Development of species identification in ducklings: I. Nature of perceptual deficit caused by embryonic auditory deprivation. In simultaneous choice tests with normal and filtered maternal calls, devocal-isolated ducklings were much more likely than vocal-communal ducklings to select the mallard maternal call in which the higher frequencies were severely attenuated, thus indicating their relative insensitivity to the higher frequency components of the maternal call. On the other hand, the devocal ducklings were as adept as vocal ducklings in selecting the normal mallard maternal cal1 when it was pitted against a low-frequency attenuated mallard call. Thus, the perceptual deficiency resulting from embryonic and postnatal auditory deprivation is selective in the sense of being relegated to the higher frequency components of the maternal call. Devocalization prevents the embryo and hatchling from hearing their own vocalizations all of which happen to be in the high-frequency range (greater than or equal to 1,500 Hz).


Role of interference in retention by rats with hippocampal lesions. Involvement of the hippocampus in memory was studied in the rat by employing a retention task with and without interpolated activity. Rats with extensive damage to hippocampus were able to relearn a preoperatively acquired single-alternation task with savings and to perform the single alternation with relatively long delays at a level similar to that of control subjects. However, hippocampals were more affected than normals by an interpolated activity that interferes with retention. The finding of normal retention combined with increased susceptibility to interference supports the view that the memory impairment in subjects with damage to hippocampus may be due to an excess of interference among stored information.


Cholinergic blockade, septal lesions, and DRL performance in the rat. Four experiments describing the effects of cholinergic blockade produced by systemic injection of either atropine sulfate or atropine methyl nitrate on the differential reinforcement of low rate (DRL) responding of rats are reported. It was shown that atropine sulfate injected either chronically or at high dosage suppressed DRL responding. Injected acutely, atropine sulfate produced disinhibitory effects. When atropine was injected either chronically or acutely into animals with septal lesions, there was suppression of responding. It was suggested that the specific behavioral outcome resulting from cholinergic blockade depends on the balance resulting from the competing peripheral and central effects of such blockade.


Interactive effects of training condition and septal lesions on perseverative responding in the rat. Rats that had received septal lesions either prior to acquisition of a position habit (Group SAR) or immediately after position habit acquisition (Group SR) were tested on two reversals of the task. Compared with control-operated rats, both groups of rats with septal lesions exhibited position-habit reversal deficits. The two groups with septal lesions could not be distinguished in terms of the total number of errors made during reversal learning, but could be distinguished on the basis of the type of error committed. Compared with Group SR, Group SAR made significantly more perservative errors on the first reversal and significantly fewer perserverative errors on the second reversal. Group SR made significantly more nonperservative errors than Group SAR on both reversals.


Interhemispheric transfer of extinction of the active avoidance reaction in rats. Cortical spreading depression (CSD) was employed in rats to study the lateralization of extinction of a jumping avoidance reaction. Under unilateral CSD, 181 nonreinforced trials were needed to extinguish the avoidance reaction acquired in three 100-trial sessions of intact-brain training. During a second extinction session, either with the same or with the contralateral hemisphere depressed, the mean number of trials to the extinction criterion (9/10) was 39 (n = 12) or 186 (n = 15), respectively. Five extinction trials performed with the brain intact 1 hr before extinction with contralateral CSD decreased the number of trials to extinction of 98 (n = 11). Thus, extinction of active avoidance can be lateralized and interhemispherically transferred in the same way as acquisition of this habit.


Pharmacolinetics of fluorocarbon 11 and 12 in dogs and humans. Blood levels and exhalation bag contents of FC-11 and FC-12 from dogs and humans were used to elucidate the pharmacokinetic model describing the time-course of these agents. The derived pharmacokinetic parameters were in good agreement with the physicochemical properties of these substances. The model was used to estimate the percentage of dose absorbed, which averaged 77 per cent for FC-11 and 55 per cent for FC-12, and to predict the level of FC-11 and FC-12 under a variety of conditions simulating both short- and long-term exposure to the maximum allowable concentrations of these agents. With similar doses, an 8-hour continuous exposure was estimated to produce levels of FC-11 and FC-12 that are much lower than the corresponding levels reported to induce cardiac sensitization in dogs.


Neonatal androgenic stimulation and adult sexual behavior in male and female golden hamsters. Neonatally and adult castrated male hamsters as well as neonatally androgenized and nonandrogenized female hamsters were tested for both mounting and lordosis behaviors during treatment with either testosterone or ovarian hormones. Neonatal androgenization facilitated mounting behavior in adult animals administered either testosterone or ovarian hormones and suppressed lordosis behavior in adult ovarian-hormone-treated animals. Early androgen effects on the display of lordosis behavior during adult testosterone treatment were complex and varied with the exact timing of perinatal endogenous or exogenous androgenization. Species differences in hormone-behavior relationships and the possible role of perinatal androgenization in the development of rodents' ability to aromatize androgens were discussed.


Demonstrations of neophobia and enhanced neophobia in the albino rat. The conditions under which neophobia and enhanced neophobia occur in the albino rat were studied. Neophobia to a .1% saccharin solution was demonstrated in a 10-min single-bottle test. This neophobia was enhanced by pairing water ingestion with a radiation exposure of 100 r. or an injection of lithium chloride 24 hr prior to the saccharin test. In addition, it was found that the differences in consumption of saccharin in a 10-min single-bottle test due to neophobia and enhanced neophobia were produced by consistent differences in drinking rates which appeared early in the 10-min period. The disappearance of neophobia and enhanced neophobia in a 1-hr single-bottle test suggested that the effects of neophobia and enhanced neophobia are short-lived and are best measured in a brief single-bottle test. Finally, enhanced neophobia was not found when 2 days of water drinking were interposed between LiCl poisoning and saccharin testing.


Relationship between absolute body-fluid deficits and fluid intake in the rat. Acute absolute body-fluid deficits were induced in rats by injection of the diuretic drug furosemide, which caused up to 20% reduction of extracellular fluid volume and up to 2% reduction of intracellular fluid volume. Water and .3 M NaCl were subsequently made available to allow the rats to replace their body fluids by drinking. The rats increased their intake of both fluids, but replaced less than half of the total deficit, thereby tolerating larger and larger voluntary body-fluid deficits as the size of the diuretic fluid loss increased. Plasma measures showed that the rats sustained hypovolemia after drinking, while intracellular fluid volume was apparently restored. Fluid-depleted rats drank normally in response to intracellular dehydration induced by a sodium chloride load. Incomplete restoration of body-fluid balance after body-fluid depletion is due to a failure to drink in response to extracellular dehydration.


Passive avoidance behavior in rats after electroconvulsive shock: facilitative effect of response retardation. Rats were trained in a one-trial passive avoidance task and then were submitted to electroconvulsive shock (ECS) or to sham ECS. Twenty-four hours later they were tested for retention, with the door opened either immediately or 30 sec after the beginning of the test. Rats initially forced to avoid for 30 sec continued to avoid for the entire test, but the others had the usual low step-through latencies seen with ECS-treated animals. Activity measures for those animals stepping through differentiated groups having received footshock from those not having footshock and ECS. A retest 5--10 min later showed "recovery" in the amnestic animals and continued avoidance behavior for those that avoided on the first test. Results are taken as evidence that ECS effects are not on memory storage but on the capacity of the animal to organize information effectively and quickly in order to produce an adaptive response.


Neocortex and feeding behavior in the rat. Consummatory behavior and weight-regulation capacity were measured in 12 normal rats and in 43 rats that survived complete (C), sequential unilateral (U), anterolateral (A), or posterior (P) neocortical ablations. Groups C and A displayed aphagia and adipsia followed by a sequence of recovery stages gualitatively identical to, but shorter than, recovery typically seen following lateral hypothalamic lesions. After recovery, Group C displayed long-term effects of finickiness and pradial drinking. These effects as well as a measure of recovery of body-weight-regulation capacity were significantly intercorrelated with lesion size, and body-weight set point remained significantly lower than normal. Group U was relatively unaffected by the first unilateral ablation and showed, relative the second ablation but displayed the long-term effects. Group P, though significantly affected by the lesion, did not display the pattern or intensity of effects described for the other bilaterally ablated groups.


Septal influences on operant responding in the rat. The afferent and efferent connections of the septum with the hippocampus (fornix) of with the hypothalamus and lower brain stem (medial forebrain bundle) were transected by means of an encephalotome near the point where these pathways enter or leave the septal area. A transection of the fornix that produced minimal direct damage to cellular components of the septum of hippocampus reproduced the effects of large septal lesions on responding in several temporally defined paradigms that involve periods of response suppression (differential reinforcement of low rates, discriminated Sidman avoidance, fixed interval). Transection of the medial forebrain bundle fibers that interconnect the septum with the hypothalamus and lower brain stem did not affect behavior in any of these paradigms. These observations should be veiwed in the context of the results of earlier investigations which demonstrated that transection of the medial forebrain bundle reproduces several other components of the septal lesion syndrome.


Asymmetrical state dependency from temporary septal area dysfunction in rats. Rats with cannulas implanted in the septal area were conditioned, tested, or both conditioned and tested shortly after intracerebral injection of local anesthetic via the cannulas. A 2 X 2 factorial design was used to determine whether the presumed state of temporary septal area dysfunction, previously shown to produce amnesia, has state-dependent properties. A state-dependent learning effect was observed in the rats both conditioned and tested in the dysfunctional stat remembered the aversive conditioning better than those conditioned in the dysfunctional state but tested in the normal state. Since rats conditioned in the normal state but tested during septal dysfunction did appear to exhibit conditioned fear when tested, the state-dependent effect was asymmetrical. Performance effects of the procaine injection were observed and accounted for in determining the state-dependent nature of temporary septal area dysfunction.


Effects of prefeeding on the DRL preformance of rats with septal lesions. Two experiments  reported the effects of prefeeding normal and septal rats prior to their daily sessions on a differential reinforcement of low rates (DRL-20) schedule. Prefeeding reduced responses and increased reinforcements in the case of septal animals, regardless of the level of body weight. In the case of normal animals, prefeeding led to a decrease in responding and an increase in the number of reinforcements obtained only when the animals were at 85% of ad-lib levels, prefeeding, although it decreased responding, also decreased the frequency of obtained reinforcements. These results implied an impairment in normal animals in the discrimination of response feedback by stimulation arising from stomach distention.


Role of estrogens in androgen-induced spontaneous activity in male rats. Three experiments tested the hypothesis that testosterone may be aromatized to an estrogen to stimulate running-wheel activity in rats. Aromatizable (testosterone propionate: TP) and nonaromatizable (dihydrotestosterone propionate; DHTP) androgens were compared with estradiol benzoate (EB) for the ability to induce running in castrated male rats. The DHTP had no effect on running. The TP increased running, but EB was more than 100 times as effective. A relatively small dose of a specific estrogen antagonist, MER-25, was shown to attenuate the effects of both EB and TP on male running. The MER-25 did not affect the running of castrated, oil-treated male rats and did not inhibit the running induced by food deprivation.


Effects of perinatal gonadal secretions on parameters of receptivity and weight gain in hamsters. Influence of ovarian and testicular secretions on lordosis was examined in 64 female hamsters ovariectomized when 1 or 43 days old and in 80 males castrated when 1, 3, 5, or 43 days old. The first of eight weekly 10-min mating tests was initiated at 57 or 113 days. Receptivity was not different among female groups except for higher initial scores for those with ovaries through puberty. Initial and maximum receptivity in males was inversely proportional to castration age. Rate of decrease from maximum appeared higher in males castrated at Days 3 and 5 than at Day 1. Age of initial test was significant for males; older animals had lower initial and maximum receptivity scores. Gonadal secretions decreased weights in both sexes.


Runway performance of rats for brain-stimulation or food reward: effects of hunger and priming. In a runway paradigm, pretrial electric stimulation of the brain (ESB), food deprivation, and to a lesser extent water deprivation increased the running speed of rats to an ESB reward. The trial-by-trail course of the change in running speed after the manipulation of food deprivation resembled the steplike performance effect seen when pretrial priming ESB is changed rather than the incremental learning effect seen when the response contingent ESB is changed. In a second experiment, pretrial ESB enhance rats' performance for an ESB reward, but act in opposing directions rats' performance for a food reward. Implications for Deutsch's model of self-stimulation are discussed.


Hyperstriatal function in the pigeon: response inhibition or response shift? Experiment 1 showed that pigeons with lesions of the anterior or posterior hyperstriatum were impaired relative to unoperated controls and to control operates having neostriatal lesions on both acquisition and reversal of a simultaneous position discrimination. The observation that hyperstriatal birds showed more tendency than controls to halt responding altogether in this situation cast doubt on the notion that the reversal deficit was due to a loss of response inhibition. A second experiment supported an alternative hypothesis, that hyperstriatal birds have a deficit in the ability to shift responding to an alternative stimulus as a consequence of nonreinforcement.


Effect of calories on appetite for palatable food in obese and nonobese humans. Palatable food stimuli were presented to 11 obese and 11 nonobese male human subjects (in three experiments) 1 hr after ingestion of 900-calorie liquid lunches and (on separate days) indentically tasting 450-calorie liquid lunches of equal volume. Salivary responses to the presentation of the stimuli (i.e., appetite) by the nonobese were inhibited by the high-calorie meal, but those by the obses were less inhibited. Hunger ratings were unaffected by calories in either group. Food stimuli were rated as more appetizing by the nonobese after high-calorie meals, but not so by the obese. Parallels with animal findings suggest that salivary responses reflect lateral hypothalamic activity.


Posttrial d-amphetamine sulfate and one-trail learning in mice. Experiments are reported which show that 2 mg/kg of d-amphetamine sulfate injected intravenously immediately after footshock on a one-trail passive aviodance learning task impairs the performance of mice in retention tests 24 and 96 hr late. When the injection is delayed by as little as 90 sec, no such impairment is seen. A similar intravenous injection immediately after the learning trail of a water-rewarded one-trail appetitive task has no discernible affect on performance in retention trails 24 hr and 6 wk later. It is argued that the effects of the amphetamines on learning behavior depend on whether reward or punishment is involoved and, further, that all such effects could be accounted for in terms of the drugs' influence on memory mechanisms.


Selection of strain, growth conditions, and extraction procedures for optimum production of lactase from Kluyveromyces fragilis. Forty-one strains of Kluyveromyces fragilis (Jörgensen) van der Walt 1909 varied 60-fold in ability to produce lactase (beta-galactosidase). The four best strains were UCD No. 55-31 (Northern Regional Research Center NRRL Y-1196), UCD No. C21(-), UCD No. 72-297(-), and UCD No. 55-61 (NRRL Y-1109). Biosynthesis of lactase during the growth of K. fragilis strain UCD No. 55-61 was followed on both lactose and sweet whey media. Maximum enzyme yield was obtained at the beginning of the stationary phase of growth. Bets lactase yields from K. fragilis UCD No. 55-61 were obtained with 15% lactose and an aeration rate of at least .2 mmol oxygen/liter per min. Supplementary growth factors were unneccessary for good lactase yeilds when yeast was grown on whey media. Best extraction of lactase from fresh yeast cells was obtained by toluene autolysis (2% vol/vol) at 37 C in .1 M potassium phosphate buffer, pH 7.0, containing .1 mM manganese chloride and .5 mM magnesium sulfate. The enzyme was concentrated and purified partially by acetone precipitation. At least 95% of the enzyme activity of the concentrated solution was retained after storage for 7 days at 22 C, for 3 wk at 4 C, and for 6 wk at -20 C.


Absorption of antibiotics by the bovine udder. Absorption of 39 antibiotics from the nonlactating bovine udder was compared with absorption of [carbon-14] urea as reference. First order kinetics characterized the absorption of urea and most of the antibiotics during the first 8 to 12 h after intramammary infusion. The absorption of polymyxin B, colistin, neomycin, spiramycin, and several tetracyclines was biexponential. The physicochemical properties of drugs which appeared to govern their absorption from the udder were the degree of lipid-solubility of the nonionized fraction and the dissociation constant. Antibiotic protein binding also influenced absorption. Lipid-solubility was the rate-limiting factor with drugs that are mainly dissociated in milk at pH 6.8. These compounds were absorbed at rates related to their degree of lipid-solubility of nonionized fraction. The concentration of the nonionized molecule in milk was the rate-limiting factor with drugs that were highly lipid-soluble. Results with a number of structurally-related antiobiotics, and with others of diverse structures and physical properties, added considerable confidence to the assumption that antibiotics are absorbed from the udder by nonionic (passive) diffusion. The blood-milk barrier behaves as an inert lipoid membrane to these drugs.


Efficiency of energy utilization by mixed rumen bacteria in continuous culture. Mixed bacterial cultures derived from the rumen were grown in a remen fluid medium in a chemostat at three dilution rates (.02, .06, and .12 per h), each at four growth-limiting glucose concentrations (5.8, 9.9, 12.7, and 25.0 mM). Microscopic observations indicated that a relatively complex mixture of bacterial species was maintained and proportions of fermentations products were similar to those of the rumen except for elevated proportions of methane and acetate. Cell concentration increased linearly with increases in glucose concentration. The range of glucose concentrations had little effect on yields of cells or products produced per mole of glucose fermented. With increases in dilution rates, the amount of butyrate and methane produced per mole of glucose fermented decreased and the amount of propionate increased. Yield glucose (grams cells produced per mole of glucose fermented) increased from 42 at a dilution rate of .02 to 84 at a dilution rate of .12. These large increases are discussed in relationship to the energy requirements for maintenance of bacteria. A theoretical maximum yield glucose of 89.3 and a maintenance requirement of .26 mmol glucose per g cells per h were calculated. Moles of adenosine triphosphate produced per mole of glucose fermented and yield of cells produced per mole of adenosine triphosphate are discussed.


Ensiled diet containing processed municipal garbage and sorghum forage for heifers. Diets of similar proximate analysis formulated with a base of sorghum forage and primarily supplemented with equivalent dry matter of 18.4% of aerobically digested municipal garbage (garbage diet) or 17.5% of cottonseed hulls (control diet) were ensiled for 52 days and then individually and group fed to 16 dairy heifers for 56 and 35 days. Apparent digestibility of dry matter, crude protein, ether extract, crude fiber, and nitrogen-free extract in garbage and control diets averaged 54.2 and 47.4, 50.0 and 41.3, 62.0 and 65.1, 53.1 and 42.3, and 61.8 and 54.5% as determined by chromium oxide technique. Potential advantages from digestibility of the garbage diet appeared to be nullified by a 12% depression of dry matter intake and a consequent deterioration of feed efficiency. Dry matter intakes of garbage and control diets during the 56-day comparison were 1.98 and 2.25% of body weight and daily gains of .42 and .57 kg required 13.9 and 11.8 kg dry matter per kilogram of gain. Over the 91 days of combined comparison feeding, the .62 kg of average daily gain from control diet was 32% above the .47 kg from the garbage diet.


Growth and carcass evaluation of Holstein steers fed liquid acid whey. Thirty Holstein steer calves, 96.5 kg, were assigned to three groups. Two groups received liquid acid whey, and one was the water control. Grain was fed either restricted or ad libitum to the whey groups and ad libitum to the water control group over three 14-wk growth periods. Hay, up to .4% body weight, reduced symptoms of bloat. Period 1: Calves started on a 20% crude protein dry ration for 7 wk and then changed to a 16% crude protein dry ration for 7 wk gained faster and were heavier than calves statred on a 30% crude protein dry ration for 7 wk and then changed to a 20% crude protein dry ration for 7 wk. Period 2: Body weights among groups were not different by the end of the period. Intakes of whey were 33.6 kg daily with grain ad libitum and 49.7 kg daily with restricted grain feeding. Water intake was 22.2 kg daily. The steers obtained 28% of their total dry matter intake from acid whey under ad libitum feeding, and 48% from acid whey under restricted feeding. Period 3: Final body weights were decreased by restricted feeding, but acid whey intake increased to 55.6 kg daily. These steers obtained 57% of their total dry matter intake from acid whey. Acid whey treatment resulted in lower carcass dressing percent, rib fat cover, and loin eye area. Grades averaged Standard for acid whey, restricted grain feeding and Low Good for acid whey, ad libitum grain feeding. Lower panel scores were given for aroma and quantity of juice for restricted grain feeding. Acid whey treatment did not change tenderness, shear values, or overall carcass desirability.


Effect of prepartal hormone administration on feed intake and mineral metabolism of cows. Subcutaneous administration of progesterone (.25 mg/kg body weight per day) to mature cows from 14 days before projected parturition until parturition increased feed intake over control cows. Incidence of milk fever and plasma calcium, phosphorus, magnesium, and hydroxyproline were not significantly different between treated and control cows. Subcutaneous administration of estradiol-17beta (.05 mg/kg body weight per day) or oral administration of melengestrol acetate (1 mg/day) from 7 days before projected parturition date until parturition decreased feed intake over control cows. Milk fever incidence and absorption of calcium, phosphorus, and magnesium were not significantly different between treatment groups. Plasma calcium was not significantly different between treatment groups during either the prepartum or postpartal periods but tended to be higher postpartum in cows treated with estrogen.


Milk progesterone in postpartum and pregnant cows as a monitor of reproductive status. Milk samples were analyzed for progesterone content by a petroleum ehter extraction and competitive protein binding assay validated for milk. In one experiment, 11 cows were sampled twice daily for 24 days beginning with an observed estrus 15 to 45 days postpartum, and again 19, 21, 23, and 25 days after breeding. Progesterone values during the estrous cycle paralleled those for blood plasma but were slightly higher at estrus (1.49 ng/ml milk) and maximum (9 ng/ml) on days 11 to 16 of the estrous cycle. After breeding, cows later diagnosed pregnant averaged 7.12 ng/ml while those later found to be nonpregnant averaged 2.36 ng/ml. All diagnoses of pregnancy were correct. In a separate experiment there was no difference between milk from front and rear quarters, but progesterone was highest in last milk, intermediate in composite milk, and lowest in first milk.


Relationships of children's grade in school, sex, and social class to teachers' ratings on the behavior problem checklist. The present study investigated the relationships of children's grade in school, sex, and social class to teachers' ratings on the Behavior Problem Checklist (BPCL). The sample consisted of 1,999 white children from kindergarten through fifth grade who were in regular classes. Three conclusions may be drawn from the study. The first is that grade and the interactions of grade with sex and social class are determinants of scores on the BPCL, but that no particular trends are characteristic of the relationships between these and the dependent variables. The second is that sex and social class are also determinants of scores on the BPCL, with boys and children from the lower social classes having more problems and girls and children from the higher social classes having fewer problems. The third is that the differences between schools and between teachers are responsible for more of the variance on the BPCL than grade, sex, and social class.


Elective mutism in a first grader: the remediation of a complex behavioral problem. Teachers frequently deal with unusual and perplexing behavioral problems in their classes. This study demonstrates how spontaneous and prompted speech were produced in a six-year-old mute by a first-grade teacher and her aide. A reinforcement system for peer-prompted speech and spontaneous speech was employed in three separate school classes in a multiple-baseline fashion. The reinforcement system produced prompted and spontaneous speech in each situation. Postchecks in the second grade indicated the child was still speaking and conversing spontaneously with his peers. This study suggests a method that teachers can use in the classroom to deal with this severely handicapping condition.


Multiple criteria follow-up of behavior modification with families. This report presents termination and follow-up evaluations of a parent training program based on behavior modification principles. Treatment termination outcome data were obtained for 22 families, and follow-up data were collected on 14 of these families 3 and 8 months after treatment. Results indicated a fairly high level of success at termination on the basis of parent-collected observational data, parent attitude change toward the children, and parent attitude concerning the process and outcome of treatment. Modest levels of success were evidenced on the basis of behavioral data recorded by trained observers in the home. Families who participated in follow-up demonstrated greater cooperation and involvement with the treatment program than those who did not participate. In all other respects, however, these two groups were similar. Follow-up data on parent attitude measures demonstrated maintenance of the treatment effects. Parent observational data were incomplete, but also showed maintenance in follow-up. For the subsample of 14 cases, home observation records indicated a nonsignificant decline in deviant behavior at termination followed by a nonsignificant increase in deviant behavior during follow-up. The meaning and implications of these discrepant findings were discussed and compared with results from other laboratories.


Contingency management of self-report and cleaning behavior. The effects of a contingency management program utilizing a reinforcing event (breakfast) were investigated in respect to cabin-cleaning and self-report behaviors in a group of nine male campers, ranging in age from 11 to 13. Control of cabin-cleaning behavior was clearly demonstrated. The large discrepancy between camper self-ratings and counselor ratings disappeared when the opportunity to line up for breakfast was made contingent upon both accuracy of self-report and improved cleaning performance.


Children vulnerable to psychopathology: the Stony Brook high-risk project. The study of children at risk for the development of schizophrenia is a promising research strategy for increasing our understanding of the etiology of schizophrenia. This paper describes the methods and procedures of such an investigation. Three groups of children are being followed: those who have a schizophrenic parent, those who have a depressive parent, and tose whose parents have no psychiatric history. There are three major foci of our assessment procedures. First, the patient, spouse, and family environment are examined. Second, the children are assessed in school from the vantage point of both peers and teachers. Finally, the children are tested with several laboratory measures of cognitive processes, attention, emotional responsivity, and social interaction.


[Phosphorus-32 test and thermography in hormonal study of breast cancers]. The results given by the P 32 test and thermography were compared in 92 cases of cancer of the breast, of which 7 appeared after oestrogens or androgens had been administered. After a hormone test of short duration it seemed that reliable results indicating hormone-dependent cancers would only be obtained with the thermographic test.


[Study of breast cancer by means of liquid crystals thermography]. Liquid crystals thermography allows a very precise study of breast cancers. It is particularly important for diagnosis of very small tumors and for follow-up of irradiated breasts. It gives pronostic and therapeutic information.


[Ultrasonic diagnosis of breast diseases]. The main interest of diagnostic ultrasound for breast diseases is the differentiation between solid and cystic masses, between benign and malignant tumors, the precise measurement of tumors. From 601 cases compiled in the litterature, ultrasonic correct diagnosis reach 88% and more than 90% if tumor size is 2 cm or more. Differentiation between cancerous and benign tumor is based on the sensitivity graded tomograms method.


[Radiology of the pathology of benign breast diseases]. The authors have presented several radiologics aspects of benign tumors insisting on the difficulty to make the limit between benignity and malignity and that in this cases one minute clinical examination can be contributive. Complementaries examinations so are cystography and galactography are often necessary to precise the diagnostic. The authors remind that it is not easy to define radiologics patterns of benignity.


[Value of breast xerography].

[Value of breast xerography]. The interest of breast xerography is: Diagnostic study of dense breast. Diagnostic study of axillar region. Follow-up of breast cancer treated by radiations only.


[Classification of radiographic findings in breast tumors]. By establishing an original protocol and pooling their results, the authors have attempted, at the level of their respective centers, to define statistically the results obtained by these methods of comparison with regard to two large groups of patient recruitment one depending on controlled consultations, the other on the consultations for early detection of disease. The comparative study of the results obtained on these two groups provides useful information on the significance which one should attribute to the frequency given by the different authors for several types of tumors.


[Prognostic classification of mammary cancers based on mammography]. The pronostic classification based upon 8 radiographic signs (concerning malignant edema, tumor size and opacity aspect) allows to precise the clinical classification and is in good aggreement with the thermography classification of these cases. Localized or diffuse malignant edema is always of poor prognosis.


[Diagnostic difficulties in mammography]. The authors point out the main causes of error in the radiology of the mammary gland. The source of these errors may be found at several levels in the diagnostic scale ranging from the object itself to the interpretation of the image by the examiner. Some of these causes are illustrated by definite examples: the absence of a radiographic translation of a tumor; round or finely irregular opacities. It is in the collaboration of radiologists with pathologists that the diagnosis is improved.


[Role of hormones in the genesis of breast cancer]. The author makes a general review of the influence of hormones on carcinogenesis of the breast. He explains the efforts wich have been made these last years in order to formulate a pronostic which could predict the efficacy of a treatment. He finally discuss the possible part hormones could play and among them principally oestrogens and prolactin in the breast cancer.


[Cytology of nipple discharge and breast cysts]. The reliability of this cytodiagnosis is less good than for malignant tumors cytology by fine needle puncture.


[Nipple discharges without palpable tumor]. In the majority of the cases of nipple discharge the cause is a benign lesion: nearly 50% are papillomas. Biopsy is always indicated in nipple discharge without palpable tumor. A long follow-up of the patients is necessary.


[Histology of precancerous lesions of the breast]. The authors are dealing with the problem of pre-cancerous lesions from data contained in the pathological archives of the Institut Gustave-Roussy. One series consists of 320 cases operated upon for benign lesions or tumors of the breast (Fibroadenomas appearing at a relatively advanced age) of which 4 developed cancers. The past histories of another series of 730 patients having had mastectomies for cancer are examined; 24 of these had been operated upon previously for benign tumours or lesions of the breast. Attention is drawn to a number of histological signs the presence of which in an "a priori" benign lesion should evoke caution: multilayered epithelium of the galactophores glands with an "en flammèche" appearance, tubular adenomatous hyperplasia, irregular lobular hyperplasia, microcalcifications... Despite careful examination of multiple sections, the pathologists decision between benign and malignant lesion continue to be difficult.


[Cytological examination. Solid breast tumors examined by means of fine-needle puncture]. The value of cytological diagnosis of solid tumours of the breast where the cells were obtained by suction aspiration through a needle has been analysed in a consecutive series of 2,401 cases, all of which were checked by histological examination. They consisted of 1,745 malignant tumours and 656 benign tumours. The cytological diagnosis of malignancy was confirmed, almost always, error being practically non-existent (4 out of 1,000). This confirms that this simple and rapid test is very valuable in the diagnosis of mammary cancer. On the other hand, when the diagnosis of a benign tumour was made a certain number of cancers were missed (3.6 per cent). This is not therefore as valuable a test when the result is negative as when the result is positive. All the same, in certain cases it can suggest the diagnosis without giving the precise type of lesion, which can only be finally diagnosed histologically.


[Correlation between histology, cytology and clinical examination]. There exist, very frequently, an excellent correlation between cytology, histology and clinical examination in breast diseases. Combination of different methods reduce the risk of false diagnosis.


[Inspection in the diagnosis of breast carcinoma]. The School of Centre Broca has improved the clinical procedures of early  detection of breast carcinoma. For 421 checked up carcinomas, including micro-carcinomas, in more than 9 out of 10 cases, the diagnosis has been based on the inspection signs. The latter has to be a dynamical inspection. Description is given of the various phases of this inspection, i.e. postural phases and phases of mobilization. The rate of the false negative clinical results does not exceed the one of each of the para-clinical investigations (mammography or thermography). An early detection of a mass may be made if each practioner contraints himself to perform systematically in his female patients the dynamic inspection of the breast.


[Telethermography of the breast].

[Telethermography of the breast]. Thermography has become indispensable for diagnosis of malignant and benign breast diseases. Technique and interpretation of the thermogram are described. The place of Thermography amongst the various breast investigations is discussed.


[Telethermographic follow-up of breast cancers treated by radiotherapy]. The study of 635 breast cancers before and after radical radiation therapy, allows us to define 4 different ways of evolution: progressive linear cooling or sterilization, persistent thermal abnormalities or non-sterilization, relighting following a cooling phase or recurrence, persistent tepid breasts, meaning a radiation sequela (radiotherapic breast). We must emphasize that telethermography allows us to define the opportunity and timing of secondary surgery.


Altered reabsorption of protein by the renal cortex in rats treated with hypertonic saline or mannitol. The reabsorption of horseradish peroxidase (HRP) by the proximal tubule cells of rat kidneys was investigated by measuring the concentration of HRP in total particulate fractions of the cortex 1/4 and 1 hr after intravenous injection, and by correlated cytochemical observations. When compared to the corresponding values of the control animals, the concentration of HRP 1 hr after injection was decreased approximately 10-fold in the renal cortex of rats which had received an intravenous injection of hypertonic saline or two subcutaneous injections of mannitol. The plasma clearance and the urinary excretion of HRP were not altered significantly after injection of hypertonic saline, but the plasma clearance was decreased and the urinary excretion increased after injection of mannitol. When the dose of injected HRP was varied, the reabsorption of HRP by the renal cortex was proportional to the dose in the experimental and the control animals. Cytochemical staining for peroxidase activity also showed that the phagosomes and phagolysosomes of the proximal tubule cells contained much less peroxidase in the experimental rats than in the control rats. After injection of mannitol, large vacuoles appeared in the proximal tubule cells. The vacuoles often contained peroxidase-positive granules (phagosomes) which varied in diameter from the limit of microscopic visibility up to several microns. Most of the vacuoles did not react for acid phosphatase activity, but lysosomes were often aggregated around the vacuoles and seemed to release acid phosphatase into the cytoplasm. Certain analogies between the reabsorption of protein and that of water by the proximal tubule cells are discussed.


Bismuth localization within nuclear inclusions by x-ray microanalysis. Effects of accelerating voltage. This report details the localization of bismuth by energy-dispersive x-ray microanalysis within characteristic nuclear inclusion bodies of renal tubular lining cells of rats following excessive exposure to this element. Peak to background ratios and analytical detection sensitivities for bismuth were found to vary for 04, 60 or 80 keV electron accelerating voltages. Optimum peak to background ratios were observed at 40 keV due to lower background generation, while greater detection sensitivities were recorded at 80 keV due to enhanced generation of bismuth characteristic x-rays.


The coating of mouse myocardial cells. A cytochemical electron microscopical study. The coating of mouse myocardial cells has been investigated with a variety of cytochemical methods. The coating of the surface membrane gives a positive reaction with ruthenium red, colloidal thorium, phosphotungstic acid (PTA) at low pH, silver methenamine after periodic oxidation (PA-silver technique) and with silver proteinate after periodic oxidation and thiocarbohydrazide treatment (PA-TCH-silver technique). The coating of the T system gives almost similar results. The nexuses do not react with PTA nor with the PA-silver and PA-TCH-silver techniques, but they are strongly stained with ruthenium red which reveals periodic structures in their gaps. The specificities of the colloidal thorium technique and PAT staining have been tested by chemical treatments (methylation, acetylation, saponification), enzymatic digestions (pronase, trypsin, hyaluronidase, neuraminidase) and carbohydrate extractions (with 0.1 N NaOH and 0.05 M H2SO4). These cytochemical data indicate, considering the specificity of the reactions, that the coating of the membrane surface and the T system contains polyanionic groups. A part of them, at least, would belong to a carbohydrate-containing material (glycoproteins), whereas at the level of nexuses the sugar residues would probably be absent.


Electrophoretic studies on the phosphorylase isozymes. The electrophoretic method of Davis, Schliselfeld, Wolf, Leavitt and Krebs (1967) for phosphorylase isozymes has been modified. By this method, five isozymes were separated in various organs of rat and pig and were disignated as phosphorylase L, LI, I, II and III. The L and III enzymes were the only forms found in liver and skeletal muscle, respectively, while the I enzyme was dominant in brain, uterus, lung and small intestine, which also contained some fractions of the II and III enzymes. The I enzyme was also dominant in adrenal, ovary and kidney, but these organs contained the L+II or L+LI as minor components. The L and LI were richly found in spleen and leukocytes of adult rats and pigs and in liver of newborn rats. Such organ-specific heterogeneity of phosphorylase was confirmed by the immunological tests with the antibodies prepared against phosphorylases I, III and L. The II and LI enzymes were found to be the hybrid molecules between the I and III enzymes, and between the I and L enzymes which have been previously reported as unhybridizable, respectively. In view of the above findings, it was concluded that the rat and pig possessed at least five molecular forms of phosphorylase.


N-acetyl-beta-glucosaminidase activity in normal and malignant leukocytes. An improved cytochemical method demonstrating N-acetyl-beta-glucosaminidase in peripheral blood and bone marrow leukocytes is described. A significant elevation in enzyme activity in circulating monocytes from patients with solid tumor malignancies was observed. In a large series of cases of acute nonlymphocytic leukemia, elevated levels were found in the vast majority of those leukemias that had a predominant monocytic component identified either morphologically or by standard cytochemical methods. This reaction would appear to be useful as a monocyte marker.


Adenosine triphosphate and phosphocreatine levels in cochlear structures. Use rate and effect of salicylates. Guinea pigs were injected with various dosages of salicylate for varying time periods. The temporal bones were removed, frozen quickly, freeze-dried, and the cochlea was dissected into essential auditory component parts and subjected to microchemical analysis for phospho-creatine (P-creatine) and adenosine triphosphate (ATP) levels. It was found that high energy phosphates were not decreased by therapeutic or acutely toxic levels of salicylate. Only when chronic intoxication with salicylate was accomplished was there a reduction in ATP and P-creatine. The data presented do not provide support for the widely held view that uncoupling of oxidative phosphorylation or inhibition of enzymes involved in energy generation in the inner ear structures studied (organ of Corti, stria vascularis, Reissner's membrane, modiolar blood vessels, cochlear nerve and spiral ganglion) are the mechanisms by which salicylates cause reversible hearing loss. The study confirms the existence of a P-creatine gradient opposite to the well known glycogen gradient in the organ of Corti (Krzanowski JJ Jr, Matschinsky M: J Histochem 19:321, 1971) and suggests a relatively uniform energy use rate of this tissue for all four turns (20 mmoles of approximately phosphorus used/kg dry weight/min).


7-Amino-actinomycin D as a cytochemical probe. I. Spectral properties. The optical absorption and fluorescence characteristics of 7-animo-actinomycin D were determined to evaluate its potential as a fluorescent cytochemical probe. At pH 7.0, the absorption maximum and fluorescence excitation maximum are both at 503 nm; the fluorescence emission is at 675 nm. When this compound forms complexes with DNA in solution, the absorption and fluorescence excitation maxima shift to 543 nm and the fluorescence emission shifts to 655 nm. The fluorescence quantum yield is 0.016 for 7-amino-actinomycin D free in solution and 0.01-0.02 for complexes with native DNA. The 7-amino-actinomycin D also exhibits fluorescence shifts characteristic of binding when put into solution with poly(dG-dC) poly(dG-dC), but not with poly(dI-dC) poly(dI-dC). The spectral characteristics are the same at pH 7.0 whether the solvent is 0.01 M PO4 with 0.0001 M EDTA or Earle's salts with 0.025 M N-2-hydroxyethylpiperazine-N1-2-ethanesulfonic acid.


Histochemical localization of trehalase activity in dorsal flight muscle of the flesh fly Sarcophaga bullata with light and electron microscopy. Trehalase activity in flight muscle of the flesh fly Sacrophaga bullata is detected histochemically at light- and electron-microscopic levels by using diaminobenzidine, glucose oxidase and peroxidase in the incubation medium. The association of trehalase activity with the inner mitochondrial membrane is confirmed. Biochemical assay shows that about 50% of the initial total trehalase activity is lost from the tissue during the histochemical processing and about 50% remains for histochemical detection.


The ultracytochemical demonstration of a formaldehyde-resistant dehydrogenase of leuco nitroxyl analogues. A dehydrogenase which is relatively stable in formaldehyde fixative is demonstrated ultracytochemically by the reduction of various leuco nitroxyl analogues in rat hepatic, renal, myocardial, skeletal muscle and prostatic tubuloalveolar glandular tissues. The nonosmiophilic tetrazolium salt, t-(2'-benzothiazolyl)-5-styryl-3-(4'-phtalhydrazidyl) tetrazolium chloride, is subsequently reduced to an insoluble osmiophilic formazan by the hydrogen ions resulting from the dehydrogenase activity. Exposure of the formazan to osmium tetroxide results in electron density enabling visualization of the reaction product in the electron microscope. Known inhibitors of various dehydrogenases were utilized in an attempt to determine the existence and/or extent of any specific characteristics of the dehydrogenase(s) involved.


Quantitative light microscopic autoradiography. Emulsion sensitivity and latent image fading. Emulsion sensitivity, latent image fading, and the effects of temperature, humidity, radiation dose and chemography on them were measured for NTB2 autoradiographic emulsion using quantitative methods. Sensitivity of NTB2 emulsion increased as the temperature during exposure increased, with the greatest increase per degree occurring between -20 degrees C. At 4 degrees C, emulsion sensitivity remained constant with time and radiation dose. Direct measurement of latent image fading showed no latent image fading for 60 weeks on slides exposed at 4 degrees C with Drierite. Slides exposed at 27 degrees C showed significant latent image fading and great variation between samples. High humidity decreased emulsion sensitivity and increased latent image fading. No evidence of either positive or negative chemography was found. The practical use of autoradiography requires an internal standard on each slide to correct for fluctuations in temperature and humidity during exposure time.


Electro-immunoabsorption in gel, application to enzyme studies (alpha- and beta-amylases from barley). A technique combining immunoabsorption, electrophoresis and enzymatic characterization reactions in the same gel medium is described using alpha- and beta-amylases from barley seeds, their corresponding immune sera, and alpha-amylases from bacteria. The sensitivity and the specificity of the technique have been determined for alpha-amylase. Two applications of this technique are presented: 1) in physiological studies to ascertain whether an anti-enzyme immune serum reacts with all the forms of the enzyme under study and, 2) for detecting, among antigenically characterized enzymes, proteins which have the same enzymatic activity but are antigenically different. The possibility of applying this technique to other enzymes is discussed.


Quantitative estimation of cytotoxic activity of immune lymphocytes using 51Cr-labelled peritoneal macrophages as target cells. Peritoneal macrophages labelled with 51Cr in suspension and cultivated for 48 hr on glass pretreated with poly-L-lysine were used as target cells for determination of the cytotoxic effect of immune lymphocytes. 51Cr release from such target cell from different strains of mice is 15.5 +/- 0.8% of the total target cell radioactivity after 20 hr incubation with normal allogeneic lymphocytes. The use of 2% sodium dodecylsulphate ensures 100 percent solubilisation of labelled target cells growing on the glass surface and permits the cytotoxic effect to be determined by both 51Cr release and measuring the label retained by the intact cells. The two methods proved to be accurate, reproducible and in accord with each other as well as with the method of direct cell counting. Determination of released 51Cr enables the cytotoxic effect of lymphocytes to be measured after 4 hr incubation with the macrophage monolayer. SaI and Mc11 ascitic sarcomas display different sensitivities to the cytotoxic effect of immune lymphocytes and require different optimum conditions for its development.


Effect of lipid solvents on protein, DNA, and collagen synthesis in human skin: an electron microscopic autoradiographic study. The effect of acetone and kerosene on the synthesis of protein, DNA, and collagen was studied by electron microscopic autoradiography using [3H]leucine, [3H]thymidine, and [3H]proline as tracers in human skin. Quantitative analyses following concomitant administration of tritiated leucine and acetone or kerosene demonstrated, at 90 min, a marked decrease in silver grains as compared to control or nonexposed areas. Incorporation of tritiated thymidine is moderately stimulated only by acetone, whereas radioactive proline distribution is not significantly affected. Electron microscopic autoradiograms revealed that tritiated leucine is distributed over all epidermal cells, mostly in the stratum spinosum of control epidermis; a marked decrease of silver grains from [3H]leucine followed both lipid solvent exposures. The autoradiographic reaction is specifically located over cytoplasmic organelles, such as polysomes, endoplasmic reticulum, and especially tonofilaments. Tritiated thymidine resulted in silver grains mostly over nuclear chromatin and these were moderatly increased after acetone application, whereas the incorporation of radioactive proline in the fibroblasts and collagen fibrils were not significantly influenced. These investigations indicate a dissociated effect of lipid solvents on protein, DNA, and collagen synthesis in human skin.


Pagetoid premalignant melanosis and melanoma: differentiation from Hutchinson's melanotic freckle. Twenty-three examples of pagetoid premalignant melanosis have been analyzed by clinical, histologic, histochemical, and microscopic techniques. Utilizing criteria based on these findings, the pagetoid lesions can be differentiated from Hutchinson's melanotic freckel and seem to be particular types of nevocytic pigment cell tumors.


New observations in the histopathology of erythema nodosum. Erythema nodosum presents variable clinical and histologic patterns of response in the vessels, septa, and fat lobules of the subcutaneous tissue. Acute or chronic phlebitis with hemorrhage may be commonly observed; acute panniculitis is observed in foci, but at time it may be the principal histologic feature; lymphocytic infiltration of fat lobules is often found, and lymphoid nodules are not infrequent; rarely, chronic granulomatous lesions involve septa or fat lobules; and proliferative lipocyte response may be observed. Because these variable histologic patterns may be coexistent, excision biopsy and multiple sections are necessary to recognize them. The variable histologic features correlate with the different clinical forms: acute nodular, chronic nodular, migrating plaque lesion, cellulitis, and the rate suppurative form. This variety of panniculus response in erythema nodosum can be explained on the basis of host-tissue response to a delayed hypersensitivity reaction to an antigenic stimulus.


Further studies of photoaugmentation in humans: phototoxic reactions. The addition of modest amounts of long ultraviolet light (UV-A) to 1/2 minimal erythema dose (MED) of sunburning irradiation (UV-B) produced erythema visible at 24 hr, the prototype of the photoaugmentation phenomenon. The results were the same whether UV-A was given before or after UV-B. Photoaugmentation could be demonstrated after an inverval of 6 hr between doses, but not after 1 day. Photoaugmentation has also been demonstrated clinically and histologically with two topical photosensitizers, coal tar and 8-methoxy-psoralen.


Pulmonary elastic tissue in generalized elastolysis (cutis laxa) and Marfan's syndrome: a light and electron microscopic study. We have studied elastic tissue changes in the lungs from patients with Marfan's syndrome, generalized elastolysis, patients with emphysema of other cause, and those dying from unrelated causes. Degenerative changes were seen in the elastic tissue fibers in patient's with Marfan's syndrome; they varied from mild to severe. Elastic fibers in the lungs of patients with cutis laxa showed by light and electron microscopy the same morphologic changes previously reported in the skin and vessels. While the alterations in individual elastic fibers in the alveolar septa appeared similar, in cutix laxa there was severe involvement of almost all fibers, whereas in Marfan's syndrome the involvement was not so severe, nor did it affect all fibers. On examination of lung sections from patients with cutis laxa or Marfan's syndrome, both were readily separable from normal and abnormal controls.


Melanogenesis from topical mechlorethamine and analogues in skin of hairless mice and in vitiligo. Progressive repigmentation occurred in vitiliginous skin of two patients topically treated with aqueous solutions of mechlorethamine. Hairless mice were found to provide what seems to be a satisfactory cutaneous system for evaluating potential melanogenic properties of topically applied test compounds.


Changing patterns of incorporation of (14C)histidine and (3H)leucine into epidermal proteins during differentiation of fetal rat skin. Synthesis of epidermal proteins has been assessed during epidermal differentiation in fetal rat skin by studies of the simultaneous incorporation of [14C]histidine (H) and [3H]leucine (L) in vitro. Relative incorporation of the two amino acids into epidermal proteins was assessed in terms of H/L ratios and absolute rates of incorporation related to DNA content. Biochemical parameters were correlated with morphologic development. An increase in incorporation of both amino acids accompanied stratification and development of granular and cornified layers between 18 days of gestation and 3 to 5 days postpartum. Relatively greater incorporation of histidine after development of mature granular cells and stratum corneum was reflected in increasing H/L ratios. These results correlated with negative Pauly staining of the initial fetal keratohyaline granules at day 18 and positive staining of mature granules at subsequent stages of development. H/L ratios appear to represent a sensitive marker for differential protein synthesis during differentiation in whole epidermis. The results suggest that biosynthesis of histidine-rich protein is associated with production of mature keratohyaline granules during fetal development.


Staphylococcal toxic epidermal necrolysis: pathogenesis and studies on the subcellular site of action of exfoliatin. An exfoliating substance elaborated by certain phage Group 2 staphylococci causes toxic epidermal necrolysis. Both in man and in the newborn mouse, intraepidermal cleavage is the predominant histologic feature following exposure to this toxin. Electron microscopic study of sequential biopsy specimens obtained from neonatal mice and from organ cultures of human skin revealed intercellular cleavage and cell separation. The extracellular nature of the exfoliative process was confirmed in several ways: (1) perfused tracers did not penetrate cells during cell separation; (2) cultured cells exposed to high doses of exfoliating fractions demonstrated no signs of injury; and (3) cleaved surfaces examined by scanning electron microscopy and surface replication demonstrated intact plasma membranes. When fractions capable of inducing exfoliation were applied to cultured keratinocytes of fibroblasts, sperm, or lymphocyte suspensions, and to human or mouse skin in vivo, they did not alter the distribution or intensity of concanavalin A binding, ruthenium red staining, pemphigus antibody binding, or HL-A surface antigens. Therefore, while the pathogenesis of staphylococcal toxic epidermal necrolysis involves intercellular cleavage, the molecular cell surface target remains unknown.


Rapid regeneration of the dermal-epidermal junction after partial separation by vacuum: an electron microscopic study. A process of rapid repair of dermal-epidermal adherence, as found in experiments with interrupted suction, was investigated electron microscopically. Biopsies in different stages of the process of suction blister formation and of the repair process were studied. Results show that suction blister formation occurs by successive detachment of hemidesmosomes from the basement membrane, and that, after partial separation of the epidermis from the dermis, a rapid regeneration of the dermal-epidermal junction takes place. This regeneration process apparently consists of two steps: realignment of basal cells to the basement membrane accompanied by autophagocytosis of detached hemidesmosomes, and de novo formation of hemidesmosomes. The time required for this structural regeneration corresponds well with the speed of the functional repair of dermal-epidermal adherence measured with the technique of interrupted suction.


Anti-inflammatory effects of antimicrobial agents: an in vivo study. Antimicrobials are used emperically in a variety of inflammatory dermatoses such as rosacea and dermatitis herpetiformis, although these diseases are not believed to be of bacterial etiology. We have used potassium iodide ointment to induce follicular pustules and have found in this in vivo model properties of antimicrobials not related to their antibacterial actions. Topical demethylchlortetracycline and erythromycin (5%) lead to suppression of KI-induced inflammation (erythema, pustules) and systemic use of these drugs as well as diaminodiphenylsulfone produces the same effect.


Treatment of psoriasis with oral mycophenolic acid. Mycophenolic acid (MPA), an inhibitor of purine synthesis, was evaluated for its therapeutic and adverse effects in 29 patients with psoriasis. MPA was administered orally for at least 12 weeks, during which time the daily dose was increased from 1600 to 4800 mg depending on occurrence of adverse reactions. Complete clearing occurred in 1 of the patients, almost complete clearing in 14, definite improvement in 13, slight or doubtful improvement in 1. The full effect of MPA required a median time of 8 weeks (range 5-14). After discontinuing MPA, relapses began at a median time of 4 weeks (range 3-8). The severity of psoriasis was scored on a 0 to 108 scale using a newly devised system. The mean severity and range before treatment was 47 (21-88); after 12 weeks, 15 (0-50). Adjustment of dose on the basis of side effects resulted in a median daily dose of 3600 mg (range 2400-4800 mg; 30-96 mg/kg ideal weight). Characteristic dose-limiting side effects were soft or frequent bowel movements, diarrhea, nausea, and anorexia. One instance of reversible, dose-related leukopenia was identified.


Ability of PABA to protect mammalian skin from ultraviolet light-induced skin tumors and actinic damage. Application of 50 para-aminobenzoic acid (PABA) to hairless mice one hour prior to ultraviolet light (UVL) irradiation will almost totally protect these animals from developing tumors induced by chronic exposure to UVL in the 290 to 320 nm range in conjunction with a chemical carcinogen. Mice exposed to UVL and not protected by PABA developed primarily squamous cell carcinomas. Two months after cessation of chronic UVL exposure, the non-PABA-treated irradiated mouse skin appeared thickened, yellow, and wrinkled while showing elevated DNA synthesis, hyperplasia, hypergranulosis, and increased amounts of elastotic material. The PABA-treated skin was grossly normal.


The inefficacy of riboflavin against ultraviolet-induced carcinogenesis. Flavins are reported to protect cellular DNA against UV irradiation injury in vitro. The possible photoprotective effects of riboflavin in vivo on UV-induced carcinogenesis were studied in three groups of HR-hairless mice. Group I served as control. Group II was painted daily with a 15 mg per ml solution of riboflavin. In Group III, drinking water was replaced with a 15 mg per ml solution of riboflavin in water. All three groups were simultaneously irradiated in a light box with two Westinghouse FS20 sunlamps from a distance of 30 cm for 5 min daily 6 days a week throughout the experiment. By the 11th month all surviving mice developed several histologically proven squamous cell carcinomas. The total numbers and times of onset of tumors did not vary in the three groups. Thus, no protective effect of massive amounts of riboflavin on ultraviolet-induced carcinogenesis in the hairless mouse could be demonstrated when such high dose rates of UV were used.


Simultaneous determination of extracellular fluid and total body water. I. A method for the simultaneous determination of extracellular fluid volume by radiosulfate-35 and total body water by tritiated water is described. Protein was precipitated from plasma with 10 per cent trichloroacetic acid. Radiosulfate-35 and tritiated water were counted in a dual-channel liquid scintillation spectrometer, using an automatic external standard to correct for quench. The sulfate space was calculated by the isotope dilution principle. Crossover counts contributed by radiosulfate-35 into the tritium channel were subtracted from the total counts in that channel. The tritiated water space was then calculated by the isotope dilution principle. Studies were performed in vitro and in 8 bilaterally nephrectomized rats. In vitro extracellular space by radiosulfate-35 and total body water by tritiated water demonstrated less than 3 per cent variation from the predicted volumes. In the rat, total body water determined with tritiated water demonstrated 4 per cent variation from that determined by desiccation. The method is simple, accurate, reproducible, and readily applicable for use in man and animals.


Volume studies. II. Simultaneous determination of plasma volume, red cell mass, extracellular fluid, and total body water before and after volume expansion in dog and man. A method for the simultaneous determination of plasma volume, red cell mass, extracellular fluid volume, and total body water is described. Plasma volume and red cell mass were determined by a standard dual gamma-tracer technique using 125radioiodinated labeled human serum albumin (125RISA) and 51radiochromate-tagged red cells (51Cr-RBC). Extracellular fluid volume and total body water were determined by a dual beta-tracer technique which utilized radiosulfate-35 (35SO4) and tritiated water (THO), respectively. Kinetic studies of each radionuclide in normal and fluid expanded states demonstrated equilibration of 125RISA and 51Cr-RBC in 5 minutes, 35SO4 and THO in 30 minutes. The results of the volume studies in dog and man demonstrated less than 10 per cent variation on repetitive study, and better than 70 per cent accuracy in estimating a known fluid change. This technique will enable a more precise and simplified investigation of the physiology of body fluid volume regulation in health and disease.


Isolation and chemical characterization of a granuloma glycoprotein that inhibits macrophage phagocytosis. A saline soluble glycoprotein isolated from 14- and 42-day polyvinyl sponge granulomas was shown to depress in vitro phagocytosis by peritoneal macrophages. The glycoprotein had no effect on polymorphonuclear phagocytosis. Chemical and physical characterization of the inhibitor protein obtained from mature (42-day) granulomas developed in guinea pigs indicated that the protein had a molecular weight of 48,500 and an isoelectric point of 5.3. It was homogeneous when examined in three polyacrylamide disc gel electrophoretic buffer systems. The carbohydrate and amino acid content of the protein are reported. The chemical and physical characteristics of the inhibitor protein suggest that it is of nonserum origin. It is postulated that the glycoprotein inhibitor from chronic granulation tissue may participate in regulation of mononuclear phagocyte (macrophage) function within a local inflammatory focus.


Indirect blood pressure measurements in the rabbit: correlations with direct aortic and ear pressures. Blood pressures in the central artery of the ear were determined in rabbits by the use of a modified Grant-Rothschild pressure capsule using two end-points defined as the complete cessation (occlusion) or restoration (opening) of the arterial blood flow. In normal rabbits, the opening values measured by the capsule were closely related to diastolic pressures measured directly in the aorta or in the central artery of the ear, whereas the values obtained during arterial occlusion were higher, by a reproducible amount, than the direct systolic recordings in both the ear and the aorta. In rabbits rendered chronically hypertensive, systolic and diastolic blood pressures measured directly in the aorta and the ear were less (in a predictable manner) than their correspondent occlusion and opening values recorded with the capsule. The amount of this difference increased proportionally as blood pressure increased. Differences between direct and capsular recordings were less consistent in rabbits made acutely hypertensive with infusions of angiotensin. Through regression analysis, systolic and diastolic pressures in the aorta and in the central artery of the ear can be reliably predicted from capsular reading.


A micromethod for the quantitative analysis of calcium, magnesium, and phosphorus in human skin. An inexpensive and simple micromethod is described for determining calcium, magnesium, and phosphorus in a 4 mm. punch biopsy of human skin. This small biopsy requires no sutures, and can be repeated frequently with minimal trauma to patients in long-term studies. Normal ranges of calcium (125 to 300 mg. per kilogram of dry defatted weight (DDW), phosphates (450 to 980 mg. per kilogram of DDW), and magnesium (75 to 112 mg. per kilogram of DDW) are similar to reported results on much larger biopsies. Skin calcium but not skin magnesium or phosphate was significantly higher in 40- to 76-year-old subjects when compared to the 20- to 39-year-old individuals. Comparison of an acid extraction method with the standard ashing procedure showed no significant differences in calcium and magnesium content, but the acid extractable phosphate was significantly lower than the total phosphorus found in the ash.


Renal vein renin in essential hypertension. A frequency distribution curve and interval percentages of variations in right versus left renal vein renin (RVR) were calculated from 227 sets of renin data from patients with mild and moderate essential hypertension (EH). A renal vein renin ratio (RVRR), large/small, of approximately 2.0 or more falls beyond the 95 per cent confidence interval, and may therefore by considered to be abnormal. Although assay variability and sampling errors may contribute to artifactually large RVRR's in EH, they usually indicate true disparity, probably secondary to asymmetrical nephrosclerosis. Recent hypotheses regarding diagnostic value of RVR in hypertension are evaluated in light of data yielded by this investigation. Simultaneous and/or replicate sampling should reduced within-patient variability and improve clinical interpretation of test results.


Correlation of radial bone mineral content with total body calcium in chronic renal failure. Loss of bone mineral of the skeleton in renal disease can be measured directly by total body neutron activation analysis (TBNAA), and also by an absorptiometric technique applied to the appendicular skeleton (radius). In the present study the results of these two techniques are compared in 25 patients with renal insufficiency, 53 patients with end-stage renal failure on dialysis, and 24 normal control subjects. It is apparent that there is good correlation between total body calcium(TBCa) and bone mineral content (BMC) in all groups studied. The correlation in the normal contrast group was 0.944 as compared to 0.919 for the renal patients and 0.892 for patients with end-stage renal failure on dialysis. In order to measure the relative deficit in TBCa in individual patients from the absolute Ca measurement, it is necessary to normalize the data for sex, age, and skeletal size. For this purpose, an empirically derived relationship was used to predict the normal skeletal Ca in each subject, based on weight, height, sex, and age. The measured TBCa divided by the predicted TBCa is referred to as the calcium ratio. This ratio is useful in expressing the relative deficit of Ca in individual renal patients. In similar manner, BMC data were normalized, with the same relationship used to obtain BMC ratios. The normalization procedures allow both the TBCa and BMC measurements to be used to quantitate the Ca deficit in individual patients with renal insufficiency. However, the correlation coefficient relating changes in TBCa and BMC in individual patients on dialysis was very poor (0.25). It is clear that the BMC measurement alone cannot always predict the level of the total body Ca in individual patients with renal failure. In like manner, TBCa measurement alone does not define the distribution of total body Ca between the skeleton and soft tissue in these patients. However, taken together, the BMC measure along with that of TBCa does suggest possible alterations in the skeletal calcium distribution associated with renal disease.


Effect of uremia on rates of ethanol disappearance from the blood and on the activities of the ethanol-oxidizing enzymes. The effect of uremia on ethanol metabolism was investigated. Uremia was induced in male Spraque-Dawley rats by removal of approximately 85 per cent of the renal mass. Control animals had a sham operation. The mean activity of alcohol dehydrogenase was markedly increased in the uremic rats to 2.12 +/- 0.13 (S.E.M.) mumoles per milligram of protein per hours as compared with a control value of 1.39 +/- 0.13 mumoles per milligram of protein per hour (p less than 0.001). There were no changes in the activity of the microsomal ethanol oxidizing system, in catalase activity present in the microsomes, or in the rates of ethanol disappearance from the blood. Uremia resulted in decreases in microsomal cytochrome -450, but no changes in cytochrome b5, NADPH-cytochrome c reductase, or in the activities of aniline hydroxylase and aminopyrine demethylase. The increase in alcohol dehydrogenase activity could not be reproduced by incubation of liver from a normal rat with uremic rat plasma, uremic human serum, or urea. Also, the increase in the enzyme activity was not associated with changes in leucocyte ascorbic acid levels. The cause and physiologic significance of the increase in alcohol dehydrogenase activity in uremia remain to be elucidated.


Effects on cancer patients of leukapheresis with the continuous-flow blood cell separator. I. Hematologic and immunologic parameters in vivo. A study was undertaken to investigate the hematologic and in vivo immunologic effects of leukapheresis of from 2 X 10(9) to 1.6 X 10(10) peripheral blood lymphocytes from 9 cancer patients and 13 normal donors on the blood cell separator. The same parameters were measured in 10 individuals who did not undergo leukapheresis and 4 individuals who underwent sham leukapheresis. Studies were performed immediately prior to and following leukapheresis and at 4 hours, 1 day, 3 days, and 7 days following leukapheresis. There was a transient decline in blood lymphocyte pool (BLP) of the normal donors which returned to preleukapheresis values within 72 hours. Six of 13 normal donors and 2 of 9 cancer patients had a fall in blood lymphocyte count which was below the lower limit of the range of change in control donors immediately following leukapheresis, but all returned to control range within 24 hours. Five cancer patients had increases in lymphocyte count. DNCB reactivity and delayed cutaneous hypersensitivity reactions to common recall antigens were performed 2 weeks before, immediately before, and after leukapheresis, at 7 days and at 4 to 6 weeks following leukapheresis. There were no differences in skin test reactivity between groups. No clinical exacerbations of malignant disease occurred which might be construed to be due to leukapheresis.


Vasodilator responses to K+ in genetic hypertensive and in renal hypertensive rats. Vascular responses to K+ were studied in 37 genetically hypertensive (GH) rats of the New Zealand strain, 12 weight-matched and 11 age-matched normotensive control rats, 21 renal hypertensive (RH) rats with one renal artery clipped and the other kidney untouched, and 18 sham-clipped normotensive control (N) rats, under intravenous chloralose and pentobarbitol anesthesia. KCI in an isosmolar solution, delivering 1.84 X 10(-3), 3.07 X 10(-3), or 4.60 X 10(-3) mEq. K+ per minute was infused intra-arterially into the isolated pump-perfused (blood, 1 ml. per minute) hindlimb vascular beds, increasing measured limb arterial plasma [K+] up to 12 mEq. per liter without changing arterial pressure. The K+ infusions at all three rates reduced limb resistance (P less than 0.01). There was a linear correlation (P less than 0.01) between initial limb resistance and magnitude of response. Analysis of covariance indicated that there were no significant differences between responses in GH and normotensive control rats (P less than 0.1). In contrast, responses in RH rats were decreased (P less than 0.01) when compared to responses in N and GH rats. Thus, the vascular response to K+ is attenuated in renal hypertensive rats, as we have previously found in renal hypertensive dogs and essential hypertensive men, suggesting an underlying defect in vascular K+ metabolism. This abnormality is apparently not shared by genetically hypertensive rats of the New Zealand strain.


Lymphocyte transformation tests and suspected drug allergy. The problems of confirming that a suspected drug allergy exists and which of the administered drugs is the allergen were studied in 43 patients in whom such a diagnosis was considered. Heparinized whole blood was drawn from each patient and 1 ml. aliquots of the supernatant leucocyte-rich plasma were cultured for 3 to 5 days. Individual drugs were added to cultures at the start of incubation. Thymidine3H was added and the incorporated radioactivity measured. Control cultures were done concurrently. Twelve patients had increased thymidine uptake by their drug-treated cells (positive lymphocyte transformation tests). Five patients with positive tests had them repeated. Thymidine uptake decreased with time after the suspect drug was stopped and all the tests eventually became negative. The lymphocyte transformation test appears to be clinically useful for some patients and can confirm suspected drug allergy at times. Its further development appears warranted.


Granulomas in nasal polyps.

Granulomas in nasal polyps. Three specimens of simple nasal polyps which were examined in a routine histopathology laboratory contained tubereuloid granulomas. One of these patients was found to have systemic sarcoidosis. The other two continue to be asymptomatic and in one of these rupture of cystic nasal mucous glands with the liberation of epithelial mucin into the stroma appears to have excited the granulomatous reaction. The causation, investigation and significance of granulomas at this site are discussed.


Transcranial orbital decompression in severe cases of unilateral exophthalmos. Intracranial transtemporal orbital decompressions in one case of massive fibrous dysplasia of temporal, parietal and maxillary bones and in two cases of meningioma of the sphenoidal region are described. Surgery for fibrous dysplasia, even if extensive, must always be modified according to cosmetic and functional aspects. In bone-invading meningioma, large decompressing resections should be made. They may save the eye and arrest the progress of the disease for long periods of time.


Conversion of 7alpha-hydroxycholesterol and 7alpha-hydroxy-beta-sitosterol to 3alpha, 7alpha-dihydroxy- and 3alpha, 7alpha, 12alpha-trihydroxy-5beta-steroids in vitro. The metabolism of 7alpha-hydroxycholesterol and 7alpha-hydroxy-beta-sitosterol (24alpha-ethyl-5-cholestene-3beta,7alpha-diol) has been compared in rat liver subcellular fractions. 7alpha-Hydroxy-beta-sitosterol was shown to be metabolized in the same manner as 7alpha-hydroxycholesterol. Thus, the following C29 metabolites have been identified: 24alpha-ethyl-7alpha-hydroxy-4-cholesten-3-one, 24alpha-ethyl-7alpha,12alpha-dihydroxy-4-cholesten-3-one, 24alpha-ethyl-7alpha-hydroxy-5beta-cholestan-3-one, 24alpha-ethyl-5beta-cholestane-3alpha,7alpha-diol, 24alpha-ethyl-7alpha,12alpha-dihydrozy-5beta-cholestan-3-one, and 24alpha-ethyl-5beta-cholestane-3alha,7alpha,12alpha-triol. The C29 compounds were generally less efficient substrates. The most pronounced difference was noted for the delta4-3-oxosteroid 5beta-reductase. Thus, 7alpha-hydroxy-4-cholesten-3-one was three to four times as efficiently reduced as the C29 analog. The oxidation of the 3beta,7alpha-dihydroxy-delta5-steroid to the 7alpha-hydroxy-delta4-3-oxosteroid, the 12alpha-hydroxylation of the 7alpha-hydroxy-delta4-3-oxosteroid, and the reduction of the 7alpha-hydroxy-5beta-3-oxosteroid to the 3alpha,7alpha-dihydroxy-5beta-steroid occurred in up to two times better yields for the C27 steroids.


Lipid compositions of cells isolated from pig, human, and rat epidermis. Epidermal slices from pig, human, and rat skin were treated with dilute buffered trypsin solution (0.005%, w/v), and suspensions of mixed basal and spinous cells were obtained in good yield. Total lipids accounted for approximately 8% of the pig, 10% of the human, and 20% of the rat epidermal cell (dry weight). Phospholipids in pig, human, and rat cells accounted for, respectively, 62%, 53%, and 35% of the total lipids. Phosphatidylcholine (34-38%), phosphatidylethanolamine (18-23%), and sphingomyelin (17-21%) were major compounds in all species. The major neutral lipids were sterols (mostly cholesterol) and triglycerides. Free fatty acids were a major lipid class in pig and human cells, whereas wax esters were a major component in rat epidermal cells. Nearly half (45%) of the sterols in rat cells but less than 10% of those in pig and human cells were esterified. Cholest-7-ene-3beta-ol accounted for 20% of the total sterols in rat cells. Cholesteryl sulfate and ceramide were minor lipids in the three species. The predominant glycosphingolipid (greater than 99%) was glucosylceramide, which accounted for 7% and 9%, respectively, of the total lipids in pig and human cells. A significant proportion (pig, 17%; human, 11%) of the fatty acids in the glucosylceramides were C26:0 and C28:0.


Different populations of pig epidermal cells: isolation and lipid composition. Preparations representing populations of (a) basal and spinous cells, (b) granular cells, and (c) stratum corneum cells were obtained by successive treatments of epidermal slices from pig skin with dilute buffered trypsin solutions. Total lipids accounted for about 8% of the cell dry weight in each of the three populations. Phospholipids, which predominated in the basal and spinous cells, accounted for only 21% of the total lipids in the granular cells and less than 0.1% in the stratum corneum. The latter cells contained more cholesterol (23% of total lipid) than either the granular cells (18%) or the basal and spinous cells (8%). The proportion of ceramide was also much higher in the stratum corneum (17%) and granular cells (9%) than in the basal and spinous cells (1%). The relative amounts of glycosphingolipid (glucosylceramide) and cholesteryl sulfate in the total lipids of stratum corneum cells were less than half those in the granular cells and basal and spinous cells. A novel phospholipid was a major component (26% of total) of the phospholipids from granular cells. The compound, which was partially characterized, contained phosphorus, fatty acids, and glycerol (molar ratio 1:3:2) and appeared to be a neutral derivative of phosphatidic acid.


Effects of age and cell size on rat adipose tissue metabolism. In order to analyze separately the effects of cell size and age on the metabolism of rat adipose tissue, fat cells of different sizes were obtained from the same animals. The rats were 4 or 15 wk old. The results show that age as well as cell size influences the metabolic rates. At a given cell size, the basal lipolysis, the lipolytic effects of glucagon and noradrenaline, the rate of glucose incorporation into the triglycerides, and the effect of insulin on glucose metabolism were considerably increased in the young animals. Furthermore, irrespective of fat cell size the lipolytic action of glucagon was reduced in old animals. The data thus show that experiments with large fat cells from old rats and with small cells from young animals cannot be directly compared because both variables may influence metabolic reactions.


Genesis of fatty liver and hyperlipemia in the fetal guinea pig. 10 to 20% of [1-14C] palmitate injected into pregnant guinea pigs was recovered in lipids of their fetuses. From these data and the rate of transport of palmitate in maternal blood, it appears that placental transport of free fatty acids can account for the accumulation of lipids in late gestational fetuses. About 80% of the labeled palmitate in the fetus appeared initially in lipids of the liver. 14C appeared in plasma triglyceride fatty acids after a few minutes and subsequently accumulated in lipids of white and brown adipose tissue, suggesting that much of the palmitate deposited in adipose tissue were derived from hepatogenous triglyceride fatty acids. By contrast, 14C was usually maximal in heart and carcass lipids before it appeared in plasma triglyceride fatty acids. Lipoprotein lipase activity in fetal adipose tissue was low, and activity of cofactor protein of lipoprotein lipase in fetal blood plasma was much lower than that observed in other mammalian species. On the basis of these and earlier observations, it is concluded that the accumulation of triglycerides in liver and blood plasma of fetal guinea pigs during late gestation is at least partly the result of the large uptake of maternally derived free fatty acids by the fetal liver accompanied by rapid synthesis and secretion of triglyceride-rich very low density lipoproteins into the blood. However, limited uptake of triglyceride fatty acids in adipose tissue may contribute to the fatty liver and hyperlipemia.


Region-specific immunoassays for parathyroid hormone. Immunoassays specific for limited regions of bovine parathyroid hormone were developed in four ways. With the heterogeneous antisera produced by immunizing with intact bovine parathyroid hormone (BPTH 1-84), the specificity of radioimmunoassays could be enhanced by presaturating either with an amino-terminal (BPTH 1-34) or carboxy-terminal (BPTH 53-84) fragment. Then, the antibodies which had not been neutralized reacted exclusively with the opposite end of the molecule, even using [125I]BPTH 1-84 as tracer. With some antisera, the appropriate fragment and intact hormone reacted identically. However, with other antisera, the fragment reacted less well than the intact hormone, possibly because these antisera contain antibodies reacting with the middle of the molcule. Using the labelled fragment ([125I]BPTH 1-34) as tracer, with heterogeneous antisera, radioimmunoassays specific for the amino-terminal region were obtained. With one antiserum, BPTH 1.34 reached identically with the intact hormone, but with another antiserum, the fragment was more reactive than the intact molecule. A region-specific radioimmunoassay was also developed using antibodies produced by immunization with a fragment of the hormone. An antiserum raised against BPTH 1-34 had high affinity for the amino-terminal fragement, but reacted less well with the intact hormone. Immunoradiometric assays, specific for the amino- or carboxy-terminal regions, developed by using immunoadsorbents consisting of a fragment (either BPTH 1-34 or BPTH 53-84) coupled to cellulose. These were used to fractionate 125I-labelled antibodies. With some of these selected antibodies, the appropriate fragment was of lower reactivity than the intact hormone. This may have been due to the presence of an incomplete antigenic site on the fragment, or to conformational differences between the fragment and the corresponding region of the intact hormone. With other selected antibodies the fragment and the intact molecule reacted identically. Careful selection of antisera and of technique is necessary to obtain an assay in which a fragment and the intact hormone behave identically.


Stimulation effect of prostaglandin F2ALPHA on the plasma concentration of testosterone in bulls. The concentrations of peripheral plasma testosterone were measured by radioimmunoassay in samples collected from five bulls, each given i.m. injections of 0, 5. 15, 30 and 60 mg prostaglandin F2alpha (PGF2alpha). Synchronized peaks in testosterone concentration occurred with maximum values 1.2h after treatment. These increases of testosterone persisted significantly longer than those observed to occur as natural episodic peaks during two 24 h periods in the same bulls. The mean peak testosterone concentration after PGF2alpha injection was related to the dose of PGF2alpha, values after 60 and 30 mg doses being significantly greater than after 15 mg. The response produced by a 5 mg dose was not significant. The results indicate that intramuscular injection of PGF2alpha, acutely stimulates synthesis and release of testosterone in fulls.


Changes in the concentration of calcitonin in the plasma of chick embryos during incubation. Calcitonin (CT) was assayed in the plasma of chick embryos at eight stages of development from  day 17 of incubation to day 1 after hatching by a rat bioassay. The concentration of CT rose steadily from 1060 mu./1 on day 17 to 4700 mu./1 at the stage when pulmonary respiration was initiated on day 20. Nine hours later, when the embryos 'pipped' the shells, the concentration of the hormone more than doubled to reach a peak of 11000 mu./1. At hatching the level had fallen to 1400 mu./1 and 24 h later it was undetectable (less than 500 mu./1). The physiological significance of these changes is discussed in relation to the development of the embryo.


Biosynthesis of gonadotrophins by rat pituitaries in vitro. A method has been developed for studying biosynthesis of FSH in the rat pituitary in vitro. Anterior pituitary glands were incubated with [3H]leucine; a specific and sensitive immunoprecipitation technique was used to isolate FSH from the pituitary homogenate. Total FSH content of the samples was measured by a double-antibody radioimmunoassay technique. Using this technique, a comparative study of LH and FSH synthesis in the same pituitary of adult male rats incubated for various intervals (0-5-6 h) was done. Increased incorporation of [3H]leucine into both LH and FSH with time was noted. The rate and amount of [3H]leucine incorporation into FSH was found to be higher than that into LH, indicating that either the rate of FSH synthesis is higher than that of LH or FSH has more leucine residues than LH. Greater susceptibility of LH to degradation by endogenous proteases during dialysis may also reflect less incorporation of [3H]leucine into LH. This method provides a reliable tool for evaluating FSH synthesis under various experimental conditions.


Effect of intraventricular administration of noradrenaline on water diuresis in goats. Duriing water diuresis in conscious goats, noradrenaline (NA), its antagonists phentolamine, phenoxybenzamine and propranolol and also atropine were administered into the 3rd ventricle. The subsequent effects on water diuresis and on the excretion rates of Na+, K+ and Cl- were investigated. Infusion of NA into the 3rd ventricle induced a strong and significant antidiuretic response and a decrease in the Na+ : K+ excretion ratio; these effects were dose-dependent. High doses of NA produced a significant increase in urinary K+ excretion. Similar results were observed after i.v. administration of arginine-vasopressin. Pretreatment with phentolamine injected into the 3rd ventricle produced a dose-dependent inhibition of the NA-induced antidiuretic effects. Phenoxybenzamine also blocked the response to NA but a dose-response relationship was not apparent. Atropine and propranolol did not block the response to NA.


Perfusion of intercellular spaces in the pars distalis and their variation with time of day. Microperfusion of the tissue parenchyma of regions of the rat pituitary gland with 1:1 dilutions of India ink revealed a network of fine intercellular spaces or canaliculi throughout the pars distalis. They were demonstrable in animals of all ages from 1-5 months to over 1 year, in both sexes, and at various times during the 24 h light-darkness cycle. However, 24 h rhythms were suggested in the radial perfusion distance (P LESS 0.05) and tissue density (P LESS 0.01) of the perfused canaliculi in adult male rats. The amplitude of the 24 h rhythmicity in these pituitary canaliculi was lower than that shown recently in pineal canaliculi of the same species. Structural regularity and evidence of rhythmic and physiologically correlated changes in the pituitary canaliculi suggest that they relate to natural features rather than being only artifactual, and that analysis of their possible functional significance is appropriate.


The synergistic action of alpha-melanocyte-stimulating hormone and testosterone of the sebaceous, prostate, preputial, Harderian and lachrymal glands, seminal vesicles and brown adipose tissue in the hypophysectomized-castrated rat. Alpha-Melanocyte-stimulating hormone was shown to act synergistically with testosterone to stimulate the sebaceous, prostate and the seminal vesicles in hypophys-ectomized-castrated rats. The sebaceous glands differed from the other three organs in that alpha-MSH not only acted synergistically, but also had a significant effect which was independent of the presence of exogenous testosterone. The response of the brown adipose tissue to testerone, considerably reduced by hypophysectomy, was not restored by alpha-MSH. The Harderian and lachrymal glands were also pituitary-dependent and their weights in hypophysectomized-castrated rats were not restored by alpha-MSH.


Differences in serum corticosterone patterns in individual rats: relationship to ovulatory cycles. Blood samples were collected on several occasions from Sprague-Dawley-derived rats by means of cardiac puncture at 8 h intervals over a 24 h period. Rats were sampled four times before ovariectomy, after ovariectomy and after replacement therapy with oestradiol benzoate. It was discovered that each rat tended to maintain a distinct pattern of serum corticosterone. While some rats developed hormonal rhythms, other rats showed no evidence of such rhythms as indicated by patterns of serum corticosterone concentation. The majority of rats that did not show daily corticosterone rhythms were found to have irregular ovulatory cycles as indicated by vaginal smears. Each characteristic hormonal pattern remained after ovariectomy and subsequent oestrogen replacement although resting levels of corticosterone were lower after ovariectomy and higher after oestrogen treatment than before the operation. It is concluded that the presence of an adrenal rhythm is usually associated with regular vaginal smear cycles.


Pituitary hormone response to brain stimulation in man. Plasma cortisol, GH and LH responses to electrical stimulation of the orbital part of the frontal lobe and the cingulate area of the brain were studied in patients undergoing limbic leucotomy. In six out of 15 patients the plasma cortisol levels increased by 5-7--18-0 mug/100 ml after orbito-frontal stimulation whereas plasma GH values did not rise during this period. Plasma LH levels remained unchanged. No definite hormone responses could be attributed to stimulation of the cingulate area. It appears that the orbito-frontal area of the brain is concerned with augmenting the release of ACTH but not that of GH or LH.


Effects of ovarian steroids and prolactin on the sequential development of nesting behaviour in female budgerigars. As intact, breeding female budgerigars approach egg-laying, they spend an increasing amount of time in the nestbox and nest hollow. The brood patch area begins to defeather and becomes vascular and the oviduct increases in weight. Precursory albumen forms in the tubular glands of the oviduct. Oestradiol (OB) treatment in combination with prolactin (OB+PL) induced ovariectomized budgerigars to display nesting behaviour which did not differ from that shown by intact females in the 3 days immediately preceding egg-laying. In contrast, OB induced only the initial phase of the nesting sequence and the effects of OB in combination with progesterone (OB+PR) were intermediate between treatments with OB alone and OB+PL. Incubation of artificial eggs occurred only in the OB+PL group and the latency to display of the incubation posture was shorter in the OB+PL group than in the OB+PR group. No incubation posture was displayed by the OB-treated group. Oviduct development was not influenced by prolactin, but progesterone induced precocious development of tubular glands in the magnum region of the oviduct. Treatment with OB+PR induced uniform development of precursor albumen in the tubular glands. Development of the brood patch occurred with both OB+PL and OB+PR treatment. However, OB+PR resulted in defeathering which was advanced in relation to vascularity when compared with intact breeding females, whereas defeathering and vascularity of the OB+PL group did not differ from that of intact females at egg-laying. These results indicate that prolactin in combination with oestradiol was more effective than progesterone not only in inducing the later phases of nesting behaviour but also in initiating incubation behaviour and defeathering of the brood patch area.