Hormonal and nutritional status: critical conditions for endemic goiter epidemiology?

Recent advances in protein metabolism and in glycoprotein synthesis bring further insight into endemic goiter epidemiology. Retinol circulates in the blood stream in close parallelism with retinol-binding protein and prealbumin (RBP-PA), a protein complex whose liver secretory rate is dependent upon hormonal and nutritional status. On the other hand, normal glycosylation reaction occurs through the formation of a retinol-linked sugar complex. It is suggested that the relative drop of serum retinol levels, as a result of modified hormonal climate and/or declining protein status, might constitute a critical factor capable of inducing a defective incorporation of mannose into native thyroglobulin, leading to an early depression of the full glycoprotein production. This concept affords a comprehensive explanation of the following unresolved data recorded in goitrous areas: (1) clinical and biochemical discrepancies between subjects living in the same morbid territory, (2) persistence of endemicity in spite of appropriate iodine supplementation, (3) similar prevalence of goiter hypertrophy in male and female prepubertal children, (4) increased frequency of goiter enlargement in the four most vulnerable groups, namely preschool children of both sexes, adolescent girls, pregnant women, and elderly persons, (5) decreased impact of thyroid swelling accompanying improved socio-economic status, even without iodine addition, and (6) resurgence of goitrous hyperplasia as an effect of seasonal or sporadic deterioration of nutritional habits, even when iodine supply remains unchanged.


Perinatal asphyxia and outcome of very low birthweight infants.

Seventy-eight very low birthweight (VLBW) infants (whose birthweights were 1500 g or less) were admitted to the Neonatal Special Care Unit in 1977. Seventy-two of them required treatment in the intensive care area; these represented 40% of admissions to that area of the Unit. The mortality rate was 20% for infants weighing 1001 g to 1500 g, and 52% for those weighing 501 g to 1000 g. An Apgar score of 0 to 3 at two minutes and five minutes was reported in 34% and 19% of VLBW infants respectively. Although there was no difference in birthweight between the groups with a high or low Apgar score, the mortality rate of infants with a five-minute Apgar score of 0 to 3 was 79% compared to 22% in those with a score of 4 to 10. Over 50% of the infants developed hyaline membrane disease regardless of Apgar score. However, in the infants with a five-minute Apgar score of 0 to 3, the severity of respiratory insufficiency was increased as indicated by increased requirement for high inspired oxygen, and the need for intermittent positive pressure ventilation. The duration of stay in the neonatal intensive care area, and the total length of hospital stay of the 49 VLBW survivors were shorter in the group with higher two-minute and five-minute Apgar scores. Long-term morbidity cannot yet be ascertained. It is likely that prevention, or prompt detection, and appropriate management of perinatal asphyxia would produce a further decline in mortality as well as morbidity for VLBW infants.


Effects of estradiol-17beta in the male Xenopus laevis: isolation and translation of cytoplasmic messenger RNA populations.

Total Xenopus liver cytoplasmic RNA isolated following long-term estrogen administration (14 days) was fractioned using Sepharose 4B chromatography. One of the Sepharose 4B peaks was shown to contain RNA with a molecular weight reported for vitellogenin mRNA (approximately 34S). The presence of estrogen-induced vitellogenin mRNA in the peak 5 RNA was determined by translation of the RNA in the oocyte and analysis of the oocyte translational products by immunoprecipitation with anti-vitellogenin. Sepharose 4B peaks 2 and 3 were also observed to contain estrogen induced mRNA populations sedimenting between 9--18S. These findings suggest that Sepharose 4B chromatography might prove useful in separating different mRNA populations following estrogen-induced gene activation.


Immobilized flounder muscle glyceraldehyde 3-phosphate dehydrogenase.

Partially purified flounder muscle (Pseudopleuronectus americanus) glyceraldehyde 3-phosphate dehydrogenase was immobilized on cyanogen bromide-activated Sepharose. The catalytic properties of the immobilized preparation were studied to determine if immobilization alters the kinetic properties of the native holoenzyme. The results indicate that the pH activity profile of immobilized glyceraldehyde 3-phosphate dehydrogenase did not differ from that of the native enzyme. The Michaelis constants (Km) for NAD and glyceraldehyde 3-phosphate were somewhat altered. The enzyme stability toward various inactivation treatments in the presence and absence of NAD was characterized and compared to that of he native enzyme. When either form of the enzyme was incubated with urea at concentrations greater than 2M, inactivation occurred very rapidly. Incubation in 0.1% trypsin for 60 minutes decreased the activity of immobilized glyceraldehyde 3-phosphate dehydrogenase by 45% and of the native soluble enzyme by 70%. The immobilized enzyme also exhibited considerably more stability than the native soluble enzyme when exposed to a temperature of 50 degrees or to 20 mM ATP. In all cases NAD either greatly reduced the rate of inactivation or completely protected the enzyme from inactivation.


[Benign recurrent cholestasis in monozygotic twin girls (author's transl)].

The cases of Monozygotic twin girls suffering from benign recurrent familiar intrahepatic cholestasis are reported. So far both children had six icteric episodes due to this disease. These episodes occurred during times of severe emotional stress therefore, it may be assumed that a latent enzyme deficiency in the metabolism of bile acids, which is determined genetically, could be influenced by psychosomatic mechanisms. During the acute phases phenobarbital and cholestyramine succesfully reduced serum bilirubin levels.


Intrinsic haematopoietic activity of cerebellar haemangioblastomas. Ultrastructural study of three cases.

Three cerebellar haemangioblastomas were studied by electron microscopy. One of these shows electron-dense granules within the tumour cells, indicative of erythropoietic activity, as previously described in a haemangioblastoma. The biological significance of these granules is discussed. Biological assay of serum erythropoietic activity was performed in one case.


Reanalysis of the preoptic afferents and efferents involved in the surge of LH, FSH and prolactin release in the proestrous rat.

In order to elucidate neural pathways concerned with the proestrous surge of LH, FSH and prolactin (Prl) release, brain transection or lesion was made acutely under ether anesthesia between 12.00 and 14.00 h of proestrus, and electrochemical stimulation was done under anesthesia with pentobarbital sodium (31.5 mg/kg b.w.) injected at 13.45 h. Transection which interrupted the connection of septum (SEPT), diagonal band of Broca (DBB) and bed nucleus of stria terminalis (BST) with the preoptic-suprachiasmatic area interfered with ovulation and surge of release of all 3 hormones. Isolation of the basal part of the suprachiasmatic area, including the suprachiasmatic nucleus (SCH), blocked ovulation also. Bilateral lesions in the medial preoptic area (MPO) with platinium-iridium electrode blocked ovulation and the surge of LH and Prl release, but not of FSH. Lesions in the SCH blocked ovulation and the surge of LH, but not of FSH and Prl. In the rat with acute isolation of the basal part of the suprachiasmatic area and SCH, stimulation of the MPO failed to induce ovulation and LH release, but was followed by FSH release. Prl release was not inhibited as in the intact rat. When the rat had the antero-SCH cut, stimulation of the SCH induced LH release but not FSH, and the inhibition on Prl release was pronounced. These findings offer evidence that the limbic-forebrain inputs are necessary for the preoptic integration in order to stimulate the proestrous surge of LH, FSH and Prl release. Furthermore, it is possible that separate pathways from the preoptic area to the medial basal hypothalamus are concerned in the stimulation of individual hormones--a restricted route for LH which may pass through the SCH, a diffuse one for FSH which may pass through either the SCH or anterior hypothalamic area, and a relatively diffuse one for Prl which may pass outside the SCH.


Induction of persistent estrus by constant light: effects of neonatal constant light and Harderian gland function.

The effect of constant light on the age at onset of persistent estrus was compared in rats exposed to constant light since birth (LL-0) and those exposed beginning at 70 days of age (LL-70). Persistent estrus occurred about 27 days later in the LL-0 rats than in the LL-70 rats. Exposure to LL for just the 1st 15 days of life (LL-0-15) and then subsequent exposure to LL at 71 days also delayed the induction of persistent estrus. Neonatal injection of a Harderian gland (HG) homogenate to LL-0-15 rats reduced the age of vaginal opening and 1st estrus and reduced the delayed onset of persistent estrus caused by the neonatal LL. Harderianectomy of LL-0 or hematoporphyrin injections in LL-0-15 rats had no effect on the onset of LL-induced persistent estrus.


Effects of adrenalectomy and constant light on the rat estrous cycle.

Adult female ARS/Sprague-Dawley rats were allowed to acclimatize to a a lighting schedule of 12L:12D (LD) for 5 weeks. At that time, half the animals were adrenalectomized, and all rats remained in LD for an additional 4 to 5 weeks. Subsequently, half of the control and half of the adrenalectomized rats were exposed to constant light (LL) for an additional 8 weeks, at which time all animals were sacificed. Operated rats with regenerated adrenal tissue, determined either by macroscopic examination or serum corticosterone assay (about 50% of the rats), were excluded from all data calculations. Acute disturbances of estrous cycle length were minor. The long-term effects revealed a significant increase in 5-day cycles among the adrenalectomized rats, although the majority of cycles recorded (80%) were still 4 days in length. None of the rats in LD showed spontaneous persistent estrus. Adrenalectomy did not affect the number of ova shed. When placed in LL, the adrenalectomized rats continued to cycle longer than the unoperated controls, but all rats showed persistent estrus (5 or more consecutive days of vaginal cornification) within 7--8 weeks. Adrenalectomized rats had significantly higher body weights than controls. Relative uterine weight was decreased in these animals in both lighting regimens but only reached statistical significance in LD. Ovarian weight, by contrast, was significantly increased among adrenalectomized rats in LD but was identical in both groups in LL. Adrenal weight of intact rats was not altered by LL. Since estrous cycles can continue for at least 6 months in the absence of the adrenal gland, the persistent estrus that occurs in LL is not merely due to the loss of a diurnal rhythm of corticosteroids. Indeed, when adrenalectomized rats are placed in LL, they continue to show estrous cycles longer than do intact rats. Adrenalectomy does appear to increase the length of the cycle in some animals, and the hormonal basis for this warrants further study.


Prevention of compensatory ovarian hypertrophy by local treatment of the ovary with 6-OHDA.

The possible role of a neural mechanism involved in the development of compensatory ovarian hypertrophy has been studied. A new technique, the use of a special plastic capsule, has been developed to allow chronic local treatment of the ovary. Local treatment of one of the ovaries with 6-hydroxydopamine (6-OHDA) resulted in a weight increase in the other ovary. In the unilaterally ovariectomized rat the local application of 6-OHDA on the ovary blocked the development of compensatory ovarian hypertrophy. Local treatment of the ovary with dopamine (DA) did not interfere with the compensatory ovarian growth of the other ovary. Data suggest that intact adrenergic afferent and efferent neural elements of the ovary are required for the development of compensatory ovarian hypertrophy.


Clinical features of subcortical arteriosclerotic encephalopathy (Binswanger disease).

Subcortical arteriosclerotic encephalopathy, a chronic vascular dementia with hydrocephalus, was characterized pathologically in five patients by severe thickening of small vessels and by diffuse regions of white matter loss with gliosis. Lacunar infarcts were also present. The clinical picture in 11 patients was characterized by: (1) persistent hypertension and systemic vascular disease; (2) acute strokes; (3) subacute accumulation of focal neurologic symptoms and signs over weeks to months; (4) long plateau periods; (5) lengthy clinical course; (6) dementia; (7) prominent motor signs and pseudobulbar palsy and; (8) hydrocephalus. The pathogenesis of subcortical arteriosclerotic encephalopathy is unknown; possible mechanisms include diffuse ischemia and fluid transudation with subsequent gliosis related to subacute hypertensive encephalopathy.


Oral contraceptives and stroke in young women: a clinicopathologic correlation.

Pathologic studies of women with fatal cerebrovascular disease who have received oral contraceptives are infrequently found in the literature. Three cases of this type are reported here. The pathologic findings included an intrinsic vascular lesion in the form of intimal hyperplasia with and without associated thrombosis, found in arteries supplying the brain. Similar vascular lesions have been reported previously in other sites of the vascular system in association with exogenous or endogenous steroids. They have also been found in other species under the influence of steroids. This hyperplasia of vessel intima may be found in association with other clinicopathologic entities, but stigmata of other diseases were not found in these three patients.


Aphasia following infarction of the left supplementary motor area: a clinicopathologic study.

The speech disturbance of a patient with a single embolic infarct of the left supplementary motor area was characterized by initial mutism, rapid recovery to fluent speech marked by short sentences with normal grammar, persistent severe impairment of writing, and frustration and anxiety related to language tasks.


Muscle wasting and carbohydrate homeostasis in Duchenne muscular dystrophy.

Carbohydrate homeostasis was evaluated in nine patients with Duchenne muscular dystrophy (DMD), and in six age-matched normal boys. Mild carbohydrate intolerance was observed in the DMD patients during an oral glucose tolerance test. Only minor differences were observed between the DMD patients and the normal subjects during an oral glucose tolerance test. Only minor differnences were observed between the DMD patients and the normal subjects during a 30-hour period of caloric deprivation. Despite obvious muscle wasting and significant hypoalaninemia, the DMD group was resistant to fasting hypoglycemia. Plasma glutamine concentrations were the same in both groups under all study conditions. Dueterium-labeled glucose and alanine flux studies documented normal glucose inflow and outflow rates and decreased alanine inflow and outflow rates in the DMD group. The 40 percent reduction in alanine turnover, however, was less than expected for a group of patients with an estimated 67 percent reduction in muscle mass. These observations suggest that there may be accelerated protein degradation in the muscles of DMD patients.


Ventricular fluid homovanillic acid and 5-hydroxyindoleacetic acid concentrations in patients with movement disorders.

Ventricular fluid concentrations of homovanillic acid (HVA) and 5-hydroxyindoleacetic acid (5-HIAA), the respective metabolites of dopamine and serotonin, were measured in 57 patients undergoing thalamotomy for relief of movement disorders. The diseases included were Parkinson disease, dystonia, cerebral palsy, multiple sclerosis, and posttraumatic or posthypoxic encephalopathy. Untreated parkinsonian patients had the lowest mean HVA level (119 ng per milliliter). Patients with multiple sclerosis or with posttraumatic or posthypoxic encephalopathy with both intellectual impairment and bilateral motor involvement had lower mean HVA levels (197 and 177 ng per milliliter, respectively) than cerebral palsy patients with bilateral motor disease (233 ng per milliliter), dystonia patients (246 ng per milliliter), or multiple sclerosis patients with normal intellect (376 ng per milliliter). The data suggest that diffuse cerebral disease may lead to diminished dopaminergic activity. Ventricular fluid 5-HIAA levels were similar in all groups of patients. Chronic cerebellar stimulation markedly increased ventricular fluid HVA and 5-HIAA levels, indicating that cerebellar stimulation affected cerebral dopaminergic and serotonergic systems.


Diminished ventricular fluid dopamine metabolites in adult-onset dystonia.

Homovanillic acid (HVA) and 5-hydroxyindoleacetic acid (5-HIAA), the respective metabolites of dopamine and serotonin, were measured in ventricular fluid obtained from 20 patients with torsion dystonia at the time of ventriculography prior to thalamic surgery. The patients could be divided into two distinct types of dystonia--childhood-onset and adult-onset--which were identifiable on clinical and biochemical grounds. In the 14 patients with childhood-onset dystonia, the first symptom appeared in one limb in early childhood and the disease usually progressed rapidly. In the six patients with adult-onset dystonia, the first symptom usually appeared in axial muscles after adolescence and the disease progressed slowly. Ventricular fluid HVA levels were significantly lower in the patients with adult-onset dystonia than in those with childhood-onset dystonia. The differences suggest diminished dopaminergic activity, possibly secondary to nigrostriatal dysfunction, in adult-onset dystonia.


Assessing segmental excitability after acute rostral lesions. I. The F response.

F responses were elicited from both hands of patients shortly after they sustained unilateral cerebrovascular lesions. In 17 of 29 patients, significant abnormalities were found; F responses occurred with decreased persistence and/or amplitude on the clinically involved side, a change which was seen only in patients studied within 4 weeks of the ictus. The most prominent changes (in comparison with the clinically uninvolved side) occurred with extensive lesions. The abnormalities of F response correlated clinically with severity of the weakness, decrease in tone, and decrease in deep tendon reflexes. These changes in F response are consistent with a decreased "central excitatory state" at the spinal segmental level during the early phase after a supratentorial stroke.


Agenesis of the corpus callosum: limits of functional compensation.

Two patients with radiologically confirmed total agenesis of the corpus callosum, and free of gross focal hemispheric pathology, received a battery of lateralized and free-field language and perceptual-motor tests. These tasks allowed a comparison of (1) agenic findings with previous results from surgical commissurotomy patients, and (2) the inter- and intrahemispheric performance for each agenic subject. In general, the results indicate that the two agenic patients do not demonstrate the marked deficits of cross-integration reported after commissurotomy. However, there was an upper limit to their integrative capacity for visual, and to an even greater extent, for fine motor and kinesthetically mediated performance. The tasks that proved particularly difficult appeared to have common factors which may be related to functional capabilities of the ipsilateral motor pathways and anterior commissure.


Kinetic evidence for a structural abnormality of lipoamide dehydrogenase in two patients with Friedreich ataxia.

Two unrelated patients with Friedreich ataxia were deficient in the activity of the enzyme lipoamide dehydrogenase (LAD). The enzymes from the patients' platelets differed significantly from controls in activity, in KM for lipoamide, and in KM for NADH. The data are consistent with a structural mutation of the gene coding for LAD.


Anal muscle electromyograms differ in amyotrophic lateral sclerosis and Shy-Drager syndrome.

Electromyography (EMG) of anal sphincter muscles was different in patients with amyotrophic lateral sclerosis (ALS) and Shy-Drager syndome. In 30 patients with ALS, EMG of the external sphincter muscle was essentially normal, with no signs of denervation. In eight cases of Shy-Drager syndrome, however, motor unit potentials of the anal sphincter had highly polyphasic forms of long duration and high amplitude. In the Shy-Drager syndrome, there seems to be specific damage of lower motor neurons that innervate the external sphincter muscle of the anus.


Association of central pontine myelinolysis and Marchiafave-Bignami disease.

Combined pathologic features of central pontine myelinolysis and Marchiafava-Bignami disease occurred in a 53-year-old man with chronic alcoholism. This association is rare despite the basic similarities of these two disorders. The combination of both conditions in the same patient suggests a common pathogenetic mechanism.


Midline hyperplasia with malformation of the fornical system.

A physically and intellectually normally developed boy had a resection of a lumbar myelomeningocele shortly after birth and a shunt was inserted for hydrocephalus. He died at age 12 years after a traffic accident. Autopsy disclosed a hyperplasia of the cerebellar vermis. An abnormal median-sagittal triangular fiber tract ran on the dorsal surface of the corpus callosum and contained more than 3 million fibers, most of them very thin and myelinated. The tract was identified as a hyperplastic fornix dorsalis. The complex malformation was attributed to hyperplasia of midline structures.


Adult onset nemaline myopathy.

A 47-year-old man had symptoms of nemaline myopathy for approximately 1 year. There were marked elevations of creatine kinase, a feature not previously described. Examination of the nervous system at autopsy failed to reveal any abnormalities.


Notalgia paresthetica.

Notalgia paresthetica was described by Astwazaturow in 1934. We have seen six cases in the past year, suggesting that it is not rare. This sensory neuritis affects the posterior rami of several spinal nerves (arising from thoracic segments T2 to T6), causing pruritus, burning, and dysesthesias. Examination reveals hypesthesia. Although the cause is not known, the course seems benign. The posterior rami of these five dorsal roots traverse a 90-degree course through the multifidus spinae muscle, making them unique among the posterior rami.


Handcuffs and cheiralgia paresthetica.

Cheiralgia paresthetica has been reported in the past, but the exact etiology is unknown. We present two cases that occurred secondary to handcuff placement.


Testicular regression syndrome.

Recently, the testicular regression syndrome has been reported as being representative of a clinical range of XY agonadal persons. A patient with aberrant fetal sexual development is described. Of particular interest is that all of the tissues examined--the rudimentary uterine horn and the 2 fallopian tubes--displayed an XY chromosome complement. Correlation was made between the known temporal events of embryogenesis of the testes and the apparent time of regression of the testes. In this patient, the insult to testicular development, with subsequent testicular regression, occurred between 48 and 60 days after fertilization. This review supports the previously reported thesis that in certain XY persons the testes are irreparably damaged at a critical stage in fetal development, and that this critical stage is represented by a range of abnormalities of genital development. Possible causes and simplified nomenclature for such gonadal damage are presented.


Ovulation induction in amenorrheic women.

Seventy-six patients with primary or secondary amenorrhea who wished to conceive were treated with clomiphene citrate, 2-Br-alpha-ergocryptine, and/or human menopausal gonadotropins (hMG). Of these 71 patients who received clomiphene citrate, 39 (55%) ovulated. Of these 71 patients, 52 had withdrawal uterine bleeding following IM progesterone, and 38 (73%) ovulated; only 1 of the 19 who did not bleed ovulated (P less than 0.001). Ovulation occurred in the former group of patients whether or not they had galactorrhea. Of the 32 patients who failed to ovulate despite treatment with the maximal dose of clomiphene, 250 mg/day for 5 days, 26 received hMG-hCG. All 26 ovulated and 15 conceived. All 8 patients with amenorrhea-galactorrhea who were treated either primarily or secondarily with bromergocryptine ovulated, and 4 conceived. Therefore, the drug of choice for ovulation induction in amenorrheic patients depends on 1) the presence of withdrawal bleeding after progesterone and 2) the presence of galactorrhea. In all patients with progesterone withdrawal bleeding with or without galactorrhea, the initial treatment of choice is clomiphene citrate. In the absence of withdrawal bleeding, hMG should be administered if galactorrhea is absent, and bromergocryptine should be administered if galactorrhea is present.


Transvitreal carbon dioxide laser photocautery and vitrectomy.

A new form of carbon dioxide laser has been developed that allows placement of infrared energy within a fluid medium. Transvitreal photocautery, vitrectomy, and laser scalpel incisions have been accomplished utilizing this delivery modality of infrared energy. Clinical trials are presently underway.


Audiologic manifestations in otitis media.

The pathologic processes that affect the middle ear transmission mechanisms in otitis media are dynamically variable and may cause different degrees of severity and changing pure tone configurations. By the same token, different disease conditions may yield similar audiometric curves. The air-bone gap is the chief indicator of middle ear abnormality but rarely provides a quantifying measure or a means of differential diagnosis. The clinician and audiologist must concern themselves singularly and together in achieving a correct diagnosis especially when there is concomitant neurosensory hearing loss. They must apply all the facilities at their disposal in order to correlate the otoscopic clinical findings with the magnitude and type of hearing loss.


Transurethral external sphincterotomy sans external sphincter.

Of 51 patients with detrusor-sphincter dyssynergia undergoing external urethral spincterotomy by transurethral resection, histological examination revealed no skeletal muscle in the resected tissue in six patients. The functional improvement which resulted in these cases despite this finding with an explanation for the same forms the topic of this paper.


Perspectives in open spaces. A geometrical application of the Thouless index.

A geometrical model for computing 'general perspectives' is discussed. It is based on the power function r = p(d/t) 1 -i, where i is the Thouless index for the phenomenal regression to the real object, r is the real size of the object, p is the apparent size, d is the distance between the subject and the object, and t is the distance between the subject and the projection plane. This model assumes that i is invariant for different distances and this was verified in seventy children and adults at distances of 15 or 120 m. A computer program draws families of curved perspectives which are well-fitted to the actual shape of large visual alleys produced by experiment in open fields.


The AC impedance of Necturus gallbladder epithelium.

The impedance of Necturus gallbladder epithelium was determined using sine wave currents of 1 Hz to 30 kHz. In control Ringer's solution the impedance locus exhibited a simple semicircle with minute shift of the high frequency end along the real axis and a minute depression of the center below the real axis (average 0.9 +/- 0.7 degrees). Neglecting the slight suppression, the impedance of 1 cm2 of epithelium can be represented by an electrical analogue consisting of a parallel RC element of 115 +/- 26 omega and 5.16 +/- 0.9 muF in series with a small resistor of 5.3 +/- 1.3 omega. In agreement with experimental results obtained under ionic or osmotic substitutions, the applicability of this simple RC analogue to gallbladder epithelium under control conditions can be explained by the influence of the paracellular shunt and by assuming the time constants of the apical and basal cell membranes to be comparable. Based on these data and on voltage divider measurements obtained with microelectrodes the capacitances of the apical and basal cell membrane can be estimated to be approximately 7 and approximately 18 muF/cm2. The latter value agrees well with estimates of the surface folding obtained from electromicrographs, if the specific cell membrane capacitance is assumed to be approximately 1 muF/cm2 as in other cell membranes.


Transcutaneous, noninvasive PO2 monitoring in adults during exercise and hypoxemia.

A new, commercially available, transcutaneous (tc) PO2 monitor was tested in adult females and in laboratory animals to assess its applicability in measuring arterial oxygen tension during physiological stress. Observed values on dogs correlated well with direct measurements of arterial PO2 and with previous data obtained from measurements of arterial blood during exercise and hypoxemia. In our female subjects the unit responded rapidly to changes in inspired ambient oxygen and electrical stability was excellent during maximal exercise tests. Transcutaneous PO2 decreased to an average of 87.8 Torr during maximum exercise breathing 20.9% O2, and to 32 Torr while breathing 12.6% O2 at maximum work. Two distinct patterns of response to tc PO2 were observed during hypoxic and normoxic exercise. The technique appears to have substantial future application both in clinical and physiological investigation involving adult subjects.


An analysis of the effect of the rate of stimulation and adrenaline on the duration of the cardiac action potential.

1. Changes of action potential duration in cat papillary muscle have been correlated with changes of peak tension. It has been assumed that peak tension is an approximate indicator of [Ca2+]i. 2. When stimulation is commenced after a rest of several minutes, or after a decrease or increase of the stimulus rate, or after rest periods of different duration the changes of action potential duration are closely related to changes of peak tension. These results suggest that [Ca2+]i is of primary importance in determining rate-dependent changes of action potential duration, including the shortening of the action potential at high rates of stimulation. 3. The results also indicate the presence of a factor which tends to prolong the action potential at high rates of stimulation. Thus the duration of the action potential at high stimulus rates is longer than at lower rates when measured at a given value of peak tension. Furthermore in low Ca2+ there can be a prolongation of the steady state action potential at high rates. Comparison with the work of Cohen et al. (1976) suggests that this factor is responsible for the polarity of the T-wave of the ECG. 4. The action of adrenaline on action potential duration has also been analysed. It is shown to have two effects--a prolonging effect probably related to the adrenaline induced increase of Isi, and a shortening effect probably related to an increase of [Ca2+]i (as judged by the increase of peak tension).


Biosynthesis of mitochondrial protein components in the liver of cold exposed or adapted rats.

Liver mitochondria of rats exposed or adapted to cold were fractionated after labelling in vivo with radioactive amino acid mixture. Specific activity (Cpm/mg proteins) of unfractionated proteins from the whole mitochondria, water soluble proteins and cytochrome c after the animals exposure to 4 degrees C for 3, 6, 12 and 24 hr was higher as compared with the controls adapted to 24 degrees C; specific activity of contractile and structural proteins was not changed. In rats exposed to cold for 7, 14 and 21 days the labelling of all fractions studied was at the level of controls. The liver weight was increased in cold adapted rats (21 days). If expressed per total liver mass, radioactivity of all fractions was higher in cold adapted rats than in controls.


Effect of inhibitors of slow calcium current on rested state contraction of papillary muscles and post rest contractions of atrial muscle of the cat and rabbit hearts.

Effect of Ni, Co and Mn ions and of D-600 on rested state contractions (RSCs) of cat and rabbit papillary muscles and on post rest contractions (PRCs) of cat and rabbit atrial muscle was investigated. Ni and Co in concentration 2 mmol/l reduced the force of RSCs in papillary muscles by 78%, increased the dip between the phase 1 and 2 of respective action potentials (APs), lowered the level of plateau and decreased the total duration of AP. Strong PRCs in atrial muscle were reduced by Ni only by 25%, while the subsequent beats were strongly inhibited. Ni completely inhibited RSCs in papillary muscles increased by caffeine (10 mmol/1) or by reduction in Na concentration by 50%. Mn ions in concentration 1--2 mmol/l inhibited strongly both RSCs in papillary muscles and strong PRCs in atrial muscle, increased the dip between phase 1 and 2 and increased total duration of AP. Mn ions stimulated 45Ca efflux from papillary muscles and atrial strips. D-600 did not affect RSCs nor the shape of respective APs. It is concluded that RSCs in papillary muscles are directly activated by Ca inflow during the respective excitation while strong PRCs in atrial muscle are activated mostly by Ca released from intracellular stores.


Intracellular Ca2+ injection causes membrane hyperpolarization and conductance increase in lacrimal acinar cells.

Membrane potential and resistance measurements were carried out on segments of superfused mouse exorbital lacrimal glands by inserting two microelectrodes into neighbouring coupled cells. Short-lasting intracellular injections of Ca2+, by the method of microiontophoresis, caused membrane hyperpolarization and resistance reduction. These effects were also observed in the presence of adrenergic and cholinergic blocking agents. From the potential and resistance changes observed the null potential for the action of Ca2+ was calculated to be -50 mV. Short-lasting extracellular Ca2+ applications caused membrane hyperpolarization and resistance reduction, but these effects were blocked by a combination of atropine and phentolamine. Intracellular Ca2+ application mimics the action of adrenaline and acetylcholine on lacrimal acinar cells.


Morphology and electrophysiological properties of cutaneous sensilla in agamid lizards.

The external morphology of agamid cutaneous sensilla has been studied by means of the scanning electron microscope (SEM). Electrophysiological recordings from single organs were obtained in response to mechanical bending of the centrally located long seta. In this way the mechanoreceptive function of reptilian cutaneous sensilla has been established for the first time.


Relaxation of the ACh-induced potassium current in the rabbit sinoatrial node cell.

Voltage clamp experiments were carried out in order to study the mechanism of the ACh action in the rabbit S-A node cell. The following results were obtained: 1. The reversal potential of the ACh-induced current behaved like a potassium electrode, confirming that the ACh-operated channels pass potassium ions selectively. 2. On depolarizing voltage jumps the ACh-induced current showed an instantaneous peak from which the current decayed to a new steady level (relaxation). On hyperpolarizing voltage jumps the initial step change in current was followed by a gradual increase. 3. The time course of the current change on voltage jumps was well fitted by a single exponential and the time constant became longer as the membrane potential was increased. 4. The instantaneous I-V curve was linear while in the steady state the curve became flatter at low negative membrane potentials and steeper at high negative membrane potentials. The results suggest that ACh opens a specific potassium channel when the drug is bound to the muscarinic receptor. The opening and closing rate constants for this potassium channel depend on the membrane potential in such a way that on depolarizing voltage jumps the fraction of open channels gradually decreases and on hyperpolarization the fraction increases.


On the nature of the neural abnormality in human amblyopia; neural aberrations and neural sensitivity loss.

In this investigation contrast threshold measurements are compared with supra-threshold perception for a group of human amblyopes. The results indicate that human amblyopia involves, in some cases, not only loss of sensitivity but spatial distortion. Thus a new group of amblyopes can now be identified in which only distortion occurs. These results have important physiological implications for both the normal and abnormal visual systems. Neurophysiologists investigating visual loss from deprivation should assess whether similar distortions occur in animals. This question may hold the answer to whether the present animal models are relevant to the human condition.


Transport and accumulation of alpha-aminoisobutyric acid (A.I.B.) in the guinea pig placenta.

Active transport of A.I.B. from mother to fetus was studied. This was done in the intact animal and using the isolated placenta, artificially perfused at both sides. It was shown that A.I.B. is actively accumulated in the placental cells. An estimate of the kinetic constants is given. It is shown that this accumulation takes place predominantly from the maternal side of the placenta. A.I.B. that has been accumulated is cleared to the maternal and fetal circulation in equal amounts. So the netto active transport from mother to fetus is brought about by an unequal distribution of carriers, the maternal side being most active.


Effect of exercise on metabolism of glycogen and triglycerides in the respiratory muscles.

It was shown that during muscular exertion the diaphragm muscle and the intercostal muscles utilize endogenous glycogen whereas only the diaphragm muscle utilizes endogenous triglycerides. The post-excercise glycogen repletion in the diaphragm muscle was much faster than in the intercostal muscles. In the diaphragm muscle, marked overshoot of the glycogen level occurred early after the exercise.


The relative dependence of the activity of Renshaw cells on recurrent pathways during contraction of the triceps muscle.

Renshaw cell activity was recorded simultaneously with motoneuronal unit discharge during vibration and tetanic stimulation of triceps muscles in decerebrated cats. The experiments confirm that, in this preparation, the motoneurones are the main source of Renshaw cell firing during muscle stretch and vibration and when motoneuronal discharge was induced through the gamma loop. However they also show that a discharge of Renshaw cells, monosynaptically coupled with triceps motoneurones through their recurrent collaterals, could be elicited during contraction of the muscle at the time when the discharge of these motoneurones had been silenced. The recording of the stretch receptors and motoneuronal unit discharge during stretch, vibration, and ventral root stimulation gave evidence of the contribution of the withdrawal of excitation by primary endings to the occurrence of the silent period during tetanic contraction of the muscle. The measurements of the critical firing level in motoneuronal units responding reflexly to held stretch and vibration of the muscles, and silencing their discharge during muscle shortening, showed that these cells are amongst the lowest ranking in the pool For these reasons, these data suggest that Renshaw cell firing during vibration and tetanic contraction of the muscle cannot be attributed only to the alpha motoneurone excitation by the Ia fibres.


The effect of procaine on the passive electrical properties of guinea-pig ventricular muscle.

Electrotonic potentials produced by rectangular hyperpolarizing current pulses were recorded intracellularly at various distances from guinea-pig papillary muscles and the results were analyzed according to the single-dimensional cable model. In normal Tyrode solution the space constant (lambda) was 0.62 +/- 0.12 mm (mean and S.D., nine preparations) and the time constant (tau) was 4.0 +/- 0.8 ms. Procaine (1 mg/ml) increased lambda to 1.20 +/- 0.29 mm and tau to 19.7 +/- 4.7 ms by increasing the membrane resistance, while the membrane capacity was only slightly increased and little change was observed in the internal longitudinal resistance. The dose-response relationship revealed that procaine inhibited the resting membrane conductance almost completely in a one-to-one manner with the dissociation constant of about 1 mM. It was suggested that potassium conductance predominant in the resting membrane conductance in guinea-pig papillary muscle was depressed by procaine and that electrical coupling is well maintained even when the membrane resistivity of apposed normal ordinary membrane at intercalated disks becomes high.


The temperature dependence of parallel and series elastic elements in the vascular smooth muscle of the rat portal vein.

The stiffness of a parallel (PE) as well as of a series elastic element (SE) in the isolated rat portal vein was determined at 37 degrees C and at 25 degrees C. The length-tension curve of the PE was obtained by a stepwise lengthening of the preparation and showed no temperature dependence for the element: the mean extension of the PE was 48.8% of the optimum length L0 at 37 degrees C, and 47.3% of L0 at 25 degrees C when loaded with the maximum active force T0. The maximum force occurred at both temperatures with the same muscle length. Even the stiffness factor, i.e. the slope 'k' of the linear function dT/dL = k . T + c showed no temperature dependence. The series elasticity was determined by means of the quick-release technique from afterloaded isometric contractions of the tetanized preparation. A distinct temperature influence was revealed by the decrease of the mean SE extension from 13.5% of L0 at 37 degrees C to 10.9% of L0 at 25 degrees C (P less than 0.0005). The stiffness factor, normalized to the actual muscle length, was 12.0 per ML at 37 degrees C and 14.7 per ML at 25 degrees C (P less than 0.025). The values obtained for the portal vein are equivalent to those calculated for other smooth muscle preparations but the stiffness of series elasticity is well below that found in the cardiac and skeletal muscle.


Thermal control of blood flow through capillaries and arteriovenous anastomoses in skin of sheep.

Using radioactive microsphere and electromagnetic techniques, hindleg vascular responses were studied in 38 conscious, chronically prepared sheep subjected to either exposure to a warm environment, and/or local warming of the hypothalamus, spinal cord, forelegs of hindlegs. The total proportion of cardiac output passing through AVA's was increased by all treatments. AVA flow in hindleg skin was increased but capillary flow was unchanged by warming the hypothalamus, spinal cord or forelegs. AVA flow was unchanged but capillary flow was increased by warming the ambient air or the hindlegs alone. Equivalent cooling treatments resulted in AVA and capillary flow changes converse to warming. It is concluded that, in sheep, blood flow through cutaneous AVA's is controlled by specific thermoregulatory reflexes, whereas capillary flow is the target of local temperature effects. A significant role for the direction of the thermal gradient across the skin is implicated.


Oronasal breathing during exercise.

The shift from nasal to oronasal breathing (ONBS) has been observed on 73 subjects with two independent methods. A first group of 63 subjects exercising on a bicycle ergometer at increasing work load (98--196 W) has been observed. On 35 subjects the highest value of ventilation attained with nasal breathing was 40.2 +/- 9.41 . min-1 S.D. Ten subjects breathed through the mouth at all loads, while 5 never opened the mouth. On 13 subjects it was not possible to make reliable measurements. On a second group of 10 subjects utilizing a different techniques which did not need a face mask, the ventilation at which one changes the pattern of breathing was found to be 44.2 +/- 13.51 . min-1 S.D. On the same subjects nasal resistance did not show any correlation with ONBS. It is concluded that ONBS is not solely determined by nasal resistance, though an indirect effect due to hypoventilation and hence to changes in alveolar air composition cannot be ruled out. It is likely that ONBS is also influenced by psychological factors.


Segmental heterogeneity of epithelial transport in rat large intestine.

Functionally isolated segments of rat colon and rectum were perfused in situ in a closed loop system. Rectum was defined as the lower 25--35% of the length of large intestine (cecum excluded). Perfusion conditions were optimized at 0.5 ml.min-1 and 3 cm H2O luminal pressure. Variation of perfusion rate between 0.2 and 2 ml.min-1 did not influence net volume transport (JNV). Luminal distension following elevation of hydrostatic pressure to 18 cm H2O reversibly increased Jnv. Under control conditions Jnv and Na+-transport rates (JnNa) of colon were 2--3 times higher than those of rectum. In colon transepithelial electrical potential difference (psims) was time independent --12 mV (lumen negative) whereas rectal psims increased with time from --6 mV, reaching a plateau of --67 mV within 6 h. Amiloride 10(-4) mol.l-1 had no effect on psims, Jnv, and JnNa in colon but did slightly depress K+-secretion in colon descendens. In contrast, psims in rectum was dose-dependently depressed, being reversed to +7 mV at 10(-4) mol.l-1. Jnv and JnNa were decreased by half. Acetazolamide in addition to amiloride lowered the positive post-amiloride rectal psims by half. Adrenalectomy had no effect on colonic psims, but abolished psims of the rectum. A single dose of 40 microgram.kg-1 b.w. aldosterone during the experiment restored the typical time course of rectal psims, but did not affect psims in colon. It is concluded that aldosterone induces an amiloride-sensitive Na+-pathway only in rectum, but not in colon, and that colon and rectum differ basically in their transport properties, quantitatively as well as qualitatively, as do the kidney distal convoluted tubule and the cortical collecting duct.


Three successive steady-state CO2-response curves. No change of sensitivity of the ventilatory controlling system for CO2.

Three successive steady-state CO2-response curves, with 10-minute intervals, were taken in seven healthy subjects at rest in normoxia. No systematic difference in the slopes between the three curves could be found. The results suggest that a previous steady-state CO2-response curve does not change the sensitivity of the ventilatory controlling system for CO2.


Microcirculation of the epimyocardial layer of the heart. I. A method for in vivo observation of the microcirculation of superficial ventricular myocardium of the heart and capillary flow pattern under normal and hypoxic conditions.

To study microcirculation of the heart in vivo, we developed a new technique of epi-illumination of the beating rat ventricular myocardium. Five tiny needles connected to the operation table were horizontally inserted into the ventricular myocardium just beneath the epicardium in order to restrict cardiac movement during contraction and to enhance the amount of light reflected from the structures under study. The in vivo light and fluorescent microscopy were performed with the Ultropak and the Fluopak systems (Leitz) combined with a highly sensitive television camera and recording system. In 142 individual in vivo measurements (6 animals) the mean capillary diameter amounted to 6.0 +/- 1.0 mu. In the same experiments, the mean intercapillary distance was 18.7 +/- 1.7 mu. In agreement with the literature, the capillaries of the epimyocardial layer of the rat heart demonstrate a mixed countercurrent flow pattern. In contrast to other authors, we observed no recruitment of resting capillaries after hypoxia.


A simple circuit for automatic continuous recording of microelectrode resitance.

Microelectrodes with tip diameters less than or equal to 0.5 micron used for intracellular recording sometimes give artefactual readings due to tip potentials. These appear to be caused by a change in the tip of the microelectrode upon impalement with a corresponding change in microelectrode resistance. A circuit is described which enables the resistance of the microelectrode to be continuously monitored throughout an experiment. The electrode is used as one half of a potential divider for an a.c. signal at 20 Hz with an amplitude of 20 mV. The other half of the potential divider is a 1000 Momega resistor. The a.c. signal across the microelectrode is approximately proportional to the microelectrode resistance in the range 0 --50 Momega. This signal is amplified, rectified and smoothed and then displayed on a chart recorder or other convenient meter.


The effects of intraportal infusions of glucagon on the hepatic arterial and portal venous vascular beds of the dog: inhibition of hepatic arterial vasoconstrictor reponses to noradrenaline.

The sympathetically-innervated hepatic arterial and portal venous vascular beds of the dog were perfused simultaneously in situ. Glucagon was infused into the hepatic portal vein (1--10 microgram/min); it caused increases in hepatic portal vascular resistance and tended to reduce the hepatic arterial vascular resistance. Extrahepatic effects of intraportal infusions of glucagon included increases in superior mesenteric blood flow and heart rate and falls in systemic arterial pressure. A test dose of noradrenaline (10 microgram) injected into either the hepatic artery or the portal vein caused both hepatic arterial and portal venous vasoconstriction. The hepatic arterial constrictor responses to noradrenaline were antagonized by intraportal infusions of glucagon. In contrast, intraportal glucagon did not antagonize the portal constrictor responses to intraarterial or intraportal noradrenaline. Elevated portal blood glucagon concentrations may "protect" the hepatic arterial blood flow from vasoconstriction due to elevated systemic levels of vasoactive substances including catecholamines.


Cholinergic and adrenergic influences upon cat skeletal muscle performance induced by stimulation of the anterior hypothalamus.

The influence exerted by stimulation of the anterior hypothalamus (zone of cholinergic vasodilatation) on the performance of triceps surae during tetanic contraction has been investigated. Hypothalamic stimulation, if combined with indirect muscle stimulation, improves muscle performance, i.e. slows down the rate of decrease of contraction. The effect is abolished by atropine (0.5 mg/kg) and insensitive to propanolol (0.1 mg/kg). The cholinergic influence is only effective if hypothalamic stimulation coincides with the beginning of motor nerve stimulation. In some of our experiments stimulation of the same central structures elicited another influence on muscle performance, associated with the release of adrenaline into the blood. In this case, contrary to the cholinergic influence, the force of contraction increases only when hypothalamic stimulation does not start earlier than 100 s after the initiation of contraction (phase of slow decline of tension). The effect is insensitive to atropine (0.1 mg/kg) and abolished by propanolol (0.1 mg/kg).


Compartmental analysis of Na efflux across ileum mucosal membrane.

A new tracer analysis technique has been developed for efflux from a three compartment series system. With this technique, results are based on pools contributing to efflux and not on total tissue pools. The use of this technique is illustrated in a study of Na efflux across the luminal membrane of rabbit ileum. Na efflux was described by two exponentials with half-times of 1.78 min and 13.5 min. The fast component, with a flux of 68.0 mumoles/h cm2 and a calculated Na concentration of 166 mM, was identified as an extracellular compartment. The slow component, with a flux of 13.2 mumoles/h cm2 and Na concentration of 86 mM, was identified with efflux across the mucosal membrane of epithelial cells.


Radioimmunoassay for adenosine in biological samples.

A sensitive and specific radioimmunoassay for adenosine has been developed. Antibodies directed against adenosine (titer 1:400--1:700) were obtained by immunizing rabbits with adenosine, conjugated via its vicinal hydroxyl groups to bovine serum albumin (periodate oxidation). Interfering adenosine deaminase activity was removed from the antisera by treatment with DEAE-cellulose. Free and antibody bound 3H-adenosine was separated by either the "second antibody" precipitation method or by a simple filtration step. The sensitivity and assay range for adenosine was 1--100 pmoles per assay tube. Structurally related purine compounds (adenine nucleotides, adenine) crossreacted with adenosine binding and were removed by a single chromatographic step. Analysis of the adenosine content in normoxic guinea pig hearts yielded 2.53 nmoles/g, a value which was confirmed by spectrophotometric analysis.


The selectivity of the delayed potassium conductance of frog skeletal muscle fibers.

A voltage-clamp technique was used to measure reversal potentials of delayed currents in frog skeletal muscle fibres immersed in solutions containing Li2SO4,Na2SO4,K2so4,Rb2SO4, or Cs2SO4. The selectivity sequence found for the underlying permeability mechanism was K greater than or equal to Rb greater than Cs greater than Na greater than or equal to Li.


Effects of sodium acetylsalicylate on thermoregulatory responses of rats to different ambient temperatures.

The effects of intraperitoneal administration of sodium acetylsalicylate (aspirin) on thermoregulatory responses (Ta) of 15, 22 and 29 degrees C were assessed. Intraperitoneal administration of aspirin produced dose-dependent hypothermia at both 15 and 22 degrees C. The hypothermia was brought about by cutaneous vasodilation (as indicated by an increase of the tail and foot skin temperatures). However, in the heat (29 degrees C), i.p. administration of the same amount of aspirin produced no change in rectal temperature, since the thermo-regulatory responses were unaffected by aspirin application at this Ta. Thus it appears that aspirin increases heat loss and leads to hypothermia in rats.


Imparied thermoregulation in pregnant rabbits at term.

Pregnant and nonpregnant female rabbits were placed in hot (33 degrees C) and cold (3 degrees C) environments and their core temperatures measured. Pregnant rabbits during the 3 days before giving birth were less able to maintain normal body temperatures in thermally adverse environments than were nonpregnant rabbits. This alteration in thermoregulatory ability may permit an environmental temperature change that is not dangerous to nonpregnant rabbits to be potentially harmful or lethal to both mother and offspring.


[Pathogenesis of the premenstrual syndrome (author's transl)].

The possible influence of estrogens, progesterone and prolactin, even as their interrelationships, in the genesis of the premenstrual syndrome are analysed. Special reference is made to their action on hydrosaline metabolism and vascular permeability. Some drugs used in the treatment of this syndrome indicate that a central role might be played by the vascular filter.


Auto-immune Addison's disease in identical twins.

Identical male twins are described, one of whom presented with clinical symptoms of Addison's disease whereas the other was shown to have a deficient adrenal cortical response to stimulation tests. Both had positive adrenal cortex antibodies.


Naloxone reversal of morphine catationia: role of caudate and periaqueductal gray.

The narcotic antagonist, naloxone, was microinjected into the head of the caudate nucleus (HC), periaqueductal gray matter (PG), and cerebellar white matter (CB) of rats to counteract the catatonia induced by systemic morphine. Naloxone produced a loss of the catatonic response when administered into HC or PG, but not when microinjected into CB. Isotonic saline in HC, PG, and CB did not counteract the catatonic effects of morphine. The reversal of catatonia was similar for naloxone injections in HC and PG. Both these areas have high concentrations of opiate receptors while CB has few opiate receptors. It is suggested that the HC and PG are involved in the reversal of the catatonic effects of morphine via the high concentrations of opiate receptors found there.


Tolerance and evidence of physical dependence to daily codeine injections in the rat.

Core temperatures, measured by telemetry, and acquisition of food pellets on a continuous reinforcement schedule were recorded every 30 min in unrestrained male rats given saline for 5 days before and 5 days after 10 daily SC injections of codeine phosphate (200 mg/kg) at 08:00 hr. After the first codeine injection rats were immobile, slightly catatonic, breathed shallowly and had elevated core temperatures, loss of body weight and inhibition of feeding activity. As injections of codeine were repeated, the initial depressant signs decreased and the period of inhibited feeding was replaced by prolonged (greater than 8 hr) post-injection bouts of feeding activity (stimulated feeding) during daylight hours. Core temperatures remained elevated during this phase of drug-induced feeding activity. Mean body weight and 24-hr food intake remained below control levels over the 10-day codeine period as diurnal feeding patterns became reversed. On the first withdrawal day core temperatures declined and feeding patterns changed from those responses on the last codeine day as the rats lost body weight and were hyperirritable. As withdrawal continued core temperature and feeding patterns began to resemble those of the saline control period, body weights increased and hyperirritability subsided. In this study, tolerance and evidence of physical dependence to daily injections of codeine could be demonstrated in rats by continuous monitoring of their diurnal feeding and temperature responses.


Pilocarpine, food deprivation, and induction of mouse killing by cats.

Effects of three treatments that induce mouse killing by rats were examined with cats. Food deprivation induced about 50% killing after 24 hr and almost 100% killing by 27 hr. Pilocarpine (at doses of 1.0 mg/kg that produced marked side-effects, and whether or not methyl atropine pretreatment blocked those side-effects) and chlordiazepoxide (at doses of 1.0--2.0 mg/kg) did not induce any killing. Pilocarpine produced a dose-related inhibition of spontaneous mouse killing (as it does in rats), but this was antagonised by methyl atropine. The side-effects of pilocarpine and chlordiazepoxide did not seem to account for their failure to induce killing. In contrast with food deprivation, the mechanisms by which pilocarpine and chloridazepoxide induce killing in rats may not have homologs in cats.


Despite various drugs, cats continue to kill mice.

Amphetamines (d- at 0.5--4 mg/kg; 1- at 2--4 mg/kg) inhibited spontaneous mouse killing by some, but not all cats. Various other drugs (drugs and maximum tested doses were: imipramine, 64 mg/kg; amitriptyline, 32 mg/kg; tranylcypromine, 2 mg/kg; tripelennamine, 4 mg/kg; scopolamine, 1 mg/kg; methyl scopolamine 1 mg/kg; chlordiazepoxide 16 mg/kg; diazepam 4 mg/kg; meprobamate, 80 mg/kg; pentobarbital, 16 mg/kg; chlorpromazine, 8 mg/kg; and haloperidol, 0.5 mg/kg) did not reliably inhibit such killing. In contrast with rats, mouse killing by cats was not consistently blocked by antidepressants or amphetamines. When individual cats were inhibited, their reduction of killing seemed related to anorexia rather than to affective arousal.


Effect of stress on brain histamine.

Stress of short duration (5 min) resulted in a significant increase in plasma corticosterone level and a significant decrease in the midbrain histamine concentration in rats. Exposure to 15 min stress caused a significant elevation in the hypothalamic histamine level. Stress of longer duration (30 or 60 min) did not affect hypothalamic, cortical or midbrain histamine concentration although plasma corticosterone level remained elevated. Repeated exposures of rats of 15 min stress did not significantly alter histamine concentration of any of the brain regions studied. Plasma corticosterone concentration was only 28% of that observed in animals exposed to single 15 min stress. Present data suggest a role of brain histamine in response to stress.


Preparation and evaluation of a sustained morphine delivery system in rats.

A new drug delivery system to induce physical dependence to morphine in rats is described. The device consists of a silicone polymer containing a water soluble "carrier" material, sodium alginate, which swells on contact with moisture to release the drug. The silicone or silastic pellets formulated to contain morphine sulfate are very easily prepared and the advantages over existing methods to induce physical dependence to morphine are discussed. In addition, a comparison of the percent of drug released and withdrawal intensities in rats was made with a silastic-morphine sulfate pellet, silastic-morphine base pellet and a microcrystalline cellulose-morphine base pellet.


[Sociotherapeutical competence in a team (author's transl)].

The author agrees with Wing in defining sociotherapy as a deliberate reshaping of the environment aiming at reducing the signs of disease. This type of therapy has proved effective alongside the other two important kinds of therapy in psychiatry, namely, physical treatment and psychotherapy. Sociotherapy is explained by means of examples which can be classified as general sociotherapy and individual sociotherapy. Its application in the in-patient field is at present only possible if the female and male nurses accept it as a challenge and of the other members of team recognise and discuss it importance. Administrative bodies must be won over as partners in sociotherapy.


Heritability of type A behavior.

Ninety-three pairs of monozygotic and 97 pairs of dizygotic middle-aged, American, male twins were studied to estimate the heritability of Type A behavior--a coronary heart disease-prone behavior pattern. Participants were given the interview assessment of Type A behavior. In addition, they completed four psychological test batteries: the Thurstone Temperament Schedule, the Jenkins Activity Survey, the California Psychological Inventory, and the Gough Adjective Check List. Type A behavior measured by interview was found to be nonheritable. Psychological test scales which significantly correlated with Type A behavior, however, generally had significant heritability estimates. Only the Adjective Check List scales, which significantly correlated with Type A, showed nonsignificant heritability estimates. Selected items from these Adjective Check List scales may provide a method for assessment of Type A behavior possibly free from genetic influence.


Comparison of behavioral arousal induced by apomorphine and N-n-propylnorapomorphine.

A preliminary evaluation of behavioral arousal in mice, as a model system for quantifying activity of presumptive antiparkinsonian and antischizophrenic agents, was made. In experiments not yet published, we have observed stereotypic cage climbing induced by two aporphines (apomorphine, APO; and N-n-propylnoraporphine, NPA) to be specifically dopaminergic. Time of peak effect was found to be 15--30 min and an ED50 of approximately 4 mg/kg was established for both drugs. In the present study we have investigated the activity of APO and NPA on behavioral arousal. As measured by electromagnetic sensors, behavioral arousal reflects several responses including spontaneous locomotor activity and repetitive movements (e.g., grooming and rearing). The procedures which we have employed minimize artifacts due to handling and injection routines while maximizing our ability to observe time of peak effect (based on blood levels). Dose and time response analyses of APO and NPA (i.p.) demonstrated a time of peak effect from 15--30 min and ED50 values of 3.0 and 2.5 mg/kg for APO and NPA, respectively. The results of our experiments show that for a 90 min period over the 1--10 mg/kg dose range employed, APO exhibits a linear dose response relationship whereas that for NPA is sigmoidal. Similarities in time of peak effect and ED50s for the two aporphines in stereotypic cage-climbing and behavioral arousal experiments suggest that the behavioral arousal induced by APO and NPA may be dopaminergically mediated.


Methamphetamine-induced behavioural effects and brain concentrations of methamphetamine and its metabolite amphetamine in mice.

(+)-Methamphetamine (MA) produced dose-related behavioural changes in mice. There was a correlation between the type of behavioural response and the peak brain MA concentration after the i.p. administration of each of the following doses of (+)-MA: 0.64 mg/kg (decreased quiescence--0.738 microgram/g MA), 2.5 mg/kg (increased locomotor activity--3.148 microgram/g MA) and 10.0 mg/kg (stereotyped behaviour--12.608 microgram/g MA). During the 90-min experimental period, there was no positive correlation between the magnitude of each type of drug-induced behaviour and the brain MA concentration. For 10.0 mg/kg (+)-MA, there was a negative correlation between the drug-induced stereotyped behaviour and the brain MA concentration. The apparent disappearance half-life of MA from brain was dependent on the dose of (+)-MA: 0.64 mg/kg (t1/2 56.6 min), 2.5 mg/kg (t1/2 66.6 min), 10.0 mg/kg (42.2 min). For the three (+)-MA doses, the metabolite amphetamine (A) also was present in the brain and the A/MA + A brain concentration ratio was 0.11--0.14. This metabolite appeared to have only a small involvement in the MA-induced behavioural effects.


Effects of long term ethanol ingestion on RNA metabolism by inner membranes of rat brain mitochondria.

Recent laboratory endeavors have been primarily concerned with determining the effects of chronic ethanol ingestion on cerebral RNA metabolism within the inner mitochondrial membrane (IMM). Toward this goal, a series of experiments were carried out by determining the RNA and protein synthetic activity of the organelle. Brain mitochondria actively incorporated [5-3H]orotic acid into RNA under in vivo conditions. In addition, data showed that a major portion of the radioactivity present in the cold TCA insoluble residue from labeled intact mitochondria could be recovered in the digitonin treated purified IMM fraction. Maximum incorporation of [5-3H]orotic acid into RNA took place within 24 hrs followed by a rapid decline in activity on the 5th day of the pulse in both 'control' and 'ethanol' ingesting rats. Data revealed that ethanol ingestion affected the degree of incorporation of labeled RNA precursor into the mitochondrial RNA fraction. The observed effect was in the form of inhibition and was dependent on the duration of the initial pulse. Thus, while at earlier time points a decreased incorporation of the precursor into mitochondrial RNA was obtained in the ethanol imbibing rats, the inhibition was not observed when the pulse time was extended to 5 days. Such results indicate the possibility of a rapid turnover rate for the brain mitochondrial RNA with the 'ethanol' group having a faster rate of turnover when compared to the 'control' group.


Effect of vasectomy on thyroid function.

Long-Evans rats vasectomized unilaterally or bilaterally at 2 months of age showed marked reductions in weight of testes, seminal vesicles and prostate glands 2 and 12 months post-vasectomy. Thyroid weight, thyroid 131I uptake, serum PB131I, circulating levels of serum T4 and chromatographic analysis of thyroid hydrolysates revealed no alterations due to vasectomy. These findings indicate that vasectomy, unilateral or bilateral, and whether of 2 or 12 months duration, did not exert an effect on thyroid function.


Detection of androgen and estrogen receptors in human prostatic carcinoma and hyperplasia by fluorescence microscopy.

The histochemical detection of androgen and estrogen receptors in human prostatic tissue was achieved employing fluorescein labeled conjugates of bovine serum albumin linked to testosterone and estradiol. Results were compared to those of dextran-coated charcoal and protamine sulfate assays and correlated in 85% of specimens. Early findings include a relatively uniform distribution of receptor in hyperplastic epithelium in contrast to marked tumor cell receptor heterogeneity in cancer. Location of receptor in nucleus and/or cytoplasm was readily determined.


Correlation between antiestrogenic and antiovulatory activity of some newer substituted coumarins.

Seven 7-(4-substituted thiosemicarbazido methoxy)-4-methyl coumarins were found to antagonize the uterotropic effects of estradiol and blocked the copper acetate induced ovulation in rabbits.


[14 cases of "anti-N" antibodies in hemodialysis patients in Marseille].

Some medical centers re-use dialysis units sterilized with formaldehyde. In a study of 239 cases, 14 "anti-N" antibodies were found only among the 59 patients of the medical centers which re-use dialysis units. The action of formol seems to be confirmed by the presence of "anti-N" in 2 patients who had undergone prosthesis several times, but not dialysis. For these prostheses, a bone cement, sterilized with formol, was used. These "anti-N" are very often associated with cold autoagglutinins, and appear regardless of the patient's MN group. The action of formaldehyde suggests the following hypotheses:--antigenic modification;--disturbances in the immune response mechanisms;--a combination of the two. In the first hypothesis: the action of formol discovered since a long time on red cells. In the second hypothesis: the existence of auto-agglutinins only among the 14 hemo-dialysis patients with anti-N antibodies.


[Hemangioblastoma of the cauda equina].

Hemangioblastomas are dysontogenetic tumors of the central nervous system. They occur as single tumors or multiple. Hereditary and sporadic cases are known. The most frequent localisations are the retina and cerebellum but they can be localized at any site of the neuraxis. In a 37 year old male patient a solitary hemangioblastoma of the cauda equina was demonstrated by myelography and totally removed by laminectomy. In the literature 17 cases of isolated hemangioblastomas of the cauda equina are described. A further 16 cases of were observed within a Lindau-complex, 10 of which remained without symptoms. For diagnosis of the type of tumor a myelography is rarely sufficient. The only successful therapeutic measure is total surgical removal.


In vitro model for stretch-induced hypertrophy of skeletal muscle.

Mechanical stretch of embryonic chicken skeletal myotubes developed in vitro leads to many of the biochemical changes seen in skeletal muscle hypertrophy. These include increased amino acid accumulation, increased incorporation of amino acids into general cellular proteins and myosin heavy chains, and increased accumulation of total protein and myosin heavy chains. This model system should aid in understanding how the growth rate of skeletal muscle is regulated by its activity.


Evidence against a role of acetaldehyde in electroencephalographic signs of ethanol-induced intoxication.

Acetaldehyde, the proximate metabolite of ethanol, when injected intravenously in rats produced electroencephalogram (EEG) changes similar to those observed after ethanol administration; that is, low doses activated the cortical EEG and higher doses caused activation followed by synchronization. However, when acetaldehyde was administered as a continuous infusion to simulate production of ethanol-derived acetaldehyde, only synchronization occurred, and then only at the higher doses. At low infusion dosage when the EEG was unaffected, concentrations of acetaldehyde in the blood were equal to or greater than those which occur during intoxication. Thus, acetaldehyde by itself cannot account for ethanol-induced EEG synchronization.


Sex pheromone in the dog.

Methyl p-hydroxybenzoate has been identified in the vaginal secretions of female dogs in estrus. When small amounts of this compound were applied to the vulvas of anestrous or spayed females, males placed with these females became sexually aroused and attempted to mount them.


The effects of some dopamine-beta-hydroxylase inhibitors on the control mechanisms of the estrous cycle in rats.

Disulfiram (DS) administered in single doses of 200--400 mg/kg i.p. before the critical period of proestrus (9--11 h), or in diestrus--2 (20--23 h), induced in most animals prolongation of the estrus, i.e. an antiovulatory action. FLA-63 had the same effect in a smaller dose (2 mg/kg s.c.) DS elicited the ovulation-blocking action only in doses known to reduce the cerebral noradrenaline level. For the central site of DS action plead its efficacy after i.v.c. administration in a much smaller dose (1 mg/rat), the reduction of the uterine weight, as well as the lack of any significant influence of the drug on the peripheral actions of estradiol. The fact that the two DBH-inhibitors provoked mostly an antiovulatory effect supports the stimulatory role of adrenergic neurons in the control of LRF secretion, because DBH is present only in these neurons and not in the dopaminergic pathways.


Circadian clock in culture: N-acetyltransferase activity of chick pineal glands oscillates in vitro.

N-Acetyltransferase activity was measured in organ-cultured chick pineal glands. A circadian rhythm of enzyme activity persisted in cultured glands for up to 4 days. The phase of the rhythm in vitro closely approximates its phase in vivo. These observations demonstrate that the pineal gland of chicks contains (or is) a self-sustained circadian oscillator.


[A comparism between lysosomal enzyme activity in normal ectocervical squamous epithelium and squamous carcinoma of the ectocervix].

A comparative study was made of the total lysosomal enzyme activity found in homogenates of normal ectocervical squamous epithelium and squamous carcinoma of this epithelium. The activities of acid phosphatase, beta-glucuronidase, cathepsin D and acid ribonuclease were higher in carcinoma tissue than in normal tissue. The most important observation made was with regard to the distribution of enzyme activity in homogenates. In carcinoma homogenates most of the enzyme activity was detected in the lysosomal fractions, whereas in controls the activity was predominantly found in the cytosol fractions. No histochemical and electron microscopical techniques were used in this study. Because it was possible to sediment the enzyme activity and to demonstrate latency, these can be referred to as lysosomal enzymes with certainty.


The fetal alcohol syndrome.

Two unrelated children with the fetal alcohol syndrome are described. Features of the syndrome include mental deficiency, growth delay, and craniofacial, limb and cardiac anomalies. The finding of this spectrum of abnormalities raises the possibility of alcohol ingestion during pregnancy. The deleterious effects of alcohol on the developing fetus are emphasized. In view of the high prevalence of alcoholism in this country the fetal syndrome must be regarded as a serious and preventable cause of morbidity.


The fetal alcohol syndrome.

Four cases of the fetal alcohol syndrome are described, and the clinical features are reviewed. The most consistently found features are pre- and postnatal growth retardation, small palpebral fissures and mental deficiency. In view of this, chronic alcoholic women shold avoid pregnancy until they have weaned off alcohol, but should it occur then the question of termination must be considered.


Synergistic effects of phorone on the hepatotoxicity of bromobenzene and paracetamol in mice.

Administration of phorone (diisopropylidene acetone), an industrial solvent, to mice caused a rapid depletion of hepatic glutathione, which is due to enzymatic conjugation of phorone with glutathione, mediated by cytoplasmic enzymes of the liver. Whereas phorone, even in high doses, did not show hepatotoxic effects by itself, combined administration of phorone with a subtoxic dose of either paracetamol or bromobenzene strongly enhanced hepatotoxicity of the latter compounds as was judged from a rise in serum transaminase activities. These findings are compatible with the concept of a dose threshold for biologically reactive intermediate compounds which are bioinactivated through glutathione conjugation.


The presence in salivary secretions of Glossina morsitans of stages of Trypanosoma (Trypanozoon) brucei other than those occurring in the salivary glands.

Using the bat wing membrane technique to study salivary secretions of Glossina morsitans infected with Trypanosoma (Trypanozoon) brucei, it was shown that flies extrude infected salivary secretions as early as day six after an infective blood meal. The non-salivary-gland stages of T. (T.) brucei were extruded intermittently and flies infected with such trypanosomes were not all destined to develop metacyclic infections. Once the salivary glands were involved, the trypanosomes appeared in the secretions each time the flies were tested. Some of the flies with gut infections, but no demonstrable salivary gland involvement, transmitted T. brucei to mice and it is suggested that these infections were intiated by some of the proventricular trypanosomes secreted with saliva.


[Proliferative kinetics of antibody-forming cells normally and exposed to vinblastine].

The proliferative kinetics of IgM antibody-producing cells (APC) of mice immunized by sheep red blood cells was studied using autoradiography and vinblastine. The incorporation index for APC was determined every 4 hours from 72 to 112 hours of the immune response. The significance of recruitment in APC exponential growth was proven by means of 3 different regimes of 3H-thymidine introduction to immunized mice. The discontinuous character of recruitment and its resistance to vinblastine were shown. It is suggested that vinblastine impared both APC and their precursors.


[Hepatic energy metabolism disorders in emotionally-painful stress and prevention of these disorders with sodium gamma-hydroxybutyrate].

Content and biosynthesis of glycogen in rat liver tissue as well as transition of 14C from main substrates of tricarboxylic acid cycle to CO2, examined in liver slices, were studied under conditions of stress caused by pain and emotion. The stress was accompanied by mobilization of the glycogen deposits; glycogen synthesis in liver tissue and oxidation of pyruvate, asparate succinate or alpha-ketoglutarate in tricarboxylic acid cycle were inhibited. At the same time, the stress was accompanied by ulcerous impairments of gastric mucosa. The phenomena observed appear to be due to increased activity of adrenergic and sympathoadrenal systems. Prior to the stress administration of sodium gamma-hydroxybutyrate, which activates the inhibitory GHB-ergic system of brain, prevented distinctly the impairments found.


[RNA transcripts of both strands of viral DNA in cells infected with vaccinia virus].

Denaturated 3H-thymidine-labeled vaccinia virus DNA was hybridized with an excess of "late" virus-specific RNA isolated from virus-infected chick embryo cell cultures 8 hours postinfection. The percentage of DNA converted into DNA-RNA hybrid under these conditions never exceeded 50%. If the RNA preparation had been self-annealed prior to hybridization, the percentage was decreased slightly. On the other hand, if the self-annealed RNA had been treated with RN-ase and the double-stranded DNA-RNA hybrids had been denaturated, they became capable of converting into hybrids at least 68% of the labeled DNA. These data indicate that transcription of both DNA strands occurs in a large portion (over 68%) of vaccinia virus genome.


[Electronoptical studies of the effect of 1-[p-(methylnitrosamino)-benzylidenamino]-adamantane on the fowl plague virus (FPV) in cell culture].

The adamantanamine derivative 1-[p-(methylnitrosamino)-benzylidenamino]-adamantane (MBAA) at a concentration of 40 microgram/ml demonstrated no effect on adsorption of fowl plague virus (FPV) on chick embryonal cells. The penetration of the virions took place by means of pinocytosis. In the final stages of penetration the virions became gradually disintegrated. Under the influence of MBAA, after break-down of the membrane of pinocytic vesicles a swollen part of the virus core remained in cytoplasm. The morphologically visible replication stages were completely blocked by MBAA. From these results it was concluded that the antiviral action of MBAA most probably depends on a block of virus replication between the final stages of the penetration process and the beginning of production of virus specific structural antigens.


[Rhodosporidium Banno: dose-effect relations, mutagenic efficiency, and spectrum of mutants in the induction of auxotrophic mutants by ultraviolet light and N-methyl-N'-nitro-N-nitrosoguanidine].

The kinetics, efficiency, and specificity of induction of forward mutations to auxotrophy by ultraviolet light (UV) and N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) was examined in stationary phase cells of Rhodosporidium (Rhodotorula) wild strain Rg1. In comparison to the spontaneous level the frequency of auxotrophic mutants was increased more than 1000 times by both mutagens, however, the mutagenic efficiency of MNNG was higher than that of UV. We found that the forward mutation rate is a linear function of the applicated UV and MNNG doses in the range to 600 J m-2 or 25 mM X min, respectively. The 35 studied biosynthetic pathways to amino acids, purines, pyrimidines, and vitamins are genetically blocked at different frequencies, but there is not any significant difference between UV and MNNG induced frequencies of mutants with a specific requirement. However, in difference to the approximately equal distribution of the MNNG-induced nic mutants among the genetic blocks of the tryptophan-nicotinamide pathway, UV-induced nic mutants occurred with a higher frequency in the genes of the tryptophan pyrrolase and the 3-hydroxykynureninase than in the genes of the other enzymes of the pathway.


[State and developmental trends of urogenital tuberculosis--20 years clinical and pathologic-anatomical experiences].

On the basis of own experiences of twenty years and taking into consideration the knowledge of other authors the developmental tendency in the treatment of the urogenital tuberculosis is demonstrated, the indications to nephrectomy, resection of the kidney, and epididymectomy are reified as well as kind and sequelae of errors in chemotherapy analysed. From 1958 to 1977 2,868 patients with urogenital tuberculosis were hospitalized in the Central Clinic Bad Berka. Of them about 41% had to undergo an operation. A decrease of the quantity of operations can be observed only in the renal resections, whereas the nephrectomy rate is unchangedly high (16.3% of the own patients) and even shows an increasing tendency since 1975. Comparative examinations show that the pathologo-anatomical picture of the ectomized kidneys has not changed during the period of observation. The knowledge of the symptom-poor course obliges also further on differential-diagnostically to take into consideration the urogenital tuberculosis. Only on this way the still large number of organ endangering complications may be encountered in time.


[Modern therapy and after-care in urogenital tuberculosis].

The present therapy of the urogenital tuberculosis is based on the effective medicaments (rifampizin, isonicotinic acid hydrazid, streptomycin, and ethambutol). It rests on an optimum dosage in connection with a best suited combination, taking into consideration the relations of sensitiveness and side effects as well as consequent long-term treatment. It is referred to the possibility of additional administrations of corticosteroid preparations and it is taken notice to the necessity also to treat unspecific mixed infections. Under the modern chemotherapy with bactericidal effect a stable negativation practically always develops within 3 months. Actual recidivations were not seen during the last 12 years. Apart from a compilation of the indications to nephrectomy references to possibilities of plastic surgical corrections of the urinary system are given. Two tables give information about the patients who were operatively treated during the last 15 years. A close collaboration of the various therapeutic institutions with a consulting urologist -- particularly in problematic and advanced cases of the disease -- nearly always saves the patient with urogenital tuberculosis from invalidism.


[Eye tuberculosis].

At present the eye tuberculosis still occurs only in its reactive form. But also these pathological processes may quite considerably disturb the vision. In the first place are chorioiditis (uveitis posterior), iritis and iridocyclitis (uveitis anterior), uveitis totalis and periphlebitis retinae are by far less frequent. Number and severity of the pathological processes considerably decreased during the last years, above all also the new diseases. Relapses are still increasedly observed. The problems of diagnostics and the necessary therapeutic measures are described.


[Method of measuring pressure using perfusion manometry].

Based on the principle of perfusion manometry, a device for the assessment of intraluminal pressures in urethra and anal canal is presented. The technical parameters are reported. The method may be utilized for clinical diagnosis in cases of disturbed micturition and defecation in children as well as for the function of esophagus.


[Changes of orbitofrontal astroglia in senile dementia (author's transl)].

The changes of orbitofrontal studied astroglia in 10 cases of senile dementia have been studied. The modification of Golgi-method by Bubenaite was used. The results reveal 4 different types of changed astroglia. A relation between changes of makroglia and the aging process of CNS is suggested. The changes of glia are not a result of nervous cell alterations, but an independent neuroglial process under the conditions of aging.


[Conditioned reactions and mediator-humoral shifts during neurotization in a probabilistic pain reinforcement situation].

Substitution of regular partial reinforcement for random one (in both cases the reinforcement frequency was 50%) acted in some dogs as a neurotizing factor: they showed unrest, stable defensive reflexes disappeared, corresponding changes were observed in vegetative reactions. At the same time activation of the sympatho-adrenal system was recorded along with a drop in concentration of acetylcholine in peripheric blood. It is noted that the development of neurotic disturbances in dogs in these conditions were to a certain degree dependent of the dominating motivation.


Immunological detection of 20beta-hydroxysteroid dehydrogenase-synthesizing polysomes from Streptomyces hydrogenans.

Immunoprecipitation of polyribosomes from Streptomyces hydrogenans synthesizing 20beta-hydroxysteroid dehydrogenase was performed by immunoelectrophoresis. Only polyribosomes from cells induced by 11beta, 21-dihydroxy-4, 11(20)-pregnadien-3-one in vivo were precipitated by immunoglobulins specific for 20beta-hydroxysteroid dehydrogenase. No unspecific precipitations with polysomes from control cells cultivated in the absence of steroids were observed. Therefore, 11beta, 21-dihydroxy-4, 17(20)-pregnadien-3-one increases the number of biological active polyribosomes involved in 20beta-hydroxysteroid dehydrogenase synthesis, presumably by specific stimulation of mRNA synthesis in Streptomyces hydrogenans.


[Radioimmunological differentiation of yeasts (author's transl)].

A microtiter solid phase radioimmunoassay is described for the differentiation or microorganisms by using six species of yeasts as a model. Rabbits were immunized with homogenized cells of the yeasts. The rabbit sera obtained were absorbed to homologous cells and after elution, the antibodies so obtained were labeled with 125I. Cross-reacting antibodies were eliminated by absorption to the corresponding yeast cells (table 1). With this radioimmunoassay it was possible to identify 51 out of 52 strains of C. albicans, C. tropicalis, C. pseudotropicalis, C. krusei, Torulopsis glabrata and Geotrichum candidum (table 2), whereas only 30 out of 52 strains could be differentiated by the conventional agglutination procedure (table 3). In the radioimmunoassay four immunoglobulin preparations directed against C. tropicalis, C. krusei, Torulopsis glabrata and Geotrichum candidum reacted only with the corresponding species. The immunoglobulin preparation directed against C. albicans reacted both with C. albicans and C. tropicalis and the preparation directed against C. pseudotropicalis reacted with C. pseudotropicalis and C. krusei (fig. 1). None of 60 isolates of 10 species of bacteria cross-reacted with the six yeast antisera, when tested in the radioimmunoassay.


[Angioblastomas, their special forms and rare locations].

Sorting over of our angioblastoma cases occurring in the period from 1954 to 1977 was carried out under the aspect of special forms and rare localisations. Among a total of 93 angioblastomas in 66 patients, there were 81 infratentorial (60 patients), 5 supratentorial (5 patients), and 7 spinal (4 patients) angioblastomas. For 8 of the infratentorial angioblastomas a participation of the brain stem was found; their prognosis was unfavourable and all these patients died. Angioblastomas occurring in a multiple manner are also involving problems unless they are restricted to the cerebellar spheres and the vermis of the cerebellum. In this group there were 37 angioblastomas occurring in 10 patients with an increased familial occurrence in four cases and a systematic affection with angiomatosis retinae in five patients. Four of these patients also died. The large number of 5 angioblastomas of the cerebrum has induced us to study these cases particularly critically. There was a good prognosis for all these cases; they all were solitary tumours (2 solid tumours and 3 typical large-syctic angioblastomas). The prognosis of the spinal angioblastomas of which 7 were found in 4 patients, is dependent upon location and the question of the systematised affection. Remarkably large is the number of young angioblastoma carriers. All 5 cerebral angioblastomas and 6 cerebellar angioblastomas were found in patients below the age of 18. From these findings conclusions can be drawn with regard to an optimisation of an early detection and the exact angiographic clarificatior in order to avoid unnecessary losses due to transfers being carried out too late and, on the other hand, to sort out inoperable findings.


[Possible experimental model of Korsakoff's syndrome].

Study of the effects of chronic alcohol intoxication on conditioned behaviour in rats revealed spatial desorientation, the lack of a stable level of alertness, "negative attitude" to novelty, automatism of motor habit and periodical impairment of temporary connection reproduction. The authors conclude that the observed changes are comparable to a certain degree with the clinical pattern of Korsakov syndrome.


[Secondary structure of condensed DNA. wide-angle, small-angle x-ray scattering and circular dichroism].

Ethanol precipitated DNA shows a CD spectrum of the +psi-type which is similar to that of DNA in the A-form. DNA condensed with cetyl-trimethylammonium-bromide shows, depending on the condensation velocity, a CD spectrum of the -psi-type, or a CD spectrum only slightly modified from that of DNA in solution. The first spectrum is similar to that of DNA in the C-form, and the second one, to that of DNA in the B-form. Using large-angle X-ray scattering of the three DNA condensates and comparing them with the scattering curves calculated from the atom coordinates for the A-, B-, and C-form of DNA it is shown that the secondary structure of the DNA belongs in all three cases to the B-family. It follows from this result that the secondary structure of DNA alone does not determine the type of CD spectrum. The CD spectrum of condensed DNA is essentially determined by the supramolecular structures of the partially crystalline DNA condensates. These supramolecular structures can be demonstrated by the small-angle X-ray diagrams. The condensation of DNA by ethanol and cetyl-trimethylammonium-bromide proceeds in the form of a partial crystallization of the DNA.


Purification of "inhibin" from human ovarian follicular fluid.

Following the earlier demonstration of inhibin-like activity in human ovarian follicular fluid a method for its purification to apparent homogeneity is described. The fluid was converted to acetone powder and subjected sequentially to ammonium sulphate fractionation, gel chromatography on Sephadex G-200, continuous gradient ion-exchange chromatography on DEAE-cellulose, first with a pH gradient from 8.0 to 4.0 and then with a NaCl gradient to 1 M at pH 5.2. The active fraction from this step was subjected to gel filtration on Sephadex G-100 and finally passed through an Amicon Centriflo membrane CF-25 (cut off point: 25,000 m.w.). The ultrafiltrate was homogeneous by SDS-polyacrylamide gel electrophoresis, had a molecular weight of the order of 23 000 and was capable of suppressing serum gonadotrophin levels in the castrated male rats in as low a dose as 25 microgram/rat.


[Assessment of the biological condition of a nonsterile preparation of cerebral dura mater during long-term storage in a formalin solution].

An allogeneic cerebral dura mater prepared under nonsterile conditions will become fully sterilized after 48 hours of storage in a 0.75% formalin solution. The long-term (up to 3 years) conservation of this tissue in the above mentioned solution preserves it in a condition permitting transplantation. The experimental transplantation of such tissue results in making the subdural space airtight. This occurs primarily because of the adhesion of the edges of the donor and recipients dura mater in the area of the defect as a result of aseptic inflammation with subsequent resolution and replacement of the transplant with the connective tissue of a similar structure with the dura mater.


Ultrastructural lens changes in X-ray induced cataract of the rat.

The effect of in vivo X-irradiation on the ultrastructure of the rat lens was investigated by electron microscopy. The left eye of each animal was exposed to a single dose of 1500 r of X-rays, while the other parts of the body were protected by a lead shield. The protected eye served as a control. Samples of the lenses were taken for electron microscopical examination at intervals of 3, 7, 30, 60, 90 and 180 days after the irradiation. The first ultrastructural changes induced by X-rays were found after three days in the epithelial cells which became vacuolated. After seven days these cells showed marked oedema and after six months the whole epithelium was shrunken. The most prominent changes in the lens fibres were swelling and vacuolization. No alterations were noted in the lens capsule. The first visible opacities of the lens were found ninety days after irradiation under the posterior capsule and three months later the entire lens was totally opaque.


Evaluation of phentolamine as a provocative test for idiopathic hypertrophic subaortic stenosis.

Intravenous injection of phentolamine potentially offers a better provocative test for aortic left ventricular outflow tract obstruction than do Valsalva's maneuver, inhalation of isoproterenol, or of amyl nitrite. In hemodynamic studies, phentolamine enhanced myocardial contractility, and decreased afterload with only induction of slight tachycardia. Phentolamine (5 mg.) was administered intravenously to five patients who had idiopathic hypertrophic subaortic stenosis, and 35 patients who had valvular dysfunctions, after which echocardiographic and phonocardiographic recordings were performed. Recordings were of high quality despite changing hemodynamics. Systolic pressures fell an average of 20 mm. Hg; no pressure fell below 90 mm. Hg; there was no notable increase in heart rate. In the five patients with typical idiopathic hypertrophic subaortic stenosis, the amyl nitrite increased the obstructive index from 39.6 +/- 12 to 51 +/- 18.9 (P less than 0.05); whereas, phentolamine increased the obstructive index to 69.8 +/- 25.6 (P less than 0.015). After a 2 week course of oral administration of 80 mg. of propranolol daily, and then either inhalation of amyl nitrite or injection of phentolamine, there was no change from the mean resting obstructive index. Phentolamine appears to be a safe, simple and specific diagnostic agent, and more potent than amyl nitrite in eliciting dynamic obstruction in IHSS; phentolamine and amyl nitrite do not affect the obstructive index in patients with beta blockade.


Effect of ethanol feeding on bone composition in the rat.

The effect of ethanol feeding for a period of 3 months on the mineral and collagen content of bone was determined in the rat. Ethanol feeding resulted in no changes in the density or in the concentrations of calcium, phosphorus, hydroxyproline, or nitrogen in the tibiae. Also, the serum concentrations of calcium, phosphorus, and 25-hydroxyvitamin D were unaffected by ethanol feeding. The development of a mild degree of osteomolacia was suggested, however, by decreases in EDTA-extractable mineral content and in the calcium/hydroxyproline ratio in  the tibiae of the ethanol-fed as compared with the control animals. The urinary excretion of glycosaminoglycans was not changed by ethanol-feeding while the urinary excretion of peptide-bound hydroxyproline was increased. The minimal bone changes found after ethanol feeding in this study are an unlikely cause for the observed increases in the urinary excretion of hydroxyproline.