Comparison of "invasive" and "non-invasive" strains of Staphylococcus epidermidis by phage typing. Seventy strains of coagulase-negative staphylococci isolated from blood of patients together with 41 strains of these bacteria isolated from the skin were typed by three different phage sets. Different percentages of phage typability by compared phage sets were found. Blood culture strains showed phage pattern Ph10/U14/U16 while other strains were of different phage patterns.


Use of a phage set for the ecological typing of coagulase-negative staphylococci. The staphylococcal flora of skin and acne lesions of 98 patients was analysed by the use of phage typing and biotyping methods. It appeared that in some individuals a relatively stable staphylococcal flora was present while others harboured 7 or more different strains. The same S. epidermidis strains were found on different skin sites and in acne lesions of a given individual. Examples of different carriage patterns were given.


Serological characterization of phages of coagulase-negative staphylococci. Selected 22 phages of coagulase-negative staphylococci were tested against group-specific antisera for Staphylococcus aureus phages using a neutralization test. Fourteen of the tested phages were classified into the serological group B and one into the group F. All other phages were resistant to the antisera against S. aureus phages but cross-reacted with the antisera produced against themselves. Therefore they could be joined together into a new serological group of the staphylococcal phages.


Activity spectrum of micrococcal and staphylococcal phages. The activity spectrum of 4 polyvalent Staph. aureus-phages, of 22 phages from coagulase negative staphylococci and of 64 micrococcal phages was established on 20 Staph. aureus-strains, 116 coagulase-negative staphylococci and 142 micrococci. Staphylococcal phages showed to be only active on strains of the genus Staphylococcus and on cocci related to this genus. Micrococcal phages on the other hand lysed only micrococci.


Cell wall structure of coagulase-negative staphylococci and its relation to adsorption of phages. The coagulase-negative staphylococcal species S. xylosus and S. saprophyticus are able to inactivate phages of the International Basic Set for S. aureus. The cell wall teichoic acids of these species contained two polyols: glycerol and ribitol. Removal of ribitol teichoic acid resulted in a parallel decrease in the ability of the cell walls to inactivate the phages.


Phage typing of coagulase-negative staphylococci. 218 bovine and 116 human strains of coagulase-negative staphylococci and 46 bovine Staphylococcus aureus strains were typed with the Verhoef-phage set for human staphylococci and the Holmberg-set for bovine staphylococci. 22.5% of the bovine strains were lysed by the bovine phages and only 3.2% by the human phages. None of the bovine Staph. aureus strains could be typed. 21% of the human strains tested were lysed by the human phages and only 5.2% by the bovine phages. These results clearly demonstrate the need of separate phage sets for the typing of bovine and human coagulase-negative staphylococci.


Preliminary results of phage typing of coagulase-negative staphylococci with the set of typing phages of Pulverer and co-workers. 120 strains of Staphylococcus epidermidis isolated from clinical material were typed with the set of 16 test phages described by Pulverer et al. (1975). 58 (48%) strains were typable with RTD and additionally 12 strains with 100 times RTD. The pattern Ph10/U14/U16 was observed most common (36 strains), followed by the pattern U14/U16 (11 strains). One strain showed lysis reactions with all typing phages. With 61 strains phage U14 gave a lysis whereas phage U20 reacted only with 4 strains. The S. epidermidis phages were not specific for this species, at least some of these showed lysis reactions with S. aureus strains. The lysis pattern most often observed was Ph10/U14/U16. There was no correlation between the patterns given by the S. aureus test phages and those by the S. epidermidis phages.


Phage typing and biotyping of coagulase-negative staphylococci. A total of 211 strains of coagulase-negative staphylococci isolated from clinical materials were tested by use of 16 phages of PULVERER's set and biochemical methods proposed by KLOOS and SCHLEIFER. It appeared that 75% of tested strains was typable by used phages and ninety different phage patterns were observed. Most strains were classified as Staphylococcus epidermidis and the rest as S. warneri, S. simulans, S. hominis, Single strains represented species: S. capitis, S. haemolyticus and S. cohnii. No segregation of different phage patterns into particular species was found.


Electron microscopic morphology of phages of coagulase-negative staphylococci. Nine phages of coagulase-negative staphylococci were studied carefully with regard to their electron microscopic morphology. Two different groups of phages were detected: the larger phages showed heads of 121 nm diameter on average and tails with 229 nm length and 23 nm width. The smaller phages were characterized with heads of about 76 nm diameter and tails of about 177 nm length and 13 nm width (negatively stained with KPT).


A proposal for further modification of the phage-typing system for coagulase-negative staphylococci. Our phage-set, published in 1975 (6) was modified in that other staphylococcal hoststrains were found more suitable for the propagation. This new typing set of 15 phages should replace our old phage-sets. In comparing the phage-sets of Dr. Verhoef, Dr. Parisi and Dr. Blouse with our phages, the advantages of our new phage-set could be demonstrated. Lysogeny induction experiment with mitomycin C and UV-rays showed all staphylococcal host strains to be lysogenic. Conclusions of the studies performed were derived from and discussed.


[Antigenic structure of Rickettsia of the tick-borne spotted fever group isolated in the Armenian SSR]. The authors present data concerning the study of the antigenic properties of rickettisa of the tick-borne spotted fever group isolated from the Ixodes ticks in the Armenain SSR. In order to determine the species of the isolated strains a method of serological identification of rickettsia in the complement fixation reaction with the species-specific immune sera of albino mice was used. The results obtained permitted to refer the Armenia-74, No. 11, 29, and 57 species to the R. sibricia species.


[Current methods of intraspecies typing of Shigella sonnei. 3. Bacteriophage typing]. Data are presented concerning the study of the phage type of Sh. sonnei isolated in various regions of the USSR. The strains isolated belonged to 64 phage types corresponding to the Hammarström's scheme. A variety of Shigella sonnei phage types both in one and in different territories of the country  provided future prospects for successful use of phage typing for the purpose of epidemiological supervision and analysis of dysentery morbidity.


[Participation of monoaminergic mechanisms and the striatum in the development of "petit mal" induced by corazole]. In gradual cumulation of subconvulsive doses of corasole in mice there are certain changes of behaviour and electrographical signs which are close to "petit mal": slow negative waves and peak-wave complexes on the EEG, myoclonic jerks. An increase of monoaminergic transmission of apomorphine, DOPA, or 5--hydroxyhyptophane weakens the preconvulsive effect of corasol, while its inhibition by aminasine, haloperidol and p-chlorphenylalanine on the contrary increases it. A low frequency electric stimulation of the striatum potentiates the expressiveness of corasole "petit mal", while its destruction limits it. A bilateral destruction of the striatum eliminates the action of apomorphine, DOPA and haloperidol but only slightly changes the effect of aminazine, 5-hydroxytryptophane and p-chlorphenylalanine.


Role of heparin in the interaction of serine proteinases with antithrombin III. To characterize the mode of action of heparin, the kinetics of inhibition of thrombin, factor Xa, and plasmin by antithrombin III was studied without and in the presence of heparin. Following the concentration dependence of inactivation a linear dependence was found between the apparent first-order inactivation rate constant and the anti-thrombin III concentration. This behaviour is typical of enzyme-activator interaction. Values of kinetic constants of the inactivation reaction could be determined. Thus, heparin acts obviously as an activator of the enzymes and enhances their affinity for antithrombin III.


Biochemical and histochemical features of human cultured cells (EUE) adapted to hypertonic medium. EUE cells from a human heteroploid line cultured in hypertonic medium (0.274 M NaCl) modify their lipid pattern: sulfolipid concentration reaches 86 to 90 microgram/mg protein whilst it ranges between 19 to 32 microgram/mg in cells cultured in isotonic medium. Ganglioside concentration reaches 2.6 nmoles of sialic acid/mg protein (after 75 days) and 13 (after 85 days) in hypertonic saline medium. Whilst it is 0.5 in isotonic medium. Phospholipid concentration does not show any similar change. Cytoenzymatic analysis reveals that dehydrogenases (lactate, G-6-P dehydrogenases, tetrahydrofolate reductase and NADH diaphorase) appear strongly enhanced in cells grown on hypertonic medium. On the contrary higher acid phosphatase and ATPase activity was demonstrable in cells grown on isotonic medium. These results are similar (except for ATPase activity) to those observed in salt secreting glands involved in strong osmotic work. The results are discussed in relation to the problem of energy supply in cells performing osmotic work.


The ejector flowmeter: an evaluation of its accuracy. The accuracy of five ejector flowmeters was assessed using three different gases and four flow-rates. A soap-bubble flowmeter was used for the calibaration. Significant variations were found between individual flowmeters and between different gas mixtures. No variation was found between the four different flowrates, indicating that the calibration is linear. The mean calibration factor was 84.8% +/- 4.1 (100% O2:87.4 +/- 3.4, 50% N2O/O2: 84.2 +/- 2.8, and 100% N2O: 83.0 +/- 4.6).


Somatostatin in the treatment of patients with extra-pyramidal disorders and patients with EEG abnormalities. The growth hormone release inhibiting hormone acts probably both as a true hypophysiotropic hormone and as a neuroregulatory substance. Neurophysiological studies have shown that somatostatin is a CNS depressant. Somatostatin might therefore be of therapeutic significance in neurological diseases. Sixteen patients with different extrapyramidal disorders and seven patients with various EEG abnormalities were tested with 2-hour somatostatin infusions and control infusions with saline. Somatostatin did not induce any improvement or deterioration of symptoms, signs, or EEG abnormalities in any patient.


Ovarian biopsy in the evaluation of amenorrhea. Endoscopic ovarian biopsies were performed on 78 amenorrheic patients in an attempt to determine the etiology of their amenorrhea and predict its prognosis, correlating the histologic examination with physical findings, endocrine patterns and cytogenetic studies. Ovarian follicles were present while gonadotropins were high in 14 cases (6 primary, 8 secondary) and there were no follicles in 4 cases (3 primary, 1 secondary) whose gonadotropins were low. Secondary sex characteristics were well developed without prior estrogen stimulation in 5 cases of primary amenorrhea who had no follicles and whose gonadotropins were either low, 3, or high, 2. The mere presence of ovarian follicles was not enough to make them responsive to gonadotropin stimulation whether endogenous or exogenous; a phenomenon that had to do with the quality and quantity of germinal follicles available. The histologic examination of ovarian tissue for the evaluation of amenorrhea has been made feasible and relatively safe through recent advances in endoscopic techniques.


Follicular development in ovaries of children with Down's syndrome. Ovaries of children with Down's syndrome were examined histologically in order to determine in what way the ovarian development differed from the normal. Twenty-six specimens obtained at autopsy at various ages between birth and 14 1/2 years were available and compared with ovaries from normal children of similar ages. All ovaries from normal children were characterized by active follicle growth. The ovaries of the children with Down's syndrome, however, showed absence or retardation of follicle growth. Furthermore the number as well as the size of the antral follicles differed from those in the normal ovary. The decrease of the number of small follicles occurs earlier in life in the ovaries of children with Down's syndrome than in the control. The possible relationship between an abnormal ovarian growth pattern and hormonal imbalance is discussed.


Contribution to the knowledge of the fine structure of chondrosarcoma of bone. With a note on the localization of alkaline phosphatase and "ATPase". Seven well differentiated chondrosarcomas of bone have been analyzed by electron microscopy, and the fine structural localization of adenosine triphosphatase and nonspecific alkaline phosphatase has been elucidated. On the basis of the fine structural appearance, two distinct cell types were shown to constitute the tumor tissue: chondrocyte-like cells and large "mitochondria-rich cells". Large, multinucleated cells in the tumor did not seem to correspond to osteoclasts but rather were likely to represent true neoplastic cells. Some chondrocyte-like cells appeared to be binucleated by virtue of deep, groove-like nuclear indentations. Adenosine triphosphatase and alkaline phosphatase were associated with the plasma membrane of both chondrocyte-like and mitochondria-rich cells suggesting that they might be of common origin. Normal chondroblasts and chondrocytes lack histochemically demonstrable adenosine triphosphatase on their plasma membrane. Presence of this enzyme in the tumor cells may indicate that they are histogenetically related to immature non-chondroid matrix forming cells (known to carry the enzymes).


Stimulation of human fetal lymphocytes by lipopolysaccharide B in culture. Studies on cells circulating in maternal blood. Lipopolysaccharide B (LPS) was used in attempts to stimulate fetal cells circulating in the maternal blood during pregnancy. Crystalline leukoagglutinin (LA), the mitogenic properties of which are identical with those of phytohemagglutinin, was used as a reference mitogen. When artificial mixtures of varying proportions of lymphocytes from mothers (XX) and their newborn male infants (XY) were co-cultured in the presence of these mitogens. LPS brought about a definite enrichment of XY mitoses, indicating that even under these conditions of co-culture, LPS preferentially, though not exclusively, stimulates the infant cells. When cells from the blood of 13 women pregnant in the second trimester with a male fetus were cultured with LPS as a mitogen, all mitoses were found to be XX. Since interphase Y chromatin occurred in uncultured lymphocytes from these women (cells containing Y chromatin were found in 5 out of 6 women tested), we conclude that LPS is unable to stimulate, or at least induce mitoses, in fetal cells circulating in the blood of pregnant women. The nature of these cells is discussed.


Blood flow, calcium deposition and heat loss in reindeer antlers. Antler blood flow was studied in a 2 year old male reindeer during the last half of the antler growth period using an electromagnetic flow probe chronically implanted around the superficial temporal artery. Arteriovenous (a-v) differences of calcium were measured on antler blood. The blood flow increased from 60--90 ml/min when the antler was half-grown to 100--120 ml/min when fully developed. Subsequently a reduction was observed towards shedding. Positive a-v plasma calcium differences (on average 0.2 mM) were recorded during the period of active growth. Two bulls maintained positive a-v calcium differences after a 48 hour starvation period, in spite of reduced arterial calcium concentrations. Exercise to near exhaustion caused a 2 degrees C rise in the rectal temperature. Antler blood flow was decreased immediately after exercise and returned to pre-exercise values usually within 5--10 min. Since no overshoot in antler blood flow was recorded during the hyperthermia it is concluded that variations in blood perfusion of the antlers are without importance in the defence against hyperthermia during and after exercise.


Distribution of maximum coronary blood flow in the left ventricular wall of anesthetized dogs. Blood flow in the circumflex branch of the left coronary artery was recorded by electromagnetic flowmeter. In a group of dogs progressive hemodilution was performed until the diastolic reactive hyperemic response to 10 s occlusion of the circumflex branch disappeared ("optimum" hemodilution). At this degree of hemodilution the distribution of blood flow in the left ventricular free wall was evaluated by measuring tissue activity concentrations of Xe-133 and radioactive microspheres after bolus injection into the aortic root. "Optimum" hemodilution was accompanied by a sixfold increase in systolic coronary flow, a 3-fold increase in diastolic flow and a relative endocardial hypoperfusion. These results indicate that the endocardial blood flow reserve is lower than the epicardial. This conclusion is supported by the influence of spontaneous oscillations of arterial blood pressure (Traube-Hering waves) on systolic and diastolic coronary blood flows before and during "optimum" hemodilution. In another group of dogs maximum coronary vasodilatation was produced by occlusion of the left coronary artery for 10 s. In this group the distribuition of Xe-133 and radioactive microspheres were measured after bolus injection into the aortic root at peak diastolic reactive hyperemia. The epi- and endocardial distribution of both Xe-133 and microspheres was uniform in the left ventricular wall, indicating a uniform flow to these regions. This might be explained by an increased endocardial perfusion during systole due to loss of myocardial contractility or by a decline towards resting level in epicardial flow at the time of injection, corresponding to a shorter duration of the hyperemic period in the epi- than endocardial region.


Pulmonary abnormalities in mitral valve disease.  Comparison between pulmonary wedge pressure, regional pulmonary blood flow and chest films. Chest films, right sided heart catheterization, and measurement of the regional lung perfusion, using 133Xe, were carried out 31 times on patients with mitral valve disease. A relationship was found between the radiologic evaluation in 3 grades, and the values of pulmonary wedge pressure and the apical and basal perfusion. Changes in flow distribution as reflected in altered appearance of the vessels and the presence of interstitial edema were found to be the most sensitive factors in the evaluation of pulmonary wedge pressure. Chest radiography was thus found suitable for the evaluation of pulmonary wedge pressure in mitral valve disease.


A cell line derived from BBN (N-butyl-N-[4-hydroxybutyl]-nitrosamine)-induced rat bladder cancer: establishment and scanning electron microscopic cell surface characteristics. This research was performed to establish a cell line from experimental bladder tumor and to discuss the biological characteristics of the cell line so established. Tissue cultures of epithelial cells were derived from a rat bladder cancer induced by BBN. The cells showed loss of contact inhibition and the phenomenon of piling up after several subcultures. Colonial cloning was used. The population doubling time of the wild strain and the colonial clones was about 30 h. The chromosomal mode ranged from triploid to tetraploid to tetraploid. Plating efficiency was well below 20%. Intraperitoneal backtransplantation into newborn Wister rats resulted in tumors in all cases. These tumors, in some parts, resembled primary transitional cell carcinoma. The major tumor cell groups, however, showed marked keratinization and the picture of squamous cell carcinoma. The nucleus/cytoplasm ratio and the numbers of nuclei, free ribosomes and intracytoplasmic microfibrils were increased. Dense microvillus arrangements characterized the electron microscopic picture. During the mitotic phase, the cells became large and globular whereas the microvilli were relatively short and were gathered profusely over the whole surface. Cells in the gap 1-synthetic phase developed lamellipodia and pseudpodia-like cytoplasmic processes and were polygonal in shape. Microvilli were present in the central part containing the nucleus, but their numbers were somewhat decreased and their height increased (scanning electron microscopy).


A study of endotoxemia in ulcerative colitis and Crohn's disease. II. Experimental study. The intestinal mucosal barrier of rabbits was damaged by carrageenan-induced ulceration of the colon, superior mesenteric artery occlusion (SMAO) and hemorrhagic shock and the values of Endotoxin (lipopolysaccharide, LPS) were determined by radioimmunoassay and the concentration of lysozyme (LZM) by the turbidimetric method. As a result, endotoxemia was observed in 13 out of 15 carrageenan rabbits, and in all of the SMAO and hemorrhagic shocked rabbits. Serum LZM concentration rose with time in all cases. As to the correlation of LPS and LZM, they changed almost in parallel in carrageenan rabbits, SMAO and hemorrhagic shock. LPS value and LZM concentration in blood were also determined in LPS injected rabbits. It was confirmed that injected LPS increased the LZM concentration of blood. On the basis of these results, it can be concluded that destruction of intestinal mucosal barrier permits an invasion of LPS into blood and then releases LZM into the blood stream.


Endotoxin receptor site. II. Specificity of endotoxin receptor of platelets and sensitivity to endotoxin in vivo. The biological specificity of the endotoxin receptor on platelet membranes was examined. The binding indices of platelets in experimental endotoxemia which was induced by intravenous administration of endotoxin (Lipopolysaccharide of E. coli, Difco) to rabbits were found to be 30% of the control at 60 min after the injection. The result suggests that the endotoxin receptor of platelets was already occupied. The binding indices of human platelets were measured after pretreatment with pharmacologically active substances which were assumed to effect platelet activity. The binding of LPS to platelets showed competitive inhibition at pharmacologically effective doses, but other substances merely inhibited platelet activity. One interpretation is that there is a common receptor on platelet cell membranes for lipopolysaccharide of E. coli and endotoxin. The sensitivity to endotoxin in vivo and binding indices of platelets were examined in rabbits and guinea pigs since their response to endotoxin is almost opposite with regard to sensitivity. The binding indices of platelets from rabbits and guinea pigs showed a positive correlation with the endotoxin sensitivity. Those findings indicate that platelets play a key role in vivo in the clinical course of endotoxemia.


Effect of propranolol on regional myocardial function in anesthetized open-chest dogs with myocardial ischemia. Effects of propranolol on ischemic segmental function were studied in anesthetized open-chest dogs. Two segment-length gauges were used for measuring the regional myocardial function: one was sutured on to the left ventricular surface perfused by the anterior descending coronary artery (ischemic zone) and the other was on to that perfused by the circumflex coronary artery (normal zone). A bolus of propranolol (0.5 mg/kg) was injected into the right femoral vein. Five min later, the left anterior descending coronary artery (LAD) was completely occluded for one mine and thereafter released. Then a second coronary occlusion for 20 min was performed; an interval of 20 min was allowed between two occlusions. Propranolol, in the ischemic segment, apparently decreased the extent of paradoxical lengthening in the late systole following one min LAD occlusion, and facilitated improvement of segmental function after release of the occlusion. Moreover, the extent of abnormal stretching induced by 20 min occlusion during early systole, was also reduced by propranolol pretreatment. In contrast, compensatory increase in shortening by the normal segment was disturbed by propranolol. These results suggest that propranolol might exert a favourable influence on the segmental myocardial function during either transient or maintained myocardial ischemia.


Cancer immunotherapy with levamisole.

Cancer immunotherapy with levamisole. Levamisole, an agent acting upon depressed cellular immunity, enhancing and normalizing it and consequently showing antitumor activity in the cancer-bearing body, was administered to patients with gastrointestinal cancer at a daily dose of 150 mg for three consecutive days every other week, starting as a rule, three days before operation. The patients were evaluated for survival. Of the 143 patients (66 with curative resection, 40 with noncurative resection and 37 without resection) who received levamisole therapy for one month or more, 57 survived postoperatively six months and of 44 treated 37 survived one year. In this study, 185 patients with gastrointestinal cancer were used for comparison purposes. The six-month survival rate was 100% (23/23) in the levamisole treated group and 95.3% (102/107) in the control group after curative resection (p greater than 0.5), 100% (23/23) and 90.5% (49/54) after noncurative resection (p less than 0.01), and 72.5% (8/11) and 33.3% (9/24), respectively, in non-resectable patients (p less than 0.01). The one-year survival rate was 100% (21/21) and 95.3% (102/107) after curative resection (p greater than 0.5), 77.8% (14/18) and 59.3% (32/54) after noncurative resection (0.05 less than p less than 0.1), and 40% (2/5) and 8.3% (2/24) in non-resectable patients (0.05 less than p than 0.1) in the levamisole group and in the control group, respectively. The difference in survival in survival rates between levamisole-treated and control groups was most prominent in the non-resectable patients followed by those undergoing noncurative resection and curative resection.


A new apparatus for visual field testing with binocular fixation. A new instrument for visual field examination with binocular fixation is described. The binocular vision was dissociated with polarizing plates. Only the point of fixation was visible to both eyes while the testing chart (Amsler chart) was visible to one eye in the use of this apparatus. The examination was done with both the patient's eyes open. With the use of this apparatus, not only was the visual line fixed steadily in order to detect various changes of the central visual field due to maculopathy or optic neuropathy and these changes were detected accurately and quickly, but also suppression scotoma associated with amblyopia or squint could be detected quantitatively.


Myelin deficiency in experimental phenylketonuria: contribution of the aromatic acid metabolites of phenylalanine. Retarded body and brain growth and a deficit of myelin in the cerebral hemispheres and the cerebellum were observed in an animal model of phenylketonuria, the p-chlorophenylalanine and L-phenylalanine treated preweanling rat. These manifestations of phenylketonuria were reproduced in rats treated with phenylacetate in amounts approximating those likely to be produced in phenylketonuria. Young rats treated with equivalent amounts of other metabolites of phenylalanine, namely, phenylpyruvate, phenyllactate, and mandelate, which also accumulate in the brain during hyperphenylalaninemia, did not exhibit any toxic effects. Phenylpyruvate did not give rise to phenylacetate in the brain, but a small percentage was converted to phenyllactate. The gross composition of myelin isolated from the brains of saline and phenylacetate treated animals was similar. At various time intervals after subcutaneous injection, phenylacetate in the brain reached levels thirty times those of phenylpyruvate and phenyllactate, although animals received equivalent amounts of the three metabolites. The retarded growth of the body and brain of the young animal treated with phenylacetate may be attributed to the formation of phenylacetylcoenzyme A in the tissues. The site of action is very likely linked to acylcoenzyme A metabolism, i.e., the synthesis and utilization of acetylCoA and acetoacetylCoA, which are involved in reactions generating ATP and energy and in the synthesis of cholesterol and fatty acids. Results of this investigation indicate that growth retardation induced by phenylacetate during the period of very rapid development of the brain is responsible for the mental retardation in phenylketonuria.


Use of the Goal Attainment Scale in the treatment and ongoing evaluation of neurologically handicapped children. Six children with multiple handicaps were treated as a pilot group by a physical therapist, occupational therapist, and a speech/language pathologist. Baseline evaluations were obtained through a compilation of traditional developmental tests. A Goal Attainment Scale technique was introduced to facilitate reevaluation of the children. The advantages of the scale were to facilitate ongoing feedback for both the professionals and the parents as well as to update specific, individualized goals in each therapeutic area. This information was also helpful to third-party payers of service. Results showed that, after an initial period of familiarization, therapists became more accurate in their expectations of progress in treatment. Therapy time spent with each child was also increased without increasing costs or preparation time for each therapist. Specifically, re-evaluation scores obtained on the Goal Attainment Scales approached a normal, expected distribution of values. The potential value of extending the system to more objectively, efficiently, and concisely display treatment results is discussed.


Goal-oriented treatment plans and behavioral analysis. A goal-oriented treatment plan is described and analyzed. Its application to occupational therapy provides the means for objective measurement of multivariant programs and is thus a significant research tool. Accountability factors and other managerial implications are discussed.


Vectorcardiographic diagnosis of right ventricular hypertrophy in the presence of right bundle branch block in young subjects. Two groups of young patients, one with right bundle branch block complicated by right ventricular hypertrophy due to congenital heart disease, the other with right bundle branch block and no right ventricular hypertrophy, could be separated on the basis of a few quantitative vectorcardiographic and electrocardiographic criteria. Vectorcardiographic criteria proved better than electrocardiographic criteria in detecting right ventricular hypertropy in individual patients with complete right bundle branch block. Criteria based on the configuration of the QRS loop were also specific but much less sensitive for the diagnosis of this association. In a similar population, that is, young patients with postoperative right bundle branch block, the existence of a residual right ventricular overload would be strongly suggested by the presence of any one of the following criteria: (1) a clockwise rotation of the QRS loop in the horizontal plane, (2) a ratio of the magnitude of the R wave to that of the S wave (R/S ratio) in lead X at less than 2.0, (3) a mean QRS vector in lead X more negative than--10 mv.msec, or (4) a maximal QRS vector located between 90 degrees and 270 degrees in the horizontal plane. In contrast, an R/S ratio in lead X that was equal or superior to 2.0 or an azimuth angle of the mean spatial QRS vector that was not between 90 degrees and 180 degrees would indicate that the right ventricular conduction defect is probably uncomplicated.


Brief reports decline of Down's syndrome after abortion reform in New York State. Incidence rates derived from prospective studies of 120,000 newborns were applied to live births and induced abortions in order to estimate the trend of Down's syndrome in New York State after liberalization of the abortion law in 1970. Women aged 35 years of older, at higher risk of Down's syndrome births, sought terminations of their pregnancies more frequently than did younger women. The estimated number of newborns with Down's syndrome in the state declined 20 percent from 1971 to 1975. In New York City, more pregnancies in the high-risk age range were aborted than were carried to term. These trends indicate that abortion reform may have made a significant contribution to the reduction of severe mental retardation.


Intelligence levels of Down's syndrome children. Intelligence levels of a sample of 180 Down's syndrome children were reported, and the results indicated that their abilities are not as limited as previously thought. The introduction of special developmental programs from birth onwards appears to have promoted an increase in intellectual development. Lack of extended educational opportunity may account for the apparent decrease in intellectual function in Down's syndrome adolescents. It is suggested that school placement be based on demonstrated present ability rather than assumed long-term potential inferred from autosomal and physical characteristics.


Genetic influence on cadmium-induced hypertension. Dahl hypertension-resistant (R) and hypertension-sensitive (S) rats were used to determine whether cadmium-induced hypertension is dependent on genetic predisposition. In experiment I, 16 wk-old R and S rats of both sexes were injected with two doses of cadmium (1 and 2 mg/kg body wt, ip), whereas the controls received the same volumes of saline. Hypertension and renal vascular changes were observed in cadmium-injected S rats but not in R rats. The S females appeared more sensitive than S males to the hypertensinogenic effect of cadmium. In experiment II, groups of weanling female R and S rats were given 0, 1, 2.5, 5, or 10 mg cadmium/liter drinking water and fed either a low-salt (0.4% NaCl) or a high-salt (4% NaCl) diet for 28 wk. Cadmium produced cardiac hypertrophy (1 mg cadmium/liter) and hypertension associated with renal vascular changes (1--5 mg cadmium/ liter), and it enhanced proteinuria (1-10 mg cadmium/liter) in S rats on a low-salt diet. Also, the development of salt-induced hypertension was accelerated in cadmium-fed (1 and 2.5 mg/liter) S rats. These adverse effects of cadmium  were not detected in R rats on either salt diet. In experiments I and II, cadmium concentrations in the kidneys and liver of S rats were higher (P less than 0.001) than in those of R rats. These data indicate that genetic differences influence the pathogenesis of cadmium-induced hypertension.


[Chromosomal anomalies and intelligence deficiency (author's transl)]. The relations between chromosomal diseases and mental retardation can be envisaged in three different ways: 1) Pharmacological approach shows a peculiar sensitivity of the cholinergic system in trisomic 21 children. A trouble in the manufacture of cholinergic mediator is plausible. 2) General biochemistry shows a slight shift of the glycolytic pathway in trisomics 21 as well as some localised abnormalities of amino-acids. 3) Gene mapping allows the localisation of the main responsable genes on band q22. 1 and among them the gene coding for superoxide dismutase 1. Also glutathion peroxidase is elevated. These disparate facts are discussed in the light of a model of the machinery regulating the production of chemical mediators. Comparison with other diseases lead to the hypothesis that rather simple and localised mechanisms could be specially important.


[Mechanism of biosynthesis of glycoconjugates at the level of the arterial walls after contact with alloplastic materials (author's transl)]. The object of this work was to show that here exists after contact with foreign substances, a construction of protein, glycoprotein and mucopolysaccharide macromolecules at the level of the intima of the great vessels. Woven Dacron prostheses have been implanted in the arterial circulation of dogs (on the subrenal abdominal aorta). After removal of vascular segments, we carried out a subcellular fractioning, controlled and studied in an acellular system in vitro the activity of the glycosyltransferases implied in the construction of glycan chains of glyccproteins. The results are discussed in relation to the duration of implantation of the prosthesis. The modifications observed differ according to the position of the sugars in the glycan chains, in particular as far as sialic acid is concerned, and lead to an interpretation of the mechanism of endovascular reactions when faced with foreign material.


Age-related changes in percentage of fiber types and mean fiber diameters of the ovine quadriceps muscles. Mean fiber diameters and percentages of each fiber type of the vastus lateralis, vastus medialis, rectus femoris, and vastus intermedius muscles from 15 sheep, ranging from 1 day to 5 years of age, were determined. Myosin adenosine triphosphatase and nicotinamide adenine dinucleotide-tetrazolium reductase stained sections were used. The vastus lateralis, vastus medialis, and rectus femoris contained 3 fiber types (I, IIA, and IIB). The vastus intermedius was composed almost entirely of type I fibers. From birth to 5 years of age, mean fiber diameters of type I fibers increased from 15.8 to 47.0 micron in the vastus lateralis, 15.6 to 50.7 micron in the vastus medialis, 17.5 to 46.5 micron in the rectus femoris, and 26.7 to 51.8 micron in the vastus intermedius. Means of fiber diameters of type II fibers increased from 16.1 to 44.6 micron in the vastus lateralis, 19.8 to 44.0 micron in the vastus medialis, and 17.0 to 44.5 micron in the rectus femoris. The percentage of type II fibers in the vastus lateralis, vastus medialis, and rectus femoris decreased from 85% to 90% at birth to approximately 72% at 5 years of age. The vastus intermedius consisted of only type I fibers in sheep 2 years and older.


Microbiology of normal and seborrheic canine skin. Quantitative and qualitative bacterial assays were performed on the skin of 15 normal and 32 seborrheic dogs. Nonionic detergent scrubs were made on areas demarcated by glass sidearm cylinders. Quantitative analysis was accomplished by the serial dilution technique, and the bacteria were identified by individual and colonial morphology and by enzyme production. Areas measured on control dogs had a markedly lower total bacterial count than similar areas measured on seborrheic animals. Control dogs had a flora consisting primarily of coagulase-negative cocci, whereas seborrheic dogs usually had a cutaneous flora composed primarily of Stahylococcus aureus, coagulase-positive.


A double logistic comparison of growth patterns of normal children and children with Down's syndrome. A double logistic model was used to compare six parameters of growth in standing height of 31 children with Down's syndrome with 136 children from the California Guidance Study. Multivariate analysis of variance of the growth data showed that while there were significant differences in all six parameters favouring the normal over the Down's children, there were no significant differences with respect to error of fit. Multivariate analysis with final height as a covariate revealed that differences between the normal and the Down's children in the prepubertal and adolescent components were explainable by differences in final height. In summary, the double logistic model, when applied to this sample of Down's children, identified those well defined logistic components which are characteristic of the growth of normal children, the differences being those of degree, not of form.


Discriminant functions and 21-trisomy mosaicism. A sample of 173 cases of cytogentically diagnosed 21-trisomy mosaicism, 225 cases of complete 21 trisomy and 302 normal controls were used to form discriminant functions for mosaics versus normal controls, and also for complete 21 trisomics versus normal controls; for each of these discriminants optimal sets of ten dermatoglyphic characters were selected. The mean discriminants and discriminant coefficients were calculated on the basis of these characters, using Fisher's method. The relative position of mosaics in respect of the mean discriminant values, was found closer to the Down's syndrome group than to the normal controls. Consequently, reasonably, good separation of the mosaics from the normal controls has been achieved: the distance between the two mean discriminants is greater than two standard deviations. The distribution curves were then constructed of individual discriminants, calculated in a majority of cases from all the three groups. The distribution curve for mosaics has been found bimodal so that more detailed study of the individuals forming its first peak was undertaken; a possible relationship between the degree of dermatoglyphic distortion and cytogenetic findings is discussed and some limitations of both methods are indicated. The results concerning discriminant function indices are recommended for further use, particularly in genetic counselling. Their application in the studies of populations of parents of Down's syndrome cases is demonstrated in the group of 79 parents of two or more Down's cases and the group of 111 parents of one Down's case. On the basis of these data it is postulated that there may be some proportion of undetected mosaics amongst the parents of Down's cases, but larger numbers are necessary to support and further specify these preliminary results.


[Geographical race typing of the causative agent of tularemia using antibiotics]. Reaction of the strains of the tularemia causative agent to erythromycin (100 gamma/ml) or oleandomycin (400 gamma/ml) is one of the taxonomic tests. The study of 82 strains of the holarctic race and 63 strains of the Central Asiatic race according to this test showed that the strains of the holarctic race were divided with respect to these macrolides into sensitive (biotype I) and resistant (biotype II). The strains of the both races were isolated at the territory of the Kazakh SSR. Such a reaction of the strains of the holarctic race is a stable feature and is not connected with virulence, the isolation source and the biochemical properties of the strains. Division of the holarctic race into the biotypes (I and II) with respect to erythromycin and oleandomycin may be of definite significance in epidemiological and epizootological examination for tularemia with a purpose of determining the source of the infection, as well as in defining the borders of the infection focus area with circulation of this or that biotype of the holarctic race of the tularemia causative agent.


[Coamide stimulation of immunogenesis during experimental levomycetin therapy]. The effect of various doses of levomycetin on immunogenesis and capacity of coamide for stimulation of immunogenesis in levomycetin therapy was studied. It was found that massive five-fold doses of levomycetin sodium succinate (I and 0.5 g/kg) administered parenterally or orally inhibited immunogenesis, the inhibition being more pronounced on administration of the antibiotic per os. When levomycetin sodium succinate was used in massive doses (1 g/kg) in combination with coamide (0.5 mg/kg) the inhibition of the immune response to the antigenic stimulation was less pronounced.


Improved radioenzymatic assay for spectinomycin. The sensitivity and reproducibility of the radioenzymatic adenylylating assay for spectinomycin were improved by modifications of the assay procedure and by partial purification of the enzyme. The presence of Bacillus subtilis ribosomes or S-150 fraction in the enzymatic reaction mixture interfered with the ability to measure spectinomycin by this method.


Primary structures of cysteine-containing peptides from the calcium ion-transporting adenosine triphosphatase of rabbit sarcoplasmic reticulum. A preliminary investigation of the primary structure of the Ca(2+-transporting ATPase (adenosine triphosphatase) protein of rabbit skeletal-muscle sarcoplasmic reticulum is reported. The preparation of derivatives of delipidated protein in a form suitable for sequence analysis is described. Tryptic peptides containing S-carboxymethylcysteine residues were isolated from the reduced carboxymethylated protein, and their sequences were partially determined. The results are consistent with mol.wt. about 105000 for the polypeptide, and the absence of extended repeated lengths of sequence. The distribution of tryptophan and cysteine residues between large, aggregated peptides and soluble tryptic peptides shows that these residues are concentrated in different regions of the primary structure. This observation agrees with other evidence that these residues are, on the whole, widely separated in the native protein. The details of the procedures used to isolate the peptides, and the evidence for the determination of their sequences, are given Supplementary Publication SUP 50085 (30 pages), which has been deposited at the British Library Lending Division, Boston Spa, Wetherby, West Yorkshire LS23 7BQ, U.K., from whom copies can be obtained on the terms indicated in Biochem.J. (1978) 169, 5.


Characterization of a region of the primary sequence of troponin C involved in calcium ion-dependent interaction with troponin I. 1. The CNBr digest of troponin C from rabbit fast skeletal muscle was shown to possess many of the functional properties of the whole troponin C molecule. 2. A peptide corresponding to residues 83-134 was isolated, which forms a Ca(2+-dependent complex with troponin I and neutralizes the inhibition by troponin I of the Mg(2+-stimulated adenosine triphosphatase of desensitized actomyosin. 3. The peptide inhibits the phosphorylation of fast-skeletal-muscle, but not cardiac-muscle, troponin I, by 3' :5'-cyclic AMP-dependent protein kinase. In this property it was as effective as whole skeletal-muscle troponin C when compared on a molar basis. 4. Biological activity was also present in other fractions obtained from the CNBr digest. 5. By gel filtration and affinity chromatography of the whole CNBr digest of troponin C, two peptides, one of which was identified as representing residues 83-134, were shown to form Ca(2+-dependent complexes with troponin I. 6. The significance of these findings for the mechanism of interaction of troponin C and troponin I is discussed.


The effect of lipid peroxidation on the calcium-accumulating ability of the microsomal fraction isolated from chicken breast muscle. The effect of lipid peroxidation on the Ca2+-accumulating and Ca2+-retaining abilities of the microsomal fraction from chicken breast muscle was investigated. At 25 degrees C, enzymic lipid peroxidation did not seriously affect either of these abilities unless ascorbic acid was present, when both were diminished. At 37 degrees C, Ca2+-concentrating ability was decreased further by the effects of heat damage to the membrane. Membrane lipid peroxidation did not affect microsomal adenosine triphosphatase activity unless the microsomal fraction was subsequently washed with albumin. This effect of albumin is possibly due to removal of lipid-breakdown products. Addition of soya-bean phospholipids to the peroxidized vesicles washed with albumin restored adenosine triphosphatase activity, demonstrating a non-specific phospholipid requirement.


[Clinical and experimental studies on the effect of benzoyl peroxide in the treatment of acne]. In recent years benzoylperoxide has become increasingly popular in the treament of acne. Beside of a dermal irritative and keratolytic effect this was attributed to the bacteriostatic quality of the substance. By in vitro autoradiography and determination of skin surface lipids in benzoylperoxide=treated skin also a sebostatic effect could be observed. Scanning electron microscopy showed that benzoylperoxide influences the horny layer in a similar way like salicylic acid.


Ipratropium bromide, salbutamol and prednisolone in bronchial asthma and chronic bronchitis. Eleven patients with bronchial asthma and 10 with chronic bronchitis were treated over four consecutive 3-day periods, firstly with aerosols either of ipratropium bromide (40 microgram four times a day) or of salbutamol (200 microgram four times daily) by random allocation, then the alternate drug, next by both drugs together, and finally with prednisolone (10 mg three times daily) in addition to both drugs. The effects of these four treatment periods were assessed both clinically and by measuring ventilatory capacity, nitrogen slope and progressive exercise testing. Ipratropium bromide and salbutamol produced approximately equal improvements in both diseases, with salbutamol showing a marginal advantage in patients with asthma. The combination of both drugs together more than doubled the FEV1 change in both groups of patients. The addition of prednisolone to both drugs produced a marginal advantage only in those with asthma.


The release of beta glucuronidase from the white cells of patients with drug rashes when incubated in autologous plasma, with and without the addition of the causal drug. In seven out of 16 patients with drug rashes, the leucocytes selectively released beta glucuronidase when incubated in autologous plasma, indicating the possible presence of immune complexes. When the white cells were incubated with the suspected drug in vitro, they tended to react in three different ways. In four out of 16 cases additional beta glucuronidase was released, perhaps due to the formation of immune complexes, in two out of the 16, beta glucuronidase release was suppressed, perhaps due to antigen excess, and in two cases LDH release was decreased while beta glucuronidase remained unaltered.


Electronic and resonance Raman spectra of iron(III) complexes of enterobactin, catechol, and N-methyl-2,3-dihydroxybenzamide. Resonance Raman electronic absorption and circular dichroism spectra and pH titration curves are reported for the trianionic ferric complexes of enterobactin, catechol, and N-methyl-2,3-dihydroxybenzamide (MDHB). The spectral signatures of the enterobactin and MDHB complexes are virtually identical and differ from those of the catechol complex in ways that reflect the influence of the amide group on the electronic structure. Excitation in either the visible charge-transfer bands or the near-ultraviolet pi-pi* bands enhances Raman bands associated with benzene ring modes, although the relative enhancements differ markedly in the two regions. The data stronly support a structural model in which iron is bound exclusively to the phenolate oxygen atoms in all three complexes.


Effects of inhibitors on the plasma membrane and mitochondrial adenosine triphosphatases of Neurospora crassa. A comparative study has been made of the effects of a variety of inhibitors on the plasma membrane ATPase and mitochondrial ATPase of Neurospora crassa. The most specific inhibitors proved to be vanadate and diethylstilbestrol for the plasma membrane ATPase and azide, oligomycin, venturicidin, and leucinostatin for mitochondrial ATPase. N,N'-Dicyclohexylcarbodiimide, octylguanidine, triphenylsulfonium chloride, and quercetin and related bioflavonoids inhibited both enzymes, although with different concentration dependences. Other compounds that were tested (phaseolin, fusicoccin, deoxycorticosterone, alachlor, salicyclic acid, N-1-napthylphthalamate, triiodobenzoic acid, cyclic AMP, cyclic GMP, theobromine, theophylline, and histamine) had no significant effect on either enzyme. Overall, the results indicate that the plasma membrane and mitochondrial ATPases are distinct enzymes, in spite of the fact that they may play related roles in H+ transport across their respective membranes.


Comparative studies on myosin ATPase of a flying and nonflying bird. Myosin was purified from the flight muscles of a flying (pigeon) and a nonflying (fowl) bird. Ki (ADP) of myosin ATPase of pigeon is higher, but the Km (ATP) is lower than that of fowl. The specific activity (mumole of Pi liberated/min/mg protein) is higher for the fowl. A0.5 (CaCl2) of myosin of both pigeon and fowl is similar. However, the two proteins differ in their interactions with ADP, ATP and p-chloromercuribenzoate. The two proteins have the same tyrosine, tryptophan and sulfhydryl contents. The electrophoretic patterns of the two myosins on SDS-polyacrylamide gels are different. These studies show significant molecular differences in the myosin derived from the flight muscles of a flying (pigeon) and a nonflying (fowl) bird.


[Isolation of glycoproteins from mitochondria and preparation of H+-ATPase and study of their ability to induce selective transport of Ca2+ across bimolecular lipid membranes]. Glycoproteins from mitochondria and ATPase preparations of rat liver were isolated. It was shown that these glycoproteins were able to induced selective transport of calcium ions across artificial bilayer lipid membranes.


Red cell diphosphoglycerate mutase. Immunochemical studies in vertebrate red cells, including a human variant lacking 2,3-DPG. Diphosphoglycerate mutase (DPGM) was purified to homogeneity from human erythrocytes. The enzyme and Freund adjuvant were injected into chickens and yielded a monospecific precipitating antibody. Radial immunodiffusion with this antibody was used to measure the amount of DPGM in hemolysates from human adult and cord red cells. Dog, rabbit, rat, chicken, and goat red cells all had DPGM during the neonatal period, but goat adult red cells had no detectable enzyme. Single bands with no spurs were present on Ouchterlony plates in which human hemolysate was placed adjacent to hemolysates from the other species tested. The amount of human red cell DPGM did not differ between young and old cells separated by centrifugation. Red cells from a patient with a DPGM genetic variant who had erythrocytosis and no detectable enzyme activity contained a reduced amount of DPGM as determined by radial immunodiffusion. The abnormal DPGM differed from normal by immunoelectrophoresis and in stability as measured by the amount of crossreacting material in young versus old erythrocytes.


Experimental cardiac hypertrophy in rabbits after aortic stenosis or incompetence or both. Four different models of experimental cardiac hypertrophy were compared : abdominal or thoracic aortic stenosis, aortic incompetence and aortic incompetence associated with a thoracic aortic stenosis. After 3 months the ventricular weight of these 4 models reaches +60% +/- 24; +23 +/- 4; +54% +/- 10 and +83% +/- 14. The maximal increase of left ventricular weight (+94% +/- 15) was obtained with the two-step overloading model. Most of the animals had an increase in the right ventricle and lung weights. The DNA content and the protein myofibrillar protein synthesis were both increased in aortic stenosis and were normal in aortic insufficiency. So far the only way to increase the heart weight experimentally more than 60%, is to combine two lesions.


Homeostatic regulation of epidermal cells in culture. The growth potential (DNA synthesis) of purified epidermal basal cells in culture, according to time reveals two peaks, at days 1 and 6. The same potential estimated in total cultures of epidermal cells (including basal and high level cells) shows only one peak at day 9. This suggests that hig-level mature cells inhibit DNA synthesis in basal cells in culture. This interpretation has been confirmed in showing that increasing amounts of mature cells inhibited DNA synthesis in basal cells in a dose dependent manner. Basal cells in culture are therefore susceptible to homeostatic regulation. However, this regulation is not tissue specific since DNA synthesis was also inhibited by mature epidermal cells in cultures of dermal as well as bone marrow cells. Assuming that the culture of epidermal cells is representative of the in vivo situation, these experiments would suggest that the specificity of action of the G1 chalone in vivo might depend as much on the target tissue as the proper nature of the inhibitor.


Effect of the skin chalone on the epidermis and other tissues in the mouse. A reappraisal of the concept of chalone specificity. Effect of a pig skin extract (72-81/ethanol precipitate from crude waterextract) was investigated on the ear epidermis, vaginal and uterine mucosae of spayed mice. This extract has a strong inhibitory effect on the epidermis. Inhibition was less marked on the vaginal mucosa while uterine epithelium was not affected. After stimulation of the proliferative activity by oestrogen a pronounced inhibition was detected in the three tissues. Purification of the crude extract by pronase treatment followed by chromatography on Sephadex G200 allowed the separation of three fractions. Two of these fractions (phenol extract and low molecular fraction) were active on epidermis vagina and uterine. The high molecular weight fraction has mainly a marked action on uterine epithelium. No effect was detectable on intestinal tissues with any fraction.


Metabolism and distribution of exogenous histamine in cats. 1 The metabolism and disposition in blood and tissues of exogenous [(14)C]-histamine was examined in cats.2 The principal metabolites in blood of histamine instilled into the small intestine (directly or by transfer from the stomach) and colon were imidazoleacetic acid and t-methylimidazoleacetic acid, being present in approximately equal amounts although in individual cats one or other acid could predominate. Only small amounts of histamine entered the circulation although in two of four cats given the largest dose (82 mumol/kg) large amounts were recovered. The amount of (14)C radioactivity absorbed varied directly with the dose instilled. The chief metabolite in kidney and urine, whether histamine was instilled into the intestine or infused parenterally, was t-methylimidazoleacetic acid. Histamine was not absorbed from the stomach and its metabolism there was negligible.3 In contrast, when histamine was infused into blood leaving the intestine (portal vein) the main metabolite in blood and tissues was t-methylimidazoleacetic acid being found in approximately 5-fold the concentration of imidazoleacetic acid. The small amount of histamine which eluded inactivation/uptake by liver, lungs, heart during the infusion was halved on circulation through the intestine. When histamine was infused into blood supplying the intestine, (cranial mesenteric artery) t-methylimidazoleacetic acid while still the major metabolite in blood was now only 1.4 times the concentration of imidazoleacetic acid. Additionally, the blood concentration of histamine during the infusion exceeded that of the metabolites.4t-Methylimidazoleacetic acid was also the principal metabolite in blood and tissues following histamine infusion into a cannula carrying a replacement venous blood supply to the liver of abdominally eviscerated cats. Imidazoleacetic acid and t-methylhistamine were present in equal concentrations and in one-quarter to one-third that of the methylated acid. The latter was also the principal metabolite following intra-arterial histamine infusion to abdominally eviscerated cats without a hepatic blood supply, although initially t-methylhistamine predominated: a large peak of histamine was present during the infusion period. When additionally the renal vessels were ligated, t-methylhistamine predominated throughout the experiment.5 In conclusion, intraduodenally instilled histamine was metabolized equally by diamine oxidase and imidazole N-methyltransferase (followed by deamination by monoamine oxidase). In contrast, imidazole N-methyltransferase was the principal inactivator of parenterally infused histamine, deamination of t-methylhistamine by monoamine oxidase becoming progressively less efficient with the cumulative exclusion of the intestines, liver and kidney from the circulation.


Rat isolated phrenic nerve-diaphragm preparation for pharmacological study of muscle spindle afferent activity: effect of oxotremorine. 1. Muscle spindle afferent discharges exhibiting an approximately linear length-frequency relation could be recorded from the phrenic nerve in the isolated phrenic nerve-diaphragm preparation of the rat. 2. Muscle spindle afferent discharges could be identified by their characteristic "spindle pause" during muscle contraction and by their response to succinylcholine. 3. Cholinergic influence on spontaneous and stretch-induced afferent discharges was indicated by the augmentation produced by physostigmine and acetylcholine. (+)-Tubocurarine, but not atropine, prevented this augmentation indicating the presence of curariform cholinoceptors in muscle spindles. 4. Acetylcholine did not appear to be involved in the genesis of spindle afferent discharges as incubation with hemicholinium-3 and (+)-tubocurarine failed to affect the rate of spontaneous and stretch-induced spindle discharges. 5. Oxotremorine markedly increased the rate of spontaneous and stretch-induced spindle afferent discharges and this effect was prevented in the presence of hemicholinium-3 and (+)-tubocurarine. 6. These results with oxotremorine are of interest in connection with the observation that muscle spindle afferents and hyperactive in Parkinsonian patients.


Leisure skill programming for severely and profoundly handicapped persons: state of the art. The purpose of this paper was to (1) review the current research available in leisure skill programming for severely and profoundly handicapped persons; (2) summarize the gaps in knowledge and point to new programming directions in recreation skill development; and (3) outline leisure skill competencies which teacher trainees must develop. In reviewing the leisure skill studies which have been conducted over the past seven years, a descriptive analysis of subject characteristics, teaching procedures, response measures, and generalization/maintenance strategies in each study was provided. The principle areas which were then identified for future programming included recreational skill sequences, self-initiated free play and toy preference evaluation. A statement of 15 recreation programming competencies was devised as a set of guidelines for preparing teacher trainees in leisure skill programming.


Hepatitis B in a hospital for the mentally subnormal in southern England. The prevalence of hepatitis B viral (HBV) infection was assessed in 340 patients and 268 staff in a hospital for the mentally subnormal in Wessex. Hepatitis B surface antigen (HBsAg), antibody to hepatitis B core antigen, antibody to HBsAg, e antigen (eAg), and antibody to eAg were used as markers of such infection. Forty patients and 10 staff had evidence of recent or current infection, while 149 patients and 50 staff had evidence of past infection. HBV markers were more common in mongols, epileptics, patients with cerebral palsy, and those of lower mental grades and reached a peak after 5-15 years of hospitalisation. eAg was detected in 12 out of 26 patients with HBsAg but in none of the four staff with HBsAg. Abnormal liver function values were found in 24 (60%) of the patients with recent or current HBV infection but in only 30 (19%) of those without HBV markers. Among the staff the prevalence of HBV markers correlated with the duration of employment and degree of contact with patients. Of those with recent or current infection, 4 (40%) had abnormal liver function values compared with 25 (12%) of those without HBV markers. Despite the high prevalence of markers clinically overt hepatitis B was rare.


Polymorphism of carbon oxidation of drugs and clinical implications. Eight volunteers previously phenotyped for their ability to hydroxylate debrisoquine (four extensive metabolisers (EM), four poor metabolisers (PM) were investigated for their metabolic handling of guanoxan and phenacetin. All three drugs are oxidised at carbon centres. Oxidative dealkylation of phenacetin was determined by measuring the rate of formation of paracetamol. The EM subjects excreted mostly metabolites of guanoxan (mean 29% of dose), whereas the PM group excreted large amounts of unchanged drug (48% of dose). The rate of formation of paracetamol was noticeably slower in the PM group, and, when analysed by minimum estimates of apparent first-order rate constants, the difference between the two phenotypes was significant. Thus the hydroxylation defect shown for debrisoquine metabolism carries over to the oxidative metabolism of phenacetin and guanoxan. Some 5% of the population are genetically defective hydroxylators of drugs. Thus methods for evaluating the metabolism of new drugs in respect of usage and side effects need to be revised.


Delivery of wheelchairs to disabled children. In a follow-up study from a children's wheelchair clinic the delivery times for 120 wheelchairs ordered during 1973--7 were analysed. Delivery delays were considerable: only 22 of the 120 chairs were delivered within one month and 69 within three months, while 21 took over six months to arrive. Factors such as the type of chair ordered, the need for modifications, and the centre handling the transaction did not influence delivery time. Administrative delays may be an important contributory factor.


The induction of X-chromosomal aneuploidy by 5-fluorodeoxyuridine (FUdR) fed to Drosophila melanogaster females. After feeding FUdR (5-fluorodeoxyuridine) to female Drosophila melanogaster, highly significant increases in the frequencies of both XO and XXY exceptions were observed in their offspring. The XXY exceptions and part of the XO exceptions result from maternal nondisjunction of the X-chromosomes. Part of the XO exceptions can be assumed to be produced by X-chromosome breakage followed by bridge formation. The analysis of the brood pattern observed suggests that interphase cells (premeiotic oocytes, oogonia) are especially sensitive in the induction of both XO and XXY exceptions by FUdR. In addition, and contrary to the results obtained with other objects, FUdR seems to induce chromosomal damage (presumably chromatid and/or isochromatid breaks) not only in interphase but also in prophase cells. The mechanisms of the induction of X-chromosomal aneuploids by FUdR are discussed.


A combined treatment approach to management of hepatic metastasis. Forty-eight patients with liver metastases were treated at Rhode ISland Hospital in a nonrandomized sequential manner between January 1972 and June 1977. Eight received 5 FUDR hepatic artery infusion, 14 hepatic irradiation, and 25 were planned for combined intra-arterial chemotherapy plus total hepatic irradiation. Those patients who successfully completed induction treatments had a median survival in the radiation only group of 140 days, in the intra-arterial chemotherapy group 270 days, and in the combined group 376 days. Hepatic radiation when combined with chemotherapy was well tolerated. Primary tumor site, disease duration, and degree of abnormality of liver function had no relationship to the response to treatment. The pretreatment performance level of the patient as determined by the Karnofsky Performance Index gave the best indication for potential response to combined therapy. Based on the results of this treatment and the reports of other series, it appears that the combination of intra-arterial 5 FUDR plus hepatic irradiation may offer prolonged and worthwhile palliation to appropriately chosen patients.


The relationship between fibrosis and lactate dehydrogenase isoenzymes in the experimental hypertrophic heart of rabbits. Cardiac hypertrophy was induced in rabbits by injecting either thyroxine or isoprenaline or by surgically constricting the abdominal aorta. An increase in heart weight was associated with a change in the lactate dehydrogenase isoenzyme pattern and an increase in fibrosis (as measured by hydroxyproline concentrations). Isoprenaline treatment led to a moderate increase in heart weight, a marked decrease in the heart/skeletal muscle subunit ratio of lactate dehydrogenase, and a marked increase in hydroxyproline. Thyroxine treatment led to a small increase in both heart weight and hydroxyproline and a small decrease in the heart/skeletal muscle subunit ration. Coarctation of the aorta, in contrast, caused a marked increase in heart weight, a moderate decrease in heart/skeletal muscle subunit ratio, and a moderate increase in hydroxyproline. These results suggest that the decrease in the heart/skeletal muscle subunit ratio of lactate dehydrogenase in the experimental hypertrophic heart reflects the extent of myocardial fibrosis, rather than changes within the hypertrophied myocardial cells.


DNA sequences of promoter regions for the str and spc ribosomal protein operons in E. coli. The DNA sequences have been determined for promoter regions of two ribosomal protein operons in E. coli, the str operon and the spc operon. The site of in vitro transcription initiation within each of these promoter regions has been determined. The start site of the str operon occurs 69 bases upstream from the initiation codon of the S12 gene. The start site of the spc operon occurs 72 bases upstream from the L14 gene, and only 91 bases downstream from the termination codon of the S17 gene (which is in the preceding S10 operon). Both promoters are similar to other sequenced promoters in that they each have an identifiable "Pribnow box" sequence 5 bases upstream from the transcription start site. The spc promoter has a long sequence of 2 fold symmetry centered within the Pribnow box; the str promoter has a shorter but similar symmetry. At positions -69 through -40 in the spc operon, another long region of symmetry is present which may be the termination signal of the preceding S10 operon. Extensive sequence similarity between the str and spc promoter regions is found downstream from the Pribnow box-that is, in a transcribed region preceding the translation start sites.


Follicular plasminogen and plasminogen activator and the effect of plasmin on ovarian follicle wall. Plasminogen, plasminogen activator, protease inhibitors, and a proteolytic activity are shown to be present in bovine follicular fluid. Much of the proteolytic activity appears to be due to plasmin. In addition, plasminogen activator activity can be demonstrated in follicle wall homogenates. Evidence that plasmin decreases the tensile strength of follicle wall preparations is also reported. The potential for the involvement of these substances in ovulation is discussed.


[Ultrastructure of the rabbit myocardium in stages of cardiac hypertrophy induced by experimental aortic valve insufficiency]. A model of aortic insufficiency was developed in rabbits by perforating the aortic valve using a metal perforator (12 cm long) introduced via the right-hand side carotid artery. The rabbit myocardium was examined by electron microscopy in the dynamic periods of cardiac hypertrophization, i. e. in the phase of cardiac hypertrophy development (days 7 to 30 after operation), in the period of the so called stablized cardiac hypertrophy (4 to 6 months after surgery), and in the phases of hypertrophy regression (6 to 8 months after operation). The ultrastructure of myocardial cells in that particular model brought evidence of two bysic processes in the myocardium, i. e. of the usual mechanisms of myocardial ultrastructure build-up (multiplication of ribosomes and polysomes, mitochondria, and contraction apparatus neoplasia), as well as of simultaneously developing degenerative changes.


In vivo validation of a thermodilution method to determine regional left ventricular blood flow in patients with coronary disease. Several methods have been used to measure left ventricular regional blood flow in humans. However, limitations and lack of validation in patients are major problems. A continuous thermodilution technique to measure regional left ventricular blood flow in patients with coronary disease was validated in vivo. This technique permits simultaneous assessment of venous blood flow draining predominantly from the anterior wall and of the total left ventricular effluent. Thermodilution measurements with simultaneous electromagnetic flowmeter recordings from anterior descending vein grafts were compared in patients with occluded or subtotally occluded anterior descending coronary arteries. The thermodilution method yielded values for both absolute anterior regional blood flow and changes in anterior regional flow that compared closely to anterior descending bypass graft flow measured independently. The multithermistor technique may be useful in monitoring flow effects of regional coronary disease over time, as well as in studies of agents purported to alter regional blood flow.


Chronic aortic regurgitation: the effect of aortic valve replacement on left ventricular volume, mass and function. Serial echocardiographic left ventricular (LV) studies were performed in 19 patients before (preop) and after (postop) aortic valve replacement (AVR) for chronic aortic regurgitation (AR); the effect of AVR on LV volume, mass and function was determined from the echocardiographic data. In the 12 patients who were considered to have successful surgical results, the average LV end-diastolic dimension fell from a preop value of 6.9 +/- 0.2 cm to 5.5 +/- 0.2 cm (P less than 0.01) at the time of the early postop study (seven to 10 days). Muscle cross-sectional area (CSA) derived from dimension and wall thickness data was used as an index of LV muscle mass (preop CSA = 26 +/- 1.3 cm2); CSA was unchanged at the early postop study, but subsequently fell to near normal within six months after AVR (20 +/- 1 cm2, P less than 0.01). There was a trend toward improvement in systolic performance by the late postop studies (12+ months). In two out of three patients with postop paravalvular AR, LV dimension increased after an initial fall. Four patients without paravalvular AR failed to show a significant reduction in LV dimension in the postop studies. In this group the preop studies showed a tendency toward a large end-diastolic dimension and decreased fractional shortening, but the single preop parameter which differentiated these four from the successfully treated group was an end-diastolic radius-to-wall thickness (R/Th) ratio greater than or equal to 4. Thus, successful AVR for chronic AR results in the normalization of LV volume and a decrease in LV muscle mass to near normal. The R/Th ratio has important prognostic value which appears to be independent of fractional shortening in some patients with chronic AR.


Prevalence of thyroid disorder in Down syndrome. Thyroid function has been studied in 121 patients between 13 and 48 years old with proven Down syndrome. Chemically, hypothyroidism was found in 17% and hyperthyroidism in 2.5% of the patients; 18% of patients had goiter. Thyroid antibodies were detected in 33% of subjects studied. The abnormal findings were almost equally distributed between the sexes above 20 years of age; however, females had significantly more thyroid disease than males in the younger age group.


A "new" autosomal dominant genodermatosis characterized by hyperpigmented spots and plamoplantar hyperkeratosis. A previously undescribed genodermatosis consisting of tiny hyperpigmented spots aggregated in irregular maculae and mainly localized in the regions exposed to light is reported. Hyperkeratotic papules in the palms and soles were also present. Autosomal dominant inheritance is concluded.


Concurrent hypertension and pregnancy.

Concurrent hypertension and pregnancy. Concurrent hypertension in pregnancy alters the diagnosis and prognosis of both the vascular disease and the gestation. Insight into the physiologic and pathophysiologic changes is essential to assessing the patient's status and to determining what antenatal care may yield the best outcome of the pregnancy. In this monograph we have presented (1) a classification, which correlates well with those currently in use, of the types of hypertension and their causes; (2) a brief review of current fact and theory regarding the effect of hypertension on maternal and perinatal morbidity and mortality; (3) a detailed approach to monitoring the physical and laboratory parameters of the parturient; (4) a rational approach to monitoring the fetoplacental unit; and (5) an analysis of currently available therapeutic regimens that may alter the course of hypertension in pregnancy sufficiently to increase fetal salvage and decrease maternal complications. Certainly more research into the mechanisms of CHP will be forthcoming as will newer and more precise diagnostic aids. Pharmacologic agents with varied hypotensive actions are constantly being developed, and combinations of these may yield more beneficial results.


Circulating antigen-antibody complexes in patients with immune complex disorders and following kidney transplantation. The presence of circulating soluble complexes antigen-antibody was investigated by means of our simple test (1) in small serum samples of patients before and after kidney transplantation. We found a higher incidence of positive test results in patients with an original diagnosis of chronic glomeruleonephritis following transplantation in 37.1%, than before transplantation (in 28.5%). In both instances, however circulating immune complexes were less frequent than in a previously studied group of patients with chronic glomerulonephritis (66.6%), or particularly in glomerulonephritis cases with the characteristics of disease activity (100%) positivity. In patients suffering from pyelonephritis, a diseases not due to immune complexes, 18% of sera were positive. After transplantation the number of positive sera rose to 35.5% in 13 patients. The reasons for this finding are being analysed.


Laparoscopy following abdominal operations. A retrospective study has been conducted to find out the effects of preceding abdominal operations on the validity of laparoscopic examinations. The study included 1658 laparoscopies performed at the Robert Rössle Institute from January 1, 1975, to June 30,1977. 467 patients had previously undergone one or several operations; in 124 patients adhesions had been started while the patient had not undergone any laparotomy at all. In the judgement of essential abdominal organs there are no differences between patients with and without adhesions, who had not undergone any operations previously. Even after laparotomies of the epigastrium, satisfactory judgement of the organs is possible. Since the result of laparoscopy is decisive for further therapeutical measures, it should be carried out also after surgical interventions, clear indication and sufficient skill of the examiner provided.


Myocardial susceptibility to ischemic damage: a comparative study of disease models in the rat. Using experimental models of various disease states, the ability of the isolated perfused working rat heart to withstand and recover from a period of severe ischemia was investigated. The results revealed that the coexistence of a diabetic state, obesity, or left ventricular hypertrophy increased the susceptibility of the hearts to ischemic damage and reduced the rate or the extent of postischemic recovery. In contrast, hearts obtained from moderately hypertensive rats exhibited a greater resistance to, and a superior recovery from, ischemia than did hearts obtained from normotensive controls.


Experience with a community screening program for hypertension: results on 24,462 individuals. A hypertension screening program was conducted by means of mobile units generally used for detection of tuberculosis and chest diseases. From 1st October 1973 to 31st July 1976, 24, 462 individuals aged 35 and over were examined. 10.7% were found to have elevated blood pressure (greater than 160/95 mm Hg). Among these subjects, 43% of the male and 24% of the female had never been told they were hypertensive. 5.6% of the men and 7% of the women had a diastolic reading of 105 mm Hg or more. Undetected hypertension decreased with age and was less frequent in women than in men. Young male hypertensives were frequently aware of their disease. When known, hypertension remained untreated in 14.5% of cases and badly controlled in 26%. One yr after screening, 400 patients who had been found to have undetected hypertension were contacted; 358 (89.5%) had seen their family doctor and 42% of them were under continuous medical treatment. These results further underline the challenge of undetected, untreated and uncontrolled hypertension.


Model studies on activation of the heart. Multiple dipole models of activation of the heart, in combination with a model of the thorax as an electrical conductor relate the action of individual cells to features of the electrocardiogram. The models can be used to develop diagnostic electrocardiographic criteria for ventricular hypertrophy, myocardial infarction or conduction disorders. Criteria derived with the use of Holt, Barnard and Lynn's model proved to be superior to well-established empirical rules. Their approach restricts position, direction and polarity of the current dipole vectors in the model. In the Selvester model, and later in the Ritsema van Eck model, in addition to these restrictions time-constraints are imposed on the dipole activity. In a validation study of the Ritsema van Eck model activation of a beating dog heart is compared in detail with simulated activation in a computer replica of the same heart. Myocardial spread of activation is found to be stimulated correctly. Simulated spread of activation along the Purkinje fiber network however, differs considerably from reality. In apical regions excitation spreads in reality much faster than in the model, in basal regions much slower. The model can be improved by slowing endocardial excitation from apex to base with the time-course of activation. Further improvement is obtained by the use of a more detailed pattern of endocardial excitation, based on studies of endocardial excitation in opened ventricles. The model can predict the time-course of activation with an accuracy of 5% of total ventricular activation time.


Projection from area 3a to the motor cortex by neurons activated from group I muscle afferents. Two receiving areas in the pericruciate cortex are known for inputs from group I muscle afferents of forelimb nerves. One focus is near the postcruciate dimple of area 3a, and the other in the lateral sigmoid gyrus of the motor cortex (area 4gamma). The cortico-cortical projection of area 3a to 4gamma, and the relay by this projection of group I muscle afferent input to the motor cortex were investigated in cats. The following results were obtained. 1. Seventy-four neurons within area 3a were antidromically activated by intracortical microstimulation of the motor cortex. 2. Although excitation evoked by stimulation of group I muscle afferents could be demonstrated for only a few (8 of 48) cortico-cortical neurons in extracellular recordings, due to the methodological limitations discussed, this input evoked EPSPs in 8 of 9 cortico-cortical neurons recorded intracellularly. Therefore, it is likely that the majority of neurons projecting from area 3a to the motor cortex have an excitatory synaptic input from group I afferents. 3. Neurons projecting from area 3a to the motor cortex were most commonly found in cortical layer III, although some were found in layer V. 4. Five of nine pyramidal tract neurons of area 3a had a strong excitatory synaptic input from group I muscle afferents. 5. A new type of pyramidal tract neuron was found which has cortico-cortical axon collaterals connecting the two cytoarchitectonic regions. These various neurons may be part of a feedback system from muscle afferents to the motor cortex.


[Possible late complications after peridural anaesthesia (author's transl)]. 140 women who had received peridural anaesthesia (PDA) during childbirth at the University Gynaecological Hospital, Basel, in 1977, were retrospectively questioned on the occurrence of backache and headache during the puerperium subsequent to peridural anaesthesia. The "matched pairs" technique was employed for the controls. The inquiry revealed that in the PDA group 69 women (49%) and in the control group 39 women (28%) complained of increased backache during the puerperium. For 30 patients (44%) the complaints were a frequently disturbing factor in their everyday work. In the control group, this was true of 11 women (28%). 46 patients (33%) of the PDA group complained of increased headache during the puerperium, against 16 patients (11%) of the control group. 22 women (49%) of the PDA group felt disturbed in their daily work against 4 women (25%) among the controls. The findings are compared with data in literature, and the aetiology of the symptoms is discussed.


Genetical and biochemical characterization of QA-3 mutants and revertants in the QA gene cluster of Neurospora crassa. The qa-3 gene, one of the four genes in the qa gene cluster, encodes quinate (shikimate) dehydrogenase (quinate: NAD oxidoreductase, ER 1.1.1.24), the first enzyme in the inducible quinic acid catabolic pathway in Neurospora crassa. Genetic analyses have localized 26 qa-3 mutants at 11 sites on the aq-3 genetic map on the basis of prototroph frequencies. Certain mutants, e.g., 336-3-10 and 336-3-3, are located at opposite ends of the qa-3 gene. Data from four-point crosses (qa-1s mutant 124 X five different qa-3 mutants in triple mutants qa-3, qa-4, qa-2) indicate the following orientation of the qa-3 gene within the qa cluster; qa-1, qa-3 mutant 336-3-10 ("left" end) qa-3 mutant 336-3-3 ("right" end), qa-4, qa-2. Ultraviolet-induced revertants have been obtained from 14 of the qa-3 mutants. The revertable mutants fall into two major classes: those that revert by changes either at the same site or at a second site within the qa-3 gene, and those that revert by unlinked suppressor mutations. The intragenic revertants can be further distinguished by quantative and/or qualitative differences in their quinate dehydrogenase activities. Some revertants with activities either equivalent to or less than wild type produce a thermostable enzyme, and others an enzyme which is thermolabile in vitro at 35 degrees. A concentration of quinic acid or shikimic acid as low as 50 micron protects the enzyme markedly from heat inactivation. The genetic organization and the orientation of the qa-3 gene are discussed with respect to its direction of transcription and to the possible localization of a promoter (initiator) region(s) within the qa gene cluster.


Human-mouse mixed lymphocyte cultures.

Human-mouse mixed lymphocyte cultures. Conditions for stimulating human lymphocytes with mouse cells are established. The proliferative and cytotoxic responses generated are shown to be specific for antigens coded for in the major histocompatibility locus.


Bilateral transverse sinus obstruction in benign intracranial hypertension due to hypervitaminosis A. Hypervitaminosis A may be associated with benign intracranial hypertension. So far, the explanation for this phenomenon has remained obscure. A 17-year-old patient with benign intracranial hypertension, following chronic vitamin A intake of 150,000 units daily for acne vulgaris, is presented. Bilateral papilledema was present and bilateral obstruction of the transverse sinuses was demonstrated in the late venous phase of cerebral angiography. Discontinuation of vitamin A and acetazolamide treatment was followed by complete regression of the signs and symptoms of intracranial hypertension. Bilateral sinus obstruction with interference of cerebral sinus outflow is suggested as a critical factor in the pathogenesis of benign intracranial hypertension in vitamin A intoxication. Menstrual dysfunction and tetracycline therapy cannot be completely excluded as possible causative factors.


Rapid identification of San Filippo disease (MPS III). Humbel's thin-layer chromatography of urine was a rapid, reliable means of identifying type of mucopolysaccharide storage disease in 30 patients. Over half had Hurler-Scheie or Hunter disease (MPS I-V or II); eight had San Filippo disease, of which four expressed the Type B form.


Effects of pulmonary congestion and of left atrial distention on breathing in dogs. Prior experiments showed that pulmonary congestion may initiate tachypnea from lung receptors and that left atrial distention has no significant effect on breathing, but in those experiments secondary reflexes could have determined the results. In this study we separately distended the entire pulmonary vascular bed, the arterial compartment, and the left atrium in dogs perfused and oxygenated by an external system while ventilating and while not ventilating the lungs. Distending pressures ranged from 20 to 70 Torr, and as output variables we measured the initial rate of inspiration, peak inspiratory magnitude, inspiratory duration, expiratory duration, and breathing frequency from the diaphragmatic electromyogram. Total vascular congestion caused prolongation of expiration and lowering of frequency without effect on inspiratory duration, its rate or magnitude. A smaller depression was induced from the arterial compartment. Left atrial distention, which failed to occur sufficiently often to be attributable to dogs in general, had much less effect. However, when a related change in breathing did occur, it was limited to a shortening of inspiratory duration.


Ultrastructural aspects of the transformation of muscle fibre type by long term stimulation: changes in Z discs and mitochondria. The criteria which serve to distinguish the slow from the fast type of mammalian skeletal muscle include differences at the ultrastructural level, in particular differences in Z disc morphology and mitochondrial content. If a fast muscle is subjected to sustained low frequency impulse activity similar to that normally received by a slow muscle, its physiological and biochemical properties become indistinguishable from those of a slow muscle. In the present study we have examined the fine structure of fast muscles stimulated in this way. The thickness of Z discs was significantly greater than that of control fast muscles and indistinguishable from that of slow muscles. Mitochondrial profiles, seen only infrequently in control fast muscles, were abundant in their stimulated counterparts. The regulatory influence of impulse activity on the differentiation of skeletal muscle thus extends to some of its most characteristic ultrastructural features.


Improving the generalized mnemonic performance of a Down's syndrome child. A training program was conducted to improve the generalized mnemonic performance, or memory, of a Down's Syndrome child. Training was directed at digit-span performance with generalization from training determined by responses to untrained mnemonic performance probes. The digit-span items varied in length from three to five digits. Each length constituted an item class, with each class trained within the framework of a multiple-baseline design. Probes consisted of untrained digit-span items, grammatical sentences, nongrammatical sentences, and match-to-sample items. A training procedure, in which 15 items from each class varied continually from trial to trial and from day to day, resulted in the percentage of correct responses to both training and probe items increasing to levels substantially above baseline. The results demonstrate the effectiveness of the training procedure in improving the generalized mnemonic performance of a Down's Syndrome child.


Studies of the chemo-mechanical conversion in artificially produced streamings. I. Reconstruction of a chemo-mechanical system from acto-HMM of rabbit skeletal muscle. Steady and uniform streamings (SUS) of HMM solutions were set up in the presence of Mg-ATP in a circular slit, on both side-walls of which a Millipore filter was fixed; F-actin filaments from rabbit skeletal muscle were bound onto the Millipore filter by cyanogen bromide in the flow. The direction of the SUS was specificially determined by that of the flow during the fixing of F-actin and was independent of the direction of the initial velocity applied externally to the HMM solutions. The SUS continued for about 90 min with a velocity of about 20 mum/s at 20 degrees C. There was a strong correlation between the acto-HMM ATPase activity and the velocity of SUS when the salt concentration was varied. Moreover, this was also the case when the ATPase activity was controlled by Ca2+, when native tropomyosin was bound to F-actin in the circular slit. Careful examination led to the conclusions that F-actin filaments are fixed on the Millipore filter with a specific polarity and that a chemo-mechanical system had been successfully reconstituted in our "stream cells," in which chemical energy from ATP is converted to the mechanical energy of streaming.


Elementary steps in the acto-H-meromyosin ATPase reaction to arterial smooth muscle. Transient and steady state kinetics were studied in the interactions of ATP with acto-H-meromyosin reconstituted from bovine arterial heavy-meromyosin (HMM) and rabbit skeletal muscle F-actin. The results showed that the rate of dissociation of the hybrid acto-HMM induced by ATP was slower than the rate of the fluorescence enhancement of HMM, and that the rate of the P1 burst of HMM was unaffected by addition of skeletal muscle F-actin. The ATPase [EC 3.6.1.3] activity of arterial HMM was activated only slightly even with addition of high concentrations of skeletal muscle F-actin. Furthermore, the rates of dissociation of the hybrid acto-HMM induced by ATP and reassociation of dissociated arterial HMM with skeletal muscle F-actin after decomposition of ATP were much lower than those of skeletal muscle acto-HMM.


Tentoxin-induced energy-independent adenine nucleotide exchange and ATPase activity with chloroplast coupling factor 1. 1. The effect of energy transfer inhibitors on energy-dependent exchange of tightly bound adenine nucleotides with washed, broken spinach thylakoids has been studied. Energy transfer inhibitors that inhibit the ATPase activity of soluble chloroplast coupling factor 1 (CF1) (e.g. phloridzin and tentoxin) do not inhibit energy-dependent adenine nucleotide exchange. Energy transfer inhibitors that block proton flux through the hydrophobic protein proton channel (CF0) (e.g. dicyclohexylcarbodiimide and triphenyltin chloride) also block light-dependent adenine nucleotide exchange. 2. Tentoxin, at relatively high concentrations, stimulates an energy-independent exchange of adenosine diphosphate. 3. High concentrations of tentoxin elicit a Ca2+-dependent ATPase activity with soluble CF1, but has no effect on the Ca2+-dependent ATPase activity of membrane-bound CF1. 4. The trypsin-activated, Ca2+-dependent, membrane-bound ATPase is not affected by high concentrations of tentoxin, whereas the dithiothreitol-activated, Mg2+-dependent ATPase is markedly inhibited. 5. The reconstitution of chloroplasts, partially depleted in CF1, with soluble CF1 is correlated with the loss of tentoxin-induced, Ca2+-dependent ATPase activity associated with soluble CF1.


Turnover of hepatic phosphofructokinase in normal and diabetic rats. Role of insulin and peptide stabilizing factor. Earlier work demonstrated that the activity of liver phosphofructokinase (PFK-L2) and immunoreactive PFK-L2 were decreased in diabetic rats and increased to normal or super-normal amounts following insulin treatment (Dunaway, G.A., and Weber, G., (1974) Arch. Biochem. Biophys. 162, 629-637). This report indicates that the decrease in levels of PFK-L2 in diabetic rats is a result of an accelerated degradation rate while the synthetic rate remains nearly normal. Following insulin treatment, the rate of PFK-L2 synthesis is enhanced 2-fold, whereas the rate of degradation appears to be greatly diminished. An inverse relationship is shown to exist between the PFK-L2 levels and the rates of PFK-L2 degradation, suggesting that the levels of PFK-L2 are primarily regulated by degradation rate. In addition, the levels of the PFK-L2 peptide stabilizing factor are inversely proportional to rates of PFK-L2 degradation. These results indicate that insulin mediates the rate of degradation of PFK-L2 by controlling the level of the peptide stabilizing factor.


Purification and characterization of DNA-dependent ATPase II from Escherichia coli. A new DNA-dependent ATPase was isolated and purified from soluble extracts of Escherichia coli. This enzyme, called ATPase II, has a molecular weight of 86,000 and exists in a monomeric state. It degrades ATP (or dATP) to ADP (or dADP) and Pi in the presence of magnesium and requires a double-stranded polynucleotide as cofactor. A correlation between the efficiency as cofactor and the melting point of the polynucleotide has been found; the lower the melting temperature, the higher the stimulation of ATPase II. The enzyme binds to single-stranded DNA and poly[d(A-T)] copolymer, but not to the double-stranded circular DNA (Form I) of simian virus 40.


Efrapeptin prevents modification by phenylglyoxal of an essential arginyl residue in mitochondrial adenosine triphosphatase. Studies of phenylglyoxal incorporation by beef-heart mitochondrial ATPase reveal one fast-reacting arginyl residue/enzyme molecule. Modification of this group proceeds at a rate which parallels the loss of enzymatic activity. Efrapeptin protects the arginyl residue from reaction with phenylglyoxal. The data suggest that efrapeptin binds at the catalytic site and blocks accessibility of an essential arginine at the adenine nucleotide binding site. The detection of a single, fast-reacting, essential arginine on an enzyme with multiple copies of the catalytic subunit, provides further evidence in support of the alternating site mechanism for ATP synthesis proposed by Kayalar et al. (Kayalar, C., Rosing, J., and Boyer, P.D. (1977) J.Biol. Chem. 252, 2486--2491).