An oculo-cardiac hypothesis of sudden unexpected death in infants. The oculo-cardiac hypothesis presented here draws attention to the evidence for links between Sudden Unexpected Death in Infants (SUD) - known in America as the Sudden Infant Death Syndrome, also as "cot death" or "crib death" - and the vagally mediated reflex slowing of the heart beat following pressure on the eye. A brief review is made of epidemiologic findings on SUD, including the fact that around 9000 infant fatalities per year are attributed to SUD in the U.S.A. alone. Evidence for excessive vagal discharge as a likely factor in SUD is discussed. The nature of the oculo-cardiac reflex discovered by Aschner is described, with particular attention to those factors which appear to make specific categories of sleeping infant more vulnerable to cardiac arrest in circumstances where this reflex is elicited. The factors include prematurity and an existing electrical instability of the heart. Regarding the manner in which such an oculo-cardiac reflex might in practice be set off, it is suggested that this could occur if the infant slept in such a position that the weight of the head could press the eye against any irregular surface which might exist on the mattress, or any object which was resting on the mattress. Evidence is cited for SUD infants being in fact more likely than controls to sleep in such a position. Children with exophthalmos would be more at risk in this respect. It is stressed that all this evidence is already published, but has not previously been drawn together to show the likelihood of a link between Sudden Dath and the oculo-cardiac reflex.


Glaucoma hypothesis: application of the law of Laplace. The objective of the proposed research is to design a test for anticipating glaucoma damage. In this project, the author is utilizing a mathematical equation defined by Laplace's law as applied to a hollow organ. Eye wall stress should be evaluated concomitantly with the intraocular pressure, in order to define the susceptibility of the eye to develop glaucoma. The idea presented in this paper allows for better understanding of different factors responsible for the pathogenesis of open angle glaucoma, of low pressure glaucoma, and of ocular hypertension. It allows one to predict how a given eye will react to a given pressure, that is, whether damage will occur or not. It might answer the question whether to treat right away, or wait and follow. It explains the higher prevalence of glaucoma in myopic eyes. It outlines easy, noninvasive, inexpensive preventive measures, which do not require new and costly facilities. The next step, in further elaboration of this project, should probably be to evaluate the relationship between the ocular pulse and pressure curve. This will be discussed and presented in the future.


Sources of energy for the brain and susceptibility to audiogenic seizures. The onset of susceptibility to audiogenic seizures (AGS) coincides with the draining of the ear canal at about 14 to 16 days of age. This is also when the mouse brain has almost attained its maximal size and weight, and also about the time of weaning from the dam's high-fat milk to the beginning of dietary self-sufficiency. During suckling, the brain is primarily dependent on ketone-body utilization as a source for brain energy; weaned mice use glucose. It is suggested that in AGS-prone mice, there may be a developmental lag in the onset of a sufficient rate of glycolysis in brain to provide adequate immediately available energy reserves to last through a brief period of an external-stimulus-induced large energy expediture until energy repletion processes can begin. As a results, ATP levels might fall below an hypothesized lower limit to subserve organized neural activity in some inhibitory area of the brain, resulting in the onset of an AGS.


Can elevated levels of copper in drinking water precipitate aucte hemolysis in G-6-PD deficient individuals? The hypothesis that elevated levels of copper in drinking water may be a factor in the precipitation of acute hemolysis in those with a G-6-PD deficiency in their erythrocytes is developed. The present U.S. EPA drinking water standards do not have a primary (or human health) standard for copper but only a secondary standard which is designed to prevent an unacceptable taste. Because of the widespread occurrence of elevated levels of copper in drinking water in areas where the water is corrosive and the households have copper piping, it is recommended that environmental health regulatory agencies develop a risk assessment concerning the effects of copper on those high risk groups who are predisposed to develop a copper induced hemolysis.


Hypercalcaemia in adult hospital population: comparison of inpatients of 1966 with those of 1976. During 1976, inpatients with hypercalcaemia at The Royal Melbourne Hospital were identified from the worksheets of the Department of Biochemistry and compared with those discovered in a similar study in 1966. In 1966, the estimation of plasma calcium level had to be ordered specifically, whereas in 1976, for technical reasons, the measurement of plasma calcium level was frequently performed when not requested. Despite a six-fold increase in plasma calcium in the rate of detection of hypercalcaemia. In both studies, malignant disease was the most common casue of hypercalcaemia, but primary common cause of hypercalcaemia, but primary hyperparathyroidism was found slightly more frequently in 1976. This study suggests that screening inpatients for hypercalcaemia is of little value.


Effect of smoking on the recurrence of malignant melanoma. Smoking has been recently shown to lead to aberrant immunological function in man. Since immunological host resistance is important in the natural history of human malignant melanoma, it was the object of this study to determine the effects of smoking on the course of this disease. Investigations on 1908 patients with malignant melanoma indicated that smoking renders men significantly more susceptible to developing metastases. The proportion of men smokers free of disease five years after melanoma diagnosis was significantly lower than that of men non-smokers. An effect of smoking similar to that recorded in men was not evident in women with malignant melanoma.


Premature rupture of the membranes.

Premature rupture of the membranes. In a consecutive series of 93 patients with premature rupture of the membranes at 20 to 34 weeks of gestation, the perinatal mortality was 23.7%. One-quater of the deaths were due to lethal congenital abnormalities, 18% were due to intrauterine infection, and 36% resulted from severe respiratory distress syndrome (RDS). Corticosteroid therapy increased the risk of incompetence, and did not reduce the incidence or severity of RDS. Almost one-third of the patients were delivered within 48 hours of membrane rupture; however, short-term treatment with salbutamol was able to delay the delivery for at least six days in 5 of the 13 patients to whom it was given. As postponement of delivery for days or weeks after the membranes have ruptured reduces the incidence and severity of Rds, this therapy may well have a place in the treatment of this condition.


Premature labour.

Premature labour. Intravenously administered salbutamol inhibited premature labour for at least 48 hours in 49 of 76 patients (64%), but was more effective (89%) when the cervical dilatation was less than 2 cm, and no apparent cause for the premature labour was evident. Even when premature labour complicated multiple pregnancy, hydramnios, or followed a small antepartum haemorrhage, suppression of labour could often be achieved for at least 48 hours, thus following the administration of betamethasone or the transfer of the patient to a hospital with intensive care facilities for both mother and child. Treatment with betamethasone, in addition to salbutamol, was associated with a less severe form of respiratory distress syndrome, and did not increase the risk of maternal or fetal infection, except in patients with cervical incompetence when 46.2% of such patients were infected.


Child abuse in the 24 hours after psychotherapy sessions. Six cases in which, unknown to the therapist, psychotherapy apparently initiated or exacerbated child abuse are reviewed. Once the connection between therapy and child abuse was recognized and pointed out to the patients, further therapy led to a significant clinical improvement. The necessity for additional support, such as is offered by Prevention, is emphasized.


Fitting below-elbow prostheses which convey a sense of touch. A myoelectrically controlled electric hand has been modified so that the gripping force between thumb and index finger may be measured. The measurement is used to control a sensory feedback device applied to the surface of the skin within the socket of the prosthesis informing the wearer of the strength of grip exerted. Two people have been fitted with this prosthesis and they report that the sensory feedback gives them reassurance when using the arm. To date there has not been any noticeable adverse tissue reponse from the applied sensory stimulus.


Bed occupancy by diabetic patients.

Bed occupancy by diabetic patients. The Royal Newcastle Hospital Diabetic Education and Stabilization Centre was instituted primarily to improve diabetics' understanding of their disease and its everyday management. Simultaneously with a five-day education course, stabilization if insulin-dependent diabetics was undertaken on an outpatient basis. In order to disseminate diabetic education as widely as possible, trained nurses from near and far were included in each course. It is believed that these nurses will be able to offer good advice to diabetics who have no other source of reliable information. By actively attempting to reduce hospital bed occupancy by diabetics there has been a reduction of 1400 bed days per year. It is recommended that similar centres be instituted throughout Australia.


Pelvic phleboliths: a study of 528 melanesian and white patients in papua new guinea. The prevalence of pelvic phleboliths was compared in 359 Melanasian patients and 169 white patients in Port Moresby, Papua New Guinea, and was found to be 12% and 51% respectively. The number and the size of phleboliths were also greater in white patients. These findings are similar to the data available from other parts of the world. The lower prevalence of pelvic phleboliths (and deep vein thrombosis) in Papua New Guineans may be related to their high fibre content diet, to their more active fibrinolytic system, or to both.


[Digoxin concentrations in plasma and tissue. A postmortal investigation (author's transl)]. Postmortal tissue digoxin concentration and prefinal and postmortal plasma digoxin concentrations from 9 patients were determined using the 125J-digoxin radioimmunoassay. The concentration of digoxin in the myocardium of the left ventricle was 61.44 +/- 45.17 ng/g. In the right ventricle the concentration was 36.78 +/- 33.11 ng/g. Higher digoxin concentrations were found in the right atrium (34.93 +/- 21.86 ng/g) than in the left atrium (25.43 +/- 14.57 ng/g). In plasma samples taken after death approximately 62% higher digoxin concentrations were found than in samples of patients in prefinal state. Histological examination revealed positive correlation between in the high varying digoxin concentrations and the pathological conditions of the tissue structure.


[Studies on the diuretic effects of etozolin (Elkapin) in heart failure - a comparison with the loop diuretic agent furosemide (author's transl)]. In 115 randomized patients with left and/or right ventricular failure, the effect of the new diuretic Etozolin (800 mg p.o.) (n = 55) is compared with that of the loop diuretic Furosemide (80 mg p.o.) (n = 60). 1. The increased diuresis after Etozolin remains constant during the entire trial period. Furosemid initially induces a more intense diuresis. 2. Analysis of the action profile shows that the higher daily urinary output following Furosemide is due to a more intense diuresis in the first fractions of the day. The action of Etozolin is more constant and lasts into the evening. 3. Both substances reduce body weight to the same extent. 4. Heart rate and arterial blood pressure decline significantly during trial. 5. Etozolin induces lesser electrolyte elimination than Furosemide in the initial phase of the trial. Potassium elimination values, in particular, remain below Na+ and Cl- elimination values for both substances. 6. During the trial period both substances had no significant effect on blood and liver values, serum electrolytes, creatinine, urea and uric acid. Etozolin may be classified as a diuretic similar to a thiazide derivative in its 24-h profile but behaves like a loop diuretic in its diuretic effect.


[Complication during the dipyridamole-test (author's transl)]. Performing the dipyridamole-test for evaluating coronary artery disease a man at the age of 57 years developed after application of 15 mg dipyridamole intravenously angina pectoris. For removal of angina pectoris 240 mg aminophylline were injected, after what bradycardia and finally cardiac arrest occurred. Resuscitation was successful. Possible reasons and some precautions were discussed.


[Replacement of mitral and aortic valve of a 12 years old boy (author's transl)]. Report of the case of a 12 years old boy, who because of acquired mitral valve insufficiency (grades II--III), after an illness of virus-carditis, became, in the first instance, a Bjoerk-Shiley-Ventil M27 prosthetic valvular replacement, and after 3 months, in one sitting, correction of a paravalvular leakage and prosthetic valvular replacement of the insufficient aortic valve with a Bjoerk-Shiley A23. The boy was well rehabilitated one year after the last operation. This is supported by the similar results of the echocardiographic, the ergometric and the pulmonary function tests carried out. The size of the replaced prosthetic valve makes the long time prognosis favourable. Double-valvular prosthetic replacement in children was hitherto carried out predominantly as a result of rheumatic diseases. The rheumatic process as well as congenital valvular malformation could surely be excluded in our patient so that the virus-process seems to be the most likely cause of the valvular defect.


[Rapid atrial stimulation in the treatment of atrial flutter (author's transl)]. Study on 35 patients suffering from atrial flutter, in which rapid atrial stimulation was made 40 times. Stimulation-catheters were introduced only by control of the intracardiac ecg without x-ray control. Sinus rhythm was restored in 31 cases, in 17 cases intermediate atrial fibrillation of varying length of duration. In 5 cases atrial fibrillation with normofrequent ventricular action was achieved. Appreciable complications were not seen. Essential advantages of the rapid atrial stimulation are the additional diagnostic information by the intracardiac ecg, the dispensable narcosis, the independence of a simultaneous medicamentous treatment, and the use in cases of sick sinus syndrome, too.


[Bronchial abnormalities in a clinic for respiratory diseases (author's transl)]. The frequency in bronchial abnormalities is generally underestimated. In patients of a clinic for respiratory diseases however 3% were found in those having had a bronchoscopy, a figure which has up to now not been mentioned in the literature. After discussing originating theories and classifying possibilities the observations are tabulated, and some of them introduced as representative examples. In the discussion it is pointed out, that the abnormalities apparently represent a locus minoris resistentiae, since pathological changes are often found in these areas.


[Early detection of bronchial cancer (author's transl)]. Compared with the results of a retrospective study (1954) of early detecting bronchial cancer, our present investigations showed, that females are relatively more concerned than formerly, that the climax of frequency has removed for about ten years to the aged, that more non-smokers are concerned than formerly (16% to 3.5% respectively) and that the time between manifestation of the first symptoms and admittance to hospital has shortened remarkably (one month 26%, three months 33% = 59% compared with 28.3%). In four patients the disease has been discovered by x-ray mass-screening, two of them were nevertheless admitted to hospital too late. Whereas the value of tomography has been established, the results of bronchoscopy ameliorated. Only one patient could be operated: perhaps the shift of age for one decade and a certain negative selection may be responsible for these disappointing results. The x-ray-examination in 2 levels must be performed in every adult male patient, even if bronchopulmonal symptoms do not exist. Moreover, exposed persons (e.g. strong smokers) must be controlled by x-ray examination in regular intervals. It is in this sense, that we see the scope of x-ray mass-screening.


[Thyrotoxicosis and sarcoidosis of the thyroid and the lung (author's transl)]. Clinical and pathological studies indicate, that sarcoidosis rarely affects the thyroid gland. The diagnosis of sarcoidosis in the lung and in the thyroid has been established by biopsies taken during surgery in a case of a 53 year old female. The manifestation of thyrotoxicosis in sarcoidosis-involvement of the thyroid has been analysed and compared with the 15 patients exhibiting sarcoidosis-involvement of the thyroid and thyrotoxicosis described in the literature.


[Transport of infants at risk (author's transl)]. We report upon a two-years experience with transportation of prematures, newborn infants and children up to two years of age. Most patients were prematures and newborn infants (1.38% of lifeborns in 1976 and 1.83% in 1977) out of the region of Aachen. They were transferred to the intensive care unit of the children's hospital (primary transport). 21.2% of them died. The mortality rate of all neonates, treated in the children's hospital, was reduced by 3.68% in comparison to the period before organized transportation system three years ago. The number of deceased was diminished by more than 40%. Some of the newborns remained in the maternity hospitals after first providing by the "transport-team". We also transported children up to two years of age with the mobile intensive care unit. Diagnostical and therapeutical procedures in other departments of the hospital of Aachen and other specialized centres became possible because of diminished risk.


[D-penicillamine in various diseases in childhood (author's transl)]. D-pencillamine, a stable not physiological amino acid, has a manifold mode of action. Of special importance there is its influence on the collagen-metabolism, the gelose of heavy metals and the effect on immunologic processes. The use of D-penicillamine is possible in different diseases, such as Wilson's syndrome, collagenoses of diverse kinds, especially the rheumatoid arthritis, further chronic hepatitis and lung fibrosis. In this paper we report about 52 children, who were treated with D-penicillamine. The biggest group presented chronic liver diseases in 24 patients and rheumaoid arthritis in 21 patients. The therapy was carried out for a longer time, in some cases over years. The dose varied from 15 to 35 mg/kg of body weight. The number of side-effects was lower in children than in adults. They were more frequent in the group of collagenoses than in the group of liver diseases. Whether later on liver damages will occur is not predictable by the pediatrician. The results were excellent for the chronic active hepatitis; we can recommend D-penicillamine for such affections. Also for the rheumatoid arthritis we could partially obtain good successes, but not as convincing as in liver-diseases.


Chromosomes and causation of human cancer and leukemia: XXXVI. The 14q+ anomaly in an American Burkitt lymphoma and its value in the definition of lymphoproliferative disorders. A case of a 10-year-old boy with American Burkitt lymphoma is presented in whom a 14q+ due to t(8;14)(q23;q32) was shown to exist in the ascitic lymphoma cells. This appears to be the first demonstration of such a translocation in uncultured material. In addition, another translocation involving the X chromosome, hitherto not observed in Burkitt tumors, was demonstrated. The karyotypic findings have been related to the cytogenetic experience in Burkitt and other lymphomas, with emphasis being put on the importance of the 14q+ anomaly in lymphoproliferative diseases.


Serial studies of serum dopamine-B-hydroxylase and urinary vanillylmandelic and homovanillic acids in neuroblastoma. Recent reports have suggested that elevations of serum dopamine-B-hydroxylase (DBH) activity may correlate with diagnosis in neuroblastoma patients excreting vanillylmandelic acid (VMA). We have serially studied serum DBH and urinary homovanillic acid (HVA) and VMA excretion during the disease course of five patients with neuroblastoma. DBH activities did not indicate clinical course, therapies, or prognosis. Dilution studies revealed an age-related alteration in DBH effectors and they suggest that these may be different in neuroblastoma.


Analysis of the significance of scattered radiation in reduced dose mammography, including magnification effects, scatter suppression, and focal spot and detector blurring. A systems analysis of reduced dose mammography with scatter removal has quantitatively specified the relationships between the several parameters in mammography systems. While the results are only preliminary in the sense that they need to be proven experimentally, they do seem to provide a good feel for the nature of the important trade-offs. The major uncertainties in the analysis probably have to do with the formal equivalence, that is implicit in the aperture theory, between large area and detail contrast, as well as the output versus focal spot relationship that was adopted. Also, there are important questions about specifying motion unsharpness as a function of exposure time in mammography examinations.


Effect of arm orientation on bone mineral mass and bone width measured using the Cameron-Sorenson technique. Bone mineral content and bone width were measured as the distal and midshaft locations in the right radius and ulna with the arm in different orientations. The values of mineral content, width, and the ratio of bone mineral content divided by width, determined at each bone site were compared to establish the effect of orientation. Seven orientations were studied, two of which involved rotations of the forearm and five of which involved rotations of the upper arm about the axis of the forearm. Rotation of the forearm was found to affect the values of one or more of the measured quantities at all of the sites. Orientation of the upper arm was found to affect the values of all quantities at the midshaft radius, but not to affect the values of any of the quantities at the other sites.


Stereo-photogrammetry for the determination of patient surface geometry. A stereo-photographic system has been developed with which surface contours of a human subject may be obtained rapidly and objectively. Nonmetric cameras are used and the results are obtained from direct measurements of the photographs. Software has been developed for interpretation of the photographic data with the assistance of a small computer and desk-top digitizer such as those routinely used in radiotherapy treatment planning. With the system the coordinates of a point on the subject may be determined with an accuracy of +/- 1-2 mm.


Attenuation in Lipowitz's metal of x rays produced at 2, 4, 10, and 18 MV and gamma rays from cobalt-60. Attenuation in Lipowitz's metal of x rays produced at 2, 4, 10, and 18 MV and gamma rays from cobalt 60 were measured to the 1% level with a narrow beam geometry. Blocks made from standard styrofoam mold (7.6 cm thick) would reduce these primary beams by 95% to 99%.


Quantum fluctuations in radiographic screen-film systems. With the recent introduction of fast rare-earth screens into the market, the question of noise and how it influences image quality becomes particularly important. In this paper a compact formula involving familiar and measurable quantities is derived for the specification of the noise arising from the spatial fluctuations of the x-ray quanta absorbed in the screens. Experimental evidence in support of this concept is also given.


Computer generated scatter dose distributions for 6-MV radiotherapy photon beams. The time required for accurate computer dose distributions is of major concern in radiation therapy. Isodose distributions were obtained by calculating the primary and scatter radiation reaching a point. A description of the primary dose distribution, especially at the edge of the beam, requires the calculation of the dose on a finely spaced grid. However, the scatter dose distributions can be described on a much coarser grid. The primary and scatter dose distribution calculations were separated into two computer subroutines which permitted choosing the appropriate grid spacing for each dose component. A more rational partition of the computing time for the primary and scatter dose was obtained. In addition, the separation of the calculation of the scatter dose from the total dose allows one to examine the calculated scatter dose distribution as the radial and angular increments used in the Clarkson-Cunningham summation are varied. Accurate scatter dose distributions were generated with a tenfold time reduction by optimization of grid spacing and radial and angular increments.


Radiographic quality, tube potential, and patient dose. Measurements were made to determine if there was an optimal kVp that would maximize radiographic contrast for various materials while minimizing average patient dose. Radiographs were made of a 17-cm-thick plexiglass phantom (to simulate a typical abdomen) with added regions of plexiglass, hydroxyapatite, and iodine with peak kilovoltages from 40 to 150 kVp and 2 mm A1 added filtration. Radiographs were also made of a 4-cm-thick plexiglass phantom to simulate a typical breast, with added regions of plexiglass, hydroxyapatite, and fat at a peak kilovoltage from 35 to 100 kVp and with 1 mm added filtration. For the thicker phantom it was found that the contrast per average absorbed dose for the added plexiglass, hydroxyapatite, and iodine increased by about 3, 2, and 0.4, respectively, when going from 50 to 150 kVp. Contrast was measured relative to a reference region on the phantom. Similar data for the thinner phantom showed an increase of about 35% in contrast per average absorbed dose for plexiglass and fat but a decrease by about 30% for hydroxyapatite as the kVp changes from 35 to 100 kVp.


Relative measurements of fast neutron contamination in 18-MV photon beams from two linear accelerators and a betatron. Fast neutron contamination in photon beams in the 20 MV range have been reported in recent years. In order to determine if the variations were due mainly to differences in measurement procedures, or inherent in the design of the accelerators, three different 18-MV (BJR) photon beams were compared using identical analytical techniques. The units studied were a Philips SL/75-20 and a Siemens Mevatron-20 linear accelerators and a Schimadzu betatron. Gamma spectroscopy of an activated aluminum foil was the method used. By comparing the relative amounts of neutron contamination, errors associated with absolute measurements such as detector efficiency and differences in activation foils were eliminated. Fast neutron contaminations per rad of x rays in a ratio of 6.7:3.7:1 were found for the Philips, Schimadzu and Siemens accelerators, respectively.


Application of information theory to the assessment of computed tomography. The imaging process has two fundamental stages: detection and display. The detection stage can be quantified rigourously using Shannon's information theory. This requires the contrast scale (CS), modulation transfer function (MTF), and noise power spectrum [N(f)] to be combined into a signal-to-noise ratio (SNR). This results in two fundamental summary figures of merit: the density of noise equivalent quanta (NEQ) in the image and the information bandwidth integral (IBWI). These algorithm-independent measures are used to quantify the recording stage. The display stage is less well understood since it couples to an external observer. Several types of decision makers are treated. Examples are drawn from first and second generation CT, demonstrating that thye are nearly quantum limited for large signals, indicating how their algorithms are matched or mismatched to the geometry, and calculating the contrast-detail diagrams for those decision makers.


X-ray depth-dose characteristics of the Toshiba LMR-16. The depth-dose characteristics of the Toshiba LMR-16 linear accelerator for 14-MeV x rays have been measured at an SSD of 100 cm using diodes and ion chambers. The surface dose and build-up depth both exhibit a considerable variation with field size. A new central axis model has been developed which takes account of these variations, and the agreement between the measured and computed data using this model is found to be excellent. Formulas are also presented to estimate the surface dose, buildup depth, and output factor as a function of field size.


Uptake of immune RNA by normal mouse spleen cells. Normal mouse spleen cells take up in vitro radioactively labeled immune RNA. RNA taken up is present in nuclei, polysomes, membranes and cytoplasm. About 20-40% of immune RNA is nonspecifically associated with cell surface. 45% of RNA taken up is degraded and reutilized inside the cells within 2 hours.


Purification and characterization of mouse glucose 6-phosphate dehydrogenase. Glucose-6-phosphate dehydrogenase was purified to homogeneity from testes and kidneys of the inbred strain of mice (DBA/2J) by a simple two-step affinity column procedure. This involved the sequential application of 8-(6-aminohexyl)-amino-AMP- and -2', 5'-ADP-Sepharose columns and biospecific elution with NADP+ in both steps. The molecular and biochemical properties of the purified enzyme were studied in detail. These include the molecular weight determination, amino acid composition, steady-state kinetics, inactivation by high temperature, urea and iodoacetate, and immunology. The purified enzyme from mouse kidneys or testes was shown to be a tetramer with a molecular weight of 220,000. The enzyme is highly specific for glucose-6-phosphate, exhibits almost no activity with NAD+ as a coenzyme and is little inhibited by AMP or ATP. Michaelis constants for glucose-6-phosphate and NADP+ were determined to be 50 microM and 10 microM respectively. NADPH is a competitive inhibitor of NADP+ and has a Ki of 18 microM. Rabbit antisera against glucose-6-phosphate dehydrogenase were raised. The antisera also cross-react with the same enzyme from human and guinea pig.


Synthesis of phosphatidly-dCMP in permeabilized normal human lymphocytes. When peripheral lymphocytes stimulated with phytohemagglutinin were permeabilized in vitro, (3H) dCTP acted as a precursor for DNA synthesis, but the formation of a compound soluble in organic solvents could also be demonstrated. The structure of the latter compound was studied analyzing the products formed after alkaline hydrolysis or an enzymatic treatment with nucleotide pyrophosphatase. Both treatments led to the formation of (3H)dCMP. When stimulated lymphocytes were labeled in vivo with (14C)glycerol before permeabilization and ulterior labeling with (3H)dCTP a double labeled compound was obtained. When this compound was submitted to alkaline hydrolysis, (3H)dCMP and (14C)glycerol-3-phosphate were obtained. It was concluded that the compound soluble in organic solvents was phosphatidyl-dCMP.


Polymorphism in fowl serum albumin. VI. Changes in in vitro protein synthesizing activity in developing embryonic fowl liver. Cell-free protein synthesizing systems were prepared from the livers of chick embryos at selected ages and the characteristics of individual fractions were compared. While polysomes showed decreasing size with older embryos, isolated polysomes did not differ significantly in amino acid incorporating activity when assayed with standard cell sap. When assayed with standard polysomes, cell sap activity decreased with increasing developmental age whether incorporation was measured using (3H)lysine, (3H)leucine, or [3H]aminoacyl-tRNA. Free amino acid concentrations in the cell sap showed reproducidble independent variation during development which was taken into consideration in calculating net amino acid incorporation. A larger increase in ribonuclease activity was observed during development; however, nuclease inhibitor activity was absent before day 15 but increased thereafter. Aminoacyl-tRNA sythetase activity did not vary significantly. It is proposed that the observed changes in the rate of cell-free protein synthesis result not only from increasing ribonuclease activity with increasing developmental age but also from changes in the activity of other soluble factors.


Growth hormone effects on creatine uptake by muscle in the hypophysectomized rat. Specific radioactive enzyme assays were developed to measure the effect of growth hormone on kidney transamidinase and liver methyltransferase in the hypophysectomized rat. In contrast to minimal changes (20%) in liver methyltransferase, kidney transamidinase was decreased threefold in the hypophysectomized rat. Enzyme activities were equal to normal values in those rats receiving growth hormone for three days. The formation of creatine from radioactive precursors and the uptake of 14C-creatine in muscle was examined under these conditions. After injection of 14C-arginine in the hypophysectomized rat, the 14C-creatine content of muscle was greatly decreased compared to sham operated controls and the 14C-creatine content was normal after growth hormone administration. After injection of 14C-guanidoacetate and of 14-creatine, the 14C-creatine content of muscle was decreased in the hypophysectomized rat, but was equal to sham control values in rats receiving growth hormone. These studies indicate that the uptake of newly synthesized creatine by muscle is impaired in the hypophysectomized rat and that growth hormone can have a role in controlling the rate of creatine uptake by muscle in addition to its effect on kidney transamidinase and to other factors involved in creatine metabolism.


The size distribution of poly(A) in newly synthesized and old Balbiani ring RNA. The size distribution of newly synthesized and old poly(A) sequences on transcripts of the giant tissue specific puffs, Balbiani rings in salivary glands of Chironomus tentans has been determined. After labeling with [3H]adenosine, poly(A) containing Balbiani ring RNA(75S RNA) was selectively collected by means of a recently developed technique. This combines electrophoretic fractionation and affinity chromatography in one run by insertion of poly(U) immobilized in glass fiber filters in an agarose gel slab. The majority of short-term labeled poly(A) chains released from poly(A) containing 75S RNA molecules is distributed within a narrow size range migrating as one peak with a mean value of 103 +/- 2 nucleotides, which is probably the initial length of poly(A). The labeling pattern of ribonuclease resistant poly(A) stretches after chase with unlabeled adenosine displays a relatively broad and heterogeneous size spectrum from at least 20 to more than 100 nucleotides. The main peak of labeled adenylate core in newly formed poly(A) containing RNA of non-Balbiani ring origin is dispersed within a broader size range than that of Balbiani ring RNA and possesses an average value of 94 +/- 2 nucleotides. During chase conditions, the relative frequency of occurrence of poly(A) chains of 75S RNA in the size range of 100 nucleotides exhibits a significant decrease in parallel with a rather uniform gain in the size classes between 20--50 nucleotides. However, the results are inconsistent with the existence of an age-dependent shortening of poly(A) chains in the balbiani ring RNA. A significant portion of 75S RNA molecules remain associated with poly(A) segments which are essentially of original size even after 21 hr in the presence of unlabeled adenosine. This finding provides support for the possibility that the initiation of the poly(A) shortening in 75S RNA is a stochastic process.


Postribosomal complexes containing eukaryotic initiation factor eIF-2. Eukaryotic initiation factors are found in the post-ribosomal subunits. We have analyzed the factor activities from the supernatant by means of zonal centrifugation followed by Sepharose-heparin affinity chromatography. They exist both as free factors, sedimenting in a broad range from 4 to 7S, and complexed with other protein(s) with a sedimentation value of 16-20S. This complexed fraction contains besides eIF-2 another activity which exhibits a profound stimulation on amino acid incorporation in crude lysates and appears to counteract the heme-regulated inhibitor.


Free cytoplasmic messenger ribonucleoprotein complexes from rabbit reticulocytes. Free cytoplasmic globin mRNA containing mRNP-particles were isolated from rabbit reticulocytes by zonal sucrose gradient centrifugation and their properties were compared with mRNP particles isolated in the same way from EDTA-dissociated reticulocyte polyribosomes. The average poly(A)-length of 9S mRNA from free cytoplasmic mRNP was 17-20 nucleotides being about two times shorter than the average poly(A)-length of polysomal 9S mRNA. The protein composition of the free cytoplasmic mRNP particles disclosed the absence of the 76,000 dalton protein which is associated with the 3'poly(A)-segment of polysomal globin mRNA. It was concluded that free cytoplasmic mRNP-particles from rabbit reticulocytes can be classified as "old" mRNP in a post-translational phase. Free cytoplasmic mRNPs were translated in heterologous cell-free systems as well as in Xenopus laevis oocytes. Addition of hemin stimulated the synthesis of alpha-globin in all systems, while the presence of the cap analogue m7G(5')p inhibited translation of free cytoplasmic mRNA completely. The latter finding suggested that free cytoplasmic mRNA has a 5' terminal "cap". Shortening of the poly(A)-segment with concomitant loss of the 76,000 dalton protein may lead to less efficient translation of free cytoplasmic mRNP.


Characterization of protein components of poly(A)-containing messenger ribonucleoproteins from cryptobiotic gastrulae of Artemia salina. Conditions for the isolation of intact poly(A)+mRNP from cryptobiotic gastruale of A. salina are described. In the presence of Mg2+ ions nucleolytic cleavage occurs in vitro in the vicinity of the 3'-poly(A) segment of mRNP during the isolation procedure. The resulting two parts of poly(A)+mRNP complex are separated by thermal elution from oligo(dT)-cellulsoe affinity column. Analysis by SDS-gel electrophoresis of protein components associated with intact poly(A)+mRNP has revealed the existence of 20--30 S RNP complex containing five major proteins with Mr 68,000, 53,000, 50,000, 45,000 and 38,000, respectively, but completely lacking the poly(A)-specific Mr 76,000 protein.


Regulation of albumin synthesis in rat liver. The present report reviews our findings on the subcellular distribution of albumin mRNA in rat liver under normal and abnormal physiologic conditions, the identification of albumin mRNA in specific mRNP complexes in liver cytosol of starved rats, and evidence fo albumin mRNA sequences in a higher molecular weight nuclear precursor to cytoplasmic albumin mRNA.


Is the cytoskeleton-plasma membrane complex involved in lens protein biosynthesis? Calf lens fiber cells contain a population of polyribosomes that direct, at least in vitro, the synthesis of a specific plasma membrane protein MP26. This protein may serve as a marker in terminal differentiation, since it is absent in the lens epithelium but appears in lens fiber plasma membranes. The MP26 manufacturing polyribosomes are found to be associated with a structural complex in which also the cytoskeleton and plasma membranes participate. They can be released from the complex by treatment with DNAse I. This result presumably reflects the involvement of actin in the linkage of the MP26 synthesizing polyribosomes to the cytoskeleton-membrane complex.


[Metabolically stable classes of nuclear messenger-like RNA. I. Detection and molecular characterization]. Two discreet in size molecular classes of metabolically stable messenger-like RNA molecules with sedimentation coefficientes about 28S and 18S have been revealed in the nuclei of pigeon bone marrow cells. The structural pecularities of 28S RNA class were investigated more carefully. It was shown to constitute the largest fraction of nuclear messenger-like RNA and is characterized by a GC/AU ratio 1.13. As pulse-labeled nuclear RNA, 28S stable nuclear RNA hybridizes with the unique and rare repeated DNA, it does not contain poly(A)-sequences and is found in a form of RNP particles with density of 1.41 g/sm3, tightly bound to chromatin.


[Bis-(2-guanidoethyl)-disulfide, when complexed with DNA, prevents its winding within the B-family]. Earlier we have shown that DNA forms stoichiometric complexes with bis-(2-guanidoethyl)-disulfide (GED), the helix being transformed from the B-like structure into the C-like one. The present work demonstrates that the DNA helix in the saturated complex does not change its conformation within a broad range of conditions: 0 less than [NaCl] less than 5.10(-2) M; 0% less than [methanol] less than 60% (v/v); 5 degrees less than temperature less than 50 degrees. Free DNA undergoes a non-cooperative winding within the B-family under all these influences. Increase in NaCl concentration beyond 5.10(-2) M results in abrupt cooperative unwinding from the C-like form to the B-like one, apparently due to GED dissociation. The obtained data are in accord with the idea that the conformational transition of DNA within the B-family is induced by change of phosphates interaction with the hydrated cations of alcaline metals; formation of strong hydrogen bonds of the phosphates with GED makes the DNA helix non-sensitive to variations of the environment.


[Conformation mobility of the universal acceptor end of tRNA]. The conformation analysis of tRNA acceptor fragment XCCA (X=A) was performed. The ribose conformation was taken rigid C(3')-endo. The optimum conformation was found for the ACCA fragment. It was shown that the omega, omega'-angle of the terminal adenine in any crystal modification of the yeast tRNAFen is not optimal. The conformation mobility of the 3'-end ACCA fragment was calculated in the vicinity of optimum conformation. Redundant energy required for keeping the correct 3'-terminal tRNA orientation about the enzyme catalytic centre during any small orientation distortions of the non-universal X-nucleotide relative to the enzyme was estimated. The distortions may occur when non-gomologous tRNA interact with aminoacyl-tRNA-synthetase. It was found that redundant energy for 3' displacement is very anisotropic and some small X-nucleotide reorientation may decrease the catalitic velocity of aminoacylation u0(4)--10(5) times.


[Conformation of the DNA molecule in alcohol-water solvents]. The influence of different alcohol-water solvents on the conformation of the native DNA molecule has been studied by the methods of flow birefringence and viscometry. The experiments have shown, that a certain content of the organic component induces a cooperative transition in the tertiary structure of the DNA molecule. The conformational transitions in the tertiary structure of DNA have been observed at low alcohol concentrations, corresponding to the desruption of the ordered spatial water structure and are caused by the alteration of the intermolecular interactions between the DNA and solvent molecules. The alcohol concentrations, corresponding to the observed transition, as well, as relative decrease of the intrinsic viscosity of DNA, depend on the chain length and branching of the hydrocarbon portion of the alcohols. The data on the optical anisotropy of the DNA molecule testify that the secondary structure of the latter doesn't change in a wide range of the alcohol concentrations.


[Nuclear RNP, containing pre-mRNA. XIV. Nature of particles, containing 5'- and 3'-end structures]. Some characteristic peculiarities of the 5'-end and 3'-end structures of pre-mRNA isolated from nuclear RNP particles have been investigated: presence of triphosphorylated nucleotides on the 5'-ends, as a characteristic of the primary product of transcription; presence of modified 5'-ends -- blocked and methylated structures -- caps; presence of poly(A) blocks attached to the 3'-end of pre-mRNA during post-transcriptional transformation of the latter. It was shown that pre-mRNA isolated from nuclear RNP particles contained triphosphorylated nucleotides as well as a "cap" structure at the 5'-ends. On the 3'-ends of pre-mRNA from nuclear RNP particles isolated in the presence of a RNAse inhibitor, the presence of poly(A) blocks have been shown. These poly(A) structures are separated very easily from pre-mRNA during mild RNAase digestion. This is the reason why they are not detected in 30S monoparticles, containing pre-mRNA fragments connected with one informofer. Almost all poly(A) complexes in this condition are combined with proteins and have the sedimentation coefficient of about 14S. It was concluded that formation of nuclear pre-mRNA containing RNP-particles take place just after the onset of RNA synthesis. All processing steps occur with pre-mRNA packed in nuclear RNP particles.


[Binding of muscle phosphorylase B by glycogen]. The binding of phosphorylase B with glycogen has been studied by means of analytical ultracentrifuge with absorption optics and a photoelectric scanner. Adsorbtion capacity for pig liver glycogen with respect to phosphorylase B (aM) and microscopic dissociation constant of enzyme -- glycogen complex (K) have been determined (aM = 3.64 . 10(-6) moles of bound enzyme per 1 g of glycogen: K = 2.6 . 10(-7) M at 12.7 degrees, pH 6.8). For oyster glycogen the value of aM is equal to 3.92 . 10(-6) moles of the bound protein per 1g of glycogen and K = 6.8 . 10(-7) M. The method of determination of microscopic Michaelis constant with respect to glycogen using known value of aM has been demonstrated.


[Peculiarities of the reassociation kinetics of fast repeating sequences of thermolabile fractions of hepatoma Zaidel DNA]. The six fractions of rat liver DNA (DNAL) and hepatoma Zaidel DNA (DNAHZ) were obtained by thermal fractionation of these DNAs on a HAP column at equivalent temperature intervals. The percent of two thermolabile fractions obtained at 62--78 degrees is approximately 10% higher for DNAHZ than for DNAL. The reassociation kinetics were carried out till Cot = 5.10(-1). Computer analysis of the kinetics showed considerable difference between the parameters (percent of the sequence and rate constant) only for these thermolabile fractions DNAL and DNAHZ. The two-fold reduction of the reassociation rate for the second thermolabile fraction DNAHZ (63--78 degrees) can be associated with the presence of short uncomplementary pieces in the fast repeating sequences. On the other hand the increase of the rate constant for the initial part of the kinetics reassociation of the first thermolabile fraction (62--73 degrees) of DNAHZ is due to the nicks which are revealed by alkali sucrose centrifugation of the DNAHZ fractions.


[Structure of nuclear pre-mRNA. XI. Triphosphorylated and blocked 5'-ends in the pre-mRNA]. The nature of the 5'-termini in pre-mRNA isolated from Ehrlich carcinoma cells has been investigated. To discriminate between triphosphorylated 5'-ends and capped structures different methods were used including treatment by alkaline phosphatase and several chromatographic methods. It was shown that heavey pre-mRNA contains a significant number of non-blocked triphosphorylated nucleotides at the 5'-end termini. However, phosphatase resistent, blocked 5'-termini were also found. 5'-terminal nucleotides in triphosphorylated pre-mRNA are G in a 3 : 2 ratio. In contrast to nuclear pre-mRNA cytoplasmic poly(A)+mRNA does not contain triphosphorylated 5'-ends but does contain the "cap" structure only. To elucidate the pre-mRNA topography the localization of homopolymeric regions of pre-mRNA, poly(A) and oligo(U), in relation to 5'terminal structures has been investigated. The experiments showed that the distance between 3'-terminal poly(A) sequences and 5'-end triphosphates is longer than 1500--2000 nucleotides. At the same time the distance between the latter and oligo(U) in pre-mRNA is much shorter.


[Steady state kinetics of DNA degradation with pancreatic deoxyribonuclease A in the presence of Mg2+]. Steady state kinetics of DNA depolymerisation in the presence of the DNAase A and Mg2+ ions were investigated at pH 5.5 and wide region of the enzyme, substrate and metal ion concentrations. A model, which is consistent with experimental results obtained is suggested. According to the model catalytically active form of the DNAase A should be a metal-bound enzyme. That species reacts with the metal-free DNA to form the Michaelis complex. The kinetics observed can be described in terms of mechanism which involves covalent enzyme-substrate intermediate formation. It was shown that the second Mg2+ ion binding to the complex Mg2+ DNAase -- DNA (KD - 2.2 . 10(-3) M) enhances the kinetic parameters of the reaction. To rationalise the effect one has to assume that the rate of the intermediate formation was accelerated as a result of the second Mg2+ binding.


[RNA synthesis and modifications of heart nuclear proteins during thyroid hormone deficiency]. RNA synthesis, correlation of various histones and acetylation and phosphorylation of the chromatin proteins were studied in the rat heart during monthly hypothyroidism. It was shown that [3H]uridine incorporation into heart RNA decreases considerably at hypothyrosis. The alteration in relative amounts of the histone H4 subfractions, which does not depend on the method of hypothyrosis reproduction (inhibition of thyroid function by 1-methyl-2-mercaptoimidazole, thyroidectomy) was detected by the method of analytical electrophoresis in 15% polyacrylamide gels containing 3.125 M urea and 0.9 N acetic acid. Increased incorporation of [32P]phosphate into histone fraction H2b and total fraction of acidic chromatin proteins was observed in vivo. Increased incorporation of labeled acetate into the total histone fraction and reduced incorporation into acidic nuclear proteins were obtained. It was shown that the increased incorporation of acetate into the total histone fraction was due to the increased acetylation of histones H3, H2b, H4 and acid-soluble chromatin proteins characteristic of tissues with a low level of replication. It is assumed that the observed changes of nuclear proteins reflect the process of chromatin reorganization caused by a prolonged deficiency of thyroid hormones.


[Electronic-conformational interactions of molecular-biological systems. II. Study of the enzyme-substrate complex with the help of qualitative methods of quantum chemistry]. The electronic-conformational interactions (ECI) of enzyme-substrate complexes are treated with the help of the method of intermolecular orbitals. The applicability of this approach is shown concerning some problems, related to ECI. The activation of N2 in the active site of nitrogenase, the proton transfer in the system, containing hydrogen bonds, and the modelling of the initial state of the reaction of lysozyme with oligosaccharides were examined.


[Interrelation of the electronic structure of nucleic acid components and their ability and specificity in template synthesis]. A hypotesis suggesting that the specificity of polynucleotide template synthesis is based not on complementarity but on the correspondence of the electronic structure of the precursor and the enzyme active site (EAS), the latter being formed by the template, enzyme, and, possibly, by the polynucleotide synthesized is described. Comparison of the electronic structure of natural nucleic bases and their analogs allows to suppose that the EAS discriminates between adenine and cytosine, and uracil (thymine) and guanine, by electrostatic features: sign of the potential in the region of exocyclic substituents at C(4) of pyrimidines and C(5) of purines. For adenine and cytosine this sign is positive while for uracil (thymine) and guanine it is negative. The second feature allowing to discriminate between purines and pyrimidines is connected with general difference of their electronic structure. The total charge of N-glycoside center, more negative for pyrimidines, can serve as an index of this difference. According to the hypothesis the compounds unable to form complementary pairs can be functionally active in the polynucleotide template synthesis and can show ambiguous functional specificity due not only to the presence of different ionic and/or tautomeric species but also to the potential in the aforementioned region being close to zero or the charge of N-glycoside center being intermediate. It can be assumed that for the formation of EAS the same features of the electronic structure of the nucleotide residues of the template are used, which are important for the interaction of the precursor with the EAS (recognition of the precursor).


[Single copy and repetitive nucleotide sequences in the genome of Echinodermata. II. Nucleotide sequence divergence of DNA of echinoderms]. The degree of divergence of short and long repetitive DNA sequences and single copy DNA of five Echinodermata species (sea urchins, starfish, sea-cucumber) was studied by the method of molecular hybridization. Different fractions of 3H-DNA of the sea urchin Strongylocentrotus intermedius were hybridized with the DNA of other species. Thermal stability of the hybridized DNA molecules was determined. The results obtained suggest that short repetitive sequences were most conservative during the evolution of Echinodermata. Single copy DNA fractions of closely related sea urchin species (S. intermedius and S. nudus) have more homologous sequences than long repetitive DNA fractions of the same species. The DNA of evolutionary distant species (sea urchin and starfish) have more homologous long repetitive sequences than the single copy ones. All DNA fractions of S. intermedius have sequences hybridized with the DNA of all other species studied: short repetitive sequences--55%, long repetitive sequences--20%, single copy sequences--12%.


[Globule size and the activation energy of an enzymatic process]. The charge transfer reactions demand the polar medium reorganization the main part in the process energy being contributed by solvent reorganization. Protein globule excludes a part of the solvent from the interaction with the charge being transfered. Thus a strong decrease of the reorganization energy and hence of the activation energy is achieved (the gain of some kcal/mole). The effect rises at first rapidly with the globule radius but it becomes practically constant after some optimal radius is reached. The estimation of the optimal radius gives values of the order of magnitude of the enzymes molecule sizes.


[Effect of temperature and degree of hydration on the mobility of spin labels in surface layers of proteins]. The mobility of separate sites of the water-protein matrix depending on temperature and degree of hydration has been investigated by means of spin labels covalently attached to surface layers of proteins (alpha-chymotrypsin and human serum albumin) and also by a spin probe in a hydrophobic "pocket" of human serum albumin. The results obtained are compared with the data on the mobility of gamma-resonance labels (57Fe) firmly bound with the protein matrix in the same samples. At certain temperature and degree of hydration both spin and gamma-resonance label show an increase in mobility. With the degree of hydration increasing one may observe a simultaneous increase in energy and in entropy of activation: rotatory diffusion of spin labels, i. e., a compensation effect takes place which confirms the concept expressed earlier that cooperation of water-protein interactions is the main reason of CEF. It should be noted that at P/PS greater than 0.8 the values of delta E =7 divided by 10 kcal/mole, and delta S not equal to = 9 divided by 11 e. e. are specific to glycerol-like systems, i. e., under these conditions (P/Ps greater than 0.8) the water-protein layer has glycerol-like properties.


[Synthesis and properties of nucleotide derivatives of poly(oligo)-L-lysine]. Nucleotide derivatives (epsilon-amino groups of lysine residues) of lysine residues) of poly(oligo)-L-lysine were synthesized. The structure of the resulting compounds in solution were studied by circular dichroism techniques. Week stacking interactions of the nucleotide bases on the polypeptide template were found to be characteristic of these compounds. It has been shown that the nucleotide derivatives of poly(oligo)-L-lysine are not involved in complementary interactions with the polynucleotides.


[Regulation of enzyme activity in adsorptive enzyme systems. II. Influence of dextran sulfate on catalytic properties of lactate dehydrogenase (isozyme M4)]. It has been shown that the binding of pig skeletal muscle lactate dehydrogenase (isozyme M4) by dextran sulfate with weight-average molecular weight 500 000 is accompanied by a decrease of the rate of enzymatic reduction of pyruvate. The hyperbolic dependence of the enzymic reaction rate on NADH concentration observed for free lactate dehydrogenase is transformed in a sigmoidal curve in the case of adsorbed enzyme form (Hill's coefficient is equal to 2.1). The experimental data have been described quantitatively using the model of adsorptive enzyme system where the enzyme interacts reversibly with the support and co-operative interaction of substrate binding sites in the adsorbed enzyme molecule are realized. It is assumed that the value of microscopic dissociation constant for the complex of the substrate with adsorbed enzyme is being changed by a constant factor during saturation of the binding sites by the substrate in the enzyme molecule. The value of parameters of the model for the adsorptive enzyme system under study are determined.


[Interfragmental interaction in peptide molecules]. Orbital and Coulomb terms in total energy of the molecule may be estimated with the use of parameters, that were calculated from experimental or estimated data for the test molecules. It has been demonstrated how the parameters for calculating the barriers of internal rotation in ethane-like molecules and amides may be selected. These parameters were used for studying the interactions between two peptide groups in 2-formamideacetamide--the primitive model of peptide.


[mRNA sequences complementary to the double-stranded regions of pre-mRNA. Hybridization experiments using RNA mercuriation and chromatography on sulfhydryl-Sepharose]. It was demonstrated that 4--6% of the sequences of mouse cell pure polysomal poly (A)mRNA are able to form stable duplexes during hybridization with the excess of double-stranded structures of nuclear pre-mRNA (double-stranded RNA). Hybridization of mRNA with the excess of mercuriated double-stranded RNA and chromatography of the hybrids on sulfhydril-sepharose was investigated. It was found that only 7--11% of the molecules of polysomal poly(A)+mRNA are able to form thermostable hybrids with sequences of double-stranded RNA. It may be supposed that in the population of mRNA there are relatively few molecules (about 5%) which contain sequences originated from long hairpin structures of pre-mRNA. Moreover, probably, there is a number of mRNA molecules (about 5% of the mRNA population) which are complementary in the entire length to "non-hairpin" double-stranded regions of pre-mRNA.


[Molecular mechanism of self-assembly of aggregated bacteriochlorophyll c]. The intermolecular interaction of bacteriochlorophyll c and its pheophytin was studied in nonpolar solvents and solid films with the aid of absorption and infra-red (in the region of 1800--1600 and 3800--3000 cm-1) spectra. The influence of water removing and its addition on these spectra has been investigated. Besides the effect of pyridine treatment and pigment concentration were examined. The self-assemblage of all types of bacteriochlorophyll c aggregated forms absorbing in the range 680--745 nm is due to the formation of intermolecular bonds in which keto groups of cyclopentanone rings take part. Keto groups form coordinate bonds with the central magnesium atom (keto-C = O...Mg). Hydroxyl groups interact coordinately with magnesium and simultaneously form hydrogen bonds with pyrrol nitrogen. In contrast to chlorophyll a and bacteriochlorophyll a, water molecules in the case of bacteriochlorophyll c do not participate in the intermolecular bond formation in the course of long-wave aggregated forms production. The thermostability of bacteriochlorophyll c aggregates and their rather high stability to desaggregating agents is related to the mentioned peculiarities of their structure. Bacteriopheophytin c in any state (solution or solid film) is not capable to form intermolecular bonds by its carbonyl groups and long-wave aggregates. The specific features of the assemblage of bacteriochlorophyll c aggregates modelling antenna of the green photosynthetic bacteria are discussed.


[Theoretical analysis of action of substrate analogs in dissociating enzyme systems]. The action of substrate analogue inable to catalytic conversion has been analysed in dissociating enzyme system of the type 2p in equilibrium with P (P is enzyme oligomer and p is its half). The regions of parameters corresponding to dependences of enzyme reaction rate (v) on substrate analogue (H) concentration with maximum are calculated. It is characteristic of dissociating enzyme systems that the appearance of maximum depends on enzyme concentration. It has also been demonstrated that at definite values of parameters and values of enzyme and substrate concentration the v versus [H]o plots may show an intermediate plateau, maximum and its preceding S-shape or maximum and minimum simultaneously.


[Selective modification of T7 DNA at the region of early genes by early RNA carrying multiple alkylating groups]. A method of selective modification of certain regions of the genome which may become useful for inactivation of certain genes or for directed mutagenesis is proposed. For this purpose RNA products of certain genes carrying alkylating groupings randomly distributed along the polymer were used. The RNA modified to an extent of 4--5 alkylating residues per 100 nucleotides retains the ability to specific formation of DNA--RNA hybrid complexes. The alkylating molecule is N,N,N'-tri-(beta-chlorethyl), N'-(p-formylphenyl)propylene diamine-1,3. The aliphatic alkylating functions serve for attachment to RNA. The aromatic alkylating function inactivated by the formyl grouping at the para-position of the benzene ring is used for modification of DNA after hybrid formation by reduction of formyl grouping with sodium borohydride. The covalently binding of modified RNA is exhibited to occur in only the case of T7 DNA H-chain, the one complementary to the RNA derivative. L-chain does not hybridize, nor does it undergo alkylation by the RNA product thus indicating high selectivity of alkylation within the hybrid complex.


[Secondary structure of RNA of influenza virus in free form and in ribonucleoprotein]. Large amounts of RNA and RNP isolated from influenza virus were obtained. This has allowed us to undertake detailed physical studies of the secondary structure of RNA of influenza virus in free form and in RNP. Analysis of CD spectrum and the hypochromic effect after thermal denaturation of RNA indicated that RNA in free form contains 58--62% double-stranded regions. By comparative studies of the secondary structure of RNA in RNP, it was estimated that 12--14% of the RNA exists in double-stranded form.


[Mobility of collagen structure and temperature adaptation of animals]. The method of hydrogen exchange is used to determine the mobility of acid-soluble collagen molecules from animals with different physiological temperature in terms of equilibrium constants of the formation of micro-unfolding or fluctuating defects of the structure. It has been shown that mobility of the collagen structure correlates with the physiological temperature of the animal from whose tissue collagen was isolated and is mainly determined by the amino acid content of the collagen. It has been shown also that at physiological temperatures characteristic for a particular species the level of collagen mobility is of the same order despite their different thermostability. The conclusion has been drawn that the level of mobility is the main criterion at the natural selection of the amino acid composition of collagens in different animals.


[Role of surface distribution of hydrophobic groups in the assembly of protein quaternary structure]. The method for two-dimensional representation of protein surfaces, based on the analogy with geographic map, and the algorithm for the search of the most favourable regions of izologous intermolecular interactions are proposed. It is assumed that the most favourable izologous interaction corresponds to an izologous contact of subunits which maximally dehydrates surface hydrophobic groups. The subunits are approximated by ellipsoids of revolution. The hydrophobic groups are assumed to be dehydrated if their C beta-atoms are inside the surface regions of the contacting ellipsoids inaccessible for contact with the sphere representing a water molecule. Using the proposed methods it is shown that for all izologous structures, known to atomic resolution, general shape of the molecule and distribution of hydrophobic groups on its surface: 1) provide a rough intersubunit recognition during assembly (deviation of the center of the experimentally localized contact region from the center of one of two-three regions obtained by us does not exceed 6--7 A); 2) choose only a few most favourable mutual orientations of the contacting regions; 3) can determine the pathway of the assembly.


[Treatment with immunocompetent cells and cellextracts (author's transl)]. The therapy of inborn or acquired defects of the cellular immune function is still in an experimental stage. Basicly, it is possible to replace the non-functioning T-cells by immunocompetent lymphocytes. Bone marrow, fetal liver and/or thymus, or cultivated thymus can serve as the source of such cells. Under certain conditions humoral factors derived from immunocompetent lymphocytes can induce a lacking immune response. Possibilities as well as limitations of these two therapeutic concepts are discussed.


[Cystometric investigations of neurogenic bladder-dysfunction in children (author's transl)]. Clinical and cystometrical studies were performed in 48 patients with myelomeningocele. From the clinical point of view four of the patients were completely continent. Fiften patients showed a so called "social continence" with periods of continence lasting for more than two hours (40%). Cystomanometric evaluations, however, revealed that there was a complete continence only in one of the 48 patients. Twenty-one patients showed a spastic or reflex bladder (44%), twentysix (54%) an adynamic bladder. The so called "social continence" could be observed as well in spastic-as in adynamic bladders. The most important parameters to realize neurogenic disturbances of micturition is the dyssynergia of the contraction of the detrusor muscle and the relaxation of the external vesical sphincter. Considering this, Stark's classification of adynamic and spastic bladders according to amplitude of the contractions of the detrusor muscle is helpful only in combination with the cystometrical and myographical datas of the bladder outlet.


[Quantitative determination of amino acids from blood-stained filter papers using high-performance thin layer chromatography and a TLC-scanner (author's transl)]. A method is described to determine amino acids by extraction from pieces of bloodstained and dried filter papers and following dansylation and separation by High-Performance Thin Layer Chromatography (HPTLC). Quantitative determination is possible by means of a TLC-Scanner measuring the fluorescent light of the dansylated amino acids. The possible use of this procedure as screening test is discussed.


[Salmonella-meningitis in the newborn (author's transl)]. Six children, out of twelve in a neonatal unit suffered from group D salmonellosis. Two patients presented in addition to intestinal manifestations massive extraintestinal symptoms, both with septicemia and meningitis. One patient died on the fourth day from massive disseminated intravascular coagulation and pyocephalus. The other patient had a complete recovery after an antibiotic therapy with chloramphenicol and ampicillin. As the source of infection the mother of case 1 was identified. In her stools salmonella group D were cultured. Cultures of the ward-personals, stool and the food were negative. It should be mentioned that only children fed with artificial food suffered from salmonellosis; whereas children on breastmilk had an unremarkable clinical course and consistantly negative stoolcultures.


Effect of cell growth rate and dose fractionation on chemically-induced  ouabain-resistant mutations in Chinese hamster V79 cells. Chinese hamster V79 cells were grown in medium containing either 10% or 2% FCS during the expression time following exposure to MNNG. The lower serum concentration was used to reduce the rate of cell replication, thereby allowing more time for DNA repair prior to "fixation" of the mutagenic lesion. In addition, fractionated and continuous exposures to MNNG and MAM, respectively, were carried out to determine their effect on the number of induced ouabain-resistant mutants. The results indicated that lowering the rate of cell growth effectively reduces the mutation frequency at low, but not at high doses of MNNG. Fractionated doses of MNNG result in a potentiation of their mutagenic effects compared to single doses. Also, continuous exposures to MAM result in an exponential increase in the mutation frequency. Collectively, these results suggest the importance of a repair process in Chinese hamster V79 cells which is dependent upon cell growth rate and the dose of the mutagen for its effectiveness.


Selectivity of the excision of alkylation products in a xeroderma pigmentosum-derived lymphoblastoid line. Lymphoblastoid cell derived from a complementation group C xeroderma patient were unable to remove 06-methyl guanine residues formed in DNA by treatment of cells with low concentration of N-methyl-N'-nitro-N-nitrosoguanidine (MNNG). The xeroderma cells were competent in their ability to excise 3-methyl adenine adducts. MNNG treatment induced excision repair in the xeroderma line and in addition the treatment resulted in the presence of numerous single-strand breaks in the DNA. The single gene, UV-excision-defective mutants of Escherichia coli, uvrA and uvrB, are able to excise MNNG-induced 06-methyl guanine adducts indicating that excision of this compound is not due to operation of UV endonuclease system.


Analysis of chromosome aberrations and sister-chromatid exchanges in human lymphocytes exposed in vitro to Hydergine. Hydergine (dihydroergotoxine mesylate, Sandoz) was examined for its capability to induce chromosome damage and sister-chromatid exchanges (SCEs) in human lymphocyte in vitro. For the chromosome-aberration study, cultures set up from 6 individuals were divided into 5 groups: negative control, positive control (caffeine, 0.5 mg/ml), and Hydergine (0.1, 0.25 and 0.5 micrograms/ml). For the SCE examination, which used 8 individuals, 4 cultures were made per person in the following way: negative control, positive control (mitomycin C, 0.1 microgram/ml), and Hydergine (0.1 and 0.5 micrograms/ml). Lymphocytes were cultivated for 72 h, being exposed to the respective treatments during the final 24 h. The results showed that Hydergine induced no chromosome damage in human lymphocytes in vitro.


Induction of sister-chromatid exchanges in human lymphocytes and Chinese hamster cells exposed to aflatoxin B1 and N-methyl-N-nitrosourea. The effect of a 1-h exposure to aflatoxin B1 (AFB1) in inducing sister-chromatid exchange in Chinese hamster ovary (CHO) cells and human lymphocytes in the presence or absence of mixed function oxidase ("S9 mix") was compared. CHO cells were also exposed to a graded series of doses of N-methyl-N-nitrosourea, a powerful inducer of SCE whose action was independent of the presence or absence of S9 mix. CHO and human cells showed a close correlation in response to SCE induction by AFB1 and in both cell systems the additon of mixed function oxidases in the S9 mix resulted in a marked enhancement of action of AFB1.


The cytotoxic, mutagenic and clastogenic effects of chromium-containing compounds on mammalian cells in culture. Examples of chromic and chromate salts have been examined for their effects on a cultured Chinese hamster cell line. The responses studied were cytotoxicity, mutagenesis and clastogenesis. Chromate (hexavalent chromium) salts of both high and medium water solubility were active in producing all three classes of response, whereas an insoluble chromate salt and a soluble chromic (trivalent chromium) salt were inactive. In addition to illustrating the value of using mammalian cells in culture for screening chemicals for biological activity, the results of this study reinforce current views regarding the genotoxic properties of chromates.


Platinum-induced mutations to 8-azaguanine resistance in Chinese hamster ovary cells. 6 platinum (Pt) compounds were compared in suspension cultured Chinese hamster ovary (CHO-S) cells with respect to their inhibition of growth, their reduction of cloning efficiency, and their induction of mutants resistant to 200 microM (30 micrograms/ml) 8-azaguanine (8-AG) and 3 mM ouabain (OUA), respectively. The toxicity of these compounds can be ranked by the medium concentrations which decrease suspension growth/or cloning efficiency by 50%: cis-Pt(NH3)2-Cl2 (0.9/1.5 microM) greater than Pt(SO4)2 + methylcobalamin (MeB-12) methylation product (20/10 microM) greater than K2PtCl4 (32/50 microM) = K2PtCl6 (34/50 microM) = MePtCl2-3 (60/50 microM) greater than Pt(SO4)2 (66/105 microM). Following 20 h exposures to concentrations which resulted in relative survivals of 80-2%, none of the foregoing compounds increased consistently the frequency of OUA(R) mutants above the spontaneous frequency (6.0 x 10(-6)). Parallel treatments with 800 microM (100 micrograms/ml) ethyl methanesulfonate (EMS) increased the OUA(R) mutant frequency 10--12-fold. Using 8-AG for mutant selection, dose-dependent increases of 5--7-fold above the spontaneous frequency (3--8 x 10(-5) were obtained with cis-Pt(NH3)2Cl2, Pt(S04)2, and the product from Pt(SO4)2 + MeB-12. Identical 20 h exposures to varying amounts of K2PtCl4, K2PtCl6, and MePtCl2-3 did not induce 8-AG(R) mutants. Optimal detection of Pt-induced 8-AG(R) mutants required 7 post-treatments, expression doublings in suspension culture. Under our selection conditions 8/8 spontaneous and 24/24 Pt-induced 8-AG(R) variants contained reduced hypoxanthine-guanine phosphoribosyl transferase (HGPRT) specific activities (means ranging from 3 to 11% of the parental CHO-S cells). When compared from linear plots of the 8-Ag(r) frequency against the initial medium concentration, cis-Pt(NH3)2Cl2 is 134 times and Pt(SO4)2 si 3.5 times more mutagenic than EMS. However, on a cell-survival basis EMS is 8--10-fold more mutagenic than these two Pt-compounds. 6-Thioguanine (10 microM) can be substituted for 8-AG to assay mutant induction by cis-Pt(NH3)2Cl2 and Pt(SO4)2 in CHO-S cells. The sensitivity of the CHO-S HGPRT locus for detecting mutagenesis by Pt complexes can be increased several fold by continuous subculture in the presence of these agents for 10--25 population doublings. By this procedure K2PtCl6 is seen to be weakly mutagenic and 20 microM Pt(SO4)2 produces 8-AG(R) mutants at frequencies requiring 7--8-fold higher concentrations when a fixed 20 h exposure is used.


Lack of evidence for cancer due to use of metronidazole. Experimental studies have shown that metronidazole is carcinogenic in rodents and mutagenic in bacteria. In 771 women given metronidazole for the treatment of vaginal trichomoniasis, more cancers developed than had been expected after exclusion of carcinoma of one uterine cervix (observed, 24 cases; expected on the basis of the Connecticut Tumor Registry, 21.7; expected on the basis of the Third National Cancer Survey, 18.4). However, the excess was not statistically significant (P greater than 0.05). The observed and expected numbers of breast-cancer cases were the same, but four lung-cancer cases were observed, whereas 0.6 would have been expected. This finding is confounded by the fact that all four lung cancers developed in women who were smokers. Overall, we observed no appreciable increase in cases of cancer.


Red-cell-membrane polypeptide aggregates in glucose-6-phosphate dehydrogenase mutants with chronic hemolytic disease. A clue to the mechanism of hemolysis. Red-cell membranes from patients with glucose-6-phosphate dehydrogenase deficiency were studied with polyacrylamide gel electrophoresis and gel filtration chromatography in sodium dodecyl sulfate. Membranes from each of five such patients who also had chronic hemolytic disease contained polypeptide aggregates within two molecular-weight ranges (4.4 X 10(5) and greater than 50 X 10(6) daltons). The 4.4 X 10(5) dalton aggregates were not detectable in red-cell membranes of patients with the enzyme deficiency without chronic hemolysis or in membranes from normal subjects, and the greater than 50 X 10(6) dalton aggregates were not found in appreciable amounts in these cells. The aggregates were dissociated by mercaptoethanol or dithiothreitol -- indicating that they were formed by intermolecular disulfide bonds. The polypeptide aggregates contained spectrin but not globin. Red-cell deformability was decreased in aggregate-containing cells. We postulate that the polypeptide aggregates are indicators of oxidant damage to the red-cell membrane, which results in decreased deformability and chronic hemolysis.


Prognostic value of exercise testing soon after myocardial infarction. The prognostic value of a limited treadmill exercises test performed one day before hospital discharge after acute myocardial infarction was studied in 210 consecutive patients who had no over heart failure and had been free of chest pain for at least four days. No complications occurred. During a one-year follow-up period 28 of 43 patients (65 per cent) who had chest pain during the test reported angina, as compared with 60 of 167 (36 per cent) who had no chest pain during test (P less than 0.001). The one-year mortality rates were 2.1 per cent (three of 146) in patients without changes in the S-T segment during exercise and 27 per cent (17 of 64) in those with depression of the S-T segment (P less than 0.001). Sudden death occurred in one of 146 (0.7 per cent) patients who showed no change in the S-T segment and in 10 of 64 (16 per cent) with depression of the segment (P less than 0.001). Thus, a limited treadmill exercise test performed before hospital discharge after acute myocardial infarction is safe and can predict mortality in the subsequent year.


Use of antimicrobial drugs in general hospitals: patterns of prophylaxis. The patterns of prophylactic use of antimicrobial drugs were reviewed in 5288 charts drawn by a random method from 20 randomly selected short-stay general hospitals in Pennsylvania. About 10 per cent of hospitalized patients received antimicrobial drugs for prophylaxis in operations or nonsurgical procedures, and prophylaxis accounted for about 30 per cent of all antimicrobial drugs administered in hospitals. The drugs used most often for prophylaxis were cephalosporins, followed by benzyl penicillins,  ampicillin and tetracyclines, in that order. Despite indications that prophylaxis, when useful at all, is effective only when given concurrently with and for 24 to 48 hours after operation, it was usually continued throughout hospitalization. Almost 80 per cent of prophylactic antimicrobial drugs were administered at least 48 hours after an operation or procedure -- suggesting that limiting prophylaxis to the first 24 to 48 hours, as currently recommended, would substantially reduce expenditures for antimicrobial drugs in hospitals.


Hepatitis after the transfusion of frozen red cells and washed red cells. The large-scale use of frozen red cells and washed red cells in this transfusion service has not been effective in reducing post-transfusion hepatitis. Seventy-eight per cent of 31,125 transfusions, excluding platelets and plasma, were given in the form of frozen or washed red cells. These transfusions were associated with 56 cases of hepatitis. In 37 cases, the recipients had received only frozen or washed red cells (or both). Post-transfusion hepatitis was of the non-A, non-B type in 95% of cases. On average, commercial blood accounted for 30 per cent of the donor base during the first four years and was involved in 44 of the 56 cases. Elimination of commercial blood from the donor base resulted in a decrease in the incidence of hepatitis from 2.1 to 0.3 per 1000 transfusions.


Natural history of bacteriuria in schoolgirls. A long-term case-control study. To define better the natural history of bacteriuria in females, we followed 60 schoolgirls with bacteriuria and 38 matched controls for periods ranging from nine to 18 years. Among the schoolgirls with bacteriuria (greater than or equal to 10(5) organisms per milliliter in two or more consecutive cultures), reflux was repaired in five, nephrectomy was performed in two, and reduced inulin clearance was noted in one subject with atrophic pyelonephritis. Serum creatinine was slightly higher in cases than in controls. Renal scars or caliectasis occurred in 16 cases but in none of the controls. Blood pressure was similar in both groups. Episodes of bacteriuria in cases and controls were, respectively: five or more episodes, 21.7 and 2.6 per cent; and episodes during pregnancy, 63.8 and 26.7 per cent. Seven children of the cases but none of the children of controls showed urinary-tract infections. Bacteriuria among schoolgirls defines a group at great risk of recurrent symptomatic infections and renal scars and at low risk of reduced renal function.


Quinidine-digoxin interaction: Pharmacokinetics, underlying mechanism and clinical implications. Administration of quinidine with digoxin increased serum digoxin concentrations in 79 patients and five volunteers. In 38 patients on a constant glycoside maintenance dose, the addition of quinidine to digoxin therapy resulted in a mean 2.5-fold increase (from 0.98 +/- 0.37 to 2.47 +/- 0.71 ng per milliliter, mean +/- 1 S.D.) (P less than 0.001). The addition of quinidine decreased renal glycoside clearance (from 91.6 +/- 27.8 to 40.6 +/- 15.8 ml per minute) (P less than 0.001). Unlike other investigations, our studies provided no evidence that quinidine displaced digoxin at specific cardiac binding sites. The elevated digoxin levels found during quinidine administration suggest a 30 to 50 per cent reduction of the digoxin dose. Adverse reactions to combined quinidine-digoxin therapy may be partly due to digitalis intoxication.


Effect of intrathoracic pressure on left ventricular performance. Left ventricular dysfunction is common in respiratory-distress syndrome, asthma and obstructive lung disease. To understand the contribution of intrathoracic pressure to this problem, we studied the effects of Valsalva and Müller maneuvers on left ventricular function in eight patients. Implantation of intramyocardial markers permitted beat-by-beat measurement of the velocity of fiber shortening (VCF) and left ventricular volume. During the Müller maneuver, VCF and ejection fraction decreased despite an increase in left ventricular volume and a decline in arterial pressure. In addition, when arterial pressure was corrected for changes in intrapleural pressure during either maneuver it correlated better with left ventricular end-systolic volumes than did uncorrected arterial pressures. These findings suggest that negative intrathoracic pressure affects left ventricular function by increasing left ventricular transmural pressures and thus afterload. We conclude that large intrathoracic-pressure changes, such as those that occur in acute pulmonary disease, can influence cardiac performance.


Mechanisms of edema formation in myxedema--increased protein extravasation and relatively slow lymphatic drainage. We assessed extravascular accumulation of albumin and fluid in primary myxedema by measuring metabolic turnover and transcapillary escape of 131I-labeled human albumin in seven patients. In the hypothyroid state, we found a low plasma volume (P less than 0.05), a reduced rate of albumin synthesis and catabolism (P less than 0.01), an increased transcapillary escape rate of albumin (P less than 0.01), a remarkable increase in the extravascular mass of albumin (1500 micronmol; P less than 0.01) and a longer mean transit time through the extravascular spaces in primary myxedema than in other states of generalized edema (P less than 0.05). All variables returned to normal during l-thyroxine treatment. The extravascular accumulation of albumin, and presumably of all other plasma proteins, is important in the generalized edema typically found in myxedema. Inadequate lymphatic drainage may also explain the formation of exudates in the serous cavities that are well known in myxedema.


[Does nutrition influence the propagation of neoplasms?]. In the last years, questions concerning the relationship between nutrition and the occurrence of neoplasms have been studied more intensively. The author discusses the possible involvement of water as a potential carrier of certain cylic hydrocarbons and radionuclides, and of nutrition per se. He treats problems related to, inter alia, bulk materials, polyethenoid fatty acids, the increase in fat consumption, trace elements, vitamins and the importance of the intestinal flora.


[Determination of aluminum in foods].

[Determination of aluminum in foods]. In connection with studies on the changes of functional properties of food constituents (e. g. solubility of proteins) by means of aluminium compounds, the elaboration of an appropriate method for the quantitative determination of aluminium has been necessary. The organic samples are mineralized with 80% perchloric acid; in case of fat-containing foods, after fat removal. After reaction with aluminon (ammonium salt of aurin tricarboxylic acid), aluminium is determined photometrically at 530 nm. The limit of detection lies between 1 and 2 ppm; the recovery rate is 103%; the standard deviation is +/- 10%. The determination (without mineralization) requires about 1 hours. The authors analyzed, inter alia, milk (1.2--1.7 ppm A1), fat cheese (9 ppm), micora (4 ppm), aluminium-stabilized protein texturates (300--1500 ppm).


[Milk proteins for food. I. Some aspects of the use of milk proteins for the protein supply to the population of the GDR]. Milk protein accounts for approximately 21% of the protein supply to the population in the GDR. All milk protein fractions have a high nutritional-physiological value and favourable functional properties. This notwithstanding, only 50% of the milk protein processed by the dairy industry are at present employed in human nutrition, the remainder is used as a provender. The reasons for this situation are discussed. Principles of procedures for the industrial production of milk protein concentrates are presented.


[Substrate specificity of a protease from Thermoactinomyces vulgaris]. The cleavage specificity of a protease from Thermoactinomyces vulgaris (thermitase) was determined by the insulin B-chain and the cleavability of casein and haemoglobin by this enzyme as compared to other proteases (trypsin, chymotrypsin, proteases from Bac. megaterium and cytophages). The most intense splitting effect on the substrates under investigation (insulin B-chain, casein and haemoglobin) is exerted by thermitase, i. e., the unspecificity of this enzyme is especially marked.


[Interactions of toxic trace elements with special regard to selenium]. The significance of the trace elements in nutrition is often decisively affected by the interaction of trace elements with other trace elements and of trace elements with other substances. These processes, which include synergistic and antagonistic effects, are of great importance not only to the essentiality, but also to the toxicity of trace elements. There is considerable experience with interactions of essential elements. There is considerable experience with interactions of essential elements or of elements in essential concentrations. On contrast, there is a scarcity of information pertaining to toxic effects that are influenced by synergisms and antagonisms. This situation is illustrated by some examples and especially by the role of selenium. It is shown that these problems deserve closer attention.


[Sweetness potency of saccharin and cyclamate in hot drinks]. The sweetness potency of sweeteners depends on temperature. At 50 degrees C the 2.4-fold concentration of saccharin and the 1.3-fold of cyclamate respectively is needed to produce the same sweetness (as related to sucrose) as in solutions at 20 degrees C. As well as in water the sweetening power decreases in chinese tea with increasing temperature. Only in case of cyclamate solutions of high sweetness this effect is diminished. In the mathematical description of the relation between stimulus and perception the decrease of the relative sweetness observed can be expressed by a comformable decrease of the concentration coefficient. The effect of temperature on the perception of sweetness can be explained by the Arrhenius' conception. The critical increments are 23 kJ/mol for saccharin and 8 kJ/mol for both cyclamate and fructose.


[Methodological bases of the nutritional-physiological assessment of the per capita consumption of foods. I. Recording and characterization of the per capita consumption]. Per capita consumption indices are reference points essential to the provision of foods and the planning of food consumption. From them global statements regarding the energy and nutrient supply can be deduced. But this requires the exact definition of the per capita consumption indices with regard to the recording level, subitems and average losses. The mode of calculation and the assortment of each of the presented food groups are characterized in detail and estimate values for the occurring losses are indicated which are needed for the nutritional-physiological balancing of the per capita consumption indices.


Statistical mechanics of supercoils and the torsional stiffness of the DNA double helix. The distribution of closed unknotted polymer chains over the writhing number is calculated by the Monte-Carlo method. For circular duplex DNA the variance of the distribution equals approximately half the observed variance of equilibrium distribution over the linking number. The balance which arises from fluctuations in DNA twisting makes it possible to estimate the torsional stiffness of the double helix.


Population biology of infectious diseases: Part I. If the host population is taken to be a dynamic variable (rather than constant, as conventionally assumed), a wider understanding of the population biology of infectious diseases emerges. In this first part of a two-part article, mathematical models are developed, shown to fit data from laboratory experiments, and used to explore the evolutionary relations among transmission parameters. In the second part of the article, to be published in next week's issue, the models are extended to include indirectly transmitted infections, and the general implications for infectious diseases are considered.


Population biology of infectious diseases: Part II. In the first part of this two-part article (Nature 280, 361--367), mathematical models of directly transmitted microparasitic infections were developed, taking explicit account of the dynamics of the host population. The discussion is now extended to both microparasites (viruses, bacteria and protozoa) and macroparasites (helminths and arthropods), transmitted either directly or indirectly via one or more intermediate hosts. Consideration is given to the relation between the ecology and evolution of the transmission processes and the overall dynamics, and to the mechanisms that can produce cyclic patterns, or multiple stable states, in the levels of infection in the host population.


The amino acid sequence of the alpha-chain of human fibrinogen. The amino acid sequence of the human fibrinogen alpha-chain reveals a structure that can be divided into three zones of unique amino acid composition. The middle of these contains the two primary alpha-chain cross-linking acceptor sites and consists of a remarkable series of internal duplications.


Temperature-dependent X-ray diffraction as a probe of protein structural dynamics. X-ray diffraction at four temperatures from 220 to 300 K coupled with crystallographic refinement yields the mean-square displacements and conformational potentials of all 1,261 non-hydrogen atoms of metmyoglobin. The results are interpreted to indicate a condensed core around the haem, semi-liquid regions towards the outside and a possible pathway for ligands. It is concluded that X-ray diffraction can provide the spatial distribution of the dynamic features of a protein.


Crystallographic studies of the dynamic properties of lysozyme. The patterns of atomic displacements in the crystals of hen and human lysozyme derived from independent crystallographic refinement are broadly similar. Analysis of the pattern indicates a close correlation with molecular structure, strongly suggestive of intramolecular motion. The active site of lysozyme is located in a region of high displacement. It is concluded that protein mobility may play a significant part in biological activity and that X-ray crystallography can contribute to its analysis.


[Participation of the lateral geniculate body in color discrimination in cats]. Responses of the lateral geniculate units to different wave length stimuli were studied in immobilized cats. The studied units were divided into two groups. Those of the first group (44%) produce high-frequency spike discharges which are not modified when the wave length of stimulus changes. Statistically significant differences are found in the unit responses of the second group (51%) to different wave length stimuli. A possible inhibitory influence of the first group units on those of the second group is suggested. The possible significance of this influence in the colour vision is discussed.


[Statistical analysis of the functional features of cat motor cortex neurons]. Recordings were made from 366 neurons situated in the motor area of m.biceps in the cortex of 6 cats trained to make instrumental placing reaction and to accept manipulation of the joints and natural cutaneous stimulation of the forelimb. From 160 neurons whose discharges changed during placing reaction performance 52 (32.5%) were demonstrated to receive an input from peripheral receptors in the forelimb. In contrast only 7 (3.4%) neurons in the group not related to the movement received such an input. From 160 neurons 31 changed discharge before movement onset, 59 after movement onset, and 70 before and during movement. Correlation between functional types of the neurons and their peripheral inputs was found.


[Functional characteristics of connections: Schaffer's collaterals to the CA1 field of the hippocampus in experiments in vivo and in vitro]. Comparative analysis of functional characteristics of connection between the fields CA3 and CA1 (Schaffer's collaterals) was performed in experiments in vivo (unanaesthetized rabbits) and in vitro (hippocampal slices of guinea-pigs) with extracellular recording of the unitary activity in the field CA1. Weakness of postexcitatory inhibition, absence of responses of the form of suppression of spontaneous activity, higher effectiveness of low-frequency stimulation of Schaffer's collaterals were observed in experiments in vitro. Posttetanic effects were more frequently observed and lasted longer in vitro than in vivo. The dominating effect in vivo was posttetanic depression and in vitro--posttetanic potentiation. The possible reasons for these differences are discussed.


[Demonstration of the sources of several descending forebrain systems using the horseradish peroxidase retrograde axonal transport technic]. Cells of cortical and diencephalic fibres descending to the mesencephalic and bulbar reticular formation and to the dorsal column nuclei were identified. According to findings neurons sending fibres to the mesencephalic reticular formation are located in orbitofrontal pole and in area 6 of the pericruciate cortex, mainly ipsilaterally. Neurons which distribute fibres to the bulbar reticular formation are concentrated mainly in area 6 and 4 of the both hemispheres, while those distributing fibres to dorsal column nuclei are arranged in areas 1, 2, 3 and 4, mainly contralaterally. Fibres descending to reticular formation from the limbic cortex, septum, substantia innominata and amygdala were also found. The functional significance of the investigated descending pathways of forebrain is discussed.