Circulating suppressor cells in aplastic anemia. In vitro proliferation and differentiation of hematopoietic stem cells was studied in a patient with aplastic anemia. Prior to therapy his peripheral blood contained a very low number of myeloid progenitors but a normal number of cells forming lymphoid colonies. Moreover, peripheral blood lymphocytes of this patient were able to suppress in vitro formation of myeloid colonies but not lymphoid colonies. This suppression effect was found to be sensitive to prednisolone and antithymocytic globulin. Following treatment with prednisolone, during which an apparent hematological recovery was observed, the level of lymphoid progenitors fell, but myeloid committed cells returned to normal and hematopoietic suppression was no longer detectable. These results indicate that cells suppressing hematopoiesis may circulate in the peripheral blood of some patients with aplastic anemia and the detection and testing of suceptibility of these cells to immunosuppressive drugs may be helpful in monitoring treatment and prognosis.


[Effect of platinum and palladium compounds on mitochondrial enzymatic systems]. Effect of platinum and palladium complexes on respiration and ATPase activity in bovine heart tissue as well as on respiration of submitochondrial particles was studied. The highest inhibitory activity was exhibited by the complexes of platinum and palladium with pi-ligands in internal coorhdinational sphere such as ethylene-C H4, norbornadiene-C7H8 and allyl-C3H5. The electron density at the central atom of the complex was not responsible for the inhibitory affect of platinum and palladium on mitochondria.


[The value of different investigation procedures in arterial hypertension (author's transl)]. 221 patients with arterial hypertension were investigated as outpatients. 198 patients were found to have primary and 23 patients to have secondary hypertension. The results of urinary analysis were pathological in 25% of patients and renal function tests were abnormal in 20% of cases. Significant bacteriuria was recorded in 19% of urinary cultures. Intravenous pyelography showed true pathological findings in 12% of cases, false positive findings in 7% and false negative findings in 5%. Isotopic nephrograms showed true positive findings in 52%, false negative in 3% and 45% showed normal results. In 53% of patients angiography of the kidneys showed normal results, whilst this investigation proved pathological in 44% of cases and gave false negative results in 3% of patients. An additional search for coronary heart disease risk factors revealed that 73% of these hypertensive patients were overweight, 47% had hyperlipidaemia, 33% suffered from diabetes mellitus and nicotine abuse was present in 21% of cases. A relevant yet inexpensive screening programme for the investigation of hypertension is formulated on the basis of the results of this investigation.


A viscosity model of polyacrylamide gel electrophoresis. In current theories of polyacrylamide gel electrophoresis, the idea prevails that molecular sieving relies on different accessibility of volume fractions and of cross-sectional area fractions (denoted "pores") to different-sized ions due to the effect of "geometric exclusion". This correlates with the assumption that all elements of a polyacrylamide network occupy fixed and unchangeable positions thus forcing colliding macro-ions to diffuse laterally in order to find an "accessible pore" and to resume motion in direction of the electrical field. However, the alternative conception would be equally well justified, i.e. the assumption that polyacrylamide chains represent smooth obstacles cleared aside under the electrokinetic pressure of a macro-ion. This explanation would even be preferable with respect to the molecular sieving effects occurring in solutions of "liquid polyacrylamide". Yet no theory exists as to describe such effects in quantitative terms. In the present article, a parameter is defined and discussed, which can be estimated by experiment, and which seems to be apt to characterize local resistivity of polymer structures against dislocation and deformation: the "fractional specific resistance". Definition of this parameter is based on the model of a "viscosity-emulsion" composed of two interpenetrating liquid compartments which are characterized by different levels of hydrodynamic friction and the spatial dimensions of which are inferred from Ogston's theory. This concept of "localized viscosity" may also serve as a link between theories of molecular sieving and of "macroscopic viscosity" of flexible polymers. The data of Morris, formerly taken as verifications of the "rigid-pore" concept, are now interpreted in terms of four factors responsible for sizediscrimination: collision frequency, duration of single contacts, size-dependent frictional force, and the extent of cooperation among fibres, due to crosslinking and to simultanous contacts of several fibres to a single macro-ion. Some functions relevant for problems of molecular weight determination by gel electrophoresis are discussed in relation to the suggested model.


Inhibition of the nitrate reductase complex by dibromothymoquinone. The plastoquinone antagonist 2,5-dibromothymoquinone was found to inhibit NO-3 reduction from NADH by the nitrate reductase complex from wheat. It accepts electrons from NADH through the NADH dehydrogenase activity of the nitrate reductase. However, it does not inhibit the reduction of 2,6-dichlorophenol-indophenol by the enzyme. This suggests that the two compounds may be accepting electrons at different places from the enzyme. Further it was observed that reduced DCIP could be oxidized by DBMIB in the absence of NADH indicating that the electron flow in the nitrate reductase complex may take place in a unidirectional way.


5-Methyltryptophan resistant cells of Catharanthus roseus. Several cell lines resistant to 5-methyltryptophan were selected from wild type cells of different Catharanthus roseus suspension cultures. The resistant cells had up to 30 times the normal levels of free tryptophan. Despite the increased pool size of tryptophan anthranilate synthetase activity of resistant cells was as sensitive to inhibition by L-tryptophan as wild type cells. The overproduction of tryptophan did not lead to intensified accumulation of tryptamine nor of indole alkaloids. This was supported by a low conversion of tryptophan to tryptamine in vivo and in vitro. The overproduction of one of the primary precursors was evidently not sufficient to stimulate the rate of indole alkaloid synthesis in Catharanthus cells.


Complex influence of cytochalasin B on actin polymerization. In the presence of very low concentrations (about 2X10(-7) M) of cytochalasin B (CB) the time course of actin polymerization is much more sigmoidal when followed by viscosity measurements than when followed by light scattering measurements. This suggests that under these conditions actin polymers do not immediately reach their final length but only via short "bent" polymers which can be detected only by light scattering but not by viscosity measurements. At higher CB concentrations (about equimolar to those of actin) CB reduces the average degree of polymerization and favors the nucleation step necessary for polymerization.


[Distribution and enzymic hypermethylation of inverted DNA repeats in different murine and human cells (author's transl)]. A specific class of DNA sequences, the inverted repetitive sequences, forms a double-stranded structure within a single linear polynucleotide chain in denatured DNA. The reassociation process is unimolecular and occurs very fast. Quantitative analyses have shown that these sequences comprise about 4--5% of the nuclear DNA of various mammalian cells (P815 mouse mastocytoma, Hela, L cells, Raji and Chang cells, and human embryonic hepatocytes) and are interspersed within sequences of other degrees of repetitiveness. After labeling the cells with L-[Methyl-3H]methionine and [14C]deoxycytidine, relative rates of enzymic DNA methylation were computed on the basis of 3H and 14C radioactivities found in pyrimidine residues of the nuclear DNA. The results indicate that DNA of inverted repetitive sequences is methylated to a level about 50% higher than the ordinary repetitive sequences and to about 300% higher than the unique and intermediary sequences. The biological function of the inverted repeats as well as the role of their enzymic hypermethylation is unknown.


[gamma-Irradiated ribosomes from Micrococcus radiodurans in a cell-free protein synthesizing system (author's transl)]. gamma-irradiation inactivation of isolated ribosomes of Micrococcus radiodurans was studied by examining poly U directed synthesis of polyphenylalanine. Ribosomes of M. radiodurans did not show significant gamma-radiation sensitivity up to a dose of approx. 11.6 k Gy. Cells of M. radiodurans take up more magnesium than E. coli cells unter the same conditions. The magnesium content of ribosomes of M. radiodurans was 18% higher than that of E. coli ribosomes. A possible relation between Mg2+-content and gamma-resistance is discussed.


[Biological effects of electromagnetic fields (author's transl)]. This résumé deals with thermal and nonthermal effects of electromagnetic fields on man. In consideration of two aspects a limitation is necessary. Firstly, there will be discussed only direct and immediate influences on biological cells and tissues, secondly, the treatment is limited to such phenomena, for which biophysical aproximations, based on experimental data, could be developed. Hazards for the human being may occur only by thermal effects within the microwave range. Regarding frequencies below approximately 30 kHz, excitation processes cannot be excluded in exceptional cases. Thermal effects are predominant, between 30 kHz and 100 kHz, before excitations can appear. Furthermore, by comparing the electrically and magnetically induced currents with the naturally flowing currents in man caused by the brain's and heart's electrical activity, a "lower boundaryline" was estimated. Regarding electric or magnetic field strengths undercutting this boundary-line, direct effects on the central nervous system may be excluded; other mechanisms should be responsible for demonstrated biological effects. The paper closes referring to some reports--presently discussed--on experimental findings of biological effects, which are observed as a result of the influence of electromagnetic fields of small field strengths.


Algal ferredoxin-NADP+ reductase with different molecular-weight forms. Ferredoxin-NADP+ reductase from the microalga Bumilleriopsis was isolated by a combination of affinity chromatography on a flavodoxin-Sepharose 4 B column and usual purification procedures. Both the elution pattern of the final gel filtration step and of the sodium dodecylsulfate (SDS) disc gel electrophoresis indicate that there are at least two different molecular-weight forms of the reductase, a monomeric form and a dimeric one.


A deterministic model for measles.

A deterministic model for measles. A deterministic model of recurrent epidemics is constructed using a non linear relationship between infection rate and number of contacts. Epidemic waves which are not damped are predicted and a relationship between community size and the period of recurrence is established. A possible explanation of measles outbreaks is suggested.


[All-or-none behaviour and bistability in a simple cell model with autocatalysis of type A+2B = 3B (author's transl)]. Nonlinear kinetics in a chemical cell model involving only one substrate (A) and one product (B), two reactions (A yields B and A + 2B yields OB), and passive diffusion of A and B through the cell wall, can exhibit complex behaviour including oscillations, bistability (switching) and spiking. One such system is presented, which shows three kinds of response as depending on the quantity of a stimulus--a sudden imput of product B: i. no response; ii, spiking; iii, switching into an alternative steady state--i.e. an "all-or flip-or-none" response.


Phenylethylamine as a biochemical marker of tiger. Pheromones of the tiger happen to be a mixture of amines which are "fixed" by lipids. One of these, found always in all the four tigers investigated, is phenylethylamine. This may be a biochemical marker at a species level.


[Development of gingival inflammations in schoolchildren instructed in proper oral hygiene in a seven-year longitudinal study conducted under clinically controlled conditions and as part of the Preventive Stomatology research project (author's transl)]. Instruction of six- and seven-year-old children (N = 1167) at the beginning of this longitudinal study was given by a stomatological nurse at weekly intervals and, later, at fortnightly and monthly intervals, respectively. Compared with a group of untreated controls were not only those children who were instructed in proper oral hygiene but children receiving additional doses of amine fluorides as well. During the seven-year period of observation there was noted a distinct improvement in oral hygiene (OHI) as well as a reduction of gingival inflammations (PM index). Whereas additional administration of amine fluorides had no appreciable effect upon both oral hygiene and the condition of health of the gingiva there was a direct relation to the frequency of instructions in oral hygiene at school.


[The systemic circulation and microcirculation of the periodontium vital microscopy and histological studies of incisors of rats (author's transl)]. A new classification of the angioarchitecture and blood flow is proposed in light of the results of vital microscopy studies of the windowed periodontium and gingiva of the incisors of rats. The flow pattern and the rate of blood flow are different in different vessels. The flow of blood in segmented and interconnected arterial and venous vascular sections in the alveolar and marginal periodontium corresponds to what is known as systemic circulation, whereas that in arterioles, capillaries, and venoles must be considered as belonging to what is referred to as microcirculation. Subepithelially, the microcirculatory elements constitute a nutritive, typically ordered capillary network as contrasted with the random spatial arrangement of capillary loops in the alveolar periodontium. Numerous anastomoses provide the basis for possible functional adaptation, leading to the formation of polygonal ring closures in the alveolar region. The interpretations of functional findings are based upon histotopological reexaminations.


[The effect of aging upon the size of cell nuclei of the spinous layer in the bony palate and cheek of man (author's transl)]. The volumes of the cell nuclei of the spinous layer of the human oral mucosa show considerable variations in dependence upon both the process of aging and the cellular metabolism. The differences in the mean volumes of cell nuclei are fairly large for the bony palate as well as the cheek, and statistical evidence has been obtained for these. Stomatologically, this investigation may be regarded as having broken new ground and will add to our understanding of the aging of human organs of mastication.


[On the clinical aspects and ultrastructure of bullous pemphigoid (parapemphigus) of the oral mucous membrane (author's transl)]. Bullous changes in the oral mucosa are often the first signs of a general dermatological disease. Successful diagnosis of such diseases is largely dependent upon the use of complex laboratory methods. Clinical and ultrastructural changes are described and discussed with particular reference to a case of parapemphigus. Atypical intracellular vacuolation and marked acantholysis observed in electron micrographs is interpreted as a secondary phenomenon of direct blistering.


[Effect of a decrease in brain noradrenaline and serotonin levels on defensive and food-getting conditioned reflexes in rats]. The influence of pharmacological and surgical interferences in the activity of serotoninergic and catecholaminergic brain systems on elaboration and consolidation of conditioned reflexes was studied in rats. Ablation of the locus coeruleus, nucleus raphe and administration of inhibitors of monoamines synthesis reduced noradrenaline and serotonin (5-OT) content in rat's brain. Ablation of the locus coeruleus and disulphiram administration impaired mainly the elaboration of defensive and alimentary conditioned reflexes. Ablation of the nucleus raphe and parachlorphenilalanin administration affected predominantly the retention of the reflexes. At the same time, the effects of surgical and pharmacological interferences differed in some respects


[Experiences obtained with the use of schulte's diagnostic program in myoarthropathies (author's transl)]. Using Schulte's diagnostic and therapeutic system of treating the pain-dysfunction syndrome, 165 patients were included in a program of myogymnastic self-treatment. The results obtained on reexamination of 96 patients confirmed the correlations observed by Schulte between the principal symptoms (painful side and lateral deviation of the lower jaw) and numerous causal factors. The diagnostic schemes used to search for causal factors may thus be regarded as having proved successful. They allow functional temporomandibular complaints to be classed in groups of diseases by taking into account the principal symptoms alone, namely, painful side and deviation of the lower jaw upon opening the mouth.


[Method of measuring soft part pressures in the oral cavity (author's transl)]. For measuring static and dynamic soft part pressures within the oral cavity, it is necessary to use specialized transducers and a suitable measuring method. The design of strain gage type pressure measuring probes is descirbed and problems of calibration and elimination of measurement errors are discussed.


[On the determination of Gm(1) in hard dental tissue (author's transl)]. Tests for the presence of Gm(1) substance were made on a total of 104 human teeth. In about 90 percent of the cases examined, it was possible to observe agreement between the serum and the Gm(1) substance. Lack of eluted dental material and a high degree of affection with caries were found to have adverse effects upon Gm(1) typification. Detection of the Gm(1) substance is another important characteristic in forensic identification.


[Importance of laparoscopy to postoperative treatment of ovarian carcinoma (author's transl)]. Indications in favour of peritoneoscopy in postoperative after-treatment of ovarian carcinomas are proposed on the basis of the authors' own experience. Postoperative laparoscopy in combination with peritoneal cytology and histology appears to be justified in support of differentiated postoperative therapy, since it enables modification of empirical and rigid decions for high-continuity after-treatment of ovarian carcinomas.


[Incidence of neurologic diseases in children]. Data concerning the distribution and the nosological structure of nervous diseases in children aged from one month to 14 years in the town of N. (76 thousand inhabitants, 16,716 children) are presented. Peculiarities of the dynamics of the disease entities with reference to the age, as well as the influence of the sex on the disease entity are shown. Ranging of the distribution data has made it possible to fix the principal rank places for individual disease entities. The data obtained served as basis for calculating the requirements for neurological beds in children's hospitals and other specialized medical institutions for children.


[Health resort treatment of children with progressive muscular dystrophy]. The results of a complex treatment at health resorts of 126 children with Duchenne myopathy and 84 children with spinal amyotrophies at the age of 5-15 years are given. The complexes included carbon-dioxide sulfurated hydrogen baths, mud application (with different localization depending on a form of the disease), fresh baths, oxygenotherapy and therapeutic physical training. The authors revealed good tolerance to procedures and the positive dynamics of the main clinical manifestations of the disease, confirmed by the electrophysiological and biochemical studies. As a result of the treatment it was possible to achieve progressiveness of the disease in all patients at different periods (from 1 month to 1 year). The authors give recommendations for the use of treatment at health resorts as a necessary link in the general chain of rehabilitative measures for children with various forms of progressive muscular dystrophies.


[Health resort treatment of preschool children with cerebral palsy]. In the Pyatigorsk resort, 226 children from 3-7 years of age with different forms of cerebral paralysis were studied. For therapeutic purposes, besides general health improvement measures, remedial gymnastic and massage, such resort factors as carbon dioxide and sulfurated hydrogen and radon baths of different concentrations and mud procedures were used. As a result of such studies, some indications for referrals of preschool children with cerebral paralysis to balneomud resorts were outlined. Differentiated complexes of resort treatment, depending upon the form and severity of clinical sings were elaborated, as well as the possibility of resort therapy in children with cerebral paralysis, complicated by the intracranial hypertensive syndrome.


[Immunoglobulin and lysozyme concentration in the serum of patients with Down's syndrome]. A study of the immunoglobulin level in the 3 main classes (IgG, IgM and IgA) and lysozymes in the blood serum of 73 patients with Down's disease (from 5 to 20 years of age) showed an increase of IgG in the younger age (up to 7 years) and older groups (over 7 years). The content of IgM was significantly lower in the younger group and did not differ from the control indices in the older group. The level of IgA corresponded to normal indices. The studies demonstrated a marked drop in the lysozyme content. The role of the abnormal system of humoral immunity and reactions of nonspecific defense in the formation of predisposition to the development of infectious diseases in this form of pathology is discussed.


Skin necrosis between parallel abdominal incisions. Four cases of skin necrosis between vertical abdominal incisions are presented. Even though many years may elapse between the abdominal operations, necrosis of the skin as well as of the underlying fascia may develop between new and old vertical incisions parallel with each other. Such necrosis probably takes place particularly in patients with impaired peripheral circulation.


Use of a new laser Doppler flowmeter for measurement of capillary blood flow in skeletal muscle after bullet wounding. A new instrument for measurement of regional muscle blood flow based on the laser Doppler principle is described. The method has been used to determine blood flow in skeletal muscle of pigs after bullet wounding. This new method constitutes a promising technique for non-invasive blood flow measurements in superficial layers of skin and muscle.


[The use of N,N'-diethylpseudoisocyaninchloride for the polarization optical detection of polyanions in the histological section (author's transl)]. In the paper a technique of the polarization optical qualitative and quantitative detection of polyanions with N,N'-diethylpseudoisocyaninchloride in the histological section is described. It is possible to prevent depolymerisation after precipitation with potassium ferricyanide and to intensify the birefringence of the histological structures. In vitro attempts and measurements of the dispersion of the double refraction and of the dichroism indicate connections between the optical appearances, furthermore it is possible to make statements about the mechanism of the arrangement of the tissue-dye-ferricyanide-complex.


[Cellular immune reactivity in patients with multiple myeloma]. The ConA-, PHA- and PWM-induced lymphocyte transformation rates were significantly decreased in 19 patients with multiple myeloma. Lymphocyte-inherent defects rather than serum factors seem to account for this decreased lymphocyte reactivity. In 58% of the patients a pathologically increased ConA-induced suppressor cell activity, which was negatively correlated with the non-paraprotein IgM-concentration, was found.


Cerebrospinal fluid protein findings in various lower back pain syndromes. Cerebrospinal fluid (CSF) total protein, albumin and IgG concentrations were measured in 53 patients with lower back pain syndromes. In the majority of the patients (81 %) the protein values were within normal ranges, a finding contrary to previous studies. In six of 28 patients with acute lumbar disc prolapse and in two of four cases with spinal stenosis, a clearly abnormal protein pattern was observed, while patients who had been earlier operated on for disc prolapse showed normal values. The calculated permeability indexes suggest that the elevation of various proteins is linked with increased permeability across the blood-brain barrier and that the local immunoglobulin synthesis in CNS is lacking. In only one of the cases with an abnormal CSF protein pattern could no evidence of the cause of the pathological finding be observed in subsequent examinations.


Posterior fusion of the lumbosacral spine. Evaluation of the operative results and the factors influencing them. The operative results of 79 patients subjected to posterior fusion of the lumbosacral spine were evaluated on the basis of a follow-up examination performed on average 5.4 years after operation. A method of evaluation was developed which measured the patients' subjective improvement and working capacity. The method proved appropriate for clinical use and gave a more correct picture of the operative result than methods relying on the patients' own opinion or the radiographic assessment as the only criterion. Sixty per cent of the patients were subjectively improved, 40 per cent had returned to their previous or a corresponding occupation and 24 per cent had a good operative result, assessed by the method applied. A statistical analysis was performed in order to find the factors influencing the operative results. Age over 40 years, heavy or moderately heavy preoperative work and over 6 months' preoperative disability had a statistically significant, unfavourable effect on the results. In the case of labourers in heavy occupations, working capacity was seldom restored to a degree sufficient for return to their previous work. The operative technique proved reliable with 91 per cent successful fusions, assessed from functional radiographs. Successful fusion did not imply a good operative result, although it did so more often than non-fusion. On the basis of this study, operative fusion of the lumbosacral spine seems to be of relatively little value in the treatment of patients suffering from low back pain, and factors other than purely medical or surgical have a considerable influence on the operative results.


The state of health of Swedish children. An attempt is made briefly to describe the present health problems of Swedish children. The report is based on data available in official statistics or collected from special studies. It is concluded that the general state of health of Swedish children is good when assessed by commonly used criteria. The mortality pattern is dominated by perinatal and accidental deaths, but also neoplasms are of importance. There are indications that genetic and handicapping disorders, and psychosocial maladjustment will receive more attention in the future.


Socio-economic status of the family and health problems in the preschool child. Lack of correlation in a Swedish sample. Recent reports from countries with a highly developed economic status point out the association of well-being of children with socio-economic factors. The aim of the present investigation was to examine the extent to which health problems, i.e. functional impairments, diseases and handicaps, in 4-year-old children are related to socio-economic factors. The analysis was based on data from 7 173 children who had undergone the routine general health screening of 4-year-olds in the county of Uppsala. In the statistical analysis the main emphasis was laid on an explanation of the variance on the individual plane. The results showed that the correlations between health problems and socio-economic factors in general were weak or non-existent. An explanation of the lack of correlation in our sample might be that Sweden had succeeded in largely eliminating the health problems associated with external living conditions of the family. If differences between population groups do exist--and in the light of findings from other investigations it seems highly probable that they do--then these differences are probably to be sought in families' way of functioning, in the internal and external pattern of communication, in the general emotional climate and in the degree of social integration in the society.


Enzyme histochemistry of non-Hodgkin's lymphomas. Fifty-two cases of non-Hodgkin's lymphomas were studied with enzyme histochemical methods. Forty-four cases of these were also investigated for surface markers with immunological techniques, and results of histochemical, routine histological and immunological observations were correlated. Twenty-one of 27 B-cell lymphomas showed prominent ATPase activity, while all 13 T-cell lymphomas, except one case, did not show such activity. Nodular lymphomas, though of B-cell nature, were often negative for ATPase and it remained negative after diffuse evolution in some. Four of 7 A1Pase positive lymphomas were of B-cell origin. Dot-like localized AcPase and beta-glucuronidase activity characterized T-cell lymphomas while 5 T-cell PDL, including lymphoblastic type with double markers, showed localized esterase activity. Enzyme histochemical characteristics of lymphomas were fairly honest reflection of those of various functional units in the normal lymph nodes. Enzyme histochemical methods appeared to be a useful tool for the study of lymphomas.


Cytological events in allo-stimulated lymphocytes triggered by exposure to stimulatory alloantigens. III. Changes in the areal density of cytoplasmic vacuoles containing endocytized Thorotrast. H-2b lymphocytes were sensitized against H-2d alloantigens by a lymphocyte culture reaction (MLR) and incubated with H-2d mastocytoma cells. Thirty minutes before incubation with the mastocytoma cells Thorotrast was added to the lymphocyte culture medium. The interaction between lymphoid cells and mastocytoma cells was stopped by fixation with glutaraldehyde. The areal densities of the cytoplasmic vacuoles were examined by electron microscopy. Two populations of lymphocytes were observed, small lymphocytes with heterochromatic nuclei and larger lymphocytes (lymphoblasts) with euchromatic nuclei. Only the lymphoblasts showed changes following interaction with target cells. The areal density of Thorotrast containing vacuoles in sensitized lymphoblasts increased during the three hour observation period, but the percentage of vacuoles containing Thorotrast in the total area of cytoplasmic vacuoles decreased in the first thirty minutes of interaction with target cells. This observation may indicate greater formation of vacuoles from the Golgi apparatus compared with the formation of vacuoles from the cytoplasmic membrane at the onset of interaction with target cells. In the multivesicular bodies (MVB) the Thorotrast was first observed inside the small vesicles and later on it was also observed in the matrix of the MVB. After three hours of interaction Thorotrast was observed laying "free" in the matrix of phagosomes along with myelin figures.


Renal cortical blood flow distribution measured by hydrogen clearance during dopamine and acetylcholine infusion. Effect of electrode thickness and position in cortex. Blood flow distribution in the renal cortex was investigated in control and during i.a. infusion of dopamine (DA) and acetylcholine (Ach) in dogs. Local blood flow in outer cortex (OCF) and in inner cortex (ICF) was measured by platinum electrodes detecting hydrogen washout rate in tissue. Mean cortical blood flow measured by hydrogen washout rate in the renal vein (CFV) was compared with renal arterial blood flow (RAF) measured by electromagnetic flowmeter. With electrodes of 0.05-0.2 mm diameter control blood flow rates in outer and inner cortex were 4.57 +/- (S.D.) 1.73 ml/min.g, and 4.35 +/- 0.57 ml/min.g, which is higher than found using 0.2-0.5 mm electrodes in this and previous studies. OCF and ICF increased proportionally during intraarterial infusion of DA or Ach. The increase in local blood flow per unit volume was about 20% less than the increase in RAF, most likely due to an increase in renal volume and a reduced vasodilatory response in the surrounding of some electrodes. CFV rose almost to the same degree as RAF, showing a diffusion equilibrium for hydrogen gas even at maximal flow rate. During vasoconstriction induced by high doses of DA, OCF and ICF fell proportionately. Thus, equal vascular responses in outer and inner cortex were observed during both vasodilator and vasoconstrictor infusion. This indicates that changes in sodium excretion with renal blood flow may not be associated with a redistribution of cortical peritubular blood flow.


RNA synthesis in permeable mouse ascites sarcoma cells. A permeable cell system for studying RNA synthesis was established. Mouse ascites sarcoma cells were made permeable to nucleoside triphosphates and alpha-amanitin by treating with a hypotonic buffer. Separate determinations of endogenous RNA polymerase I, II and III activities in permeable cells were conducted using the different sensitivities of these enzymes to alpha-amanitin. The endogenous activity of RNA polymerase II under optimal conditions was one tenth of total RNA synthetic activity in isolated nuclei, and one third of that in permeable cells. The extremely low ratio of RNA polymerase II activity to total RNA synthetic activity in isolated nuclei was thought to be caused by increase of RNA polymerase I activity and decrease of RNA polymerase II activity. These and other results suggested that RNA synthesis in permeable cells reflects more precisely the in vivo state of RNA synthesis than thatin isolated nuclei. The permeable cell system will provide a useful method for studying the separate activities of RNA polymerases I, II and III in situ.


Effects of some polyamines, polyanions and antitumor drugs on replicative DNA synthesis and unscheduled DNA synthesis in vitro. The effects of various compounds on replicative DNA synthesis in permeable mouse ascites sarcoma cells and on unscheduled DNA synthesis in permeable cells or in isolated rat liver nuclei were studied. Polyamines such as spermidine, putrescine and cadaverine inhibited replicative DNA synthesis. Unscheduled DNA synthesis was inhibited by spermidine and cadaverine, but slightly stimulated by putrescine at low concentrations. Aurintricarboxylic acid, a low molecular weight polyanion, inhibited both replicative DNA synthesis and unscheduled DNA synthesis. Replicative DNA synthesis was inhibited by heparin, a high molecular weight polyanion, whereas unscheduled DNA synthesis was stimulated at low heparin concentrations. Antitumor drugs such as daunomycin, neocarzinostatin and bleomycin inhibited replicative DNA synthesis. Unscheduled DNA synthesis was inhibited by daunomycin, slightly induced by neocarzinostatin and highly induced by bleomycin. The present system was thought to be useful for studying the separate effects of various drugs on either replicative DNA synthesis or unscheduled DNA synthesis in vitro.


Sequential radioimmunoassay of unconjugated and conjugated estrogen in male human plasma. A sequential radioimmunoassay procedure for unconjugated and conjugated estrone, estradiol-17 beta and estriol in male human plasma was developed. The blank values in this assay for unconjugated estrone, estradiol-17 beta, estriol conjugated estrone, estradiol-17 beta and conjugated estriol were 0.36 +/- 1.14 pg, 3.90 +/- 2.75 pg, 2.25 +/- 2.08 pg, 0.92 +/- 1.51 pg, 5.02 +/- 2.86 pg and 3.12 +/- 2.97 pg, respectively. Mean values of unconjugated estrone, estradiol-17 beta, estriol, conjugated estrone, estradiol-17 beta and conjugated estriol in plasma from 28 normal adult males were 38.4 +/- 13.4 pg/ml, 32.6 +/- 9.90 pg/ml, 4.06 +/- 3.68 pg/ml, 34.2 +/- 13.8 pg/ml, 40.4 +/- 12.3 pg/ml and 31.8 +/- 7.41 pg/ml, respectively. Both unconjugated and conjugated estrogen levels in patients with liver cirrhosis were elevated and conjugated estrogen, especially estriol levels, in patients with renal insufficiency were markedly elevated.


Partial purification and biological activities and properties of chick growth factors. Cellular stimulating factors on cell proliferation in the supernatants of chick embryo carcases and adult muscles were studied. There were plural stimulating factors in embryonic and adult muscular supernatants that promoted cell proliferation without any supplement of sera and other materials. Salting-out methods with ammonium sulfate, ethanol fractionation, and isoelectric precipitation were used to isolate the stimulating factors, and these three methods proved the presence of plural stimulants on cell proliferation in the supernatants of chick embryo and adult muscles. The stimulants had altered physico-chemical properties and biological activities due to embryological development. The embryonic stimulants enhanced the synthesis of DNA and protein remarkably, and RNA synthesis in whole cell systems slightly. The muscular stimulants enhanced protein synthesis without any stimulation of DNA and RNA synthesis. Partial purification of the stimulants from the ethanol fractions was performed by DEAE-cellulose chromatography and Sephadex gel chromatography.


Characteristics of pressure sensing balloons made of various polymeric materials. A variety of polymeric materials (polyurethane, polypropylene, polyethylene and polyvinylidine copolymer) have been evaluated for suitability in making of air-filled balloon to detect intraluminal pressure. The polyurethanes, in particular ECD, proved to be most suitable because of the ease of fabrication, low permeability to air and high frequency characteristics. Polyvinylidine copolymer was adequate but suffered from difficulties in fabrication. Polypropylene and polyethylene, available in film, were troublesome in making balloon and displayed low frequency characteristics.


Lymphocyte cytotoxicity against allogeneic cultured cells in gynecologic malignancy. Peripheral blood lymphocytes from patients with gynecologic cancer were tested by micro-cytotoxicity assay against two types of allogeneic cultured cancer cell lines: squamous cell carcinoma and adenocarcinoma. Lymphocytes from cancer patients with squamous cell carcinoma or adenocarcinoma were equally cytotoxic against these target cells. In addition, lymphocytes from healthy controls and myoma patients were also cytotoxic for these cell lines. No significant difference in cytotoxic activities was detected among the cancer patients and controls. However, a good correlation was observed between cytotoxic activity and non-specific lymphocyte responses. It was concluded that this assay sysetm is not suitable for measuring cell-mediated immunity against tumor specific antigens but does estimate non-specific resistance against cancer.


Heat stable cell growth inhibiting factor isolated from rat liver microsomes. A heat stable cell growth inhibiting factor was isolated from rat liver microsomes by hot salt extraction, ethanol fractionation and the hot phenol method. The factor was contained in the RNA fraction (designated as mhRNA). mhRNA inhibited the growth of mouse fibroblast (L-929) cells at a relatively low concentration (55 microgram/ml of culture medium). The molecular weight of mhRNA was about 27,000 and the base composition was guanine and cytosine rich.


Determination of the disappearance rate of azathioprine from circulating rat blood by high-pressure liquid chromatography. A rapid and specific method of high-pressure liquid chromatography for determining 6-(1-methyl-4-nitro-5-imidazole) mercaptopurine (azathioprine) in the blood was developed using mu Bondapak C18 as adsorbent and 30% aquous methanol as eluent. Azathioprine was completely separated from related compounds in blood. The standard curve showed a linear relationship at least between 0.6 and 30 micrograms per ml of serum. Recovery was satisfactory and the analytical time needed was less than 20 min. Disappearance rates of azathioprine from circulating blood in rats were 0.026 in probenecid-treated rats, and 0.103 in intact rats.


Fulminant hepatic failure during remission from leukemia: three cases associated with massive liver cell necrosis and hepatitis B virus. Three patients at various stages of remission from leukemia died following the development of massive liver necrosis within only 4-6 days. All had either hepatitis B surface antigen or antibody in their sera, and two of them experienced severe epigastric pain before the onset of liver injury. Hepatitis B surface antigen appeared in two of these patients after remission from leukemia. Serum gamma-globulin levels increased with decreasing doses of prednisolone and other antileukemic drugs, and hepatic cell necrosis occurred extensively. Localization of hepatitis B surface antigen in their livers revealed a strong positive reaction in the phagocytic cells. These observations strongly suggest that hepatitis B virus may be causally related to the fulminant hepatic failure at least in two of the reported leukemic patients.


Bartter's syndrome--case report.

Bartter's syndrome--case report. A 26-year-old female with Bartter's syndrome associated with Graves' disease is reported. This patient had a history of Graves' disease from the age of 22 and anti-thyroid drug (Methimazole) had been administered for 2 years. Thyroid function returned to normal but general fatigue and polyuria continued. Hypokalemia was diagnosed at 25 years of age and she was referred to our hospital for evaluation. Blood pressure was normal and laboratory data revealed normal thyroid function, hypokalemic alkalosis, high plasma renin activity and high plasma aldosterone concentration. She showed normal pressor sensitivity to norepinephrine infusion, grossly diminished pressor sensitivity to exogenous angiotensin II infusion compared with the normal. A renal biopsy specimen showed juxtaglomerular cell hyperplasia. Electron microscopy confirmed lacis cell (agranular cell) proliferation.


A case of ectopic renin-secreting orbital hemangiopericytoma associated with juvenile hypertension and hypokalemia. An unusual case of orbital tumor with high renin content and severe hypertension is described. The patient was a 15-year-old girl with juvenile hypertension (200-140 mmHg) associated with right exophthalmos and hypokalemia. The patient showed extremely high levels of plasma renin activity and plasma aldosterone concentration. No difference was present in plasma renin activity from either side of the renal veins. Preoperatively, hypertension responded to treatment with spironolactone. The tumor could not be completely removed because of intracranial metastasis and infiltration, and the hyperreninemia and secondary hyperaldosteronism persisted. The renin content in the orbital tissue was 1,403-2,225 ng/angiotensin I generated/h/g wet weight of tissue. The postmortem histopathologic diagnosis was orbital hemangiopericytoma. This is the first case of extrarenal (ectopic) renin-secreting (or -producing) hemangiopericytoma of the orbital origin. Furthermore this case is worthy of note in the point of view of the presence of the extrarenal renin-angiotensin system, particularly in the brain.


Q waves and coronary artery disease.

Q waves and coronary artery disease. In a consecutive series of 234 patients admitted for selective coronary arteriography, 78 had pathological Q waves. In 32 of these 78 patients, ECG showed left ventricular hypertrophy, QRS duration of greater than or equal to 0.12 sec, incomplete left bundle branch block, or left axis deviation. Fourteen (44%) of these 32 patients had coronary artery disease (CAD), while 40 (87%) of the remaining 46 patients without these ECG changes had CAD (p less than 0.0005). Among the 46 patients, 34 of 35 with angina pectoris had CAD compared to 6 of 11 without angina pectoris (p less than 0.01). Our study thus shows that Q waves may be reliable predictors of CAD especially in patients with angina pectoris.


Dynamics of kallikreinogen under hemodialysis. There are many complications due to hemodialysis, causes of which seem to lie under disorders of the coagulation system, fibrinolytic system, and kinin system. Therefore, it is important to understand the dynamics of these systems during hemodialysis. Accordingly, kallikreinogen, plasminogen, plasmin inhibitors, contact factor, antithrombin, and prothrombin were assayed during the experimental dialysis, experimental ultrafiltration and clinical hemodialysis. Plasmin inhibitors decreased remarkably by dialysis. They then recovered the pre-dialytic values as time went on. Kallikreinogen did not show any definite tendency immediately after the beginning of dialysis, but two hours later its value rather increased relative to thepre-dialytic value. It was supposed that this increase was caused by reactive hyperproduction due to gradual consumption of kallikreinogen. Contact factor slightly decreased by dialysis, whereas prothrombin and antithrombin decreased apparently. When hemodialysis is practiced, it is necessary to fully realize that the coagulation system, fibrinolytic system, and kinin system might lose their balance.


Ultrasound of arterial graft surgery complications. The value of gray scale ultrasound in evaluating primary diseases of the abdominal aorta and peripheral vessels has been well documented. However, only limited attention has been given to complications associated with arterial graft surgery. Twelve patients with a variety of complications are reported. These include 10 anastomotic pseudoaneurysms, one abscess, two "aneurysms" in degenerated graft material, and four serous fluid collections around intact Dacron grafts. The latter two complications are previously unreported.


Cardiovascular malformations in the fetal alcohol syndrome. Cardiovascular anomalies are a frequently reported feature of the fetal alcohol syndrome, but only rarely have such children been catheterized. This article fully described the cardiac anomaly in two infants with this syndrome. The malformations found in both cases include a ventricular septal defect, and the rather unusual finding of pulmonary artery dysplasia.


Effects of cardiac hypertrophy secondary to hypertension on the coronary circulation. For many years clinicians have suspected that hypertrophied ventricles have an inadequate coronary circulation. Recent studies have confirmed early observations that flow per gram in hypertrophied ventricles is normal at rest. However, coronary vascular resistance is greatly increased when hypertension is the cause of left ventricular hypertrophy. Studies that have employed labeled microspheres to assess regional myocardial perfusion have shown that the transmural distribution of myocardial perfusion is often abnormal in dogs with left ventricular hypertrophy. In addition, studies of cardiac hypertrophy in many animal models have shown that maximal coronary vasodilatation is limited substantially. Furthermore, when hypertrophied hearts are subjected to a physiologic stress that induces coronary vasodilatation, endocardial underperfusion occurs frequently. Thus, studies in animals suggest that cardiac hypertrophy adversely affects the coronary circulation. The availability of new techniques for estimating phasic and transmural coronary blood flow in man should make it possible to extend these studies to patients with cardiac hypertrophy.


Echocardiographic dimensions in borderline and sustained hypertension. Echocardiographic dimensions and hemodynamic indexes were determined in 42 patients with borderline hypertension and in 22 with sustained hypertension and the results were compared with findings in 33 normal subjects. In patients with borderline hypertension the thickness of the interventricular septum (IVS) was significantly increased (P less than 0.001), whereas the posterior wall PW) thickness remained within normal range. The IVS/PW ratio was significantly elevated (P less than 0.001) and was correlated negatively with the cardiac index (P less than 0.01) and positively with the preejection period (P less than 0.01). In patients with sustained hypertension a symmetric cardiac hypertrophy was observed, and there was a significant positive correlation between the IVS/PW ratio and diastolic pressure (P less than 0.05). The study suggested that (1) in sustained hypertension the symmetric cardiac hypertrophy was secondary to a progressive increase in pressure load, whereas (2) in borderline hypertension the asymmetric cardiac hypertrophy could not be directly related to the level of blood pressure and was probably associated with abnormalities of the sympathetic nervous system.


Cardiac hypertrophy: its characteristics as a growth process. The causal relation between cardiac function and growth is analyzed in this review article. Three different levels of development are discussed: cytodifferentiation, embryogenesis and postnatal development. The earliest stage of cardiac morphogenesis, that is, the appearance of cell-specific proteins and of spontaneous contractions, appears to be independent of hemodynamic forces. Also, the first major morphologic transformation of the primitive heart, looping, is the intrinsic property of the heart itself. However, at any later stage of life, hemodynamic function in both health and disease is closely coupled to cardiac growth.


Is arterial pressure the sole factor responsible for hypertensive cardiac hypertrophy? Increased arterial pressure is obviously the major stimulus to cardiac hypertrophy in hypertension. However, different studies suggest that in addition to the pressure load, other factors could play participating roles in determining the degree of ventricular hypertrophy in response to the hypertensive disease as well as the degree of its reversal after control of arterial pressure. These other mechanisms include genetic factors and concimitant processes such as aging and the presence of cardiomyopathy or other disease. Two neurohumoral influences, namely, the adrenergic and the renin-angiotensin systems, may also participate, and the early evidence supporting these possible contributing factors is cited. Further studies are needed to determine the relative importance of each of these factors in different types of hypertension and in their response to different modes of antihypertensive therapy.


Idiopathic hypertrophic subaortic stenosis: evaluation of anginal symptoms with thallium-201 myocardial imaging. The evaluation of angina pectoris in patients with idiopathic hypertrophic subaortic stenosis is difficult in those in the age group prone to coronary artery disease. Ten patients with angina pectoris, normal coronary angiograms and idiopathic hypertrophic subaortic stenosis were studied with thallium-201 myocardial imaging performed in conjunction with submaximal treadmill exercise testing. The resting electrocardiogram demonstrated left ventricular hypertrophy with S-T segment abnormalities in seven patients, thereby vitiating the further increase in S-T segment abnormalities that developed in these patients during exercise or in the postexercise period. Of the three patients with a normal resting electrocardiogram, one had significant exercise-induced S-T segment depression. Thallium-201 myocardial imaging revealed no significant perfusion defects in 9 of the 10 patients (90 percent). In one patient with severe left ventricular hypertrophy significant perfusion defects developed after exercise that were not present at rest. Stress thallium-201 myocardial perfusion imaging is a useful noninvasive technique that assists in ruling out the presence of significant coronary artery disease in patients with idiopathic hypertrophic subaortic stenosis.


Neoplasms of immunoregulatory cells.

Neoplasms of immunoregulatory cells. This paper provides an overview of neoplasms which appear to be derived from immunoregulatory cells. Normal T cells play a critical role in the regulation of humoral immune responses by acting as potentiators (helper cells) or inhibitors (suppressor cells) of the B cell transition into immunoglobulin-secreting plasma cells. Certain patients with leukemias or lymphomas of T-cell origin may provide a resource for obtaining homogeneous populations of cells which act as either helper cells (e.g., some patients with the Sézary syndrome) or suppressor cells (e.g., some patients with acute or subacute T-leukemia). The clinical and theoretic implications of such immunoregulatory cell neoplasms are discussed.


Comparison of DRO and DRI on rate of suppression of self-injurious behavior. Two procedures were used to compare the effects of differential reinforcement of other behavior (DRO) and differential reinforcement of incompatible behavior (DRI) on self-injurious behavior (SIB) of three profoundly retarded head-bangers in a multiple-schedule within-subjects design. We found that rewarding a response specifically incompatible with SIB suppressed it more rapidly than applying DRO without specifying an alternative response. The relationship of collateral behaviors to SIB were dependent upon the repertoires of the individual clients.


Isolation and characterization of myosin in the human term placenta. The major contractile protein myosin was isolated and characterized from the smooth muscle of human term placentas. Placental myosin originates chiefly in the anchoring villi which bridge the fetal and maternal surfaces of the placenta. The molecular weight of placental myosin is about 460,000; it is composed of two heavy chains of 200,000 molecular weight and two pairs of light chains with 13,500 and 17,500 molecular weights. The adenosine triphosphatase (ATPase) of the myosin is activated by potassium and calcium and it is inhibited by magnesium. Placental actomyosin ATPase is activated by magensium. Contraction and relaxation of the smooth muscle in the anchoring villi are thought to adjust the volume of the intervillous space; thus, actin-myosin interaction is implicated in the regulation of placental hemodynamics.


Immune complex injury of the lung.

Immune complex injury of the lung. Abundant evidence currently exists to suggest that immune complexes play an important role in inflammatory diseases of the lung. Clinically, idiopathic pulmonary fibrosis, eosinophilic granuloma of lung, and systemic lupus erythematosus have been shown to be associated with the presence of immune complexes both in lung and in the serum. Experimentally, there is compelling evidence that acute lung injury can be triggered by the deposition of complexes in vascular walls or by the presence of performed immune complexes instilled into the airways. The observed reactions are, as expected, complement- and neutrophil-dependent. The morphologic changes in lung caused by products of complement activation (C5a and related peptides) depend on whether complement activation occurs within the vasculature or within the airways. Airway activation is associated with intraalveolar accumulations of neutrophils, while intravascular activation leads to intracapillary sequestration of neutrophils. The chronic formation of immune complexes within the vasculature (in the model of "chronic serum sickness") leads to an interstitial fibrotic reaction and a thickening of basement membranes. Recent studies of intravascularly infused preformed immune complexes indicate a proclivity for certain types of complexes to localize within lung. These "lung-seeking" complexes differ from non-lung-seeking complexes only in the ratio of antigen to antibody. Complement does not seem to alter the tendancy for certain complexes to localize within lung. These studies emphasize the potential importance of immune complexes in lung injury and point out the variety of mechanisms involved in both the localization process and the injury process.


Myofibrillar ATPase activity in rat heart after chronic propranolol administration. A previous study has shown that chronic chemical sympathectomy brought about by 6-hydroxydopamine injections results in a dpression in myocardial contractile function which is accompanied by reduced myofibrillar ATPase activity. To determine whether chronic beta-adrenergic receptor blockade elicits similar alterations in cardiac contractile-protein ATPase activity, adult rats were given twice-daily injections of propranolol 7 days/wk for 2 wk. Effective beta-adrenergic receptor blockade was verified by the lack of hemodynamic responsiveness to isoproterenol infusion. Myofibrils were prepared from left ventricular tissue and analyzed for ATPase activity. Myofibrillar ATPase activity was 295 +/- 8 nmol Pi.mg-1.min-1 in controls. Enzyme activity was not significantly different in propranolol-injected rats. The results demonstrate that chronic propranolol administration does not alter the ATPase activity of cardiac myofibrils. Therefore, it seems likely that the altered contractile-protein enzymatic properties resulting from chronic chemical sympathectomy do not occur as the result of a reducted level of cardiac beta-adrenergic receptor stimulation.


Temperature-  and Mg-ATP-dependent regulation of Ca2+ sensitivity of smooth muscle actomyosin ATPase. Many smooth muscles on metabolic depletion undergo a contraction that is insensitive to EGTA [ethylene glycol-bis (beta-aminoethylether)N,N-tetraacetic acid]. Chicken gizzard actomyosin shows a progressive loss of Ca sensitivity accompanied by activation of EGTA-Mg-ATPase at temperatures near 37 degrees C with decreasing ATP concentrations. Ca2+-dependent phosphorylation still occurs under these conditions when the ATPase is Ca insensitive. Activation of EGTA-Mg-ATPase at low ATP concentration is not due to a pseudo-ATPase, or due to denautration of the actomyosin at 37 degrees C. Magnesium concentrations above 1 mM are required for observing the enhanced EGTA-Mg-ATPase activity and the Ca sensitivity is very markedly influenced by the magnesium concentrations of medium at low ATP. When the Mg-to-ATP ratio (5:1) was kept constant for varying ATP concentrations, activation of EGTA-ATPase was not observed. This activation was not due to the characteristics of the ATP regenerating system (phosphoenolpyruvate and pyruvate kinase) because with phosphocreatine and creatine phosphokinase similar results were obtained. Thus the EGTA-insensitive rise in tension during metabolic depletion is due to activation of Mg-ATPase and loss of Ca sensitivity at 37 degrees C, a temperature at which mammalian smooth muscles normally function.


Changes in the sensitivity of left atrial receptors following reversal of heart failure. Recordings were made from left atrial type B receptors in six mongrel dogs after recovery from the cardiac effects of a chronic AV fistula. All animals showed hemodynamic and clinical signs of congestive heart failure after 44.5 +/- 3.6 days with a patent Dacron shunt between the aorta and inferior vena cava below the level of the renal arteries. The stimulus-response curves of the left atrial stretch receptors (change in spikes/cardiac cycle or in spikes/minute vs. change in left atrial pressure) after 45.2 +/- 7.2 days of shunt closure were similar to those seen in sham-operated dogs from a previous study. However, the slope of the stimulus-response curve of the dogs in which the AV fistula was closed was significantly greater than the slope of the curve from the AV fistula dogs with heart failure. Radiographs indicated that after shunt closure, cardiac dilatation had regressed. This study incidates that a decrease in the sensitivity of left atrial receptors in dogs with congestive heart failure is a reversible phenomenon and that the initial depression is most likely related to the concomitant cardiac dilatation that accompanies the failure state.


Sports for the physically disabled. The 1976 Olympiad (Toronto). The 1976 Olympiad for the Physically Disabled was the first olympiad with full competition for blind, paralyzed, and amputee athletes. More than 1,500 from 38 countries took part in wheelchair (12 events), blind (8 events), and amputee (11 events) games. Participants were classified by an international team of doctors. The athletes were accomodated in university residences with small infirmaries. A school near the games site was used as a field hospital. Rest areas were also set up. Volunteers served on the medical staff (three doctors, three  nurses, three receptionists, and three physical therapists on each of two shifts per day). In addition doctors, nurses, trainers, and physical therapists rotated around various venues at the games site. Physicians treated 285 patients (184 were athletes; others were spectators) for a variety of problems, physical therapists treated 119 athletes, and trainers treated 114 athletes. Contigency plans in case of mass disaster were made but were not needed. Disabled athletes are slightly more vulnerable to stress and fatigue than able-bodied athletes. The Toronto games will probably be remembered as the turning point in the emergence of sports for the disabled from a purely rehabilitation measure to a true sporting event in its own right.


[Intratissular immune complexes in experimental pathology (author's transl)]. Immune complexes are responsible for tissue lesions in human pathology and in experimental pathology. In this review are considered the various models in which immune complexes may be responsible for tissue lesions in experimental pathology. The methods of study are first considered. Four essential models are then described. Knowledge of these models is probably very important for better understanding of human diseases. Finally are considered the circumstances favouring the formation of immune complexes in a tissue, the affected organs and the possible pathogenic effects of these immune complexes.


Occupational diseases.

Occupational diseases. This paper does not deal with occupational diseases in the narrow legal sense of the word but as part of all public health risks. Occupational health risks of the modern large-scale animal production on intensive farms differ radically from those of the traditional mixed small production farms. The main groups of occupational diseases in intensive large-scale animal production are: 1) Zoonoses. Their occurrence obviously depends on the epizootological situation. They are divided into the following groups: classic zoonoses, zoonoses with complicated ecologic relations, zoonoses associated with soil, zoonoses with natural foci or with reservoirs outside farms. 2) Lung diseases: chronic bronchitis, farmers' and brewers' lung precancerous conditions. 3) Skin diseases and allergies: dermatites, eczema and allergies. 4) Affections due to physical and mental stress: changes in the locomotor system and CNS, contribution to the development of "civilization diseases". 5) Accidents, poisoning, noise and vibration effects.


The role of serotonergic mechanisms on amphetamine-induced stereotyped behaviour. The effects of 5-hydroxytryptophan (5-HTP) and p-chlorophenylalanine (PCPA) on amphetamine-induced stereotyped behaviour (ASB) and on the behavioural and EEG effects of caudate nucleus stimulation have been studied in the cat. After a pretreatment with 5-HTP (10--30 mg/kg) the threshold dose of amphetamine to induce ASB remained the same, but its pattern assumed a more organized character with reduced amplitude of stereotyped movements. On the contrary, after PCPA (200 mg/kg) a disorganized pattern of ASB was observed. 5-HTP increased and PCPA decreased the threshold of the arrest reaction induced by low frequency stimulation of ventro-lateral parts of the head of caudate nucleus. 5-HTP and PCPA also influenced in the opposite direction caudate-induced spindle waves in the neocortex. The effects of amphetamine on behavioural and EEG pattern of arrest reaction due to stimulation of the caudate nucleus were antagonized by 5-HTP and potentiated by PCPA. It is supposed that serotonergic mechanisms present in the ventro-lateral regions of the caudate nucleus can modulate stereotyped behaviour triggered by amphetamine.


Bovine plasma cold-insoluble globulin: gross structure and function. Bovine plasma CIg, like human CIg, is a glycoprotein with a molecular weight of approximately 450,000 daltons and consists of two homologous subunits, the alpha and beta chains. These subunits are covalently linked through disulfide bridges in their carboxyl terminal domains. The carboxyl terminal regions are presumed to contain the fibrin-reactive transamidation site. The covalent incorporation of CIg into fibrin has been conclusively demonstrated by isolation of the S-carboxymethyl derivative of the CIg-fibrin-alpha chain complex and by determination of its terminal amino acid sequences. Cold-insoluble globulin has been shown to exert a stimulatory effect on the urokinase-mediated activation of bovine plasminogen to plasmin.


[Inflammatory variable epidermal naevus (atypical I.L.V.E.N.? A new entity?) (author's transl)]. The authors report a case of two sisters, having one of them left hemiatrophy, with congenital verrucose lesions, in plaques and lineary, bilateral, in extremities, presenting bouts of inflammatory extensive evolution (mostly on the atrophic side), with spontaneous resolution. Histologically the lesions match with those of Nevil's. The authors discuss the nosologic data with that of Nevil's, with epidermic nevus of Solomon and with variable erythrokeratodermis.


[Acne-like eruption induced by pseudo-xanthoma elasticum (author's transl)]. Pseudoxanthoma elasticum can induce acne-like eruption. The lesions are located on the latero-cervical parts and consist of comedones, cysts and inflammatory nodules. Histologically, there are no transepithelial eliminations or follicultitis, but a very important granulomatosus tissue with epithelioid cells and a giganto-cellular reaction with elastotic fibres phagocytosis. These findings are different from the cases with association of P.X.E. and elastosis perforans, but they are closely related to it. We think that these features are of a very great interest for the dermatological practice.


Pearson and the patient.

Pearson and the patient. This lecture covers some subjects of direct concern to the medical profession contained within the Pearson Report. Each injury group was examined by the Royal Commission, both here and abroad, particular attention being paid to the relationship between tort and social security. By consensus it was proposed that in the majority of fields no-fault compensations should be extended but that the tort system should continue to have a role. Recommendations were also put forward that no damages should be permitted for non-pecuniary loss during the first 3 months and that the full value of the social security benefits should be deductible from all tort damages. Damages for permanent injury or death should be index-linked periodic payments. A new no-fault compensation scheme for road accidents was described as well as a new disabled children's allowance of 4 pounds per week with a mobility allowance at the lower age of 2 years. Medical injury was examined carefully, but it was decided that negligence liability should continue unchanged, with the proviso that the no-fault compensation schemes in New Zealand and in Sweden should be followed. These two schemes have therefore been described in some detail.


[Oral contraceptives and trisomy 21. A retrospective study of 730 cases (author's transl)]. A retrospective study of 730 cases of trisomy 21 and of 1 035 cases of abnormal children without a detectable chromosomal aberration, allows the study of the frequency of use of oral contraceptives by their mothers. The statistical analysis shows no notable differences for mothers 30 years old and younger. Among the mothers 30 to 38 years old, these is an excess of pill-taking by mothers of trisomy 21 children. For this second category of mothers (30 to 38 years) this excess is significant (a) when the delay between the cessation of pill-taking and the conception of the child is six months of less; (b) when the duration of pill-taking has been longer than one year; and (c), when those two factors are present simultaneously. Moreover, the frequency of males is significantly reduced in trisomy 21 children when their mothers have taken the pill. As a whole, for the subsample of mothers 30 and older, a correlation is observed between the three factors analysed, pill-taking, sex ratio, and trisomy 21. In view of the fact that decrease of the sex ratio and the increase of the frequency of trisomy 21 both are correlated with maternal aging in the general population, it seems remarkable that a correlation between these two variables and the use of oral contraceptives is observed only when the women had already passed the first of their reproduction period.


D-penicillamine and immune complex deposition. Dense, granular immunoglobulin deposits have been identified at the epidermo-dermal junction in 4 out of 10 patients who developed toxic reactions to D-penicillamine therapy for rheumatoid arthritis. Three of 4 patients developing a lupus-like syndrome while on penicillamine had similar findings on skin biopsy. Serum immunoglobulin and complement levels decreased significantly in patients treated with penicillamine. It is suggested that, in addition to penicillamine nephropathy, other side effects of this drug may be related to widespread deposition of immune complexes.


The Pasteur effect and catabolite repression in an oxidative yeast, Kluyveromyces lactis. The presence of the Pasteur effect in Kluyveromyces lactis grown in glucose was shown by azide-stimulated glucose fermentation. Extracts from these cells contained ATP-sensitive phosphofructokinase activity. Cells grown on succinate oxidized glucose slowly at first without azide-stimulated rates of fermentation. Phosphofructokinase in these cells was ATP-insensitive. The activity of NAD+-isocitrate dehydrogenase in cell extracts did not require AMP activation. These results suggested the presence of a Pasteur effect in glucose-grown but not in succinate-grown K. lactis, mediated by (a) ATP inhibition of phosphofructokinase (b) possibly via feedback control of glucose transport, but not by AMP activation of isocitrate dehydrogenase. Azide inhibition of the Pasteur effect during growth of the cells did not lead to catabolite repression of respiratory activity. The results therefore suggest that the Pasteur effect does not inhibit the development of a Crabtree effect in oxidative yeasts.


Prosepctive analysis of heart biopsies in coronary artery surgery. In a prospective analysis of 36 biopsies from human hearts performed at the time of elective coronary operation, several morphological changes were identified in the myocardium. Some of these changes (fibrosis, vacuolation, edema, and amyloid deposition) are of clinical signficance and may affect the long-term prognosis for patients undergoing revascularization procedures. It appears, therefore, that knowledge of the morphological state of the myocardium at the time of operation can prove useful in elucidating further the long-term effects of coronary artery bypass on the left ventricular myocardium.


Immediate operation for ectopia cordis.

Immediate operation for ectopia cordis. Forty-one infants with thoracoabdominal ectopia cordis have been reported to date; 9 of them survived. Among the patients with an omphalocele as the abdominal wall defect, however, only 2 survived. Death in this group of patients occurred almost exclusively as a consequence of either attempted coverage of the heart or secondary to the associated intracardiac lesion. We report here the case of a patient recently treated in whom coverage with a temporary Silastic prosthesis protected the exposed heart from infection and rupture of the sac, thus permitting full cardiac investigation before operation.


Relationship of endogenous ATP to flagellar beat frequency in ejaculated bull spermatozoa. The relationship between endogenous ATP and flagellar beat frequency of bull spermatozoa was investigated using cinematographic and biochemical criteria. ATP content was measured by the luciferin-luciferase method. Potassium, sodium, chloride, and viscosity were used to alter motility to establish the concomitant effects on ATP content. Beat frequency was correlated to endogenous ATP in potassium-supplemented media. Increased sodium concentration was related to ATP content, but not to beat frequency. With increasing viscosity of the medium, the frequency of flagellary beat decreased dramatically, while ATP content of the cells remained unchanged.


[Partial trisomy 21].

[Partial trisomy 21]. Three mentally retarded children with partial trisomy 21 who looked like children with complete trisomy 21 had increased activity of superoxide dismutase A. This emphases the pathogenic role of the 21q22 band in this condition.


The environment as a support system for independent living. In extended interviews and visits with 150 physically disabled young adults living independently in Berkeley, CA, the author studied the environment as they experienced it and evaluated its accommodation to their special needs. The environment in this study is considered in physical and psychosocial terms, that is, as a support system for the multifaceted needs of the whole person. The framework for organizing the data was Mayer Spivak's construct of "archetypal place" in which he defines 13 fundamental places in terms of the behaviors they support: shelter, sleep, mate, groom, feed, excrete, store, territory, play, route, meet, compete, and work. For purposes of the present work, shelter and mate are discussed--shelter, because of the clarity of its relationship between existence and physical form, and mate because of its more abstract relevance to physical form.


Iliolumbar syndrome as a common cause of low back pain: diagnosis and prognosis. Most cases of low back pain fall into the category of nonspecific low back pain in which no specific pathology can be detected by x-ray, laboratory tests, or biopsy. In the authors' experience about 50% of the patients falling into this group have a clinical picture characterized by symptoms and signs localized at one iliac crest. The symptoms can be abolished temporarily by infiltration of the posterior iliac crest with lidocaine. Because of the location of the findings and the unknown etiology the term iliolumbar syndrome is suggested. Distinguishing the iliolumbar syndrome from the root irritation syndrome may avoid unnecessary surgery. Chronic iliolumbar syndrome is a frequent cause of permanent low back disability, a fact not commonly recognized.


Dilation of synthetic grafts and junctional aneurysms. Dilation of prosthetic graft has been noted by authors in association with junctional aneurysm between the synthetic graft and host arteries. Dilation of graft materials was suspected as one of the etiologic factors of the junctional aneurysm. Increase in transverse diameter was observed as early as a few minutes to five years postimplantation in clinical cases. The phenomenon of dilation was studied experimentally. Nine different types of graft materials were tested using intraluminal pulse pressure of 100/60 mm Hg, and the transverse diameters were measured at various time intervals. Knitted grafts showed the more pronounced changes compared with the woven. Degree of dilation differed considerably among the different types of knitted grafts.


[Localization of ATPase in the cerebral cortex and its role in the functional activity of neurons]. By analogy of defensive conditioned reflex formation in rats using a cytochemical method, dependency of localization and concentration of the product of ATP-ase activity on neuronal and synaptic functional activity has been demonstrated. It corresponds to the notion that only a part of the cortical cells are simultaneously at the state of structural-functional activity. The experimental data demonstrate that the CNS excitation in the animals during the process of learning is connected with increasing ATP-ase activity in ultrastructures of the nucleolus, pericaryon and synapses of some neurons participating in the formation of trace processes in the brain.


[Formation of the circulatory bed of the neuromuscular spindles in forearm and hand muscles]. The data are presented on the formation and main constitutional principles in the blood supply of the neuromuscular spindles in the human forearm and hand during embryogenesis and early postnatal life. It has been stated that the neuromuscular spindles posses their own microcirculatory bed which is formed by the vessels of the surrounding muscular tissue, tends to separate in the course of development and subdivides into two parts: extracapsular and intracapsular. The vessels of the extracapsular part form dense capillary nets on the external surface of the capsule and follow extracapsular parts of the intrafusal muscular fibres. The intracapsular vessels either cover the internal surface of the capsule, or adjoin the intrafusal muscular fibres, or else run in the free subcapsular space.


[Morphogenesis of immune complex glomerulonephritis]. Morphological changes in the kidneys in nonspecific ulcerative colitis were studied and the following variants of the kidney involvement were established: (1) allergic changes manifested by membraneous and mesangio-proliferative glomerulonephritis, renal vasculitis, phenomena of stromal desorganization with lymphoid and histiocyte infiltrations; (2) metabolic changes manifested by various kinds of degeneration of the tubular apparatus including changes typical of potassium-deficient nephropathy; (3) toxic -- necrotic nephrosis and (4) infectious -- nonsuppurative and suppurative interstitial nephritis.


The dental care of handicapped children in South Australia. Sixty-two per cent of handicapped children had a dentist willing to provide treatment; 55 per cent and 41 per cent were examined and were treated at least annually. Approximately 58 per cent were reported by their guardians to be manageable in general dental practice. Treatment was provided under general anaesthesia for 29 per cent of the children, although 39 per cent were considered by their guardians to require this procedure. Factors related to type and frequency of dental treatment are discussed.


Post-mortem electrical stimulation of muscle and its effects on sarcoplasmic reticulum adenosine triphosphatase. Sarcoplasmic reticulum (SR) was isolated from control muscles and from muscles which had been subjected to short-term post-mortem electrical stimulation. Both preparations had similar protein compositions but the SR from electrically stimulated muscle had a lower 'extra' ATPase activity. The ability of the SR preparations from electrically stimulated muscles to accumulate Ca2+ was about the same as the controls. There was, therefore, an apparently greater efficiency of Ca2+ transport in the isolated vesicles, the reason for which is not known, but an alteration in the 'leakiness' of the membrane may be involved. Purified ATPase isolated from control and stimulated SR contained, in addition to the ATPase protein, a polypeptide of molecular weight about 30 000. The purified ATPase vesicles from electrically stimulated muscle had a reduced activity as measured by ATP splitting activity, phosphoenzyme formation from either inorganic orthophosphate (Pi) or ATP, or by an ATP in equilibrium Pi exchange reaction. These reduced activities probably result from an alteration in the binding affinities of the ATPase for ATP and Pi. The low affinity site for calcium binding was not affected by electrical stimulation. Purified ATPase vesicles from stimulated muscle were more susceptible to proteolytic attack, suggesting that the conformation of the protein or its association with the membrane lipids had been altered.


The management of gastroschisis.

The management of gastroschisis. A review of gastroschisis treated at the Royal Alexandra Hospital for Children, Sydney, in the ten years between 1967 and 1976, was carried out. Early postoperative deaths occurred in those with poor general condition before and immediately after the operation. The presence of a gastrostomy appears to be most effective in the immediate postoperative period to assist in decreasing intraabdominal pressure. The results of three initial operative methods are discussed. The three procedures are the Gross method; prosthetic closure; and the Savage and Davey method of transverse incision and closure. The purpose of this paper is to suggest that the procedure described by Savage and Davey has been a most successful procedure in providing reliable and safe method of closure of gastroschisis, avoiding the complications and morbidity of staged closure using prosthetic material.


Isolation and partial characterization of magnesium ion- and calcium ion-dependent adenosine triphosphatase activity from bovine brain microsomal fraction. Microsomal fraction was prepared by ultracentrifugation of homogenates of cortical tissue from bovine brains. The preparation displayed ATPase (adenosine triphosphatase) activity in the presence of Mg(2+) (6.4mumol of P(i)/h per mg of protein) and Ca(2+) (3.4mumol of P(i)/h per mg of protein). Kinetic analysis of the activation of the enzyme preparation by Ca(2+) resulted in the demonstration of two apparent K(m) values for Ca(2+) (6.0x10(-8)m and 1.2x10(-6)m). Treatment of the microsomal membranes with Triton X-100 resulted in solubilization of the ATPase, though with some loss of activity. The solubilized microsomal proteins were incorporated into liposomes. By incubation of the liposomes in media containing (45)Ca(2+) an ATP-dependent uptake of Ca(2+) was demonstrated. The solubilized preparation was subjected to preparative isoelectric focusing in granulated gel beds. Two distinct peaks of Mg(2+)- and Ca(2+)-dependent ATPase activity were observed at pH4.8 (peak 4.8) and at pH6.3 (peak 6.3). The material isolated in peaks 4.8 and 6.3 was focused in polyacrylamide gel with pH gradients. The material corresponding to peak 4.8 consisted of a single protein, whereas peak 6.3 contained one major and at least one minor protein. Sodium dodecyl sulphate/polyacrylamide-gel electrophoresis confirmed these results and indicated that the major component of peak 4.8 and the protein of peak 6.3 both had a molecular weight of 105000. The material in peaks 4.8 and 6.3 was assayed for ATPase activity in the presence of various concentrations of Ca(2+). Kinetic analysis of the results for peak 4.8 demonstrated an apparent K(m) value for Ca(2+) of 4.1x10(-8)m. The enzyme isolated at pH6.3 had an apparent K(m) value of 3.8x10(-6)m. However, when the material from peak 4.8 was incubated in the presence of 1mm-Mg(2+) the ATPase could not be activated by Ca(2+).


[Long term effect of ipratropium bromide on gastric secretion]. In a randomised clinical trial in 10 patients, the effects of a new anticholinergic, 8-isopropyl-3 alpha-DL-tropoyloxy-1 alpha H, 5 alpha H-tropanium hydroxide (ipratropiumbromide, active principle of Atrovent), on pentagastrin-stimulated gastric secretion was investigated. The study was performed in comparison to placebo, using the double-blind technique. Each patient served as his/her own control. As earlier test results seemed to indicate that ipratropium bromide had a particularly long duration of action, the special aim of the trial was to clarify whether an oral dose of 30 mg of the product inhibits gastric secretion for more than 11 h after administration. The findings show that basal acid secretion (BAO) was significantly reduced 11 ts following placebo. On the other hand, upon determination of maximum acid secretion (MAO) 12--13 h following administration, there was no difference between the anticholinergic and placebo. The results of the study of the study are discussed.


Additional pharmacological aspects of orgotein, a metalloprotein with superoxide-dismutase activity. Orgotein is a copper- and zinc-containing protein with superoxide-dismutase activity which can be isolated from bovine liver and erythrocytes. The effects of this drug on adjuvant -induced arthritis in rats, and particularly on the changes in erythrocytes sedimentation rates and plasma fibrinogen levels induced by this experimental infection, were studied. Orgotein was also assayed on nystatin-induced paw edema, passive cutaneous anaphylaxis and Arthus reaction, in rats. Finally, studies on platelet aggregation and the prostaglandin system were conducted. Given at doses of 2.5 and 5 mg/kg i.p. for 14 days to arthritic rats, orgotein normalized the serum changes, inhibited the foot swelling and improved the performance time on the rotating bar. The drug reduced, after a single dose, the nystatin-induced edema, whilst it showed no effects on the immunological inflammations, platelet aggregation and prostaglandin system. The probable mechanism of action is discussed.


Morbidity in gynaecological day-case surgery. A comparison of two anaesthetic techniques. The effectiveness of fentanyl, given as part of the anaesthetic technique, in reducing abdominal pain following outpatient gynaecological surgery has been examined. It was found to reduce significantly the frequency of abdominal pain in the period extending from discharge from hospital to the first evening, while not compromising surgical conditions nor increasing the frequency of other post-operative sequelae such as nausea and vomiting.


Comparison of anti-pollution modifications of Mapleson A and D anaesthetic systems. Hafnia A and Hafnia D anaesthetic systems are non-polluting modifications of the Mapleson A and D systems. The excess gas is vented in the Hafnia systems directly and continuously via a calibrated ejector flowmeter. Sixteen adult patients anaesthetized for abdominal surgery were ventilated and either Hafnia A or D systems at six different fresh gas flows. No difference between the Hafnia A and D systems could be demonstrated in the values of arterial carbon dioxide tension measured with the same fresh gas flow, despite gas flows in opposite directions.


Contrasts in the actions of protein antibiotics on deoxyribonucleic acid structure and function. The protein antibiotics neocarzinostain (NCS), macromomycin (MCR), and auromomycin (AUR), which is closely related to MCR, have been compared for their in vitro and in vivo actions on deoxyribonucleic acid (DNA). NCS, markedly stimulated by 2-mercaptoethanol, is much more active in inducing strand scissions in superhelical pMB9 and linear duplex lambda DNA than AUR, which is slightly inhibited by 2-mercaptoethanol. Purified MCR, even at very high levels, does not give any significant amount of cutting with either DNA substrate. 2-Propanol stimulates the activity of NCS but inhibits that of AUR. On the other hand, the antioxidant alpha-tocopherol strongly inhibits DNA breakage by both drugs. The intercalating drugs ethidium bromide, daunorubicin, proflavin, and actinomycin D at low concentrations inhibit DNA scission by AUR. The levels of intercalators required to inhibit NCS activity to comparable levels are about 10 times higher than those for AUR. Although MCR has virtually no in vitro DNA cutting activity, it is, like AUR and NCS, cytotoxic, as measured by the inhibition of DNA synthesis and induction of DNA strand breakage in HeLa cells.


Fluorescence energy transfer between subfragment-1 and actin points in the rigor complex of actosubfragment-1. The fast-reacting thiol (SH1) of myosin subfragment-1 (S-1) was covalently and specifically labeled with (iodoacetamido)fluorescein (IAF), while Cys-373 of actin was also covalently and preferentially labeled with N-(iodoacetyl)-N'-(1-sulfo-5-naphthyl)ethylenediamine (1,5-IAEDANS). The method of fluorescence energy transfer was used to examine the spatial proximity between the two sites, i.e., SH1 and Cys-373, in the rigor complex of acto-S-1. Approximately 30% fluorescence energy transfer was observed from the 1,5-IAEDANS on actin as a donor to the IAF on S-1 as an acceptor in their rigor complex; under certain assumptions this corresponds to a distance of ca. 6.0 nm.


Rapid kinetics of calcium ion transport and ATPase activity in the sarcoplasmic reticulum of dystrophic muscle. Vesicular fragments of sarcoplasmic reticulum were isolated from pectoralis muscle of normal and dystrophic chicken. Purification of both preparations was equally satisfactory, as shown by a prominent ATPase band in electrophoresis gels. Measurements of ATPase phosphorylation, Ca2+ transport and Pi cleavage by rapid quench methods revealed a lower specific activity of the dystrophic vesicles with respect to all of these functions. On the other hand, Ca2+-independent ATPase activity was found to be increased in dystrophic vesicles. It is suggested that a fraction of ATPase units of dystrophic sarcoplasmic reticulum is not activated by Ca2+, owing to an altered protein assembly within the membrane bilayer. In fact, when the membrane structure is perturbed by detergents normal and dystropic preparations acquire an equally high Ca2+-dependent ATPase.


DNA damage and repair in relation to cell killing in neocarzinostatin-treated HeLa cells. To elucidate the mechanism of the cell killing activity of neocarzinostatin on mammalian cells, the drug-induced damage of DNA and its repair were examined. Very low doses of neocarzinostatin, at which high survival of cells was observed, clearly produced single-strand breaks of DNA and decomposition of the 'DNA complex', but these damages appeared to be repaired almost completely. At higher doses of neocarzinostatin, single-strand breaks were repaired to a considerable extent while double-strand breaks seemed not to be repaired. The number of non-repairable single-strand breaks was about twice that of double-strand breaks. This implies that single-strand breaks are repaired except for those constituting double-strand breaks. Although at low levels of neocarzinostatin repair of double-strand breaks may occur, the correlation existing between the colony-forming ability of cells treated with neocarzinostatin and non-repairable DNA breakage suggests that production of a small number of critical non-repairable double-strand breaks per cell may be responsible for the cell killing activity of the drug.


Strand scission of superhelical and linear duplex DNAs by the antitumor protein macromomycin. Relationship of in vitro DNA damage to cell growth inhibition. Macromomycin, a protein antitumor drug, was found to cause strand scissions in vitro in superhelical PM2 and SV40 DNA as well as linear duplex lambda DNA. DNA damage appeared to be single rather than double-strand scissions, and there is an indication that DNA breaks occur at some preferential base sites. The DNA breaks were predominantly true single-strand scissions as opposed to alkali-labile bonds. The cutting reaction was inhibited by low temperature (0 degrees C) and reached a maximum at 45 degrees C. The reaction was not affected by 2-mercaptoethanol, although EDTA did cause a slight decrease in the reaction rate. MgCl2 was found to be an effective inhibitor of the strand scission activity of the drug. The rate of DNA cutting was linear over a wide range of DNA substrate levels. There appeared to be a correlation between the drug's ability to damage DNA and to inhibit cell growth in that similar losses of these two activities occurred as the drug was thermally denatured.


ATPase and alkaline phosphatase activities of chick and rat small intestinal mucosa. The alkaline phosphatase and (Ca2+ +Mg2+)-ATPase (ATP phosphohydrolase, EC 3.6.1.3) of chick and rat small intestine have been investigated. The same pH optimum was found for membrane-bound and solubilized alkaline phosphatase, whereas those of the corresponding ATPases differed. The solubilised ATPases had inhibition and activation characteristics similar to those of alkaline phosphatase but markedly different from those of the membrane-bound ATPase. These results suggest that membrane-bound alkaline phosphatase and ATPase are not the same enzyme.


[Exogenous orthophosphate regulation of ATPase activity of E. coli cells]. The effect of exogenous orthophosphate and mutations in genes, regulating the Pi transport system, on the ATPase activity of E. coli subcellular fractions was studied. It was shown that the orthophosphate starvation resulted in the cessation of the increase in the ATPase activity of membranes and was accompanied by the increase in the analogous activity of a soluble fraction at the expense of the derepression of alkaline phosphatase possessing this activity. The disturbance, resulted from the mutation of protein components participating in the specific binding and transport of orthophosphate, changed the ATPase activity of subcellular fractions: increased the ATPase activity of soluble fraction (independently of the presence of orthophosphate in medium), did not affect significantly the activity of membrane--bound ATPase in the presence of orthophosphate and decreased this activity in the absence of orthophosphate. The data obtained point to the fact that components, binding exogenous orthophosphate and transporting it into a cell, affect the rigidity of the ATPase bound E. coli cytoplasmic membrane. Mutations resulting in the defect in these components relax this bound and lead to the detection of ATPase proper in the periplasm.


[Inactivation of factor X by plasmin].

[Inactivation of factor X by plasmin]. Plasmin does not activate factor X into the enzyme--factor Xa. On the contrary, the enzyme inactivates factor X, rendering it incapable of conversion into factor Xa during incubation in 25% sodium citrate. After proteolysis by plasmin the prothrombin preparations contaminated with factor X lose their ability to generate thrombin. This ability is partially restored by an addition of factor X.


[Energy-dependent uptake of phenazinemethosulfate in isolated chloroplasts]. The concentration and absorption of methylphenazinium cations (MP+) in suspensions of pea chloroplasts are simultaneously lowered during rapid (approximately 10s) illumination. The light-induced changes of absorption and concentration of MP+ reveal similar sensitivity towards some inhibitors and uncouplers and are determined by MP+ uptake by the thylakoids. The time-course of light-induced MP+ uptake was found to be modified in the presence of dithioerythritol, Mg2+ and ATP, i. e. under conditions which induce the ATPase activity and ATP hydrolysis in chloroplasts. The kinetic curve of light-induced MP+ uptake under these conditions consists of a relatively fast (approximatley 10 s) and a slow (approximately 10 min) components. The slow ATP-dependent component of MP+ uptake is enhanced by low concentrations of gramicidin and is completely inhibited by the energy transfer inhibitor--dicyclohexylcarbodiimide. The data obtained suggest that the light-induced energization of the chloroplast membrane is accompanied by the transport of MP+ into the thylakoids against the electrical potential and concentration gradients.


Quantification of muscle tremor of Huntington's disease patients and their offspring in an early detection study. Accelerometer measurements of muscle tremor yielded significant findings for both Huntington's disease (HD) patients and their genetically at risk offspring. Although affected individuals are usually characterized by gross involuntary muscle movements, alterations in minute muscle tremor were also found in our sample of ten HD patients. Irregularities in tremor patterns were intensified with increased time since onset of the disorder and in addition reflected the effects of drug therapy for those on medication. The use of accelerometer measurements of muscle tremor may therefore, prove to be useful in evaluating new medications for affected individuals. For high risk immediate family members currently there is no safe and reliable method to identify, prior to clinical onset, any among them who will develop HD. Aberrant muscle tremor patterns resembling that shown by HD patients were found in one-third of a sample of 15 genetically at risk offspring. In the event an effective method of treatment is developed, early recognition of HD gene carriers by accelerometer tremor measurement could result in control of the disorder prior to substantial neurological damage.


[Kinetic differences in induction of the killers and producers of the macrophage migration inhibitory factor (MIF) in primary and secondary mixed murine leukocyte culture test]. Conditions are selected for the killer induction during primary and secondary responses in the one-way MLC, stimulated by x-irradiated or killed allogenic lymphocytes. MIF is found in the MLC culture medium as a sharp peak on the 2nd or the 3rd day of the primary reaction, or as a plato from the 1st day of the secondary reaction. In contrast, the killers are shown to be induced much later reaching their maximum on the 5th and the 4th days, respectively. If heated, instead of irradiated, allogenic lymphocytes were used for stimulation of the primary MLC reaction, the MIF-producer kinetics was not changed, but the killer induction was found to be delayed.


[Blood serum as a factor of chromatin condensation in trisomy-21 (Down's syndrome)]. The influence of blood sera from patients with Down's syndrome and healthy ones, and different serum fractions on the structure of the deoxyribonucleoprotein systems (DNP-system) has been studied. It was demonstrated that non-fractionated sera of the patients produce a condensation effect on the DNP-system in contradistinction to the sera from healthy people. The analysis of the action of single serum fractions showed that different condensation effect results from the activity of high molecular nondialysable thermosensitive components whose action disappears at gel-filtration of serum proteins. A possibility of the humoral control over chromatin structural organization in vivo is discussed in terms of the evidence on the similarity of serum proteins and chromosomal nonhistone proteins.