[Recognition of onomatopoeias and animal cries during focalized lesions of the cerebral cortex (author's transl)]. The recognition of animal cries and their onomatopoeias was compared during the course of right or left unilateral cortical lesions. A double dissociation is noted; in left-sided affections there is a more severe deficiency to onomatopoeia than to cries, whereas in right-sided lesions the quality of the performances is reversed. These results suggest that the right hemisphere is dominant in the auditive recognition of familiar sounds, and supply information as to the linguistic value of onomatopoeias.


Long-term analgesic effects of inescapable shock and learned helplessness. Although exposure to inescapable shocks induced analgesia in rats, the analgesia was not manifest 24 hours later. A brief reexposure to shock, however, restored the analgesia. This reexposure to shock had an analgesic effect only if the rats had been shocked 24 hours previously. Further, long-term analgesic effects depended on the controllability of the original shocks and not on shock exposure per se. Implications of these results for learned helplessness and stress-induced analgesia are discussed.


Treatment of thrombotic thrombocytopenic purpura with plasma infusions and cyclophosphamide. Our patient presented with thrombotic thrombocytopenic purpura. Treatment failed despite splenectomy, corticosteroids, dextran, and antiplatelet drugs. Plasma infusions induced neurologic recovery, but hematologic improvement could not be sustained when they were discontinued. Cyclophosphamide, however, induced a sustained remission.


Schistosomiasis japonica in Barrio San Antonia, Basey Samar, in the Philippines: III. The plasma circumoval precipitin test-procedure and use in epidemiologic studies. A plasma circumoval precipitin test is proposed as the basic diagnostic tool for epidemiologic studies on schistosomiasis japonica in the Philippines. The collection of plasma, the preparation of the COP test slide, and the reading and interpretation of results are described in detail with pertinent comments. The cost, advantages and usefulness of the test are also discussed.


Schistosoma japonicum-like ova in liver and rectal biopsies of three cases in Sabah, Malaysia. Three cases of schistosomiasis in 2 Filipinos and one Chinese in Sabah are reported. Diagnosis was based on incidental histological findings of Schistosoma japonicum-like ova in the liver and rectal biopsies. As these 3 patients are immigrants to Sabah, it is assumed that they are imported cases, and that Sabah has been free of the disease from 1970 to 1977.


Paralytic shellfish poisoning. A report of 17 cases in Cape Town. An outbreak of 17 cases of paralytic shellfish poisoning in humans occurred in Cape Town during May 1978. The clinical features were typical and no deaths occurred. Efforts to correlate the severity of disease with the amount of toxin ingested, to demonstrate a protective effect of alcohol, and to demonstrate the immunogenicity of the toxin proved unsuccessful. The regional ecological effects are described. Continued monitoring for the presence of toxic dinoflagellates must be conducted, and the dangers of the consumption of mussels from the Cape west coast should be widely publicized.


Transmission experiments with hepatitis B surface antigen and the common bedbug (Cimex lectularius L). Hepatitis B surface antigen (HBsAg)-positive blood meals were fed to a colony of the common bedbug (Cimex lectularius L) in a series of 5 experiments. Antigen persisted in the bugs for at least 7 1/2 weeks, but was undetectable after 18 weeks. Trans-stadial transmission was demonstrated through one moult only, and transovarial transmission did not occur. Antigen was successfully transmitted by adult bugs into 3 out of 35 canisters of HBsAg-negative blood. Antibody of HBsAg was detected in the serum from a rabbit on which HBsAg-positive adult bugs had fed as well as in the serum of 2 out of 10 guinea-pigs on which HBsAg-positive 4th and 5th nymphal instars had fed. The results as a whole indicate that biological multiplication and biological transmission do not occur in C. lectularius, but mechanical transmission has been demonstrated. This is probably an important means of hepatitis B virus transmission among humans in South Africa.


Assignment of temperature-sensitive mutations of BHK cells to the X chromosome. A class of recurring, noncomplementing, recessive, temperature-sensitive mutation of BHK-21 cells has been assigned to the X chromosome. X-linkage was determined by complementation, karyotypic, and enzymatic analyses.


Splenectomy for hematologic disease.

Splenectomy for hematologic disease. One hundred and thirty splenectomies were performed at the University Hospital in Birmingham for hematologic disorders during a 12 year period. There were seven deaths of which four were related to sepsis in patients with malignant growths which probably impaired immune competence. Splenectomy was found to be uniformly satisfactory for hereditary hemolytic anemia, for hypersplenism complicating rheumatoid arthritis and for the rare instance of primary hypersplenism. Splenectomy was usually salutary in didopathic thrombocytopenic purpura and in antoimmune hemolytic anemia. When done for diagnosis, splenectomy was definitive in about 50 per cent of the instances. Individual patients with thrombotic thrombocyeosinophilia syndrome benefited. Splenectomy for hypoplastic or aplastic anemia in an actual circulation offered only questionable benefit and is rarely necessary for hyperplenism secondary to portal hypertension.


Electron microscopy of the plexiform lesion. Pulmonary arteries from a case of plexogenic pulmonary arteriopathy were studied with the electron microscope. Many muscular pulmonary arteries showed intimal fibrosis of concentric or "onion-skin" type. The cells embedded within this fibrosis resembled smooth muscle but since they also possessed some features of fibroblasts we refer to them as myofibroblasts. Myofibroblasts also occurred in plexiform lesions together with fibroblasts and "fibrillary cells". These fibrillary cells contained numerous, prominent filaments with a random orientation. They lined the vascular channels of the plexiform lesions as well as being present within the stroma. They appeared to phagocytose fibrin and then to organise the plexiform lesion into a fibrous scar. Fibrillary cells closely resemble vasoformative reserve cells and the cells of the cardiac myxoma and so-called "papillary tumour" of heart valves. They may, therefore, be primitive multipotential cells found throughout the entire cardiovascular system.


[Epidemiological aspects of Uncinaria stenocephala infections in the Netherlands (author's transl)]. A series of experimental infections in a total number of twenty-two dogs showed that transmission of the parasite Uncinaria stenocephala from one dog to another is readily achieved by oral route. Cutaneous infection was only successful when large doses were used. From the topographical distribution of some intestinal U. stenocephala worm populations in dogs it was concluded that the hookworm population is concentrated in the proximal part of the ileum. The expulsion of worms observed may be evidence of the size or persistence of the worm population. The prepatent period was found to be (at least) thirteen days, both in dogs and in foxes. Daily worm-egg counts showed a fluctuating rhythm, particularly during the first 2-3 weeks of the patent period. Relatively high peaks were also recorded in some cases. The maximum number of worms eggs was estimated at well over 5,000 eggs per female U. stenocephala worm (in dogs). U. stenocephala eggs and larvae are capable of surviving at low temperatures. U. stenocephala infection was found to be present in twenty-five (86 per cent) out of twenty-nine foxes obtained and examined in 1975, the worm load varying from one to 176 hookworms and averaging thirty worms per fox. From the preliminary results of a number of experimental transmissions it was concluded that foxes and dogs harbour adapted strains of U. stenocephala, which prevents cross infections between these reservoirs from occurring to more than a limited extent.


[Experimental infection of soft ticks with Dipetalonema witei (author's transl)]. The intermediate host of Dipetalonema witei, the soft tick Ornithodoros moubata, can be infected experimentally with microfilariae. Microfilariae isolated from the blood of infected donor animals were injected into the dorsal haemocoel of the ticks where they developed to infectious filariae within approx. 50 days. The rate of infection of ticks was 100% when more than 100 microfilariae were injected. An average of 23% was recovered as infectious filariae. Up to 450 ticks can be infected with 1000 microfilariae each from a single donor animal within one year, whereas donor animals can only be used for about 1 month if ticks are naturally infected. The method described has advantages compared to natural tick infections with respect to the rate of infection of ticks, the development of microfilariae, and the amount of infectious material produced.


Urethral pressure profile using microtip catheter in females. The use of urethral pressure profilometry in the clinical investigation of dysfunction of the female lower urinary tract is discussed. Included is a description of the use of two-channel microtip profilometry in the urethral syndrome, urinary retention, detrusor hyperreflexia, stress incontinence, and normal females. Dual-channel profilometry improves the diagnostic accuracy of urethral profile studies and aids in the understanding of lower urinary tract pathophysiology.


[Humoral reactions in BALC/c mice with sarcomatous Moloney-induced tumor]. In a progressive course of the blastomatous process induced by MSV-Moloney the antitumor antibodies level in the whole blood serum was practically unchanged, while the level of antibody-forming cells (AFC) in the spleen of these mice was considerably decreased as compared with that in the spleen of intact mice of the same age. If the tumor development was followed by its subsequent resorption, a biphase character of enhancement of the cytotoxic activity both of the whole serum and its fractions was noted. In the utmost developed tumor a reduced AFC level was observed, while in its resorption -- a gradual restoration of the AFC values up to the level characteristic of intact animals of the same age group.


[Animal experimental study on placental passage of testosterone. Experiments in dogs]. There are still open many questions concerning the diaplacentary effect of medicaments. This above all concerns the steroid hormones and their proper and possible conversion. The problems of the placental barrier as to the permeability for sexual hormones are discussed. In an experimental study in dogs may be proved that a male sexual hormone (TTP) given to a pregnant animal passes the placenta. For this pleads the significancy of the biological androgen proof.


[Lipolytic activity from milk isolated strains of the species Thermoactinomyces vulgaris, Tsiklinsky 1899 (author's transl)]. Thirty strains of the species Thermoactinomyces vulgaris (Tsiklinsky, 1988) were isolated from milk and tested for their lipolythic activity. After incubation for 120 hours at 55 degrees C they formed distinct diffusion zones on culture media containing tributyrin and tween-80. In all strains exocellular lipases were found. Their action on the milk fat increased the number of the free fatty acids. Triglycerides, free fatty acids as well as diglycerides and monoglycerides were identified as split products chromatographically. The activity of the endolipases was lower. In four of the most active endolipases cholesterol was identified as split product of milk fat in addition to those mentioned above.


[Probabilities and ethologic analysis of the zoosocial behavior of grouped and isolated mice]. The effectiveness of probabilistic and ethological approaches to the analysis of normal and pathological animal behaviour is shown. The probabilistic analysis of the frequency, duration and sequence of a large variety of behavioural acts and postures permits to single out the most significant events and diad transitions in the interaction between two animals (previously isolated or grouped). Computer and probabilistic analysis reveals sharp differences in the structure of these acts and their interdependence in isolated and in grouped mice. It is noted that in isolation there occur fixation of the program of aggressive behaviour, a sharp narrowing of the spectrum of possible transitions from aggression to other forms of intraspecific behaviour, aggression being little controlled by intraspecific inhibitory factors which is regarded as pathology of behaviour.


[Effect of hippocampal damage on emotional stress in rats]. Motor reactions and ECGs were recorded in rats with lesioned hippocampus and in intact animals during elaboration of conditioned switching over of heterogeneous conditioned reflexes (alimentary and defensive). In hippocampectomized rats, in contrast to intact ones, the formation of this complex conditioned activity is not accompanied by pronounced vegetative reactions and changes in the ECG. The data obtained point to an active involvement of the hippocampus in formation of emotional stress and confirm the concept of the hippocampus as a brain structure, providing for responses to signals of events with low probability.


Therapy of Crohn's disease with metronidazole -- an uncontrolled trial --. Twelve patients with Crohn's disease (C.D.), in whom there was no improvement of symptoms and signs under protracted corticosteroid and salicylazosulphapyridine medication, were treated with 1 000 mg metronidazole (M.) daily. Crohn's Disease Activity Index (CDAI) was used as a criterion of therapeutic response. Seven patients showed improvement of symptoms with a concomitant fall of the CDAI from 300 +/- 84 to 56 +/- 32 (mean +/- SD) after 10 to 45 days. In one patient, therapeutic success was judged to be doubtful, a negative result being obtained in 4 patients. During follow-up, which was maximally 21 months, patients failed to relapse while receiving a maintenance dose of 250 and 500 mg of M. per day. -- Judicious attempts at drug withdrawal were undertaken during the first 6 months but were invariably followed by a relapse. -- Metronidazole given over a protracted period did not give rise to side-effects. -- A reduction of anaerobic bacterial invaders of the intestine is suggested to underlie the favourable therapeutic effect of M.


Intrauterine progesterone contraceptive system as an alternative in cases where conventional IUD's are unsuitable. A progesterone intrauterine device (IUD), Progestasert, was prescribed for 25 patients unable to use an ordinary non-hormonal IUD. Both the amount of menstrual bleeding and the discomfort was observed to decrease more often than increase during the period of use of the progesterone IUD. Hemoglobin, hematocrit and the serum iron levels either remained static or increased. Continuation rate was 76 per cent after one year. The authors consider Progestasert a suitable alternative to the ordinary non-hormonal IUD in women with dysmenorrhea or menorrhagia and those in whom a previous IUD had been associated with pain or increased menstruation.


Receptivity of female rats.

Receptivity of female rats. Receptivity of female rats has been investigated under chronic experimental conditions. A receptivity index has been worked out for quantitative evaluation. It proved suitable for disclosing stimulatory (2.5 mg noretynodrel, oestradiol propionate) as well as inhibitory (etynodiol diacetate) effects. 2.5 mg noretynodrel has a biphasic effect; causing an inhibition and later an increase in receptivity. Receptivity of untreated female rats is low and can be increased by various steroids; the best treatment was 50 micrograms oestradiol monopropionate administered twice weekly, but this resulted in an inverse mating reaction, with frequent copulations in every phase of the cycle. In untreated females the number of copulations varied widely. Previous deliveries did not influence receptivity and frigidity was also observed.


Myasthenia gravis and Werlhof's disease. A case of Werlhof's disease (immune thrombocytopenia) associated with myasthenia gravis is described. The two disorders developed within a few months of each other. The immunological and practical aspects of the association are discussed.


Pregnancy in a patient with porcine valve xenografts. The course of pregnancy and successful vaginal delivery of a healthy infant in a 23-year-old woman with previous aortic and mitral valve replacement with porcine xenografts if presented. Unlike the management of pregnant patients with conventional mechanical prostheses, anti-coagulation may not be necessary with xenografts, particularly when there are no other thrombogenic conditions. Other management issues include congestive heart failure, arrhythmias, prophylaxis against subacute bacterial endocarditis, and expeditious labor and delivery.


Structural changes in a porcine xenograft after implantation for 105 months. Morphologic studies including light microscopy and transmission and scanning electron microscopy were performed on a formaldehyde-fixed porcine xenograft prosthesis that functioned well for 8 years and had been implanted for 105 months in the tricuspid valve position. It is the oldest implanted valve studied in this manner. Although all leaflets had some gross deterioration, only one had adherent thrombus. The degenerative changes in the connective tissue from all leaflets were similar to those recently reported in glutaraldehyde-fixed porcine valves implanted for shorter periods. The surfaces of the two nonthrombosed leaflets and small portions of the surface of the thrombosed leaflet were endothelized, and the endothelium appeared to have little or no effect on the degenerative changes in the subjacent connective tissue. Further, the endothelium did not extend over the examined portion of the synthetic anulus of the prosthesis, suggesting that its origin was possibly from cells circulating in the blood.


The effect of estrogen on epithelial cell proliferation and differentiation in the crypts of the descending colon of the mouse: a radioautographic study. The regulatory role of estrogen on cell population kinetics in the descending colon was studied in intact female and ovariectomized mice. In the colonic crypts from intact mice, the crypt size (the number of epithelial cells per crypt column) and the proliferative activity of epithelial cells fluctuated slightly during the estrous cycle. Peak cellularity per crypt column was exhibted during estrus and early diestrus, whereas peaks in labeling index were seen during estrus and late metestrus. While the population size of mucous cells showed a minimal variation, the number of proliferative vacuolated cells per crypt column varied inversely with that of differentiated columnar cells during estrous cycle. The vacuolated cells were increased in number in the preovulatory phase and the columnar cells in the postovulatory phase. Three weeks after bilateral ovariectomy, the colonic crypt appeared to reach a new steady state, which was characterized by a small crypt size, a decrease in the number of differentiated cells, an increase in the relative number of proliferative cells and a relative increase in the proliferative activity of the crypt as compared to intact mice. When ovariectomized mice were treated with estrogen, the number of 3H-thymidine-labeled cells in the crypt was decreased as compared to untreated ovariectomized mice, the decrease being greater after a single injection than after multiple injections of estrogen, and the vacuolated-columnar cell line being affected more than mucous cell line. Meanwhile, the crypt size as well as the population size of differentiated cells in the crypt failed to return to normal after estrogen treatments. Thus, estrogen did not promote differentiation of epithelial cells in the crypt.


Sexual and somatic determinants of the human Y chromosome: studies in a 46,XYp- phenotypic female. A case of a 46,XYp- phenotypic female provided an opportunity to evaluate both sexual and somatic determinants for the Y chromosome. The patient had multiple stigmata of Turner syndrome, but normal stature. Laparotomy revealed a normal uterus and tubes, with 1.5 cm undifferentiated gonads. Serological tests for H-Y antigen (ostensibly the product of Y-chromosomal testis-determining genes) indicated absence of the H-Y+ phenotype normally associated with the intact Y chromosome. We conclude that genes exist on the short arm of the human Y chromosome which both suppress some of the somatic stigmata of Turner syndrome and determine normal expression of H-Y antigen and testicular differentiation of the primitive gonad. Our data are consistent with the view that H-Y genes comprise a family of testis-determinants, and that loss of a critical moiety is inconsistent with normal development of the male gonad.


The Limulus amebocyte lysate endotoxin assay: current status. Research conducted during this decade has clearly established the Limulus amebocyte lysate (LAL) test as the most sensitive assay for bacterial endotoxin. In addition, the assay is easily performed, relatively inexpensive, specific for endotoxin, and can be used to test materials that are toxic to rabbits employed in the rabbit pyrogen test. The LAL test has been used in the diagnosis of meningitis, urinary infection, mastitis, and endotoxemia. Other broad applications of the test include quality assurance of parenteral solutions and medical devices as well as the microbial quality of food and water. A review of recent developments in LAL testing is presented and experimental applications of the assay are discussed.


Ultrastructural effects of estrogen replacement on postmenopausal endometrium. Endometrial adenocarcinoma occurs almost exclusively in postmenopausal women, and excessive or unopposed estrogen stimulation is suspect as a causative factor in its pathogenesis. Furthermore, the incidence of endometrial adenocarcinoma has increased in women undergoing estrogen replacement therapy. In the present study, the cellular response of premenopausal and postmenopausal endometrium to estrogenic stimulation was compared with endometrial adenocarcinoma by the electron microscope. Tissues were obtained at hysterectomy, endometrial biopsy, or endometrial curettage and were processed routinely for light and electron microscopy. Ultrastructurally the endometrium from postmenopausal patients undergoing estrogen replacement therapy was similar to normal cyclic endometrium in the late proliferative phase. At least three features of the estrogen-treated postmenopausal tissue resembled those observed in adenocarcinoma of the endometrium: accumulation of lipid droplets, irregular nuclei, and perinuclear whorls of microfibrils.


Comparison of serum prolactin, plain radiography, and hypocycloidal tomography of the sella turcica in patients with galactorrhea. Hypocycloidal tomography of the sella turcica is being used with increasing frequency in patients with galactorrhea in order to establish the diagnosis of pituitary adenoma. In 201 patients with galactorrhea, serum prolactin (PRL) levels were correlated with anteroposterior (AP)--lateral plain radiographs and hypocycloidal tomography of the sella turcica. Plain films were normal in 167 and abnormal in 34 patients. Of the 167 patients with normal AP-lateral plain films, 80 had normal tomograms and normal serum prolactin levels while 80 patients had normal tomograms and elevated serum PRL levels (21 to 256 ng/ml). The remaining seven of the 167 patients had normal plain films with abnormal tomograms and elevated serum PRL levels (28 to 176 ng/ml). All patients with abnormal plain radiographs had abnormal tomograms and had either elevated or normal serum PRL levels. In view of these findings, sella tomography is only necessary in patients with normal plain radiographs and elevated serum PRL levels.


Serum vitamin A and retinol-binding protein in malnourished women treated with oral contraceptives: effects of estrogen dose and duration of treatment. Malnourished women who had been treated with combination-type oral contraceptives containing 0.03 mg or 0.05 mg of ethinyl estradiol and 0.15 mg d-norgestrel had significantly higher levels of serum retinol-binding protein (RBP) and vitamin A after two or five cycles of treatment compared with untreated control subjects. The values tended to return to normal by the twelfth cycle of treatment, the trend for reversal being more marked for RBP than for retinol.


Long-term propranolol therapy in pregnancy: maternal and fetal outcome. Propranolol, a beta-adrenergic blocking agent, has found an important position in the practice of medicine. Its use in pregnancy, however, is an open question as a number of detrimental side effects have been reported in the fetus and neonate. Ten patients and 12 pregnancies are reported where chronic propranolol has been administered. Five patients with serial pregnancies with and without propranolol therapy are also examined. Maternal, fetal, and neonatal complications are examined. An attempt is made to differentiate drug-related complications from maternal disease--related complications. We conclude that previously reported hypoglycemia, hyperbilirubinemia, polycythemia, neonatal apnea, and bradycardia are not invariable and cannot be statistically correlated with chronic propranolol therapy. Growth retardation, however, appears to be significant in both of our series.


Pigmentary degeneration of the retina in the Hallervorden-Spatz syndrome. Dizygotic twins developed a progressive neurologic disorder at age 6 months. When examined at age 7 1/2 years each had spastic quadriparesis and dystonia. Neither had ever spoken a complete sentence. The fundi showed bone spicule formation, a conspicuous choroidal circulation, and a striking accumulation of yellowish-white globular masses of varying sizes and shapes. Because our patients developed both the pigmentary degeneration and clinical signs of Hallervorden-Spatz syndrome at a much younger age than patients without retinopathy, we believe this case demonstrated a distinct nosologic entity.


Ovaries and adrenals in murine Schistosomiasis mansoni. II. Some observations on the function of the ovaries in acute infection. In mice with acute schistosomiasis mansoni the mean serum level of progesterone, as determined by radioimmunoassay, was significantly lower than in non-infected control animals, probably due to the atrophy of corpora lutea and the discontinuance of their development described in an earlier paper. In spite of the histopathological changes in the ovaries and the decreased level of progesterone in the blood, estrus was present in some infected animals.


Duration of bupivacaine intradermal anesthesia when the bupivacaine is mixed with chloroprocaine. In a double-blind trial in 20 human volunteers, the duration of intradermal anesthesia with a mixture of bupivacaine, 0.5 mg, and chloroprocaine, 3 mg, was compared with the duration of intradermal anesthesia obtained with either bupivacaine, 0.5 mg, or chloroprocaine, 3 mg, alone. The duration of intradermal anesthesia produced by the bupivacaine mixed with chloroprocaine, 36 +/- 16 (mean +/- 1 SD) minutes, was significantly less than the duration of the same amount of bupivacaine alone, 139 +/- 78 minutes. Duration of anesthesia with chloroprocaine alone, 24 +/- 11 minutes, was similar to the duration of anesthesia with chloroprocaine plus bupivacaine. A possible explanation for these results is that bupivacaine competes with chloroprocaine for nonspecific receptors at the biophase and in the surrounding nerve tissue.


Muscle contractures and adenosine triphosphate depletion in porcine malignant hyperthermia. This study compares several methods for diagnosing susceptibility to malignant hyperthermia, using two groups of Poland China swine narrowly defined as genetically susceptible or normal (five pigs each) depending respectively on their response to halothane or to halothane and succinylcholine. Vastus medialis muscle biopsies were excised under thiopental-N2O-O2 anesthesia and used for examination of (1) contracture responses to halothane, (2) contracture responses to caffeine and halothane-caffeine, and (3) adenosine triphosphate (ATP) depletion with and without halothane. All studies were performed in organ baths at 37 C. Halothane alone produced contractures  in two susceptible and one normal preparation; caffeine always produced a contracture at lower concentrations in susceptible muscle; caffeine-halothane contractures in susceptible muscle occurred at lower mean caffeine concentrations, but there was some overlap of individual values; mean ATP depletion was greater in susceptible muscle, but with considerable overlap. Comparisons with the findings of others were hampered by use of absolute rather than comparative values for tension, e.g., grams, rather than grams per cross-sectional area or fraction of peak tension. Examination of the complete dose-response curve provided the best comparative information and caffeine was the consistent predictor of susceptibility.


Cardiovascular responses to clamping of the aorta during epidural and general anesthesia. The cardiovascular responses of aortic cross-clamping and declamping with normal and high ventricular filling pressures were compared during epidural and nitrous oxide-morphine anesthesia in 32 male patients undergoing reconstructive aortic surgery. The patients were divided into four groups. Groups I and II had lumbar epidural blocks with bupivacaine and received nitrous oxide in oxygen to breathe; groups III and IV were anesthetized with morphine (2 mg/kg) and nitrous oxide. During aortic occlusion groups I and III received Ringer's lactate at a rate which maintained mean pulmonary capillary wedge pressure (PCWP) 3 to 4 torr above pre-anesthetic values whereas groups II and IV were given Ringer's lactate rates which kept PCWP similar to pre-anesthetic values. Prior to cross-clamping mean arterial blood pressure and systemic vascular resistance were lower in groups I and II than in groups III and IV but cardiac output, PCWP, and pulmonary vascular resistance were similar in the four gropus. Cross-clamping of the aorta produced no significant change in any cardiovascular variable measured in any group. Declamping did not significantly alter any variable in groups I and III but produced moderate hypotension in group IV and severe hypotension in group II as well as significant decreases in PCWP in both groups. Our data demonstrate that aortic cross-clamping and release result in little change in cardiovascular dynamics in patients anesthetized with epidural or morphine-nitrous oxide and given balanced salt solutions intravenously in amounts adequate to increase left ventricular filling pressures prior to release of the aortic cross-clamp. Our findings also indicate that hypotension can occur in patients in whom left ventricular filling pressures are maintained at normal levels prior to cross-clamp release, especially in patients given epidural anesthesia.


Cumulative dose-response curves for gallamine: effect of altered resting thumb tension and mode of stimulation. Neuromuscular blockade studies often use the thumb adductor twitch response to ulna nerve stimulation. Two factors that may influence the results are the resting muscle tension (initial fiber length) and the pattern of the stimulus wave form. This study was undertaken to improve understanding of the effect of these factors and lead to better controlled study conditions and more consistent data. During nitrous oxide-barbiturate-narcotic anesthesia in 10 normal adult patients, as the resting thumb tension was increased from 50 to 200 g, the evoked thumb adductor twitch response (Grass stimulator, 0.25 Hz) was augmented by 28%. There was only a 2.5% increase in the evoked (developed) tension when the resting tension was further increased from 200 to 300 g. Developed tension at 50 g was significantly (p less than 0.001) less than at the other resting tensions. The developed tension at 100 g was also significantly (p less than 0.05) less than at resting tensions of 200 or 300 g. Cumulative dose-response curves for gallamine in nine patients were not significantly altered by increasing resting tension from 50 to 200 g. Biphasic (Block-Aide monitor) or single square wave (Grass stimulator) stimuli wave forms in nine normal adult patients yielded gallamine dose-response curves that were not statistically different. The muscle response to biphasic stimulation during a non-depolarizing blockade was not affected by the average muscle refractory period. Because of the significantly lower developed tension at resting tension settings of 50 to 100 g, a practical consideration during neuromuscular function studies would be to have the resting thumb tension adjusted and rechecked for each patient and kept within the 200-300-g range to ensure maximum uniform developed tension. The type of stimulus wave form selected will not affect results as long as it is used consistently throughout the study.


Pharmacokinetics of intravenous procaine infusion in humans. Pharmacokinetic data during and following the continuous intravenous infusion of procaine are lacking. We studied 12 women undergoing hysterectomy during N2O-O2 and narcotic anesthesia. A constant infusion of 2% procaine was administered at a rate of 1 mg/kg/min to six patients (group I) and at a rate of 1.5 mg/kg/min to the other six (group II). Procaine plasma levels were determined by flame ionization gas-liquid chromatography. Using a two-compartment pharmacokinetic model, disposition kinetics were studied. Steady-state plasma levels were achieved within 20 to 30 minutes after commencement of the infusion. Following termination of the infusion the drug disappeared with a distribution half-life (t1/2 alpha) of 2.49 +/- 0.36 minutes and an elimination half-life (t1/2 beta) of 7.69 +/- 0.99 minutes at both infusion rates. In group I, the fraction of drug in the central compartment was 65%, the volume of distribution at steady-state was 0.79 +/- 0.14 L/kg, and total body clearance 0.08 +/- 0.01 L/kg/min. In group II, the fraction of drug in the central compartment was 82%, the volume of distribution at steady-state 0.34 +/- 0.07 L/kg, and the total body clearance 0.04 +/- 0.01 L/kg/min. These data indicate that procaine is a drug of limited distribution and tissue uptake with a short duration of action.


Depression of lung mucociliary dlearance by thiopental and halothane. It has previously been demonstrated that an induction dose of thiopental, 25 mg/kg, without continuing anesthesia did not depress peripheral lung mucociliary clearance in the dog, whereas 2 hours of anesthesia with halothane, 1.2 MAC, did depress clearance. To determine whether this was because thiopental depresses the mucociliary apparatus less than halothane, this study compared mucociliary clearance after 2 hours of anesthesia with halothane with clearance after 2 hours of anesthesia with thiopental, 40 mg/kg. With thiopental, 40 mg/kg, 50% mucociliary clearance of tantalum from peripheral airways required 280 +/- 65 (SEM) minutes, which was comparable to clearance obtained with halothane, 1.2 MAC, 382 +/- 27 (SEM) minutes. Hence thiopental depresses mucociliary clearance as much as halothane does when both are administered in equivalent anesthetic doses for equal periods of time.


Epinephrine-induced arrhythmias: effect of exogenous prostaglandins and prostaglandin synthesis inhibition during halothane-O2 anesthesia in the dog. Prostaglandins (PG) modify sympathetic and parasympathetic neurotransmission and have antiarrhythmic properties. Inhibitors of PG synthesis sensitize the heart to certain experimentally induced arrhythmias. This study examined the arrhythmogenic dose (AD) of epinephrine in dogs during halothane-O2 anesthesia as modified by the infusion of PG and by treatment with an inhibitor of PG synthesis. Dogs were anesthetized with 1.25 MAC halothane. The AD of epinephrine was established by a series of 3-minute epinephrine infusions at 10-minute intervals. The AD of epinephrine was then redetermined during infusions of PG(PGE1--1 microgram/kg/min and PGF2 alpha--1 microgram/kg/min), after indomethacin, 3 mg/kg, and after aminophylline, 10 mg/kg. The AD remained unchanged from control during both of the PG infusions and following indomethacin. Only following aminophylline did the AD decrease significantly. Our study suggests that pretreatment of surgical patients with nonsteroidal antiinflammatory drugs which inhibit PG synthesis does not increase the likelihood of ventricular arrhythmias during halothane-O2 anesthesia.


Nitrous oxide: effect on accumulation rate and uptake of bowel gases. Breathing 79% nitrous oxide (N2O) in oxygen increased the rate of accumulation of bowel gas during intraluminal bowel segment infusions of hydrogen, methane (CH4), air, or carbon dioxide (CO2) in four pentobarbital-anesthetized dogs more than did breathing 100% oxygen. A N2O-associated increase in the volume of naturally produced intestinal gas in five halothane-anesthetized ponies corroborated the findings in the dog studies. In a second group of four dogs a bolus of CH4 or CO2 was injected into the bowel lumen. When the dogs breathed O2 the bowel gas volume decreased. Gas was virtually absent in the CO2-containing segment within 20 minutes. Breathing N2O increased the volume of the segments containing CH4 while the CO2 segments decreased less rapidly than during O2 breathing. Breathing O2 after 30 minutes of N2O breathing caused little change in the rate of decrease in CO2 segment volumes. However, the CH4 segment volume ceased to increase and eventually returned toward control volumes.


Serum inorganic fluoride levels in obese patients during and after enflurane anesthesia. Serum ionic fluoride levels in 24 markedly obese patients (127.6 +/- 6.0 kg) and seven nonobese control subjects (67.3 +/- 1.2 kg) were compared during and following enflurane anesthesia (less than 2.0 MAC hr). Peak serum fluoride levels were higher (28.0 +/- 1.9 vs 17.3 +/- 1.3 micrometers/L, p less than 0.01) and the rate at which fluoride levels increased was more rapid (slope 5.6 vs 2.5 micrometers/L/hr) in obese patients than in control patients. No clinical evidence of nephrotoxicity was found in either group. Vasopressin resistance tests were not performed, and thus it is inknown whether subclinical nephrotoxicity occurred in either study group. Possible reasons for increased enflurane metabolism in obesity are discussed. These possibilities include differences in fluoride ion kinetics, hepatic delivery and penetration of volatile anesthetics, and altered hepatic microsomal enzyme activity. Obesity rather than weight is an important determinant of anesthetic biotransformation.


Comparison of domperidone, droperidol, and metoclopramide in the prevention and treatment of nausea and vomiting after balanced general anesthesia. Women (185) undergoing elective orthopedic surgery under balanced general anesthesia were given 5 or 10 mg of domperidone, 1.25 mg of droperidol, 10 mg of metoclopramide, or a saline placebo intravenously in a double-blind random fashion 5 minutes before the end of anesthesia to prevent postoperative vomiting. Administration of the same antiemetic was repeated intramuscularly during the first 24 hours postoperatively if the patient complained of nausea or retched or vomited. Sigificantly (p less than 0.05 to p less than 0.001), fewer of the patients given droperidol were nauseated (25%) or vomited (17%) in comparison with patients given saline (incidence of nausea was 55% and vomiting 40%). Incidences of nausea and vomiting were similar in patients given domperidone, metoclopramide, or saline. Furthermore, 39 to 45% of the patients given domperidone, metoclopramide, or saline needed additional doses of the same drug, whereas only 22% of the patient given droperidol required a second dose. It is concluded that droperidol is effective in the prevention and treatment of postoperative nausea and vomiting after balanced general anesthesia but that domperidone or metoclopramide are not.


Anterior uveitis in ankylosing spondylitis: a histocompatibility study. The occurrence of acute anterior uveitis in ankylosing spondylitis was compared in 53 HLA-B 27 positive and 12 HLA-B 27 negative patients with this disease. Uveitis was found in HLA-B 27 positive patients only. These results suggest that uveitis and ankylosing spondylitis are independent diseases occurring on their own and strongly associated with HLA-B 27.


[Effect of gentamycin in combination with prodigiozan on the immunological reactivity of the body]. The effect of gentamicin sulphate and its combination will prodigiozan on antibody formation in experiments and the levels of the immunobiologic reactivity of patients with purulent inflammatory processes was studied with a purpose of developing rational schemes of antibiotic therapy of infectious diseases. A decrease in the titers of the antibodies to Aeromonas and the number of antibody-forming cells in the spleen was noted on repeated administration of gentamicin to albino mice in a dose of 20 mg/kg. This was prevented by the use of prodigiozan in a dose of 500 micrograms/kg once every 4 days. The use of gentamicin in patients with purulent inflammatory diseases in doses of 40 or 80 mg twice a day for 7--10 days had no significant effect on the titers of IgA, IgG, IgM, lysozyme blood serum levels, serum bactericidal activity and absorption activity of the peripheral blood neutrophils. Still, it induced a marked suppression of the neutrophil digestive capacity as compared to the initial levels, especially on administration of gentamicin in a dose of 40 mg twice a day. An increase in the level of IgM and no suppression of the neutrophil digestive capacity were noted after completion of the therapy in the patients treated with gentamicin administered in a dose of 40 mg twice a day and prodigiozan administered in a dose of 50 micrograms once every 4 days. It is recommended to use prodigiozan in combinaed therapy with gentamicin for correction of the changes in the specific and nonspecific protective forces of the host.


Chitin-binding hemagglutinin produced by Conidiobolus strains. A hemagglutinin was produced by strains of Conidiobolus which also produce beta-N-acetylglucosaminidase. Activity of the hemagglutinin was inhibited by D-glucosamine, N-acetyl-D-glucosamine, D-mannosamine, and beta-N-acetyl-D-glucosaminides but not by D-glucose, D-mannose, and alpha-N-acetyl-D-glucosaminides.


[Taxonomic reconsideration of Entomophthora obscura Hall & Dunn]. A set of slides and strains designated as Entomophthora thaxteriana Petch, E. obscura Hall et Dunn and E. ignobilis Hall et Dunn were compared on morphological, physiological, pathological and biochemical bases. It is concluded that E. thaxteriana (name invalidated by Humber, 1978) must be replaced by E. obscura and not by E. ignobilis, this species being considered as nomen dubium. Some intraspecific variations within the species E. obscura were found particularly with regard to the ability to produce resting spores and cystidia.


Noninvolvement of beauvericin in the entomopathogenicity of Beauveria bassiana. Development of a microbiological autobiographic assay procedure permitted a detailed investigation of the possible role of beauvericin (a toxic ionophoric antibiotic produced by Beauveria bassiana) in the entomopathogenicity of B. bassiana against corn earworm (Heliothis zea) larvae. Analysis of spent media of B. bassiana and the hemolymph of infected and moribund larvae revealed that beauvericin was not present in a soluble form during the time that most (about 90%) larvae died of fungal infection (4 days). Intrahemocoelic injections of up to 6 micrograms of synthetic beauvericin failed to induce any deleterious effects. In addition, although methanol-soluble ionophores, such as valinomycin and bassianolide, were toxic to corn earworm larvae, no methanol-soluble toxin could be detected in the hemolymph of moribund larvae.


[Experimental infestation of Cochlicella ventricosa with L1 larvae of protostrongylids (author's transl)]. Young land-snails (Cochlicella ventricosa) were infested with a plurigeneric mixture of first-stage larvae of Protostrogylids. Cochlicella ventricosa is good host for Cystocaulus and Neostrongylus. Only one larva is able to ensure its complete evolution at a first infestation. A second larva follows the same process, at a second infestation. Such a regulation of the infestation recalls the limitation phenomenon. Hypothesis concerning this regulation process are discussed.20


[Dipetalonema dessetae--Aedes aegypti: study of the infected adipose tissue (author's transl)]. Histological and ultrastructural study of the adipose tissue of Aedes aegypti has shown that infection with the filaria Dipetalonema dessetae locally induces a highly active synthesis of proteins (formation of ribosomes, endoplasmic reticulum and Golgi complexes, multiplication of mitochondria). This phenomenon appears similar to the effect of beta-ecdysone after the up-take of blood. Mosquitoes let to starve during the development of the filaria show a quick disappearance of storage substances (lipids and glycogen) and involution forms of the induced ergastoplasma (after seventh days only), so that the infected tissue degenerates and the development of the filaria is arrested.


[Additional findings on the distribution and prevalence of Tetrapetalonema (Esslingeria) streptocerca (Macfie and Corson, 1922) in West Africa (author's transl)]. Human streptocerciasis has been found in the Accra district (Ghana), in southern Ivory Coast, and in Upper Volta in migrants. During a survey in the forest part of the Volta Region (Eastern Ghana), 119 cases were discovered in ten villages between 6 degrees 50' N., and 7 degrees 50' N., indicating local transmission of the parasite. The parasitic load has always been low. In the area, the presence of T. streptocerca cannot modify the results of a direct diagnosis of onchocerciasis based on the emergence of microfilariae from skin snips in distilled water or normal saline solution. The parasite has not been found in surveys undertaken north of the 8 degrees N., neither in Ghana, nor in Togo or Ivory Coast. The presence of T. streptocerca in villages located on the Togolese border confirm that this filaria exists in Togo too, although no mention is made in the literature.


Toxic effects of some alcohol and ethylene glycol derivatives on Cladosporium resinae. Eleven commercially available alcohol and ethylene glycol derivatives were tested for their toxicity toward a problem organism in jet fuel, Cladosporium resinae. In the presence of glucose, 20% (vol/vol) ethylene glycol monomethyl ether prevented spore germination and mycelial growth, and 10% (vol/vol) 2-ethoxybutanol, 10% 2-isopropoxyethanol, 10% 3-methoxybutanol, 5% 2-butyloxyethanol, 5% ethylene glycol dibutyl ether, and 5% diethylene glycol monobutyl ether were found to have similar effects. In a biphasic kerosene-water system, 3-methoxybutanol, 2-butyloxyethanol, and diethylene glycol monobutyl ether were again found to be more toxic than ethylene glycol monomethyl ether. Considerable potassium efflux, protein leakage, and inhibition of endogenous respiration were observed in the presence of the more toxic compounds. 2-Butyloxyethanol also caused loss of sterols from cells.


Bovine superoxide dismutase and copper ions potentiate the bactericidal effect of autoxidizing cysteine. When cysteine is oxidized by oxygen, hydrogen peroxide is formed, and hydrogen peroxide is very toxic to Peptostreptococcus anaerobius VPI 4330-1. Native and inactivated superoxide dismutase increased the rate of oxidation of cysteine and thereby potentiated the toxic effect of cysteine. A similar increase in the rate of oxidation of cysteine and in the toxicity of cysteine was obtained with Cu2+.


Side-by-side pairing of the XY bivalent in spermatocytes and the ubiquity of the H-Y locus. The pairing mechanism of the XY bivalent, the possibility of crossing-over between X and Y chromosomes during meiotic prophase, and the location of the H-Y locus are of interest with regard to genetic control mechanisms, male gametogenesis, and testicular organization. A whole-mount electron microscope technique has permitted the study of a large number of mouse and hamster spermatocytes to evaluate the spatial relationship of sex chromosomes and autosomes. X and Y chromosomes showed a transient, extensive side-by-side pairing segment along most of the length of the Y chromosome. This extensive pairing segment may cause genetic exchange between X and Y chromosomes. The finding of a small unpaired paracentromeric region of the Y chromosome could be related to a locus of totally sex-linked gene(s) that determine the development of the testis from the undifferentiated embryonic gonad.


Treatment of idiopathic oligozoospermia by kallikrein: results of a double-blind study. Ninety subfertile men with idiopathic oligozoospermia were treated orally with either 600 units porcine pancreatic kallikrein or placebo daily for 7 wk. Kallikrein caused an increase in the number of spermatozoa (3.1 X 10(7) with a maximum 2--3 mo after onset of therapy. There was an improvement of the quantitative and qualitative sperm motility with a maximum at the end of treatment. Five months after onset of therapy, pretreatment values were regained. There were no major side effects. Conception rates within a period of 1 yr were 16% for placebo and 38% for kallikrein.


The prevention by creatinol O-phosphate of myocardial lesions evoked by isoprenaline. Isoprenaline 30 mg/kg has been injected subcutaneously in rats pretreated or not with Creatinol O-phosphate (200 mg/kg intraperitoneously). Isoprenaline-induced cardionecrosis and the associated alterations of the ionic composition of the heart were reduced when Creatinol O-phosphate was injected 4 hr before isoprenaline.


Modification of pharmacological and toxicological effects of acetophenazine, chlorpromazine and thloridazine in morphine-dependent mice. The pharmacological and toxicological responses of three phenothiazine neuroleptics, acetophenazine, chlorpromazine and thioridazine were determined in morphine-dependent mice. The mice were rendered dependent on morphine by implantation of a morphine pellet for 3 days. The control animals received placebo pellets. The pellets were removed and at 6, 24, 48 and 72 hr after the pellet removal, naloxone ED50's for the stereotyped jumping response were determined. The effect of phenothiazine derivatives administered intraperitoneally, at 6, 24 and 72 hr after pellet removal were determined on the 24 hr LD50, locomotor activity and body temperature. The LD50 of all phenothiazines was decreased significantly in mice from which morphine pellets were removed for 6 hr in comparison to placebo pelleted mice. This was the time when maximum degree of dependence on morphine was observed. At 24 and 72 hr after pellet removal, the LD50's in morphine and placebo treated mice were not different. The relative decrease in locomotor activity by all the phenothiazines was less in morphine withdrawn mice as compared to placebo withdrawn mice. The hypothermic response of phenothiazines was enhanced in morphine withdrawn mice. It is concluded that the effects of phenothiazine neuroleptic drugs can be modified in narcotic-dependent subjects. Possible mechanisms of such altered effects are discussed.


The effects of oleandrin on cardiac contractility in the normal dog. The effects of oleandrin, a cardiac glycoside, were tested on the cardiovascular system of anesthetized dogs with an intact circulation. Oleandrin, administered intravenously, at dosages of 0.01 (Group I), 0.02 (Group II), and 0.05 (Group III) mg/kg, did not affect the mean heart rate significantly in any of the groups of dogs studied. Results were most consistent with 0.05 mg/kg of oleandrin in Group III producing a significant increase in aortic systolic, aortic mean, and left ventricular peak pressures. Oleandrin increased the inotropic state of the heart in all groups of dogs to some extent and the magnitude of change was directly related to the amount of the drug injected. The increased contractility was expressed as a rise in the indices of max dp/dt and max dp/dt/IP, and as a decrease in t-dp/dt. In Group III, with 0.05 mg/kg of oleandrin, left ventricular contractility increased by over 50% as judged from these indices. Oleandrin, in the majority of the dogs, shifted the pressure-velocity curves upward and to the right, increasing both VCE and Vmax. In Group III the increase in Vmax was 32%. The results indicate that oleandrin in the intact, normal dog produced responses that are both qualitatively and quantitatively similar to those seen with the better known cardiac glycosides.


[Clinical and statistical study on the allergy of type 1 to mycetes (author's transl)]. From 1963 to 1977 the authors have examined 5700 patients; 11.5% of those positive to intradermal test were sensitive to Mold spores. 78 individuals showed allergic sensitivity exclusively to Mold spores; 89% were affected by bronchial asthma. Symptom onset was observed more frequently in subjects 30 to 50 years old. The authors intend to stress the important role played by the allergy to Mold spores in determining type 1 immunologic reactions.


Twenty-four-hour rhythm of prolactin depressive patients. Twenty-four-hour rhythms of serum prolactin (PRL) levels were studied in seven depressive patients. Blood was collected through an indwelling catheter and the PRL level was determined by homologous double antibody radioimmunoassay. Findings showed a different pattern of secretion of prolactin among depressives as compared to the normal 24-hour rhythm of the hormone. A statistically significant elevation of PRL levels during the evening, several hours before sleep, was found. Morning PRL levels were slightly higher and the average increase of PRL level from one determination to the consecutive one was higher among the depressives. It is assumed that there may be a connection between the diurnal rhythmicity of mood, characteristic of vital depression, and the different 24-hour rhythmicity of PRL level.


[Ultrastructure of the neuroepithelial cells of the respiratory portion of the lungs in experimental inflammatory diseases of the lungs]. Neuroepithelial cells (NEC) and neuroepithelial bodies (NEB) were found in the lungs of rats among cells of the alveolar epithelium. The peculiar features of NEC structure included microvilli with microfibrils penetrating deep into the cytoplasm, and a complicated structure of the endoplasmic reticulum: reticulum membrane complex. NEC's are arrayed on the alveolar basal membrane singly, in pairs and in larger numbers forming NEB. The latter consist of cells differing in shape, size, and ultrastructure. Most of them have no microvilli with microfibrils inside. In chronic pneumonia NEC's occur more frequently, the ultrastructure of most cells being well-developed.


[Sudden cardiac death and hypothalamo-hypophyseo-adrenal activity]. The paper presents current concepts on possible mechanisms of sudden heart death and on systems of neurohormonal heart regulation changes in which may cause sudden heart death. The importance of the main humoral and hormonal changes in possible disorders of electrolyte cardiac balance determining the development of electric instability and ventricle fibrillation underlying most cases of sudden heart death is described. Some morphological changes both in the heart itself and neurohormonal systems regulating it are dealt with.


X-linked recessive congenital muscle fiber hypotrophy with central nuclei: abnormalities of growth and adenylate cyclase in muscle tissue cultures. Muscle cells in cultures established from biopsy specimens of two children with an infantile-fatal form of X-linked recessive muscle fiber smallness with central nuclei showed an unusual ability to proliferate through numerous passages. Ultrastructurally, the cultured muscle fibers appeared very immature even after several weeks. The nuclei were large, the number of ribosomes was greatly increased, the myofibrils remained unstriated, and glycogen was accumulated in large lakes. The plasmalemma bound concanavalin A, alpha-bungarotoxin, and ruthenium red normally, but with tannic acid it did not show the dark binding of mature fibers. Biochemically, in the cultured muscle fibers, beta-adrenergic receptors were quantitatively normal. The level of adenylate cyclase in membranes was less than in cultured normal muscle; this defect could be responsible for impaired control mechanisms resulting in the other abnormalities observed.


Etiologic factors in secretory otitis.

Etiologic factors in secretory otitis. We investigated the possible etiologic factors of secretory otitis and dysfunction of the Eustachian tube in 278 healthy 2-year-old children based on screening tympanometry and medical history. We found that catarrhalia was the most frequent etiologic factor, with acute otitis being the second most frequent factor. It was demonstrated that secretory otitis may develop without a preceding infection of the middle ear. It is probable that dysfunction of the tube plays a primary role in the development of secretory otitis. Allergy did not seem to be an etiologic factor. Antibiotic treatment does not promote the development of secretory otitis, but is probably unable to prevent it. Parental disposition could not be related to the children's ear diseases.


The failure of a prostaglandin F2 alpha analogue, cloprostenol, to initiate lactation in cattle. An experiment was designed to determine if the analogue of prostaglandin F2 alpha, cloprostenol, at a dose sufficient to cause luteolysis, was lactogenic in cattle. The mammary glands of eight Friesian heifers were developed by treatment with progesterone plus oestrogen. Lactation was then initiated by administration of cloprostenol and subsequent milk production was compared to that of heifers lactating after a normal pregnancy. Injection of cloprostenol failed to initiate lactation. The level of prolactin but not cortisol in blood was substantially elevated following treatment. The results cast further doubt on the importance of prolactin in the lactogenic process but indicate the likely involvement of glucocorticoids.


Carbohydrate metabolism in chicks after administration of toxins from a Phomopsis sp. Soybeans inoculated with Phomopis sp. were incubated for weeks and then extracted with methanol and ether, and the culture filtrates were intubated into crops of chicks. Activities of glucose-6-phosphatase and glucose-6-phosphate dehydrogenase in liver were increased, and glycogen stores and plasma glucose concentrations were reduced. Histologically, severe hepatocytic necrosis was found in chicks treated with the toxic culture filtrate. Significant clinical signs were loss of body weight and reduced feed consumption. The metabolic changes responsible for the findings are discussed.


Copper metabolism in mottled mouse mutants: copper concentrations in tissues during development. The copper content of various organs of ;brindled' female heterozygotes and male mice affected by this X-linked mutation are documented at the last day of intrauterine development, at 1 day after birth and at 11 days of age. The findings indicate defective placental transfer of copper in utero, and an even more marked defect in intestinal absorption of copper after birth. In addition there is an abnormal distribution of copper among the tissues of the body once it is absorbed. The mutation produces abnormal accumulation of copper in kidney, in gut mucosa and in testis, whereas liver, brain, plasma and most other organs show diminished copper concentrations. The intestinal malabsorption of copper is accompanied by accumulation of abnormal amounts of the metal in the intestinal-mucosa cells. Copper concentrations in both mucosa and luminal contents rise progressively from duodenum to ileum. Defective upper-intestinal absorption, consequent progressive increase in luminal copper concentration and pinocytosis in the ileum would seem to explain the findings. Radioisotopic studies eliminated the possibility of excessive excretion of copper in bile or across the intestinal mucosa. Detailed comparison with findings in humans with Menkes' syndrome is difficult because of the different stages of development at which the studies have been performed, but the results seem in general to conform very satisfactorily. Those differences seen are probably explicable by known species differences. All the findings are in accord with a hypothesis that the basic defect involves accumulation and retention of copper in the cells of affected tissues such as kidney, gut mucosa and placenta.


Copper metabolism in mottled mouse mutants: copper therapy of brindled (Mobr) mice. Copper therapy was applied to brindled mouse mutants, which suffer from lethal hypocupraemia, by using cuprous and cupric solutions. The method of treatment was a single subcutaneous injection of 50 microgram of copper at 7 days of age. Early effects of the dose were: prevention of the tremors and spasms seen in untreated mutants, raising to normal and near-normal of caeruloplasmin oxidase and lysyl oxidase activities and pigmentation of skin and fur. Growth of mutants was retarded up to 23 days of age, but thereafter they rapidly gained weight to be nearly normal by 60 days of age. At 3 days after injection, copper concentrations in previously deficient mutant organs apart from liver were at least as much as those of treated normals, which had remained unchanged. Copper in mutant livers had increased only slightly in comparison with the normal control. A state of copper deficiency recurred in mutant tissues by 25 days after injection. A solution of Cu+, retained as such by an alkyl polyether, and sebacic acid resulted in greater growth rates after 23 days than did three other copper treatments. Cu+ may have resulted in an improved growth response owing to it being more readily metabolized than C12+. Delayed release of copper from the site of injection may have played an important role.


Copper metabolism in mottled mouse mutants: distribution of 64Cu in brindled (Mobr) mice. 1. Duodenal injection of 64Cu in treated adult mutant mice (Mobr/y) revealed severe malabsorption of copper. In suckling mutants, malabsorption was less severe, owing to delayed absorption between 2 and 5 h after injection. Pinocytosis at the distal small intestine seems the likely explanation for this difference, and this is supported by results of ileal injection of radioisotope in the suckling mice. 2. The distribution of 64 Cu in various organs was measured in suckling normal, mutant and heterozygote mice and in adult normal and mutant mice during 48 h after intracardiac injection. Excessive accumulation of radioisotope was observed in most extrahepatic organs of mutant and heterozygote mice and was most pronounced in kidney. This could not be explained by initial copper deficiency. The livers of suckling mutant and heterozygote mice lost radioisotope rapidly after normal initial uptake. This pattern was not seen in adult mutants.


Q wave T wave vector discordance in hypertrophic cardiomyopathy: septal hypertrophy and strain pattern. Hypertrophic cardiomyopathy is a common cause of prominent non-infarctional Q waves. A retrospective analysis of previously published cases confirmed a characteristic Q wave T wave vector discordance in hypertrophic cardiomyopathy. In 41 of 44 cases with predominant Q waves (as part of QS or Qr complexes where Q wave amplitude exceeded R wave height), the T wave was positive, and in all cases with QS type complexes the T wave was positive. This characteristic electrocardiographic sign probably represents a pattern of septal hypertrophy and strain (Q waves with positive T waves and ST segment elevation) which is the inverse of the classical pattern of left ventricular hypertrophy and strain (tall R waves with inverted T waves and ST segment depression).


Fatty acid composition and thermal behavior of natural sphingomyelins. We found significant differences in the fatty acid composition of several bovine brain, egg yolk and sheep erythrocyte sphingomyelins. These differences in fatty acid composition influence the thermal behavior of hydrated sphingomyelin as recorded by differentail scanning calorimetry. Significant differences were also found in the temperature and complexity of the order-disorder phase transitions of bovine brain sphingomyelin obtained from different sources which, in general, correlate with the relative content of the saturated fatty acids (palmitic (C16:0) and stearic acid (C18:0) acids) and the long unsaturated nervonic acid (C24:1).


In vitro lipid metabolism in the rat pancreas. III. Effects of carbamylcholine and pancreozymin on the turnover of phosphatidylinositols, 1,2-diacylglycerols and phosphatidylcholines. 1. The turnover of phosphatidylinositols and other glycerolipids was examined in rat pancreatic fragments incubated in the presence of carbamylcholine and pancreozymin used at a concentration inducing maximal alpha-amylase hypersecretion. 2. In stimulated tissue, [1-14C]acetate-labeled fatty acids were incorporated into phosphatidylinositols, 1,2-diacylglycerols, and phosphatidic acids in preference to phosphatidylcholines, phosphatidylethanolamines, triacylglycerols, monoacylglycerols, and free fatty acids. Variations in the percent distribution of 14C among fatty acids and in specific activity of individual fatty acids in each lipid class suggested that the secretagogues reduced selection of newly synthesized 1,2-diacylglycerols which occurred in the resting state before their incorporation into phosphatidylinositols. Secretagogues also promoted recycling of endogenous 1,2-diacylglycerols (produced from hydrolysis of unlabeled glycerolipids) for the biosynthesis of phosphatidylinositols. 3. Increased rate of incorporation of [1-14C]palmitate, [1-14C]linoleate, [1-14C]arachidonate and [1(3)(n)-3H]glycerol into phosphatidylinositols was detrimental to phosphatidylcholines. 4. The lipolytic effects of carbamylcholine and pancreozymin as illustrated by the release of 1,2-diacylglycerols and free fatty acids, were markedly inhibited in calcium-free medium enriched with 1 mM EGTA but increased turnover of phosphatidylinositols as determined from incorporation of radioactive precursors was only moderately affected.


Leghaemoglobin from Trifolium subterraneum. Purification and characterization. Leghaemoglobin from the subclover, Trifolium subterraneum cultivar Woogenellup, has been fractionated into at least four electrophoretically distinct components using the ion-exchange chromatographic procedure described by Appleby et al. (Appebly, C.A., Nicola, N.A., Hurrell, J.G.R. and Leach, S.J. (1975) Biochemistry 14, 4444--4450) for soybean leghaemoglobins. Unlike those of soybean, the subclover leghaemoglobins showed no evidence of autoxidation under identical isolation procedures, implying that these proteins have an unusually stable ferrous oxidation state. Circular dichroism in the far-ultraviolet (200--240 nm) indicated a high helicity (approx. 70%) as has been reported for other species of leghaemoglobins. However, circular dichroism in the near-ultraviolet region (240--300 nm) indicated that the haem-protein interactions may be considerably different in the subclover leghaemoglobins and this may explain their atypical resistance to autoxidation and the absence of nicotinate binding in these proteins.


A cytolytic protein from the edible mushroom, Pleurotus ostreatus. Aqueous extracts of the edible mushroom, Pleurotus ostreatus, contain a substance that is lytic in vitro for mammalian erythrocytes. The hemolytic agent, pleurotolysin, was purified to homogeneity and found to be a protein lacking seven of the amino acids commonly found in proteins. In the presence of sodium dodecyl sulfate it exists a monomers of molecular weight 12 050 whereas under non-dissociating conditions it appears to exist as dimers. It is isoelectric at about pH 6.4. The sensitivity of erythrocytes from different animals correlates with sphingomyelin content of the erythrocyte membranes. Sheep erythrocyte membranes inhibit pleurotolysin-induced hemolysis and the inhibition is time and temperature dependent. Ability of membranes to inhibit hemolysis is abolished by prior treatment of membranes with specific phospholipases. Pleurotolysin-induced hemolysis is inhibited by liposomes prepared from cholesterol, dicetyl phosphate and sphingomyelin derived from sheep erythrocytes whereas a variety of other lipid preparations fail to inhibit. It is concluded that sphingomyelin plays a key role in the hemolytic reaction.


Animal model of depression.

Animal model of depression. A behavioural procedure is described which may provide an animal model for some aspects of human depression. Rats or mice when forced to swim in a restricted space will rapidly cease attempts to escape and become immobile. Immobility is reduced by many clinically effective antidepressant treatments suggesting that the immobile behaviour may reflect a state of lowered mood in the animal. If so the method could be useful as a simple experimental tool for research into the biology and therapeutics of depression.


Polarized fluorescence in an electric field: comparison with other electrooptical effects for rodlike fragments of DNA and the problem of the saturation of the induced moment in polyelectrolytes. Electrical birefringence, electrical dichroism and polarisation of fluorescence in an electric field experiments have been performed at high fields on sonicated fragments of DNA labelled with Acridine Orange. The latter electrooptical effect gives access to the field dependence of the fourth moment of the orientation function while the two former give access to the field dependence of the second moment. The origin of the large departure from an E2 dependence at rather low degrees of orientation is extensively discussed. Following a suggestion of Shirai on the calculation of orientational averages for a saturated induced moment, we can show that this model rationalizes the existence of a linear E dependence of the orientation factor at intermediate fields and explains very well our experimental results. When applied to previous dichroic data at higher fields it shows that the low value of the dichroism at saturation introduced to fit with other models, in contradiction with the absence of base tilting in the B form of DNA, is not required for a quantitative fit with this new orientation mechanism. The transition from an E2 dependence at low fields to an E dependence at intermediate fields gives an estimate of the field required for the saturation of the ionic polarisation E approximately 6 kV/cm.


Cerebral blood flow and oxygen consumption during ethanol withdrawal in the rat. The ethanol withdrawal syndrome in man and animals is characterized by signs of CNS hyperactivity although a direct measurement of a physiological variable reflecting this CNS hyperactivity has never been performed in untreated man or in animals. We induced ethanol dependence in the rat by means of intragastric intubation with a 20% w/v ethanol solution, thus keeping the animals in a state of continuous severe intoxication for 3--4 days; during the subsequent state of withdrawal characterized by tremor, rigidity, stereotyped movements and general seizures a 25% increase in cerebral oxygen consumption (CMRO2) could be measured; this increase was not due to catecholamines originating from adrenal medulla as adrenomedullectomized animals showed a similar increase in CMRO2 (28%); the withdrawing animals showed a corresponding cerebral blood flow (CBF) increase. The elevated CMRO2 and CBF could be reduced to normal by administration of a beta-adrenergic receptor blocker (propranolol 2 mg/kg i.v.), and hence the increased CMRO2 during ethanol withdrawal could be related to catecholaminergic systems in the brain, e.g. the noradrenergic locus coeruleus system which is anatomically well suited as a general activating system. This interpretation is supported by the earlier neurochemical finding of an increased cerebral noradrenaline turnover during ethanol withdrawal. The exact mechanism underlying the increased cerebral oxygen consumption during ethanol withdrawal and the effect of propranolol on cerebral function during this condition remains to be clarified.


Effects of innervation by ciliary ganglia on developing muscle in vitro. Electrophysiological and pharmacological properties of neuromuscular junctions formed in tissue culture between chick ciliary ganglia and chick skeletal muscle cells have been studied. Functional neuromuscular junctions are formed already within 24 h. No functional acetylcholine (ACh) esterase is present at these end-plates. The neurites conduct action potentials to the neuromuscular junctions, where EPPs are generated. Tetrodotoxin (TTX) blocks this nerve conduction but in the presence of TTX MEPP-like potentials remain whose amplitudes are lowered when the Mg2+/Ca2+ ratio in the medium is raised. It is speculated that these large TTX-resistant potentials are multiquantal. The relatively high resting membrane potential in non-innervated muscle fibers was not changed by innervation. ACh-sensitivity was determined by iontophoretical application of ACh to the myotubes. Non-innervated myotubes exhibited an evenly distributed ACh-sensitivity. Local differences in ACh-sensitivity were always gradual and never exceeded a factor of 3. Innervation did not alter the overall ACh-sensitivity, but on functionally innervated muscle cells loci hypersensitive to ACh were found. Hypersensitivity was located within sharply defined areas. Apparently the parasympathetic neurons of the ciliary ganglion are able to form functional neuromuscular junctions with skeletal muscle cells in tissue culture and to induce the formation of regions of high ACh-sensitivity.


Interspecies aggression in the rat: the role of the diagonal band of Broca. Electrolytic lesions of the diagonal band of Broca were made in rats which had previously not killed mice (DBPt) and in rats which had no experience with mice prior to the beginning of the experiment (DBN). The lesions induced killing in 12 of the 20 naive (DBN) rats, but in only 1 of the 16 pretested (DBPt) rats. The region of the diagonal band is projected upon or has extensive projections to many regions of the central nervous system in which lesions have previously been found to induce muricide. The behavior induced by diagonal band lesions and lesions of these other regions was compared.


Delayed glaucoma after implantation of a Choyce intraocular lens. A Choyce intraocular lens was inserted nine years after a routine intracapsular lens extraction. A year after this second operation, an acute pupil block glaucoma developed. Three weeks after the onset of the glaucoma, repeated laser iridotomies controlled the glaucoma. Pupil block glaucoma may be a complication long after intraocular lens implantation.


Optimization on the selection of auxotrophic mutants in Candida utilis by snail enzyme treatment. The determination of the best conditions for the application of the snaill enzyme digestion method in the enrichment of auxotrophic mutants in Candida utilis was carried out following Box and Wilson's mathematical method. The selection procedure proposed was tested in the enrichment of auxotrophic mutants from a mutagenized culture of a wild-type strain. Mutant frequency was increased 46-fold by treatment with snail enzyme. The method also proved useful in the selection of additional auxotrophic mutations from single auxotrophs.


Structural and immunochemical characterization of the acidic arabinomannan of Mycobacterium smegmatis. A serologically active, acidic arabinomannan has been isolated from Mycobacterium smegmatis. The polysaccharide contains approximately 56 arabinosyl and 11 mannosyl residues, and 2 phosphate, 6 monoesterified succinate, and 4 ether-linked lactate groups. After saponification to remove succinyl groups, the polysaccharide can be separated into phosphorylated (55%) and nonphosphorylated (45%) forms, the former containing a little more arabinose and a little less mannose than the latter. The structures of these polysaccharides were investigated by 1H- and 13C-n.m.r. spectroscopy and methylation analysis, before and after selective cleavage of furanosyl linkages. The phosphorylated and nonphosphorylated forms of the polysaccharide were found to have similar, if not identical, structures. The main structural feature of the polysaccharides is the presence of chains of contiguous arabinofuranosyl residues linked alpha-(1 leads to 5). These chains are attached at 0-4 of arabinopyranosyl residues that are present in a core region of the polysaccharide that also contains mannopyranosyl residues. Immunochemical studies demonstrated that the polysaccharide is an effective, precipitating antigen with antisera from rabbits immunized with cell walls or heat-killed cells of M. smegmatis. The polysaccharide is, however, more effective as a precipitating antigen after removal of the succinate groups, and completely ineffective after removal of arabinofuranosyl residues. The polysaccharide therefore contains an important antigen in common with the arabinogalactan lipopolysaccharide of the cell wall of the bacterium, i.e., chains of contiguous alpha-(1 leads to 5)-linked arabinofuranosyl residues.


Operant conditioning of pontine gigantocellular units. In order to investigate the behavioral role of pontine gigantocellular field (FTG) units, we have operantly reinforced discharge in these cells in unrestrained cats using lateral hypothalamic stimulation as the reinforcing stimulus. Cats readily learned to increase discharge rate in reinforced FTG cells relative to simultaneously recorded, non-reinforced control cells. Increased FTG discharge was associated with elevated levels of motor activity and often with stereotyped movements. Our results are compatible with the hypothesis that FTG unit discharge is related to specific movements.


The tanycyte of the rat median eminence. I. Synaptoid contacts. The present ultrastructural study proves the existence of nerve terminals closely apposed to the plasmalemmata of tanycytes in the rat median eminence. Several of these "axo-tanycytic" endings display remarkable accumulations of agranular endoplasmic reticulum in the form of pleomorphic vesicles which are closely apposed on either side of the plasma membrane of each cell compartment. Some of these vesicular profiles give the impression of structural continuity across both membrane systems. This phenomenon is discussed in the context of being a potential substratum for communication between both cell compartments.


The outer boundary of the cytoskeleton: a lamina derived from plasma membrane proteins. We prepared the cytoskeletal framework by gently extracting cells with Triton X-100. Lipids and soluble proteins were removed, leaving a complex meshlike structure which contains the cell nucleus and is composed of the major cell filament networks as well as the microtrabeculae with attached polyribosomes. The surface sheet or lamina covering this structure contains most of the cell surface proteins by the following criteria. Intact cells are labeled externally with radioiodine and then extracted with detergent. The iodinated poteins remain almost entirely with skeletal framework. A new major integral protein, the coat protein of Sindbis virus, is inserted into the plasma membrane of infected cells. This new protein is heavily iodinated and remains almost completely associated with the framework after extraction. Lectin binding and poliovirus binding sites are also retained after detergent extraction. Our results indicate that plasma membrane proteins form a sheet or lamina upon removal of lipids. This lamina reproduces even complex surface convolutions and appears to be supported by and intimately connected to the underlying skeleton. In this case, the surface lamina, and hence the plasma membrane of the original intact cell, might be viewed as a component of the cytoskeletal framework.


Pinocytosis in L cells: its dependence on membrane sterol and the cytoskeleton. Pinocytosis in L-cells, grown in serum-free medium, was depressed when cultures were treated with oxygenated derivatives of cholesterol which inhibited sterol synthesis and reduced the sterol concentration of the plasma membranes. Noninhibitory sterols, such as cholesterol or desmosterol counteracted the effects of the inhibitors. Treatment with polylysine increased the rate of pinocytosis in sterol-depleted cells to a level similar to the enhanced rate found in polylysine treated control cells. Drugs which interfere with cytoskeletal systems (microfilaments, microtubules) also depressed pinocytosis but their effect could not be overcome by treatment with polylysine.


Regulation of initiation of DNA synthesis in relation to mitosis in cultured hepatoma cells. The commitment of Reuber H 35 hepatoma cells to DNA synthesis was studied by exposing cells which were synchronized by serum depletion, to serum. It is shown that the period of commitment is 6--8 during the G2 period of the previous cell cycle.


Diurnal variations of estriol and cortisol in serum and urine in late pregnancy with and without fenoterol-therapy. The serum concentration of unconjugated estriol, total estriol, cortisol in one hour intervals and the urinary excretion of total estrogens and cortisol in three hour intervals was determined in eleven apparently healthy women between 26 and 40 weeks of gestation. They were divided into two groups, in order to study the influence of Fenoterol treatment on the daily variation of the measured parameters. Six patients were treated with Fenoterol and five patients received no medication. Between the two groups no statistical differences could be detected for the measured parameters. Regular and marked diurnal variations in cortisol have been observed, whereas total and unconjugated estriol showed small and irregular daily changes. These daily variations of "estriol" were of the same magnitude as the two-fold methodical standard deviation. For this reason it is not necessary to standardize the sampling time.


Prader-Willi syndrome and chromosomal mosaicism 46,XY/47,XY,+mar in two cases. Two cases of the Prader-Willi syndrome with 46,XY/47,XY,+mar are reported. The majority of Prader-Willi patients with chromosome abnormalities have either 15/15 translocations or mosaicism. Both of these aberrations presumably occur after fertilization. A possible relationship between high parental age and chromosome abnormalities in the Prader-Willi syndrome is discussed.


[Formaldehyde in hair shampoos].

[Formaldehyde in hair shampoos]. In most hair shampoos commercially available in Western Germany formaldehyde or formaldehyde liberating substances serve as efficient preservatives especially in shampoos of the lower price group. Besides, PHB-ester, mercury containing substances and since recently brome compounds are used for this purpose. We observed a 15 year old patient who developed an allergic contact dermatitis from formaldehyde in a hair shampoo. However, compared to the widespread opportunities of exposure allergic contact dermatitis caused by hair shampoos is not very frequent. For this rarity of formaldehyde dermatitis caused by shampoos the short period of application and the low concentration because of the high dilution and perhaps the low contact dermatitis reactivity of the scalp are responsible. After all only two out of thirtyone thoroughly questioned patients, who had acquired a professional formaldehyde sensitivity elsewhere, reported a contact dermatitis caused by shampoos, which by the way appeared in the orbital region as typical. Probably allergic contact dermatitis from formaldehyde in shampoos will be expected in patients with a formaldehyde sensitivity acquired formerly elsewhere, especially professionally. To those patients formaldehyde free hair shampoos should be recommended. The declaration of formaledehyde in cosmetics, which will be legally obligatory in Germany in 1979, will be valuable for finding out the alternate products free of formaldehyde.


A multi-generation toxicity evaluation of p,p'-DDT and dieldrin with Japanese quail. I. Effects on growth and reproduction. A toxicity Evaluation of DDT and dieldrin was conducted using Japanese Quail. The effects of feeding DDT (5 and 50 ppm of diet) and dieldrin (0.1 and 1.0 ppm of diet) in this four generation study (parental, F1, F2 and F3) were examined in terms of growth, viability, and/or reproduction of offspring. Ten groups (including controls and replicates of groups) contained 21 birds/group for the parental generation, and 21-35 chicks for each respective generation study. At 50 ppm DDT, a marginal decrease in egg hatch-ability of F2 generation was evidenced; the decrease appeared related to a slight decrease in fertility rather than egg production or hatchability of fertile eggs. Data accumulated from all other experimental groups were within the expected range and were comparable to control data.


Diurnal variation in serum uric acid of rats fed potassium oxonate. The uric acid plasma levels produced in rats fed a hyperuricemic diet including uric acid and potassium oxonate are highly variable and do not attain steady-state blood levels. The levels are dependent on the time of day that the blood was collected.


Diurnal rhythm of pituitary-thyroid axis in male rats and the effect of adrenalectomy. Levels of TSH, thyroxine (T4) and triiodothyronine (T3) were measured by radioimmunoassay in plasma (TSH, T4, T3) and pituitary (TSH) of 60-day old male Long-Evans rats. Definite diurnal rhythms were demonstrated in pituitary TSH, plasma TSH and T3 in intact rats, evidenced by the statistically significant differences between zenith and nadir for pituitary TSH, plasma TSH and T3. The zenith value of pituitary TSH and the nadir values of plasma TSH, T4 and T3 were observed at the same time (2400 h) as were the nadir value of pituitary TSH and the zenith values of plasma TSH, T4, and T3 (at 1200 h). Our results indicate that the rhythmicity of pituitary TSH content is a mirror image of that of plasma TSH. Adrenalectomy not only reduced plasma corticosterone levels to almost zero, but also decreased plasma T3 and T4 levels. In adrenalectomized rats, the absolute concentration of pituitary and plasma TSH increased at 1200 h and at 2400 h and, in both cases, the difference between values at 1200 h and at 2400 h persisted. The differences in plasma TSH, T3 and T4 between 1200 h and 2400 h were also observed in sham-adrenalectomized rats. These results suggest glucocorticoids do influence the pituitary-thyroid axis, but that the rhythmicity of the pituitary-thyroid axis does not seem to depend on the rhythmicity of glucocorticoid secretion.


Inhibition of estrous behavior by progesterone in rats: role of neural estrogen and progestin receptors. Sexual receptivity can be induced in ovariectomized rats with sequential injections of 17 beta-estradiol-3-benzoate (EB; 2 micrograms sc) and progesterone given 24 h apart. If a high dose of progesterone is used, estrous behavior is followed by a period during which sexual receptivity cannot be reinduced with a second progesterone injection (sequential inhibition). We have examined the effects of a hormone treatment which causes a sequential inhibition on levels of estrogen and progestin receptors in the hypothalamus-preoptic area-septum of ovariectomized rats. In a preliminary experiment, a single injection of 2 micrograms EB caused a significant increase in the concentration of brain cell nuclear estrogen receptors, Peak levels were seen at 12-24 h and remained significantly elevated as long as 72 h after EB. In a second experiment, we found that 48 h after EB, brain cytoplasmic estrogen receptors were significantly depressed and nuclear estrogen receptors were significantly elevated. However, a single progesterone injection (5 mg, sc) 24 h after EB had no significant effect on either cytoplasmic or nuclear estrogen receptor levels. Forty-eight hours after EB, brain cytoplasmic progestin receptors were significantly elevated compared with oil-injected controls. In a third experiment, progesterone (5 mg, sc) given 24 h after EB reduced neural cytoplasmic progestin receptors to levels significantly below those of oil-injected controls at 48 h. These results are consistent with the suggestion that progesterone does not interact with neural estrogen receptors to inhibit lordosis in rats. Rather, we suggest that progesterone may induce a behavioral refractoriness to subsequent progesterone treatments, at least in part, by reducing the concentration of neural cytoplasmic progestin receptors.


Modification of yeast uricase with polyethylene glycol: disappearance of binding ability towards anti-uricase serum. Uricase from Candida utilis was modified with activated polyethylene glycol (2-O-methoxypolyethylene glycol-4,6-dichloro-s-triazine) of molecular weight of 5,000 daltons. The modification of 43% of the total amino groups in the uricase molecule gave rise to a complete loss of the binding ability towards anti-uricase serum from rabbit. This modified uricase retained 15% of the enzymic activity of non-modified uricase.


N6-[N-(6-Aminohexyl)carbamoylmethyl]-coenzyme A. Synthesis and application in affinity chromatography and as an immobilized active coenzyme. The synthesis of a new coenzyme A analogue, N6-[N-(6-aminohexyl)carbamoylmethyl]-CoA, suitable for immobilisation through its terminal amino group to support matrices, is described. The synthetic route starts with bis(CoA) and involves the following steps: alkylation with iodoacetic acid and rearrangement yielding bis(N6-carboxymethyl-CoA), elongation of the carboxymethyl terminal with 1,6-diaminohexane using carbodiimide to yield bis(N6-[N-(6-aminohexyl)-carbamoylmethyl]-CoA) and finally the splitting of this bis[CoA analogue) through reduction with dithiothreitol to give the final product in approximately 10% overall yield. This CoA analogue showed 'coenzymic activity' with the enzymes acetyl-CoA synthetase, phosphotransacetylase and succinic thiokinase. Covalent binding of the CoA analogue to Sepharose 4B was normally carried out using its S-(5-thio-2-nitrobenzoic acid) derivative as this allows a convenient way for determining the amount of ligand coupled, based on the amount of 5-thio-2-nitrobenzoic acid liberated from the gel after reduction with dithiothreitol. After covalent binding of the CoA analogue to water-soluble activated dextran 70, the analogue was recycled while present in an ultrafiltration cell using the enzymes phosphotransacetylase and citrate synthase. The reaction was followed by measuring the citrate formed on addition of acetylphosphate and oxaloacetate. In affinity chromatographic studies it was shown that the CoA-Sepharose preparation could bind the CoA-dependent enzymes citrate synthase and succinic thiokinase and these could be biospecifically eluted using soluble CoA.


Reaction of formaldehyde with calf-thymus nucleohistone. The reactions of formaldehyde with calf thymus nucleohistone were analyzed in the following ways: measurement with fluorescamine of the decrease in primary amino groups resulting from hydroxymethylation and crosslinking reactions, measurement with dodecylsulphate-gel electrophoresis of formation of histone oligomers, measurement of fixation of histones to the DNA in nucleohistone, and measurement of changes in the circular dichroism spectrum in the region of 250--300 nm. In the presence of formaldehyde, the primary amino groups of histones decreased very rapidly, attaining an equilibrium within 60 min, and successively intermolecular crosslinks were also formed between histone molecules, the resulting dimers and oligomers being separable by dodecylsulfate-gel electrophoresis. Whereas the fixation reaction proceeded much more slowly. The extent of fixation could be measured more accurately by dodecylsulfate/sucrose centrifugation analysis than by sulfuric acid extraction. After removal of formaldehyde from the reaction mixture, the fraction of masked amino groups decreased, perhaps due to the reverse reaction, but the extent of fixation of histones continued to increase with time. No specificity was observed among five molecular species of histones in the fixation reaction. With increase in formaldehyde concentration, the ellipticity of nucleohistone decreased to a minimum with about 0.4% formaldehyde, and then increased.


Action of posterior pituitary neuropeptides on the nigrostriatal dopaminergic system. The effect of vasopressin, oxytocin and the C-terminal tripeptide of oxytocin, prolyl-leucyl-glycinamide (PLG), were tested on rotational behavior, following unilateral 6-OHDA-enduced lesion of the dopaminergic cell bodies in the substantia nigra. Intraventricular injection of lysine8-vasopressin, oxytocin or PLG caused ipsilateral (towards the lesioned side) rotation, as did peripheral administration of amphetamine. Direct local microinjection of the peptides into the substantia nigra on the intact side was without effect. The data suggest that posterior pituitary neuropeptides (vasopressin and oxytocin) caused presynaptic activation of the nigrostriatal dopaminergic terminals.


Clonidine reversal of increased norepinephrine metabolite levels during morphine withdrawal. The production of the norepinephrine metabolite 3-methoxy-4-hydroxyphenethyleneglycol (MHPG) in brain regions innervated by the locus coeruleus was increased during naloxone-precipitated withdrawal from chronic morphine treatment. This MHPG increase was reversed by subcutaneous administration of clonidine. Changes in MHPG levels paralleled the elctrophysiological changes found by Aghajanian (1978) in locus coeruleus firing rate with similar treatments, demonstrating the usefulness of MHPG changes as an index of central noradrenergic function.


Naloxone-induced contracture of ileum from stressed guinea pigs. The in vitro preparation of guinea-pig ileum taken from animals which had been stressed by swimming for 5 min in water at 20 degrees C responded by a dose-dependent contracture to the narcotic antagonist naloxone. This response was antagonised by atropine (8 X 10(-8) g/ml). Ileum preparation from non-stressed guinea pigs did not respond to naloxone in concentrations up to 1 X 10(-5) g/ml. The possibility that this response is a consequence of the stress-induced release of endogenous opiate peptides is discussed.


Interactions between serotonergic and dopaminergic systems in rat brain demonstrated by small unilateral lesions of the raphe nuclei. Unilateral lesions in the dorsal raphe (DR) resulted in decreased concentrations of 5-hydroxytryptamine and 5-hydroxyindoleacetic acid and increases in homovanillic acid and 3,4-dihydroxyphenylacetic acid in the ipsilateral substantia nigra (SN). Unilateral lesions in the median raphe (MR) caused similar biochemical changes in the corpus striatim (CS). Apomorphine and amphetamine caused turning behaviour in the lesiond animals which was ipsiversive after DR lesions but contraversive after MR damage. The animals turned in the opposite direction to that induced by these drugs after treatment with 5-methoxy-N,N-dimethyltryptamine and in the same direction after treatment with phenelzine plus L-tryptophan. All the drug-induced turning behaviour was blocked by haloperidol. The turning induced by 5-methoxy-N,N-dimethyltryptamine and in the same direction after treatment with phenelzine plus L-tryptophan. All the drug-induced turning behaviour was blocked by haloperidol. The turning induced by 5-methoxy-N,N-dimethyltryptamine was blocked by methysergide. This work suggested that the DR and MR nuclei send projections differentially to SN and CS respectively. These projections may exert a tonically active inhibition of dopamine metabolism in their respective terminal areas.


Behavioral changes produced in the cat by acute and chronic morphine injection and naloxone precipitated withdrawal. To address the issue of feline manic responses to morphine, studies were designed to examine the effects of low doses of intravenous morphine on cat behavior with emphasis placed on motor activity changes. An adaptation of an existing scoring system was used in an effort to quantify and describe behavioral patterns or shifts in activity patterns occurring during a cycle of addiction. The acute administration of 1, 2 or 4 mg/kg of morphine induces a response pattern characterized by sitting with fixed staring. An increase in motor activity with dose was also observed. When naloxone was administered prior to morphine injection all behavioral changes normally elicited by morphine were blocked completely. After 7 days of daily morphine injections certain changes in activity profiles occurred, indicating that some degree of tolerance although not complete, was beginning to occur by this time. Naloxone administered to cats maintained for 12 days on1, 2 or 4 mg/kg/day consistently produced a number of withdrawal signs including wet-dog shakes and a catatonic-like posturing. This is the first report describing behavioral responses of the cat during a complete cycle of addiction to low doses of morphine. We not only found that morphine will elicit definite quantifiable changes in behavior in the absence of any feline mania but that cats become readily dependent on these low doses of morphine as evidenced by a characteristic naloxone precipitated withdrawal syndrome.


Pinitol, a larval growth inhibitor for Heliothis zea in soybeans. A search for insect growth inhibitors in methanol extracts of soybean leaves resulted in isolation of pinitol. Pinitol caused a 50% reduction in weight gain (ED50) of Heliothis zea larvae at about 0.7% when added to a synthetic diet. Although myo-inositol is a normal component of the insect diet, it also caused growth inhibition at higher concentrations; ED50 4%.