Synaptic atrophy in the senescent hippocampus.

Quantitative analyses of electron micrographs have shown a decrease in the number of synapses in the dentate gyrus of the senescent Fischer-344 rat. The loss of synapses, involving both dendritic spines and shafts and axon terminals of more than one population of presynaptic neurons, did not depend upon the antecedent loss of postsynaptic neurons or their dendrites. These findings suggest that the age-related loss of synapses in the dentate gyrus may depend upon an inability of presynaptic elements to maintain the structural integrity of synapses in senescence. It is proposed that a change in the glycoprotein component of presynaptic plasma membranes resulting from a deficiency in axonal transport mechanisms in the septo-hippocampal pathway may underly this presynaptic malfunction. The resulting partial deafferentation of neurons in the dentate gyrus in senescence appears to be associated with a secondary atrophy of dendrites, which results in a loss of postsynaptic membranes before a loss of postsynaptic neurons can be documented.


Multigene families, histocompatibility systems, transformation, meiosis, stem cells, and DNA repair.

Aging is probably not directly traceable to changes along the whole genome, but to a small portion thereof. The main histocompatibility complex appears to be one among the postulated sets of multigene families responsible. The immortality of transformed cells, the germ line, and possibly certain pluripotential stem cells may suggest common qualitative and/or quantitative differences in DNA repair mechanisms between these cell populations and committed, normal cell populations. A relationship between HLA and at least two diseases showing defective DNA-repair suggests that the same chromosome carrying the main histocompatibility complex may control some repair processes. The correspondence of variation in lifespans in different mouse strains with the DNA repair capabilities and degrees of autoimmune susceptibility of the same strains lends further support to the idea that DNA repair, immune dysfunction and aging in higher animals may be intimately related.


The hippocampus: organizational patterns in health and senescence.

The human hippocampal-dentate complex and the adjacent entorhinal cortex undergo a sequence of histological changes during the process of aging and senescence. Such alterations show a loose correlation with the age of the individual, and a more precise fit with the degree of clinical and psychosocial deterioration demonstrated prior to the individual's death. The structural changes are more or less idiosyncratic to the specific area involved but, in general, include loss of dendrite spines. distortion and swelling of the cell-body dendrite complex, and progressive destruction of the dendrite domain. Since one-third to two-thirds of the complement of archicortical neurons may be involved, a very significant fraction of synaptic connections are lost, and with them, much of the computational power of these areas. Psychophysiological studies strongly suggest a relationship between the human hippocampus-entorhinal complex with memory formation and/or retrieval. Animal studies indicate a possible role for the hippocampus as a cognitive mapping system which generates working models of the environment. The utility of such models might lie in part in facilitating selection of context-dependent behavior in a changing spatio-temporal setting. Progressive alteration of hippocampal function with aging and senescence could thus contribute significantly to patterns of increasing confusion and disorientation so common in the senile individual.


Spontaneous mutations balance reproductive selective advantage and genetically determine longevity.

The theory is presented that the genetic potential for longevity of a given species in a protected environment is determined by the rate of predation in the wild and by the frequency of spontaneous mutations. A common genetically determined lifespan representative of rare, long-lived individuals in the wild results from the slight selective advantage conferred by genotypes which do not cause early death. The selective advantage of reproductive rare survivors is limited by the rate of spontaneous mutations from a common potential longevity to those which limit lifespan to shorter times. The equilibrium frequency of life-limiting genes increases exponentially with increasing age when the rate of mutations is uniform for different degrees of life-shortening.


Polygamy and the evolution of human longevity.

An alternative to previous explanations of the rapid increase in man's longevity and intelligence during the several million years of his recent evolution from pre-hominid, clearly shorter-lived and less intelligent, primate ancestors is presented. The general thesis is that a very greatly accelerated rate of incorporation of favorable genes or gene combinations can be achieved in surprisingly few generations among social animals provided that dominant males become the patriarchs of many descendents by virtue of their partial or complete monopoly on available females. The conclusion is that man probably differs from his ancesters of 0.5 to 5 million years ago by many thousands of genes (both structural and regulatory) rather than the dozens or few hundreds that have been postulated on the basis of more classical treatments of selection pressures, gene frequency changes and mutation rates. The concepts developed here formally apply only to two alternative alleles, rather than to groups of genes which segregate independently, or to characters determined by multiple alleles. The appropriate mathematical treatment of the latter real situation is not readily visualized; nor is account taken of the likelihood that different tribes of pre-humans developed different specializations via the above mechanisms which were then (later) combined into an emerging human stock through matings between members of different tribes. The very great variability both in longevity and in intelligence between different races of animals such as dogs, which have been the objects of deliberate genetic selection by humans for particular heritable traits, may parallel our own recent history, even though the selection mechanism (deliberate human selection vs. polygamous dominance) is quite different in the two cases. The onset of civilizations consisting of amalgums between smaller, previously competing tribes, together with the humanitarian responsibilities to each other we share as a species, ironically has probably arrested further evolution of human longevity (and perhaps of intelligence) in the modern world. Possibly even retrogressive changes are occurring, except in those rare sub-populations in which special social and cultural practices tend to favor selective perpetuation of characteristics which are usually viewed as beneficial.


Abnormal haemoglobin in Finnsheep.

An abnormal type of haemoglobin in one ewe and one of her four lambs of Finnish breed has been reported. This type of haemoglobin in Finnsheep seems to be similar to HbC reported in some Norwegian breeds and in anaemic Merino sheep.


[Reactive immunologic changes during intraarterial methotrexate therapy in patients with carcinoma of the oropharynx (author's transl)].

The immunity deficiency as colateral effect of intra arterial therapy with methotrexate in oropharynx carcinoma was measured by lymphocyte stimulation tests. Ten patients taken in two groups were treated with different doses of methotrexate and citrovorum factor. In determined stages of the cellular cycle an extensive reactive trauma to the lymphocytes was detected. This is not the case in the usual measurement of the number of lymphocytes, leucocytes and thrombocytes. This method seems to be appropriate in order to establish the doses, period of time and frequency for application of the intra arterial perfusion with methotrexate.


[Preserved human cartilage grafts and autogenous viable transplants for nose and middle ear (author's transl)].

57% of the preserved human cartilage chips being implanted in the nose lead to a remarkable up to a complete resorption. 94% of the patients have nevertheless a sufficiently or well working function of the nose; besides that they are as well satisfied with the shape of their nose. The most important reason for the resorption are mechanical factors; this has been shown by comparing the load of implanted tissue on the columella and on the dorsum of the nose. We can't exclude the possibility of late immunologic reaction. Comparing these results with those of the middle ear by missing any mechanical load, we registered nevertheless a remarkable loss of the volume of the cartilage. This is an intense indication for an immunologic reaction, especially because there is a more intense vascularisation in the middle ear and a strong activity of fibroblasts based on the mesenchymal potency of middle ear mucosa. It's only in the middle ear that preserved cartilage can be substituted by connective tissue, viable cartilage or viable bone.


[A combined allogenic implant for the dorsum of the nose (author's transl)].

Report of three patients with small bony defects on the lateral bony wall or the bridge of the nose. Reconstruction was performed with a combined cushion like implant of lyodura polsted with merthiolate preserved allongene crashed cartilage. Over a follow up time period of two years the cosmetic results are good. The histological behavior of these implants was studied in animals.


[Morphological changes in the hypopharynx-esophageal region following laryngectomy. II. Median-sagittal infolding above the ventral aspect of the hypopharynx-esophageal region (author's transl)].

This paper deals with the morphological findings in the hypopharynx-esophageal region of two patients following laryngectomy. In these patients we found a median-sagittal infolding, situated above the ventral aspect of the hypopharynx-esophageal region. This infolding was due to the surgical closure of the ventral wall of the esophagus, following laryngectomy. Histological examination revealed a hernia-like prolapse of the tunica mücosa, m. mucosae and tela submucosa with numerous proliferated macrophages and blood vessels, but no lymphatics. These macrophages are concerned with the removal of an edema, which, however, is only imperfectly removed and finally turns out into a fibrous tissue. The functional meaning of this infolding is not yet clear, but it seems intimately related to the altered function of the hypopharynx-esophageal region following laryngectomy.


[Tracheal transplantation in inbred strains of rats. II. Survival rates and gross findings after auto-, iso- and allogenous tracheal transplantations (author's transl)].

Report of gross findings and survival rates in 148 cases of tracheal transplants in and between isogeneic strains of rats. The results imply that the composite graft of tracheal tissue apparently possesses only minor organ specific antigenicity.


[Effects of pull upon the growth of the trachea (author's transl)].

The effect of pull following segmental resection with subsequent anastomosing was studied in animal experiments in regards to the growth of the trachea. A corresponding decrease in body-weight is demonstrated following resection of 4-7 tracheal segments. Even a small pull leads to a decrease of cartilage thickness of the entire trachea. The correlation between the number of the resected cartilage segments and the resulting stenosis in the region of the anastomosis is significant. The decreased area of the canal in the anastomosed region amounts to a maximum of 66% after resection of 7 tracheal segments without the appearance of disorders of ventilation in form of an in- and expiratory stridor. After resection of up to 3 tracheal segments telescopic cartilage overlappings are observed. The mucosa shows a metaplastic regeneration at the anastomosis.


[Ear pains by alterations of the mandibular joint (author's transl)].

17 patients with alterations of the mandibular joint complained of pain of the external auditory canal, the tragal region and the side of the face. In women between 25 and 35 an unphysiologic stress of the joint, in patients over 45 insufficient or missing prosthetics were identified as cause. Other symptoms such as inner ear deafness, vertigo and globus hystericus were not seen.


[Problems in visiometry examining tracheo-bronchial-secretions (author's transl)].

For documentation of the influence of secretolytica tracheo-bronchial-secretions of 60 tracheotomied patients were examined with a modified cone and plate viscosimeter. The reliability of this method is discussed and compared wtih other technics of viscosimetry.


[A new method to get pure nasal secretions (author's transl)].

A new method to get pure nasal secretions is introduced. In comparison to the other methods, which are described in the literature, by this method it is possible to get qualitative and quantitative estimable amounts of nasal secretions. The advantage of this method is discussed. First results are reported about protein concentration and diskelectrophoretic separations of the nasal secretions.


[About progressive deafness after a detonation and explosion trauma (author's transl)].

A case is reported in which deafness was caused by an explosion trauma during wartime. In an expertise in 1954 a causal relationship between the explosion and the deafness was rejected. Advances in medical technology and research into deafness resulting from acustic trauma led to a revision of the previous decision, therefore in 1978 the deafness was acknowledged as war damage and this statement was confirmed by court judgement. The possibilities of a progressive development of ear or skull trauma due to sound is discussed. The point is stressed that there can be longtime intervals between the trauma and the onset and development of resulting deafness. This fact should induce therapeutic consequences, some of the so far tried approaches in therapy are reported.


[Remarks on the medical opinion of noise induced hearing loss (author's transl)].

Analysis of 763 debatable examinations by experts and the study of 104 bulletins. It because clear that the results of language-audiometry can not at all be reproduced in the same way as the results of tone-audiometry. The reason for this is not only a different technique of measure, but obviewsly the patient accommodates himself to being examined. Therefore a sole deterioration of any language-audiogramme without the deterioration of the tone-audiogramme must be critically deliberated by any expert.


[The semiautomatic speech audiometry (author's transl)].

In co-operation with the Viennatone Company we developed an apparatus to perform a "semiautomatic speech audiometry (SAS)". The patient is instructed to repeat the understood words into a cassette recorder when a signal lamp is on. The sequence of the test including the attenuation of intensities and a programmed change of the ear to be tested is automatically controlled. The evaluation of the patient's answers can be carried out by the assistent at any time that is suitable. The advantages of the SAS are a gain in time and the fact that during the test performance the assistent is free to pursue other activities. With the means of the SAS the possibility is now available to perform speech audiometry in very well frequented surgeries of specialists. In a surgery the apparatus was tested in 700 patients with success.


[Electric response audiometry (brainstem potentials, late auditory potential N1): observations at patients suffering from menière's disease or sudden hearing loss (author's transl)].

At some patients suffering from Menière's disease or sudden hearing loss the late auditory potential N1 and the brainstem potentials were registered. It could be shown, that an exact differential diagnosis between these both illnesses was not possible by means of these acoustically evoked potentials. A statistical analysis of the measured values of the brainstem potential IV ascertained this statement. Furthermore it was not possible by means of these potential to predict an improvement of hearing at patients with sudden hearing loss. Finally the potentials showed an increasing of their latencies which was greater at patients with sudden hearing loss than at patients with Menière's disease.


[The anatomic and physiologic foundations of the measuring of time in hearing (author's transl)].

Hornbostel and Wertheimer proved in 1920, that human hearing is able to measure a time difference of 0,03 msec. This "Hornbostel-effect" surpasses by more than a hundredfold the average efficiency of the nervous system. It is only possible by: 1. unusually even diameter of the nervus acusticus fibres 5 micron (Lorente de No 1933), 2. the short way of the nervus acusticus (ca. 4,0 cm) and only two switch-communications (Keidel 1975) from the cochlea to the analysing nucleus accessorius (Galambos and Schwartzkopff 1959), 3. the "miniaturisation" of the cochlea (Keidel 1975), 4. the equal length of the nerve fibres in the cochlea through spiral of the cochlea tapering off to the top (Heermann 1958), 5. ascertainment of statistic average results of numerous simultaneous nerve actions by a neuro-physiologic computer. By altering the speed of speech records and tapes by more than 130% the time pattern, absolutely necessary for understanding language is distroyed, whereas a reproduction of music remains intelligible. By installing an adjustable loop between the high and deep pass sound heads of Matzker's binaural summations test apparatus monaural presentations showed a small deterioration at a retardation of more than 10 msec. At a 90 msec. retardation complete deterioration of speech was observed. At a retardation of 20 msec. the plosives and the short consonants disappear first; next follow the other consonants, whereas vowels remain intelligible at a 100 msec. retardation.


[Air caloric test: as useful as the water caloric test (author's transl)].

Twenty normal probands were examined by us with air (60 sec, 121/min, 45 degrees/29 degrees C) and 25 with water (30 sec, 30 cm3, 44 degrees/30 degrees C) caloric test. Additionally we evaluated the influence of flow rate and tip position on the temperature near the tympanic membrane during the irrigation, using a polyacryl copy of the external auditory canal. A high flow rate and a reproducible tip position very near to the tympanic membrane during the irrigation appeared to be essential to achieve reliable results in air caloric test. Measurements of the actual temperatur should be done therefore at the irrigation tip delivery in every caloric test with air. Lower heat capacity of air, air jamming near the tympanic membrane and heat losses through the meatus wall are the main reasons of more distinct temperature drops and a higher  variability in air caloric test, than in the common caloric test with water. Therefore, the air caloric test as a reliable instrument should be reserved for those cases, were water is contradicted.


[Resistometry-improvement of the hydrodynamic function test of sinus frontalis duct system (author's transl)].

The biophysical and technical base as well as clinical applications of a new functional diagnostic system of sinus frontalis disorders are described. The system consists of a ventilation test and the so called "resistometry". The principle of the resistometry is the generation of a fluid flow in the frontal sinus duct system by a pressure regulated injector, the measurement and registration of flow and pressure and the calculation of the hydrodynamic resistance of the duct system. The resistance is determined in "Resistance Units" (RU). The possibilities of the proposed diagnostic system in differential diagnosis are shown in 156 cases. Apart from the quantitative assessment of the classical inflammations of the frontal sinus the functional diseases of the duct system may be discriminated with certainity.


[Concentrations of antibiotics (ampicilline, doxycycline) in the chronic-hyperplastic alterated mucosa of the maxillary sinuses (author's transl)].

Surgical treatment of chronic sinusitis is usually preceeded by the attempt of curing the disease by antibiotic and antiphlogistic therapy. Since no studies on the concentration of antibiotics in chronic-hyperplastic mucosa of the maxillary sinuses could be found in the literature, two groups of each 20 patients were subjected to treatment with ampicilline (Binotal) and doxycycline (Vibramycin) respectively and the concentrations of the antibiotics in the maxillary sinus tissue gained during operation were measured. It was shown that therapy with doxycycline produces higher tissue levels than with ampicilline. So it can be assumed that with doxycycline the treatment of chronic-hyperplastic sinusitis will be more frequently successful than with ampicilline. But, with regard to the tissue concentrations found in the study, also with doxycycline only part of infections (e. g. due to certain grampositive cocci, hemophilic bacteria, Pasteurellae) seems to be controllable. Since bacteria of different species could be isolated from the excided mucosa of about 50% of the patients and, on the other hand, the serum levels especially in case of doxycycline were constantly high, the prophylactic use of this drug before operation is recommended in order to avoid inflammatory complications.


[The electromyography as an aid the for differential diagnosis of laryngeal movement disturbances (author's transl)].

Laryngeal movement disturbances especially require a differential diagnosis between innervation disturbances and other organic causes. Although this is to be achieved by means of electromyographic examination of the intrinsic muscles of the larynx only, this relatively easy and almost riskless method has been applied for clinical-diagnostic purposes only rarely until now. After a brief description of the technical procedure a few cases (secundary fixation of the cricoarytaenoid joint after an old paralysis of the recurrent nerve; lesion of the recurrent nerve by compression after endotracheal intubation; late lesion of the vagal nerve after operation; paralyses of N. laryngicus cranialis after thyroidectomy; congenital bilateral anchylosis of the cricoarytaenoid joints; prove of re-innervation after surgical repair of the recurrent nerve) are reported to demonstrate that this diagnostic aid is necessary as therapy often depends on the electromyographic findings. Electromyography may give valuable informations about the prognosis of vocal cord paralysis and may become quite important for forensic questions.


[X-ray-Kinematographic examinations of the movement of the velum during the process of sneezing in comparison with cough (author's transl)].

Because of X-ray examinations during the process of sneezing the report of Weber is confirmed, that the cavity of the mouth is sealed against the nose in the moment of sneezing. So sneezing can only be done through the mouth. At the same time a spcial middle phase of the velum is described, i.e. its lifting by an active contraction before the actuel exspirational thrust as an essential difference to the coughing reflex. While coughing the movement of the velum is purely passive because of the exspirational thrust. The seal between the nose and cavity of the mouth is often not complete.


[Analysis of motility disturbances due to a combination of different orbital lesions by means of the synoptometer (author's transl)].

There is no clear cut symptomatology of the ocular motility in blow-out fractures. It is essentially dependant on the number of muscles involved, what muscle in particular and where the muscle in incarcerated. Besides the blow-out fracture an additional impairment of motility can occur, for example central nerve palsy or Brown's syndrome of traumatic origin. For the exact analysis of the deviation measurement from 10 to 10 degrees is essential which can best be achieved with the synoptometer of Cüppers.


[Toxoplasmosis and otolaryngology (author's transl)].

A 5-year-Toxoplasmosis material of the Otorhino-laryngological Department of University School, Szeged has been analyzed on the basis of age, sex, laboratory data and literature. The occurance of the disease was most frequent in the 20--35-year-old population in both sexes. The diagnosis was proved by serological and histological investigations. A one month administration of Tindurin (25 mg Pyrimethamin) combined with Sulphonamid has been used in the therapy with satisfactory effect. The etiological role of toxoplasmosis is emphasised in the differential diagnosis of the cervical lympadenopathy.


[Measurements of temperatures in gold-light endoscopical optics (author's transl)].

Measurements in 5 several Hopkins-Optics demonstrated temperatures up to 121,9 degrees Celsius. The electric light was produced by a normal 150 Watt light source and a special Xenon light source.


Fatty acid metabolism in the calanoid copepod Paracalanus parvus: 1. Polyunsaturated fatty acids.

The metabolic fate of radioactive linoleate and alpha-linolenate administered to the South Atlantic copepod Paracalanus parvus was studied. The wild copepod was able to incorporate the labeled acids dissolved in seawater. The radioactive linoleate was elongated to 20:2omega6 and 22:2omega6 and desaturated by a delta6 desaturase to 18:3omega6. alpha-Linolenate was also desaturated by a delta6 desaturase to 18:4omega3 and elongated to 20:3omega3. The copepod was able to convert alpha-18:3 to 20:5omega3 and 22:6omega3.


Fatty acid metabolism of the calanoid copepod Paracalanus parvus: 2. Palmitate, stearate, oleate and acetate.

The de novo biosynthesis of fatty acids in the wild, calanoid copepod Paracalanus parvus was studied. The incubation of labeled acetate proved the de novo biosynthesis of saturated and monounsaturated even fatty acids from 14 to 20 carbons and the 22:1 acid. Saturated and monounsaturated uneven fatty acids from 15 to 21 carbons were also synthesized. The copepod could not synthesize linoleic and alpha-linolenic acids. By administration of [1-14C]palmitate, [1-14C]stearate and [1-14C]oleate, it was possible to elucidate the general pattern of the de novo biosynthesis of fatty acids in the wild P. parvus.


Lipid composition of Yoshida ascites hepatoma and of livers and blood plasma from host and normal rats.

The lipid composition of Yoshida ascites hepatoma cells was analyzed together with that of ascitic plasma and of livers and blood plasma from host and normal rats. In comparison to normal livers, host livers showed no significant differences in the content of the various lipid classes, but contained a higher percentage of palmitic acid and a lower proportion of arachidonic acid in the major phospholipid classes. In addition, tumor growth induced a marked hypertriglyceridemia in host animals; changes in the concentration of other plasma lipid classes were not statistically significant. The ascitic plasma contained small amounts of lipids mainly constituted by cholesteryl esters and phospholipids. Yoshida hepatoma cells contained less phospholipids in comparison to both host and normal liver, while the increased level of triglycerides and the decrease of free fatty acids were not statistically significant. Hepatoma cells showed appreciable amounts of ether-linked lipids associated in part to neutral lipids (as glyceryl ether diesters) and, in part, to ethanolamine and choline phosphoglycerides. The alkyl groups in GEDE as well as in ethanolamine and choline phosphoglycerides were mainly constituted by C16:0 and C18:0 followed by C18:1. The alk-1-enyl groups in ethanolamine and choline phosphoglycerides were C16:0 and C18:0 with only a minor proportion of C18:1. In comparison to both host and normal liver, Yoshida hepatoma cells showed significant changes in the fatty acid composition of neutral lipids and phospholipids. Some of the major changes consisted of an increase of monoenoic acids associated with a decrease of arachidonic and docosahexaenoic acids in phosphatidylethanolamine, phosphatidylcholine, and phosphatidylinositol.


Apoproteins in association with Intralipid incubations in rat and human plasma.

Intralipid was incubated with rat and human plasma and examined for changes in lipid and aproprotein composition. Upon incubation in rat plasma, Intralipid acquired an apoprotein complement similar to that found in chylomicrons following plasma incubation or in chylomicrons after alimentary lipemia. Since the apoproteins of lipoproteins probably govern their metabolism, these results suggest that Intralipid and chylomicrons undergo similar metabolic fates. This pattern is characterized by a predominance of Apo E (the arginine-rich apoprotein) and Apo C. Incubation of Intralipid with human plasma showed the uptake of Apo A-I and Apo A-IV as well. Density fractionation of the plasma into separate lipoprotein classes identification of high density lipoprotein as the major apoprotein donor to the Intralipid. When rat lipoprotein-free plasma (delta greater than 1.21) was incubated with Intralipid, a different apoprotein pattern appeared in the particles of Sf greater than 400 depending on whether the entire Intralipid preparation or only the Sf greater than 400 fraction alone was incubated. The difference consisted of a virtual total absence of the arginine-rich protein on the Sf greater than 400 particles in whole Intralipid incubation. Density fractionation of the Sf less than 400 particles of Intralipid and recombination of these fractions with the Sf greater than 400  fraction before incubation revealed the major inhibitory fraction to be delta less than 1.006 (Sf 20-400).


Characterization of branched-chain fatty acids from fallow deer perinephric triacylglycerols by gas chromatography-mass spectrometry.

Branched-chain fatty acids of perinephric triacylglycerols of semi-feral fallow deer (Dama dama dama) were analyzed by high resolution gas chromatography-mass spectrometry. Of the total fatty acids, 15.50% were Branched-chain components including 8.96% iso acids, mostly 14-methylpentacanoic acid, 2.85% anteiso acids and 1.73% of other monomethyl-substituted acids; dimethyl-branched acids with an iso structure (1.05%) and with an anteiso structure (0.18%) were also present. Whereas the predominant iso acids and methyl-substituted iso acids had chain lengths of 13 and 15 carbon atoms, the anteiso acids and methyl-substituted anteiso acids had chain lengths of 14 and 16  carbon atoms. Methyl substitution occurred on the even numbered carbon atoms relative to the carboxyl group. The general composition is also given of the fatty acids comprising the triacylglycerols of subcutaneous (rump area) and perinephric adipose tissue.


Comparison of lipid status in the hearts of piglets and rats on short term feeding of marine oils and rapeseed oils.

A series of 4 experiments with piglets and one experiment with rats has been conducted to establish the cardiac lipid status of weanling (3 weeks old) male animals fed fats with different contents of docosenoic fatty acids. Experimental fats were rapeseed oil (RSO) (48.0% 22:1), refined fish oil (RFO) (14.6% 22:1), partially hydrogenated fish oil (PHFO) (14.3% 22:1) and lard (0% 22:1) combined with sunflower seed oil (SFO) in different proportions in diets with 21% total fat. Lipidosis could not be detected in piglets as increased heart weights, by chemical assay for myocardial contents of triglycerides, or by accumulation of docosenoic fatty acids or nonesterified fatty acids (NEFA). In rats, diets with RSO at a level of 16% increased myocardial triglyceride and docosenoic fatty acid contents about 7 times while the effect on cardiac NEFA was inconsistent. Histological examinations of the hearts revealed stainable intracellular fat droplets in some piglets fed 16% RSO for 8 to 13 days, but not after 2, 4 and 6 and 16, 19 and 22 days of feeding. After 10 days of feeding, mild to moderate histological lipidosis was found in piglets fed diets containing 2% or more of 22:1 fatty acids, with no significant difference between RSO, RFO and PHFO in this respect. The same diets in rats gave about 5 times more histological lipidosis than in piglets. This is attributed to a difference in species response, the rat reacting in a more pronounced manner than the piglet. The cardiac lipidosis no-effect level in piglets corresponded to a daily intake of docosenoic fatty acids of 0.4 g per kg body weight. Mild lipidosis was also found in a few animals on docosenoic acid-free diets.


Cholesterol metabolism in the liver and intestine of the chick: effect of dietary cholesterol, taurocholic acid and cholestyramine.

The effect of feeding cholesterol, taurocholic acid, or cholestyramine to chicks on cholesterogenesis from [1-14C] acetate in liver and intestine was determined in vitro using tissue slices, and in vivo by i.v. injection of [14C] acetate. The conversion of cholesterol to bile acids in liver in vivo was measured in the same treatments after i.v. injection of [3H]  cholesterol. Hepatic cholesterogenesis in vitro and in vivo was depressed by dietary cholesterol and taurocholate and enhanced by cholestyramine. Intestinal cholesterogenesis in vivo was depressed only by taurocholate whereas ileal cholesterogenesis in vitro was reduced by dietary cholesterol. Conversion of cholesterol to bile acids was enhanced by dietary cholesterol and cholestyramine and depressed by taurocholate. Hepatic cholesterol metabolism in the chick appears to be regulated by mechanisms similar to those reported for other species.


Influence of elevated levels of linoleic acid on the thermal properties of bovine milk fat.

The thermal properties of bovine milk fat containing 15.5% linoleic acid have been compared with those of milk fat containing a normal level (1.8%) of linoleic acid in order to examine the influence of altered triglyceride (TG) composition on their physical characteristics. The total TGs of 18:2-rich milk fat melted over the range -38 to 30 C compared with the range -33 to 34 C for control milk fat. Polymorphism exhibited by the high mol wt TGs of control milk fat was absent in the same fraction of 18:2-rich milk fat. Similarly, the complex melting thermogram of the low mol wt TGs of control milk fat and its obvious polymorphic behavior contrasted with the single broad melting peak of the low mol wt TGs of 18:2-rich milk fat. This solid miscibility in the 18:2-rich milk fat could be a consequence of the lower proportion of saturated TGs or the presence of high proportions of diene and triene TGs containing 18:2 instead of monoene and diene TGs containing 18:1.


Effect of lecithin on jejunal absorption of micellar lipids in man and on their monomer activity in vitro.

The effect of lecithin on jejunal absorption of fatty acids and octadecenoylglycerol was studied in healthy volunteers with a jejunal perfusion system which excluded pancreatic and biliary secretions from the test segment. Lecithin significantly reduced the absorption of oleic acid (P less than 0.05) and octadecenoylglycerol (P less than 0.01), while it had no effect on the absorption of ricinoleic acid. In vitro, lecithin reduced monomer activities of all three lipids; the changes were greater for oleic acid and octadecenoylglycerol than for ricinoleic acid (P less than 0.02). From these data it is concluded that lecithin reduces monomer activity of fatty acids in mixed micellar solutions and that it can thereby reduce the absorption rates of micellar lipids. Intact lecithin is not absorbed under these conditions. Maldigestion of lecithin in pancreatic insufficiency may, therefore, aggravate the steatorrhea observed in this condition.


The use of essential fatty acid deficient rats to study pathophysiological roles of prostaglandins. Comparison of prostaglandin production with some parameters of deficiency.

In a retrospective study on essential fatty acid deficient (EFAD) rats used to study pathophysiological roles of prostaglandins (PGs), slight increases in the linoleic acid content of the diet were found to gradually restore the depressed growth rate and to increase the reduced endogenous PG production. These apparently poorly deficient animals had a serum triene tetraene (omega9:omega6) ratio much higher than the value of 0.4 used as a criterion for EFA deficiency by nutritionists. Changes in body weight, serum omega9:omega6 and platelet PG production were not correlated with each other. Feeding rats on a diet containing less than 0.1 mg/g/linoleic acid led to decreasing platelet PG production as the degree of EFA deficiency increased. At this high level of deficiency, a serum omega9:omega6 ratio of 6 or over was achieved. This high ratio may be taken as an indicator of the degree of EFA deficiency required for studies on PG deprivation, but PG production by the tissue investigated or by platelets should preferentially be measured.


[The evaluation of vaginal smears in cytological hormone diagnosis: a pilot study (author's transl)].

The estimation of the composition of the vaginal smear of the cytological hormone diagnosis is given by a sampling method. The results show that the cells should be distributed in a more uniform way on the slide than it is the case within conventional smears.


[Sexual differentiation of newborn rabbits with karyotype analysis for experimental use (author's transl)].

The sex of newborn rabbits is differentiated. A three-day blood culture of the blood of the retrobulbar venous plexus and a short term culture within one hour was followed by the preparation of the chromosome metaphases. The mitoses have a good spreading, and they are numerous for the sex differentiation. The sex determination is carried out with the Focomat microscope (E. Leitz, Wetzlar) after having photographed the metaphases.


Optical detection of cell-surface changes associated with malignant transformations in vitro.

A need exists for new experimental approaches for the direct detection of cell-surface changes associated with malignant transformations. The usual methods of fractionating the cell to obtain plasma-membrane segments are disruptive and are influenced by uncertainties that frustrate most attempts to distinguish between the cell memebrane in the normal and malignant states. Here we describe a non-destructive microprobe technique using a light beam to monitor cell-surface changes in situ. Many investigations of tumor-cell behavior in culture are based on substrate-adherent populations of cells. By choosing the substrate to be optically dense and transparent, and by striking the substrate/cell interface by a light beam from the substrate side at an angle of incidence greater than the critical angle of total-internal reflection, an evanescent electromagnetic wave interacts with the peripheral zone of the substrate-adherent cells. Both the intensity and ellipse of polarization of the reflected wave can be monitored as the malignant transformation takes place, either chemically or virally. This technique should also provide new information concerning the molecular organization of the cell periphery from measurements on living cells.


Freeze-etching of dispersions without contamination of the fracture faces.

The physical processes occuring while the fracture face of a dispersion is being freeze-etched are described and the resulting opportunities for elimination of contamination phenomena are discussed. An anticontamination device which can be used in combination with a drop freeze-fracture apparatus is described. The main advantages of the device, high effectiveness and great simplicity, are demonstrated by several practical examples.


Some physicochemical characteristics of an immune lymphocyte product which inhibits the multiplication of toxoplasma within mouse macrophages.

In response to antigenic stimulation, the splenic lymphocytes from Toxoplasma-infected mice produce a factor which is called by the authors the Toxoplasma growth inhibitory factor (Toxo-GIF) and which inhibits the multiplication of Toxoplasma within nonimmune macrophages in vitro. In this study, partial characterization of murine Toxo-GIF was examined using Sephadex G-100 gel-filtration, isoelectric focusing, zonal electrophoresis and heat and enzymatic treatment. Peak activity of Toxo-GIF was found in a Sephadex G-100 fraction with a similar molecular size to that of the ovalbumin. The molecular weight of Toxo-GIF was calculated to be between 38,000 and 55,000. Toxo-GIF was stable to heating at 56 C for 30 min but lost its activity at 80 for 30 min or by exposure to pH values of 5 and 2. Exposure of Toxo-GIF to water-insoluble chymotrypsin or neuraminidase markedly decreased its ability to induce enhanced microbicidal activity of cultured macrophages, suggesting that Toxo-GIF was a glycoprotein. Furthermore, Toxo-GIF migrated in a region cathodal to mouse albumin on agar zone electrophoresis. Isoelectric focusing of active Sephadex fractions showed a well-defined peak of Toxo-GIF activity with an isoelectric point of pH 4.9 to 5.9.


[Growth of Ectothiorhodospira shaposhnikovii on media with various sulfur compounds].

Ectothiorhodospira shaposhnikovii, strain 1, can use thiosulphate, sulphide, sulphite, sulphate, cystein, methionine and glutathione as a source of sulphur during its growth in the light and in the dark. Thiosulphate, sulphide and sulphite are used by the bacterium also as electron donors in photosynthesis so that it can grow in anaerobic autotrophic conditions. Growth of the cultures in the presence of various sulphur compounds depends on the concentration of sodium and potassium salts in the medium, particularly when the bacteria grow in the light and in the dark under aerobic conditions in the presence of such sulphur sources as sulphate, cysteine or methionine. The cells of E. shaposhnikovii produce thiosulphate reductase independent of a source of sulphur and growth conditions. The activity of sulphite reductase can be detected when the cells are cultivated in the presence of sulphates. The activity of APS-reductase has not been found in the cells grown under different conditions.


[Participation of methylcobalamin in the methylation of Propionibacterium shermanii DNA].

Propionibacterium shermanii is characterized by a high content of 5-methylcytosine (5 MC). The level of 5-MC in B12-deficient cells of the culture is twice as low as in the control. The in vitro treatment of DNA isolated from the B12-deficient cells with methyl-cobalamin in the presence of the extract of control cells possessing the activity of DNA-methylase increases the content of 5-MC to the control level. No additional methylation of DNA in vitro takes place in the absence of the methylase system and in the presence of other forms of corrynoids. The methylating activity is displayed either in the presence of methionine or without it. The inhibitor of methylcobalamin, i.e. diftorchlormethyl-cobalamin, blocks methylation of DNA. Small quantities of S-adenosylmethionine are necessary for the reaction of methylation.


[Bacillus thuringiensis plasmid DNA].

Plasmid DNAs were isolated from Bacillus thuringiensis and their physico-chemical properties were studied. The DNAs were purified using ultracentrifugation in a CsCl2 density gradient. The molecular weight of these extrachromosomal DNAs determined by electrophoresis in 0.6% agarose gel and by electron microscopy was 6 . 10(6)--10 . 10(6) daltons; a DNA with a molecular weight of 90 . 10(6) daltons was also found. Digestion with restriction endonuclease EcoRI yielded fragments of the plasmid DNAs with cohesive ends; these were further identified by means of electrophoresis in 1% agarose gel.


[Change in the morphological structure of the population and in the flavin level in the cells of Candida guilliermondii yeasts under periodic cultivation].

The growth of Candida guilliermondii on media with glucose and acetate is described by statistical functions for cell volume (size) distribution. Special instrument has been used to measure the volume of cells and volume distributions. Changes in the morphological structure of populations (both in the average size of cells and in the extent of the size heterogeneity) were detected throughout the whole period of the cultural growth including the exponential phase. These changes hardly differed during the growth on media with glucose or with acetate. The content of flavins in cells also varied in the course of periodic growth. Their total level in cells, as well as the level of FAD, was higher in the exponential phase of growth than during the subsequent phases. Changes in the intracellular level of flavins were found also in yeast populations synchronized by nitrogen limitation.


[Change in the structural organization of the respiratory apparatus of Mycobacterium rubrum depending on the cultivation conditions].

Changes in the respiration apparatus of Mycobacterium rubrum were studied in the lag phase. The number of mitochondrial analogues was found to increase in parallel with the cellular growth, reaching a certain density of distribution per unit surface of the cells. The analogues of mitochondria were very labile. They rearranged easily, depending on the conditions of bacterial cultivation, but were always present in the cells as a discrete structure. The cellular growth and an increase of the mitochondrial analogues in them at 24 and 37 degrees C ceased by the 6-8th hr, regardless of the presence of glucose in the medium. Transition of the culture to the log phase at 24 degrees C was delayed to 16-18 hrs. After division, cells cultivated in media containing glucose were much larger than those grown in media without glucose, and the density of distribution in them of the mitochondrial analogues was higher. A decrease of temperature had no effect on the bacterial growth, but inhibited their division. The rate of oxygen uptake by cell suspensions at different periods of the lag phase correlated with the content of the mitochondrial analogues in them.


[Lysogeny of Rhizobium japonicum and the sensitivity of these cultures to phages isolated from soil].

Twenty cultures of Rhizobium japonicum of various origin were tested for lysogeny using a cross technique with a preliminary UV induction and without it as well as by electron microscopy. None of the cultures was found in the lysogenic state. Phages active against Rh. japonicum were detected in four soil samples on which soybean plants were grown; 27 phages were isolated by the enrichment method and 3 phages without enrichment. The phages were capable of lysis of only Rh. japonicum cultures and differed in the spectrum of lytic action. Some of them were very specific: 9 phages caused lysis of only one among the 28 tested cultures, and 10 phages lysed 2 cultures. Phages with a broad spectrum of lytic action induced lysis of 7-9 cultures. Some of the phages isolated from soils of different type were identical and some were similar in the spectrum of lytic action. Among 28 cultures of Rh. japonicum, 8 cultures were sensitive to all of the 30 phages isolated from soil and 2 cultures were sensitive to most of the phages; the remaining cultures were sensitive to 1-8 phages. Phages and cultures have been selected which can be used for experimental preparation of lysogenic systems and further studies of lysogeny in Rh. japonicum.


[Electron microscopic structure of the Oidium, Oospora fragrans, a producer of lipase].

The fungus Oospora fragrans Berkh. was studied by electron microscopy. Both aerial and submerged oidia were found to be formed by division (septation) of mycelial hyphae in the course of growth. The ultrastructure of the aerial and submerged oidia was identical as was established by the techniques of ultratomy and freezing-etching. The latter technique revealed a certain difference in the morphology of the cytoplasmic membrane of these cells. The oidia of this fungus (arthrospores) differed in their structure from the arthrospores of actinomycetes.


[Effect of prolonged, continuous fermentation on the morphology and physiology of fixed yeasts].

As a result of long continuous fermentation of brewing wort by fixed yeast cells, the number of cells in the fermenter increased as well as their wet weight. The average dimensions of cells (length, width, volume) also increased. The length-to-width ratio of cells decreased. The fermenting activity decreased if calculated per wet weight but remained at the same level if calculated per cell. The overall productiveness of the fermenter with a carrier increased in proportion to the number of cells but not to their weight. The morphological and physiological properties of yeast cells changed as compared to the original ones.


[Deformation of lucerne root hairs caused by the growth substances and culture broth filtrates of Rhizobium meliloti].

Deformation of lucerne root hairs caused by the action of beta-indolylacetic acid (IAA) and alpha-naphthylacetic acid (NAA) differs from deformation induced by Rhizobium meliloti. High concentrations of IAA brought about abnormal deformation of root hairs wherease the action of average concentrations of IAA resulted in corkscrew-like winding and wavy structures. No deformation was observed under the action of low IAA concentrations or the cultural broth of Rhizobium. Infective filaments in root hairs were found only upon infection with pure cultures of Rhizobium.


[Hydrocarbon-oxidizing microflora of uncontaminated seawater].

The distribution of hydrocarbon-oxidizing microflora in noncontaminated sea waters was studied in the northern region of the Pacific Ocean in the vicinity of the Copper Island. The total number of microorganisms was assayed as well as the number of heterotrophic, oligocarbophilic and hydrocarbon-oxidizing microorganisms. Oligocarbophilic bacteria were the most abundant group (from 120 to 24,000 cells per 1 ml), and predominated in 12 stations among 23. The number of heterotrophic organisms was not great and did not exceed 200 cells per 1 ml in 13 stations. A solid medium with an oil product (1%) which was used to determine the number of hydrocarbon-oxidizing bacteria gave overstated results due to the growth of oligocarbophilic forms that could survive in the presence of high hydrocarbon concentrations in the medium. A silica gel medium with an oil product is recommended. Despite the absence of oil contaminations in littoral waters, hydrocarbon-oxidizing bacteria were found in all samples and their content was high in some stations. This can be accounted for by the variety of nutrient requirements of these microorganisms and, apparently, by the presence in water of high molecular weight aliphatic lipids inding the capacity to oxidize hydrocarbons. Organisms belonging to the genera Mycobacterium and Arthrobacter prevailed among hydrocarbon-oxidizing bacteria.


[Submicroscopic organization and spore formation of Desulfotomaculum nigrificans].

The submicroscopic organization and spore formation were studied in two strains of Desulfotomaculum nigrificans, 435 and 781. Cross-sections of cells fixed with osmic acid and contrasted with uranyl acetate and lead citrate revealed a cell wall devoid of the outer lipoprotein membrane, which was typical of gram-positive bacteria. The cell wall consisted of three electron-dense layers and two layers of lower electron density. A layer of a microcapsule having fibrillar structure and a thickness of 23-33 nm was detected on the surface of the cell wall. The cytoplasmic membrane and intracellular membrane structures were represented by the Robertson membrane about 9 nm thick. The cytoplasm contained electron-dense polyribosomal granules and inclusions having fine-granular structure. The nucleoid was located in the central part of the cell as an electron-transparent zone penetrated with electron-dense DNA threads 2.5 nm thick. The paper presents microphotographs of the main stages of spore formation which follows the mechanism described for bacteria of the Bacillus genus. The poles of spindle-like cells have electron-dense disk-shaped formations covered with a three-layer membrane and containing electron-dense granules, apparently, corresponding to polyribosomes.


[Relationship of hydrogen bacteria to carbon monoxide].

The purpose of this work was to study the ability of various cultures of hydrogen bacteria to grow in a gaseous mixture containing, apart from H2, O2 and CO2, carbon monoxide at a concentration of 10% (v/v) and higher. In contrast to CO-oxidizing bacteria, these organisms could not use CO as a sole source of energy. Among 17 studied strains of hydrogen bacteria, only those belonging to the group Alcaligenes eutrophus could withstand 10% of CO (v/v) in a gaseous mixture.


[Vertical distribution and the characteristics of the species composition of the microorganisms of some stratified lakes in Estonia].

The total number, vertical distribution, and special composition of microorganisms from three stratified lakes in the South-Eastern Estonia containing hydrogen sulfide and ferrous iron were studied in March, 1976. The number of bacteria was lowest in surface water samples (1.2-1.9 x 10(6) cells/ml). It increased first in the zone where oxygen disappeared (2.4-7.6 x 10(6) cells/ml), then slightly decreased, and again increased near the bottom where it became maximal (3.7-14.0 x 10(6) cells/ml). The vertical distribution of individual microbial species corresponded to ecological niches. The content of Spirillum and Flexibacter, colonies of parallel rods containing gaseous vacuoles, was highest in the zone in which oxygen was still present. Iron bacteria, purple sulfur bacteria, colourless sulfur bacteria, and green bacteria Chloronema appeared deeper, in the microaerophilic conditions. Ancalochloris perfilievil, Chloroplana vacuolata, Chlorochromatium aggregatum, Pelochromatium roseum, Hyalosoris sp., and Peloploca sp. were found in the strictly anaerobic conditions. Morphological forms of microorganisms were most versatile in the region of contact between the aerobic and anaerobic zones. Most of the morphologically peculiar species of microorganisms were detected in all three lakes, but some bacterial forms were typical of some of the lakes.


[Amnestic episode (transient global amnesia) (author's transl)].

The appearance of the amnestic episode is discussed by presentation of 4 own cases and by means of literature. The amnestic episode is a mental disorder, which exclusively affects short-term memory with a sudden onset and a duration of some hours, seldom up to several days, and often it is connected with a retrograde amnesia. The latter disappears in all cases, but there remains a permanent lack of memory for the time of the episode. Recidivism is rare. Internal, neurological and neurophysiological findings during and after the amnestic episode regularly are normal, at least certainly without characteristic findings. The main age of manifestation lies between the 40th and 70th year of life, there is no priority between women and men. Probably a disturbance of blood flow in the supplying area of the basilaric arteria is responsible, though the proof is still missing.


Positron emission tomography.

Conventional nuclear imaging techniques utilizing lead collimation rely on radioactive tracers with little role in human physiology. The principles of imaging based on coincidence detection of the annihilation radiation produced in positron decay indicate that this mode of detection is uniquely suited for use in emission computed tomography. The only gamma-ray-emitting isotopes of carbon, nitrogen, and oxygen are positron emitters, which yield energies too high for conventional imaging techniques. Thus development of positron emitters in nuclear medicine imaging would make possible the use of a new class of physiologically active, positron-emitting radiopharmaceuticals. The application of these principles is described in the use of a physiologically active compound labeled with a positron emitter and positron-emission computed tomography to measure the local cerebral metabolic rate in humans.


Gamma cameras--state of the art.

The growth of nuclear medicine has paralleled the development and acceptance of gamma cameras, which are stationary instruments that produce an image of an isotope distribution. The most successful gamma camera is based on a large, single crystal of the scintillator sodium iodide coupled to an array of photomultiplier tubes and electronic networks to determine the location of a gamma ray. Current cameras are capable of spatial resolution of 4.0 mm or better. Other types of gamma cameras have been developed, including the multi-crystal camera and a limited number of instruments using gas detectors and semiconductor detectors. The scintillation type of gamma camera will continue to be the dominant camera for the next 5 to 10 years, and will continue to gradually improve. Most significant improvements will result from application of digital electronics to position circuits.


Computers in nuclear imaging.

Currently, the practice of nuclear medicine in larger institutions is practically dependent upon the availability of a computer system. Gamma cameras are connected online to mini-computer systems which have the ability to collect image data in a number of different formats. This permits sophisticated analysis techniques to be used so that quantitative data may be extracted from the images. In some instances, as in tomography, data are reconstructed into images to give views of organs that would otherwise be impossible to obtain.


[First experiences in severe intoxications with diaethylpentenamide (author's transl)].

14 patients suffering from diaethylpentenamide-intoxication were treated in the medical School Hannover, in the period from January 1 to June 6, 1978. 7 of the patients had to be treated in the intensive care unit, and of these 5 received haemoperfusion therapy. The indications for haemoperfusion were severe clinical symptoms and a plasma diaethylpentenamide-level in excess 285 mu mol/l. The duration of coma was significantly less for patients treated by haemoperfusions than for those without haemoperfusion. Although preparations containing diaethylpentenamide are only available through prescription in Germany now, it can be expected that these drugs will continue to be used in cases of suicidal intent. Haemoperfusion seems to be the most effective therapy of diaethylpentenamide-intoxication.


Criteria for determining steam sterilization cycles for lubricated and nonlubricated mechanical equipment.

Requirements and procedures for determining steam sterilization cycles for lubricated and nonlubricated, complex, mechanical equipment are established. Factors affecting exposure times are discussed, as are procedures and data needed to determine the penetrability of steam into mechanical equipment, and the effect of lubricating oil in impeding steam penetration to the spore. The total effects of these factors in sterilizing times are presented. Sterilizers with a prevacuum cycle, which can remove air from the equipment efficiently and replace it with saturated steam, are recommended for complex mechanical equipment.


Scintillation probe detector in the assessment of cardiovascular disease.

A simple device that permits measurement of cardiac function in humans after intravenous injection of technetium-99m-labeled albumin or red blood cells is described. The device (nuclear stethoscope cardiac probe) is based on the application of microprocessor technology to a scintillation detector. It can be used to monitor ventricular function continuously and in exercise testing for the detection of coronary heart disease.


Patterns of the pediatric pneumogram.

The pediatric pneumogram (PPG) is a technique that permits continuous, magnetic-tape recording of the respiratory pattern of infants over an extended period of time. The technique, introduced in 1975, uses an impedance method. As a diagnostic tool, PPG can objectively quantify rate of respiration, the respiratory rhythm, the relative amplitude of respiratory activity, and the incidence of apnea, as well as any resultant bradycardia. Investigations are presently under way using PPG to study the relationship between apnea and sudden infant death syndrome.


[Clinical and endoscopic radiologic results after transduodenal papilloplasty (author's transl)].

The study comprises 56 patients, who underwent transduodenal papilloplasty. More than 15% were symptom-free at least 4 years following surgery. All the symptoms the patients suffered from were nonspecific and the pathological findings of the blood samples were not correlated with the width of the orificium of the papilla of Vater or the diameter of the common bile duct. In 49 patients the ERCP was performed. In 48 cases the retrograde cholangiography was successful, in 1 case only the retrograde pancreatography was possible. In all patients we found normal efflux of contrastmedium out of the papilla. Bile stones, one localized in the common bile duct and the other in the cyst remnant were the most important findings. The diameters of the common bile ducts varied considerably and were not dependent on the velocity of the efflux of the contrast medium. Contrary to the observations of other authors, in only 15% of our patients free air bubbles were found in the bile tree. Peripapillary diverticula of the duodenum were detected in 15% of our patients, but did not lead to compression or obstruction of the common bile duct. Even without histologic examination of the liver, we believe that a broad papilloplasty of the papilla prevents an ascending cholangitis or other related complications.


[Benign liver-cell-tumors and oral contraceptives (author's transl)].

The report concerns two female patients who had taken contraceptives for a period of eight to ten years and were found to have benign liver-cell-tumor. The possibility of liver-cell-tumor induced by oral contraceptives is discussed with regard to the literature.


[Complications following aorto-iliac surgery (author's transl)].

We report on complications following vascular surgery of the aorto-iliac segment. Recurrent occlusions were observed in 15.3% of our cases. The operative mortality was 1.8%. The etiology of anastomotic false aneurysms is discussed. One deep graft infection was successfully managed. Ureteric lesions following aortic surgery are exceptional. No ischemic colitis occurred among our patients. Two cases of aorto-intestinal fistulae are described.


[Infection prophylaxis with cefamandole. Clinical evaluation in the open heart-surgery and the prosthetic vascular reconstruction (author's transl)].

The experience with the cefamandole prophylaxis in 244 patients with open heart-surgery, and another 84 patients operated upon on prosthetic vascular reconstruction was evaluated. No case of endocarditis, sepsis or massive wound infection with infected prosthesis was found in the reviewed patients. Considering the fact that patients undergoing open heart-surgery and prosthetic vascular reconstruction are subjected to much more bacterial contamination than patients undergoing any other surgical procedure, the cephalosporin treatment (in our study cefamandole) should be considered the antibiotic of choice in preventing of infection during and after such surgical intervention.


[Pregnancies without complications of patients with jejuno-ileal bypass because of extreme obesity (author's transl)].

Report about 3 pregnancies without complications of patients, who had been treated by jejuno-ileal bypass because of extreme obesity. There is no increased risk for the successful finishing of a pregnancy of these patients. A close cooperation between the treating doctors is necessary to cope with possible problems.


[Clinical aspects and morphology of placenta increta and placenta percreta (two case examples) (author's transl)].

The cases of a female patient with placenta increta and of another patient with placenta percreta and rupture of the uterus are presented. Both women were 41 years old, multiparae and had a history of multiple abortions as well as a Caesarean section. In both cases a Caesarean section, followed by a hysterectomy and supracervical amputation of the uterus respectively was done. Frequency, clinical aspects, histology and aetiology of the above described disorders of placentation are discussed.


Epidemiology of influenza in Lower Saxony during the period 1968-1978 with particular emphasis on subtypes A(H3N2) and A(H1N1) in winter 1977-78.

The influenza surveillance in Lower Saxony is based mainly on laboratory investigations, and especially those which involve the isolation of influenza viruses throughout the year. These investigations have provided information on the circulation of influenza viruses and of the antigenic drift during the Hong Kong period which resulted in many different variants. Since the advent of the Hong Kong virus subtype, a high excess mortality was observed only in the winter of 1969-70. In most of the other years there was a low excess mortality which coincided with the circulation of the influenza A viruses in the population. During the last winter 1978, influenza A viruses were not isolated before February. In February and March, the two distinct subtypes H3N2 and H1N1 circulated simultaneously. The influenza A(H1N1) virus attacked only children and young adults whereas the patients infected with influenza A(H3N2) virus ranged over all age groups.


Encapsulated strains of Bacteroides fragilis in clinical specimens.

Studies were made of the presence of capsules in 294 strains of the Bacteroides fragilis group of bacteria isolated from clinical infections and in 30 strains from the fecal flora using the Indian ink and ruthenium red staining methods. A total of 77% of the B. fragilis strains were encapsulated; higher figures were observed in isolates from blood and wound infections. Of the B. ovatus, B. distasonis, B. vulgatus, B. uniformis, and B. thetaiotaomicron isolates from clinical infections, 17% were encapsulated. The percentage of encapsulated Bacteroides strains isolated from feces was approximately the same as in the strains isolated from clinical infections.


Phagocytosis and intracellular killing of coagulase-negative staphylococci.

The phagocytosis and intracellular killing of different coagulase-negative staphylococcal species by polymorphonuclear (PMN) leukocytes from one healthy donor were compared. The uptake of strains belonging to a given species varied from 60 to 80% with an average of 70% after 20 min incubation at 37 degrees C. Up to 95% of intracellular bacteria were killed after 10 min. There was no correlation between uptake capacity and species or biotype. The average rates of phagocytosis and killing strains whether isolated from urinary tract infections or from the skin were virtually the same.


The effect of methanol extraction residue of BCG on the cellular immune response in patients with malignant melanoma.

Twenty-one patients with malignant melanoma stage III and IV were treated by intradermal injections of MER--methanol extraction residue of Baccillus Calmette-Guérin (BCG). Twelve of the patients, all with active disease, received chemotherapy in addition. Tests of skin reactivity to recall antigens and in vitro lymphocyte transformation by phytohemagglutinin (PHA), purified protein derivative (PPD), Canadidine, and Varidase were performed in 19 of the patients before and after the MER therapy. The skin reactivity improved in 8 patients, 5 patients maintained their cutaneous competence, 3 remained incompetent, and in 3 other patients a decrease in reactivity occurred. Improvement or maintenance of cutaneous response was more common in stage III than in stage IV patients. The in vitro lymphocyte stimulation tests have shown that reactivity increased or remained at a high level in 9 of 11 patients in stage III. It dropped or remained low in 2 patients in respect to all antigens used in spite of repeated MER injections. In most patients with stage IV disease no improvement could be detected. MER seems to be a potent immunostimulator in patients in stage III. The side effects were tolerable in all patients and consisted of local reactions and influenza-like symptoms. In 4 patients treated with MER by intralesional injections, transient flattening of nodules occurred but no complete regression was observed.


Thirty-six-hour preoperative high-dose methotrexate infusion in patients with squamous carcinoma of the head and neck.

Twenty 36-hour infusions of high-dose methotrexate were given preoperatively to 10 patients with head and neck cancer. Plasma methotrexate levels of greater than 1 X 10(-5) M were maintained for 36 hours and declined with primary and secondary plasma half-lives of 1.7 and 9.2 hours following the end of the infusion. Toxicity of this infusion regimen was minimal (10% incidence of significant (WBC less than 2000/mm3) myelosuppression; no renal toxicity) and all patients underwent surgical resection within 3 weeks of therapy without obvious increase in operative complications. Four of ten patients responded to chemotherapy. Further comparison of the therapeutic efficacy of this prolonged preoperative infusion regimen with surgery alone or schedules employing conventional doses or 6-hour infusions of high-dose methotrexate appears warranted.


Bone marrow biopsy in children: a study of 111 patients.

Closed trephine needle biopsy of the bone marrow has become an established procedure in the evaluation of many malignant and benign diseases in adults; however, its role in pediatric pathology has not yet been defined. In the period from February 1974 to April 1978 we have performed 164 such biopsies in 111 children under 15 years of age. A representative specimen has been obtained in over 80% of cases. This series included, in order of frequency, non-Hodgkin lymphomas, Hodgkin lymphomas, aplastic anemias, rhabdomyosarcomas, neuroblastomas, miscellaneous solid tumors, and single cases of histiocytosis X, malignant histiocytosis, sarcoidosis, malignant histiocytoma, and Castleman lymphoma of the hyaline-vascular type. Histology has been found superior to cytology in the detection of neuroblastoma invasion; the evaluation of the true cellularity in aplastic anemia, and the detection of granulomatous tissue in the only case of sarcoidosis. In other diseases histology and cytology gave similar information, except for the few cases of acute leukemia in partial relapse, which has been better defined in the aspirate smears than in the core specimen. Further evaluation of this technique in other patient series appears advisable.


Granulocyte transfusions in infected neutropenic children with malignancies.

Thirty-six febrile neutropenic episodes were treated by granulocyte transfusions in 33 children. Septicemia and mucous membrane ulcerations were most commonly associated with the fever. Infection cleared in 81% of the episodes, eight per cent ended in death from bacterial infections, 11% from nonbacterial infections or hemorrhage. The median number of polymorphonuclear leukocytes given was 1.1 X 10(10)/m2/transfusion. Two to twenty-eight (median 8.5) transfusions were given over 3--34 days (median 10.5). The source of cells (parental or random) and the method of collection did not seem to affect the outcome. None of the 23 patients whose marrow recovered during the transfusions died of bacterial infections. Infection cleared even without marrow recovery in 62% of the patients, but then only 25% lived for more than two months after clearing of sepsis. In a subgroup of patients with nonlymphoblastic leukemia on the same chemotherapy and antibiotic treatment protocol, 8/11 (73%) survived bacteremia when white cell support was available; only 2/11 (18%) of a historical control group survived when such support was not available. Granulocyte support appears to be a valuable tool in helping neutropenic patients overcome their infections or, at the very least, helping them survive long enough for normal marrow recovery to occur.


Management of carcinoid syndrome.

Two patients who had severe carcinoid syndrome are presented. In one patient prednisone relieved symptoms for 20 months, and in the second patient chemotherapy appears to have precipitated fatal carcinoid crisis. Changes in mentation, increased frequency and intensity of flushing, and hypotension indicate increased risk of a chemotherapy induced carcinoid crisis. Since prednisone may produce relatively long control of carcinoid syndrome, it should be tried before chemotherapy in patients who have increased risk of carcinoid crisis. If chemotherapy is given, doses should be decreased by 50%, and patients should be followed closely.


On optimizing the xeromammographic image.

This work undertakes a detailed system-based analysis of the xeromammographic process starting from basic considerations. Both the edge enhancement and wide-recording latitude, the two principal characteristics of xeroradiography, are shown to bear an intimate relationship to the electric-field distribution. Criteria and methods are formulated for optimizing xeromammographic image quality and a procedure is developed for calculating the white gap. Densitometric curves are derived for both positive- and negative-mode xeroradiography and found to be in excellent agreement with experiment. The question of image linearity is examined carefully and a threshold value of the electrostatic contrast is established, which sets a natural criterion for the application of Fourier analysis. Furthermore, it is shown that, in xeromammography with its inherently low-contrast structures, an optimal exposure exists which optimizes simultaneously all low-contrast edges. This last finding, coupled with experimental results, suggest immediately the possibility of an automatic exposure termination in xeromammography. Beam hardening is also investigated and it is shown that increased filtration combined with a lower bias potential leads to substantial dose reduction without significant loss of image quality. The paper concludes with a discussion of scattered radiation and how it affects xeromammographic image quality.


Computer generation of dose distributions for a fast-neutron therapy beam.

A system has been developed for the computer generation of dose distributions for the MANTA-NRL fast-neutron radiotherapy beam. This program is based on scatter-air ratio (SAR) techniques. A method has been developed to unfold the effect of the neutron-beam profile in the derivation of SARs so that the SARs obtained are those which would be derived if the beam profile were flat. Tables of zero-area tissue-air ratios and SARs are presented. Comparisons of calculated and measured dose distributions are shown. An empirical correction to the usual SAR methods was required to obtain agreement between calculated and measured dose distributions at source-to-skin distances (SSD) which are different from the SSD at which the SAR are derived.


Measurement of the effect of inhomogeneities and compensating bolus in clinical pion beams.

Measurement of the effects of Telfon and air inhomogeneities on the ionization distributions of clinical negative-pion beams have been made at the Los Alamos Meson Physics Facility. Inhomogeneity location and pion-beam energy vary the effect of multiple coulomb scattering on the dose distribution lying in the penumbra of the inhomogeneity. CH2 bolus adequately corrects for the effects of these inhomogeneities. Bolus misalignment less than 0.5 cm does not seem critical because of large multiple coulomb scattering of the pion beam. However, this and secondary particles emitted from pion stars prevent the pion beam from being precisely shaped with sharp edges, as demonstrated by measurements under a patient bolus.


High-LET pion dose contours under the LAMPF biomedical channel by plastic track detector scanning.

Cellulose-nitrate plastic track detectors have been tested as high spatial-resolution dosimeters at the Biomedical Channel of the Clinton P. Anderson Meson Physics Facility (LAMPF) at the Los Alamos Scientific Laboratory during pilot clinical trials with negative pi mesons (pions). Six plots of dose contours are presented. Reliable macrodosimetry with track detectors would in principle require detector calibration for the particular conditions of geometry and beam parameters in every case but it is interesting that absolute dose values, estimated from data taken with a quite different calibration geometry, were within 20% of agreement with dose values obtained by electronic dosimetry methods. The track detectors measure only the high linear energy transfer (LET) components produced by the pion beam; it is these components which are of special interest in the negative-pion therapy program. Plastic track detectors appear to have many favorable properties for pion dosimetry.


Characterization of Clinac-18 electron-beam energy using a magnetic analysis method.

Clinac-18 electron-beam energies and spectral energy distributions were measured by a magnetic analysis method to verify results obtained by the standard range method. A comparison of these measurements with nominal energies quoted by the manufacturer indicates that electron-beam measured by both methods are in agreement with the manufacturer's specifications to +/- 0.6 MeV. Spectral energy distribution of the electron beam was measured to be approximately 1 MeV (FWHM) at all energies.


Specific gamma-ray constant and exposure rate constant of 192Ir.

Calculated values of the 192Ir specific gamma-ray constant, Gamma range from the low value of 3.948 R cm2h-1mCi-1 recommended in NCRP No. 41 to a high of 4.89 R cm2h-1mCi-1. Measured values of Gamma range only from 4.85 to 5.0 Rcm2h-1mCi-1. Discrepancies in reported calculated values exist because the isotope decay scheme and other nuclear spectroscopy data pertinent to these calculations were not well known. Using the 28 gamma rays and relative intensities from the most recent Evaluated Nuclear Structure Data File (ENSDF), Gamma is  calculated to be 4.62 +/- 0.05 Rcm2h-1mCi-1 and the exposure rate constant Gamma delta is 4.69 +/- 0.05 Rcm2h-1mCi-1. These new calculations are presented and previously reported values of Gamma and Gamma delta are reviewed.


An interesting form of high-energy gamma-ray--detector interaction and its effect on spectral peak centroid determination.

The pulse-height continuum produced in a radiation detector following the interaction of photons by pair-production is discussed. The event when one annihilation photon escapes from the detector without interaction while the other escapes after one Compton scattering interaction produces a characteristic component in the pulse-height spectrum. The significance of this component in influencing the accurate determination of the centroid of the double-escape peak is examined and shown to be negligibly small.


Empirical equation for tissue-maximum ratios/scatter-maximum ratios for indirectly ionizing radiotherapy beams.

A six-parameter equation has been fitted to the tissue-maximum ratio/scatter maximum ration (TMR/SMR) tables for 60Co, 4-, 6-, and 10-MV photon beams as well as the 35 MeV d leads to Be neutron beam. The empirical equation has been shown to fit the 60Co tissue-air ratio/scatter-air ratio (TAR/SAR) data equally well. The TMR/SMR model was developed from a three-parameter equation designed to eliminate the graphical extrapolation of zero-field size TARs.


Extraction of information from CT scans at different energies.

The image displayed in computed tomography is a scaled representation of attenuation coefficients within the patient's body. A number of authors have presented methods by which additional information (such as electron density, effective atomic number, and extrapolated attenuation coefficients for therapy applications) can be extracted from CT scans carried out at different energies. In the present paper, the dual-energy method described by Rutherford has been used to produce complete images of effective atomic number and electron density of a known phantom (the AAPM phantom) in order to investigate the usefulness of applying this method to current commercial scanners.


Staphylococcal nuclease reviewed: a prototypic study in contemporary enzymology. III. Correlation of the three-dimensional structure with the mechanisms of enzymatic action.

This is the third in a series of four articles in which the chemical, enzymological and crystallographic work on Ribonucleate (deoxribonucleate)-3'-nucleotidohydrolase, EC 3.1.4.4 (staphylococcal nuclease, micrococcal nuclease) will be reviewed and correlated. This article describes the structure of the nuclease and of a nuclease-inhibitor complex as determined by x-ray crystallography. The crystal structures are correlated with some of the known chemical and enzymological properties of the enzyme, and the three areas combined to propose a mechanism of action.


Inhibitors of oxidative degradation of protein: gerontological implications.

Compounds were studied that inhibit the oxidative degradation of human serum albumin by peroxidase and the enzyme model, iron hydroxide. Differences between the two oxidants gave clues for the mechanism of inhibition. The inhibitors studied were inorganic anions, phosphate, sulfate, carbonate and molybdate; organic anions, decanoate and glycocholate; and the nonionic species, glycogen. Such inhibitors might be considered as adjuvants in senescence: by decreasing the rate of enzymic oxidation of essential body proteins, they would, in the course of aging, reduce some of the physiological changes occurring as a result of accumulation of degraded protein.


Protein biosynthesis in isolated human scalp hair follicles.

The present study demonstrates that protein biosynthesis can be studied in single isolated human scalp hair follicles. The matrix and the sheath are the main regions where amino acids are built in. Incorporation is linear for at least five hours. The newly synthesized proteins can be separated into a water-soluble, a urea-soluble and a urea-insoluble fraction. Product analysis has been performed on the first two fractions, revealing different protein patterns.


Differences in the incorporation of [3H]-glucosamine into nascent polypeptide chains on free polysomes and two fractions of membrane-bound polysomes in mouse myeloma cells.

The incorporation of [3H]-glucosamine into polypeptides of three fractions of polysomes in MPC-11 cells was studied. After short term incubation greatest incorporation was observed in a fraction of membrane-bound polysomes, which after nitrogen cavitation of cells, remained bound to the endoplasmic reticulum (ER) associated with the nucleus (fraction 2). Polypeptide chains on membrane-bound polysomes in the microsomal fraction (fraction 1) and free polysomes contained much less radioactivity. Since nascent polypeptide chains contained within membrane-bound polysomes of fraction 2 are glycosylated at an earlier stage than those in fraction 1 it is likely that this represents a difference in type of proteins synthesized in the respective fractions of ER.


Polyadenylated RNA in the lower eukaryote Physarum polycephalum.

Utilizing a method which quantitatively extracts high molecular weight RNA, including intact precursor as well as mature ribosomal RNAs, adenylated molecules have been isolated from nuclear- and cytoplasmic-enriched fractions of Physarum microplasmodia labeled with [3H]-uridine. Electrophoretic analysis of denatured adenylated RNA from the nuclear-enriched fraction indicated the presence of a population of large molecules not found in the cytoplasmic-enriched fraction.


Intracellular distribution of biotin-14COOH in rat liver.

Biotin clearance, its distribution in liver and liver fractions after intravenous administration of 5 muCi/100 g body weight (21.55 microgram) of biotin-14COOH in normal and biotin-deficient rats are reported. In the biotin deficient animal there is a more rapid disappearance of the labeled biotin from the blood stream. Biotin-14COOH incorporation in the liver of the deficient rat is more rapid and larger than the incorporation in normal rat liver. Almost all the biotin recovered from liver homogenate is found in the mitochondria and in the pH 5.2 cytosol fraction; whereas in the microsomes only a very small amount is present. The intracellular distribution of biotin is in agreement with its known metabolic roles.


[Several kinetic features of nitrogenase reactions].

The dependence of the nitrogen reduction rate on N2-concentration under high nitrogen pressures was measured. The reason for the sharp break of the Arrenius curves in nitrogenase reactions at 20 degrees C was examined. The influence of nitrogen on isotope effect catalyzed by nitrogenase was studied. The kinetic schemes that explain the peculiarities of the nitrogenase reactions were analyzed by the graph's theory. On the base of new conception of inhibitor-"interceptor" of electrons the literature data were discussed.


[Graph method of analyzing the stationary kinetics of polyenzyme systems].

Methods based on the graphical representation of relations between metabolites concentrations were worked out for the description and analysis of the steady-state kinetics of the multienzyme systems. The properties of graphics characterizing various steady-state regimens were investigated. Relations relevant to the analysis of regulatory phenomena were derived for the concentration of non-adjacent metabolites. Rules are presented for the kinetical description of multienzyme systems posessing external inputs and outputs. Certain branchings occuring in multienzyme systems were considered. The developed methods allow generalization concerning multisubstrate multiproduct reactions as well as systems containing regulatory enzymes with non-michaelian kinetics. It is suggested that the generalized methods may be helpful for the analysis of the metabolic regulation.


[Physical mapping of the genome of phage Cd].

The effect of 7 specific endonucleases EcoRI, BamHI, BglII, SalI HindIII, XhoI, SmaI, on the genome of the phage Sd was studied. The molecular weight of the genome was estimated as 45.10(6). BamHI, EcoRI, HindIII, BglII, SmaI have altogether 15 sites of restriction SalI and XhoI do not hydrolyse the phage DNA. Fragmentation of the phage DNA in conditions of partial hydrolysis and simultaneous action of several enzymes have allowed to draw a physical man to the phage Sd DNA is more resistent to the action of restriction enzymes than DNAs from other phages. The mean size of Sd DNA fragments exceeds the statistical value almost by one order of magnitude.


[Complementary interaction of multialkylated polyribonucleotides].

Effect of modification of polyinosinic acid (poly(I)) by alkylating agent 4-N,N-bis (beta-chloroethyl) aminobenzaldedehyde on its complementary interaction with polycytidylic acid (poly(C)) was investigated. The data demonstrate that when no more than 10% of inosine residues are modified poly(I) still retains its capacity to form complementary complex with poly (C) this capacity disappears after modification of 11--13% of inosine residues. However when more than 3,5% of inosine residues were modified the poly(I). .poly(C) complex became sensitive to RNAse T1 and its Tm decreases, indicating that single-stranded regions (loops) are formed under these conditions. The data suggest that modified polynucleotides carrying alkylating groups on their surface can be applied for the directed action on the complementary regions of the genome.


[Nuclear ribonucleoproteins containing pro-mRNA. XIV. Structural study using ethidium and fluorescamine].

Nuclear 30S RNP particles were studied by means of fluorescence techniques. It's shown that fluorescamin interacts with NH2-groups of protein molecule. As a result, covalent fluorescent label is formed. Quantum yield (rho), fluorescence spectra, lifetime of excited state (tau) and polarization of fluorescamin complexes with 30S particles were studied. Excitation spectra have their maximum at 395 nm, and fluorescence spectrum at 480 nm. These figures correspond to spectra of fluorescamin complexes with NH2-groups of lysine. Mean quantum yield (rho = 0.27) and lifetime of excited state of fluorescence (tau = 7.8 nsec) were measured. It's shown that fluorescamin forms two types of fluorescent complexes in 30S particles. These complexes differ only by their rho(rho1 = 0.11, rho2 = 0.30) and rho(rho1 = 3.6 nsec, rho2 = 10.0 nsec) by 2.7 times. Migration radius between fluorescamin bound to protein and ethydium bromide adsorbed on double-stranded regions of pre-mRNA in RNP-particles was measured. It's equal to 32 A. Adsorbtion isotherms of ethydium bromide were measured by fluorescence in 0.1 and 0.4 M NaCl. Data obtained showed that 6% of pre-mRNA in 30S particles bound the dye as a strong complex, i. e. this part of pre-mRNA is double-stranded. RNase treatment of RNP had no effect on this value. But the increase of NaCl concentration up to 0.4 M caused the dissociation of protein subunits to some extent followed by appearance of up to 40% free NH2-groups interacting with fluorescamin. Measuring of energy migration from fluorescamin to ethydium bromide showed that double-stranded pre-mRNA regions strictly bound to protein sticked out from RNP particle at a distance of about 27 A. The increase of NaCl concentration up to 0.4 M leads to disruption of this strict bond of double-stranded regions with protein. As a result, these regions of pre-mRNA become labile and move away from the RNP particle at more than 30 A. According to theoretical calculations, there is about 1--2 pre-mRNA hairpins (18--9 base pairs respectively) per one 30S particle.


[Study of the complex of myoglobin with nicotinic acid by the method magnetic circular dichroism. Nature of the double hemochromogen].

The complex formed by myoglobin and nicotinic acid exhibits unusual spectral properties. Instead of the usual two bands in the visible region the complex shows four bands assigned to the so called twin hemochromogen. Some attempts were previously made to clarify the nature of the twin hemochromogen, but the interpretation given was somewhat doubtful. We have shown that the combination of two spectral methods, namely magnetic circular dichroism and absorption spectra, give evidence that unusual absorption spectrum of the myoglobin complex with nicotinic acid is not attributed neither to the presence of the other hemochromogen nor to the soft vibrations but is due to the strong splitting of the pure electronic Q00 band into two Qox and Q0y bands. The splitting is caused by the distortion of heme structure by its asymmetrical environment.


The distribution of spontaneous chromosome aberrations in BHK21/C13 fibroblasts.

Previous investigations of spontaneous aberrations in mammalian cells have been carried out on large heterogeneous samples of individuals, each of whom had had a different exposure to exogenous clastogens. In the present analysis using Syrian Hamster cells, a large number of metaphases were analysed from one sample of control cells. In this way all cells were exposed to the same doses of any unknown clastogens. The overall distribution of spontaneous breaks was found to be nonrandom. Breaks involved in different types of aberration had a nonrandom distribution, which was specific for each type. (e.g. terminal deletion and rearrangement).


[Reaction between the protein of gene 32 of phage T4 with DNA. Comparison of the properties of native protein and the product of its limited hydrolysis].

Interaction between DNA and limited hydrolysate of T4 gene 32 protein has been studied. This limited hydrolysate is obtained when 8000 dalton segment of native 32 protein is removed proteolitically, its molecular weight being 26,000 dalton. It is shown that the melting temperatures of DNA as well as that of the synthetic homopolymer poly[d(AT)] complexed with this modified protein are more than 60 degrees lower than that of pure DNA and poly[d(AT]. The secondary structure defects in DNA promote its unwinding by the modified 32 protein. As follows from the analysis of the melting curves of the modified 32 protein -- DNA complex, this protein cooperatively binds to denatured DNA. The binding constants and cooperativity parameters are found to be equal to 10(8)--10(10) M-1 AND 10(3) respectively. It is shown that the gene 32 protein in the same environmental conditions does not destabilized native DNA and poly[d(AT)].


Studies of X-ray-induced chromosome aberrations in cells of the black-tailed wallaby. I. Non-random exchange in peripheral blood cells irradiated in Go.

The distribution of exchanges between individual chromosome arms in mitotic peripheral blood cells following X-irradiation in Go has been measured. It was found that, although all arms exchanged with each other, there were small but significant departures from the frequencies expected on the basis of random breakage and exchange. It is suggested that non-randomness may reflect the non-uniform state of condensation of chromatin in Go lymphocytes.


Procarbazine-induced specific-locus mutations in male mice.

Procarbazine is used in drug-combination treatment of Hodgkin's disease. The specific locus method was used to test and confirm the ability of procarbazine to induce gene mutations in pre- and post-meiotic germ cells of male mice. The lowest dose of procarbazine that significantly increased the mutation frequency in As spermatogonia over the control frequency was 400 mg/kg (P = 0.003). The corresponding dose for the post-spermatogonial germ-cell stages was 600 mg/kg (P = 0.009). The dose--response was linear for the point estimates of the mutation frequencies after treatment of As spermatogonia with 0, 200, 400 and 600 mg/kg. The point estimate of the mutation frequency at the 800 mg/kg level was one-third of that expected from a linear extrapolation. Variation in mutation rates among the 7 loci between the lowest (a locus) and the highest (p locus) was 12-fold. Only 24% of procarbazine-induced specific locus mutations in As spermatogonia were lethal in the homozygous condition. From the mutation spectra and the viability tests, it is concluded that procarbazine-induced mutations may be mainly due to base-pair changes. Procarbazine-induced specific-locus mutations fulfilled the criteria for the estimation of the doubling dose, the dose necessary to induce as many mutations as occur spontaneously. The doubling dose of procarbazine in As spermatogonia of mice was 114 mg/kg. The therapeutic dose for procarbazine is about 215 mg/kg. If man and mouse were equally sensitive, this dose would induce 1.9 times as many mutations as arise spontaneously. From the incidence of patients with Hodgkin's disease (1 : 42 000) the calculated population dose of procarbazine is 5.12 micrograms/kg. Assuming equal sensitivity between the sexes we can calculate, for an estimated number of 30 000 genes, the induction of about 22 mutations per million children due to procarbazine treatment. The same number of induced mutations can be calculated if the risk of patients is used for the estimation of the genetic hazard.


Increased frequencies of aberrant sperm as indicators of mutagenic damage in mice.

We have tested the effects of TEM in 3 strains of mice using the sperm morphology assay. In addition, we have made an attempt to evaluate this test system with respect to experimental design, statistical problems and possible interlaboratory differences. Treatment with TEM results in significant increases in the percent of abnormally shaped sperm. These increases are readily detectable in sperm treated as spermatocytes and spermatogonial stages. Our data indicate possible problems associated with inter-laboratory variation in slide analysis. We have found that despite the introduction of such sources of variation, our data were consistent with respect to the effects of TEM. Another area of concern in the sperm morphology test is the presence of "outlier" animals. In our study, such animals comprised 4% of the total number of animals considered. Statistical analysis of the slides from these animals have shown that this problem can be dealt with and that when recognized as such, "outliers" do not effect the outcome of the sperm morphology assay.


Cis-platinum(II) diamine dichloride causes mutation, transformation, and sister-chromatid exchanges in cultured mammalian cells.

The anti-tumor agent cis-platinum(II) diamine dichloride caused dose-dependent toxicity in V79 Chinese hamster cells and in secondary Syrian hamster embryo cells. Chromosome aberrations were induced and positive dose--response relationships were observed for induction of sister-chromatid exchanges and 6-thioguanine-resistant mutations in V79 cells and morphologic transformation of secondary Syrian hamster embryo cells. The findings suggest that this chemical is a potential human carcinogen.


Private cost containment.

Physicians should recognize that a more competitive health-care market would provide the best defense against government regulation. Aside from group-practice health-maintenance organizations, the cost-containment steps that might be taken in such a market are not well understood. In particular, little attention has been paid to how private health insurers might redefine their coverage to limit the cost-increasing effects of third-party payment. Insurer-provider agreements negotiated in a competitive environment would seem to be especially promising. Competing insurance plans would be variously organized and operated according to provider and consumer preferences. Traditional doctor-patient relations as well as fee-for-service payment could be preserved. The antitrust laws, while curbing concerted effort to prevent change, should assure that physicians are not exploited by dominant buyers. Lucrative opportunities already exist for enterprising and efficient providers.


Frequency and clinical description of high-cost patients in 17 acute-care hospitals.

To assess the potential impact of national "catastrophic" health insurance on the medical-care system, the frequency and clinical characteristics of high-cost patients were surveyed at 17 acute-care hospitals in the San Francisco Bay Area. The percentage of patients whose yearly hospital charges exceeded $4000 in 1976 ranged from 4 at a community hospital to 24 at a referral hospital. Hospital costs charged to these patients ranged from 20 to 68 per cent of total billings, with the highest percentages generally occurring at large referral hospitals. Forty-seven per cent of adult high-cost patients had chronic medical conditions, and only one in six suffered from an acute medical "catastrophe." In addition, more than 13 per cent of high-cost patients died in the hospital. National catastrophic health insurance is likely to pay for much chronic illness and terminal care and divert resources toward acute-care hospitals.