain bases, while the grey matter gangliosides in case-2 seemed to be similar to those of normal human brains. Also, unusual fatty acid compositions of galactosphingolipids (cerebrosides and sulfatides) were observed to a somewhat extent in the grey matter of case-1.


A new procedure for transabdominal resection of esophagocardial cancer and cervical anastomosis obviating thoracotomy. A new operative technique for esophagocardial cancer was reported with resection and re-establishment of alimentary continuity at cervical esophagus which obviates thoracotomy but still retains adequate removal of the lesion. Ten cases of esophagocardial cancer thus treated were presented and the clinical data were analyed. The distance between esophageal stump and esophagocardial junction measured on the resected specimen ranged from 3.0 to 6.7 cm with an average of 5.1 cm. No remaining tumor cells were detected microscopically on the oral cut margin of the specimen in all cases. To compensate for the inadequated lymph node dissection intensive postoperative adjuvant irradiation and/or chemotherapy was advocated.


Double aortic arch with aneurysm-a surgical case report. An unusual case of double aortic arch with aneurysm is described. A 61-year-old, hypertensive and syphilitic male patient complained of increasing difficulty in swallowing of approximately five months duration. Barium swallow and subsequent aortography showed the presence of an aneurysm of the ascending aorta involving the left (anterior) arch of the double aortic arch. The tightening of the vascular ring by aneurysmal dilatation of the left aortic arch appeared to be responsible for the delayed onset of the symptom. Surgical correction was made by removing the aneurysmal ascending aorta and left aortic arch and a Dacron graft was inserted between the ascending aorta and the right (posterior) aortic arch. The patient died of cerebral complication about forty hours postoperatively. Surgical problems associated with this unusual condition were discussed retrospectively from the operative and autopsy findings. In reviewing the pertinent literatures this case appeared to be the first operated case of double aortic arch associated with aneurysm.


A role of extracorporeal circuit in the post-perfusion thrombocytopenia: a scanning electronmicroscopic observation. Thrombocytopenia is one of the adverse effects of extracorporeal circulation (ECC) but the mechanism of which has not been fully understood. Blood-gas interface, mechanical agitation, rough surface of extracorporeal circuit and sequestration in the liver have been considered to be a cause of platelet loss. Extracorporeal circuit which provides large artificial surface for contact of blood has been blamed as the site of platelet destruction during oxygenation. However, the part of the oxygenator responsible for platelet loss has bot been located. This study was designed to identify the sites of extracorporeal circuit responsible for platelet loss during ECC with scanning electron microscopy (SEM) of the post-perfusion circuit. The accumulation of platelet aggregates was most pronounced at the defoaming net and blood filter where a sudden changes in velocity of blood flow take place. The aggregates were considered to be formed locally at these sites. However, there were no accumulation and/or adherence of platelet aggregates of significant degree at the other parts of the circuit, namely venous and arterial tubings, venous colum and arterial reservoir. Platelets seem to be removed from the circulation during each passage by defoaming net and blood filter. However the other parts of the circuit seem to be less blamed for the platelet loss. It was not possible to conclude whether the formation and trapping of platelet microaggregates at the defoaming net and blood filter or the destruction by oxygen bubbles is mainly responsible for the plateletloss during ECC.


Specificity of social-anthropological studies of ritual. Many fruitless controversies about 'ritual' are based on the multivocality of the word. By recent work by Tinbergen in ethology confines the term to rigid, highly formalistic, exaggerated behavior by animals in situations of compromise formation, where the animal is moved by contrary impulses to action. Similarly, in psychoanalytic writings the word is reserved for rigid formalistic actions which are defence mechanisms. These uses of the term are congruent with that social-anthropological use which has found that in tribal societies, in situations where there occurs sharp conflict of processes based on inconsistent, discrepant and contrary social principles of values, persons tend to be required to perform rigidly prescribed actions that exaggerate their normal social roles. Illustrations are given from initiation and political ceremonies; and these lead to an analysis of how ritual symbols transmute (sublimate) to ideological values energy roused by emotive stimulants. Thus ritual is directed to assert that social harmony prevails precisely in those situations where this harmony is most imperilled.


Interaction analysis of change in social performance and personality functioning in a therapeutic community introduction. This is an introductory presentation of research carried out at the Henderson Hospital, London, England. The hospital is a therapeutic community for young people diagnosed as personality disorders [24,32]. The sample includes all patients admitted to the hospital during one year commencing 1/3/1971. Rather than studying either personality or performance separately this study is an attempt to learn more how social performance is relevant to personality change. This is done through interaction analysis. Within the scope of this paper I shall also attempt a brief description of the focal problems, examined, their operationalization in research methods, expected results, and a preliminary discussion of three demonstrative cases.


Role of life events in accident causation. The concept of stress as causative in human illness has been documented in studies relating significant illnesses to major life changes (i.e., marriage, parenthood, divorce, employment changes, etc.). Although some studies have related accidents to stress, the various types of stress involved were either poorly-defined or narrowly delineated by the specific interests or professional training of the investigators. Our current study represents an attempt to investigate traffic accidents as a function of multi-dimensional stresses which result from life changes experienced by the driver. In addition we have attempted to assess the subject's feelings and responses to these life changes as well as his general adjustment to the total environment. Our ultimate goal is to develop a questionnaire to identify drivers who are highly susceptible to traffic accidents. This questionnaire will be designed to be self-administered and easily scored. It is intended to provide help in traffic safety countermeasure programs that will focus on cause rather than effect. Only by developing a comprehensive stress-accident model will comprehensive and workable accident prevention programs be developed to replace the current patchwork of existing programs.


A model for differential treatment of the juvenile delinquent. In this model, the symptom neurosis is contrasted with the ego syntonic deviance. Whereas most of psychotherapeutic practices are geared to neurotic patients, this model represents treatment procedures and techniques aimed at the acting-out character disorders. This comparison related to: a) internal tension and readiness for change b) level of differentiation between Actual and Potential Identity c) perception of the Logic of Events Furthermore, the model describes the ego-defenses of the delinquent, and finally relates them to the more specific techniques of treatment.


Nonpsychotic personality disturbances: a re-evaluation and reclassification. The classical notion of neurosis as the prototypical form of nonpsychotic personality disturbance must be rejected in favor of the categories of (a) personality pattern disturbance and disorder of life style, and most especially, (b) character disorder. Category (a) would include schizoid, paranoid, and cyclothymic personality pattern disturbances and compulsive and hysteroid personality as disorders of life style. Each of these would occupy one end of a 'psychotoid' continuum, at the other end of which would be a familiar type of psychosis such as paranoid schizophrenia or pseudoneurotic schizophrenia. The most numerous of the nonpsychotic disturbances (in the tens of millions in the USA alone) come under category (b), the character disorders, involving a special sort of failure to inhibit impulse and unsocialized self-seeking. Character disorders are seen by us as turning on an eccentric axis, alternating between the two foci of 'dependency' and 'aggression'.


Introduction of intensive milieu therapy in a traditional psychiatric unit. In spite of a growing interest in clinical psychiatry to experiment with new treatment programs, not least in the field of milieu-therapy, the effect of these programs on the behavior of patients and staff are rarely subjected to systematic evaluation. So the progress in the field is hampered by a lack of clearly defined behavioral data which lends itself to critical analysis, and generally speaking is based on rather loose clinical impressions which make scientific verification difficult the present describes an admittedly crude attempt at systematic evaluation of what happened to staff's and patients' behavior when a relatively intensive milieu-therapy program was introduced in a traditional psychiatric unit, using relatively simple but clearly defined parameters of change in behavior over time. Certain hypotheses about what would happen in terms of group behavior if the new program worked according to its intentions were tested, and generally speaking the conclusion was that the program developed successfully as far as this could be measured by the selected parameters. Data about the patients' evaluation of the effect of the treatment program on themselves, and how this relates to attitudes towards own mental disorders and expectation towards psychiatric treatment at admission to the clinic, as well as social background and group behavior, is analysed, and wil be published in a subsequent paper. So the present paper should be considered as a preliminary report, mainly focusing on certain methodological aspects.


Medical oncology: the new subspecialty.

Medical oncology: the new subspecialty. The creation of medical oncology as a new subspecialty of internal medicine required a definition of the scope of involvement of the physician in this new area. Objectives for training programs were established and provisions provided for certification of specialists as medical oncologists. The area of medical oncology encompasses a broad aspect of medicine and requires a frim foundation in the principles of internal medicine. As an advocate of the cancer patient, and in many instances the primary physician, the medical oncologist has the opportunity to effectively interact with many scientific skills in order to effectively control or even cure neoplastic diseases.


Adriamycin: a new effective agent in the therapy of disseminated sarcomas. Thirty-six patients with disseminated sarcomas were treated with adriamycin according to an intermittent single high-dose schedule based on our prior pharmacologic observations. The dose of 60 mg/M2 IV q 3 weeks was reduced 50-75% in the presence of liver disease. Complete remission occurred in 9%, parital remission in 32%, and improvement in 21% for median durations of 37, 18, and 15 weeks, respectively. Survival was prolonged in responding patients. Hematologic suppression was mild in the absence of liver disease or prior extensive radiotherapy. Congestive heart failure, a well-known long-term complication of therapy with anthracycline drugs, occurred in two out of four patients who had cumulative doses of 600 mg/M2 or more. Mucous membrane toxicity was not observed. Adriamycin is an effective new agent in the therapy of disseminated sarcomas and can be used with relative safety by following pharmacologic principles.


Evaluation of cell-mediated reactivity and serum blocking factors in melanoma patients on chemotherapy. Sequential assays for cell-mediated reactivity (CMR) and serum blocking factor (SBF) were performed in a group of 12 melanoma patients who were treated with one or both of the clinically available imidazole carboxamide derivatives, DTIC and TIC Mustard, in order to consider the effects of treatment and changing patterns of disease on the results of in vitro tests in individual patients. Microcytotoxicity assays and the dilute agar colony inhibition test were employed. Of the 12 patients, 8 had no change in CMR and 5 had no change in SBF. Three patients demonstrated a fall in both CMR and SBF to nondetectable levels, and 3 additional patients showed a fall in SBF only. From these results, we conclude that there is no significant depression of CMR in melanoma patients by either of the imidazole carboxamide derivatives used. The results of SBF are less conclusive and more open to question, since it is just a likely that any depression to undetectable levels may be due to a change in disease status rather than to coincident drug use. It appears that microcytotoxicity assay results on individual patients may be fortuitous and difficult to interpret, even though results seen in patients as a group indicate important trends. The microcytotoxicity assay is a useful tool for the experimental tumor immunologist, but its clinical usefulness in individual patients is limited.


The use of low-dose prednisone and melphalan in the treatment of poor-risk patients with multiple myeloma. A study was designed to evaluate the effectiveness of prednisone therapy in poor-risk patients with multiple myeloma. Patients were treated with melphalan alone or in combination with prednisone at doses of either 0.6 mg/kg or 0.3 mg/kg. The group of patients receiving melphalan and prednisone 0.6 mg/kg had significantly improved responses in hemoglobin, lowering of the M-protein concentration, and reduction of azotemia. Significant benefits attributable to prednisone were not demonstrated in the group receiving 0.3 mg/kg. Good responses have been shown to produce improved survival. The combination of melphalan and prednisone is effective in producing good responses, but the dose of steroids is important. A dose of prednisone of 0.6 mg/kg in gradually decreasing doses has been found to be effective in production of good responses, especially in the uremic patient.


Antibody response to poliovirus immunization in childhood leukemia. Polio antibody titers were determined in 29 children with ALL in various clinical stages, including a group of five patients in continuous remission for over five years and who, at the time of study, were off all therapy for at least six months. Regardless of the stage of disease, no detectable gamma M response was elicited. The five children described above displayed the same depressed response as did the other children with ALL. This strongly suggests an inherent defect in the immune system of these children with ALL unrelated to therapy.


The influence of chemotherapy on the prognosis of rhabdomyosarcoma. A study of 77 consecutive cases of childhood rhabdomyosarcoma treated initially at the Children's Hospital of Los Angeles from 1950 to 1972 demonstrated an impressive improvement in survival of patients when intensive chemotherapy was occurred in Stage II and Stage III disease. Eight out of 9 patients with a primary lesion of the lower extremities developed intra-abdominal disease. A general approach for treatment of Stage II, III, and IV rhabdomyosarcoma is proposed which involves intensive chemotherapy, following biopsy, as the principle treatment, with radiation and surgery used as a adjuvants.


Non-Hodgkin's lymphoma in children.

Non-Hodgkin's lymphoma in children. In a study of non-Hodgkin's lymphoma in children, 104 children were treated and followed at Memorial Sloan-Kettering Cancer Center from 1964 throughout June 1974. Forty-three patients, previously treated and untreated, received a nonspecific group of various chemotherapeutic agents and attained an 11% disease-free survival rate. A second group of 18 previously untreated patients, who received a chemotherapeutic regimen consisting of cyclophosphamide alone, achieved a 33% disease-free survival rate. The last group, 43 previously untreated patients (77% of whom had far advanced disease and 86% of whom had diffuse histological types) who received a new and intensive multiple-drug regimen (the LSA2-L2 protocol) consisting of induction, consolidation, and maintenance phases, has maintained an 81% disease-free survival rate after a median observation time of 21+ months. Although nervous system involvement and recurrence or metastases at any time are poor prognostic factors, initial marrow involvement and the amount of bulky disease are no longer considered negative prognosticators when intensive treatment is initiated immediately after diagnosis, is continued for 2--3 years, and includes radiation therapy to sites of bulky disease and CNS prophylaxis. The LS2-L2 treatment is effective in accomplishing the dual aims of not only increasing the numbers of disease-free patients but also prolonging their survival.


The effect of short-term cyclophosphamide on estrogen therapy in metastatic breast cancer. Stimulation of tumor growth and induced hypercalcemia both may occur during the initiation of estrogen therapy in breast cancer. This study was conducted to determine whether cyclophosphamide (CTX) as an adjuvant to estrogen therapy might (1) prevent induced hypercalcemia or (2) achieve a higher tumoricidal effect during the phase of tumor stimulation. Fifty postmenopausal women with inoperable or recurrent disseminated breast carcinoma were divided into two random groups. Results could be evaluated in 44 patients; 21 received diethylstilbestrol (DES), and 23 received DES plus a 4-week course of cyclophosphamide (DES + CTX). The response rate was 5/21 (24%) in the DES group and 8/23 (35%) in the DES + CTX group (p greater than 0.05). The median duration of response for both groups was 9 months. The survival rate at 24 months was 52% in the DES group and 25% in the DES + CTX group (p = 0.05). Induced hypercalcemia occurred in 3 patients treated with DES + CTX. Short-term cyclophosphamide adjuvant to estrogen therapy did not prevent induced hypercalcemia nor prolong the duration of response or survival.


Three dose regimens of adriamycin for induction of remission in acute leukemia in children: a Southwest Oncology Group Study. Three therapeutic regimens (6-hr intervals for 6 doses daily for 3 days, and a single infusion) utilizing the same total dose of adriamycin for the induction of remission in children with late-stage acute leukemia were evaluated in 150 patients. Complete remission rates were 15%, 28%, and 25%, respectively. Twenty-five children who achieved complete bone marrow remissions with adriamycin therapy were treated a second time after subsequent relapses. Of these children 20% achieved second bone marrow remissions.


Active specific immunization in malignant melanoma. The effects of active specific immunization with nonirradiated autologous and irradiated cultured allogeneic melanoma tumor cells (TC) on cell-associated immunity was studied in 11 patients with widespread malignant melanoma receiving chemoimmunotherapy. Immunization with 1 X 10(6)-8 X 10(7) TC was done in the draining area of a BCG scarification on day 7 of the study. The in vitro lymphocyte blastogenic response (BR) to autologous TC was studied in terms of the stimulation index on day 1, 7, 14, and 21. The stimulation index (SI) was the counts per min (cpm) in the TC stimulated culture minus the cpm among the TC alone divided by the cpm in the unstimulated controls. A positive BR was considered as a SI equal to or greater than 3. Six out of 11 patients had a significant increase in BR lasting 7-14 days after immunization. The pre- to post-immunization changes in the SI of the 6 patients were 2.5 to 7.5; 0.7 to 3.2; 0 to 5.2; 0 to 16; 0.1 to 6.6; and 6.5 to 30.0. Nine out of 11 patients showed a delayed local inflammatory reaction at the immunization site. Five out of 11 patients mounted a cutaneous delayed hypersensitivity reaction to autologous tumor cells at a separate test site following immunization. There were no side effects. Active specific immunization in the drainage of a BCG reaction appears to be safe. Since a positive BR to autologous TC correlates with a good prognosis in patients with solid tumors, studies of the immunotherapeutic efficacy of this approach may be warranted.


Hypocalcemia complicating acute leukemia. Eighteen of 54 adults with acute leukemia developed severe hypocalcemia during a 20 month period. Hypocalcemia (mean lowest serum calcium 6.3 mg/100 ml with a range of 4.1 to 7.0 mg/100 ml) lasted 2-29 days and was symptomatic in all but one patient. Six patients were hypocalcemic at the time of death, 5 died within 1 week of hypocalcemia, and 2 had antibiotic-induced respiratory arrest. All patients had severe infections; 17 of 18 were with gram-negative organisms. No patient had severe azotemia, diarrhea, alkalosis, or hypoalbuminemia. Hypophosphatemia was seen in 14 patients, suggesting no hypoparathyroidism. The serum calcium of patients with acute leukemia should be measured frequently, especially when they have infection. Hypocalcemia is a sign of poor prognosis and should signal the need for careful observation of ventilation, caution in the use of aminoglycoside antibiotics, and vigorous attempts at calcium administration.


'Normal' and 'lesional' traits of personality according to Sjöbring: re-tatings and prognostic implications. The Lundby project. As a supplement to findings made in two studies of the same rural population with a 10-year interval, the 'reliablity' of various subjective ratings of normal personality was looked into: the variants in validity, solidity, and stability as described by Sjobring. In addition the findings of Hagnell, according to which the above-mentioned normal variants of personality hardly influenced first incidence of mental disorder during the period of observation, while so-called 'lesional' variants did, were further investigated and confirmed.


The exerience of pain in depressed patients. A clinical and experimental study. An experience of pain according to Merskey's definition was found in 24 out of 40 consecutive patients with depressive disorders. No age or sex differences were found between patients with and those without an experience of pain. In a comparison of ratings using the Cronholm-Ottosson depression rating scale, patients with an experience of pain were found to have a more severe type of depression, more psychic and vegetative anxiety, more motoric restlessness, more local tension, more thoughts of suicide, more hypochondriacal ideas, more sleep disturbances and a higher total depression score. On the other hand, no difference was found as regards depressive ideas, intellectual, conative or emotional inhibition or psychomotoric retardation. In the experimental part of the study, 30 patients -- 18 with an experience of pain -- were investigated with pain measures and visual averaged evoked responses. No differences were found in pain measures between patients with and those without an experience of pain. Out of 18 patients with an experience of pain, 15 were found to be augmenters as measured by visual averaged evoked responses. In the group of patients without pain only 4 out of 12 patients were augmenters.


Early detection and prevention of mental illness: the Mauritius project. A preliminary report. The experimental manipulation method is in general not feasible in studies of the etiology of severe mental illness, whereas this method can be used in studies pertaining to primary prevention, because possible preventive methods would most likely be of a protective or beneficial nature. Preventive experimentation requires early detection of those individuals who will eventually become seriously mentally deviant. A study of children at a high genetic risk for schizophrenia is described. This study suggested certain autonomic nervous system variables as predictors of later serious mental breakdown. In a WHO-sponsored project in Mauritius the authors used these results for the selection of a group of children at risk for mental illness. 1,800 3-year-old Mauritian children were studied socially, psychologically, pediatrically and psychophysiologically between 1972 and 1973. 100 of these children were selected for experimental preventive intervention during their daily presence in two modern kindergartens. Members of this group were characterized by either abnormally fast autonomic recovery or autonomic nonresponding, or normal autonomic responding. A matched group of another 100 children served as a community control. The paper presents preliminary results from the screening of the 1,800 children.


Norepinephrine metabolism in mouse heart after lithium and rubidium treatment. This report describes the effects of treatment with lithium (Li), rubidium (Rb) and sodium (Na; 1 mEq/kg/day) for 7 days on norepinephrine (NE) turnover in mouse heart. The effects of several drugs which modify the uptake and storage of NE were also studied in similarly pretreated mice. A method based on the combustion of tissue tritium to tritiated water was used to assay tritiated l-norepinephrine (l-NE-3H) concentrations in individual hearts. The rate of decline of tissue tritium concentrations in groups of pretreated mice maintained at ambient temperature (23--24 degrees C) or in the cold (4--5 degrees C) was determined. The results indicate that, compared to Na, Li and Rb did not modify the tritium turnover rate in mouse heart. Pretreatment with Li or Rb did not modify the uptake of tritiated NE in the heart. The effects of desipramine. cocaine, bretylium and chlorpromazine on NE uptake were not altered by the alkali ions. Further, pretreatment did not modify NE release by tyramine, metaraminol and guanethidine. These studies suggest that Li and Rb do not modify NE uptake, release and storage in mouse heart.


Comparison between some biological clocks regulating sensory and psychomotor aspects of perception in man. Regular repetition of one monitor of sensory perception and another of psychomotor perception revealed similar frequency and amplitude aspects of spontaneous endogenous free-running cycles of perception and others of vigilance. The ultradian periodicities of these cycles distinguish between persons with intact nervous systems and those with brain damage.