Q-, C-, and G-banding patterns in the germ-line and somatic chromosomes of Miastor sp. (Diptera: Cecidomyidae). Q-, C-, and G-banding patterns are described for the germ-line and somatic chromosomes of Miastor sp. The chromosome number in the germ line is 36, which is 3 less than that previously reported for the same cultured line 18 years ago. There are 8 chromosome groups: 8 large acrocentrics, 11 large and medium submetacentrics, 4 medium metacentrics, 4 medium subtelocentrics, 6 medium telocentrics, one medium acrocentric, one small submetacentric, and one small telocentric. All 8 large acrocentrics have a Q-band and an interstitial C-band in the short arm, suggesting that these chromosomes are at least partially homologous (or homeologous) and that the germ line originally was polyploid. Only one other germ-line chromosome, the small submetacentric, has a Q-band and an interstitial C-band. In somatic cells there are 8 chromosomes, 28 chromosomes having been eliminated during early cleavage. Three of the four pairs of somatic chromosomes are heteromorphic, despite the indications of a polyploid origin of the germ-line chromosomes and despite the presence of somatic pairing. Furthermore, there is a great deal of restriction on which chromosomes are retained in somatic cells, and it may be that the same 8 chromosomes are retained by all embryos. The G-banding pattern is not as clear as the other two banding patterns. The findings are discussed in relation to observations in other cecidomyids, and a model for the evolution of the chromosome system of Miastor is presented.


Independent replication of the ribosomal RNA genes in the polytrophic-meroistic ovaries of Calliphora erythrocephala, Drosophila hydei, and Sarcophaga barbata. By filter saturation hybridizations the ribosomal (r)DNA contents of the ovaries Calliphora erythrocephala, Drosophila hydei, and Sarcophaga barbata have been measured in comparison to the rDNA percentages of their diploid brains. The measurements of the ovarian rDNA have been carried out on ovaries where the nurse cells in the distal egg chamber of the ovarioles had reached their highest ploidy level. The diploid rDNA content of each of the respective species was chosen as a 100% standard and the rDNA amounts of the ovaries were related to this 100% level. The results show that the ovaries of C. erythrocephala contain 135% rDNA whereas the rDNA contents in the ovaries of D. hydei and S. barbata are only 51% and 47%, respectively. Measurements carried out on isolated nuclei of the nurse cells and follicle cells in D. hydei show that both have a reduced rDNA content in comparison to the brains (45% and 70%, respectively). The data are discussed in relation to the problem of an rDNA amplification in the germ cells and an rDNA underreplication in polyploid nuclei.


Nucleolar RNA synthesis of meiotic prophase spermatocytes in the human testis. Human meiotic prophase spermatocyte nuclei were studied by electron microscope autoradiography after a 3 hours 3H-uridine labeling pulse, followed by postincubation in non-radioactive medium. In autosomes, 3H-uridine nucleolar labeling reaches a peak during early-middle zygotene  prior to the peak labeling of chromosmal RNA species at middle pachytene. Transcription activities of sex chromosomes are inconspicuous when compared with that of autosomes. An increasing condensation of nucleolar-associated chromatin in acrocentric bivalents contributes to the formation of basal knobs in human pachytene spermatocytes. Upon completion of knob formation, nucleolar components segregate and the uptake of 3H-uridine decreases. These findings suggest that the template capability of ribosomal DNA cistrons, located next to the basal knob region, is largely associated with a dispersed state of chromatin whereas increased chromatin condensation is correlated with a restriction of ribosomal RNA transcription.


Replication of DNA in mammalian chromosomes. III. Size and RNA content of Okazaki fragments. A study of sedimentation and buoyant density of Okazaki fragments from mammalian chromosomes along with electron microscopic studies indicate that fragments from about 200 to 1200 nucleotides long may have RNA segments covalently attached. The fragments in some CsCl isopycnic gradients banded in two rather distinct bands. One band corresponds to the density of single-stranded DNA, but the other has a higher buoyant density which could be conferred by a segment of RNA up to 180 nucleotides or more in length. The RNA was not removed by denaturing conditions which separated DNA strands consisting of several thousand nucleotide pairs. When the material of higher buoyant density was spread for electron microscopy under conditions which would extend single-stranded DNA chains,  but leave RNA in a coil or bush the chains with a higher buoyant density usually had a bush attached at one end. Under conditions that were thought to favor gap filling over chain elongation near growing forks, the DNA produced by pulse labeling with bromodeoxyuridine had a buoyant density which would indicate substitution to about 15 percent in one chain. If this substitution represents filling of gaps occupied by RNA before the pulse, the segments would be about 180 nucleotides in length assuming about 1,000 nucleotides between each segment.


Chromosomal basis of dosage compensation in Drosophila VIII. Faster replication and hyperactivity of both arms of the X-chromosome in males of Drosophila pseudoobscura and their possible significance. 3H-thymidine and 3H-uridine labeling patterns of the X-chromosome arms of Drosophila pseudoobscura have been examined autoradiographically. Results show that in all phases of replication, namely, initial, middle and terminal, both arms of the X-chromosome in the male are advanced by one or two steps of 3H-thymidine labeling in comparison with the autosomes, and both arms in the female show more or less similar labeling profile as the autosomes. Both the arms in the male show pale stainability and enlarged width ratio, as reported in other species. The 3H-uridine labeling patterns also reveal that both arms in the male incorporate twice as much precursor as the individual X in the female. Results, therefore, suggest that both arms of the X in D. pseudoobscura are faster replicating and hyperactive in the male, although it is considered that XL is homologous to the X and XR to part of the third chromosome of D. melanogaster.


Studies on Macronuclear DNA from Paramecium aurelia. Macronuclear DNA was isolated from purified macronuclei of Paramecium aurelia and the size distribution was determined with regard to growth phase and method of extraction. DNA molecules as long as 105 microns and as short as 0.2 microns were observed. It was concluded that the method of extraction affected the observed length of DNA extracted and that macronuclear DNA isolated from cells in balanced growth was less susceptible to nuclease degradation than was DNA isolated from cells in stationary phase. Renaturation studies were performed on macronuclear DNA and a kinetic complexity of 22-times E. coli DNA was determined. This value was similar to those values reported for Tetrahymena and Stylonychia macronuclear DNA. Correcting for GC base content yielded a kinetic complexity for Paramecium macronuclear DNA  of 11-times E. coli DNA which corresponded to 3 X 10(10) daltons. There would be about 1400 copies of a unit genome of this complexity within each newly replicated macronucleus. Density gradient analysis indicated that the genes coding for ribosomal RNA had a greater density in CsCl than the bulk DNA. Molecular hybridization studies indicated that the genes coding for 25 S RNA represented 0.14 percent of the total macronuclear DNA. Correcting for GC base content, this corresponded to 30-35 25 S RNA genes per unit genome. These results on Paramecium are discussed in relationship to other ciliate macronuclear DNA.


Genes controlling chromosome activity; the role of genes blocking Y-lampbrush loop propagation. Characterization of two more X-linked Y-affecting mutations in D. hydei is presented; ms(1) XL24 is less extreme than the previously described mutation, ms(1)XL2, but its general effect on the propagation of Y-lampbrush loops is similar qualitatively; ms(1)XL24 is located at the distal end of the X-chromosome and associated with a suppressor-of-white phenotype. The other X-linked sterile, ms(1)XL4, is the least extreme of the three mutations examined to date. It is recessive, located ca 2 c.o. units to the right of white, and causes different patterns of Y loop response. -- From a comparison of the effects of the three single mutations, as well as from the analysis of the various double-sterile combinations, we surmise that: 1) if specific activator genes for the Y-lampbrush loops do exist, they are not likely to be located on the X-chromosome of Drosophila; 2) every lampbrush loop is composed of several functional repeats, each of which operates when unfolded; 3) the Y-affecting mutations arrest preferentially, but not exclusively or specifically Y-lampbrush loop propagation probably indirectly through their independent metabolic effects. Since the mutations are not specific for germ line cells, and exhibit various pleiotropic effects, especially with regard to viability, they should be considered tissue conditional lethals.


Retinal pigment epithelium dystrophy in central serous detachment of sensory epithelium. The incidence of central serous neuro-epithelial detachment in the polulation living in the health district Prague-10 was found to be one in 22,000 inhabitants a year. The cases were classified into three types: A. Inkblot diffusion 60%; B. upward diffusion 25%; C. congregation type 15%. The site of leakage was usually in the upper part of the detached retina or slightly below the horizontal line. Relapses were observed in 16 out of 79 patients, 20%, usually stemming from the original leak. The average re-attachment time was 98 days. In 10% a chronic course led to extensive dystrophy of the pigment epithelium.


On slit-lamp microscopy.

On slit-lamp microscopy. Theoretically the contact lens with a refractive power of -64 dioptres is superior to the concave pre-set lens (Hruby lens) or the convex lens (Bayadi). In practice the results are as follows: With the convex lens the examination of the vitreous is unsatisfactory. The reversed image with the convex lens will become familiar with some experience as one will also get used to the mirror images of the three-mirror contact lens. However, the abnormal curvature of the image is really a nuisance. On the other hand the large field of view is an advantage. The convex lens is only practically useful when it can be firmly attached to the slit-lamp microscope, as otherwise the new adjustment necessary for searching the fundus is too difficult. Attachment to the microscope is also of advantage with the Hruby lens. The concave contact lens of 64 dioptres is best suited for detailed examination of vitreous and fundus and for measurements. When no value is placed on a minute examination and a quick simple orientation suffices, the concave pre-set lens (Hruby lens) has the advantage that the lens does not have to be placed on the eye. If it is centred to the middle axis of the microscope, it facilitates especially quick observation. There will be cases where the pre-set lens will be the only answer, especially shortly after an operation or with very sensitive patients. Furthermore, the Hruby lens is preferable to the Bayadi lens because the vitreous can be better examined. The Hruby lens is also advantageous for examination of the region in the middle, lateral periphery of the fundus, 30 degrees - 60 degrees, and is superior in this area to the simple concave contact lens. The Bayadi lens seems to us only indicated for fundus examination of extremely high myopes. There it definitely offers advantages over and above the concave lens. For the most peripheral fundus, expecially below and above, the three-mirror lens with its modification is so far the best method. Especially for examination of the vitreous good brightness of the slit image is required for stereoscopic examination with as large an angle as possible between microscope and illumination. The lateral parts of the most peripheral fundus cannot be examined with the vertical slit in connection with the three-mirror lens. However, this is possible with the horizontal and tilted position of the slit and intermediate positions with an oblique slit. The slit must form an angle with the microscope in order to examine vitreous and fundus in optical section. With the indentation contact lenses ciliary processes and pars plana are now accessible to slit-lamp microscopy.


Sector retinitis pigmentosa. Electrophysiological and psychophysical study of the visual system. Combined clinical, psychophysical and electrophysiological examinations of the visual function were performed in two patients affected by sector retinitis pigmentosa. Psychophysical dark adaptation measurements, the electroretinogram (ERG) and the electro-oculogram (EOG) revealed that a larger area of the neural retina and pigment epithelium were pathologically involved than revealed by ophthalmoscopy and visual field. Five years of observation showed a stationary retinal defect in one patient, while in the other a slight clinical but a marked electroretinographical deterioration was found over a period of twelve years. However, visual acuity and the visually evoked potential (VEP) remained normal. In spite of subnormal ERG amplitudes, the photopic and scotopic peak latencies were normal in both cases. In the ophthalmoscopically normal relatives of one patient slight dark adaptation impairments, as well as EOG and ERG disturbances, were detected.


Congenital nystagmus waveforms and foveation strategy. Accurate eye movement recordings of sixty-five subjects with congenital nystagmus (CN) provides a firm foundation for the classification of the many types of waveforms observed and results in objective definitions based on measurable quantities rather than subjective clinical impressions. The careful scrutiny of these records along with the utilization of laser-target cinematography have yielded insights into the mechanism of this ocular motor instability. Prolongation of target foveation emerges as the dominant factor in many of the resultant waveforms. This enhances the visual acuity of the subject with CN. An additional observation, related to fixation bias reversals of the CN subject, may be a physiological indicator of foveal function.


Dominant cone-rod dystrophy.

Dominant cone-rod dystrophy. Six generations of a family were studied extensively allowing the description of an autosomal dominant dystrophy of both rods and cones. The dystrophy is characterized by onset between ages 6 and 8 with gradual decrease in vision and progression to the point of no light perception. Abnormalities of color vision, visual field, refraction, fixation behavior, fundus appearance, fluorescein angiography, electroretinography, electrooculography and dark adaptation are presented. The importance of this family in the classification of inherited retinal dystrophies is stressed and the need for an expanded classification is discussed. The role of genetic counseling is stressed in such severe diseases.


Entrainment analysis of the circadian locomotor activity rhythm in specimens of the crayfish, Faxonella clypeata, having activity peaks at different times of the solar day. Locomotor activity rhythms in the crayfish, Faxonella clypeata, were recorded under conditions of controlled light and temperature. In LD 12:12, dark active rhythms with a major activity onset at lights-off, and bimodally active rhythms with onsets at both lights-on and lights-off were recorded. In DD, most of the LD dark active rhythms retained the lights-off activity onset. However, among the majority of the LD bimodally active crayfish, only the lights-on activity peak persisted in DD. A small number of the LD bimodal rhythms remained bimodal in DD. DD records revealed free-running period lengths both greater and less than 24 hrs. An hypothesis stating that the two recorded LD rhythms represent two basically different rhythmic types is presented. The dark active crayfish appear to entrain to the lights-off position, but the bimodally rhythmic crayfish appear to entrain to the lights-on position.


Relative value of light and food as synchronizers of liver phosphorylase circadian rhythm. The role played by light and feeding schedules on the circadian rhythm of glycogen content and phosphorylase activity of the liver has been studied. In one experiment, mice were subjected to a regimem of constant darkness during 21 days and compared with mice kept in 12 hrs of light alternating with 12 hrs of darkness. Both groups received food and water ad libitum. Liver glycogen content as well as phosphorylase activity showed, with slight differences, similar circadian variations. In a second experiment, mice under similar lighting conditions (LD 12:12), with water access ad libitum, were divided into two groups; one was offered food ad libitum while the other group recieved food from 0700 to 1800 only. This experiment allowed up to compare two different schedules of food intake; ad libitum, normal schedule (from 1800 to 0600) and reversed schedule (from 0700 to 1800). A complete reversal of the circadian rhythm was observed after 21 days in the group with the reverted feeding schedule. We conclude that food can function as the primary synchronizer in spite of the lighting regimen.


[Photochemotherapy of psoriasis: clinical experiences with 152 patients (author's transl)]. Photochemotherapy, a recently developed method of treatment, is based on the effect of light on a systemically administered photo-active substance. 152 patients with severe generalized psoriasis were exposed, after oral administration of 8-methoxy-psoralen, to a high-intensity UVA light source radiating at a continuous spectrum between 320 and 390 nm (maximum at 365 nm). Radiation doses ranged from 1.4 to 4.8 J/cm2 and were progressively increased. Complete remission occurred in 141 patients, satisfactory improvement in the remaining 11. It required 12+/-6 radiation sessions (-/x +/- s) to obtain remission, mean duration of treatment being 22 +/- 14 days. Apart from a neutral ointment no other local or systemic therapy was used. Photochemotherapy completely healed the psoriatic foci leaving evenly tanned, cosmetically appealing skin. All patients were treated at intervals as out-patients (average once a week or ev-ry other week), and remained without recurrence for up to 400 days. No local treatment is required with photochemotherapy, which is very effective, simple, harmless and does not stress patient or doctor. Interval treatment maintained the cure.


[The effect of long-term oral administration of a bronchodilator, a sustained-release aminophylline preparation, on pulmonary function (author's transl)]. Various aspects of pulmonary function were measured in eight patients with chronic bronchial obstructive disease, after five-month oral administration of a sustained-release aminophylline preparation (BY 108: Euphyllin retard). In addition to a sustained bronchodilator effect there was an improvement in static pulmonary volumes and a marked increase in forced expiratory volumes. The reduction in residual volume and of midcapacity is felt to be of particular importance in the prevention of pulmonary emphysema.


[Acceleration of passage through the small intestine by caerulein (author's transl)]. Passage through the small intestine was significantly accelerated after intramuscular injection of ceruletide (synthetic caerulein, F.I. 6934), 0.50 to 0.75 mug/kg body-weight. Average passage took 62 +/- 41 min (106 patients, with various suspected or demonstrated small-intestinal involvement, excluding malabsorption syndrome, sprue or collagen diseases) after caerulein, while in a control group of 83 patients with radiologically normal small intestine it was 126 +/- 62 min (P less than 0.001). In 75% of patients there was no evidence of induced change in radiological pattern of the small intestine. Increased local contractions were observed in a quarter of patients, but did not impair the diagnostic interpretation.


[Classification and immunosuppressive therapy of systemic lupus erythematosus: long-term follow-up of 31 patients (author's transl)]. The course of systemic lupus erythematosus (SLE) in 34 patients receiving prednisone and immunosuppressive (cytotoxic) drugs is described. 31 patients are in continuous ambulatory care, 27 of them 3 to 17 years. Only two were hospitalized for therapeutic purposes: one patient because of exacerbation of lung tuberculosis; the second patient, who discontinued prednisone therapy despite active SLE, because of severe autoimmune haemolytic anaemia. The retrospective analysis of symptoms demonstrated that only 22 of the 31 patients manifested 4 or more of the prelimievious reports. Two patients with severe lupus glomerulonephritis and azotaemia at the time of initial evaluation did not benefit from combined therapy. Nine patients with mesangial and focal glomerulonephritis have normal kidney function up to 12 years after diagnosis (in two cases kidney function improved after therapy).


Role of prostaglandin F2alpha in ovulation. Using radioimmunoassay procedures, the levels of plasma, uterine and ovarian prostaglandin (PG) F2alpha, and those of plasma estradiol and progesterone were measured in intact, hysterectomized or ovariectomized immature female rats pretreated with PMS and subsequent HCG. Occurrence of ovulation was confirmed at 8 hours after the HCG administration not only in the intact rats but also in the hysterectomzied rats. The levels of plasma estradiol and progesterone, and of uterine and ovarian PGF2alpha rose with the PMS injection alone, but they did not reach the peaks before the HCG administration. Both plasma estradiol and uterine PGF2alpha showed a peak at 2 hours after the HCG injection. These peaks were antecedent 2 or 6 hours before the peaks of ovarian and plasma PGF2alpha, respectively. However, such increase of uterine PGF2alpha does not seem to be indispensable for ovulation, because ovulation could occur in the hysterectomized rats. The levels of ovarian PGF2alpha showed a high plateau from 4 to 8 hours after the HCG injection, and then rapidly decreased after ovulation. The levels of plasma PGF2alpha peaked not only in the intact rats but also in the hysterectomized rats at 8 hours after the HCG treatment. But in the ovariectomized rats, this plasma PGF2alpha peak at 8 hours disappeared and there was no statistical change of plasma PGF2alpha throughout the PMS-HCG treatment. Plasma progesterone gradually increased and reached the maximum at 10 hours after the HCG injection. These results conclude that the main source of increased plasma PGF2alpha during the ovulatory process induced with the PMS-HCG treatment is the ovary, and it is strongly suggested that a rapid increase of PGF2alpha in the ovary may play some important role(s) in the ovulatory process.


Plasma estradiol concentrations and effect of HCG on plasma estradiol and testosterone in normal subjects and patients with endocrine disorders. Plasma estradiol concentrations were determined by radioimmunoassay in various endocrine disorders using antiserum to estradiol-17beta succinyl bovine serum albumin. Clinical significance and diagnostic value of plasma estradiol were assessed in hypothalamic-pituitary, adrenal and gonadal disorders. In general, estradiol concentration was correlated well with the degree of sexual maturity and was of great diagnostic use. Plasma estradiol in females mainly originated from the ovary, while the testis is the principal source of estradiol in males. The adrenal gland seemed to play a minor role as a source of estradiol at least in normal males and females. The role of estradiol in gynecomastia and in liver disease was also investigated. More than a half of the cases with gynecomastia had elevated concentrations of plasma estradiol, which probably explains the pathogenesis of this manifestation. Cirrhotic patients showed frequently hyperestrogenemia probably due to delayed disappearance of estradiol. In the study of stimulation with human chorionic gonadotropin (HCG), 3,000 IU daily for three days in ten normal men, the peripheral concentrations of esradiol showed maximum and fourfold increases 24 hours after the 1st injection of HCG. The testosterone levels, on the other hand, increased stepwise and reached a maximum of about two times preinjection levels 24 hours after the 3rd injection. In gonadal disorders, HCG produced various patterns of plasma estradiol and testosterone in accordance with the gonadal conditions and dissociated response patterns of both sex hormones were frequently found. The determination of plasma estradiol was useful in the study of the function of not only the ovary, but also the testis and the simultaneous measurement of plasma estradiol and testosterone after HCG administration presented interesting informations about pathophysiology of gonadal disorders.


Effect of estrogen administration on activities of testosterone 5alpha-reductase, alkaline phosphatase and arginase in the ventral and the dorsolateral prostates of rats. Daily treatment with 5 or 500 mug of estradiol benzoate of male adult rats for 7 days did not change the activity of testosterone 5alpha-reductase in the ventral prostate, while the activity decreased slightly in the dorsolateral prostate. The activity of alkaline phosphatase was increased by 60% over the respective control in the ventral prostate from rats treated with the larger dose of estrogen, but the estrogen treatment did not affect the alkaline phosphatase activity in the dorsolateral prostate. On the contrary, the estrogen treatment evoked three-fold elevation in the arginase activity of the dorsolateral prostate in contrast to the decreased arginase activity in the ventral prostate following estrogen administration. From these results, it was concluded that the alterations in some enzyme activity of the ventral and the dorsolateral prostates evoked by estrogen treatment were different from those observed in the respective lobes from castrated animals, although both estrogen administration and castration induced atrophy of the tissue. Furthermore, it might be also worth-while to mention that the ventral and the dorsolateral prostates of rats responded in a different manner to estrogen administered.


Radioimmunoassay for estimation of thyroglobulin in human serum. A specific double antibody radioimmunoassay has been develop for the measurement of thyroglobulin in human serum. Human thyroglobulin was purified by combined DEAE-cellulose and affinity chromatography using Sepharose 4B-bound Concanavalin A. Sensitivity of test serum was 10 ng/ml. Thyroglobulin was not detectable in half of normal subjects, and half showed values between 10 and 180 ng/ml. In the patients with simple goiter and secondary hypothyroidism, serum thyroglobulin was usually in the normal range. In Hashimoto's thyroiditis, many sera having precipitating antibodies or high hemagglutination antibodies for thyroglobulin showed a high thyroglobulin concentration in serum probably due to a false positive reaction. In hyperthyroidism, an increased thyroglobulin level was observed in 64% of patients. However, there was no correlation between serum thyroglobulin and thyroxine levels in untreated hyperthyroidism. Serum thyroglobulin was increased significantly in some cases for several weeks after isotope therapy for the hyperthyroidism.


Suppressive effect of cyproheptadine on L-DOPA-induced growth hormone release in man. In order to elucidate the relationship between dopaminergic and serotoninergic mechanisms in regulating secretion of human growth hormone (hGH), the effect of cyproheptadine, an antiserotoninergic agent, on l-DOPA-induced hGH secretion was studied in normal subjects. Oral administration of 500 mg of l-DOPA caused a rise in plasma hGH in 6 of 7 subjects studied. This rise in plasma hGH was significantly blunted by the intravenous infusion of 5 mg of cyproheptadine. These results suggest the close relationship between dopamine and serotonin in the control of hGH secretion.


A new method for the simultaneous measurement of the movement of inertia, the damping coefficient and the location of the centre of mass of a body segment in situ. A new method which permits, in a single measurement, the determination of the moment of inertia, the angular damping coefficient of the joint and the location of the centre of mass of a body segment in situ is presented. The underlying principle is the theory of small, damped oscillations of a system about its equilibrium position. The fact that the oscillogram contains information about certain parameters of the oscillating system is used to find these parameters. The application of the method is simple and does not require highly sophisticated instrumentation. The results are very reproducable and immediately available.


[Study of the circadian variation of different circulatory and respiratory functions at submaximal and maximal ergometer work (author's transl)]. The maximal aerobic power of six highly trained young cyclist, mean age 16.3 years and mean VO2max 4.9 l/min, was directly measured at intervals of 4 hrs. A Latin square design was used for the test order. At submaximal work of O2-consumption 2.4 to 4.4 l/min no circadian variation of any single function was found. However, at maximal work load the differences between the maxima and minima values were 12.4% for maximal work output (W max), 7.8% for expiratory minute volume (V Emax), 5.7% for maximal aerobic power (VO2max) and 3.4% for maximal heart rate (H Rmax). All the functions--with the exception of VO2max-had their minima at 0300 hrs; the minima of VO2max was reached already at 2300 hours. The maxima-values of V Emax and VO2max were measured at 1500 hrs, of W max and H Rmax at 0700 and of H Rrest at 1900 hrs correspondingly. A one-tailed test showed significant differences between the maxima and minima values of all variables (P less than 0.05). The results suggest a decreased cardiopulmonary working capacity at night. However, this impairment is only of practical importance if the work will be done near the limit of endurance capacity. Besides it will suggest, that the indirect methods for assessing the cardiopulmonary capacity based on VO2max and W170 are not useful at nighttime, because the presuppositions for these methods are limited of the time of day.


Maximal steady state versus state of conditioning. Criteria for the identification of maximal steady state as related to state of conditioning were evaluated. 13 volunteers walker and/or ran during a series of 15 min tests on a treadmill. The speeds ranged from mild to exhaustive. Heart rate was monitored continuously; VO2 was determined from 6 min to 9 min; and venous blood was obtained at 10 min and 15 min for lactate analyses. Max VO2 was established for each subject. Subjects were classified on level of conditioning according to the quantity and quality of their activity record for the previous 6 months. The 10 min heart rate associated with a blood lactate level of 2.2 mM/L (MSSHR) was the best predictor of conditioning. The relative VO2 (% of max VO2) found with a 10 min blood lactate concentration of 2.2 mM/L (RMSSVO2) was almost as accurate as MSSHR in predicting state of conditioning. Changes in blood lactate levels between 10 min and 15 min were not significantly related to conditioning.


[Changes of pulse rate caused by sonic bomms during sleep (author's transl)]. In two experimental series (19 resp. 53 nights, 2 different persons in each series, test-time 10.30 p.m. to 3.00 a.m.) pulse rate after sonic booms had been recorded during sleep. In the first 3 nights the subjects slept undisturbed by noise. In the following 11 resp. 30 nights sonic booms were applied alternately 2 or 4 times. In the main series after 10 more nights without any noise 4 nights with 8 and 16 sonic booms alternately followed. The last 6 undisturbed nights in both series were used as comparison phase. The interval between two sonic booms was 40 min in nights with 2 booms, 20 min in nights with 4 sonic booms and in the nights with 8 and 16 sonic booms 8.6 resp. 4.6 min. Sound level of the sonic booms ranged from 0.48 mbar to 1.45 mbar, 1 mbar [83.5 dB (A)] in the average. The first sonic boom was applied if one of the two subjects had entered the deepest stage of sleep. Sonic booms induced a biphasic reaction in pulse rate. After an initial increase in frequency with a maximum in the 4th sec pulse rate decreased below the value before sonic boom; it was followed by a slow increase towards the baseline value. This reaction was analysed with special regard to the following factors: 1. Intensity. Due to very fast increase of noise intensity there was no significant correlation between the intensity of sonic boom and the pulse reaction. 2. Exogenic variables. There is no significant connection between postboom pulse rate and noiseless time before the sonic boom, the duration of the test series and the ambient temperature. 3. Endogenic variables. No correlation could be found between the stage of sleep and the reaction. On the contrary a very significant correlation was found between the maximum of postboom increase of pulse rate and the pulse rate before boom. With increasing pulse rate the extent of reaction becomes smaller.


The influence of varying oxygen tensions in inspired gas on 133Xenon muscle clearance and fatigue levels during sustained and dynamic conctractions. Isometric and isotonic endurance levels of both elbow flexors and knee extensors were tested during inspired gas mixtures of ca. 10%, 21% or 100% oxygen in nitrogen. The four work loads were set a 25, 50, 60 and 70% of maximal volitional isometric strength (IS). The isotonic exercise routine was carried out using weight lifting techniques of 20 repetitions per min from 75 degrees to 105 degrees of elbow flexion and knee extensions respectively. Prior to, during, and after the endurance experiments 133Xe clearance was monitored by light weight scintillation counters. A depot of 0.1 to 0.2 ml of isotonic saline containing 50 to 150 muCi of the isotope was used as an intramuscular tracer. The exercise clearance values varied inversely to the test load during isometric exercise. Isotonic exercise for both elbow flexors and knee extensors showed increasing clearance values up to 60% IS. Above this level a decrease in total clearance was recorded. Oxygen tension had no statistical effect on the clearance values. However, the relatively large scatter of the 133Xe clearance method, and an inhomogenous perfusion of skeletal muscle may have masked any anticipated effect of the various O2 tensions. Variations due to the raised intramuscular pressure appeared to be much more dominant than the hypothezised variation due to the 3 set oxygen tensions.


Blood circulation of long bones in trained growing rats and mice. The effect of physical training on the blood circulation of long bones was studied in growing rats and mice of NMRI-strain. The animals to be trained and their controls were about 2 weeks old at the beginning of the training. The training took place on a 5 degree inclined treadmill 5 days a week for 3 weeks in experiment I and 7 weeks in experiments II and III. The duration of the daily exercise was progressively increased over 3 weeks. The final exercise bouts were 80 min for moderate and 180 min for intensive training programs. The circulating red cell volume (ml/100 g bone) of the humeral, femoral and tibial bones of the trained animals was lower compared to the controls in all three experiments mainly due to reduced hematocrit values. The circulating blood volume (ml/100 g bone) decreased in the tibial bones of the trained animals in experiment I and showed a decreasing tendency in experiment III, but no significant differences between the groups were observed in the humeral and femoral bones. Yet, when related to the volume of the bones the circulating blood volume (ml/100 ccm bone) was significantly higher in the femoral bones of the trained animals, while the changes in the humeral bones were negligible (experiment III). The results suggest that the vascularity of long bones is affected by physical training. The varying responses in different bones are perhaps due to the amount of mechanical stress during physical activity.


[Dependence of mean duration of heart period and of arrhythmia during dynamic muscular work on the greatness and differences of work load and during static muscular work on the greatness of work load (author's transl)]. Mean duration of heart period (DHP chi) and its standard deviation (SD), indicating heart arrhythmia and significantly correlating with DHP chi, decreased with stepwise increase of dynamic muscular work on a bicycle ergometer and static muscular work of the right upper arm flexor beyond the limit of permanent performance. This correlation, however, can be understood globally only, since the decrease of DHP chi and SD was not always continuous, but frequently changing, with alterations of increase and decrease from step to step of dynamic work load and from minute to minute of static muscular strain. This concerned particularly SD. A continuous decrease of DHP chi in dynamic muscular work was obtained only by load differences of 40 W, not by differences of 10 or 20 W. A more continuous decrease of SD was also noted during greater load-differences. The significant correlation of DHP chi and SD was lost at a load-difference of 10 W on the 60 W-step and at a load-difference of 40 W on the 180 W-step. Great loads caused at the same load-step less frequent variations of DHP chi, not of SD, than little loads. If no preceding work took place, a contary reaction of DHP chi and SD was noted often at the first load-step. Static work with greater holding force caused a more continuous decrease of DHP chi, in a lower degree of SD, than static work with lower holding force. DHP chi decreased mainly in the first minute of strain. The adjustment of mean heart rate and heart arrhythmia on a level corresponding to increase of load is influenced essentially by the difference of muscular strain appearing between two periods of work load or periods of holding. The regulation of the mean duration of heart period and of heart arrhythmia does not necessarily depend on each other.


Impact of daily work-load during pregnancy on the microstructure of the rat heart in male offspring. In two series of experiments the development of body weight, heart weight and the microstructure of the rat heart in the male offspring from exercised and control inactive mothers was followed. In 50-day-old male offspring the total body weight and heart weight did not differ; in 100-day-old male offspring the heart weight was significantly higher in those from mothers exercising daily for 1 hr (run on a treat-mill with the speed 14 to 16 m/min, i.e. mild exercise of an aerobic character) throughout pregnancy. As regards microstructure of the heart, the differences were significant both in younger and older animals. The number of exercised mothers. The capillary: fiber ratio was significantly higher and the diffusion distance significantly shorter in male offspring of exercised mothers. During the prenatal period a favorable effect of work-load for the offspring could be induced more easily even with mild aerobic and quite short daily exercise than later during postnatal life as shown by experiments reported previously.


Cytochrome components of plant microsomes. The electron transport components of the microsomal fraction of cauliflower buds and mung bean hypocotyls were investigated using split-beam and dual wavelength spectrophotometry under a variety of reducing conditions. Cauliflower microsomes were found to contain an ascorbate-reducible component, termed cytochrome b-559.5 [E'0 = +135 +/- 20 mV; lambdamax (reduced minus oxidised) = 559.5, 527 and 429 nm at 23 degrees C], cytochrome b5 [E'0 = -20 +/- 20 mV; lambdamax (reduced minus oxidised) = 556, 526 and 425 nm at 23 degrees C], cytochromes P-450 and P-420. On the basis of binding studies with ethyl isocyanide, degradation of cytochrome P-450 to P-420, redox potential, aniline binding, and relative rates of reduction by NADPH and NADH, it is suggested that the cytochrome P-450 system is analogous to that mammalian microsomes. Other components, reducible only by dithionite, may also be present. Mung bean microsomes were found to contain an ascorbate-reducible component, termed cytochrome b-562 [E'0 = +120 +/- 20 mV; lambdamax (reduced minus oxidised) = 562, 528 and 430 nm at 23 degrees C], cytochrome b5, and a low potential component which was reducible only by sodium dithionite. No cytochrome P-450 or P-420 could be detected. A general method of analysis of the cytochromes was developed and applied to the microsomes from a variety of plant sources. The results indicate that large variations, both in type and amount of components, occur between the microsomes from different plant materials.


Solid-state protein kinase. A tool for post-synthetically modifying and radioactively labeling proteins in vitro. The capacity of partially purified rat muscle protein kinase coupled to cyanogen-bromide-activated Sepharose 4B to (radio-)phosphorylate proteins in vitro was evaluated using histones from calf thymus and rat liver and certain proteins as substrates. Data are presented which point to a low substrate specificity of this enzyme. It is demonstrated that even within a short time period histones are efficiently phosphorylated without the introduction of contaminating (phospho-)proteins. Therebye phosphoserine residues are formed. The phosphorylation reaction usually performed at 30 degrees C is shown to function quite efficiently also at 4 degrees C. It proceeds even at 30 degrees C for several hours at pH values close to the physiological range without the release of proteins from the solid matrix. The phosphorus transfer can be largely increased with the use of high ATP concentrations. The stability of the substrates is sufficient to suggest a wide applicability of this solid-state protein kinase in the phosphorylation of proteins either for labeling or as a tool to modify proteins post-synthetically under gentle conditions. The solid enzyme seems to be suitable for radioactively labeling proteins of more complex biological structures, such as membrane surfaces.


Studies on the specificity of action of bacteriophage T4 lysozyme. Lysozyme from bacteriophage T4 was found to digest a soluble, uncrosslinked peptidoglycan which is secreted by cells of Micrococcus luteus when incubated in the presence of penicillin G. Analysis of the enzymatic degradation products shows that T4 acts as an endo-acetylmuramidase capable of cleaving glycosidic bonds only at muramic acid residues that are substituted with peptide side-chains. The results indicate that the secreted peptidoglycan may consist of a mixture of chains, approximately half of which are substituted by peptide side chains on most of their muramic acid residues, while the other half is made up of chains in which the muramic acid moieties are unsubstituted.


Determination of protein-ligand binding constants at equilibrium in biological samples. Protein-ligand complexes can be separated functionally into two classes. "Specific" binding is characterized, in relative terms, by a high affinity for the ligand and a low binding capacity. "Non-specific" binding is characterized by a low affinity and a very large capacity. The calculation of equilibrium binding constants for any specific protein-ligand interaction requires the exact determination of the unbound ligand concentration and the specifically bound ligand concentration. These determinations usually require corrections for the contribution of non-specific binding. The use of two correction terms, kn and f, is proposed: kn is the product of the affinity constant k times the number of binding sites n of the non-specific components, while f is the fraction of the non-specific binding included in the experimental estimates of bound ligand. Several theoretical solutions using these terms are proposed for the calculation of specific binding constants. The practical choice of the correction factor may be different when the simultaneous measurement of the affinity constant and maximum number of binding sites, or when only the latter, is desired. In the case of complex binding systesm containing more than one specific component, the individual constants can be determined by non-graphical methods, using computer-aided iterative statistical calculations. A complete solution is given for a system containing two specific plus non-specific interactions and actual experiments are reported for steroid hormone-receptro complexes.


Changes in guinea-pig dermal collagen during development. Guinea-pig dermis was digested with pepsin and the solubilized collagen molecules separated by differential salt precipitation at pH 7.5. Differences in subunit composition and amino acid analysis were noted between type I and type III collagen. Incorporation of radioactive proline into the developing foetus enabled isolation of labelled type I and type III collagens. Comparison of the specific activity of the isolated collagen molecules showed that type III collagen had a high specific activity in the early stages of foetal development, which decreased dramatically during foetal development. The specific activity of pepsin-solubilized type I collagen remained fairly constant during foetal development.


Calcitonin biosynthesis: evidence for a precursor. Calcitonin biosynthesis has been studied in chicken ultimobranchial glands incubated in vitro in the presence of radioactive amino acids. The results obtained suggest the existence of a biosynthetic precursor of higher molecular weight or procalcitonin. This precursor has been identified by pulse-chase experiments, molecular weight determinations, biological activity measurements and analysis of tryptic peptides. Its molecular weight is about 13000 (calcitonin, about 3500) as determined by polyacrylamide gel electrophoresis. Procalcitonin is present in small amounts in chicken ultimobranchial glands and it is biologically active in rats.


Radioactive labelling and characterization of the products of activated mouse lymphocytes. For chemical characterization of the products of activated lymphocytes a radioactive double-label technique was developed which allows one to distinguish those products synthesized either de novo or in increased amounts by the stimulated culture. Spleen cells from Balb/c mice were cultured in serum-free medium in the presence or absence of concanavalin A and simultaneously labelled with radioactive leucine. Optimal culture conditions were established by determining parameters such as cell density, mitogen concentration, and kinetics of protein synthesis following stimulation. Combined supernatants of stimulated and unstimulated cultures each labelled with either [3H]leucine or [14C]leucine were fractionated on Sephadex G-75. Materials derived from control or stimulated supernatants both yielded a qualitatively similar radiolabelled profile. The isotope ratio of stimulated to nonstimulated culture, however, showed a broad peak at KD 0--.35 (approx. mol. wt 75000-20000) which was further analyzed by isoelectric focusing. Pools of every two fractions were focused in polyacrylamide gels at pH 3.5-10. By determining the isotope ratio, the isoelectric point, and the KD (mol wt), it was possible to distinguish at least 24 molecules which had been produced only, or in greater degree, by the stimulated culture.


Effect of fasting on two postheparin plasma triglyceride lipases and triglyceride removal in obese subjects. A new method was used for selective measurement of lipoprotein lipase and hepatic lipase in human postheparin plasma. Hepatic lipase was assayed in 1.0 M NaCl withour addition of serum, and the activity of lipoprotein lipase was determined in 0.1 M NaCl after immunoprecipitation of hepatic lipase with specific antiserum. The activity of both these enzymes and the total lipolytic activity were measured in plasma samples taken during a 4-h infusion of heparin. Each of the activities was related to basal serum triglyceride concentration and to the fractional removal constant (K) of Intralipid in 13 obese subjects before and after prolonged fasting. During a normal isocaloric diet the lipolytic activities showed a biphasic response to heparin infusion in all subjects. A peak activity was reached within 30 minutes ("early response") and thereafter the lipase activities decreased to a constant level maintained during the rest of the heparin infusion ("late response"). The early response of lipoprotein lipase showed a significant inverse correlation with the basal serum triglyceride level (r = -0.85) and a significant positive correlation with the fractional removal rate of Intralipid (r = 0.84). The late response of lipoprotein lipase was not related to either of these parameters. The early response of hepatic lipase was not correlated with basal triglyceride concentration or Intralipid removal, whereas the late response of this enzyme showed a significant negative correlation with the removal rate of Intralipid (r = -0.82). After fasting for several days the acute response of all lipolytic activities to heparin was markedly decreased or totally abolished, but the magnitude of the late response was similar to that seen in the fed state. The fractional removal rate of Intralipid was slightly increased by starvation. All correlations between postheparin plasma lipases and serum triglyceride concentration and removal disappeared in fasting subjects. It is concluded that the rapidly releasable lipoprotein lipase probably reflects the activity of the tissue enzyme(s) which is responsible for the primary removal of very low density lipoprotein (VLDL) triglycerides and chylomicrons. It is probable that this component of the postheparin plasma lipolytic activity is derived from the endothelial lipoprotein lipase pool. This enzyme plays a key role in the efflux of plasma triglycerides under normal conditions, and it is thus one determinant of plasma triglyceride level. Prolonged fasting obviously changes the triglyceride removal sites and mechanism but does not impair the removal efficiency.


Alteration of drug metabolism during cholestasis in man. The morphological and functional alterations of the smooth endoplasmic reticulum of the liver cell related to biliary stasis have brought attention to drug biotransformation during cholestasis. The metabolism of meprobamate, pentobarbital and tolbutamide was assessed in subjects with intrahepatic recurrent cholestasis (3), cholestatic hepatitis (6), extrahepatic biliary obstruction (7) and normal controls (16). In the patients with recurrent intrahepatic cholestasis no differences in drug metabolism were noted as compared to the control group. In cholestatic hepatitis the plasma half-lives of meprobamate (828 +/- 422 min.) and pentobarbital (39+-65) were significantly longer than in in controls (444 +/- 37 and 25.4 +/- 1.1 respectively). Tolbutamide plasma half-life appeared unchanged. The most striking variations were observed in the patients with extrahepatic biliary obstruction. In such cases while meprobamate half-life was unchanged, pentobarbital half-life was significantly prolonged (31.2 +/- 2.5) and the in vitro metabolism of the drug, using liver preparations, was decreased to less than 50% of the control value. In contrast the metabolism of tolbutamide was accelerated as evidenced by a significant decrease of plasma half-life (165 +/- 48 min. versus 384 +/- 76 of the controls) and an enhanced urinary excretion of the drug's metabolites. However the metabolism of tolbutamide in vitro did not show any difference between normal and cholestatic liver. Whatever the mechanism of the peculiar behaviour of tolbutamide in extrahepatic biliary obstruction it seems to be related to the increased bile dalt concentration during cholestasis. In fact the low values of plasma half-life increase significantly either relieving the biliary obstruction or producing a bile salt depletion with cholestyramine. Preliminary results in vitro suggest the bile salt could displace tolbutamide from albumin binding thus increasing the amount of free drug available for biotransformation by the liver. In conclusion cholestasis may affect drug metabolism depending on the degree of biliary stasis, liver cell injury and the type of drug tested. The mechanism could be that of an impaired biotransformation in the smooth endoplasmic reticulum or could involve extrahepatic factors.


Endothelial injury induced by bacterial endotoxin: effect of complement depletion. The role of complement activation in the pathogenesis of endothelial injury caused by bacterial endotoxin was investigated in the rat. DNA synthesis in aortic endothelium was compared 48 hours after an intravenous injection of endotoxin (50 - 500 mug) in normal rats and in rats depleted of haemolytic complement by purified cobra venom factor. At the time of endotoxin administration the rats treated with cobra venom factor had less than 3% of the normal haemolytic complement level, their fibrinogen level was increased and clot retraction was impaired. Endotoxin stimulated endothelial DNA synthesis to the same degree in normal and in complement-depleted rats. Cobra venom factor alone did not stimulate endothelial DNA synthesis. The complement-depleted rats given 500 mug endotoxin were less thrombocytopenic than normal rats at the time of sacrifice, but the difference was not statistically significant. We conclude that the injurious effect endotoxin has on endothelium is not mediated by activation of late components of complement.


Fatty acid pattern of lipids in normal and dystrophic human muscle. The fatty acid distribution of the main lipid fractions: triglycerides (TG), phosphatidylcholine (PCh), phosphatidylethanolamine (PE), and sphingomyelin (Sph) of muscle from 6 patients with progressive muscular dystrophy (p.m.d.), Duchenne, 8 to 12 years old was estimated and compared with normal controls of different age. In view of the results of several authors about varied fatty acid distribution in immature muscle a third group comprising samples of neonatal muscle was studied. 1. The fatty acid pattern of the lipid fractions TG, Sph, and PE from muscle of patients with p.m.d. shows no important variation in comparison to normal controls. In contrast to this the fatty acid distribution in PCh is extremely varied: the percentage of 18:2 is decreased and corrrespondingly the content of 18:1 is increased. In view of the high percentage (nearly 10%) in which linoleic acid is substituted by oleic acid in PCh, effects on the plasma membrane are to be expected. 2. The fatty acid pattern in neonatal muscle shows in narly all positions of the fractions TG, Sph, PE, and PCh a different distribution from normal or dystrophic muscle. In view of the most important variation in dystrophic muscle it must be stated that generally 18:2 is decreased. This deficit was replaced by an increase of all other fatty acids (not only at a substitution by 18:1 as given in p.m.d.). Therefore the diminished content of linoleic acid in PCh of neonatal and dystrophic muscle cannot be interpreted as expression of a corresponding or similar lipid metabolism in both tissues. The results were seen as signs of significant qualitative alterations especially of PCh in p.m.d. They were discussed as proof of our thesis that the basic defect in p.m.d. concerns the specific acylation of PCh with linoleic acid.


Interaction of secretin and insulin on human forearm metabolism. The effect of secretin on forearm metabolism (muscle compartment) was examined in the presence of low and high concentrations of insulin. Continuous infusions (30 min. duration) of secretin 12 ng/min. (SEC), insulin 160 ng/min. (INS) or these doses of insulin and secretin together (INS + SEC) were delivered into the brachial arteries of normal volunteers. SEC alone was without significant effect on forearm metabolism. INS as previously reported, stimulated glucose and potassium uptake and inhibited the output of some amino acids from the deep venous bed. The two hormones together (INS + SEC) increased maximum lactate (p less than 0.025) and alanine output (p less than 0.005) beyond that observed with INS alone. A marked calcium output occurred (p less than 0.001) with the combined infusion which was not observed with either hormone alone. Potassium metabolism with INS + SEC was similar to that observed with INS alone. These results suggest that these two hormones, acting in concert, stimulate glycolysis and net calcium efflux. This joint action of insulin and secretin may have a physiological role in the immediate postprandial period.


Colchicine administration to mice: a metabolic and ultrastructural study. A single injection of colchicine has been administered to normal albino mice, and the metabolic effects as well as the hepatic ultrastructural changes resulting from this treatment have been studied at various time intervals. A marked decrease in circulating triglyceride levels was evident 4 hours after colchicine injection and was maximum after 11 hours. It coincided with a marked increase in hepatic triglyceride content. Twenty hours after colchicine administration, plasma triglyceride levels and hepatic triglyceride content had returned to normal values. Similar changes in the levels of circulating proteins were observed although their magnitude was less than that observed for triglycerides. Ultrastructurally, colchicine treatment resulted in the virtual disappearance of the microtubules from the hepatocytes, and in the appearance of many clusters of vesicles containing very low density lipoprotein-like particles which eventually transformed into lipid droplets. These ultrastructural alterations were also completely reversible, the reversibility coinciding with the morphological reappearance of microtubules. Finally, colchicine treatment resulted in marked metabolic changes that are interpreted as representing an attempt, by the organism, to keep adequate energy sources during the period of lack of circulating triglycerides.


Effect of lipids on insulin, growth hormone and exocrine pancreatic secretion in man. Influences of fat on release of insulin, growth hormone and pancreatic enzyme secretion were studied in 35 metabolically healthy subjects. A fat solution containing 40 g of soy bean oil was administered, I.V., orally and intraduodenally. In all cases there was a similar increase of insulin but the rise in serum insulin after oral or intraduodenal fat administration was not related to the changes in plasma free fatty acids, free glycerol and triglyceride levels. Blood surgar responded according to insulin secretion. The route of fat administration may possibly influence growth hormone secretion. Following intraduodenal fat administration volume and bicarbonate contents of the duodenal juice rose slightly whereas trypsin and bilirubin content increased considerably. These results suggest that insulin secretion after oral or intraduodenal administration of fat is influenced by intestinal factors. Cholecystokinin-pancroezymin and gastric inhibitory polypeptide are qualified to serve as such factors.


Erythropoiesis in the X-irradiated, bled rat. Exposure to low levels of x-irradiation (50R) followed by phlebotomy (50% blood volume) one month post-irradiation, resulted in identifiable alterations of the erythropoietic status of the rat. The red cell indices revealed a decrease in mean corpuscular volume and an increase in mean corpuscular hemoglobin concentration. The half-life of 51Cr-labeled erythrocytes was 16.7 days versus 14.4 days for the untreated controls. These subjects also demonstrated hyperplastic marrows with an approximate 60% mean increase in marrow cellularity. A reproducible mortality of 25% was seen at 17 weeks post-irradiation; the one group of animals followed for an extended period exhibited an 86% cumulative mortality at 23 weeks. The observations supported the concept that x-irradiated rats exposed to a relatively low dose of X-rays (less than 10% LD/50) maintain a latent or residual injury of the bone marrow. These animals, when subsequently challenged by phlebotomy, are placed at greater risk with respect to their ability to survive.


150 MeV proton medical cyclotron design study. A brief design study has been done for a 150 MeV proton sector cyclotron. The object was to minimize cost but maintain good reliability and easy maintenance. The use of the proton beam would be for therapy, radiography and isotope production.


Proton and heavy ion therapy.

Proton and heavy ion therapy. Penetrating ion beams are considered interesting supplements to the types of radiation, mostly electrons and gamma rays, that have dominated in radiation research and radiotherapy during the last decades. Biomedical experimentations and clinical studies ar larger ion accelerators (100-1000 MeV/amu) are therefore undertaken in order to exploit their possible clinical use in cancer therapy. It is concluded that an accelerator that permits effective use of protons (ca. 200 MeV) and deutrons (ca. 50 MeV, for neutron therapy) located in a central hospital would represent a convenient tool for clinical investigations at a larger scale.


Meson radiobiology and therapy.

Meson radiobiology and therapy. High-linear energy transfer radiation (neutrons, heavy ions, and pions) have a greater relative biological effectiveness than low-linear energy transfer radiation by depositing a high density of ionization in irradiated cells. This overcomes the protective effect of oxygen; decreases the variation in sensitivity among the several stages of the cell cycles; and, inhibits the repair of sublethal damage as compared to x-rays, gamma rays, electrons and protons. Negative pi mesons (pions), appear particularly suited for radiation therapy as their penetration and depth-dose profile lend themselves to shaping the high dose area to the tumor size and location. Preliminary biological experiments with pions produced at the Los Alamos Meson Physics Facility studied cell survival at various radiation depths and cell cycle sensitivity. Histologic study of data from the first human experiments indicated severe tumor cell destruction by pions as compared to x-rays in treating malignant melanoma skin nodules, without increased effects on dermal elements.


Fast-neutron radiobiology and radiotherapy. The application of fast neutrons, negative pions or heavy ions will only provide an advantage for the radiotherapy of cancer if, in comparison with conventional radiations, e.g., X-rays, gamma rays and electrons, better depth-dose and collimation characteristics or specific radiobiological dose response relationships result in greater local control probabilities for tumours without increased frequencies of severe noraml tissue damage. Differences in intrinsic radiosensitivity and the presence of hypoxic cells are considered to be the main factors which can cause values of the relative biological effectiveness (RBE) for responses of tumours to be larger than RBE values for normal tissue tolerance. Clinical studies on lung metastases irradiated with single dose of 15 MeV neutrons indicate that RBE values for tumour growth delay can vary between 1.2 and 4.0, while RBE values for damage to several normal tissues are estimated from corresponding animal data to be approximately 2.5.


Surgery of the "pretherapeutic" experiments with fast neutrons produced with the 50 mev deuteron beam of cyclone. The physical and radiobiological experiments performed with the fast neutron beams at the cyclotron of the University of Louvain are described and discussed in view of their therapeutic applications.


Installation of a compact, variable-energy cyclotron in a hospital and preliminary results obtained. The setting up of a compact, variable-energy cyclotron within a preexisting hospital structure and the way by which have been resolved the setted technical restraints are described. Some preliminary results obtained are also given.


Applications of the compact cyclotron of the German Cancer Research center in nuclear medicine, neutron therapy and radiation biophysics. The present facilities of the medical cyclotron in the German Cancer Research Center are outlined. This summary includes methods and thick target yields for radionuclide production and their applications in nuclear medical diagnosis and dosimetry in preparation of radiotherapy with fast neutrons.


The potential and applications of cyclotrons in biomedical fields. Applications of cyclotrons in biomedical fields like radioisotope production; activation and reaction analysis with charged particles and neutrons both in-vitro and in vivo types; production of fast neutron beams for therapy, etc. are described. Production yields of various isotopes in use through different nuclear reactions have been compared with the yields calculated using experimentally measured or empirically constructed excitation functions. Detection sensitivities of various elements in tissue through activation induced by protons, deuterons and alphas of different energies are presented. Fast neutron beams produced from Be, D2, D2O and 7Li targets with different sized and priced cyclotrons are critically compared. It is suggested that a Li-7, deuteron or even a heavy water target would produce a more penetrant neutron beam with relatively smaller cyclotrons than the commonly used Be target.


Production of short-lived radioisotopes for medical applications using high-energy reactions at JULIC. The advantages of high energy nuclear reactions for the production of some special short-lived carrier-free radionuclides for allication in nuclear medicine are outlined. The routine production of 11C (T = 20.3 min), 123I (T = 13.3 h) and 28Mg (T = 21.1 h) at the Julich Isochronous Cyclotron JULIC via the 12C(p,pn) 11C-, 127I(d,6n) 123Xe(beta+, EC) 123I- and 27Al(alpha,3p) 28Mg-reaction, respectively, is described. Some areas of fast labelling and its applications are given.


Transmission detectors for cyclotron in-vivo irradiations with neutrons. The neutron fluence imparted to the irradiated subjects needs to be measured accurately in order to obtain meaningful results from diagnostic irradiations. A convenient neutron detector for this purpose is in the form of a transmission chamber, which covers the whole beam directed at the subject. In one design the detector is an ionization chamber, filled with propane gas, in another a thin sheet of plastic scintillator is coupled to a pair of photomultipliers.


Non-computerized off-axial tomography with 580 MeV protons. Tomography so far has used a "passive" property of radiation absorption, i.e., variation of the transmission rate. Computerized tomography reconstructs (Fourier analyses) a 20 picture of of a sequence of 10 transmission profiles. The resulting image is therefore axially oriented. The use of the stereoscopic effect of two views of the same object (slice), taken at two slightly different angles, is, in such a base, not feasible. "Protoscopy" is based on an "active" property of radiation absorption, i.e., large angle nuclear scattering. The vertices of the large angle scattered protons are individually measured. The spatial resolution of the detectors and the Coulomb multiple scattering are responsible for the existence of an "elementary volume". Stereo display is under study. Despite the fact that "protoscopy" requires a (still) expensive proton source of 600 MeV, a scanning system, the "protoscope", is proposed to challenge all the excellent performances of the most advanced X-ray tomography techniques, such as the automatic computerized transverse axial (ACTA)-scanner.


The potential of proton radiography.

The potential of proton radiography. The properties of two types of proton radiography, MARGINAL-RANGE and MULTIPLE SCATTERING are described briefly and examples of the radiographs shown. A practical application of one of the techniques, MARGINAL-RANGE, to an industrial problem is described. Certain outstanding features of MULTIPLE SCATTERING radiography which may lead to its use in the future are mentioned.


[Cortico-cortical connections of the orbito-frontal cortex]. Using strychnine neuronography, the connections of proreal and orbital convolutions with different sections of the neocortex were studied, in cats. The proreal cortex was found to have direct efferent connections with premotor, motor, and associative sections of the sigmoid gyrus and with the anterior lateral convolution. Besides, the orbital convolution has connections with the auditory, visual, and associative sections of the neocortex. The orbital cortex was concluded to be the basic efferent system of the orbito--frontal cortex providing the latter's conncetions with different sections of the neocortex; the proreal cortex projects efferents only to adjacent sections of the frontal cortex.


[Transcallosal modulation of the focus of maximal activity in the visual cortex]. In cats, EPs on binocular and monocular adequate stimulation in 270 symmetrical points of the visual cortex (the 17, 18, and 19 fields, and the medial portion of the suprasylvian gyrus), were studied. Charts of the maximal activity foci were drawn. Callosal transection was shown to enlarge the foci. The phenomenon of narrowing foci of maximal activity in animals with intact callosal system was found to be due to suppressing (resiprocal) interhemispherical influences increasing from the periphery towards the center of the focus. A spatial transcallosal modulation of the thalamo-cortical activation was suggested to exist in the visual cortex.


[The relationship between oscillatory potentials of the electroretinogpam and components of the visual cortex evoked response]. In the electroretingram of rabbit, the oscillatory potentials (OPs) were shown to appear in response to a wide range of the light stimuli intensities (0.023--120 joules). The minimum time required for the OP onset was 10 msec. The OP duration was independent of the stimulus intensity and ranged between 6--7 msec. The number of OPs, their amplitudes, latency, and peak latency varied along with the intensity of the stimuli. OP1 occurred during developing of "a" wave, while OP2, OP3, OP4--at the ascending phase of "b" wave of the electroretinogram. The latency and the peak latency of the OP1 were always shorter than the respective parameters of the first component of evoked potential in the visual cortex. A definite time correlation between the formation of OP1 and OP2 and the first two components of the evoked potential was revealed. Interrelationship between OP3, OP4, and later components of evoked potentials in the visual cortex was much more complicated.


[A new variation of the schematic eye].

[A new variation of the schematic eye]. Analysis of the eye optical system showed  the presently existing variant of the schematic eye with its of , accommodation mechanism to be inadequate to a real eye. On the basis of accomodation occurring simultaneously with change of the crystalline lens focal distance and displacement of the retina, a new variant of the schematic eye which seems to be more adequate to a real eye, has been suggested.


[The skeltal muscle recovery process following disorders in impulse activity]. Unilateral transection and partial resection of the sciatic nerve after intensive muscular activity entail changes in the biochemical restitution processes in both denervated and contralateral intact muscles. The data obtained reveal the obvious metabolic changes in muscle fibers due to nervous deprivation.


[Afferent activity in the renal nerves of awake dogs treated with diuretics]. In alert dogs with electrodes implanted into the kidney nerves the afferent activity following the influence upon kidney receptors, was studied with the aid of lazix and mannitol administration against the background of the water-milk uptake. The water-milk uptake was followed by no significant changes of nervous activity. Metabolic disturbances due to lazix altered the kidney nerves activity. Acceleration of the kidney filtration due to mannitol was followed by a short-lasting unstable decrease in the afferent nerves activity.


[The state of the anticoagulant system following perfusion of the isolated kidney with thrombin, N-acetyl-thrombin or trypsin]. Tripsine perfused through the rabbit humorally isolated kidney with preserved innervation evokes, like the thrombin, an activation of the second anticoagulating system (SAS). N-acetyl-thrombin lacking in coagulating effect due to blockade of free aminogroups, did not evoke the activation of the SAS under the same conditions.


[The effect of environmental temperature on the state of the blood coagulation system]. Drop of external temperature to +2 degrees C followed by muscle shivering activated the coagulating and depressed the anticoagulating and fibrinolytic processes. On overheating of the organism and development of the hyperemia, a tendency to hypocoagulation appeared.


[The contractile activity of amphibian vein smooth muscle cells]. In frogs, the contractile activity of the antetior abdominal, femoral, and of the major skin veins was studied. The electric transmural stimulation, potassium chloride ions, and catecholamines were found to activate the contractile apparatus of the veins. Spontaneous mechanical activity was not characteristic of the vessels under study; acetylcholine and a rapid stretching of a vein's segment were followed by no active contractile response.


[Changes in blood pressure and impulse activity in intestinal nerves during exposure of small intestine interoreceptors to lactic acid]. I. a. administration of threshold concentration (0.2 ml 7.8 mM) of lactic acid into the small intestine was found to increase afferent and efferent impulsation in the intestinal nerves as well as the systemic arterial blood pressure in anesthetized cats. Increase in the lactic acid concentration up to 250 mM/l resulted in two-phasic augmentation of the nerve responses and of the pressor reflexes. In the range from 7.8 to 62.5 mM/l of lactic acid concentration the absolute magnitude of pressor reflexes was 2.3 +/- 0.6--4.2 +/- 0.5 mm Hg. Further increase in the lactic acid concentration (up to 250 mM/l) produced on augmentation in the reflexes magnitude up to 18 +/- 2.8 mm Hg. A possible functional role of afferent impulses generated by the tissue receptors following an increase in metabolites concentration in the organs, is discussed.


[Participation of the small intestine in carbohydrate metabolism]. Participation of the small intestine in the intermediate carbohydrate metabolism was pointed out by appearing of glucose in the small intestine secret within 2-3 hrs after carbohydrate uptake in the concentration comparable or even exceeding that in the blood. The glucose concentration in the blood drops just when it increases in the intestinal juice, while increase in the blood sugar coincided with reducing of the glucose concentration in the small intestine secret. This suggests that the small intestine lumen can serve as one of the depots for carbohydrates: a kind of temporary depot for monomeres.


[The relationship between temperature adaptation and the effect of noradrenaline on central control of thermoregulation]. In rats cold--adapted (1--3 degrees C) or warmth--adapted (26--28 degrees C) for 4--5 weeks, the body temperature, oxygen uptake, electric muscle activity were continuously recorded before and after intraventricular injection of noradrenaline (NA) at a total volume of 5--8 mcl. At the ambient temperature of 25 degrees C, extremely small doses (5--8 mcg) of NA raised the body temperature due to shivering. Injections of NA were more effective in the cold--adapted rats. Injections of NA at a low ambient temperature (10 degrees C) evoked greater thermoregulatory responses in the warmth-adapted rats.


[Use of a mathematical model to assess cutaneous blood flow and heat loss during a thermoregulatory reaction]. The general blood flow and heat loss were determined in the rabbit ear with the aid of a mathematical model and on the basis of measurements of ambient, hypothalamic, and the ear temperatures, while the ambient temperature changed from--10 degrees C to + 40 degrees C. A static dependence of ear's heat loss on the blood flow intensity at different ambient temperatures, was quantitatively determined.


H-2-associated quantitative traits; statistical analysis of the relative contributions of the H-2 linked genes and the residual genotype. Several associations have been recently reported of the kind that a certain H-2 haplotype tends to be accompanied by a low value and another H-2 haplotype by a high value of some quantitative traits. This includes also the weights of lymphoid and reproductive organs. In order to throw more light on the seeming clustering within the H-2 gene complex of the genetic determinants of such traits, statistical analysis of the relative contributions of the H-2 and the total residual genotypes to the variations in the weight of the thymus, spleen, lymph nodes, testes, seminal vesicles and ovaries was performed. Ten genotypically uniform populations of 2-month-old mice, each consisting of 31 males and 31 females, were analyzed using two different statistical procedures. Four of them were mice of the inbred strains A (H-2a), B10 (H-2b), A.BY (H-2b) and B10.A (H-2a) and six were various F1 hybrids derived from these four strains. The conclusion based on both approaches was that the relative contribution to the variations in the weight of the tested organs from the H-2 haplotype is much smaller or maximally not greater than the contribution from the total residual genotype.


The relative effect of H-2 disparity between irradiated host and injected bone marrow cells on their total proliferative and erythropoietic activities in the host's spleen. Previous experiments showed that in the spleen of non-syngeneic (H-2 disparate) irradiated hosts, the colony-forming performance of injected bone marrow cells may be markedly lower than the standard syngeneic performance. There were also some indications that the deficit was due to a deviated differentiation of the pluripotent stem cells into an alternative pathway. In the present study, the total proliferative activity of donor bone marrow cells [B10.A(2R)] in the syngeneic or allogeneic [B10.A(5R)] hosts was measured as the rate of uptake of 125IUdR and the erythropoietic activity as the rate of uptake of 59Fe. Since both activities are linear functions of the number of injected cells, their inhibition in allogeneic hosts could be judged by the relative slopes of the comparable regression lines. Well reproducible results showed that the erythropoietic activity was inhibited more than the total proliferative activity; this suggests that the residual component of the total proliferative activity must be inhibited less (or even stimulated) in the allogeneic host. The possibility that the differential effect of the allogeneic host environment on the total and erythropoietic activities might be due to a deviated differentiation of some pluripotent cells into the lymphopoietic pathway is discussed.


Lymphocyte trapping and activation in the regional lymph node stimulated by cellular and soluble antigens. Cellularity and intensity of RNA synthesis in the popliteal lymph nodes of mice treated with different types of antigen injected subcutaneously into the hind footpads were followed. The percentage of lymphocytes with nucleoli synthesizing the RNA, incorporation of 3H-uridine and cellularity increased in the lymph node draining the site of antigenic stimulation. This activation occurred as early as 1 day after injection of living cells and the time of maximal RNA synthesis preceded the time of maximal cellularity. The response was seen as late as 3-7 days after injection of dead cells and soluble antigens. In contrast to living cells, soluble antigens induced the trapping of cells before the increase of the formation of ribonucleic acid. The described testing of stimulation of the draining lymph node may serve as a rapid, and economical assay for immunogenicity of unknown substances.


Peripheral blood lymphocyte nucleoli of rats with Yoshida ascitic sarcoma and the effect of cyclophosphamide. Changes in the leucocytes, lymphocytes and peripheral blood lymphocyte nucleoli of Yoshida ascitic sarcoma bearing rats untreated and treated with cyclophosphamide were studied. In the course of the growth of Yoshida ascitic sarcoma lymphocytes with "active" nucleoli (compact nucleoli and nucleoli with nucleolonemas) first increased and then, in the terminal stage of the disease, decreased in number. The number of lymphocytes with ring-shaped nucleoli ("reversibly inactive") and micronucleoli was rising throughout the disease. The increase in numbers of micronucleoli in the lymphocytes produced increased values of nucleolar coefficient. After administration of cyclophosphamide to rats with transplanted tumour the number of lymphocytes with both "active" and "reversibly inactive" nucleoli decreased and the number of lymphocytes with micronucleoli increased. The increase in the proportion of micronucleoli also led to increased values of nucleolar coefficient. After cessation of cyclophosphamide treatment and when the signs of the neoplastic disease had disappeared, the changes observed in the white blood cell picture returned to the values before sarcoma transplantation.


Protection against long ultraviolet and/or visible light with topical dihydroxyacetone. Implications for the mechanism of action of the sunscreen combination, dihydroxyacetone/naphthoquinone. Dihydroxyacetone (DHA) chemically induces long ultraviolet (UV) and/or visible photoprotection into the stratum corneum as demonstrated by (a) long UV protection of albino rats which were psoralen-photosensitized to black fluorescent light and (b) sunlight protection of five patients with long UV and/or visible photosensitivity. Previously, DHA treatment of skin was considered to provide no protection against UV. For clinical use, the combination of DHA and lawsone (2-hydroxy-1,4-naphthoquinone) is preferred to DHA alone, because it provides rapid, positive protection over a range extending from short UV into the visible region of sunlight.


Treatment of psoriasis with long-wave ultraviolet light. The effect of long-wave ultraviolet light on psoriasis was studied in 10 patients, using the method of paired comparisons. The radiation failed to have any demonstrable effect.


Incontinentia pigmenti et achromians.

Incontinentia pigmenti et achromians. A case is reported, apparently the first of its kind in the literature, of a female child in which there were not only pigmented lesions of incontinentia pigmenti but also hypopigmented lesions of incontinentia pigmenti achromians. The title incontinentia pigmenti et achromians is suggested for this combined disorder. The child also had associated lesions in the form of nail dystrophy, delayed dentition and epilepsy.


Visken as supplementary drug in the treatment of pemphigus. Results of combined treatment with low doses of steroids (50-10-5 mg) and Visken (7.5-15 mg) in 5 cases of pemphigus erythematosus and 5 cases of pemphigus vulgaris are presented. Treatment lasted from 30 days to 1.5 years. Some of the patients had been previously treated with steroids and immunosuppressive drugs, but had active lesions or frequent recurrences. In pemphigus erythematosus, very good results were obtained in 3 of 5 cases, and failure in 2 cases was probably related to insufficient dosage of steroids, or no treatment with steroids at all. In pemphigus vulgaris results were not satisfactory. Visken can serve as a supplementary drug in the treatment of pemphigus erythematosus. No complications were observed, and the drug may be regarded as safe.


Generalized mastocytosis, relapsing herpes zoster and polyradiculoneuritis. A 68-year-old woman suffering from a longstanding urticaria pigmentosa with mast cell infiltrations in bones had two attacks of herpes zoster. The second herpes zoster attack was followed by a severe polyradiculoneuritis (Guillain-Barré syndrome). The sequence of events suggests an immunological deficiency.


Vitamin A acid in the topic treament of plantar warts. An ointment with 2% vitamin A acid was applied under occlusion to 50 patients with plantar warts. Only 17 could be considered as cured after 2-10 weeks of treatment.


Lichenoid eruption following penicillamine. A case report with some biochemical observations. The phenomenon of lichenoid eruptions following medication with antimalarial, anti-arthritis and antibacterial medication is well documented in the literature. We report here the first case to be described as a result of anti-arthritis treatment with penicillamine, together with some biochemical studies of the effect of this compound on the enzyme glucose-6-phosphate dehydrogenase.


Effect of pentagastrin and gastric alkalinization on lower esophageal sphincter pressure in diffuse esophageal spasm. The purpose of this study was to evaluate the effect of intravenous pentagastrin and gastric alkalinization on the lower esophageal sphincter (LES) pressure in seven patients with diffuse esophageal spasm as compared to nine normal controls. Intravenous injections of 0.2 and 0.4 mug pentagastrin/kg body weight increased LES pressure significantly more in patients than in control subjects (p less than 0.05, p less than 0.01). Following gastric alkalinization both groups showed increases in LES pressure, but these were significantly greater for patients with diffuse esophageal spasm (p less than 0.05) than for controls. The results of our study indicate that the LES in patients with diffuse esophageal spasm is supersensitive to pentagastrin and gastric alkalinization.


Serum C3 and C4 complement components in ulcerative colitis and Crohn's disease. Serum C3 and C4 complement components were estimated in patients with Crohn's disease and ulcerative colitis. In Crohn's disease, serum C4 concentrations were significantly higher than those of controls. In ulcerative colitis, significantly higher concentrations of C3 and C4 were associated with severe or extensive disease, and C4 concentrations may remain high, years after total colectomy.


Effects of somatostatin on gastric secretion and gastrin release in man. Somatostatin, a recently synthesized hypothalamic growth hormone release-inhibiting factor (GIF), was used in the cyclic and linear form. In all subjects studied, the cyclic GIF inhibited gastrin secretion during basal conditions as well as during a standard food stimulus, with immediate rebound after the infusion was stopped. Similar responses were observed in a hypophysectomized patient, indicating that this effect of GIF was independent of suppression of growth hormone secretion. Cyclic and linear GIF, when administered in normal subjects during an infusion of synthetic human gastrin I, almost totally suppressed gastric secretion. The results indicate that GIF is a potent inhibitor of gastric secretion and gastrin release.


Long-term clinical, radiological and manometric follow-up of patients with achalasia of the esophagus treated with esophagomyotomy. Twenty adult patients with achalasia of the esophagus were treated with an anterior esophagomyotomy and fundic patch. A significant decrease in resting gastroesophageal sphincter pressure was obtained immediately after surgery (p less than 0.001). One case was lost and the rest were followed up for 34 months. Patients had no esophageal symptoms and resting gastroesophageal sphincter pressure remained in low values. Surgical procedure is an adequate and definitive treatment for this disease.


Early inhibition of hepatic bilirubin conjugation after paracetamol (acetaminophen) administration in the rat. Administration of paracetamol (acetaminophen) 13.3 mmol kg-1 body weight to rats led 2 h later to an impaired capacity to conjugate an intravenous load of bilirubin, in the absence of biochemical signs of liver damage and before the reactive metabolite of the drug had become bound within the liver. In addition, paracetamol inhibited the excretion into the bile of conjugated bilirubin, although the plasma levels of the uncomjugated pigment only were elevated. This study provides additional evidence that hepatic glucuronide conjugation is impaired early after paracetamol overdose, and that this precedes the accumulation and binding of the hepatotoxic metabolite of the drug within the liver cells.


EEG in ulcerative colitis.

EEG in ulcerative colitis. Electroencephalographic tracings of 50 patients with ulcerative colitis (UC) were compared with those of 75 controls. In the UC patients a 24% incidence of abnormal tracings was found as compared with an 8% incidence in the controls. A higher incidence of abnormal electroencephalograms was found among active cases of UC than among those in remission. The meaning of these results is not yet clear.


Effect of fatty acids on the stimulated gastric secretion in man. Solutions and emulsions of sodium or potassium salts in a series of saturated fatty acids from C8 to C18 were given in a dose of 0.5 g intraduodenally to healthy males or patients with healed duodenal ulcer. A double-lumen Sarles tube with a balloon placed in the proximal duodenum was used. The substances were instilled after a plateau of gastric acid secretion induced by a continuous infusion of pentagastrin was reached. In order to exclude unspecific effects, the test solutions were adjusted to a pH around 7.0 and to plasma isosmolality. Compared with the other tested substances, the emulsion of 0.5 g sodium-oleate was the most effective in inhibiting the stimulated gastric acid secretion. Sodium caprinate and caprylate had a considerable, but smaller effect than oleic acid on the secretory plateau. Palmitate and laurate provoked only a slight decrease in acid secretion. Myristate was ineffective. These results could suggest that different receptors are responsible for fat-induced inhibition of the gastric acid secretion.


[Spontaneous degeneration of neurons of the Nucl. tractus mesenceph. n. trigemini during the perinatal period of an ontogenic series of Albino mice]. The spontaneous degeneration of neurons of the Nucl. tractus mesenceph. n. trigemini of 33 male NMRI-mice between 19 and 60 days of ontogenesis has been analyzed fitting the exponential function (see article). The number of neurons decreases from 1500 at birth to 1200 at the adult level. The damping of the curve is 4.8. This nucleus is compared with other nuclei of the albino mouse (Nucl. n. oculomotorii, Nucl. cochleares dorsalis et ventralis). The spontaneous reduction of the number of neurons seems to be a common phenomen during the perinatal time of the mammals. There is a heterochronous reduction for the different analyzed nuclei.


[Genesis of C-cells of the thyroid gland in Wistar rats]. Proliferation of the C cells of the rat thyroid gland under conditions of prolonged hypercalcemia induced with vit. D3 leading sometimes to a formation of adenoma-like nodules was observed. Metaplasia of the follicular epithelium into the C cells observed in the process of nodules formation seems to point out that the C cells and the follicular cells of the thyroid gland arise from a common maternal cell.


[Non-traumatic subluxation of the scaphoid bone of the hand]. It is demonstrated in three clinical case reports that a subluxation of the scaphoid bone and a diastasis between the scaphoid and the lunate can occur in association not only with traumatic injury but with chronic inflammatory conditions of the wrist. In one case the etiology was purulent synovitis, in the 2nd an unspecific synovitis with serous exudate, and in the 3rd case rheumatoid arthritis.


[Late results in the surgical treatment of camptodactylia]. Fifteen patients with camptodactyly were treated operatively by flexor tendon transfer for reconstruction of the muscle balance with or without arthroplasty. If necessary skin plasties were performed (Tab. 3). The follow-up time ranged from 3 to 12 years. The results show that the principal cause of the malformation is an imbalance between the flexion and extension forces. The best methods for correction of the flexion deformity were transfer of the superficialis tendon to the extensor apparatus or simple reinforcement of the apparatus in the region of the proximal interphalangeal joint. A major conclusion was that successful result will be obtained only in children and adolescents. Corrective operations in adults should therefore be no longer recommended.


[Luxations and subluxations of the scaphoid bone]. The rare occurrence and the difficulties in diagnosis make partial and total luxations of the scaphoid to a problematic chapter in hand surgery. The main part in diagnosis lies in the correct interpretation of the X-ray pictures from which the different formes of displacement may be recognized. These include isolated luxations of scaphoid in palmar, radial or dorsal directions, varying degrees of scapho-lunate subluxations and luxations and the special type of isolated subluxation of the scaphoid bone. In the first part of the paper the diagnostic criteria and in particular the radiologic signs are described. Most important is the recognition of the alteration in the shapes of the scaphoid bone due to its tilting on several axes and the overlapping of its outline with that of the adjacent bones. The displacement of the whole carpal region can extend as far distal as the metacarpals. A diastasis of the scaphoid and lunate is typically due to rupture of the ligaments between these bones and the radius.


[2 Kirschner wires as simplified external fixation devices in finger joint arthrosis]. A new technique for arthrodesis of the PIP joint is described; after resection of the joint two percutaneous Kirschner wires of diameter 1.2-1.3 mm are placed transversely through the two phalanges. The wires are twisted together on each side of the finger to produce a compression effect on the bone surface. Additional external immobilisation is used for five days only, but the wires are left in place for six weeks. The method has been used without complication in ten patients. The average length of time off work was seven and a half weeks. In the author's view the advantages of this method lie in its technical simplicity and in the free movement of other finger joints.


Surgical treatment of the carpal tunnel syndrome. Surgical decompression was performed in two hundred ninety one cases of carpal tunnel syndrome with good results in 80%, fair results in 10% and poor results in 10% of the cases.


[Occupational therapeutic measures before and after surgical correction of hands with congenital malformations]. The task of the occupational therapist following surgical procedures on deformed hands is discussed. In the child with congenital malformations, we must not only be concerned with treatment of the deformity but we must be concerned about the psychic problems which can develop following prolonged hospitalization or overprotection. One must be keenly observant to detect these problems early. Preoperative testing utilizing a standardized gripping test is carried out by the occupational therapist. The necessity for this is demonstrated by the example of the radial clubhand. In this way complications such as correction of clubhand in the face of a stiff elbow or pollicisation in the presence of inadequate clubhand correction can thus be avoided. After operation training in the new functions is begun as early as possible; preferably with individual supervision. Daily repetative and progressive exercises should result in maximum utilization of gripping ability provided by the operative procedure. The treatment program also includes the adaptation of clothing, the production of appliances and splints, in co-operation with the orthopedic technician, as well as specially designed functional exercises. All these factors are as important as the operative procedure itself in contributing to maximum benifit. All essential findings and their variations must be written down. Also the photographic documentation of the functions is the job of the occupational therapist. Sufficient time should be allowed prior to discharge to inform the parents about the newly acquired functions and the use of the applicances. The maintenance and further development of the newly acquired functions is insured through the continued ambulatory supervision by the doctor and the occupational therapist. The occupational therapist thus has a significant job as a member of the team in a special unit for children with congenital malformations.


The second-in-command syndrome.

The second-in-command syndrome. Individuals who are second in command in organization have common problems that result from their role, as illustrated in a hypothetical example of the relationship of a first-in-command and second-in-command in establishing a day hospital. The authors believe that first and seconds can funtion most effectively by accepting inevitabilities--for instance, that competition exists and that perfect communication is impossible--and recognizing that the relationship has great potential for destructiveness as well as many advantages. They discuss the needs to define boundaries on the basis of skills and personality variables and to respect individual identity.


A unit for delivering multiple drug treatment and prevention services. A diverse group of drug abusers in New Haven has benefited from a multifaceted treatment program at the Connecticut Mental Health Center's drug dependence unit. The unit is also involved in research, training, and community education: Treatment approaches include methadone maintenance, long- and short-term therapeutic communities, a day program for adolescents, and a low-intervention program using narcotic antagonists. Out of approximately 2400 applicants, 1600 have entered treatment, and 550 are considered drug-free program graduates. A long-term follow-up study is in progress to validate and extend those initial results.