The lateral decubitus view: an aid in evaluating poorly defined pulmonary densities in children. The upper lung on a lateral decubitus chest radiograph is uniformly better expanded than on a frontal upright chest radiograph. The lateral decubitus view is useful in distinguishing pulmonary vascular structures mimicking pneumonia from actual pulmonary infiltrates in infants and young children in whom deep inspiratory chest films are difficult to obtain. This study included 20 children whose initial radiographs could not be obtained in deep inspiration and demonstrated equivocal areas of pulmonary infiltrate. Clinical follow-up was possible in 16 of the 20 patients. We reviewed the routine chest radiographs and lateral decubitus views independently and retrospectively. The decubitus films showed more appropriate correlation with the subsequent clinical course and consistently allowed more confident interpretation of the radiographs.


Huge splenic cyst in a newborn: comparison with 10 cases in later childhood and adolescence. Radiographic, sonographic, and histologic findings in a case of a huge splenic cyst in a newborn are presented. The patient had the characteristic findings, particularly the visceral displacement, associated with splenic cysts in a series of 10 older children and adolescents. The occurrence in a newborn of a large splenic cyst histologically similar to those found in older children supports the hypothesis that they are developmental rather than traumatically acquired.


Spontaneous disappearance of gastric polyps: report of four cases. During follow-up radiologic observations of 88 subjects with benign gastric polyps, four rare cases were encountered. In two of these, the polyps had become detached; in the other two, they decreased in size. One of the latter eventually disappeared. Possible causes, though not yet established, are considered. These four cases are discussed in light of earlier reports in the literature.


Hysterography before and after myomectomy. Pre- and postmyomectomy hysterograms were compared in 12 consecutive cases. In 11 cases, the uterine cavity was of normal shape and size after surgery, irrespective of the degree of preoperative uterine distortion. In two cases fallopian tubes were not visualized before surgery but were found patent after removal of the fibroids. In all cases studied, preoperative hysterography was valuable in confirming the presence and localization of myomata but of limited value in predicting the feasibility of the procedure.


Bipedal lymphangiography in malignancies of the uterine corpus. Bipedal lymphangiography was performed in 116 selected patients with primary endometrial malignancy since 1970. A total of 32 were interpreted as positive and  84 as negative. Although histologic confirmation of nodal interpretation was seldom obtained, short term follow-up indicates that a positive interpretation is associated with an extremely poor prognosis. Lymphangiograms are recommended in all stage I patients except those with well differentiated histology, a small corpus, and no deep myometrial invasion. This study is also recommended for all stage II and III patients and for selected patients with stage IV disease.


Computed tomographic evaluation of the retrocrural prevertebral space. Abdominal computed tomography (CT) scans of 151 patients were reviewed for the presence of discrete structures between the vertebra and the diaphragmatic crura. A distinct retrocrural structure larger than 6 mm in diameter was present in 39 patients. In 112 patients the retrocrural space contained discrete structures smaller than 6 mm or showed no definable structures. Of the 39 patients with retrocrural structures larger than 6 mm in diameter, 37 had clinical and other CT evidence as well as biopsy or lymphangiographic evidence of middle to upper abdominal paraaortic adenopathy. Only three of the 112 patients exhibiting retrocrural structures smaller than 6 mm had such evidence of associated retroperitoneal adenopathy. These three were found to have enlarged nodes, but in the lower rather than the middle or upper abdomen. It is concluded that discrete retrocrural structures larger than 6 mm represent enlarged lymph nodes. Smaller retrocrural structures represent azygous veins or normal lymphatic structures.


Voluntary glenohumeral dislocation.

Voluntary glenohumeral dislocation. Voluntary dislocation of the shoulder is a rare condition with radiographic findings similar to traumatic dislocation. Although these dislocations may be anterior, the majority are posterior. Three cases of spontaneous dislocation are described. While two of these cases had previous trauma to the joint, it is possible that there is no causal relationship. Voluntary dislocations are usually elicited in abduction and extension; frontal and axillary views are most helpful in demonstrating glenohumeral subluxations.


Radiologic aspects of diffuse idiopathic skeletal hyperostosis in the spine. Radiographs of 175 patients with diffuse idiopathic skeletal hyperostosis (DISH) of the spine or ankylosing spondylitis were reviewed. DISH most frequently began in the middle and lower portions of the thoracic spine; it was rare in the upper portion. A few vertebrae were first affected, and then involvement extended, sometimes throughout the thoracic spine. The anterior and lateral aspects of vertebral bodies were mainly affected. Hyperostosis vertically spanning the anterior aspects of the vertebrae varied in thickness up to 10 mm, and the rate at which the hyperostosis proliferated was not specific for any vertebra. Males were 12 times more frequently affected than females, especially in the older age groups. Diabetes mellitus and hypertension have reportedly been associated with DISH, but no such correlation was found in this study. Despite the existence of criteria for differential diagnosis, it is sometimes difficult to distinguish ankylosing spondylitis from DISH radiologically. The radiologic features helpful in the differential diagnosis are described, and a review of the pertinent literature is included.


Pathophysiology and medical management of angina pectoris. Myocardial oxygen demand is a function of the product of heart rate and blood pressure. Agents such as nitroglycerin not only produce coronary vasodilatation, which increases oxygen supply, but also reduce myocardial oxygen demand secondary to a reduction in both preload and afterload. Beta-adrenergic blockers are useful in angina because they reduce myocardial work and, hence, oxygen demand. A heart rate in the 50s does not preclude an increase in the dosage of propranolol when necessary.


Lactase deficiency--a comparative study of diagnostic methods. The diagnostic value of 1-14C-lactose breath test was compared with the standard lactose tolerance test and lactase assay in jejunal biopsies in 16 control subjects, 14 patients with lactase deficiency (LD) proven by lactase assay and 20 patients with irritable bowel syndrome (IBS). 14CO2 specific activity in the 2-hr breath collection after administration of 1-14C-lactose (5 muCi) provided a satisfactory separation between the control and LD group. Values were 7.0 +/- 2.0% dose administered/mmoles 14CO2 X 10(-3) (mean +/- SD) in the control group versus 2.1 +/- 1.5 in LD (P less than 0.001) versus 4.9 +/- 2.3 in IBS (P less than 0.01). 1-14C-lactose breath test was superior to standard lactose tolerance test in specificity (P less than 0.05) and provided a satisfactory correlation between 14C-lactose absorption and lactase assay (r = 0.77). The prevalence of LD in IBS was 40% by the breath test and 35% by lactase assay, suggesting that lactose malabsorption may play a role in the symptoms in the population of some patients with IBS. It appears that 1-14C-lactose breath test is a sensitive, specific and accurate method for the diagnosis of LD in clinical practice and suitable for large scale epidemiological surveys.


Effect of large amounts of vitamin E during pregnancy and lactation. The effects of excessive intake of vitamin E during gestation and lactation on female rats and their progeny were studied. Pregnant rats receiving large doses of vitamin E (22.5 to 2252 mg/kg per day) had larger livers, higher levels of lipids and vitamin E in plasma, and higher concentrations of vitamin E in the livers than did controls. These deviations from normal were not, however, observed for all levels of supplementation. No obvious teratogenic effects were observed in the newborn young of the vitamin E-supplemented rats. Some eye abnormalities were seen in the older pups of rats given extremely high amounts of the vitamin. The survival rate, weight of the pups, and litter size were unaffected. However, the pups of the mothers who had received 500 mg of vitamin E per day (2252 mg/kg per day) during gestation and lactation had a much higher concentration of vitamin E in their livers and plasma than did controls. This study also confirmed the observation that vitamin E transfer across the placenta is negligible and that mammary transfer of this vitamin is quite efficient.


Some effects, in baboons, of chronic ingestion of glycerol with sucrose or glucose. Six mature male and six mature female baboons were given fat-free diets high in sucrose or glucose together with glycerol, a chow diet with glycerol, and a fat-free high sucrose diet without glycerol. In the male animals, the concentration of triglyceride, cholesterol, glucose, and glycerol in fasting serum was significantly greater when sucrose and glycerol were given together compared with the other diets. The fasting serum triglyceride and cholesterol were significantly greater in the females on the sucrose + glycerol diet compared to the glucose + glycerol diet. It is suggested that glycerol and fructose (in sucrose) share a metabolic pathway that leads to an enhancement of serum lipid concentrations.


Essential fatty acid deficiency induced by total parenteral nutrition and by medium-chain triglyceride feeding. In hospitalized infants receiving either prolonged total parenteral nutrition without fat or a formula of medium-chain triglyceride, the fatty acid composition of platelet, red blood cell, and plasma lipids was determined. The results showed that the changes in the fatty acid composition occurred not only in plasma but also in platelets and red blood cells, and the decrease in linoleic and arachidonic acid and the concurrent increase in 5,8,11-eicosatrienoic acid were confirmed to be dramatic evidence of essential fatty acid deficiency. There was no effect of essential fatty acid deficiency upon the phospholipid distribution in red blood cells or plasma.


Acute erythroid hypoplasia in malnourished infant squirrel monkeys fed isolated soy protein. Infant squirrel monkeys fed low protein diets using an isolated soy protein develop an acute anemia. To investigate this syndrome, four groups of animals fed diets containing adequate or restricted amounts of casein or soy protein were studied from 1 through 16 weeks of age. The low protein groups, in which growth was prevented by adjustment of the protein content between 2 through 8 weeks, showed no difference in caloric intake or plasma albumin concentrations. However, the low soy group developed a severe anemia (hemoglobin 4 to 7 g/dl) after 4 to 6 weeks of dietary treatment. The anemia was characterized as normocytic, normochromic, and was associated with reduced reticulocyte concentrations. Bone marrow specimens showed an increased myeloid/erythroid ratio due primarily to an absolute erythroid hypoplasia. Juvenile animals fed similar low soy diets did not become anemic. The selective effect of this isolated soy protein, demonstrable only during the transitional period of early infancy, was attributed to the interaction of the malnourished animal with a component of the isolated soy protein per se. The potential role of soy glycoproteins is discussed.


Malnutrition and malabsorption. Effect of nutritional rehabilitation on gastrointestinal function in kwashiorkor and marasmus--a longitudinal study. The effects of long-term feeding of an adequate diet on the progressive changes in the biochemical parameters including gastrointestinal functions in children suffering from marasmus and kwashiorkor are presented. In both groups fasting bloos sugar, blood urea nitrogen, hemoglobin, serum total proteins and albumin at admission were significantly lower than in matched controls. These parameters improved after proper dietary therapy over a period of two years. The improvement in the biochemical parameters correlated with clinical and anthropological measurement. On admission, the gastrointestinal function as assessed by various tests was poor in both the groups. This returned to normal or near normal after nutritional rehabilitation. The return was much quicker for glucose and fat absorption than for lactose and d-xylose absorption. The rate of improvement in marasmus was slower than that in kwashiorkor.


Clinical and pathologic features of Waldenström's macroglobulinemia in seven patients with serum monoclonal IgG or IgA. The clinical, hematologic and pathologic findings in seven patients were similar to those of Waldenström's macroglobulinemia, but unexpectedly the serum monoclonal immunoglobulin belonged to the IgG class in five patients and to the IgA class in two. The bone marrow and lymph node lymphoid proliferation was pleomorphic, with the simultaneous presence of small lymphocytes, normal mature plasma cells and transitional lymphoplasmacytic cells. Immunofluorescence studies showed that a monoclonal immunoglobulin similar to that found in the serum was detectable on the membrane or in the cytoplasm of all the proliferating cells, which thus belonged to the same B cell clone. The study of these patients is in accordance with the concept that lymphoid disorders featured by a pleomorphic monoclonal B cell proliferation constitute a distinct clinicopathologic entity, which is not restricted to IgM-producing clones.


Primate model for the evaluation of vaginal contraceptives. A good animal model that simulates the human subject has not been available for the evaluation of the in vivo effectiveness of vaginal contraceptives. After careful consideration. The stumptailed macaque (Macaca arctoides) was studied for its applicability since it has a reproductive tract similar to that of the woman, is easy to handle, does not require tranquilization or anesthesia when the contraceptive is deposited, and breeds and conceives readily under caged conditions. The reported observations show the usefulness of this animal. Both postcoital sperm motility studies and breeding experiments were performed with the use of Delfen vaginal cream and K-Y jelly. K-Y jelly had no effect on the motility of vaginal spermatozoa or on the conception rate of the primates. Although Delfen vaginal cream consistently immobilized all spermatozoa in the postcoital test, half of the animals became pregnant within an average of 3.7 breeding cycles. These results illustrate the discrepancy between spermicidal tests and fertility measurements, and it is recommended that primate-breeding experiments be performed before a spermicide is evaluated in women as a contraceptive.


Hydroxyurea as a radiation sensitizer in women with carcinoma of the uterine cervix. Hydroxyurea was evaluated as a possible radiation sensitizer in 130 evaluable women with Stages IIB and IIIB (International Federation of Gynecology and Obstetrics) carcinoma of the uterine cervix. This was a prospective double-blind randomized study in which hydroxyurea or placebo was compared in conjunction with continuous or split-course radiation therapy. Of all patients with Stage IIB cancer without biopsy proof of aortic node metastasis, a significant improvement in survival (P less than 0.01) was achieved in the hydroxyura group (74.0%) as compared to the patients receiving placebo (43.5%). In women with Stage IIIB cervical cancer there was a trend toward longer survival in those receiving hydroxyurea (52.1%) as compared to those receiving placebo (33.3%). However, there was a statistically significant improvement in survival in those women with Stage IIIB cervical cancer who had staging done at operation, were found to have negative para-aortic nodes, and subsequently received continuous radiation therapy (90.9%) as compared to those receiving split-course therapy (29.4%) (P = 0.005).


Reduced dose of Rho(D) immune globulin following induced first-trimester abortion. A double-blind study of women after first-trimester abortion supports the efficacy of low-dose Rho(D) immune globulin (human) in the prevention of Rh sensitization. Twenty-seven per cent of patients demonstrated a fetomaternal blood leak based on Kleihauer-Betke stains. In follow-up testing, the percentage of positive titers and the absolute titer of detectable antibody at various intervals were related to the dose of administered immune globulin. This study confirmed the possible risk of sensitization in Rh-negative postabortal women and suggests the practical use of single low-dose immune globulin preparations in prevention.


Temperature gradient between fetus and mother as an index for assessing intrauterine fetal condition. Temperature gradient between fetus and mother (deltaTF-M) was measured in 29 pregnant baboons. Thermocouples were implanted in the fetal esophagus and the maternal colon, and, in some instances, thermistor probes were also placed in the fetal esophagus, scalp, and shoulder muscle. Under steady-state conditions, the fetal temperature was found to be higher than that of the mother. Temperatures in the fetal esophagus, scalp, and shoulder were 0.47, 0.28, and 0.19 degrees C. respectively, higher than those in the maternal colon. There was an increase in deltaTF-M during acute fetal stress induced by asphyxia, secondary to occlusion of the umbilical cord, maternal aorta, or inferior vena cava, or to acutely increased uterine activity. This increase in deltaTF-M most likely reflects impairment of heat dissipation from the fetus to the maternal compartment. A decreased deltaTF-M was observed when the stress on the fetus was subacute and prolonged. This is probably the result of a diminution of heat production by the fetus as the metabolic rate is lowered during prolonged hypoxia. Ten to 30 minutes after the cessation of vital signs of the fetus, the deltaTF-M became zero.


Failure of parathyroid hormone to cross the nonhuman primate placenta. Following infusion of parathyroid extract (PTE), parathyroid hormone (PTH) did not cross the placenta from the monkey mother to her fetus. Although maternal PTH levels increased four- to 12-fold, fetal PTH levels remained at the base line at all times tested. To determine if PTH crossed the placenta from fetus to mother, PTE was infused into the fetal aorta while the monkey baby remained in utero. PTH in the fetal serum increased ten-fold without a significant change in maternal serum PTH. Thus, PTH does not cross the placenta in either direction. Blood ionized calcium levels in nonpregnant female monkeys, following infusions of ethylenediaminetetra-acetate (EDTA) were shown to decrease, with a subsequent increase in blood PTH levels. Thus, the monkey arathyroid gland was shown to be physiologically responsive to lowered calcium levels. Biological half-life disappearance times of beef PTH in monkey fetuses and their mothers were similar to those found in human beings.


Cytogenetic investigation of cat-eye syndrome. Using multiple chromosomal banding techniques, we studied a child with typical cat-eye syndrome and ocular retraction syndrome. Although the mother was was chromosomally normal, other maternal relatives showed features of the cat-eye syndrome, suggesting the basic abnormality is heritable. The abnormal chromosome in our case was most likely the product of reciprocal translocation where short arm plus centromeric chromatin from two separate acrocentric chromosomes fused together. The chromosomes involved were probably No. 22 and either Nos. 13 or 14. The basic underlying defect in cat-eye syndrome may be a heritable fragile site or some other predisposition leading to complex chromosomal interchange.


Chromatic patterns of cone photoreceptors. 1976 Glenn A. Fry Award Lecture. The operations of vertebrate visual neurons must eventually be expressed in terms of the spectral classes and spatial distributions of photoreceptors that constitute inputs to those neurons. By using a cytochemical probe that permits visualization of the responses of cone photoreceptors to light stimulation, it has been possible to describe the spectral classes and spatial patterns of cones in a lower vertebrate, the goldfish, and in a primate, the baboon. This information is an important first step in analyzing the connections between cones and retinal neurons.


Astigmatism among institutionalized and noninstitutionalized mentally retarded. Astigmatism was measured retinoscopically for 709 subjects residing in an institution for the mentally retarded and for 56 noninstitutionalized mentally retarded subjects at a community training center. About 60% of the subjects were between 15 and 45 years old. Compared to an intellectually normal sample of young men, astigmatism in the mentally retarded was greater in frequency and degree. For subjects with greater degrees of mental retardation, the prevalence of high astigmastism was significantly greater for whites than for nonwhites. There was no difference in astigmatism between institutionalized retardates and those living in a community setting, a finding that implies that the institutional environment was not the cause of the astigmatic differences between retarded and normal subjects.


Body weight: its relation to tissue composition, segment distribution, and motor function. I. Interspecific comparisons. The composition of skin, muscle, and bone and their distribution throughout the body are compared for "advanced" or "specialized" species (Alouatta, Macaca, Canis, Felis, Lepus); smaller, more closely related species (Tupaia and the Lorisidae); and several species within the same ecosystem (Barro Colorado Island, Panama). Among the most significant variables, the skin of sloths, howlers and macaques constitutes more than 12% of body weight, whereas greyhound skin is 5% of weight; sloth and howler muscle are 25% of weight, macaque muscle about 40% of weight, greyhound and agouti muscle over 50% of weight. In tree shrews and galagos muscle is heavier (35%) than in pottos and slow lorises (below 28%), but bone and skin are lighter. All species differ in the segmental distribution of weight. Cats have light tails, light feet and heavy thighs, whereas howlers have heavy tails, heavy feet, and light thighs. The galagos have heavy hindlimbs and tails, the pottos and lorises have reduced tails and approximately equal fore- and hindlimbs. Convergences in segment pattern (sloths with pottos and lorises, marmosets with tree shrews, owl monkeys with galagos, cebus with macaques) as well as divergences are documented. All weight-of tissue and weight-of-segment variables are correlated directly with locomotor adaptation.


Body weight: its relation to tissue composition, segment distribution, and motor function. II. Development of Macaca mulatta. The relative composition of skin, muscle, and bone and their distribution patterns throughout the body are given for a series of Macaca mulatta from 171 days conceptual age through adulthood. In terms of percent of total body weight, the musculature of these animals doubles during the firs postnatal year whereas bone and skin decrease. Regionally, the muscles of the thighs, back extensors, truncal-forelimb and upper arms increase most markedly. The thighs double and the upper arms increase whereas the trunk, hands, feet, and tail decrease. The biomechanical implications of these changes for motor development are discussed.


The lorisiform wrist joint and the evolution of "brachiating" adaptations in the hominoidea. In lorisines (Loris, Nycticebus, Perodicticus, Arctocebus), the tip of the ulna is reduced to the dimensions of a styloid process, a new and more proximal ulnar head is developed, and the pisiform is displaced distally away from its primitive contact with the ulna. In some Nycticebus, intra-articular tissues separate the ulna from the triquetrum. These traits are not seen in other quadrupedal primates, but they are characteristic of extant hominoids. Among hominoids, these features have been interpreted as adaptations to arm-swinging locomotion. Since hominoid-like features of the wrist joint are found in lorisines, but not in New World monkeys that practice arm-swinging locomotion, these features may have been evolved in both lorisines and large hominoids to enhance wrist mobility for cautious arboreal locomotion involving little or no leaping. Most of the other morphological traits characteristic of modern hominoids can be explained as adaptations to cautious quadrupedalism as well as to brachiation, and may have developed for different reasons in different lineages descended from an unspecialized cautious quadruped resembling Alouatta.


Sensitizing effect of treatment with estrogens on TSH response to TRH in male rats. Daily administration of estradiol benzoate (10 microgram/100 g body wt) to intact male rats led to a twofold increase of the plasma TSH (thyroid-stimulating hormone) response to thyrotropin-releasing hormone (TRH) after 4 and 7 days of treatment whereas the basal plasma TSH level was not affected. The basal plasma PRL concentration and the PRL response to TRH were both markedly increased by estrogen treatment. The TSH pituitary content remained unchanged, whereas the PRL pituitary content increased in parallel with the effect on PRL secretion. Treatment with estrogens for 1 wk sensitized the TSH secretory response to low doses of TRH (10 ng), whereas no significant effect on the response was found at high doses of the neurohormone. The present data show that the stimulatory effect of estrogens on the TSH response to TRH is due to true sensitization of the thyrotrophs to the action of the neurohormone, whereas that on prolactin secretion can result partly from increased pituitary prolactin content.


Vascular prostaglandin synthesis in the spontaneously hypertensive rat. Vascular prostaglandin synthesis was studied in tissues (aorta and inferior vena cava) obtained from spontaneously hypertensive rats (SHRs) of the Aoki-Okamoto strain and age-matched Wistar-Kyoto (WKYs) controls. PGE2 synthesis in aortas from SHRs was significantly enhanced at 10 wk of age (5.3 +/- 0.7 nmol PGE2/mg protein per 10 min vs. 1.9 +/- 0.03 nmol PGE2/mg protein per min in the WKYs, P less than 0.001) and increased progressively until 22 wk of age; PGE2alpha synthesis in SHRs was not significantly different from WKYs. In the venous walls from SHRs, PGF2alpha was the prostaglandin predominantly synthesized (7.1 +/- 0.6 vs. 1.9 +/- 0.05 nmol PGE2alpha/mg protein per 10 min in the WKY controls, P less than 0.01). The activities of 15-hydroxy prostaglandin dehydrogenase and PGE 9-ketoreductase were also compared in the two groups of animals. The only difference detected was a significant increase in venous PGE 9-ketoreductase of SHR's (7.3 +/- 0.06 vs. 4.8 +/- 0.04 nmol PGF2alpha/mg per min, P less than 0.01). The results suggest that increased vascular synthesis of prostaglandins accompanies the development of spontaneous hypertension and may serve to attenuate the effects of blood pressure elevation.


House-to-house, community-wide chemoprophylaxis for meningococcal disease: an aggressive approach to disease prevention. During an outbreak of meningococcal disease in a rural community in southwest Alabama in 1975-76, we undertook an aggressive campaign of house-to-house, community-wide chemoprophylaxis distribution. Over a three-day period 1,045 households were visited and 4,454 persons received medication. The 1970 census lists 967 households with 4,067 persons residing in the community. To evaluate compliance we cultured for meningococcal carriers before and after the chemoprophylaxis campaign. All of the previously discovered carriers were negative three weeks after the drug distribution. The cost of the campaign ($26,520) was very small compared to the possible benefit achieved. The methods of planning and executing this campaign are described in detail.


Complement depletion following envenomation by Russell's viper and Echis carinatus (saw-scaled viper) in the rhesus monkey. Significant depletion of C3 was observed following administration of lethal and sublethal doses of Russell's viper and Echis carinatus venom to rhesus monkeys. A sequential study carried out over a period of 3 weeks following sublethal envenomation showed a steady rise in the C3 level from 48 hours onwards. By the 20th day the C3 values had attained the pre-envenomation levels. The extent of depletion of C3 was similar in both Russell's viper and E. carinatus envenomation. Because of the close immunological similarity of monkey and man, the rise in C3 which corresponded with recovery of the animals in this experimental model could serve as a useful parameter of recovery in clinical cases of snake poisoning.


Quantitative aspects of pyrimethamine-sulfonamide synergism. The experiments described in this report have dealt with the dimensions of therapeutic potentiation achieved when combinations of pyrimethamine and sulfadiazine were administered to rhesus monkeys infected with a drug-susceptible strain of Plasmodium cynomolgi or its pyrimethamine-resistant variant and to owl monkeys infected with strains of P. falciparum and P. vivax of varying degrees of resistance to this pyrimidine. These evaluations showed: 1) that when delivered in combination, the activities of both pyrimethamine and sulfadiazine against infections with any of the above strains were enhanced significantly; 2) that in infections with the Ro and Ro/PM strains of P. cynomolgi and the Vietnam Palo Alto strain of P. vivax, concomitant delivery of the two agents resulted in a 32-fold increase in the activity of pyrimethamine and a 50- to 100-fold increase in the activity of sulfadizine; 3) that as a result of this synergism, infections with the pyrimethamine resistant Ro/PM and Palo Alto strains could be cured with a fraction of the maximum tolerated dose of this drug; 4) that in marked contrast to the above result, infections with the Malayan Camp and Vietnam Smith strains of P. falciparum could not be cured regularly by combination regimens which included the maximally tolerated dose of pyrimethamine. This poor response has been attributed to the high levels of pyrimethamine-resistance possessed by these strains. It is believed that the comparatively small but not insignificant incidences of treatment failures associated with delivery of pyrimethamine-sulfonamide combinations to both patients and human volunteers infected with multidrug-resistant strains of P. falciparum rest on a similar basis.


The activity of a benzothiopyranoindazole (IA-4 N-oxide) against Schistosoma mansoni infection in rhesus monkeys. The prophylactic and therapeutic efficacies of IA-4 N-oxide against Schistosoma mansoni in rhesus monkeys (Macaca mulatta) have been evaluated. Ten monkeys were divided into 5 groups of 2 monkeys each. All monkeys were exposed to S. mansoni cercariae on day 0 and treatment groups were established as follows: untreated controls, oral prophylactic administration, intramuscular prophylactic administration, oral therapeutic administration, and intramuscular therapeutic administration. Analysis of parasitologic and pathologic criteria indicate that the compound is most effective when administered as a therapeutic regimen. Complete cures were effected in these monkeys. Prophylactic treatments resulted in a delay in onset of patency and reductions in fecal egg excretion, worm burdens, and tissue damage.


[Retinal adhesion after retinal detachment surgery (author's transl)]. The effect of cryotherapy was studied in experimentally detached retinas under conditions similar to those in retinal detachment surgery. When cryotherapy was applied to the pigment epithelium and to the retina and the retina was reattached, a strong adhesion developed, characterized by the occurrence of true cell junctions between pigment epithelium and retinal cells. When only the pigment epithelium was treated, the adhesion after reattachment appeared weak due to the absence of microvillous interdigitations normally present between pigment epithelium and retina.


The characterization of some of the antigens and allergens in ragweed pollen. Ragweed extract (RW) and antigens E, K, BPA-R and Ra3 were characterized by  electrophoresis on starch and polyacrylamide gels. RW extract and antigen E were also subjected to crossed immunoelectrophoresis. All the antigens contained isomers and contaminating proteins. RW separated by starch gel electrophoresis was skin tested and allergens unrelated to antigens E, BPA-R, Ra3 and K were found.


Effect of storage on bovine erythrocyte cholinesterase activity. Bovine whole blood and washed erythrocyte samples with either sodium heparin or EDTA as the anticoagulant were stored at -24, 2 to 3, 21, or 37 C for up to 8 weeks to determine the stability of erythrocyte cholinesterase (ChE) activity. An automated colorimetric method was used to measure ChE activity. Regression analysis was used to estimate the rate of decline of ChE activity of samples to 95% of normal. Samples stored at -24 and 2 to 3 C were very stable, and ChE activity was maintained for several weeks or longer. Samples stored at 21 C maintained an activity level not less than 95% of normal for at least 9 days and those stored at 37 C for at least 2 days. The type of anticoagulant used did not appear to affect significantly the stability of activity.


Histopathologic study of experimental Sarcocystis hemionilatrantis infection in fawns. Mule deer fawns (Odocoileus hemionus hemionus) inoculated with sporocysts of Sarcocystis hemionilatrantis became infected, developed clinical signs of disease, and died, due to the infection itself or from intercurrent pneumonia. Clinical signs were first noticed 18 days after infection and fawns died from postinfection days 27 to 63. Histopathologic examination revealed early lesions in skeletal muscle which consisted of perivascular necrosis with mononuclear and neutrophilic cell infiltration, accompanied by edema, degeneration, and focal necrosis of muscle. Subsequently, this reaction subsided and the cellular infiltrate dissipated. An infected macrophage usually remained in the vacuolated muscle space; each macrophage was surrounded by a clear halo. Developing Sarcocystis schizonts were identified in the cytoplasm of the macrophages, and the cytoplasmic membrane eventually ruptured releasing merozoites. The merozoites then developed into typical muscle cysts. Results of the present study indicated that S hemionilatrantis is a pathogen of mule deer under experimental conditions. Pathogenicity should be investigated to determine if S hemionilatrantis causes death or debilitation in wild mule deer under natural conditions.


Asynergy in coronary heart disease. Evolving clinical and pathophysiologic concepts. The widespread use of cardiac ventriculography has focused interest on the frequency with which asynergy accompanies coronary heart disease as well as on its clinical and prognostic implications and dynamic nature. Recently, "intervention ventriculography" using nitroglycerin or postextrasystolic potentiation has indicated that asynergic zones may be more accurately classified as reversible (implying viable myocardium) or irreversible (nonviable or scarred myocardium), and thus the ventriculographic definition of aneurysm must reflect not only the severity of asynergy but its contractile reserve. Surface electrocardiogram Q waves, the severity of asynergy, and degree of coronary occlusion all adversely affect the potential for reversibility, whereas coronary collaterals enhance it. Important clinical applications include assessment of the potential utility of coronary bypass surgery in improving asynergy and of vasodilators in the treatment of patients with left ventricular failure. With refractory sequelae of aneurysms (heart failure, ventricular tachyarrhythmias, and systemic emboli) and a discrete aneurysm, surgical resection has been increasingly used with generally good results.


Development of bacteriophage phi29 in sporulating and non-sporulating cells of bacillus subtilis 168. Infection by bacteriophage phi29 of Bacillus subtilis 168 and of its asporogenous mutant spoOA-3NA has been studied in exponential and stationary phases. As first observed with phage phie infections, the burst-size decreases during the stationary phase much more rapidly in wild type than in mutant cells. In addition, the two strains are shown to differ even during growth in their response to phage phi29 infection. During a short period in the exponential phase, no phage production occurs when infected bacteria (whether spo+ or spo-) are incubated in their growth medium, but phage is produced when incubation takes place after transfer to fresh medium. From these and other unexpected findings it is concluded that any causal relation between sporulation and phage development must be considered with caution. Phage infection of spo+ cells at the end of the growth period does not affect the time required for mature spore formation.


[An acellular vaccine from Pseudomonas aeruginosa. II. -- Estimate of immuneserum protective effect by measure of bacterial clearance (author's transl)]. The protective antibodies obtained in mice with an acellular vaccine P2 from Pseudomonas aeruginosa have been titered in vivo by a bacterial clearance technique. The kinetics of the bacterial disappearance from the circulating blood were compared in mice which had been vaccinated or had received injection of specific serum, and in normal mice. The following results were obtained; (a) the disappearance of the bacteria from the blood is quicker in immunized animals; (b) the rate of bacteria in the blood depends on doses of injected serum; (c) the titers of protective antibodies expressed by 99% clearance dose is directly in relation with the vaccinating dose.


[Lipolysis and aflatoxin production in Aspergillus flavus (author's transl)]. Lipolysis in relation to toxinogenesis has been studied in various strains of Aspergillus flavus. Toxinogenic strains show a lipolytic activity which is twice the activity of non-toxinogenic strains. This enzymatic activity seems to be directly linked to the biosynthesis of toxins.


Acetone sterilization in ophthalmic surgery. Acetone is a potent bactericidal agent and has considerable value for the routine disinfection of surfaces. The reason for the poor showing of acetone in previously reported tests was that it was not used in concentrated form, and our tests also confirmed its relative ineffectiveness when diluted. The inability of acetone to eliminate spores is an important disadvantage but most commonly used bactericidal agents also are deficient in this respect. Although acetone is active in the presence of protein it does not penetrate blood clots. Therefore, instruments should be cleaned of blood and tissue fragments before using acetone to disinfect them, as with other methods of sterilization. Acetone can make ordinary sterilizers unnecessary in our offices. I believe that it is a superior antiseptic for use in sterilizing sharp instruments in the operating room and can be used for all instruments when autoclaving or gas sterilization is not feasible or not available.


Cervical esophagostomy in dogs: endoscopic, radiographic, and histopathologic evaluation of esophagitis induced by feeding tubes. Prolonged tube feeding is frequently necessary in patients with head and neck cancer, facial trauma, or central nervous system disease. The advantages of cervical esophagostomy over nasogastric and gastrostomy tube feeding are established. One frequently overlooked complication of tube feeding is distal esophagitis and subsequent stricture formation. This complication has been widely reported in the medical literature although the pathophysiologic mechanism has in part been speculative. We have completed a prospective, randomized, controlled animal study in an attempt to delineate the mechanism of feeding tube esophagitis and to devise a method of avoiding it. Twelve dogs underwent cervical esophagostomy and were studied by endoscopy, contrast fluoroscopy, gross and microscopic pathology. The esophageal effects of placement of polyethylene and silicone rubber esophagostomy tubes in the customary position, through the cardioesophageal junction into the stomach, were compared with placement of the distal end of the tube only as far as the midesophagus. Midesophageal placement of silicone rubber tubes greatly reduced esophageal injury inherent is esophagostomy tube feeding. A new esophagostomy feeding tube is presented with advantages over previously used tubes.


Intramural pseudodiverticulosis of the esophagus. Intramural pseudodiverticulosis of the esophagus is a rare benign disease, developing most frequently in older males, but occurring in both sexes, at all ages. In some patients symptoms from early childhood suggest congenital origin. The characteristic appearance of "pinhead" outpouching from the lumen of the esophagus is seen with contrast esophagram. The major symptom is dysphagia with episodic exacerbations, often with foreign body lodgement. The pseudodiverticula are formed by abnormally dilated adnexal glands and ducts which lie in the submucosa of the esophagus. Secondary infection, most commonly monilial, is the rule, and surrounding inflammatory infiltration may progress to submucosal fibrosis and stenosis. Treatment with dilatation and appropriate antibiotics usually produces rapid relief. Prognosis is good.


Human cochlear aqueduct and its accessory canals. The anatomy of the adult human cochlear aqueduct and its surrounding structures, and their normal variations at tomography, microdissection and plastic molding are described. The mean length of the aqueduct is 12.9 mm and the mean width of its funnel-shaped external aperture 4.2 mm. The mean width of the narrowest portion is 0.14 mm. No difference in aqueductal width was found between the youngest and oldest age groups. Complete bony obstruction was revealed at microdissection in 3 out of 82 specimens. In the remaining 79 the entire aqueduct was patent. The aqueduct usually runs parallel to the internal auditory canal when seen from above, and the AP projection is therefore most suitable for tomography. At tomography the entire aqueduct was visualized in 60% of the specimens. The isthmic portion was not visible in 40%. Major reasons for nonvisualization of the entire aqueduct are: 1) a luminal width less than 0.1 mm, 2) a high jugular fossa, 3) a posteriorly directed aqueductal convexity (10%), and 4) bony obliteration (4)%). Accessory canals close to and often wider than the aqueduct may complicate tomographic evaluation of the aqueductal patency. Nonvisualization of the aqueduct at tomography does not necessarily indicate nonpatency.


Caloric testing. 1. Effect of different conditions of ocular fixation. Twelve normal subjects received standard caloric testing under the following conditions: 1) fixation, 2) Frenzel glasses in a dimly lit room, 3) eyes open in total darkness, and 4) eyes closed. Multiple nystagmus response parameters were evaluated and statistically compared for each condition. Fixation markedly diminished induced nystagmus and produced the largest coefficient of variation for each response parameter. Caloric testing with eyes closed resulted in periodic nystagmus suppression and a less distinct saw-toothed pattern. As with fixation, the coefficient of variation was consistently higher with eyes closed compared to eyes open in darkness or Frenzel glasses. It is concluded that caloric testing of the vestibulo-ocular reflex arc should be performed with eyes open in darkness or with Frenzel glasses.


Caloric testing. 3. Patients with peripheral and central vestibular lesions. Results of bithermal caloric testing in 83 patients with unilateral peripheral vestibular disease, cerebellopontine angle tumors and vertebrobasilar insufficiency were compared in order to find which response measurements identified the most abnormal responses in each disease category. A laboratory digital computer was used to quantitatively assess each caloric response and a large digital computer was used to statistically compare 110 measurements generated from each caloric test. Of the commonly used response parameters maximum slow component velocity (SVMx) and sum of slow amplitudes (SSA) were most sensitive in each category and duration of response (TDUR) was least sensitive. This order was maintained for the vestibular paresis (VP), directional preponderance (DP) and temperature effect (TE) formulas. The magnitude of DP was significantly correlated with the magnitude of spontaneous vestibular nystagmus and both occurred with approximately the same frequency in peripheral and central disorders. There was no reliable way of separating end-organ from VIII nerve or peripheral from central disorders on the basis of the caloric responses.


Caloric testing 2. results in normal subjects. A large number of variables were examined simultaneously for 43 normal subjects over the four irrigations of a caloric test. Care was used for every step of the testing procedure and data analysis to eliminate as much of the variance in the caloric responses as possible. The normality of each variable's distribution was examined using the Wilk-Shapiro W test and corrected if necessary by the best of several transformations. The means, standard deviation, and 95% confidence intervals of the resultant data were derived. Statistical tests of temperature, sidedness, and directionality were done on the variables and several important sources of variance were found and explained.


[2 new species of gregarines parasites of annelides: Pleurocystis eiseniellae of Eiseniella tetraedra Sav.)Oligochaeta), Pterospora petaloprocti of Petaloproctus terricola Quatr. (Polychaeta)]. The first species belongs to the genus Pleurocystis (in the Oligocheta host, Eiseniella tetraedra). It is characterized by early syzygies with lateral connection and navicular sporocysts with similar poles. It differs from the only species already described of the genus and is named Pleurocystis eiseniellae n. sp. The second one is related to the genus Pterospora (in the Polychaeta host, Petaloproctus terricola) but differs from the three species already known by its size and number of terminal digitations in specimens always found in syzygy. The sporocysts with dissimilar poles (one rounded, the other neck-shaped) show a loose epispore. This Gregarine in named Pterospora petaloprocti n. sp.


[Interrelationship of the mass transfer coefficient with regard to O2 and CO2 in the process of antibiotic biosynthesis]. A complex of studies on the effect of technological parameters on the mass transfer coeficients with respect to O2 and CO2 was carried out. It was shown that the ratio between the mass transfer coefficients with respect to O2 and CO2 was constant and equal to 20 for the fermentation broths of the antibiotic-producing organisms studied.


[Conjugation transfer of plasmid resistance to gentamycin and other antibiotics in clinical strains of Ps. aeruginosa]. A possibility of conjugation transfer of the markers of the plasmid resistance to gentamicin and other antibiotics from 10 clinical strains of Ps. aeruginosa, isolated from burn patients to the recipient strain of Ps. aeruginosa PTO 629 Rfr was shown. The marker of gentamicin resistance was transferred to 100 out of 110 of the exconjugants, i.e. 86.2 per cent. The rate of the conjugation transfer in the crosses between the clincal strains of Ps. aeruginosa and the recipient strain PTO 629 Rfr with respect to the gentamicin marker was about 10--7. The plasmid resistance markers in the clincal strains Ps. aeruginosa were transferred in various combinations. Transfer of the markers of resistance to streptomycin, carbenicillin, neomycin and combinations Sm, Nm and Sm, Nm, Cm was not achieved.


[Antibiotic sensitivity of the causative agents of suppurative surgical infection]. Sensitivity of 1492 strains of the causative agents of the surgical purulent infections, i. e. pathogenic Staphylococcus, Proteus, Ps. aeruginosa and E. coli to benzylpenicillin, streptomycin, levomycetin, tetracycline, erythromycin, oleandomycin, monomycin, kanamycin, novobiocin, ampicillin, oxacillin, ceporin, gentamicin and rifampicin was studied. Gentamicin was most active against all the bacterial species tested. The staphylococci were in addition sensitive in a high percentage of the cases to rifampicin, novobiocin, ceporin, monomycin and kanamycin. The isolates of E. coli were in addition sensitive to ceporin, monomycin and kanamycin. Sensitivity of the strains of Ps. aeruginosa and Proteus was low to all of the antibiotics except gentamycin. Most of the strains of the causative agents of the surgical purulent infections were multiresistant to 4 antibiotics. The number of the staphylococcal strains sensitive to benzylpenicillin, streptomycin and levomycetin increased in 1976 as compared to 1975 on the background of a limited use of these antibiotics in clinics.


[Experience with studying suspension media in actinomycete lyophilization]. Viability, cultural features and antibiotic-production properties of the organisms producing tetracycline, chlortetracycline, erythromycin, neomycin, oxytetracycline and polymyxin were studied after their storage for 2 years in ampoules at a temperature of 4--10 degrees in lyophilized state with the use of sodium glutamate, polyvinylpyrrolidone, their combination and horse serum. The highest growth rate was observed in most of the cultures lyophilized in sodium glutamate. The growth of the cultures lyophilized in the solution of polyvinylpyrrolidone alone was mainly scanty or moderate. The antibiotic production level in some strains lyophilized in sodium glutamate or its combination with polyvinylpyrrolidone was after storage for 2 years somewhat higher than that in the control. The cultural features, i.e. the colour of the aerial and substrate mycelium and pigment secretion did not significantly differ in the lyophilized cultures and the cultures maintained on agarized media.


Activity of netilmicin compared with those of gentamicin and tobramycin against enterobacteria and Pseudomonas aeruginosa. The inhibitory activity of netilmicin against 500 isolates of gram-negative bacteria was compared with those of gentamicin and tobramycin. Netilmicin was considerably less active than tobramycin and slightly less inhibitory than gentamicin for Pseudomonas aeruginosa but was at least as active against Escherichia coli and Klebsiella pneumoniae as were the other two antibiotics. A few Klebsiella and Serratia isolates resistant to gentamicin and tobramycin were inhibited by netilmicin. All three antibiotics were strongly bactericidal for E. coli, K. pneumoniae and P. aeruginosa but had less lethal activity against the otherwise susceptible Serratia isolates tested. Some necessary precautions in reading minimal inhibitory concentrations on agar media are stressed, and some possible advantages of a 4-h bactericidal test, using a constant antibiotic concentration, are defined.


Synergistic activity of trimethoprim and amikacin against gram-negative bacilli. The in vitro effect of trimethoprim on the inhibitory and bactericidal activity of amikacin against 20 strains each of Klebsiella pneumoniae and Serratia marcescens, 15 strains of Escherichia coli, and 10 strains of Pseudomonas aeruginosa was examined by the checkerboard technique in microtiter plates. Trimethoprim had a synergistic effect on the inhibitory and bactericidal activity of amikacin against the majority of non-pseudomonas strains tested. The mean +/- standard deviation fractional inhibitory concentration indexes were 0.59 +/- 0.19 for the Klebsiella strains, 0.48 +/- 0.18 for the Serratia strains, and 0.60 +/- 0.22 for the E. coli strains tested. Respective mean +/- standard deviation fractional bactericidal concentration indexes for these organisms were 0.55 +/- 0.17, 0.54 +/- 0.29, and 0.61 +/- 0.22. A total of 40% of the Klebsiella strains, 80% of the Serratia strains, and 46% of the E. coli strains had a fractional inhibitory concentration equal to or less than 0.25 for both of these antimicrobial agents and were considered to be synergistically inhibited by the combination. By applying this criterion to bactericidal activity, synergy was demonstrated against 50, 65, and 46% of these strains, respectively. All of the Enterobacteriaceae tested were inhibited by clinically achievable concentrations of trimethoprim and amikacin. Antagonism was not demonstrated with any of the organisms tested. Trimethoprim had no antibacterial effect on the Pseudomonas strains and did not alter amikacin's activity against these bacteria.


Comparison of the effects of two lipophilic acids, hexachlorophene and decanoate, on Bacillus subtilis. The minimal growth-inhibitory amount of either hexachlorophene (HCP) or decanoate stopped growth, respiration, adenosine 5'-triphosphate synthesis, and amino acid transport of Bacillus subtilis in a culture containing amino acids and citrate as carbon sources. The electron transport system was not affected by this dose. Addition of 27.8 mM glucose or 10 mM malate to an inhibited culture did not reverse the binding of HCP or decanoate to the cells, but it allowed resumption of growth, respiration, and adenosine 5'-triphosphate synthesis, as the glucose or malate then supplied the needed carbon. The addition of glucose or malate did not reverse amino acid transport inhibition caused by decanoate, but it did reverse that due to HCP. However, if the dose of HCP was raised in the presence of glucose or malate, only growth and amino acid transport were affected; this indicates that both HCP and decanoate act at their minimal growth inhibitory doses by inhibiting substrate transport. As active transport of amino acids and ketoacids depends on the proton gradient and the membrane potential of the cells, we conclude that the primary effect of these lipophilic acids is the destruction of the proton-motive force.


Identification of drug resistance loci in various clinical isolates of Neisseria gonorrhoeae. Extending previous results obtained for three strains of Neisseria gonorrhoeae, four naturally occurring, multiply resistant isolates were used in transformation studies. Six drug resistance loci corresponding to those found in the previously studied strains were identified. In addition, the mtr and ery-2 loci were found to be allelic.


Toxicity of Diplodia maydis to laboratory animals. Ten strains of Diplodia maydis isolated from commercial corn samples and grown on whole yellow corn at 25 degrees C for 6 weeks were toxic to ducklings and rats. The degree of toxicity depended on the incubation period and temperature. Minimum incubation periods of 3 to 4 weeks and 6 weeks were necessary to cause mortality in ducklings and rats, respectively. Cultures incubated at 31 and 25 degrees C were much more toxic than those kept at 16 and 20 degrees C. Heat treatments at 80 to 90 degrees C destroyed most of the toxicity of moldy meal. Mild lesions of a similar histopathological nature were found in subclinically and lethally poisoned rats. These included toxic myocarditis, enteritis, focal renal tubular necrosis, degeneration and peripheral necrosis of the islets of Langerhans, and a generalized venous congestion.


Surface-decontaminating action of glutaraldehyde in the gas-aerosol phase. The surface disinfectant effect of glutaraldehyde in the gas-aerosol phase was investigated at different relative humidities and temperatures. At a gas-aerosol concentration of 15 to 20 mg/m3 and a relative humidity of about 80%, glutaraldehyde had a good disinfectant effect against both vegetative bacteria (decimal reduction time, less than 5 min) and bacterial spores (decimal reduction time, less than 45 min). In spite of its low volatility, glutaraldehyde was more effective than formaldehyde when the two substances were compared on an "added amount" basis.


Dry-heat resistance of selected psychrophiles. The dry-heat resistance characteristics of spores of psychrophilic organisms isolated from soil samples from the Viking spacecraft assembly areas at Cape Kennedy Space Flight Center, Cape Canaveral, Fla., were studied. Spore suspensions were produced, and dry-heat D values were determined for the microorganisms that demonstrated growth or survival under a simulated Martian environment. The dry-heat tests were carried out by using the planchet-boat-hot plate system at 110 and 125 degrees C with an ambient relative humidity of 50% at 22 degrees C. The spores evaluated had a relatively low resistance to dry heat. D(110 degrees C) values ranged from 7.5 to 122 min, whereas the D(123 degrees C) values ranged from less than 1.0 to 9.8 min.


Parathion utilization by bacterial symbionts in a chemostat. A continuous-culture device was used to select and enrich for microorganisms, from sewage and agricultural runoff, that were capable of using the organophosphorus insecticide parathion as a sole growth substrate. Parathion was dissimilated by the highly acclimated symbiotic activities of Pseudomonas stutzeri, which non-oxidatively and cometabolically hydrolyzed the parathion to ionic diethyl thiophosphate and p-nitrophenol, and P. aeruginosa, which utilized the p-nitrophenol as a sole carbon and energy source. Ionic diethyl thiophosphate was found to be inert to any transformations. Methyl parathion was dissimilated in an analogous way. The device functioned as a chemostat with parathion as the growth-limiting nutrient, and extraordinarily high dissimilation rates were attained for parathion (8 g/liter per day) and for p-nitrophenol (7 g/liter per day). This is the first report of parathion utilization by a defined microbial culture and by symbiotic microbial attack and of dissimilation of an organophosphorus pesticide in a chemostat.


Removal of Escherichia coli in wastewater by activated sludge. Removal of bacteria from wastewater treated with activated sludge was studied by the use of a streptomycin-resistant Escherichia coli strain. The removal appeared to be a biphasic process. A rapid sorption of bacteria to the sludge flocs took place in the first hour after seeding mixed liquor with E. coli. Thereafter, slower elimination of E. coli was observed. The latter process was due to predation on E. coli by ciliated protozoa. This was shown by: (i) appearance of fluorescent food vacuoles of ciliates when fluorescent E. coli cells were added to mixed liquor; (ii) inhibition of predation either in the presence of cycloheximide or under anaerobic conditions; and (iii) absence of predation in bulking and washed sludge.


Clinical significance of basal cell layer antibodies. Circulating antibodies in humans were found to antigens present only in the basal cell layer of stratified squamous epidermis by the immunofluorescence technique. Such antibodies were uncommon, being present in only 38 (1.5%) of 2,500 sera. They usually occurred in the presence of immune disorders involving the skin, although they were not associated with a particular disease.


Degradation of carbaryl by soil microorganisms. Four days after carbaryl-naphthyl-1-14C was mixed with soil from a field treated 6 months previously with 4 lb/A of the same insecticide, only 28% of the radiocarbon remained. Approximately 90% remained in soils with no history of pesticide applications. However, dissipation of the carbaryl-14C residues from the latter soils continued at a rather steady rate over a 120-day test period, whereas there was little dissipation after 4 days from the former. Consequently, the total 14C-residue levels were about the same, 15 to 20% of applied, when the last samples were taken. Carbaryl, per se, was the only apolar 14C-residue recovered from the soil and only small quantities, less than 2% of the amount applied, of extractable polar metabolites were encountered. Almost all of the terminal residues were unextractable from the soil with mixtures of acetone and water. Much of the loss of 14C-residues from the soil was attributed to the liberation of 14C-carbon dioxide as a result of microbial degradation of the naphthalene ring. Several fungal and bacterial isolates degraded carbaryl in the same manner as observed with soil incubations, but the rates of degradation were much slower.


Substrate interaction in intravenous feeding: comparative effects of carbohydrate and fat on amino acid utilization in fasting man. Data are presented on the metabolic and endocrine effects of intravenous infusions in normal fasting man observed under highly controlled conditions over a period of six to eight days duration. There are comparative data on a variety of intravenous feeding programs. The data on total starvation are based on studies from the literature, some of which were carried out in this laboratory. The data on low dose glucose, high dose glucose, glycerol, fat emulsion, and amino acids, each given separately, demonstrate changes seen with simple infusion of a single substrate in fasting. These data are now compared with the utilization of amino acid infusions when accompanied by low dose glucose, high dose glucose, glycerol, and fat emulsion. In all, nine experimental intravenous feeding programs are presented, based on data from 35 subjects observed over a total of 370 subject-days. The findings show a strong interaction between glucose or lipid and protein metabolism. In fasting, glucose had protein sparing effect, most evident when given at high dose. Glycerol, in an amount equal to that contained in 2000 ml of ten per cent fat emulsion, had a mild protein sparing effect. Fat emulsion was no more effective. When amino acids were given alone, normal fasting human subjects were always in negative nitrogen balance with the daily nitrogen loss half that seen in starvation alone. Although amino acids given alone have a protein sparing effect, this is accomplished only at the expense of a high nitrogen excretion including an amount equivalent to the entire infusion plus an additional loss from the body's native proteins. The provision of energy yielding non-protein substrates with the amino acids markedly improved nitrogen economy in the following order: glycerol, low dose glucose, fat emulsion and high dose glucose. When caloric provision with glucose approached the isocaloric level for normal diet, the utilization of amino acids was maximized. When given with amino acids, fat emulsion was more effective than the available glycerol alone. THE ACCOMPANYING ENDOCRINE AND BIOCHEMICAL CHANGES SUGGEST THAT THE MILIEU FOR IDEAL UTILIZATION OF INFUSED AMINO ACIDS IS VARIABLE: ketones at low range (carbohydrate) or moderately elevated (fat emulsion); insulin elevated (carbohydrate) or unchanged (fat emulsion). The utilization of the infused amino acids was markedly improved in both endocrine settings, suggesting that it is the provision of energy as substrate as well as the endocrine setting that determines amino acid utilization. There were other changes in plasma intermediates, particularly fatty acids, glucose and urea, all consistent with the concept that when amino acids are given without other substrates, the amino acids must be maximally utilized for gluconeogenesis. When other substrates are provided (particularly glucose at high dose) then this mandate no longer exists and protein synthesis from the amino acids is favored. Several of the plasma amino acid concentrations responded to glucose when added to amino acid infusion. Amino acids alone produced increases in concentration of all the amino acids found in the infusion with the exception of alanine, arginine, and threonine. Many of these increases were abated by the addition of glucose to the amino acid infusion, suggesting an increased utilization rate. Glycerol and fat emulsion, while modulating increases in the plasma amino acid concentration, did so to a lesser extent than did glucose. This lowering of amino acid concentration was unaccompanied by an increase in urinary excretion. The assumption is therefore made that the provision of the added glucose favors the incorporation of amino acid into protein. There is no evidence from these data to suggest that a rising concentration of ketones in the blood favors amino acid utilization or protein synthesis.


[Immunogenicity of L5178Y cells modified by different reagents]. Lymphoma L5178Y cells were treated with neuraminidase of Vibrio cholerae, potassium iodine, dithiotreitol (DTT), mercaptoethanol, glutaraldehyde, iodoacetamide, merthiolate, sodium periodate, urea, papaine, trypsine and EDTA, to increase immunoreaction in tumor cells. Mice were immunized with modified tumor cells every week for one month. Thereafter non modified tumor cells were transplanted to previously immunized mice. Only the immunization with neuraminidase-treated cells rejected the tumor. Although the immunization with cells treated with potassium iodine, DTT and mercaptoethanol did not reject tumor, prolonged significantly span of life. The other reactives had neither effect on tumor rejection nor on span of life.


[Immunology of histoplasmosis: isolation of a polysaccharide-protein complex with immuno-specific activity from Histoplasma capsulatum]. A polysaccharide protein complex (PPC) with a high specificity in immunodiffusion in gel (IDG) was isolated from a Histoplasma capsulatum strain. Although unaffected by proteolytic enzymes (pronase) and heat, the PPC antigen activity was destroyed by beta-glucosidase. These results suggest that the specificity of the PPC antigen might be located in the polysaccharide fraction. Polyacrylamide gel electrophoresis of the PPC antigen gave only one brand detected by Schiff's reagent (PAS).


Influence of electric fields on photophobic reactions in blue-green algae. The effect of external electric fields on photo-accumulations of Phormidium uncinatum in light traps has been studied. 1. In direct current fields the phobic reaction of trichoms leaving the light field is not impaired if a voltage of 2.5 V is not exceeded. With voltages between 3 and 7 V the trichoms are motile, but phobic reactions are cancelled, provided the organisms are oriented more or less parallel to the electric field lines. Higher voltages cause the algae to die within minutes. 2. Only alternating current fields of very low frequencies (less than or equal 10(-3) Hz) have similar effects. Sine waves are more effective than triangular ones, but less than square waves. A hypothesis is proposed according to which sensory transduction of photophobic reactions in blue-green algae is mediated by changes in the endogenous membrane potential. This potential might be interfered with by the application of an external electric field, thus inhibiting photophobic reactions.


Elongation and cell division in Bdellovibrio bacteriovorus. Elongation and division of Bdellovibrio bacteriovorus were studied in axenic synchronous cultures. The cells elongate unidirectionally from one end attaining a length of several "unit cells", and then divide into the corresponding number of cells. The length of the filament and, consequently, the progeny number, vary within the range of two to several dozen cells, according to the conditions used. A protein and a low molecular weight component are required for normal division.


Micromorphology of Gram-negative hydrogen bacteria. I. Cell morphology and flagellation. The cell morphology, the arrangement and fine structure of flagella and the piliation of the following Gram-negative aerobic hydrogen bacteria have been studied: Alcaligenes eutrophus, Alcaligenes paradoxus, Alcaligenes ruhlandii, Pseudomonas flava, Pseudomonas pseudoflava, Pseudomonas palleronii, Pseudomonas facilis, Aquaspirillum autotrophicum, Paracoccus denitrificans, Corynebacterium autotrophicum, and strains MA 2 and SA 35. The identity of the bacteria was examined by their substrate spectra and type of flagellation. Three types of flagellar fine structure were differentiated. The presence of pili was noted in strains of Alcaligenes paradoxus, Pseudomonas flava, P.pseudoflava, P.palleronii, and P.facilis.


Identification of intracellular immunoglobulin in extramedullary myeloma. We describe a patient with multiple myeloma characterized by clinically evident extramedullary metastasis and marked anaplastic alterations of neoplastic cells. We describe the technique that detected the presence of intracytoplasmic immunoglobulin IgGk in mature plasma cells from paraffin-fixed tissue obtained from an iliac lesion and in anaplastic tumor cells infiltrating a lymph node from which a biopsy specimen was taken three years later. These data confirm that both tissues were composed of a cell with identical origin. In addition, the immunohistochemical technique is applicable for the identification of other antigens present in paraffin-embedded tissue.


Nutritional management of cancer patients in a variety of therapeutic regimens. The various therapeutic modalities for the control of neoplastic disease create metabolic disturbances necessitating special nutritional management. Negative nitrogen balance as a result of cell destruction, especially during chemotherapy and radiotherapy, is common. Nutritional support would be beneficial both in the early and in the late stages of cancer treatment. The mode of feedings should be individualized depending on the specific problems of each patient. For successful nutrition intervention, an understanding of the rational for integrated medical, nursing and nutritional approaches in the management of the patient is important.


Double gastroenterostomy tube in gastric surgery. This report describes a new double gastroenterostomy tube. It has been used in patients where delayed oral feedings are anticipated, ie, a perforated duodenal ulcer, suture-plicated, with stenosis of the duodenum; a duodenal ulcer with outlet obstruction treated with vagotomy and gastroenterostomy; and patients with chronic lung disease undergoing gastric surgery and requiring postoperative respiratory assistance. Its use has proved to be beneficial, and it is cheap and allows early enteric feeding.


[Use of parenteral and elementary enteral nutrition in the treatment of Crohn's disease and ulcerative colitis in children]. Nine children, aged 2 to 16 years, presented with severe Crohn's disease (5 cases) and ulcerative colitis (4 cases). They were given exclusive parenteral feeding 6 times and elementary enteral feeding at constant flow 9 times. In 6 cases, an anti-inflammatory treatment and/or surgical excision were associated. In all cases, immediate results were excellent and permitted to overcome an acute phase. Considering these results, the authors discuss the relative indications of these techniques of nutrition, in the treatment of severe cases of Crohn's disease and ulcerative colitis in children.


[Interstitial cells of the kidney medulla and the content of prostaglandins in the kidneys of rats after administration of indomethacin]. A parallel study on the content of prostaglandins (PG) in the kidneys, the morphological condition of the medulla interstitial cells, and the activity of prostaglandin-dehydrogenase in rats given indometacyn for 5 days in a dose of 5 mg/kg was carried out. A considerable decrease in the content of PGA2 and PGE2 and an increase in PGF 2alpha in the kidneys of the experimental animals as compared with the controls was noted. The number of lipid granules in the interstitial cells of the renal medulla was also increased. A significant rise in the activity of prostaglandin-dehydrogenase was observed in the kidneys of the animals given indometacyn. The experimental results confirmed the suggestion that the medulla interstitial cells took a direct part in synthesis of renal PG. Indometacyn was shown to be able to decrease the PG content in the kidneys not only by inhibiting the activity of prostaglandin-dehydtogenase, as it was thought, but also by increasing the activity of prostaglandin-dehydrogenase.


Methyl alcohol poisoning III. Ocular toxicity. The ocular toxicity of methyl alcohol has been investigated in six rhesus monkeys. All the animals developed fundus changes within 43 to 171 hours after its ingestion. The only fundus lesion seen was optic disc edema and associated changes, usually of a marked degree. Fluorescein fundus angiography confirmed the findings. The retinal and choroidal circulations, including the retinal capillary bed, were normal. Ophthalmoscopically and angiographically, optic disc edema in methyl alcohol poisoning was indistinguishable from that seen in raised intracranial pressure, except that no increased intracranial pressure was observed. It is postulated that optic disc edema in methyl alcohol poisoning is due to an axoplasmic flow stasis.


[The psychogenic clubfoot. A rare posttraumatic condition (author's transl)]. At the beginning of this century and during World War I psychogenic contractures were very common; later on they became rare.--The author reports and demonstrates 3 cases of psychogenic supination contractures of the foot (functional clubfeet) following a slight trauma of the ankle, the treatment of which was carried out in 1946, 1974 and 1976. All of these patients were women. The deformity of the foot was caused by a permanent contraction of the tibialis-muscles without an underlying organic disease. The therapy consisted of an arthrodesis of the midtarsal joints along with a transfer of the tibialis-anterior-tendon to metatarsus V. In all three cases both deformity and pain disappeared. The quantity and quality of the patients' mobility improved to near normal.--With this article the author intends to remind the orthopedic surgeons and the neurologists of this functional contracture.


[Cancellous bone from the head of the tibia as autologous graft material (author's transl)]. In the operative treatment of 93 lower leg and ankle fractures at the Kreuzspital Chur cancellous bone from the head of the tibia of the same leg was used to brigde bone defects. The advantage of this procedure lies in the fact that operative site and donor site are identical.


Effect of otolith end organ ablation on pendular rotation nystagmus in squirrel monkeys. Damped pendular rotation nystagmus was studied in squirrel monkeys before and after otolith end organ ablation (two-stage operations). After each operation, the nystagmic slow phase eye speed toward the operated side was reduced (to about 73% of that before the operation) and that to the non-operated side did not show any marked change. A few subjects showed spontaneous nystagmus with amphetamine administration but only in dark (could not be found in light) immediately after the operation, and it disappeared rapidly. Therefore, this post-ablative reduction of the slow phase eye speed is considered to result from the loss of inputs from the otolith end organs.


Variability of fibroblast lysosomal acid hydrolases with reference to the detection of enzyme deficiencies. The ranges of variability of eight lysosomal acid hydrolases were examined in 47 cultured human skin fibroblast lines through 5 successive subcultures. No overall trend in activity values was found for any of the enzymes tested between the first and final subcultures. Similarly, no significant differences could be found between the overall ranges of fibroblast enzyme activity between 20 clinically normal children and 27 individuals being investigated for non-specific metabolic diseases. It is concluded that for diagnostic reference purposes, wide ranges of normal enzyme values must be established. Such ranges can be validly drawn from a continuation of both clinical groups irrespective of the passage number (up to 5) of the cells at the time of isolation. It is noted that in certain cell lines derived from Fabry and Gaucher patients the 'residual' activity of the expectedly deficient enzyme could not easily be distinguished from the lowest values observed in normals, whereas, as expected, the activity of cells derived from patients with GM1 and GM2 gangliosidoses was markedly reduced.


Considerations in the prenatal assessment of lysosomal enzyme deficiency in eight cases at risk. Some of the factors which are to be considered in the antenatal diagnostic evaluation of lysosomal enzyme levels in cultured amniotic fluid cells are discussed in the light of eight consecutive cases in which the foetuses had a 1 in 4 chance of being homozygous for a lysosomal storage disease. There were 2 possible cases of GM1 gangliosidosis, 2 of neuropathic Gaucher's disease, 1 of Krabbe's disease and 2 of Pompe's disease. Each infant was predicted to be unaffected; the assessments were confirmed to be correct postnatally--7 by enzyme studies. Using a micro technique, 5 of the assessments were available in 28 days or less following amniocentesis. It is concluded that in certain circumstances skin fibroblasts may be used as valid controls and that the variability of assay results strongly militates against the confident assignment of heterozygous status and may cause difficulties in the identification of the homozygote in cases where 'residual' enzyme activity is high; concomitant family studies assist in the resolution of such problems.


Intestinal brush border and lysosomal enzymes and immunoglobulin absorption in the newly-born lamb. Activities of the brush border enzymes alkaline phosphates, leucine aminopeptidase and lactase and the lysosomal enzymes alpha-mannosidase and beta-N-acetylglucosaminidase increased in the serum of newly-born lambs fed colostrum. Feeding lipid and protein components of colostrum and bovine serum resulted in enzyme responses similar to those observed after feeding colostrum. Activities of each of the enzymes increased in mesenteric lymph collected from newly-born lambs when immunoglobulins were being absorbed from the jejunum and ileum.


Recent advances in the management of spinal injuries with paralysis. In the last decade, by application of detailed methods of care, the previously accepted complications of urinary infection, pressure sores and motor skeletal problems of contractures and spasm, have largely been eliminated from the clinical picture of patients with spinal paralysis. Many professionals in medicine have contributed to these advances. Long-term or extended care in the area of tetraplegia and paraplegia need further stimulation, with continued application of all those methods used in acute rehabilitation in properly organized spinal units.


Portions of the central nervous system controlling reproductive behavior in Drosophila melanogaster. Drosophila melanogaster sex mosaics were tested in their courtship interactions with females and then with males. The distribution of genetically male and female tissues in each mosaic was determined with respect to an external cuticle marker and an internal enzyme marker. Performance of malelike courtship was correlated with the genotype of various tissues, with special attention being paid to the genotypes of head and thoracic ganglia. Male tissue in the left or right dorsal brain is necessary and nearly always sufficient to trigger early courtship actions--following of females and wing extension at them--but male tissue in both the dorsal brain and thoracic ganglia is necessary for attempted copulation to occur. Female tissue on or in the abdomen is nearly always necessary and sufficient for a mosaic to be courted by a male.


Identification of avian mycoplasma isolates by the agar-gel precipitin test. Recent isolates of Mycoplasma gallisepticum and Mycoplasma synoviae were readily typed by the agar-gel precipitin test with antigens prepared by freezing and thawing, sonic vibration, or sodium dodecyl sulfate. Specific antisera prepared in rabbits or in foot-pad-inoculated chickens were adequate for culture typing. Relatively few sera from chickens and turkeys in naturally infected flocks reacted positively. The precipitin reaction was highly specific, however.


Precocious development of uridine diphosphate glucuronosyltransferase activity during organ culture of foetal rat liver in the presence of glucocorticoids. 1. Precocious development of mammalian UDP-glucuronosyltransferase (EC 2.4.1.1.7) induced by endogenous compounds of known chemical composition is reported for the first time. 2. This development occurs in cultured explants of foetal rat liver when exposed to corticosteroids possessing a pregn-4'-ene structure and a hydroxy or an oxo group at C-11. 3. Explants from 14-day foetuses cultured for 3 days in a chemically defined medium containing dexamethasone exhibited transferase activities towards o-aminophenol within adult male values. Those liver transferase activities attained in utero by 17 days were still negligible. 4. Evidence from several approaches indicated that the explants required glucocorticoids for expression of the transferase, not for maintenance of viability. 5. Glucocorticoid-dependent stimulation of transferase activity required incorporation of L-[14C]leucine into protein, as judged from the pulsing of cultures with cycloheximide. 6. The relevance of these culture experiments to the situation in vivo is discussed.


Effect of some bacterial products on platelet electrophoretic mobility (PEM). Bacterial LPS, used in our experiments, are able to decrease PEM at concentration of 100 microgram/ml after incubation with 1 X 10(7) platelets/ml for 30 min at 37 degrees C. Such effect is statistically significant for Bacteroides fragilis LPS, S. enteritidis and S. typhi. E. coli LPS 026:B6 W and E. coli 055:B5 W are not effective at all, S. minnesota (incomplete) LPS 595 and 345 free of 0-polysaccharide and partially lacking core in their molecule did not influence PEM, while S. minnesota LPS (S form) (a complete LPS) strongly decreased PEM. This fact could suggest that 0-polysaccharide is involved in this inhibitory effect on PEM. Klebsiella enterotoxin and B. cereus enterotoxin are able to decrease PEM at concentration of 100 microgram/ml, after incubation with 1 X 10(7) platelets for 30 min at 37 degrees C, while no inhibition of PEM was seen when Shighella enterotoxin and V. parahaemoliticus enterotoxin was used in similar way. The AA. conclude that endotoxin and enterotoxin are able to change the electrokinetic charge (negative) of platelets, thereby, causing a decrease of PEM.


Distribution of water and electrolytes in normal and thermally damaged skin. The alterations in contents of Na, K and water in thermally injuried explants of guinea-pig flank skin involve changes in both the cells and the interstitial material of the tissue. A full interpretation of the distribution of such changes can only be obtained if the volumes of cellular and extracellular fluid are known. This work examines the techniques of measuring extracellular fluid volume using 14C-inulin and 51Cr EDTA. Although it was found that the inulin preparation was excluded from a considerable part of the extracellular fluid of the skin explants, the space which it defined altered with increasing severity of thermal damage. The relationship of the inulin space with total water and with 51Cr EDTA space, which probably measures the total extracellular volume, provides an insight into the possible importance of changes in the nature of connective tissue in trauma. Alterations in fluid and cation balance between cells and their environment have been discussed in relation to increasing thermal damage. A clear sequence of events following the onset of the injury can be observed.


Production of antibody to staphylococcal delta-haemolysin in the rabbit. Gamma-globulin and IgG from the sera of rabbits immunized with either "insoluble" or "solvent-transferred" staphylococcal delta-haemolysin precipitated with, and neutralized both forms of lysin. Similar preparations from the same rabbits before immunization did not; nor did those from rabbits made hyperimmune to other antigens. In these tests "insoluble" and "solvent-transferred" lysin could not be distinguished antigenically, nor could "insoluble" lysin from two different strains of staphylococci, each grown on two different media. An appendix presents further evidence for antigenicity of delta-lysin, based on affinity chromatography.


Factors affecting fetal survival after intrauterine transfusion for rhesus isoimmunization. Intrauterine transfusion of the fetus is described in 165 pregnancies. The overall fetal survival rose from 28 per cent in 1964 to 1969 to 42-5 per cent in 1973 to 1975. Apart from technical complications of the procedure itself, the factors most likely to affect fetal survival were the gestational age and amniotic fluid optical density difference before the first intrauterine transfusion, the birth weight and the cord blood haemoglobin level.


Carbonic anhydrase activity in human cervical mucus and its response to various contraceptives regimes. Carbonic anhydrase activity is present in human cervical mucus throughout the normal menstrual cycle. Lowest activity occurs in the ovulatory phase. A similar pattern of activity is seen in the presence of either an 'inert' or copper-releasing intrauterine contraceptive device (IUCD). The overall levels of activity are not significantly altered by the presence of either type of IUCD. A cyclic pattern of activity is retained even though endogenous ovarian function is suppressed by combined oestrogen-progestogen oral contraceptives.


An improved method for the microbiological assay of available amino acids in proteins using Tetrahymena pyriformis. 1. A standard microbiological procedure for the assay of available amino acids in proteins using Tetrahymena pyriformis has been modified by evaluating cell growth from the tetrahymanol content of the cultures by gas-liquid chromatography (GLC). 2. This modification improves the precision of the method compared with cell-counting techniques and provided automatic injection facilities are available for the GLC, the procedure is not excessively time-consuming. 3. It has been confirmed that enzymic predigestion is essential for all except the most soluble proteins and a satisfactory method using pronase has been incorporated into the microbiological procedure. 4. After enzymic digestion of the sample, growth of Tetrahymena with many proteins can be measured turbidimetrically, but particulate matter still persists with a proportion of samples, particularly those of plant origin, and the GLC method is therefore more widely applicable. It is also more precise. 5. Good agreement has been obtained between a chick bioassay and the modified Tetrahymena assay for available lysine in eight different proteins, including heat-damaged fish meals. 6. The modified procedure appeared to give good results for available tryptophan and methionine. 7. When cystine was omitted from the standard culture medium it was possible to test for available methionine plus cystine, but further work is required to assess the reliability of this particular assay.


Isolation and characterization of a unique galactoside from male Drosophila melanogaster. A ninhydrin-positive compound with presumptive hormonal activity, previously considered to be a peptide (Chen, P.S., and Bühler, R. (1970), J. Insect Physiol. 16, 615), has been isolated from adult male Drosophila melanogaster. Chromatographic analysis of the acid-hydrolyzed material revealed the presence of ethanolamine, phosphorus, galactose, and glycerol. Chemical analysis showed these to be present in equimolar amounts. Based on its phosphorus content, the nonreducing material took up 2 equiv of periodate, and released 1 equiv of formaldehyde. Characterization of the compound as 1-O-(4-O-(2-aminoethyl phosphate)-beta-D-galactopyranosyl)-x-glycerol was achieved by gas chromatography-mass spectroscopy and 1H and 31P NMR using model compounds. In vivo synthesis from labeled precursors is in accord with the proposed structure.


Investigation of immunological relationships among myosin light chains and troponin C. Two classes of myosin light chains can be distinguished functionally: those that restore calcium regulation to "desensitized" scallop myofibrils, and those that do not (Kendrick-Jones, J., et al. (1976), J. Mol. Biol. 104, 747--775). Despite this functional classification, chemical analyses reveal few patterns unique to regulatory light chains, and, indeed, sequence comparisons suggest structural similarities between both classes of myosin subunits (Collins, J. H. (1977), Nature (London) 259, 699--700; Kendrick-Jones, J., and Jakes, R. (1977), in International Symposium on Myocardial Failure at Tegernsee, Riecker, G., and Boehringer, Ed., Munich, West Germany, Springer-Verlag, pp. 28--40). Immunological assays using antisera to regulatory and to nonregulatory light chains showed no correlation between antigenic activity and the presence or absence of regulatory function. Weak cross-reactivity was observed, however, among myosin light chains and troponin C, consistent with the suggestion made on the basis of sequence homologies that these subunits contain similar structural domains (Weeds, A. G., and McLachlan, A. D. (1974), Nature (London) 252, 646--649). Unexpectedly, the strongest cross-reactivity observed was that between the vertebrate myosin alkali 1 and DTNB light chains.


Addition of glucosamine and mannose to nascent immunoglobulin heavy chains. We have investigated the process of protein glycosylation in an attempt to answer the question of whether glucosamine and mannose are added to nascent chains prior to chain completion or only to completed chains after release from the ribosome. The MPC 11 mouse plasmacytoma cell line used in these studies synthesizes a glycosylated gamma2b heavy chain which accounts for 12% of the total protein synthesis. Nascent chains were separated from completed chains by ion-exchange chromatography of solubilized ribosomes on QAE-Sephadex. Our results indicate that both glucosamine and mannose are incorporated into nascent heavy chains prior to chain completion and release from the ribosome. Gel analysis of specifically immunoprecipitated nascent chains indicates that the carbohydrate moiety can be added to the nascent heavy chains very soon after the presumptive asparaginyl glycosylation site (CH2 domain) is synthesized on the ribosome.


Synthesis in vitro of ribosomal protein S20 and its precursor. I have purified and characterized two products synthesized in vitro in a system for coupled transcription and translation programmed by DNA from a transducing bacteriophage carrying the gene for ribosomal protein S20. One of these polypeptides appears to be identical with authentic S20 by several criteria, including its electrophoretic and chromatographic mobilities, and its ability to bind to 16S RNA. The second polypeptide is less basic than S20, but exhibits all the structural and functional properties of a precursor to S20, including the presence of an additional methionine residue, apparently as N-formylmethionine. Moreover, it is converted, albeit slowly, to S20 in cell-free extracts. The persistence of the precursor form of S40 may be functionally significant as well.


Characterization of the "microprotease" from Bacillus cereus. A zinc neutral endoprotease. The neutral protease isolated from Bacillus cereus (BRL-70) has been purified by affinity chromatography and characterized. The enzyme exhibits a single band on sodium dodecyl sulfate-polyacrylamide gel electrophoresis, has a molecular weight of 34 000 by ultracentrifugation, and contains one enzymatically essential zinc atom per 34 000 g. These data together with the amino acid composition, response to metal substitution, chemical modification, and substrate specificity all indicate that this protease is monomeric and is a typical bacterial neutral metalloprotease.


Mechanism of the irreversible inhibition of gamma-aminobutyric acid-alpha-ketoglutaric acid transaminase by the neutrotoxin gabaculine. Gabaculine (5-amino-1,3-cyclohexadienylcarboxylic acid), a naturally occurring amino acid isolated from Streptomyces toyacaenis, is an irreversible inhibitor of bacterial pyridoxal phosphate linked gamma-aminobutyric acid-alpha-ketoglutaric acid transaminase with a t 1/2 (25 degrees C) of 9 min at 3 X 10(-7) M. Gabaculine is a substrate for gamma-aminobutyric acid transaminase. The measured KI is 2.86 X 10(-6) M, and the kcat for its turnover is 1.15 X 10(-2) S-1 at 25 degrees C. When gabaculine is transaminated by the enzyme, it is converted to a cyclohexatrienyl system with one exo double bond. Upon spontaneous aromatization, this high energy intermediate is transformed into a stable m-anthranilic acid derivative (m-carboxyphenylpyridoxamine phosphate), which results in the covalent and irreversible modification of the cofactor. This adduct is bound tightly to the active site of the enzyme and can be liberated under denaturing conditions.


Biochemical and immunological analysis of a basic protein from newborn rat epidermis. A basic protein, solubilized in buffered salt solutions from keratohyalin granules of newborn rat epidermis, has been purified by ion-exchange chromatography. The relative molecular weight of the protein was determined as 12 800 +/- 200 from its mobility on sodium dodecyl sulfate-polyacrylamide gel electrophoresis. The protein is relatively rich in lysine, glycine, alanine, and valine which together comprise about 60% of the total amino acid residues. Using an antibody to this protein, which we have designated fraction 4, we have found that it is specific to rat epidermis and is not present in any other rat tissues or in epidermal extracts from other species. The cells of the four epidermal layers were separated and the amount of fraction 4 in each cell layer was measured by radioimmunoassay. The protein is localized mainly in the upper layers of epidermis. The protein, which binds to DNA, appears in the epidermis just prior to birth, increases during the first week of post-natal life and declines sharply thereafter. Fraction 4 represents about 7% of the total solubilized protein in 7-day-old rat epidermis.


Involvement of precursor-specific segments in the in vitro maturation of Bacillus subtilis precursor 5S ribosomal RNA. In vitro maturation of precursor 5S ribosomal RNA (p5A) from Bacillus subtilis effected by RNase M5 yields mature 5S RNA (m5, 116 nucleotides), and 3' precursor-specific segment (42 nucleotides), and a 5' precursor-specific segment (21 nucleotides) (Sogin, M.L., Pace, B., and Pace, N.R. (1977), J. Biol. Chem. 252, 1350). Limited digestion of p5A with RNase T2 introduces a single scission at position 60 of the molecule; m5 is cleaved at the corresponding nucleotide residue. The complementary "halves" of the molecules could be isolated from denaturing polyacrylamide gels. The isolated fragments of p5A are not substrates for RNase M5, suggesting that some recognition elements can be utilized by RNase M5 only when presented in double-helical form. In exploring the involvement of the precursor-specific segments in the RNase M5-p5A interaction, substrate molecules lacking the 3' or 5' precursor-specific segment were constructed by reannealing complementary "halves" from p5A and m5 RNA. The artificial substrate lacking the 5'-terminal precursor segment was cleaved very much more slowly than the lacking t' segment; the 5' precursor-specific segment therefore contains one or more components recognized by RNase M5 during its interaction with the p5A substrate.


Necessity of a membrane component for nitrogenase activity in Rhodospirillum rubrum. Acetylene reduction catalyzed by nitrogenase from Rhodospirillum rubrum has low activity and exhibits a lag phase. The activity can be increased by the addition of a chromatophore membrane component and the lag eliminated by preincubation with this component, which can be solubilized from chromatophores by treatment with NaCl. It is both trypsin- and oxygen-sensitive. Titration of the membrane component with nitrogenase and vice versa shows a saturation point. The membrane component interacts specifically with the Fe protein of nitrogenase, the interaction being ATP- and Mg2+-dependent.


The effect of phosphatidylcholine to sphingomyelin mole ratio on the dynamic properties of sheep erythrocyte membrane. Sheep red blood cells are shown to incorporate phosphatidylchline when incubated in human plasma in the presence of EGTA. This treatment results in up to a 5-fold increase in mol ratio of phosphatidylcholine to sphingomyelin. By replacing EGTA with Ca+ the increase of phsphatidylcholine content is completely inhibited, due to the activation of the membrane bound lecithinase which rapidly degrades the incorporated phosphatidylcholine. Analogous treatments of the isolate membranes resulted in similar phosphatidylcholine incorporation but in the presence of Ca+ a residual phosphatidylcholine uptake was still oberved. These results suggest that in the isolated membranes small amounts of phosphatidylcholine can be incorporated into an additional region which is unavailable for the membrane lecithinase. The increase in the phosphatidylcholine to sphingomyelin mol ratio in sheep red blood cells is concomitant with an increase in lipid fluidity, as well as increase in osmotic fragility9


Growth-dependent factors in the regulation of aminoacyl-tRNA synthetase activities of Tetrahymena pyriformis. Changes in phenylalanyl-tRNA synthetase (L-phenylalanine : tRNAPhe ligase, EC 6.1.1.20) and leucyl-tRNA synthetase (L-leucine : tRNALeu ligase. EC 6.1.1.4) activities were studied during the growth cycle of Tetrahymena pyriformis. High levels of charged tRNA observed during exponential growth were associated with elevated aminoacyl-tRNA synthetase activities. Low levels of charges tRNA in the stationary phase culture were associated with decreased aminoacyl-tRNA synthethase activities together with a concomitant accumulation of factor(s) which inhibited the enzyme activities. The inhibitory factor(s) has been partially purified and evidence is presented to rule out RNA, RNAases, proteases and ATPases as the responsible inhibitory factor(s) of the aminoacyl-tRNA synthetases.