The normal calvaria indices of the human skull. 1. Absolute measurements. 2. Proportional measurements. Using the bony reference points: Nasion (N), Tuberculum sellae (Ts), Bregma (B), Lambda (L) as well as Twining's line (Tw) the normal position of bregma, lambda and internal occipital protuberance can be expressed in proportional measures by the ratios: N-Ts/B, N-Ts/L and N-Ts/Tw. Thus the growth rate of the human calvaria is expressed as a proportion of the anterior cranial base and found to be independent of the shape and age of the skull.


Regional enteritis in children: small bowel disease with normal terminal ileum. Regional enteritis in children may affect the small bowel without involvement of the terminal ileum. We have noted this distribution of disease in 4 of 20 consecutive cases of Crohn's disease. The clinical and radiologic features of these 4 patients are reported together with a review of similar observations in the literature.


Unusual presentation of appendiceal abscess on barium contrast studies. The defect of an appendiceal abscess on a barium enema is most often seen on the medial aspect of the cecum. However, the site of involvement may vary depending on the location of the appendix. This paper illustrates some of the unusual radiographic findings that were found on barium enemas in six pediatric patients with appendiceal abscess that were not involving the medial cecum.


Posterior urethral valves as a cause of neonatal uriniferous perirenal pseudocyst (urinoma). Two neonates with uriniferous perirenal pseudocysts (urinomas) secondary to posterior urethral valves are presented. Early diagnosis was achieved and both patients survived. The characteristic roentgenographic appearance of the pseudocyst is described. An investigation for lower urinary tract obstruction should always be undertaken when pseudocyst or ascites is seen in the neonate. Prompt diagnosis and treatment is essential to avoid irreversible renal damage, electrolyte or fluid imbalance, or respiratory compromise.


Fused labia. Clinical and radiological findings. The clinical and radiological findings in fused labia are described. Some of the patients were asymptomatic. The others were referred because of a suspicion of urinary infection. Micturating cystourethrography showed collection of contrast material above the labia and marked reflux into the vagina in all patients examined. These findings were not seen after separation of the labia. Although the diagnosis is usually a clinical one, it is suggested that labial fusion may first be recognized by the radiologist through these cystourethrographic findings and while catheterizing the child.


Focal osseous lesions in congenital lues. Five babies, aged between one to three months presented with clinical and serological evidence of syphilis. In addition to the usual periosteal and metaphyseal bone lesions of lues, areas of focal lucencies and sequestra were present. The association of sequestra in focal diaphyseal erosions may represent a non-dystrophic manifestation of the disease. The lesions were attributed to the syphilitic process. Trivial trauma to disorganised metaphyses, dystrophic changes and possibly focal osteomyelitis account for the spectrum of bone lesions in congenital syphilis. No tubular bone appears immune to these processes.


Syndromes of congenital bowing of the long bones. Ten patients with congenital bone disease in whom bowing of the long bones was the predominant or only sign are described. The group was composed of three patients with Campomelic dwarfism, one with long bones bowing of Caffey's type, four with femoral bowing (two of them familial), one with bowing of the long bones of the lower limbs and one with bowing of the forearm bones.


General lymphangiomatosis in a child.

General lymphangiomatosis in a child. The lymphographic findings in a 4 year old girl with general lymphangiomatosis are presented. The number of iliac and lumbar lymphatics had increased markedly and the lymph nodes were enlarged with very loose structure and with contrast medium distributed in scattered droplets and filiform channels.


Acute bursitis calcarea trochanterica in an infant, with perforation into the hip joint demonstrated by arthrogram. A case of bursitis calcarea trochanterica acuta is reported in a boy aged four months. The calcification was amorphous, and arthrography revealed extension into the hip joint. The lesion was treated surgically.


Acrodysostosis. A case of peripheral dysostosis, nasal hypoplasia, mental retardation and impaired hearing. Acrodysostosis--a rare congenital malformation syndrome--is described in a 4 1/2 year old boy with peripheral dysostosis, nasal hypoplasia, mental retardation (PNM syndrome) and impaired hearing. The differential diagnosis includes pseudo (PH)--and pseudo-pseudohypoparathyroidism (PPH). The patient described here had severe peripheral dysostosis, typical of PNM as opposed to the above-mentioned conditions with only moderate peripheral dysostosis. Furthermore, there were no soft tissue calcifications and no intracranial calcification as can be seen in PH and PPH. Laboratory findings were normal.


Hereditary malformation of the toes and fingers in a family with double translocation heterozygosity. A hereditary malformation of the metatarsophalangeal joints, called here "tear drop" deformity, and a cut off appearance of the distal phalanges of the toes is described in a family with double translocation t (7; 12), t (2; 6) heterozygosity. A bracydactyly E was also found. These disorders seemed unrelated to the chromosomal aberration.


The radiological features of Histoplasma pericarditis. The radiographic features of pericarditis due to Histoplasma capsulatum are described in 5 children. This diagnosis is suggested when enlargement of the cardiac silhouette is associated with pneumonia, parenchymal nodules or adenopathy. These findings are particularly significant if the patient lives or has lived in an area which is endemic for histoplasmosis. While pleural effusion is rare in primary histoplasmosis, it is frequently present in patients with histoplasma pericarditis.


Effect of saliva from cystic fibrosis patients and from normal subjects on red blood cell sodium transport. Saliva, whether taken from patients with cystic fibrosis or from normal subjects, caused an increase in red blood cell Na+ efflux (in the presence or absence of ouabain) of 19-29% as compared with non-saliva controls. However, there was no significant difference between the effects of cystic fibrosis saliva and normal saliva.


The role of pulmonary corticosteroid 11-reductase activity in lung maturation in the fetal rat. Injection of 11-ketoprogesterone into fetal rats at day 17 of gestation reduced the pulmonary C-11 activation index (an indicator of net gain or loss of glucocorticoid activity) as measured at day 21 (P less than 0.001) and resulted in elevated levels of the inactive hormone 11-dehydrocorticosterone (P less than 0.001), but unchanged corticosterone levels. Adrenal weight was significantly increased (P less than 0.001). 11-Ketoprogesterone-injected fetuses had considerably larger lungs (P less than 0.001) with reduced saturated phosphatidylcholine content (P less than 0.001).


Acid and neutral lipases of cultured adipocytes of infants and children. In order to determine whether the mobilization of intracellular triglycerides observed in cultured human adipocytes is associated with changes in the activities of acid and neutral lipases, the activities of both enzymes were measured weekly on cultured adipocytes for several months. The activity of acid lipase was initially very low, but rose to levels 40 times the original activity within 3 months. The activity of neutral lipase decreased rapidly within the first 2-4 weeks and remained at approximately 25% of original levels thereafter.


Arginine vasopressin response to an osmotic stimulus in the fetal sheep. Baseline plasma osmolality (pOsm) and plasma arginine vasopressin (pAVP) were measured in chronically catheterized fetal sheep. Mean baseline pAVP in fetuses from 101-120 days was 1.9 +/- 0.46 muU/ml (mean +/- SEM) with a pOsm of 293 +/- 1.8 mOsm/kg. In fetuses of 121-141 days of gestation, mean pAVP was significantly lower, 0.77 +/- 0.19 muU/ml (P less than 0.05), with a similar pOsm (293 +/- 1.9 mOsm/kg). The logarithmic baseline pAVP values were linearly correlated with pOsm for both groups. Hypertonic saline infusion resulted in a similar increase in the log pAVP corrected for the rise in pOsm in the 101-120-day fetuses and in 121-141-day fetuses. The slope of this response was similar to that of the steady state relationship. The data indicates that the fetal osmoreceptor system for control of arginine vasopressin secretion is fully functional in the last trimester of pregnancy.


Effects of cortisol and aminophylline upon survival, pulmonary mechanics, and secreted phosphatidyl choline of prematurely delivered rabbits. Rabbits delivered at 27.0 days of gestation were studied after administration of cortisol (2 mg/kg/day), aminophylline (6.25 mg/kg/day), or sterile saline to the does on days 24-26 of gestation. Survival at 60 min was 52.9% in the aminophylline-treated group and 22.2% in the control and cortisol-treated groups with all animals being in a warm, oxygen-enriched environment and receiving frequent tactile stimulation. Lung volume at 30 cm H2O was lower in the cortisol-treated group than in the controls or aminophylline-treated group in animals surviving for 60 min (Table 2). The aminophylline-treated group retained significantly more gas at low pressures on the deflation curve (Table 2) and had significantly more phosphatidylcholine recovered in lung lavage fluid (Table 3) than the other groups. Aminophylline appears to have enhanced lung maturation better than cortisol in this experimental model.


Inotropic response of the neonatal canine myocardium to dopamine. The inotropic responsiveness of the developing myocardium to dopamine and isoproterenol was evaluated using isolated, perfused ventricles and atrial strips from puppies ages 15 hr to 33 days. Responses were compared to those in adult animals. The maximum percentage of increase of left ventricular dF/dt increased from 12 +/- 5 (mean +/- SEM) at 0-7 days (n = 6) to 100 +/- 40 at 21-33 days (n = 3) of postnatal age. At 7-14 days (n = 4) and 15-20 days (n = 5) of age the maximum percentage of increase of left ventricular dF/dt was 28 +/- 10 and 39 +/- 17, respectively. Puppy ventricle responded to isoproterenol at all ages equally (maximum percentage increase of left ventricular dF/dt = 46 +/- 13). Atrial muscle strips from puppies, ages 15 hr to 35 days (n = 22), and adult dogs (n = 19) demonstrated equal responsiveness to dopamine as well as to isoproterenol. The maximum percentage of increase of dF/dt was 117 +/- 18 with dopamine. Maximum percentage of increase of dF/dt with dopamine after propranolol (10(-7) M) was 52 +/- 18. Haloperidol (1.10(-7)-2.10(-6) M) did not alter responsiveness of atria to dopamine.


A defect in branched-chain amino acid metabolism in a patient with congenital lactic acidosis due to dihydrolipoyl dehydrogenase deficiency. In a case of dihydrolipoyl dehydrogenase deficiency, there was not only an elevation of lactate and alpha-ketoglutarate but also of branched chain amino acids. The levels of branched-chain amino acids varied from the normal range to three times the upper limit of normal during the patient's lifetime, and alloisoleucine was detectable at all times. Examination of postmortem tissues revealed that the activity of branched-chain keto acid dehydrogenases was between zero and 10% of that in control tissues. It is suggested that the multiple defects seen in oxidative decarboxylation in this patient is the consequence of a single genetic deletion of an enzyme common to pyruvate dehydrogenase, alpha-ketoglutarate dehydrogenase, and branched chain keto acid dehydrogenases.


Oxygen toxicity: comparison of lung biochemical responses in neonatal and adult rats. Neonatal rats (4--7 days old) and adult rats (approximately 80 days old) were continuously exposed to either 96--98% oxygen or air. Examination of the lungs of neonatal rats, who survived 5 days of oxygen exposure with no evidence of respiratory distress, showed significant increases in the pulmonary superoxide dismutase (SOD) activity (peak value: 144% of air-exposed controls), glutathione peroxidase (GP) activity (126%), glutathione reductase (GR) activity (122%), reduced glutathione (GSH) level (176%), and glucose-6-phosphate dehydrogenase activity (151%). Adult rats, most of whom succumbed within 3 days of oxygen exposure, did not show any significant increase in the activities of pulmonary SOD, GP, GR, and the level of GSH as compared to the air-exposed adult animals. Glucose-6-phosphate dehydrogenase was significantly elevated in the 72-hr oxygen-exposed adult rats. It is concluded that increases in the lung complement of SOD, GR, GP, and GSH in the neonatal rat during oxygen challenge may provide the mechanism(s) for their increased tolerance to hyperoxia-induced lung injury as compared to the adults.


Electrolyte economy and its hormonal regulation in congenital chloride diarrhea. The economy of Cl-, K+, and Mg++, extracellular volume (ECV) and plasma volume, and the role of hyperreninemia and hyperaldosteronism were explored in 22 patients with congenital chloride diarrhea. Stool volume was in significant correlation with its Cl-, Na+ and K+ content, the correlation being significantly better with Cl- content than with the Na+ content. Low fecal Cl- concentrations were seen in chronic hypochloremic contraction, but acute episodes did not cause reduction of fecal Cl- concentration from the basal level of 140--150 mmol/liter. The adequate condition (defined as normal serum electrolyte concentrations and bl;od pH, and presence of Cl- in urine) was associated with high total exchangeable Cl- and ECV. This excess Cl- and ECV roughly equalled the high daily fecal amount of Cl- and volume. Reduced ECV was accompanied by high renin activities and hyperaldosteronism, but in the adequate condition these were normal. Hyperaldosteronism caused a decrease in urinary Na+-K+ ratio and, after the age of 2--6 months, in the fecal Na+-K+ ratio. Total exchangeable K+ was normal in the adequate condition. No Mg++ depletion was present, although the patients lack Mg++ substitution. The adequate condition could be maintained with an oral supplement of NaCl, KCl and water.


Insulin effect on fetal glucose utilization. Insulin infused into a sheep fetus over a 3-hr period at the rate of approximately 0.24 U.kg-1.h-1 increased fetal glucose uptake (utilization) from 4.4 +/- 0.7 mg.min-1.kg-1 to 6.9 +/- 0.9 mg.min-1.kg-1 as compared to a noninsulin control period. Insulin administration did not alter fetal oxygen consumption (8.6 +/- 0.7 ml.min-1.kg-1 vs. 7.7 +/- 0.7 ml.min-1.kg-1), umbilical blood flow (220 +/- 1 ml.min-1.kg-1 vs. 209 +/- 16 ml.min-1.kg-1), or the placental clearances of antipyrine (114 +/- 7 ml.min-1.kg-1 vs. 109 +/- 8ml.min-1.kg-1) and urea (24.5 +/- 2.2 ml.min-1.kg-1 vs. 25.0 +/- 2.1 ml.min-1.kg-1). Fetal plasma glucose concentration fell significantly (0.22 +/- 0.01 mg.ml-1 to 0.16 +/- 0.01 mg.ml-1) during insulin infusion. The insulin effect on fetal glucose uptake occurred over a range of maternal glucose concentrations (0.32 leads to 0.78 mg.ml-1), which were not altered by the infusion of insulin in the fetal compartment. Insulin has a specific effect on increasing fetal glucose uptake and utilization.


Metabolic activity of developing rabbit lung. The uptake and metabolism of [3H]leucine, [U-14C]glucose, and [3H]palmitate were studied in rabbits aged --3, 1, 7, 28, and 90 days up to 1--1.5 years. Although lung composition did not change markedly, there were great differences in lung metabolism between the perinatal period (late fetal and newborn) and later stages of development. Leucine incorporation into lung protein was highest (3.1--3.4 nmol/mg protein/hr) in late fetal and newborn rabbits and decreased rapidly thereafter. Palmitic acid incorporation decreased during the first week after birth from 150 nmol/100 mg/hr to 85 nmol/100 mg/hr at 7 days of age; it increased thereafter to 170 nmol/100 mg/hr at 4 weeks of age and remained at that level throughout the entire period studied. Glucose uptake and lactate production were higher in fetal lungs than in all other age groups. Lipid biosynthesis from glucose was 2--4 times higher in fetal lungs than at all other ages; furthermore, more than 60% of glucose carbon atoms channeled into lipid was incorporated into fatty acids, whereas at all other ages glucose was chiefly a precursor of lipid glycerol.


The lymphocyte transformation response of fetal hemolymphatic tissue to mitogens and antigens. Lymphocyte transformation responses to three different mitogens (phytohemagglutinin (PHA), pokeweed mitogen (PWM), and concanavalin A (Con A)) as well as four antigens (streptolysin O (SLO), keyhole limpet hemocyanin (KLH), streptokinase-streptodornase (SKSD) and tuberculin purified protein derivative (PPD)) were studied ontogenetically in 30 human fetuses ranging in gestational age from 6-19 weeks. In most organs lymphocyte responsiveness to Con A in human fetuses seemingly develops in concert with responsiveness to PHA and PWM. One 19 week fetus had an apparent antigen specific response to SLO with stimulation of cord blood and bone marrow lymphocytes. The same fetus also had mitogen responsiveness in bone marrow.


Erythrocyte membrane proteins of premature and full-term newborn infants. Erythrocyte membrane proteins of premature and full-term infants were analyzed by polyacrylamide gel electrophoresis. There were no qualitative or gross quantitative differences in the pattern of membrane proteins from premature infants, full-term infants, and adults.


Whole body protein synthesis in relation to basal energy expenditure in healthy children and in children recovering from burn injury. Dynamic aspects of whole body nitrogen metabolism in children recovering from burn injury have been examined in relation to basal metabolic rate (BMR). A continuous administration of [15N]glycine was used to estimate the rates of whole body protein synthesis (S) and breakdown (C) in five acutely burned children (ages 5-16 years) and in nine healthy subjects (ages 9-18 years). S (grams of protein per kg body wt per day) and BMR were significantly correlated (r = +0.73; P less than 0.01). There was no significant correlation of C with BMR. The ratio of S (grams of protein per day) to BMR (kilocalories per day) was the same in burned and healthy children; the mean value for all children was 0.10 +/- 0.03 g protein synthesis/basal kcal. Calorie intake and S were significantly correlated (r = +0.70; P less than 0.01). There were significant correlations between BMR and percentage of total body surface area burned (r = +0.66; P less than 0.01), and BMR and age (r = -0.57; P less than 0.05). Age did not correlate significantly with percent of total body surface burned.


Iron deficiency in the rat: biochemical studies of brain metabolism. Studies were performed to determine the effects of iron deficiency on brain metabolism in rats. Concentrations of cytochrome pigments, oxidative phosphorylation, and catalase and monoamine oxidase activities in brain tissue were unaffected by iron deficiency. However, activities of aldehyde oxidase, a key enzyme in the pathway of serotonin degradation, were significantly reduced, and concentrations of serotonin and total 5-hydroxyindole compounds were elevated in brain tissue of iron-deficient animals. Aldehyde oxidase activities and concentrations of 5-hydroxyindole compounds in brain tissues returned to approximately normal values one week after treatment of iron deficient animals with iron dextran.


Asymptomatic hyperammonemia in low birthweight infants. At 0-3 days of age the plasma ammonium concentration in full term appropriate for gestational age (AGA) infants was (mean +/- SEM) 27.5 +/- 0.5 micron; a value similar to that reported in adults. Ammonium levels in low birthweight AGA and SGA groups were 47.0 +/- 2.0 micron and 45.1 +/- 3.3 micron respectively; significantly elevated (P less than 0.001) as compared to the full term group. These increased ammonium levels persisted at 3-5 weeks of age. Associated with the hyperammonemia was a significant (P less than 0.01) decrease in plasma alpha-ketoglutarate concentration: 11.8 +/- 1.0 micron, in the low birthweight AGA as compared to 20.7 +/- 0.6 micron in the full term AGA infants. There was an inverse linear correlation between plasma concentrations of ammonium and alpha-ketoglutarate r = -0.86, P less than 0.001. Urinary orotate excretion was significantly elevated (P less than 0.05) in low birthweight AGA infants. There was no difference in the plasma concentrations of glutamine, glutamate, or alanine among the various groups. Hyperammonemia was not associated with neurologic dysfunction.


Essential fatty acids, prostaglandins, and respiratory distress syndrome of the newborn. The lungs are a major metabolic site for the synthesis, release, and degradation of prostaglandins. Prostaglandins of the E and F series exert a potent physiological effect on the smooth muscle of blood vessels and the tracheobronchial tree; prostaglandin E dilates while prostaglandin F constricts. Thus, altered prostaglandin metabolism may contribute to the pathophysiology of respiratory distress syndrome (RDS). Twenty-one infants with RDS and ten age- and weight-matched controls were studied by analyzing their plasma for prostaglandins and their precursor essential fatty acids. The two groups showed no differences in the essential fatty acid prostaglandin precursors, dihomo-gamma-linolenic and arachidonic acids. During the acute phase of RDS, plasma levels of the primary prostaglandins E and F are significantly elevated compared with control values and the ratio of prostaglandin E to prostaglandin F significantly reduced. Prostaglandins E and F returned to control values on recovery from the acute stage of the disease. Two infants with persistent patent ductus arteriosus had significantly elevated prostglandin E values in their plasma compared with controls. The elevated levels of circulating plasma prostaglandins E and F and the reversal of their ratio during the acute phase of RDS may have adverse pulmonary and multisystem effects.


The epidemiology of Staphylococcus aureus in a newborn nursery from 1970 through 1976. Results of seven years of epidemiologic surveillance for Staphylococcus aureus in a newborn nursery are presented as a follow-up of a study from this same institution published in 1969. Surveillance of the previous study included years 1961 through 1968. A continued rise in S. aureus colonization rates among newborns occurred from 1973 through 1976 as compared to previous years studied. This was related primarily to the discontinuance of hexachlorophene (HCP) bathing. Other contributing factors were the addition in 1972 of the umbilical (as well as anterior nares) site for culturing, potentially doubling the S. aureus retrieval; the use, beginning in 1972, of an HCP-inhibiting medium for staphylococcal culturing; and probably the presence in previous  years of the Hawthorne effect. Clinical infection rates with S. aureus also increased significantly (P less than .001)when HCP bathing was in abeyance. Antibiotic sensitivity patterns of S. aureus isolated from 1970 through 1976 have remained the same. Five phage types were recurrent in causing clinical infections throughout the seven years. A recommended program for control of staphylococcal disease in the newborn nursery includes concentration on improvement of each staff member's individual technique, continuous epidemiologic surveillance, and routine umbilical care with triple dye or bacitracin. Bathing of infants with HCP should be considered a temporary treatment to be terminated as acute disease is controlled.


An attempt at prevention of obesity in infancy. A study of The Prudent Diet in early infancy was undertaken in a test group of 80 infants as an attempt to prevent overweight in a private practice setting. This group was compared with another group of 50 infants born in 1964 who were fed the standard infant diet then in use. Although an incidence of 34.1% overweight was present in the comparison group as compared with 25% in the diet group at age 3 months, by age 3 years the comparison still showed a 25.5% prevalence of overweight as compared with the study group with a significantly lower incidence of only 1.28%. These results require confirmation from other investigators, as well as long-term follow-up observation of patients before one could consider recommending such a diet for widespread use.


Mother-child relationships in the premature nursery: an observational study. In an attempt to develop objective criteria for the process of mother-child bonding, 18 premature infants with a birth weight of less than 1,501 gm were regularly observed alone and together with their mothers during each nursery visit and three home visits, one, two, and three months after discharge from the hospital. Results indicate that (1) mothers visit longer and increase their caretaking behaviors over visits and remain consistent in the rank order of their caretaking behaviors over time. (2) Caretaking behaviors are highly intercorrelated and mothers can be divided into those who show a consistently high, medium, and low amount of interaction with their infants. (3) Highly interacting mothers also visit and telephone the nursery more and stimulate their infants more at home. Mothers who stimulate their infants little in the nursery also visit and phone less and stimulate them little at home. (4) Infant behaviors showed that infants whose gestation was less than 29 weeks did not respond to any type of maternal stimulation. Infants whose gestation was more than 29 weeks, however, showed significantly more eye-openings when their mothers touched them.


Teaching interviewing skills to pediatric house officers. Interviewing skills of 34 pediatric house officers were compared with those of five practicing members of the clinical faculty. Interviews with a programmed mother were videotaped to evaluate physician-patient interaction, data gathering, hypothesis formation and provision of therapy education, reassurance, support, and anticipatory guidance. In addition, eight pediatric interns (PL-Is) were assigned to a study group and five to a control group at the beginning of their outpatient department rotation. The study group received feedback after the videotaped interviews and a 1 1/2-hour didactic session designed to teach interviewing skills. The control group received neither feedback nor the didactic session. Both groups were reevaluated at the end of the outpatient department rotation, again using the videotaped interview technique. Results showed that data-gathering ability increased significantly; that the focus of attention shifted from a more disease-oriented to a more patient-oriented interview; that data were obtained by means of less direct, less leading questions; and that more support and reassurance were provided as the level of training and experience increased. After the outpatient department rotation, members of both the study group and the control group of PL-1s had improved significantly and approached the proficiency-level of practicing pediatricians.


Arthrogryposis multiplex congenita as part of an inherited symptom complex: two case reports and a review of the literature. Two first cousins appear to have an autosomal recessive disorder consisting of arthrogryposis multiplex congenita (AMC), pterygium coli, congenital cervical spine fusions, and some features of the Eagle-Barrett syndrome. A review of the literature is summarized including the broad concepts of AMC as well as some syndromes in which AMC is but one manifestation.


HLA-B27-negative sacroiliitis: a manifestation of familial Mediterranean fever in childhood. Familial Mediterranean fever is a polysystemic disease seen most frequently in persons of Mediterranean ancestry. Arthritis is one of the common manifestations. Both symptomatic and asymptomatic sacroiliitis have been reported in adults. We report on two children with familial Mediterranean fever with radiographic abnormalities similar to those described in adults. Although sacroiliitis is strongly correlated with the presence of HLA-B27 in most arthropathies, these children were HLA-B27-negative. The diagnosis of familial Mediterranean fever was delayed in both patients because the association of sacroiliitis with familial Mediterranean fever in childhood was not recognized.


The Gianotti-Crosti syndrome.

The Gianotti-Crosti syndrome. The Gianotti-Crosti syndrome is an infrequently recognized disorder with distinctive characteristics. The eruption, which lasts for two to eight weeks, consists of large, flat-topped, nonpruritic papules on the face, buttocks, and limbs. Its onset may be preceded by fever and upper respiratory tract symptoms. Associated findings include generalized lymphadenopathy, anicteric hepatitis, and HBs antigenemia. Two children with the syndrome are described to bring this entity to the attention of pediatricians.


Bronchial reactivity in cystic fibrosis. There is considerable dispute regarding the prevalence of asthma in patients with cystic fibrosis (CF). We studied 50 patients with CF and compared their responsiveness to inhaled histamine with that of asthmatic children. The incidence of positive responses to inhaled histamine was 24% in the patients with CF and more than 90% in the asthmatic patients. We found no correlation, in the patients with CF, between the histamine response and several indexes of atopy (clinical allergic disease and positive allergen skin tests). Positive responders to histamine were not evenly distributed over the disease spectrum of CF. Instead, positive responses occurred only in those patients whose prechallenge pulmonary function was abnormal. We conclude that the heightened bronchial reactivity in patients with CF reflects the severity of their underlying lung disease rather than the presence of coexistent asthma.


Injuries in high school sports.

Injuries in high school sports. A two-year study was made of injuries received in high school sports. Athletic trainers were placed in four high schools to conduct the investigation. Injuries occurred in women's sports at a rate of 22 per 100 participants; men's injuries occurred at a rate of 39 per 100 participants. Football and wrestling accounted for the highest injury rates; tennis and swimming accounted for the lowest rates for both sexes.


Medical correlates of infant development. Attempts to correlate developmental outcome with medical complications affecting the fetus and infant have focused on the prenatal, intrapartum, and postnatal periods. The time beyond the newborn stage has not been explored in detail. The aim of this study was to relate events occurring during the gestational and neonatal periods as well as the infancy periods to later performance by the use of four medical scales. A total of 126 preterm infants were followed up prospectively from birth to 2 years of age. Medical complications occurring during the prenatal, intrapartum, and postnatal periods as well as the first nine months of life were recovered. No relationship was found between obstetric and neonatal events and developmental outcome. Significant correlations were seen between medical events of later infancy and development at 2 years of age.


Variability of prior practice in learning and retention of a novel motor response. The schema theory prediction that variability of practice would influence the strength of the motor response schema was investigated. Three groups of subjects, defined by much, little, or no variability of distances moved in prior practice on a linear-slide apparatus, completed 12 initial practice trials. Subjects then had 10 trials to estimate a novel distance from a new starting point. Knowledge of results was provided on the first three trials and withdrawn on the last seven trials. No differences in accuracy of production of the novel distance were noted although evidence for a stronger-schema by the group with little variability was noted on the second transfer trial. On the trials on which knowledge of results was withdrawn this stronger schema group maintained performance while the other two groups showed a decrement in performance.


Nasality and precision of articulation.

Nasality and precision of articulation. Two reading passages, one with nasal consonants and one without, were tape-recorded for 72 subjects: 34 selected as having precise articulation and 38 selected as having imprecise articulation. These speech samples were evaluated for degree of precision and also for degree of nasality by the psychological scaling method of equal-appearing intervals employing a 7-point scale. Analysis indicated a relationship between degree of precision and degree of unpleasant nasality, that is, a tendency for decreases in precision to be accompanied by increased nasality and a tendency for males to be more imprecise in articulation and more nasal than females.


Conceptual deficits and aging: the Category Test. Category Test performance of 41 bright aged normals was compared with the performance of 40 young normals and a group of 43 patients with suspected neurological dysfunction. The aged normals were not only as deficient as the neurologic patients but showed a similar pattern of deficits on Category subtests. The extreme difficulty experienced by aged normals and patients on Subtests III and IV was explained as a function of task complexity rather than of conceptual difficulty of conceptual principles and task complexity in a variety of impaired groups was suggested.


Physical activity, motor development and self-concept: race and age differences. To investigate the effect of organized physical activity on the development of specific motor skills (body coordination and self-concept) of elementary age children, 344 children from the ethnic origins, black and white, were administered the Schilling Body Coordination Test and the Martinek-Zaichkowsky Self-concept Scale for Children. Motor development (body coordination) and self-concept scores were significantly higher for the group who participated in the physical activity program than for controls who did not. There was a linear trend in motor skill improvement, with Grades 2, 3, 4, and 5 showing significantly higher gains than Grade 1. The self-concept scores indicated a significant decline for Grades 3, 4, and 5. There were no significant differences between blacks and whites. A two-way interaction was found between grade and race in motor development, with blacks demonstrating lower mean scores than whites in Grade 2 but higher mean scores in Grade 5. Correlations between self-concept and motor development were non-significant.


Effects of subliminal stimulation on masculinity-femininity ratings of a male model. The effects of subliminal stimulation on masculinity-femininity ratings of a male model were tested for 100 male undergraduates, randomly divided into four groups and individually shown a slide of a male model. One group received no further stimulation. A second group received a subliminal flash of white light across the image of the model; a third group was presented with the subliminal message "masculine," while a fourth group was presented with the subliminal message "feminine." Subjects were asked to rate the model on a six-point scale of masculinity-femininity. The differences in ratings among groups were not significant, indicating that subliminal stimulation did not influence masculinity-femininity value-norm-anchor judgments. There were no significant differences in the reported perception of additional stimuli or the tendency to be relaxed among the four groups. However, subjects who received the "masculine" message and reported that they were more relaxed did tend to rate the model higher in masculinity.


Eyewitness testimony: an exploration of question wording upon recall as a function of neuroticism. Two experiments are reported in which subjects viewed films and were interrogated with questions employing the definite or the indefinite article. A significant interaction existed betweed a witness's level of neuroticism and question wording. There were also significant correlations between Neuroticism and errors resulting from questions containing the indefinite article.


Lifted-weight difference thresholds as a function of hand. A study was conducted to determine if the two hands of right-handers are differentially sensitive to changes in perceived weight. Using the method of limits, the left and right hands of 20 college students were tested at each of three reference weights: 90, 100, and 110 gm. Results indicated that, over-all, difference thresholds for the two hands were not reliably different, though a trend did emerge toward greater right-handed sensitivity to weight changes at smaller weights and greater left-handed sensitivity at greater weights.


Relationship between birth order and leadership style for nursery school children. 36 nursery school children were given a revised form of Fiedler's (1967) least preferred co-worker scale designated as the least preferred playmate scale. The purpose was to investigate the relationship between least preferred playmate scores and the birth order of young children. A 2 X 2 contingency table was constructed between birth order (first and later born) and leadership style (high and low). The resulting chi squares were insignificant for the total population and for males. However, for females the results were significant with a higher percentage of firstborns being task-oriented (low score) and a higher percentage of later borns being relation-oriented (high score).


Heart rate, recall, and reaction-time measures of levels of processing. A problem of circularity emerges in any attempt to index depth by retention alone. In the present study, reaction time (RT), and heart-rate response were used to index the three qualitatively distinct levels of physical, phonemic, and semantic processing. An additional objective was to distinguish between the three levels under incidental vs intentional learning conditions. Subjects were 46 male undergraduates who were given 30 trials. A trial consisted of the presentation of an orienting question and an imperative word-stimulus separated by a 6-sec. interval. There were three types of questions in order to induce processing to one of the three target levels. The results indicated that recall as well as heart-rate acceleration distinguished between two (physical vs phonemic and semantic) rather than three levels of processing in the incidental condition. Heart-rate change differentiated between incidental and intentional, the intentional condition showing a smaller change. Semantic and phonemic RTs were faster than physical RT, but there were no differences between semantic and phonemic RTs. Intentional recall was superior to incidental recall. It is suggested that psychophysiological indices can provide independent evidence for 'levels of processing.'


Visual processing of simultaneously presented peripheral and foveal stimuli. Results are reported for an experiment in which subjects were required to detect simple stimuli presented tachistoscopically to the periphery and/or fovea. Three modes of stimulus presentation were employed: an SMf mode in which foveal stimuli were presented alone; an SMp mode in which peripheral stimuli were presented alone; and an SIMfp mode in which peripheral stimuli were presented simultaneously. Stimulus detection was significantly better under SMf and SMp modes of presentation than under an SIMfp mode of presentation. Results are discussed in terms of a limited-capacity attentional model in which selective factors operate in the initial processing of visual stimuli and prior to short-term memory.


Searching for multiple targets simultaneously: is it really possible? In an attempt to clarify the findings of Neisser and his associates with respect to parallel processing of multiple target items in a visual search task, subjects were tested in a multiple-target search situation in which the various target sets were not nested. 20 sessions were run for each subject with 12 trials per day. The targets used were geometric forms, allowing for manipulation of the number of features in each form. The results do not confirm those of Neisser, in fact, the interaction of session x target-set size was in a direction opposite to that predicted by a parallel preattentive processing may in fact have reflected a tendency for subjects to scan for a master set of targets, regardless of which subset of that set was actually present on a given set.


Task difficulty and visual similarity increase a distractor's effects on random shapes. Recognition of random shapes followed by a visual distractor is altered by the type of distractor and whether the distractor needs to be attended. Three experiments tested which characteristics modify a visual distractor's effect on random target shapes presented for 75 to 150 msec. Exp. 1 showed that increasing the number of digits to be remembered (1, 3, or 8) increased the effectiveness of digits as distractors. Exeir effect as visual distractors for random target shapes. Random shapes were highly effective as distractors, while pictures of faces or comples colored pictures had a relatively small effect. In Exp. 3 decreasing the presentation time for novel visual distractors decreased recognition of the distractors but not of random target shapes. However, adding a three-digit distractor after the novel visual distractor did decrease recognition of target shapes. Exps. 2 and 3 showed that the order of the recognition tests of the target and distracting stimuli altered target recognition if and only if subjects did know which was to be reported first. These experiments indicate that the effect of a visual distractor depends on both the extent to which it is allotted attention and its visual similarity to the target stimulus.


Test expectancy and encoding of pictures and words. Undergraduates were shown pictures or corresponding labels and then were tested for recognition either in the same mode or in a cross-over mode. Significantly more items were recognized in the picture-picture condition than in the picture-word and word-picture conditions. Informing subjects in advance of the change in modality significantly improved picture-word performance.


Performance on a reciprocal tapping task with variations in intertapping interval. Fitts' law was investigated in a study of the effect of the index of difficulty (ID) and intertapping interval upon reaction time (RT) and movement time (MT) for a reciprocal tapping task. ID showed its well-established relationship with MT as described by Fitts' law: MT = aID + b. Improvement in the linearity of this relationship was, however, demonstrated by expressing MT in logarithmic units. While ID had an unsubstantial (though significant) effect on RT, increases in intertapping interval from zero to any level of discrete tapping led to significant increases in RT of about 135 msec. The results are interpreted as lending support to Fitts' thesis that RT and MT reflect independent phases of information processing.


Performance of institutional retardates on standard and new forms of the Quick Test. 121 institutionalized mentally retarded patients were tested on Forms 1-3 and 4-6 of the Quick Test; IQs were correlated with other IQs available from institution records. The forms of the Quick Test correlated significantly with the more traditional and time-consuming tests of intellectual performance. It was concluded that the Quick Test is an excellent tool for experimenters and educators who need an efficient and reliable estimate of intellectual development.


Visual short-term memory, response delay, and age. Recall and recognition memory performance of 12 young (M = 19 yr.) and 12 older (M = 72 yr.) females was studied in relation to response delay (5, 25, and 125 sec.) and stimulus complexity (6.1 and 13.7 bits of information). The subjects were matched on verbal IQ, visual acuity, and educational levels. Stimuli were abstract, black and white, 4 X 4 square matrices. Age-related decrements in memory performance were associated with stimulus complexity but not with response delay. Older subjects also reported experiencing encoding difficulties during the registration phase. The results were discussed with reference to the locus of age-related decrements in visual short-term memory.


Affective response to exceptional children by students preparing to be teachers. A semantic differential was administered to 56 majors in early childhood, elementary, and middle school at the University of Georgia. Subjects' affective response to exceptional children was higher when they perceived having only a single exceptional child vs many in a regular classroom.


Motor development profiles of preschool deaf and hard-of-hearing children. 11 deaf and hard-of-hearing preschool children generally exhibited normal or at-age profiles of motor development. The few delays in certain functional areas were assumed to be due partially to lack of training and play experience rather than to deafness or hearing impairment. Two boys had a variety of motor and physical problems. Also some of the at-age children functioned above-age in a few skill areas. Two of the 4 children who demonstrated specific balance skill deficits had had meningitis at an early age; this supported the rationale that there was a relationship between etiology of meningitis and specific balance difficulties.


Reliability of selected psychomotor measures with mentally retarded adult males. Reliability estimates were determined for 24 moderately mentally retarded adult males on three psychomotor tasks. For four consecutive days measures were taken on reaction time, auditory and visual, 15 trials daily for each; grip strength, dominant and non-dominant hand, two trials daily for each; and standing long jump, three trials daily. Analyses of variance, adjusted for day-to-day trend, were applied to the data. Intraclass reliability coefficients for both dominant (R = .96) and non-dominant (R = .94) hand-grip strength were high. The reaction time scores for both the auditory (R = .87) and visual (R = .83) data were moderately reliable. A low reliability coefficient (R = .49) was obtained for the standing long jump.


Sex-role self-perceptions and sex-role stereotypes. 827 undergraduate students, 549 males and 278 females, responded to a set of 18 questions relating to individual self-perceptions. A second group of 35 males and 29 females responded to the questions in terms of population sex-role stereotypes for both sexes. It was hypothesized that the sexes would demonstrate convergence in self-perceptions when compared with their sex-role stereotypes. The results tended to support the hypothesis, with females demonstrating a greater deviation from the traditional sex-role stereotypes than males. The possible relationship to much publicized social movements was noted.


Teaching reading and writing skills to a teenaged spastic cerebral palsied person: a long-term case study. After a 2-mo. combined reading and writing training period followed by a 1 1/2-yr. lapse, an initially 16-yr.-old paraplegic cerebral palsied boy received 1 yr. of reading training followed by 2 3/4 yr. of writing training. Reading speed increased from 5 pages/hr. to about 40 pages/hr. Tolerance for protracted reading increased from a maximum of 15 min. to well over 2 hr. Writing progressed from the printing of letters more than 1/2 in. high with a fist grasp of the pen, to cursive writing of letters 1/8 to 1/4 in. high. Writing speed increased to about one-third of the normal rate. Training modes ranged from biofeedback methods employing EMG, electrooculogram, inertia detector, strain gage, contact detector, and amplified-image closed-circuit TV to discussions of attitudes, task orientation, and time scheduling. Intermediate were methods employing intrinsic feedback mechansims. Results demonstrate the effectiveness of this approach, as well as trainability of this spastic boy well beyond childhood. The methods devised provide a base for further application and investigation.


The lateral tongue reflex in human neonates. We undertook an investigation of the lateral tongue reflex to determine whether reflex sensitivity was systematically related to selected perinatal factors. The subjects were 24 male and 27 female newborns with a mean age of 28.9 hr. (SD = 16.8, range 5--72 hr.). The lateral tongue reflex was elicited by applying tactile stimulation of varying intensity to the lateral edge of the tongue approximately 1 cm off midline. Eight different stimuli from the Semmes-Weinstein esthesiometer were used; forces ranged from 68 mg to 3.6 gm. A total of 32 stimulations were given in two repetitions of 16 each (8 on the right side and 8 on the left side). The mean number of positive responses was 19.9 (SD = 3.2, range 13--25), with a 5% response at the lowest level of stimulation and a 100% response at the highest level. There were not differences in total number of positive responses or thresholds on the right and left sides, or in Repetitions I and II. There were no differences between males and females, vaginally and caesarian delivered infants, or resuscitated and non-resuscitated infants. No systematic differences were observed as a function of length of labor, obstetric medications, postnatal age at time of testing, Apgar scores, birth weight, or gestational age. The results suggest that the lateral tongue reflex is a stable and reproducible response that could be used to measure oral sensation, both in normal neonates and in subjects with various anatomical and/or neurosensory deficits.


Retention of bilateral performance as a function of practice order. The purpose of this study was to investigate the effect of practice order and initial performance hand on the bilateral retention of a simple tracking skill for 44 undergraduate volunteers. The apparatus was a Lafayette Model 30014 photoelectric rotary pursuit. The circle template was employed with rotation speed set at 20 rpm. Subjects were given 20-sec. trials and required to reach a criterion of 70% time on target twice in succession with both hands. For original practice, subjects were randomly assigned to one of four practice groups: preferred serial, non-preferred serial, preferred sequence and non-preferred sequence. Subjects' performance was recorded as the number of trials required to achieve criterion for both hands. One month later subjects were retested and scored in the same manner. A 2 X 2 X 2 analysis of variance with repeated measures on the last factor was used to determine the effects of initial hand, order of practice, testing periods, and the appropriate interactions. The results indicated that subjects' performance for the two testing periods differed significantly; retest was superior. Order of practice was significant and the sequential order more efficient during both learning and retest.


Dimensions of assertiveness: factors underlying the college self-expression scale. A total of 447 Israeli students, both males and females, from four educational institutions were administered the College Self-expression Scale, a measure of assertiveness. The obtained responses were factor analyzed using the principal axis solution and the varimax rotation method. The results showed four main factors which included 43 of the 50 items of the original scale. These factors were identified as the willingness to take risks in interpersonal interactions, the ability to communicate feelings, setting rules and rectifying injustices, and the presence or absence of a tendency to invoke a self-punitive attitude. The findings were interpreted as adding support to the validity of the scale as a measure of assertiveness.


Correlation between handedness and birth order: compilation of five studies. Bakan has suggested that left-handedness is the result of left hemishperic pyramidal motor dysfunction following perinatal hypoxia. To a degree support for the validity of this hypothesis rests on Bakan's (1971, 1977a) findings that left-handed college students were more likely the progeny of birth orders designated as "high-risk" than right-handed students. Attempts by others to replicate Bakan's data have been unsuccessful. To achieve a more powerful test of this relationship than has been provided by any single study, the data from the five studies which have considered it were pooled and tested. The resulting correlation between birth order and handedness was near zero.


Visual perseveration in normal and mentally retarded children. Visual perseveration was investigated within mentally retarded and second, fifth, and eighth grade normal children (Ns = 12 each group). Subjects matched an auditorially presented click to the onset and offset of visually presented stimuli. Time differences between visual stimulus offset and the point at which subjects reported simultaneity of the click and  visual stimulus offset was assumed to reflect visual perseveration. Results showed: (a) no differences between the normal children as a function of age; (b) no difference between groups for stimuli of 100 msec. or longer duration; and (c) retarded subjects judged stimuli of 20 and 50 msec. to be of shorter duration than did normal subjects. This highly specific distinction between retarded and normal subjects suggests a difference in an early stage of perceptual processing.


Disturbances of rhythm formation in patients with Parkinson's disease: part I. Characteristics of tapping response to the periodic signals. A tapping test in which the tasks required a synchronous response to a periodic sound signal by the finger tapping was performed by 27 normal subjects and 146 patients with Parkinson's disease. Some patients could not maintain a synchronous response at a critical frequency of 2.5 or 5 Hz (taps per second) and showed a hastened tapping of 5  6 Hz, independent of the input signal frequencies, i.e., the 'hastening phenomenon.' The other patients and normal subjects could respond synchronously up to 5  7 Hz. Autocorrelational analysis of the sequential tapping intervals suggested that the synchronized response was performed by a feedback control with the input signal as target except at 2.5 and 5 Hz, whereas the hastened tapping of patients was a random process. The frequency-dependence of the error in the tapping was interpreted as representing an intrinsic oscillation in the central nervous system, which would be masked in normal subjects but released in patients with Parkinson's disease. Around 2.5 or 5 Hz the error or response becomes so large that some patients can no longer maintain the synchronized response and show a hastened tapping due to this intrinsic oscillation.


Disturbances of rhythm formation in patients with Parkinson's disease: part II. a forced oscillation model. The origin of the characteristic disturbances of rhythm formation in patients with Parkinson's disease (the hastening phenomenon) was discussed, using a second-order system of the periodic response. The input signal was regarded as a pulse series of a Dirac function. The output process of the system had maximal errors of response at input frequencies of f = omega0/n (n = 1, 2, . . .), where omega0 was the intrinsic frequency of the system. Damping coefficient epsilon represented a function of an inhibitor against these maximal errors and the errors diverged to infinity when epsilon = 0. The solution of this forced oscillation system indicated that the intrinsic oscillation of the system has a possibility to be excited at these critical frequencies f = omega/n. Inferred from data on the tapping test, the frequency of an intrinsic oscillation was 5 Hz in the central nervous system, then the critical frequencies were predicted 5/n = 5, 2.5, . . . Hz. On the tapping test the errors of response become maximum around 2.5 and 5 Hz (taps per second), and their peak heights increased from the minimum in well trained normal subjects to the maximum in patients. An inhibitory mechanism against the maximal error would function well, i.e. epsilon greater than 0, in normal subjects but so insufficiently (epsilon leads to 0) in patients that the excited intrinsic oscillation would control their response directly. Thus some patients could no longer maintain a synchronous tapping response at 2.5 Hz or 5 Hz and showed a hastened tapping of 5  6 Hz independent of the signal frequency.


Effects of a stimulant drug on extraversion level in hyperactive children. 7 hyperactive children in a pilot study, and 15 hyperactive and 15 non-hyperactive control children in a later study, were assessed for salivation to lemon juice stimulation, reactive inhibition on an audio-vigilance task, and visual-motor maze errors. Hyperactive children were tested under stimulant drug and nondrug conditions and nonhyperactive children twice under nondrug conditions. Pilot study hyperactive children displayed significantly fewer maze errors and somewhat greater salivation and lesser reactive inhibition levels under the drug than the nondrug conditions. Follow-up study control children did not differ significantly between test occasions on any measure, while the hyperactive children displayed significantly fewer maze errors, more salivation, and less reactive inhibition under the stimulant drug, indicating significant decreases in extraversion after the stimulant drug.


Hearing test for a profoundly retarded human subject. A profoundly retarded 28-yr.-old female was trained to avoid an aversive but harmless shock to the foot by withdrawing the foot upon presentation of a visual cue. She was later unable to learn to avoid the shock consistently upon presentation of an auditory cue, confirming the ward staff's contention that she had a hearing disability. The audiometric technique using negative reinforcement bridges the problems of (1) difficulty in finding positive reinforcers for patients of low functioning and (2) satiation which may result from the continued use of positive reinforcers. The use of aversive stimuli raises ethical concerns. The growing trend in research is that aversive stimuli are permissible for individuals for whom positive techniques have not been effective and when used by trained professionals under careful review.


Panic-fear in asthma: a divergence between subjective report and behavioral patterns. The reported frequency of occurrence of Panic-Fear symptoms during asthmatic attacks varies widely and is related to treatment response independently of the objective severity of asthma. In a previous study, symptom minimizers (Low Panic-Fear) requested few as-needed (PRN) medications and treatments while hospitalized, even on days when significant airway obstruction was present. In contrast symptom emphasizers (High Panic-Fear) requested PRNs frequently, even on days when no airway obstruction was present. In the present study, these behavioral differences toward PRNs occurred despite the similar ability of patients in various Panic-Fear groups to perceive and report changes in airway obstruction. Together these results suggest that specific behavioral strategies, which do not derive from differences in symptom perception, influence the treatment response of asthmatic patients differing in Panic-Fear symptomatology.


Complexity, incongruity, pre-exposure and the familiarity effect in visual selection. A consistent finding in the literature concerning visual selection is that subjects spend more time viewing unfamiliar stimuli than familiar stimuli. In the present investigation a procedure to measure competitive viewing times to familiar and unfamiliar stimuli was used. Results of the analyses of viewing times showed that the magnitude of the familiarity effect was a positive function of the duration of stimulus pre-exposure. In addition no differences were found in subjects' "preference" for familial and unfamiliar stimuli as measured by "like-disliked" ratings.


Prevalence of precipitating antibodies against mycoplasmas and viruses in egg-laying flocks in Northern Jutland. Antibodies against infectious laryngotracheitis virus, influenavirus and Newcastle disease virus were not demonstrated. The prevalence of infections caused by adeno- and reovirus in egg-laying flocks was 85 and 74% respectively. Approximately 25% of the flocks had antibodies against infectious bronchitis virus and infectious bursal disease virus. A raised prevalence of antibodies against mycoplasmas was found with increasing age.


[Tension band wiring of canine and feline supracondylar epiphyseal femoral fractures (author's transl)]. The present investigation describes the treatment of 27 cases of canine and feline supracondylar epiphyseal--metaphyseal femoral fractures with tension band wire. The wire was passed through transversal parallell drill holes, one in each fragment. The wires intercrossed dorsally. Stable fixation followed tightening of the wires. 20 out of 25 primarily successful cases were re-examined. 19 were completely well. One case showed a slight transient lameness following hard exercise.


[Ultrastructural study of experimental cerebrocortical necrosis in calves (author's transl)]. Cerebrocortical necrosis (CCN) was experimentally induced in three calves with the thiamine antagonist Amprolium. The calves were followed clinically. At the time of development of typical clinical signs of CCN the calves were killed and necropsied and a complete histopathologic examination was performed. The light microscopic lesions of the cerebral cortex were those of middle laminar necrosis and deep laminar edema. The necrotic zone consisted of fine vesicles and differed only slightly from the edema zone. In the former some neurons were morphologically normal, others showed signs of injury, while in the latter all neurons were injured. The lesions are consistent with those found in natural cases of CCN. Biopsies from the cerebral cortex were taken at the time of early clinical signs. Ultrastructural studies of these biopsies showed no clear difference between the zones of necrosis and edema observed light microscopically. The ultrastructural changes were characterized by dilatations in the neuropil. The cytoplasm and foot plates of the astrocytes had a "watery" appearance and contained dilated mitochondria and large vesicles. The vesicles were continuous with the granular endoplasmic reticulum. It was concluded that the initial morphologic changes in CCN in calves were indicative of a cytotoxic edema of the astrocytes. This may be due to a cytotoxic edema with subsequent loss of cell volume control. The primary astrocytic changes could then lead to neuronal injury.


Combined action of plant estrogens, F-2 toxin and natural estrogens. The investigation concerns the interaction of plant estrogens, F-2 toxin, and natural estrogen (estradiol-benzoate) as causative factors of eostrogenic changes. Plant estrogens and F-2 toxin were applicated at three and estradiol-benzoate at two dosage levels. The estrogenic effect was studied by bioassay on immature rats taking uterine weight, uterine liquid and vaginal opening as criteria. When uterine weight is taken as a criterion, plant estrogens and F-2 toxin, no matter if they are administered alone or together, regularly increase the effect of estradiol-benzoate, but when uterine fluid is taken as a criterion they always decrease the effect of estradiol-benzoate. According to the present results it seems obvious, that the mode of action of estrogenic substances occurring in plants considerably differ from that of natural estrogens. Thus the mechanisms which cause disturbances may be different from those of natural estrogens.


[Hodgkin's disease: the value of prognostic criteria and of the combination of radiotherapy and chemotherapy in localised lymphoid stages (I and II). 94 patients undergoing laparotomy (author's transl)]. Criteria reputed to be of grave prognostic significance were studied in 94 patients suffering from Hodgkin's disease at stages I and II, after laparotomy and splenectomy. The parameters studied (age, general signs, histological type, mediastinal involvement) are less prognostic factors than indications of unrecognised extension of the disease: almost 1/3 of unrecognised lesions in the presence of one of the criteria; almost 2/3 with two or more. Exploratory laparotomy revealed lesions unsuspected on the basis of clinical evaluation only in 10% of patients with no criteria of poor prognosis. The long term prognosis of the disease depends, in fact, not upon the existence of these criteria but upon the method used in initial treatment. Five year survival and cure rates are significantly better in patients treated with combined polychemotherapy (MOPP) and radiotherapy than in those treated with radiotherapy alone. These results would indicate that routine laparotomy should be abandoned in patients with a localised clinical staging if it is decided to begin treatment with a combination of radiotherapy and chemotherapy. So-called prognostic factors could then be used simply to vary the intensity of the treatment prescribed.


[Systolic strangulation of the anterior interventricular artery : a rare cause of myocardial ischaemia (author's transl)]. The relationship between myocardial ischaemia and the muscular bridge over the anterior interventricular artery with systolic strangulation has now been demonstrated. This forms part of the aetiology of angina pectoris with radiologically "normal" coronary arteries. A case is reported where the severity of the clinical picture justified surgery to divide the muscular bridge, without touching the underlying artery. The course has been satisfactory, with a two years follow-up.


[Tubal sterility: Disturbances in haemostasis and cardiac arrest during the shirodkar manoeuvre (author's transl)]. Over a period of 10 months (august 1975 to may 1976), the authors observed 6 successive accidents during the Shirodkar manoeuvre during operations for sterility of tubal origin: 1) 4 cases involved disturbances in haemostasis only, clinical manifestations being seen in only one case. In the laboratory, these quite atypical manifestations suggested either fibrinolysis or disseminated intravascular coagulation. 2) In 2 cases there was cardiovascular collapse with cardiac arrest. In the first patient, cardiac arrest was followed by a period of coagulopathy quite similar to those seen previously. In the second case resuscitation failed, leading the authors to abandon use of the Shirodkar manoeuvre, which brought the study to an end. We are unable to provide any satisfactory pathological interpretation of these complications, thought two factors are worthy of consideration:--The hydrocortisone suspension used;--The uterine trauma related to peroperative manipulations.


[Deep selective myocardial hypothermia (author's transl)]. This new method of myocardial protection was used to prevent complications of cardiac ischaemia during clamping of the aorta. 4 litres of Ringer lactate at 4 degrees C are used to perfuse the coronary arteries and produce a total, uniform and deep fall of all the pericardial and myocardial system. This results in a flat electrocardiogram, i.e. the interruption of electrical activity of the cardiac cells. This effect persists until the aortic clamp is released which results in reoxygenation, a rise in temperature and the restoration of function. The method has been used in more than 250 operations with extracorporeal circulation (valves, bypass procedures, transplants). Up until the present, it has proved superior to techniques of coronary perfusion or hypothermia obtained using Shumway's technique.


[Familial sarcoidosis 26 cases in 12 families (author's transl)]. The analysis of 12 families with 2 or more members suffering from sarcoidosis led a number of findings:--the increased prevalence of sarcoidosis in persons of mixed race from the French Caribbean), which would suggest the intervention of a racial component in the pathogenesis of sarcoidosis;--the rarity of cases where sarcoidosis affects more than 2 members of the same family;--the preponderance within the same family of subjects of identical sex, whether direct collaterals or a parent-child relationship (20 cases out of 26).--the importance of mother-child transmisstion (5 cases) as opposed to father-child transmission (1 case).


[Microbiological verification of the cleanliness of the hands in surgery (author's transl)]. A technique for sampling organisms on the hands, the so-called "disc method" was tested in three surgical departments, in parallel with the classical method of direct finger print on a gel medium. The respective value of 6 products for washing the hands was assessed in order to demonstrate the possibilities offered by the technique proposed, which is truly quantitative. In particular, it was shown, "in the field", that three products had a very valuable action (Chlorhexidine, Hexachlorophene and a quarternary ammonium salt), but simple washing with Marseille soap followed by rincing with alcohol gave good results, limited only by the absence of any persistent bactericidal action.


[Auto-immune haemolytic anaemia and mediastinal dysembryoma in a 6-year-old child (author's transl)]. In a six-year-old girl, suffering from an auto-immune haemolytic anaemia, routine radiological examination revealed the presence of a mediastinal tumour which was removed surgically and proved to be a multiple tissue polycystic dysembryoma. Haemolysis and signs of anti-erythrocyte auto-immunisation disappeared after the operation and total and stable cure obtained with a follow-up of 15 months. The target antigen of the anti-erythrocyte autoantibody could not be found within the tumour. However, the latter contained lymphoid tissue and a considerable quantity of antibody. Although indirect, these findings offer arguments in favour of the secretion of autoantibodies by the dysembryoma.


[The excision of villous tumours of the rectum via a trans-sphincterian anal approach (author's transl)]. Cleavage in the thickness of the internal sphincter and of the circular layer of the rectum is performed. By progressive drawing down, this method makes it possible to obtain complete excision, passing at a distance from the tumour in its different planes.


[Prolonged treatment with acebutolol: surveilance of ocular status (author's transl)]. A very through ocular examination was made in 48 hypertensive patients treated for 18 months with acebutolol in a daily dose of between 400 and 2400 mg. Abnormal symptoms in the form of a prickling sensation were seen in two cases. Microscopic punctate lesions of the conjunctive were seen in 9 subjects, either with the Bengal Pink or fluorescein tests. These very slight microscopic lesions were found in general only in the region of the palpebral slits, a zone normaly exposed to microtrauma, which decreases the value of this finding. The results of a Schirmer test were considered to be abnormal in six patients. These ocular abnormalities were generally mild and it could not be shown conclusively that they were related to treatment with acebutolol. Ocular surveillance, with examinations repeated every six months, indicated the absence of any harmful effect on the eye of prolonged used of acebutolol in the treatment of hypertension.


[Arterial hypertension: the role of the central nervous system. II. Experimental and clinical study (author's transl)]. Several models of experimental hypertension are described (neurogenic, mineralocorticoid, renovascular and genetic hypertension). An activation of the sympathetic nervous system is seen in these situations (increases in sympathetic nervous discharge, in the synthesis of noradrenaline and in the level of plasma catecholamines). This activation may be connected with biochemical abnormalities within the medulla which have been noticed for catecholamines and serotonin. These medullary abnormalities could themselves depend on abnormalities situated at higher levels (hypothalamus). The factors which determine the central problem and their mechanism of action are still hypothetical (e.g. the direct effect of sodium on the brain, the effect of stress and the environment as well as genetically determined biochemical abnormalities of the central nervous system). In the case of essential hypertension in man, available data are limited to the levels of plasma catecholamines which suggest an increased sympathetic activity of central origin when these levels are elevated.


[Immunological changes during the immediate postoperative period (author's transl)]. Postoperative variations in the different parameters of humoral and cellular immunity were studied in 18 adult patients in general surgery. Levels of immunoglobulins G (igG) fell and those of immunoglobulins M (igM) increased significantly. Lymphocytic proliferation under the influence of PHA showed a significant fall. Neither polynuclear function nor total complement activity were modified. Patients in whom the postoperative course was complicated by sepsis differed from the others by a lower activity of the lymphocyte transformation test and by a higher level of igG and igM on the day prior to surgery. In addition, deficiency in the lymphoblastic transformation test increased during the postoperative period, there was a further fall in IgG and IgM increased less in these patients than in those in whom the postoperative course was uncomplicated.


[The prognosis in primary chronic glomerulonephritis in the adult. 298 clinicopathological cases (author's transl)]. The study involved 298 cases of chronic glomerulonephritis (GN) in adults. The results of renal biopsy were used to classify the patients into four groups: Membranous GN, 81 cases; focal glomerulo sclerosis, 80 cases; Membrano-proliferative GN, 62 cases; GN with mesangial deposits of IgA, 75 cases. The patients were observed over a period ranging from 1 month to 36 years. The average period of surveillance for each category was between 4 and 6 years. The course in each histological type was assessed on the basis of actuarial tates of renal death, of moderate renal insufficiency (plasma creatinine greater than 1.5 mg%( and of hypertension. Renal survival at 10 years was was arounds 90% for membranous GN. 85% for GN with mesangial deposits of IgA, 70% for focal glomerulo sclerosis and 50% for membrano-proliferative GN. The prognosis should be based upon a combination of histological and clinical findings. Severity of prolonged nephrotic syndrome, regardless of the histological type of the nephropathy, is worthy of emphasis. In the group fo focal glomerulo sclerosis, prognosis differs greatly in relation to the presence or absence of a nephrotic syndrome. Complete remission may be seen in the group of focal glomerulo sclerosis, and in membrano-proliferative GN despite the persistence or worsening of histological lesions seen on repeated biopsies.


[Clinical usefulness of saralasin in human hypertension (author's transl)]. We have studied the effects of intravenous infusion of saralasin, a competitive antagonist of angiotensin II, in 27 hypertensive patients: 13 had essential hypertension, 14 had renal lesions which involved the renal artery in 9 cases. In essential hypertensives saralasin administration did not significantly lower blood pressure, even after mild salt depletion. It induced a decrease in blood pressure in 7 patients with renal abnormalities (5 with renal artery stenosis, 2 with unilateral parenchymal disease). It may be suggested that in these cases hypertension was dependent, at least partly, on the renin-angiotensin system. In agreement with other investigators, we have found a relationship between the level of plasma renin activity and the blood pressure decrease obtained by saralasin. In patients with unilateral renal artery stenosis, blood pressure decrease was related to renal vein ratio of plasma renin activity.


[Cystic pneumatosis of the small intestine following jejuno-ileal by-pass for obesity (author's transl)]. The case reported is that of a young woman who underwent a termino-terminal jejno-ileal by-pass procedure for obesity which was refactory to usual forms of treatment. Eight months later, a cholecystectomy was carried out for lithiasis, presenting with abdominal pain. At the time of operation, lesions of cystic pneumatosis were discovered on the excluded length of small bowel. This complication frequently manifests itself in the form of pseudosurgical abdominal pain, or as diarrhoea. More rarly, it is a radiological finding. The pathogenesis remains a subject of discussion. The mechanical theory would seem the most logical, since colonic intraluminal pressure is higher than that in the intestine excluded from the circuit. Bacterial proliferation, classical in blind loops, would be a farourising factor.


[Merits of the assay of plasma catecholamines in a glucagon test to diagnosis of pheochromocytoma (author's transl)]. In one female patient suffering from an extra-adrenal pheochromocytoma, a stimulation test with glucagon was performed. In spite of the absence of an increase in heart rate and blood pressure, a pronounced increase in plasma catecholamines showed this test to be positive. The authors discuss the reliability criteria of this test, and confirm its good tolerance.


[Current concepts of bronchial fluidifiers (author's transl)]. Having summarised recent studies of the biochemical and rheological nature of bronchial secretions, the authors envisage different types of drugs which modify bronchial secretions: mucolytic agents, drugs modifying local water equilibrium and mucoregulators. According to the modes of action of these drugs and the nature of the secretory disturbances, the authors propose new therapeutic schemes. The treatment of chronic bronchial hypersecretion should not necessarily aim to fluidify the secretions but should normalize their rheological properties in order to improve mucociliary transport. The various fluidifiers and regulators of bronchial secretions are in no way interchangeable and should only be used when appropriate.


[Hepatic arterial embolisation. 35 cases (author's transl)]. Thirty five cases of hepatic arterial embolisation are reported. The analgesic effect in association with tumour pathology (27 cases) was virtually constant (80% of cases). Arterial embolisation should thus replace surgical disarterialisation in the management of malignant tumours of the liver. It improves the quality of survival in painful tumours, above all when they are hypervascularised. Two fatal complications as a result of the technique emphasise the absolute need to respect its contraindications: portal thrombosis, even segmental, or hepatic failure. Two cavernous haemangiomas and one angioma with arterioportal fistula complicated by haemobilia were also successfully embolised. Five traumatic vascular lesions, two of which resulted in severe haemobilia, also benefited from superselective embolisation.


[Spontaneous rupture of the renal pelvis. A non-surgical acute abdomen (author's transl)]. The authors report a case of rupture of the renal pelvis in a young man, the course of which was spontaneously favourable over a period of a few days. No aetiology was determined, despite complete clinical, biological, pyelographic and arteriographic studies. The patient recovered completely without surgical or urological treatment. This condition is rare, 50 cases having been published in 1975.


Studies of the transcription of viral genome in adenovirus 5 transformed cells. Transcription of the human adenovirus 5 genome in transformed rat embryo cells (DFK3) was investigated using two different approaches. Preferential digestion of transcribed viral sequences by DNase I was analysed using kinetics of renaturation of 32P-labeled Ad5 HpaI restriction fragments in the presence of material which was stable after nuclease treatment. The second approach was the hybridization of 32P-labeled nuclear RNA from transformed cells with Ad5 restriction fragments which were attached to a nitrocellulose filter. These two methods gave similar results. It was found that not all integrated regions of the Ad5 genome are active in transformed cells. 2,5 copies of the HpaI-E fragment of Ad5 DNA were found in transformed DFK3 cell line. Nuclear RNA from these cells hybridized to HpaI-E fragment of Ad5 DNA, but only about half of sequences of the integrated HpaI-E fragment was sensitive to DNase I digestion.


The location of the globin mRNA sequence within its 16S precursor. The coding sequence of globin mRNA has been located at or very close to the 3' end of its poly(A)-containing 16S precursor. The 16S RNA was annealed to globin cDNA and the hybrid digested with ribonuclease H. The undigested fragment did not bind to oligo(dT)-cellulose and its size was that expected for the intact 5' portion of the precursor.


Human uracil DNA N-glycosidase: studies in normal and repair defective cultured fibroblasts. Uracil DNA N-glycosidase, an enzyme which participates in the excision of uracil from DNA, was measured in extracts from fibroblasts lines cultured from normal subjects, from several subjects with the genetic disease xeroderma pigmentosum, and from a subject with ataxia telangiectasia. The cell lines representative of complementation groups A and D of xeroderma pigmentosum and of ataxia telangiectasia had roughly the same level of activity as did the normal cells. On the other hand, cells from two xeroderma pigmentosum variants (XP4BE and XP13BE) had roughly half the normal level of activity, and cells from the heterozygous mother of XP4BE had an intermediate level of activity. In spite of these quantitative differences, no systematic alterations in reaction characteristics, apparent Km for substrate, or purification characteristics were noted for enzyme from any of the lines. Thus a causal relationship, if any, between levels of activity and the disease symptoms is equivocal.


Helix geometry of single stranded DNA 'A' and 'B' forms from minimum energy conformations of dimeric subunits. Low energy conformations with dihedral angles similar to those occurring in fibers of the 'A' and 'B' forms of DNAs have been calculated for the deoxydinucleoside phosphates dApdA, dCpdC, dTpdT, dGpdG and dGpdC (1-3). These conformers have been used as building blocks for generating larger single stranded polymers, whose helical parameters we have calculated. We find that single stranded 'A' and 'B' form helices tend to be narrower and more tightly wound than the duplexes obtained in fibers (4,5). This is consistent with experimental observations on single stranded fibers of poly (rC) (6). We also find that the different sequences have different helix geometries. In addition, it is observed that large variations in helix geometry for a given sequence are achievable at little energetic cost.


Thermal denaturation of nucleosomal core particles. Thermal denaturation of very homogeneous preparations of core particles from chicken erythrocyte chromatin is studied by several techniques. The change in absorbance, which is very closely paralleled by changes in heat capacity, which is very closely paralleled by changes in heat capacity, is a biphasic process with inflexions at 60 degrees C and 74 degrees C. In contrast, isolated DNA of the same length denatures in a single transition around 44 degrees C. Monitoring the circular dichroism of the cores during thermal denaturation reveals biphasic changes in the secondary structure of the DNA, preceding the base unstacking by 10 degrees C in the first and 3 degrees C in the second phase. However, measurable alterations in the secondary structure of the histones are confined to the second phase with a melting temperature at 71 degrees C. Increase in the ionic strength of the buffer from 1 mM to 10 mM leads to almost monophasic melting curves as measured by absorbance and CD, while not causing any measurable conformational changes at room temperature. The melting of core particles is interpreted as a denaturation of about 40 base pairs in the first phase, followed by a massive breakdown of the native structure of a tight histone-DNA complex, which frees the remaining 100 base pairs for unstacking.


The interaction of ethidium with synthetic double-stranded polynucleotides at low ionic strength. The interaction of ethidium with synthetic DNA and RNA double-stranded polymers at 0.01 M ionic strength, pH 7.0, has been studied by fluorimetry at low drug to nucleotide ratios. Binding constants have been calculated assuming an excluded-neighbouring site model for the interaction of ethidium with double-stranded polymers. The values obtained are poly d(AT).poly d(AT), 9.5 X 10(6) M-1; poly dA.poly dT, 6.5 X 10(5) M-1; poly d(GC).poly d(GC), 9.9 X 10(6) M-1; poly dG,poly dC, 4.5 X 1-(6) M-1; poly d(AC); poly d(GT), 9.8 X 10(6) M-1; poly d(AG).poly d(CT), 1.3 X 10(6) M-1; poly rA.poly rU, 4.1 X 10(7) M-1. The displacement of ethidium from poly d(AT).poly d(AT) by 9-aminoacridine and an acridine-containing antitumor agent (NSC 156303; 4'-(9-acridinylamino)methanesulphon-m-anisidide) has also been examined.


Effect of DNA on poly (ADP-ribose) glycohydrolase and the degradation of histone H1-poly (ADP-ribose) complex from HeLa cell nuclei. A poly(ADP-ribose)-H1 histone complex has been isolated from HeLa cell nuclei incubated with NAD. The rate of poly(ADP-ribose) glycohydrolase catalyzed hydrolysis of the polymer in the complex is only 1/9 that of free poly(ADP-ribose), indicating that the polymer is in a protected environment within the complex. Comparison of the rate of hydrolysis of free poly(ADP-ribose) in the presence or absence of H1 to that in the complex synthesized de novo indicates a specific mode of packaging of the complex. This is further indicated by the fact that alkaline dissociation of the complex followed by neutralization markedly exposes the associated poly(ADP-ribose) to the glycohydrolase. The complex also partially unfolds when it binds to DNA as evidenced by a 2-fold increase in the rate of glycolytic cleavage of poly(ADP-ribose). This effect of DNA is not due to a stimulation of the glycohydrolase per se since hydrolysis of free polymer by the enzyme is strongly inhibited by DNA, especially single-stranded DNA. Inhibition of glycohydrolase by DNA results from the binding of the enzyme to DNA and conditions which decrease this binding (increased ionic strength or addition of histone H1 which competes for DNA binding) relieve the DNA inhibition.


Investigation of activation of phosphate groups in mono- and oligonucleotides with mesitoyl chloride. It has been demonstrated with the use of 31P NMR pulsed spectroscopy that the reaction of mesitoyl chloride (MsCOCl) both with terminal and internucleotide phosphate groups pA, d(MeOTr)TpT and dpTpT (Ac) proceeds in a quantitative fashion within less than 2 min at 0 degrees C with the respective mixed anhydrides being thereby formed. The anhydrides of phosphomonoesters are resistant, unlike those of phosphodiesters which may be readily split by water, alcohol or amine without the internucleotide bonds being broken. Treatment of poly(U) with an excess of MsCOCl leads to rapid cyclization followed by formation of phosphotriesters. A comparatively easy hydrolysis leads to partial cleavage and isomerization of internucleotide bonds. A similar treatment of UpC showed that about 20% of the internucleotide bonds are cleaved, the remaining UpC being a mixture of approximately equal amounts of 3'-5'- and 2'-5'-isomers.


Two initiation sites for adenovirus 5.5S RNA. Adenovirus specific 5.5S RNA is heterogeneous at its 5' terminus. Complete pancreatic RNase digests of the RNA reveal a 5' terminal oligonucleotide (pp)pApGpCp in addition to the major 5' terminal (pp)pGpGpGpCp (1). Both 5' termini are detected early as well as late after adenovirus infection. In isolated nuclei, alpha-amanitin inhibits all 5.5S RNA transcription at a concentration of 200 microgram/ml, indicating that both initiation sites are recognized by RNA polymerase III.


Initiation of transcription in nuclei isolated from adenovirus infected cells. Initiation of adenovirus transcription was analyzed by incubation of isolated nuclei from virus infected cells in the presence of beta-32P GTP or beta-32P ATP. Nucleotide analysis of RNA from nuclei incubated with beta-32P GTP shows that the label is incorporated exclusively into pppGp and ppGp. Under similar incubation conditions, the label from beta-32P ATP was incorporated primarily into the 5' phosphate of 5', 3' mononucleoside diphosphates, but label was also detected in pppAp, pppGp and in the 3' nucleoside monophosphates. Analysis of RNA, synthesized in the presence of different concentrations of alpha-amanitin, shows that only RNA polymerase III initiates virus specific transcription in isolated nuclei. The virus specific transcripts containing pppAp and pppGp in their 5' termini were identified as the 5.5S and 5.2S viral RNA species by hybridization and finger printing.


HeLa DNA polymerase alpha activity in vitro: specific stimulation by a non-enzymic protein factor. A non-enzymic protein factor that increases the in vitro rate of synthesis by HeLa DNA polymerase alpha 15- to 30-fold with denatured DNA as template has been partially purified from the cytoplasmic fraction of HeLa cells. The stimulatory effect is highly specific for HeLa DNA polymerase alpha and for DNA templates that contain extensive regions of single-strandedness. Synthesis with denatured DNA as template presumably proceeds from 3'-hydroxyl termini formed at loop-back regions since the synthesized DNA product and template are covalently linked. The stimulatory protein factor chromatographs as a basic protein, has an approximate molecular weight of 30,000 daltons and binds with moderate affinity to denatured DNA cellulose, being eluted by o.4M NaCl. The purified factor lacks detectable DNA polymerase, exo- and endodeoxyribonuclease and RNA polymerase activities. It also does not promote helix-coil transitions with poly[d(A-T)] and Clostridium perfringens DNA.


Proximity and accessibility studies of histones in nuclei and free nucleosomes. Histone proximity in chromatin was studied with the cleavable crosslinking reagent, dithiobissuccinimidyl propionate. Crosslinks between H4 and H2a, H4 and H2b, H4 and H3, H2a and H2b, H2b and H3 were found. H1 is also crosslinked to the nucleosomal histones. In nuclei, unsheared chromatin, and H1 depleted chromatin, the four nucleosomal histones are crosslinked at similar relative rates both in 5 mM salt and 100 mM salt. After micrococcal nuclease treatment to generate nucleosomes, H2a and H2b are crosslinked faster than H4 and H3. C14-NEM titration of thiopropionate residues bound to each histone shows that H2a and H2b are more accessible to this reagent after nuclease treatment but that the increased binding was not sufficient by itself to explain the increase in crosslinking. Bolton Hunter reagent was used to further study the accessibility of the four nucleosomal histones in whole chromatin and nuclease digested chromatin. These studies showed that salt increases the accessibility of all four histones while nuclease treatment decreases H4 accessibility.


Oestradiol-receptor complexes in subnuclear fractions of rat uterine tissue. The subnuclear distribution of 3H-oestradiol-receptor complexes was studied in uterine tissue of ovariectomized adult rats. Nuclei were sonically disrupted and 8 different subnuclear fractions were isolated by discontinuous sucrose density gradient centrifugation. 3H-Oestradiol-receptor complexes, measured by hydroxylapatite column chromatography, were localized in a light chromatin fraction as well as in a heavy chromatin fraction. Using the hydroxylapatite chromatography technique it was possible to demonstrate three classes of oestradiol-receptor complexes which differ in affinity for the chromatin. Oestradiol-receptor complexes with a high affinity for the chromatin were predominantly localized in the heavy chromatin fraction, whereas complexes with a lower affinity for their acceptor sites were present in the lighter chromatin fraction.


Further procedures for sequence analysis by computer. A previous paper(1) described programs for sequence data handling and analysis by computer. The facilities of this basic set are extended by further easily used programs.


Failure to detect "cap" structures in mitochondrial DNA-coded poly(A)-containing RNA from HeLa cells. The structure of the 5'-termini has been investigated in mitochondrial DNA-coded poly(A)-containing RNA from HeLa cells. For this purpose, mitochondrial RNA isolated from cells labeled for 3 hours with [32P]orthophosphate in the presence of 20 microgram/ml camptothecin, and selected for poly(A) content by two passages through oligo(dT)-cellulose, was digested either with the nuclease P1 or with a mixture of RNases: the digestion products were then fractionated by two-dimensional electrophoresis. No "cap" structures were detected under conditions where the presence of such structures in one out of five to ten RNA molecules would have been recognized. It is, therefore, likely that "cap" structures are completely absent in HeLa cell mitochondrial poly(A)-containing RNA.


Complexity of poly(A+) and poly(A-) polysomal RNA in mouse liver and cultured mouse fibroblasts. RNA excess hybridization experiments were used to measure the complexity of nuclear RNA, poly(A+) mRNA, poly(A-) mRNA, and EDTA-released polysomal RNA sedimenting at less than 80 S in mouse liver and in cultured mouse cells. With both cell types, poly(A-) RNA was found to contain 30-40% of the sequence diversity of total mRNA. In the case of liver this represents 5,700 poly(A-) molecules and 8,600 poly(A+) molecules for a total of approximately 14,300 different mRNAs. Comparison of the complexity of mRNA with that of nuclear RNA revealed that in liver and in cultured cells, mRNA has only 10-20% of the sequence diversity present in nuclear RNA. This latter observation is consistent with existing data on mammalian cells from this and other laboratories.


Estrogen receptor in hen oviduct chromatin, digested by micrococcal nuclease. Nuclei from laying hen oviduct were prepared according to Hewish and Burgoyne i.e. in the presence of spermine and spermidine and in the absence of divalent cations and were then moderately digested by micrococcal nuclease. When the resulting chromatin was analysed by ultracentrifugation on a sucrose gradient, a peak of specific estradiol-binding sites was observed, sedimenting slightly faster (13-14 S) than the mononucleosomes (12 S). When the chromatin was centrifuged on a gradient containing heparin (5 microngram/ml) the sedimentation coefficient of the estradiol receptor peak shifted to 7-8 S; it returned to the 13-14 S position in the absence of heparin, when target organ chromatin was also present in the gradient. The preparation of the chromatin is described and the validity of the method to explore receptor localisation is discussed, as is the specificity of the receptor-DNA interaction.


Fractionation of chromatin by differential solubility in dilute salt. Chromatin prepared from the livers of rats was fractionated on the basis of solubility in dilute NaCl. Neither of the fractions obtained was enriched in newly synthesized DNA. The salt-soluble fraction had a higher protein content (usually up to 50%) relative to the DNA, and contained 72% or more of the rapidly synthesized RNA. This RNA was found to be complexed with the salt-soluble deoxyribonucleoprotein, not merely co-solubilized with it. Also, polylysine-binding studies showed that about 70% or more of the nucleic acid phosphates were accessible as compared to about 40% in the unfractionated chromatin. These properties suggested that the soluble fraction was enriched in activity transcribed chromatin. In contrast molecular hybridization studies showed that the complexity of the DNA and its homology with cDNA transcribed from rat-liver polysomal mRNA were the same as those of DNA from unfractionated chromatin, or from the salt-insoluble fraction. This suggests that the criteria commonly accepted as distinguishing between euchromatin and heterochromatin in vitro are not invariably valid.


Characterization of inverted repeated sequences in wheat nuclear DNA. The properties of inverted repeated sequences in wheat nuclear DNA have been studied by HAP(1) chromatography, nuclease S1 digestion and electron microscopy. Inverted repeated sequences comprise 1.7% of wheat genome. The HAP studies show that the amount of "foldback HAP bound DNA" depends on DNA length. Inverted repeats appear to be clustered with an average intercluster distance of 25 kb. It is estimated that there are approximately 3 x 10(6) inverted repeats per haploid wheat genome. The sequences around inverted repeats involve all families of repetition frequencies. Inverted repeats are observed as hairpins in electron microscopy. 20% of hairpins are terminated by a single-stranded spacer ranging from 0.3 to 1.5 kb in length. Duplex regions of the inverted repeats range from 0.1 to 0.45 kb with number average values of 0.24 kb and 0.18 kb for unlooped and looped hairpin respectively. Thermal denaturations and nuclease S1 digestions have revealed a length of about 100 bases for duplex regions. The methods used to study inverted repeated sequences are compared and discussed.


Form of DNA and the nature of interactions with proteins in chromatin. Studies of native chromatins and of isolated nucleosomes (from calf thymus) show that the DNA is in the B form or modified B form. This was determined by Raman spectroscopy of chromatins, of nucleosomes (from calf thymus) and of DNA fibres and directly correlated with X-ray diffraction studies. The Raman spectra of three forms of DNA (A, B and C) have been characterized in fibres both by X-ray diffraction and Raman spectroscopy on the same sample. In particular, the Raman spectrum of the C form of DNA is characterized by a band of about 870 cm(-1). For the first time, chromatins of different origins with increasing content of non-histone proteins have been investigated by Raman spectroscopy. The site of interaction of the non-histone proteins appears to involve the N7 position of guanine while the histone core does not interact at this site. It is proposed that the mechanism of specific recognition in chromatin involves the large groove.