Topography of estrogen target cells in the forebrain of goldfish, Carassius auratus. The topographical distribution of estradiol-concentrating cells in the brain of male and female teleost, Carassius auratus, was determined by autoradiography, after injection of 3H estradiol-17beta. Radioactively labeled neurons are found in specific regions of the forebrain, with a similar topographical distribution both in males and females. Regions of accumulation of estrogen target cells include the supracommissural area of the telencephalon, the preoptic area, the central hypothalamic area and the thalamic area. Unlabeled estradiol injected prior to the administration of 3H estradiol reduces or eliminates nuclear uptake of radioactivity. The autoradiographic results demonstrate the existence of estrogen target neurons in the teleost forebrain at sites similar to those described in mammalian brains. However, under the conditions of the experiment, there exists no pallial representation of estrogen target cells.


Sources and terminations of callosal axons related to binaural and frequency maps in primary auditory cortex of the cat. The distributions of sources and terminals of callosal fibers in the high-frequency representation of AI were related to binaural and frequency maps in combined anatomical and electrophysiological experiments. Sources of callosal axons were retrogradely labeled with HRP. Distributions of axon terminals were determined by autoradiographic labeling with [3H]-proline and anterograde degeneration following callosal section. Regions in which cells exhibit summation or ipsilateral dominance and suppression contain higher concentrations of sources and terminals of callosal fibers than do regions in which cells exhibit monaural contralateral responses or contralateral dominance and suppression. Callosal axon terminals aggregate into columns. In sections cut parallel to the cortical surface callosal columns take on complex forms that exhibit certain consistent features. Two prominent elongated columns separated by a narrow zone of sparse callosal innervation run in a rostrodorsal to caudoventral direction through AI crossing several octaves of the frequency representation. Ventral to these columns, along the AI-AII border, less densely labeled callosal columns are in evidence. Low frequency representations of AI are interconnected but details of their innervation patterns were not worked out. Outside of AI there are regions that contain complex configurations of callosal columns. Several morphologically distinct types of neurons, located in laminae III through VI, were retrogradely labeled following injections of HRP into the opposite AI. About 94% of callosal neurons are pyramidal cells of layers III and IV.


Some features of the spatial organization of the central nucleus of the inferior colliculus of the cat. A series of neuroanatomical and neurophysiological experiments have been conducted within the central nucleus of the inferior colliculus (ICC) of the cat in order to determine some features of the spatial organization of the nucleus. Results from these experiments have demonstrated: (1) the origins of the auditory brain stem afferents to ICC and the topography of those projections in relation to the cochleotopic organization of ICC; (2) the segregation of at least some of those brain stem projections within ICC; and (3) ICC neurons with similar response properties (response properties which are often similar or identical to those of neurons in brain stem auditory nuclei) are often clustered within the nucleus. These results provide evidence that the laminated division of the ICC probably consists of anatomically, physiologically, and functionally distinct subdivisions and that some aspects of auditory sensation may be encoded or represented separately (i.e., in spatially distinct "regions") within the nucleus.


Isogenic grasshoppers: genetic variability in the morphology of identified neurons. Although identified neurons are defined as constant and unique from animal to animal within the same species, we might expect to find phenotype variability in the number, morphology, and physiology of identified neurons if we examined them in enough sexually reproduced animals of the same species. Morphological variability and axonal abnormalities were previously encountered in a study of the large ocellar interneurons in 50 grasshoppers. Both the somata and arborizations in the brain of the ocellar interneurons from one or more ocelli can be stained easily and repeatedly with cobalt, so that one can routinely examine the morphology of large numbers of cells in large numbers of animals. In the present study, the large ocellar interneurons were examined in three types of animals: (i) animals from two different breeding populations and their offspring, (ii) the offspring within clutches from single mated pairs of known phenotypes, and (iii) isogenic animals from the parthenogenetic clones of single unmated females. The soma location, axonal pathway, location of arborizations, and fine branching patterns of 14 of the large ocellar interneurons were examined in 430 grasshoppers. The large ocellar interneurons were examined in 11 clones raised in nearly constant and identical conditions. In most of the clones, the morphology of interneurons L5L and L5R was normal; all of the 82 animals examined from clones 4, 7, 9, 10, 12, 13, 16, and 17 were normal. Clones 8 and 2 had high percentages of animals with axonal abnormalities of interneuron L5: 16 out of 24 animals (66%) in clone 8 and 37 out of 42 animals (88%) in clone 2. All of the ocellar interneurons except for L5 were normal in all of these animals. Thus, the abnormal development of at least one identified interneuron, L5, can occur with a high degree of genetic control and a high degree of specificity. The axonal abnormality of interneuron L5 was not the same in each of the 37 animals from clone 2, although common mistakes and patterns were detected.


Proliferative and degenerative events in the early development of chick dorsal root ganglia. I. Normal development. Development of the chick dorsal root ganglia was examined in 4.5- to 9.5-day embryos. Tritiated thymidine (3H-TdR) and autoradiography was used to analyze proliferative activity and the Feulgen procedure to analyze degenerative activity in ganglia 12-17. Proliferative activity was found to be elevated through 4.5 days of incubation when as many as 14% of the ganglionic cells become labelled following a one-hour exposure to 3H-TdR. By 6.5 to 7.5 days proliferative activity decreases to 2-4% in the lateroventral (LV) regions and to approximately 1% in the mediodorsal (MD) regions of the ganglia. However, there appears to be increased proliferative activity by the end of the experimental period at 9.5 days. Birthdate studies demonstrate that large-scale neuronal production occurs between 4.5 and 6.5 days in the LV regions and between 4.5 and 7.5 days in the MD regions. After those times ganglionic proliferative activity must be largely nonneuronal in nature. This nonneuronal proliferation is greater in LV than in MD regions and in brachial than in nonbrachial ganglia. Degenerative activiy was found to be absent from the ganglia until after 4.5 days of incubation. It then increases rapidly, and by 5.5 days 5% of the LV cells in nonbrachial ganglia are degenerating. Degenerative activity then declines but is still present at 9.5 days. In contrast to results of an earlier study (Hamburger and Levi-Montalcini, '49), degenerative activity was also found in the LV region of brachial ganglia and the MD regions of brachial and nonbrachial ganglia. The pattern of LV degenerative activity in brachial ganglia is similar to that in nonbrachial ganglia, but the level of activity is lower. In the MD regions degenerative activity increases throughout the experimental period, and by 9.5 days as many as 4% of the MD cells are degenerating.


Proliferative and degenerative events in the early development of chick dorsal root ganglia. II. Responses to altered peripheral fields. Responses of chick embryo dorsal root ganglia to early wing bud amputation were examined histologically using tritiated thymidine (3H-TdR) and autoradiography to analyze proliferation and the Feulgen procedure to visualize degenerating cells. Right wing buds were amputated at stage 15 or 16. At 4.5 to 9.5 days of incubation embryos were given a 1-hour exposure to 3H-TdR and fixed. Feulgen-stained autoradiographs were examined for percentage of cells labelled (labelling index) or degenerating (degeneration index) in lateroventral (LV) and mediodorsal (MD) regions of brachial (G14-16) and nonbrachial (G12, 13, 17) ganglia. The earliest response to amputation was a highly significant increase in degeneration indices of LV and MD regions of ipsilateral brachial ganglia at 5.5 days. Significant brachial LV responses were observed throughout the remainder of the experimental period. Two peaks occur in this response: at 5.5 days, corresponding to the peak seen in normal nonbrachial ganglia, and at 8.5 days, having no counterpart in normal development. In brachial MD regions significant degenerative responses occur at most times examined. Significant responses also occur at 7.5 and 8.5 days in MD regions of nonbrachial ganglia. The presence of MD responses in our material indicates that maturation of at least some MD neurons occurs earlier than previously thought. Significant labelling responses occur in brachial LV regions from 7.5 days on. Because other studies (Carr and Simpson, '78a) show that this time is after the end of large-scale neuronal production, this labelling response must be nonneuronal in nature. We conclude that this response is a secondary response to amputation, consequent to the greatly increased cellular degeneration. Results of experiments involving addition of limb buds at the brachial level are also presented.


Characteristics of adenylate cyclase activity in pig coronary arteries. Characteristics of adenylate cyclase activity of the intima plus media layer of pig coronary arteries have been studied. Enzyme activity in the 10,000 xg particulate fraction was linear with respect to time and protein during short incubations. Linear kinetics were observed for MgATP as a substrate and free Mg2+ as an activator. Mn2+ added in excess of ATP concentrations was only slightly stimulatory or inhibitory. Adenosine, GTP and GPP(N)P inhibited enzyme activity. Adenosine decreased the Vmax and the Ka for Mg2+ but had no effect on the Km for MgATP. The inhibition by adenosine was reversible, while that by GPP(N)P appeared to be irreversible. Although preincubation of the enzyme with GPP(N)P for short times caused irreversible inhibition, preincubation for more than 15 min caused up to 3-fold activation. Isoproterenol added to the incubation produced no or very slight stimulation with or without GPP(N)P or GTP, and preincubation with isoproterenol alone caused irreversible inhibition. However, preincubation with isoproterenol plus GPP(N)P for 30 min caused irreversible activation exceeding that observed with GPP(N)P alone. These observations suggest that vascular adenylate cyclase, like the enzyme from the other tissues, can exist in multiple states of activity and responsiveness.


Adenylylimidodiphosphate: effect of contaminants on adenylate cyclase activity. Commercially available adenylylimidodiphosphate, APP(NH)P, appears to be contaminated with a variety of compounds. The effects of unpurified APP(NH)P on adenylate cyclase activity closely resembled the effects of guanylylimidodiphosphate (GPP(NH)P); that is, APP(NH)P alone caused a time-dependent, quasi-irreversible activation, and the stimulation of adenylate cyclase by APP(NH)P in combination with epinephrine was synergistic, eliminating the need for GTP. The GPP(NH)P-like activity of APP(NH)P could be separated from APP(NH)P by purification of the analogue on DEAE cellulose columns or by paper chromatography. The purified APP(NH)P does not appear to interest at the GTP site.


Activation of epinephrine and glucagon-sensitive adenylate cyclases of rat liver by cytosol protein factors. Role in loss of enzyme activities during preparation of particulate fractions, quantitation and partial characterization. The role of cytosol components in the loss of rat liver adenylate cyclase activity which occurs during the preparation of particulate fractions from crude homogenates was studied. Epinephrine (5 micron)-, glucagon (10 micron)-, and fluoride (5 mM)- stimulated activities of twice-washed particulates were 31%, 58% and 67% of the homogenate activities, respectively. Addition of cytosol (100,000 X g supernatant devoid of adenylate cyclase activity) restored these activities to 82%, 88% and 80%. Cytosol also increased particulate basal activity from 60% of homogenate activity to 98%. The cytosol components capable of increasing adenylate cyclase activity were heat labile, nondialyzable, stable to freezing at -20 degrees, resistant to change of pH between 2 and 12, and unaffected by EGTA and NAD. Pretreatment with pepsin destroyed the effects of cytosol on both epinephrine- and glucagon-sensitive activities, whereas trypsin destroyed the effect of cytosol only on epinephrine-sensitive activity. The cytosol effect on adenylate cyclase was specific, since several purified proteins and ubiquitin, did not stimulate enzyme activity. Only part of the cytosol effect could be attributed to its GTP content. GTP at the concentration present in cytosol stimulated epinephrine-sensitive activity but significantly less than did cytosol, while GTP had no effect on glucagon-sensitive activity. Dialyzed cytosol retained its effectiveness even after removal of most (97%) of its GTP to a concentration where GTP had only a minimal effect on epinephrine-sensitive activity. Cytosol, unlike GTP, stimulated rather than inhibited activation by fluoride. Cytosol thus appears to contain at least two different protein components, which increase the activity of the two hormone-sensitive adenylate cyclases and presumably account in part for losses of adenylate cyclase activities seen during the preparation of particulates from homogenates.


Lysozyme activity of high-leucocyte-count milk and the effect of heat and potassium dichromate on lysozyme activity. No support could be found for the hypothesis that mastitis, as evidenced by increased leucocyte counts in milk, is accompanied by an increase in lysozyme activity. The presence of potassium dichromate in the preserved milk samples did not seem to affect lysozyme activity. The sensitivity of lysozyme to heat was demonstrated. All lysozyme isolates and purifications were made with deaminated chitin affinity chromatography.


Rumen epithelial cell proliferation accelerated by rapid increase in intraruminal butyrate. Two pairs of adult castrated male sheep were given intraruminally 2 g/kg body weight per day of sodium n-butyrate rapidly 10 s at noon or slowly over 20 to 24 h from noon in four trials in which they received only mixed minerals and water ad libitum. Their ruminal papillae were biopsied just before each administration and 24 h after the final administration. Mitotic indices of the epithelial cells were observed. Mitotic indices were lower than .48% before butyrate administration. In sheep rapidly administered butyrate, mitotic indices increased to 1.29%, 2.33%, 2.65%, and 1.84% in 1 day after the first administration in four trials and tended to decline on later days. In sheep slowly administered butyrate, mitotic indices stayed lower than .50% and did not show significant fluctuations. Our data support our hypothesis that an increase in the rate of intraruminal production of volatile fatty acids promotes proliferation of epithelial cells of the organ.


Heinz body formation in calf erythrocytes. Heinz body formation was induced in calf erythrocytes by a daily dose of 8 mg phenylhydrazine/kg body weight. Body weights and feed intakes were not affected, the glutathione content of erythrocytes was reduced, but the hemolysis rate of erythrocytes was not changed. Morphological changes in erythrocytes were shown by light and high resolution scanning microscopy. The appearance of Heinz bodies may have value as an indicator of oxidative stress under conditions such as copper toxicity or deficiency of selenium-vitamin E.


Hemodynamic effects of acetate in man.

Hemodynamic effects of acetate in man. To determine the action of acetate in man, 1.7mEq/ml of sodium acetate was infused in 10 patients on chronic hemodialysis. It was administered intravenously in 1.5mEq/min for 5 min followed by 3.8mEq/min for another 5 min. As control, 1.71mEq/ml of sodium chloride was infused in a similar manner. Following the infusion of sodium acetate, heart rate increased slightly but significantly (p less than 0.01). Limb blood flow measured in an upper limb by the venous occlusion method, showed an increase in all of them and it was significant( p less than 0.001). The peripheral vascular resistance (=mean arterial blood pressure/limb blood flow) showed a significant fall (p less than 0.001). The analysis of systolic time interval showed a change suggestive of depression of heart function at the end of sodium acetate infusion (p less than 0.05). Such a vasodilating effect or a change in heart function was not observed following sodium chloride infusion. A depressant action of acetate upon the cardiovascular system may be, therefore, concluded.


The evaluation and applications of hemodialyzers for pediatric patients. It is difficult to determine which pediatric hemodialyzer to use in a given clinical situation since there is no comprehensive comparison of pediatric hemodialyzers. We evaluated five currently available disposable pediatric hemodialyzers in vitro and in vivo during treatment of pediatric patients. Two dialyzers, Gambro Mini-Minor and Viva Cell 0.2 are well suited to small pediatric patients weighing less than 10 kg. Three of the dialyzers are well suited to the pediatric patients weighing greater than 10 kg (Gambro Minor, Cordis Dow 0.6, Viva Cell 0.5). By considering the clinical status of the child and the performance characteristics of the dialyzer (solute removal, priming volume, ultrafiltration, etc.) it is possible to employ a hemodialyzer which more precisely meets the needs of the child without increasing risk factors associated with pediatric hemodialysis.


Dialysability of theophylline.

Dialysability of theophylline. We have shown that theophylline is highly dialysable with an average dialysis clearance of 76 ml/min approaching 63% of urea clearance with hemodialysis. Implications include dose adjustment during dialysis and efficacy of dialytic technique in the treatment of theophylline intoxication.


Pulsatile flow in hemodialyzers.

Pulsatile flow in hemodialyzers. The present work is concerned with the calculation of NaCl transfer in flowing solutions and its dependence upon flow characteristics at hemodialyzers. A theoretical analysis of the solute transfer in a hemodialyzer is presented. Experiments were carried out with a continuous flow flat-plate dialyzer. Permeability of cuprophane membranes were calculated both for pulseless and pulsatile flows. It was found that the membrane permeability increases with flow rate but the asymptotic value of pulsatile flow is remarkably higher than that of the pulseless flow. The difference between the transfer capabilities of the two flow regimes was found to be more than 100 percent.


Equipment for control of ultrafiltration in the absence of diffusion. Two devices have been developed for direct control of ultrafiltration during sequential dialysis therapy. Precise control of ultrafiltrate flow rates (+/- 1 ml/min) is obtained over the range of 0 - 38 ml/min.


Ultrafiltration followed by haemodialysis. A longterm trial and acute studies. Separate ultrafiltration followed by haemodialysis (U.F.-H.D.) using Gambro Major or Cordis-Dow hollow-fiber dialyzers were evaluated in 10 dialysis patients over a mean period of 4 1/2 months and 455 U.F.-H.D. procedures. Fluid control was facilitated in oedematous patients but the number of hypotensive episodes during the combined procedure requiring intravenous 5% saline did not significantly decrease. No significant improvement in hypertension was noted. Ultrafiltration (U.F.) alone for acutely water overloaded, azotaemic patients proved very useful. Two to five liters of oedema fluid could be removed asymptomatically in one to three hours using transmembrane pressures of 250 to 500 mmHg and U.F. rates of 10 to 42 ml/min. Two patients became acutely and symptomatically hypotensive. One was an insulin dependent diabetic in whom 3800 ml were removed in 75 minutes and the other a hypertensive patient undergoing treatment with Minoxidil and propranolol.


Evaluation of three dry-sterilized hollow fiber artifical kidneys. We investigated three new dry sterilized hollow fiber artificial kidneys (HFAK) (Cordis Dow CDAK 1.3, Travenol CF 1200, Extracorporeal Tri-Ex 1). Dry sterilization makes these dialyzers more economical by shortening set-up time. Dry sterilization also eliminates iatrogenic administration of residual sterilant. Water of imbibition can significantly increase the blood compartment volume of the dialyzer during dialysis. Consequently, a corrected blood volume for each dialyzer was established; these corrected volumes varied from 13--36% greater than the volume determined before dialysate flow. With low dose heparinization of these dialyzers there was between an 18 and 45% decrease in the post dialysis volume, presumably due to fiber clotting during dialysis. This volume added to the residual blood loss measured by a colorimetric technique accounted for a possible blood loss ranging between 26.9 and 53.9 ml per dialysis for these three dialyzers. Our results suggest that a relationship between dialyzer clotting and decreased dialyzer efficiency may exist. These three capillary flow dialyzers had a much lower platelet drop (0--9% pre to post) when compared to 30--40% drop of flat plate dialyzers. These dialyzers were found to be safe and easy to use but the high fiber clotting warrants further investigation in chronic dialysis patients on high dose heparin.


Evaluation of permeance in peritoneal dialysis. Evaluation of permeance in peritoneal dialysis. Relations were developed to calculate permeance based on a minimum number of experimental measurements. Permeance is the product of the effective peritoneal area times its mass transfer coefficient. The relations were used on clinical data obtained with and without nitroprusside, a direct vasodilator, added to the dialysate. Nitroprusside increased permeance 34% for BUN and about 100% for creatinine and inulin. The equivalent increase in clearance in a 50 minute exchange protocol would be 24, 60, and 83%. Normalized consecutive concentration data obtained every ten minutes in several long exchanges agree well with calculated values supporting the adequacy of the approach. An expression is also given to calculate the residual dialysate volume left from the previous dialysate exchange. The values calculated ranged from 200 to 500 ml.


Intraperitoneal infusion of a nonabsorbable steroid in hemodialysis-associated ascites. Ascites occurring in long-term hemodialysis patients continues to be a difficult management problem. Several modalities have been employed with varying success. Because of the similarities between uremic pericardial effusion and hemodialysis-associated ascites, infusion of the nonabsorbable steroid, triamcinolone hexacetonide, was attempted in five patients with the latter ailment which had become intractable. None of the patients responded and in two there were adverse effects. We conclude that for the management of this variety of ascites, intraperitoneal administration of a nonabsorbable steroid is ineffective and may be accompanied by undesirable reactions.


Hemodialysis and thyroid functions in children. Evaluation of thyroid functions in 16 children receiving maintenance hemodialysis for a mean duration of 17 months showed that the serum T3, T4 and TSH were below normal concentrations for age. However, the measurements of these variables before and after the dialysis procedure did not show any significant changes. The possibility that the chronic uremia may give rise to abnormal TSH secretion and low T3, T4 concentrations is not tested in this study.


Control of bleeding from cannulation sites with topical thrombin in dialyzed patients. Topical thrombin was applied to the cannulation sites during and after withdrawal of the needles. The duration of bleeding was reduced by 50% compared to the control period in patients with various internal arteriovenous communications undergoing maintenance hemodialysis treatment. Accordingly, use of topical thrombin appears effective in saving patients and staffs time, minimizing the blood loss in these anemic patients, and preventing the possible injurious effect of prolonged compression of vascular access to accomplish hemostasis.


Correlation of biochemical parameters in serum and saliva in chronic azotemic patients and patients on chronic hemodialysis. In patients who are receiving chronic hemodialysis treatments, concentrations of creatinine and uric acid in serum correlated significantly with those in simultaneously drawn unstimulated whole saliva, both before and after dialysis. Similar correlation was shown also in a group of moderately azotemic patients who had not yet entered the chronic hemodialysis program. Use of whole saliva in these tests instead of blood samples may reduce the iatrogenic component in anemia, the frequency of venipunctures and of blood samplings. This may be a boon particularly in pediatric patients and in other patients where, due to a variety of reasons, this is desirable.


The composition of a simulated American diet. Comparison of chemical analyses and estimates from food composition tables. Chemical analyses were carried out on a food mixture that approximated the average daily per capita use of foods in the U.S. as of 1965-66. The food items selected were chosen from a list (items and quantities brought into the average household) generated by the USDA's 1965 Household Food Consumption Survey. Our analyses are compared with food table calculations of the items in the homogenate and with the Recommended Dietary Allowances (RDAs). Data are given for total and constituent energy supplies per person per day. The protein:fat:carbohydrate distribution of energy was found to be 18:44:38%. Unavailable carbohydrates totaled 19.1 gm. per person per day (6.8% of total carbohydrate); available carbohydrate fraction is itemized in terms of mono- and di-saccharides, starches, and dextrins. Fat content was 135 gm. per person per day; analyses showed that 16:0, 18:0, 18:1, and 18:2 fatty acids made up 89% of total fatty acids, with a P:S ratio of 0.4. Cholesterol content was 576 mg. per person per day; plant sterols, 228; beta-sitosterol, 165; and squalene, 28. Protein content was 115 gm. per person per day (over twice the recommended allowance); amino acid analyses showed concordance with the RDA estimated requirements of the essential amino acids. Major mineral and vitamin contents are also reported. Calculations and chemical data agreed well in many instances, the largest differences being for total protein, dietary "fiber," and certain vitamins.


Food preferences of enlisted personnel in the Armed Forces. A food preference survey, consisting of 378 food names, was administered to approximately 3,900 personnel of the U.S. Army, Navy, Air Force, and Marine Corps. The survey required the respondent to indicate how much he liked each food (hedonic scale) and how often he wanted it served (preferred frequency scale). Overall, food preferences showed relative popularity of beverages, breakfast foods, and entrées, unpopularity of soups and vegetables, and moderate popularity of the other food classes. Items of particularly high or low preference are statistically identified within each food class. The collection and presentation of these data are intended to assist menu planners of the Armed Forces, as well as others interested in this age group (young men under twenty-six years of age.


Effect of nutritional supplementation in pregnancy. II. Effect on diet. Women judged to be at high risk of delivering low-birth-weight infants were assigned to one of three supplements--high-protein beverage, low-protein beverage, or a vitamin-mineral preparation--to determine: (a) The acceptability of a liquid dietary supplement to pregnant women. (b) The effect of the dietary supplement on diets normally eaten by pregnant women. Acceptance of the high-protein beverage by the women in this study was low. Fifty per cent of the dropouts indicated a dislike for the beverage because of either poor flavor or an inability to tolerate it. The women generally consumed "adequate" diets, although there were variations. Increases in intakes of calories and protein in Group 1 were statistically significant, suggesting the high-protein beverage served as a supplement for both calories and protein; that is, these nutrients were added to the women's existing intake. For the low-protein beverage women (Group 2), statistics revealed the beverage was used as a substitute.


Hierarchical structure of selected behaviors of dietitians on the job. The rationale for learning sequences and hierarchies is presented and briefly discussed. Two methods for identifying hierarchies--Guttman scalogram analysis and ordering theory analysis--are described and demonstrated, using seven items from the Dietitians' Behaviorating Scales, a performance appraisal instrument for dietitians. Scalogram analysis indicated that the seven items did not constitute a linear cumulative scale (CR = 0.75). Ordering theory analysis showed that the seven items constitute a complex branched hierarchy, which is graphically presented. Implications for dietetic education are discussed.


Menu item forecasting systems in hospital foodservice. A cost comparison of two- and three-echelon systems. The forecasting efficiency of two- and three-echelon menu item forecasting systems was compared. Two forecasting models were used with each system, adaptive exponential smoothing and a Box-Jenkins model. The two systems were compared in terms of forecast error costs. The two-echelon system, using adaptive exponential smoothing, was recommended. This technique resulted in the lowest forecast error costs at a majority of the lead times which probably would be used most frequently. Also, this technique was the least complicated of the four techniques which were compared.


Activity sampling in two nursing home foodservice systems. Activity sampling was conducted in the foodservice department of two Wisconsin skilled care nursing homes with bed capacities between 100 and 160. Two seven-day sampling periods about one month apart were conducted in each home with 100 random observations being made each day. Analysis of variance of data indicated that the modified activity sampling technique was reliable in analyzing activities of personnel in nursing home foodservice systems with similar organizational and operational characteristics. In both homes, approximately 81, 9, and 10% of total labor time were spent in direct work, indirect work, and delays, respectively. Mean labor minutes per meal equivalent served (7.48 in Home X and 7.43 in Home Y) were similar. The consistent values for minutes per meal equivalent from Monday through Friday suggest that future activity sampling studies in nursing homes could be less than seven days. When evaluating staffing patterns in nursing home foodservice systems, consideration should be given to both quantitative indexes (minutes per meal, food cost per meal, labor cost per meal and qualitative indexes (sensory, microbial, and nutrient quality of food served), as well as to employee and resident satisfaction with the system.


Insight and creativity.

Insight and creativity. The similarities between the process of creativity in art and science and the phenomenon of insight in psychoanalysis are examined according to the four criteria of thought: categorization, abstraction, context, and association. The thesis is that both creativity and insight are based on a synthesis of the operational modes of the primary and secondary processes.


Psychoanalytic study of an unusual perversion. The psychoanalysis of a case of an unusual perversion demonstrated the historical determinants of the ritual. Drive and defense, bisexual disposition, and identifications were represented. At the beginning of the analysis the patient appeared to have borderline character traits; but as the analysis unfolded, an oedipal situation was revealed and character development occurred. The factors that determined the particular outcome for this patient, instead of homosexuality, or transsexualism, are discussed. In some cases of perversion, such as the one herein described, only psychoanalytic exploration can determine whether a level of personality structure and object relations had been reached that allows for the analysis of the perversion and a shift to heterosexuality and mature object relations.


A selective review of the psychoanalytic literature on theoretical conceptualizations of narcissism. This paper places recent theoretical conceptualizations of narcissism in the context of general psychoanalytic theory. It traces the major changes in the general theory that have relevance for the concept of narcissism. The literature review is organized to examine the concept of narcissism as it relates to drive theory, ego-ideal development and function, the concept of self-esteem, and self- and object relations. Remaining inconsistencies and disagreements between major theoreticians are clarified and areas of conceptual consensus are identified. An overview of the various theories of narcissism is presented with a suggestion for their possible synthesis and integration into the general psychoanalytic theory.


Qualitative change from quantitative change: mathematical catastrophe theory in relation to psychoanalysis. The relation of qualitative change to quantitative change is important to psychoanalytic theory. Until recently no tools were available for dealing with the problem, but the development of catastrophe theory has provided methods for studying it. Psychoanalytic investigators might benefit from the methods of catastrophe theory, and dilemmas arising from the supposed impossibility of relating quantity to quality are seen to allow of solution.


Interpositional arthroplasty for rheumatoid carpometacarpal joint disease. Over the past 3 years the Swanson great toe prosthesis was used in an interpositional arthroplasty at the carpometacarpal joint in 21 thumbs of 19 patients with rheumatoid arthritis and three thumbs of two patients with lumpus arthritis. In selected patients with advanced disease, this prosthesis has the advantage of allowing for correction of deformity while preserving carpal stock which may be important if a surgical procedure is required at the wrist. Stable capsular closure does not require reinforcement by adjacent tendon. Twenty-two thumbs of 19 patients were improved, although in three the prosthesis was malpositioned. Two patients required reoperation and removal of the prosthesis: one for infection, and one for failure to correct deformity. Overall functional results often were affected by the status of disease in other joints, but in general were acceptable.


Assessing ulnar instability of the metacarpophalangeal joint of the thumb. Seven hundred and fifty normal thumbs were examined to determine the normal range of radioulnar mobility of the metacarpophalangeal joint with the joint in full extension, 15 degrees of flexion, and full flexion. Full flexion was the position of greatest stability. Twenty-five adult unembalmed cadaver thumbs were examined to determine the optimal position for testing the metacarpophalangeal joint for ulnar collateral ligament stability. When radial stress was applied to the metacarpophalangeal joint of 20 specimens after cutting the adductor aponeurosis and capsule, minimal ulnar instability was found. However, further sectioning of the ulnar collateral ligament revealed marked ulnar instability most significantly when the thumbs were examined in full metacarpophalangeal flexion. Finally, division of the adductor aponeurosis, dorsal capsule, ulnar collateral ligament, accessory collateral ligament, and volar plate resulted in complete instability of the metacarpophalangeal joint in all positions tested.


A complete dislocation of the thumb metacarpal. Multiple dislocations of a single finger are rare. We report a patient with complete dislocation of the thumb metacarpal, a condition not reported previously. A 9 year follow-up shows the patient to have a normal-appearing, strong, and painless hand.


Abductor digiti minimi opponensplasty in congenital radial dysplasia. Satisfactory results were obtained in 20 of 21 abductor digiti minimi opponensplasties performed in children with congenital radial dysplasia. A modified technique left the muscle attached to the pisiform and did not require complete dissection of the neurovascular structures. An adequate subcutaneous tunnel was made to accept the transferred muscle and laxity of the ulnar collateral ligament of the metacarpal-phalangeal joint of the thumb, a consistent finding in patients with isolated aplasia of the abductor pollicis brevis and opponens pollicis muscles, was repaired by imbrication and suture of one of the tendinous slips to the ulnar capsule.


A clinical study of forces generated by the intrinsic muscles of the index finger and the extrinsic flexor and extensor muscles of the hand. A study of the forces generated by the intrinsic muscles of the index finger and coordinating muscles of the hand found that the intrinsic muscles of the index finger contributed combined forces equivalent to approximately 80% of those generated by the flexor profundus and superficialis, and to 73% of the moment for the motion of metacarpopalangeal flexion with simultaneous interphalangeal joint extension. No current tendon transfer operation can correct this deficit, though several supply sufficient force at the metacarpophalangeal joint to counterbalance the extrinsic extensors.


Aneurysmal bone cysts occurring in the metacarpals: a report of three cases. In three patients an aneurysmal bone cyst occurring in a metacarpal was treated by excising the involved bone and substituting bone grafts. There was no evidence of recurrence in 1, 3, and 8 years of follow-up. In two patients with open epiphyses, growth of the metacarpal was not impaired.


Factors affecting the acquisition of resistance against Schistosoma mansoni in the mouse. I. Demonstration of resistance to reinfection using a model system that involves perfusion of mice within three weeks of challenge. The degree of resistance acquired by Schistosoma mansoni-infected mice against homologous challenge has been determined by perfusion of the animals within three weeks of the challenge, at which time the challenge-derived organisms were morphologically distinguishable from the primary infection which induced the resistance. The method has been compared with assays based on determination of the number of organisms migrating through the lung, and with perfusions at a later time when the challenge has matured. The results obtained with the three week perfusion method, showing that resistance was acquired by eight weeks after a primary infection, were confirmed by the longer survival of, and reduced egg excretion rates and tissue egg burdens in the experimental animals relative to respective challenge control animals. However, some discrepancy in challenge-derived worm numbers was found between animals perfused three weeks after challenge and those autopsied at later times. The possible reasons for this difference are discussed. The degree of resistance that was acquired was to some extent dependent on the size of the challenge infection.


Factors affecting the acquisition of resistance against Schistosoma mansoni in the mouse. 2. The time at which resistance to reinfection develops. Mice developed a partial resistance against homologous challenge with Schistosoma mansoni as early as two weeks after primary infections of 35 to 75 cercariae, and the degree of protection increased to an apparent maximum by 6 weeks. Animals given a primary infection of only 25 cercariae required a longer period to acquire maximum resistance.


Experimental infection of Ancylostoma caninum in mice. III. distribution of larvae after repeated exposures to infection. Different groups of mice were infected with various single or repeated doses of larvae of Ancylostoma caninum. Considerable loss of larvae occurred in the immunised groups when compared with their counterpart unimmunised groups. Larval migration and distribution in the different tissues was less in immunised mice, as most larvae were expelled from the gastrointestinal tract. This resulted in a poor onward larval migration to liver, lungs, brain and muscle regions in immunised groups. The heavily immunised group infected five times was most affected and a significant lesser larval distribution in various organs and muscle region observed.


Tapeworms of the Chaco Boreal, Paraguay, with two new species. Mathevotaenia paraguayae sp. n. is described from Euphractus sexcinctus. It differs from M. didelphidis (Rud.) in having a transverse cirrus pouch anterior to the vagina. Monoecocestus mackiewiczi sp. n. was found in Phyllotis sp. It differs from M. parcitesticulatus Rego in having a much smaller scolex, a poral ovary, and a cirrus pouch 360 to 440 micrometers long. Other species reported are Taenia macrocystis, Taenia omissa, Spirometra mansonoides, Spirometra gracilis, Spirometra longicollis, Diphyllobothrium trinitatis, Atriotaenia parva, and Mathevotaenia tetragonocephala.


Allohymenolepis palawanensis sp. n. (Cyclophyllidea: Hymenolepididae) from the Philippine bird, Nectarinia jugularis (Tweeddale 1878). Allohymenolepis palawanensis sp. n. from a yellow-breasted sunbird, Nectarinia jugularis, in Palawan, Republic of the Philippines, is characterized by possessing a sucker diameter of 52-56 micrometer, a scolex of 120 X 157-166 micrometer, ovary 25-40 X 71-90 micrometer, and a vitelline gland of 17-25 micrometer.


Paratrichosoma crocodilus n. gen. n. sp. (Nematoda: Trichosomoididae) from the skin of the New Guinea crocodile. A new genus of nematode (Paractrichosoma crocodilus) is described from Crocodilus novaeguinae. Adults have typical trichuroid features but elongated stichocytes (over 1 mm in female). Males are one third to one half as long as females and have no spicule or sheath.


The influence of physical factors on the behaviour and infectivity of miracidia of Schistosoma mansoni and S. haematobium. III. Effect of contact time and dispersion in static and flowing waters. The scanning and infective capacity of Schistosoma mansoni and S. haematobium miracidia were tested under limited exposure times in small volumes of water, and under increasing mutual dispersion in vessels of different sizes also over increasing horizontal distances, and under different flow rates of water. It was found that the miracidia of both species retained their infective capacity for up to 1 hour in the presence of susceptible snails. The infection rates decreased with decreasing miracidial densities but was still over 50% at 0.4--0.8 miracidia per litre. Both species of miracidia produced high (36--44%) infection rates in host snails situated at a distance of 5 m and equally high infection rates (39--40%) in snails placed in water flowing at a rate of 12--15 cm/sec. The application of any of these physical factors in the control of schistosomiasis is discussed.


Revision of the genus Paracooperia Travassos, 1935 (Nematoda: Trichostrongylidae). Only five of the eight species assigned to the genus Paracooperia are considered valid and are  redescribed. P. petrowi Memmedov, 1961 and P. indiana Ali and Deshpande, 1970 are considered synonyms of P. nodulosa (Schwartz, 1928) Travassos, 1937 and the synonymy of P. matoffi Le Roux, 1950 with P. nodulosa is confirmed. A key to the species of the genus is given and their hosts and geographical localities are listed.


Life history of Genarchopsis goppo Ozaki, 1925 (Trematoda: Hemiuridae) from the freshwater fish Channa punctata. The life cycle of Genarchopsis goppo a hemiurid trematode found in the stomach of Channa punctata has been worked out in detail. The egg contains a fully developed miracidium at the time of liberation. The miracidium contains a ciliated covering, a long apical gland and a crown of spines at the anterior end. The snail Amnicola travancorica acts as the first intermediate hose inside which the miracidium passes through sporocyst and redial generations. The cercaria is of cystophorous type and is identical to Cercariae Indicae Sewell XXXV. Metacercaria occurs in the ostracods Stenocypris malcolmsoni and Eucyoris capensis. The fish Aplocheilus panchax serves as the paratenic host. The entire developmental cycle from egg to egg producing adult takes 3 months.


Localization of chitin in algal and fungal cell walls by light and electron microscopy. Chitin was visualized in cell walls after hydrolysis with potassium hydroxide and subsequent postfixation of the deacetylated polysaccharide (chitosan) in OsO4. Areas of chitin deposition appeared dark borwn by light microscopy and electron dense in the electron microscope. With this method, the presence of chitin was demonstrated in the cell walls of the green alga Pithophora oedogonia (Montagne) Wittrock and two fungi, Ceratocystis ulmi Buism. (C. Moreau) and Blastocladiella emersonii Cantino and Hyatt. Most of the chitin in P. oedogonia ws found in the crosswall disk and small amounts occurred in the outer longitudinal walls. The septal disk of C. ulmi also contained chitin, but significant amounts were present in the inner and outer regions of longitudinal walls as well. Chitin was present throughout the walls of B. emersonii. Small amounts of chitin were not easily demonstrated by this technique, but removal of chitosan by exposure to dilute acetic acid before osmium fixation disrupted cell wall integrity, suggesting that small amounts of the structural polysaccharide had been removed.


Device for quantitative cytochemistry: a computerized scanning microdensitometer 'grain counter'. A computerized scanning microdensitometer and autoradiographic grain counter was able to provide quantitative data on the cytochemical final reaction product formed within a single cell and also quantitate the kinetics of its formation. Optical density and area measurements were performed on hundreds of leukocytes from slides previously stained to demonstrate any one of a variety of reactions. These included cellular glycogen, lipids, peroxidase, esterases, alkaline phosphatase, and acid phosphatase. In addition to these slide studies, chamber studies with an adapted Dvorak-Stotler Chamber allowed the measurement of enzyme kinetics within single cells.


Ultrastructural localization of alkaline phosphatase in rat eosinophil leucocytes. The ultrastructural localization of alkaline phosphatase in eosinophil leucocytes, obtained from experimentally-induced peritoneal exudates in rats, has been studied using an osmiophilic technique with 2-naphthylthiolphosphoryl dichloride as substrate, fast Blue BBN as diazonium salt and postosmication with 1% aqueous osmium tetroxide. With this method identical incubation procedures could be used for both light and electron microscope examination. Eosinophils were the only cells which contained alkaline phosphatase. The enzyme was predominantly associated with the outer surface of the plasma membrane, being present in much lower concentrations in cytoplasmic cisternae. Eosinophil granules only rarely showed reaction product. The plasma membrane location of alkaline phosphatase in eosinophil leucocytes is identical to that recently demonstrated in the human neutrophil.


Permanent fluorescent staining of nucleic acids in isolated cells. Staining of fixed cells, blood smears and chromosomes with 0.1% w/v of 3, 5, 7, 2', 4'-pentahydroxyflavanol (morin dehydrate) in 70% ethanol after brief mordanting with 5% w/v aluminum ammonium sulfate results in permanent fluorescence of cellular nucleic acids. Incubation in ribonuclease solution before mordanting, or 5-min hydrolysis with INHCL at 60 degrees C selectively abolishes RNA fluorescence, while the incubation in deoxyribonuclease solution abolishes DNA fluorescence. The morin-mordant complex bound to nucleic acids is stable to photodegradation and up to five years of storage.


Simultaneous localization of an hepatic binding protein specific for galactose and of galactose-containing receptors on rat hepatocytes. The hepatic binding protein, specific for galactose-terminated glycoproteins (asialoglycoproteins) and the receptors for the Ricinus communis lectin, specific for galactose residues (RCA1), were simultaneously localized on isolated rat hepatocytes by the gold method. The marker for the binding protein was prepared from gold granules (5 nm in diam.) labeled with ceruloplasmin and desialylated. The marker specific for galactose-containing receptors consisted of granules (17 nm in diameter) labeled with RCA1. It was established that both markers did not interact. Hepatocytes (fresh or briefly fixed with glutaraldehyde) were successively incubated with the asialoceruloplasmin and the RCA1 marker. Examination of thin sections by electron microscopy indicated that the binding protein and the RCA1 receptors were often in the proximity of each other on the plasmamembrane. Using the same technique, wheat germ agglutinin (WGA) receptors were generally found on area of the plasmamembrane poorly marked by the RCA1 gold marker. The binding of asialoceruloplasmin gold markers was studied as a function of the size of the granules. It became insignificant when the size was above 17 nm. Previous results have shown that the binding of RCA1 is low when the marker reaches 50 nm in size while WGA markers up to 75 nm are well bound by hepatocytes. It is therefore hypothesized that the binding protein and RCA1 receptors are located between glycoprotein brushes of increasing spacing while part or all of the WGA receptors are located at the periphery of the brushes.


Lactate-dehydrogenase activity in the rat testis: a comparison between fluorometric assay of freeze-dried sections and histochemical localization with phenazine methosulphate. The activity of lactate dehydrogenase (LDH) in freeze-dried sections of rat testes was determined by using a fluorometric assay method and found to be 4.47 +/- 0.23 moles/Kg dry weight/hr (MKDH +/- S.E.M.) in whole sections, 3.31 +/- 0.16 in tubules and 12.0 +/- 1.9 in interstitial tissue. The activities and regional variation are similar to those measured in nervous tissue and are well correlated with the histochemical localization of LDH activity when phenazine methosulphate (PMS) is not used as an electron carrier. LDH and lipoamide dehydrogenase activity have the same histochemical distribution and there is no nonspecific staining with either method. The use of PMS results in reduced dependence on substrate and coenzyme and does not indicate higher interstitial activity but may provide an indication of developing lactate metabolism in maturing sperm. It is recomended that methods with and without PMS be used in studies of LDH activity in the testis.


Developmental distribution of microperoxisomes in the rat submandibular gland. The present study investigated the size, number, and distribution of microperoxisomes (MP) during the prenatal and postnatal development of the rat submandibular gland (SMG). A three-fold increase in MP number per cell was observed in the cells of the rudiment from the 15th to the 16th day of gestation. The early secretory and striated duct cells contained about 9.0 MP. The number of MP per secretory cell decreased such that 3.5 MP were found in each mature acinar cell. In the striated duct cells, MP number progressively increased to 40.0. As the convoluted granular tubule cells (CGT) developed from striated duct cells there was an increase in MP number from 16.0 to 26.0/cell. At maturity, the convoluted granular tubule cells contained only 14.0 MP. Throughout development of the SMG, intercalated duct cells showed only rare MP. The data suggests that the number, size, and distribution of MP changes as a function of the particular path of differentiation followed by the various cells in the rat SMG.


Stereotype content and social distance: changing views of homosexuality. This project examined effects of stereotype content and uniformity on social distance regarding homosexuals. Administration of an adjective checklist and social distance scale to 538 undergraduates resulted in identification of "traits" that change social distance. Those traits that positively correlated with distance at or beyond the .05 level were: "cowardly," "sly," "suspicious," "shrewd," "stupid," "impulsive," and "ignorant." Traits that correlated with reduced distance ("sensitive," individualistic," "intelligent," "honest," "imaginative," "neat," "reserved," "alert," "kind" "faithful," "courteous," "sophisticated," and "artistic") were more uniform. Both clusters of negative and positive traits were moderately intercorrelated within and suggest that they each represent underlying dimensions. It is suggested that sterotypes about homosexuals are changing in a more positive direction.


Sexual orientation survey of students on the San Francisco State University Campus. This study examined the sexual orientations of students on the campus of San Francisco State University. The sample consisted of 1,039 students who responded to a questionnaire administered in their classes. The results were as follows: (a) significantly more males than females reported the homosexual orientation for both behavior and feeling; (b) about the same proportion of whites and nonwhites reported the homosexual orientation for behavior; and (c) significantly more students in majors emphasizing "divergent" thinking than those in majors emphasizing "convergent" thinking reported the homosexual orientation for behavior. The first two findings were explained in terms of the differentiated and related development of social sex-roles and sexual orientation in females and males and minority and majority groups. The last finding was explained in terms of divergent and convergent thinking of students who choose particular disciplines.


Sex-role self-concepts of homosexual men and their attitudes toward both women and male homosexuality. A nonclinical sample of 88 homosexual males responded to a questionnaire that assessed their sex-role self-concept and their attitudes toward both women and male homosexuality. Results indicated that in terms of socially valued masculine and feminine characteristics, the majority of homosexual males viewed themselves as predominantly androgynous. These respondents also favored equality between the sexes, reflecting positive attitudes toward women. Similarly, those homosexual men who supported equality between the sexes also held more positive attitudes toward male homosexuality.


"Personals" advertisements of lesbian women. Based on a design adapted from previous content analyses of the "Personals" advertisements of heterosexual men and women and of homosexual men, advertisements for lesbian partners were studied in the light of predictions derived from exchange theory and from the findings of other studies of lesbianism. Lesbians' advertisements, as hypothesized, were found to emphasize positive characteristics and to de-emphasize the negative; to be more like those of nonlesbian women advertisers than like those of men of either sexual orientation; and to tend toward an androgynous style. Implications of these and other findings are discussed.


Men who advertise for sex.

Men who advertise for sex. This content analysis of 1,111 paid ads in the Advocate identifies 17 self-descriptive categories in the "Personals" (PER) and "Models, Masseurs, and Escorts" (MME) sections of the "Trader Dick" supplement. Advertisers place primary emphases on sex and masculinity. Among MME, youthfulness, handsomeness, and sexiness are important, promoting versatility in place of specificity when mentioning sexual acts. PER advertisers, however, indicate concerns about age, race, and finding lovers. They also detail specific sexual interests and reject a variety of unacceptable behaviors.


Food choice and the US dietary goals.

Food choice and the US dietary goals. Nobody has a completely free choice of food, but we may be so used to the limits of our choice that we are not aware of them. The purpose of this paper is to review proposals which have been put to the US Government and which, if followed through, would change the boundaries of food choice. To begin with, therefore, the framework of food choice is briefly considered. The paper falls into three parts: a general discussion on food choice, a review of the US proposals, and a discussion of their implications.


Anorexia nervosa: dietary treatment and re-establishment of body weight in 20 cases studied on a metabolic unit. This paper reviews the nutritional treatment and weight progress of 20 patients with anorexia nervosa studied in a teaching hospital metabolic unit between January 1974 and August 1977. The classification of patients, their pre-admission dietary intakes and weight status are compared. The method of re-establishing weight by closely monitored normal nutrition under conditions of bedrest and chlorpromazine medication are described. It is illustrated by the progress of one 14-year-old girl patient and the study of the rate of increase in weight of the whole group. Satisfactory weight levels were attained by all patients with acceptable time limits.


A trial of bran and bran biscuits for constipation in mentally handicapped and psychogeriatric patients. Six elderly psychiatric and 17 mentally handicapped individuals suffering from severe constipation received 3 week periods of treatment with 10 g unrefined bran, three bran biscuits, and Senokot syrup daily or three times weekly. There was no significant difference in the number of bowel movements or enemas or in the consistency of the motions. The results suggest that bran may be substituted for laxatives.


Determinants of pediatric care utilization. The purpose of this paper is to understand the determinants of utilization of pediatric care--care rendered to children by all physicians. Multivariate techniques are employed to examine four measures of pediatric care utilization in a national sample of children between the ages of 1 and 5. These measures are the probability of contacting a physician within the past year, the probability of obtaining a preventive physical examination within the past year, the number of office visits to physicians in private practice by children with positive visits, and the average quality of these visits.


The norms hypothesis and the demand for medical care. Our results cast doubt on the validity of the norms hypothesis--that physicians treat patients in accordance with the average or modal insurance coverage in an area. The one study in the literature directly supporting this hypothesis is misspecified; when more correctly specified, it provides no support for the hypothesis. Two versions of the hypothesis are distinguished. the stronger maintains that physicians do not take account of within-area variation in insurance coverage. This version is firmly rejected by the data. A weaker version says that the physician does take account of within-area variation but that between-area differences in average coverage have an independent effect on demand. Little or no support is found for this version, but our data do not permit very powerful tests.


Illness prevention and medical insurance. A theory of demand for preventive medical services is developed from a model of an expected-ultility-maximizing consumer. Preventive medical care is said to alter the probabilities of illness as well as the final health outcome in sick states. The value of preventive medical care depends upon pure health gains (which directly increase utility), work-loss-time avoided, and out-of-pocket medical expenses avoided. Studies cited from the literature show that many commonly accepted screening procedures have no observable payoff in health status or medical expenses saved. In stark contrast, personal behavioral decisions, such as smoking and dietary patterns, appear to have dramatic effects on health and mortality. Public policy appears to be better directed toward inducement of such health-producing behavior than inducement of further medical preventive procedures.


Physician-induced demand for medical care. This paper addresses the theoretical models designed to ascertain the existence of a variable level of physicians' activity in shifting the demand of their patients. Two basic approaches are followed: equilibrium models of the demand for health care, and disequilibrium models. Within the former category, both competitive and monopolistic behavior are studied. Using the monopolistic model, a statistical test of the hypothesis of "no induced demand" is constructed, and fails to reject it. The disequilibrium analysis of other writers is analyzed and alternative specifications of such a model are set out.


The effects of advertising--lessons from optometry. We examine the effect of advertising bans on the price of optometric examinations. Advertising is viewed as an information medium which enables consumers to search for lower prices, to the relative disadvantage of high-cost, low-volume sellers. Self-interest leads these sellers to support bans on advertising. An empirical section shows that price is 16 percent higher in states that ban optometric and optician price advertising, when examination length, procedures, and office equipment are held constant. The two advertising bans work by interaction--both must be present to raise significantly the price of eye examinations.


The supply of surgeons and the demand for operations. This paper presents a multiequation, multivariate analysis of differences in the supply of surgeons and the demand for operations across geographical areas of the United States in 1963 and 1970. The results provide considerable support for the hypothesis that surgeons shift the demand for operations. Other things equal, a 10 percent increase in the surgeon/population ratio results in about a 3 percent increase in per capita utilization. Moreover, differences in supply seem to have a perverse effect on fees, raising them when the surgeon/population ratio increases. Surgeon supply is in part determined by factors unrelated to demand, especially by the attractiveness of the area as a place to live.


On the rationing of health services and resource availability. Government controls on availability of physicians and hospital resources can counteract some undesired aggregate consequences of reimbursement insurance. Given aggregate controls, many important questions arise concerning nonprice rationing of services by physicians. A theoretical model of rationing should be consistent with existing items of evidence on delays, disequilibrium, and "availability effects." The model discussed in this paper has a foundation in the mutual advantages of a long-term association between an individual client and physician; these advantages motivate an implicit contract for rationing with a variety of testable implications.


Medical staff characteristics and hospital costs. In order to test the hypothesis that medical staff physicians affect hospital behavior, this paper relates cost data for a sample of non-major-teaching, short-term hospitals to information on the characteristics of the medical staff which treats patients in those hospitals. Measured characteristics of the staff include specialty mix of attending physicians, board-certification status, and the concentration of hospital output among attending physicians. Medical staff variables are found to be as important as measured casemix in explaining cost variation across hospitals. The results are shown to have implications for behavioral models of the hospital and for hospital reimbursement policy.


beta-Estradiol reduces natural killer cells in mice. beta-estradiol was administered to mice continuously by diffusion from a silastic tube that was implanted subcutaneously at 4 weeks of age. Four to 6 weeks of estrogen administration caused a substantial reduction in natural killer cell activity in the spleens from mice of either sex. Androgen (5alpha-dihydrotestosterone) did not. Castration of male or female mice did not affect natural killing and did not alter the effect of beta-estradiol. Estradiol did not affect natural killing in vitro and the loss of natural killing was not due to a soluble or a cellular suppressor of natural killing. The effects of estradiol were not dependent on the thymus, since estradiol reduced natural killing in mice that had been neonatally thymectomized. After removal of the estrogen implant, natural killing recovered over a period of 8 weeks. The loss of natural killing may reflect a loss of bone marrow secondary to estrogen-induced osteosclerosis.


Structural studies on the murine IA alloantigens. II. Molecular weight characterization of the products of the I-A and I-E/C subregions. Murine splenocytes were radiolabeled with 3H- and 14C-amino acids; the Ia alloantigens encoded by the I-A and I-E/C subregions were isolated by immunoprecipitation and analyzed for structural variation by polyacrylamide gel electrophoresis. The I-A subregion products (k, d, and b haplotypes) are composed of two polypeptides, alpha and beta, with m.w. of 34,000 and 26,000 daltons, respectively. Haplotype-associated differences in m.w. were detected in the I-E/C products of the k, r, p, and d haplotypes. The alpha and beta chains of E/Ck and E/Cr are 34,000 and 28,000 daltons, respectively; E/Cp and E/Cd molecules are composed of 31,000 and 29,000 dalton polypeptides. Thus, there is both subregion (I-A vs I-E/C) and haplotype (E/Ck, E/Cr vs E/Cd, E/Cp) associated variation in the m.w. of the Ia alloantigens. Additionally, the covalent vs noncovalent association of the Ia subunits was examined and it was found that the alpha and beta chains of both I-A and I-E/C are not covalently associated. However, the I-A alpha and beta chains tend to associate through disulfide bonds during detergent lysis; the presence of alkylating agents during cell lysis prevents this association, and only free alpha and beta chains are observed under nonreducing conditions.


Induction of lymphocyte colony formation in vitro by protein A. Human lymphocyte colonies were grown in semi-solid culture in the presence of staphylococcal protein A. The best results were obtained when 1 X 10(6) lymphocytes were cultured for 5 to 7 days with 25 to 50 microgram of protein A per dish. A lineal relationship was observed between the number of cells seeded and the number of colonies developed. An increased number of colonies was seen in cord blood culture compared with that in child and adult peripheral blood. The addition of 5 X 10(-5) M of 2-ME to the culture approximately doubled the colony counts. The cells harvested from the colonies contained about 70% of E-RFC and 20% of EAC-RFC.


Immune response to a mammary adenocarcinoma. V. Sera from tumor-bearing rats contain multiple factors blocking cell-mediated cytotoxicity. Sera from Fischer rats 3 to 13 days after i.p. injection of syngeneic 13762A mammary adenocarcinoma contain three factors specifically blocking cell-mediated cytotoxicity (CMC). The major blocking factor is a 160,000-dalton IgG that combines specifically to cytolytic lymphocytes but not to tumor cells or tumor antigen, and that is not dissociated after treatment with 8 M urea. The other factors have been putatively identified as tumor antigen (less than 70,000 daltons) and as soluble antigen-antibody complexes (greater than 200,000 daltons). Injecting the tumor antigen into tumor-free rats induced spleen cells specifically cytotoxic to the 13762A tumor and provided partial protection to challenge with live tumor cells. Treating soluble antigen-antibody complexes with 8 M urea decreased the size of the blocking activity from greater than 200,000 to less than 70,000 daltons. Although the IgG fraction dissociated from the complex did not block CMC, it did recombine with the tumor antigen fraction to transfer activity to the greater than 200,000-dalton fraction. In contrast, mixing tumor antigen with the IgG fraction that did block CMC did not alter the size of the blocking activities.


Rat mast cell-eosinophil interaction in antibody-dependent eosinophil cytotoxicity to Schistosoma mansoni schistosomula. The involvement of IgG2a antibodies and mast cells in antibody-dependent eosinophil cytotoxicity suggested a possible interaction between mast cells and eosinophils for in vitro killing of Schistosoma mansoni schistosomula. Cell purification procedures showed that a minimum ratio of mast cells was required to obtain eosinophil cytotoxicity. The incubation of mast cells with heat-aggregated IgG2a immunoglobulins before addition to a mast cell-depleted eosinophil population induced a significant degree of inhibition of cytotoxicity, Similarly, the heat-aggregated IgG2a Fc fragment had a strong inhibitory effect whereas incubation of mast cells with Fab fragment failed to inhibit the cytotoxic effect. The Fc portion of IgG2a immunoglobulins therefore seemed to be involved in binding to the mast cell surface. Furthermore, it was demonstrated that soluble mediators released after mast cell activation either by compound 48/80, or by IgE, or IgG2a-dependent reaction had the same effect as intact mast cells. These observations suggest that the eosinophil-dependent cytotoxicity mechanism requires a signal provided by soluble mast cell mediators in addition to antibody.


The binding of activated C3 to polysaccharides and immunoglobulins. The nature of the acceptors for activated C3 present on immunoglobulins was studied by using the fixation of C3 to Sepharose beads after activation with trypsin as a model system. C3 fixation to Sepharose is a property exclusively linked to the short active state of C3. This binding could be inhibited by various carbohydrates and their affinity for C3 was calculated from the extent of the inhibition of the binding of C3 to Sepharose. Mono-, di-tri- and tetrasaccharides showed on a molar basis an increasing but still weak affinity for active C3. The C3 fixation of Sepharose could be inhibited by immunoglobulins and the degree of inhibition was proportional to the hexose content of the immunoglobulin preparations. The isolated polysaccharide moiety of IgG gave the same inhibition as the intact IgG. In addition cell wall polysaccharides of Salmonella abortus equi were found to have a high affinity for active C3. Thus, the more complex polysaccharides such as those present on immunoglobulins and cell walls might function as acceptor for activated C3.


Evidence for a silent or null gene in hereditary C2 deficiency. Three generations of a family with hereditary C2 deficiency were studied, Six members heterozygous for C2 deficiency were identified by serum C2 levels that were approximately 50% of normal C2 values and the identity was supported by HLA analysis. All six members with low C2 levels had only a single electrophoretic variant. Two of four children did not have the variant found in the parent from whom they inherited the partial C2 deficiency. It is inferred that the low levels of C2 result from the inheritance of a silent or null gene, C2D allelic with the structural genes controlling the electrophoretic variants.


The rapid isolation of ribonuclease-free immunoglobulin G by protein A-sepharose affinity chromatography. A rapid method is described for the simultaneous removal of contaminant ribonuclease activity and isolation of immunoglobulin G from fractionated or whole serum using insolubilized protein A. Protein A, isolated from the Cowan I strain of Staphylococcus aureus, was covalently attached to Sepharose CL-4B resin and used as a specific affinity absorbent for immunoglobulin G. Affinity column-purified immunoglobulin G preparations were examined for the presence of contaminating serum proteins, retention of antibody activity, and retention of antigenic properties. Following chromatography on protein A-Sepharose, immunoglobulin G preparations were devoid of contaminating serum proteins, in particular ribonuclease activity, that are not normally removed using conventional techniques of salt precipitation in combination with ion-exchange chromatography. There was no significant alteration of either antibody activity or antigenic properties of protein A-Sepharose purified immunoglobulin G.


Tissue typing of cells in culture. I. Distinction between cell lines by the various patterns produced in mixed haemadsorption with selected multiparous sera. From over 3000 sera of multiparous women about 150 were selected that reacted with some (between 1--50%) of a panel of 20--30 non-HeLa cell lines, mostly of tumour origin. In the mixed haemadsorption method the diameters of zones formed by certain sera on particular cultures were measured and scored. The haemadsorption culture patterns produced by 70--135 discriminating sera were compared in pairs with the patterns formed on other cell lines. Comparisons between replicate cultures gave 'significant' differences with 0--10% of the sera used. In these instances deviations were in one direction, whereas in every other pair comparison, deviations were in both directions. It is concluded that in cases where pair comparisons initially give only 10%, or fewer significant differences, tests using carefully selected sera or typing for HLA-antigens should be performed. When comparisons yield more than 10% significant differences and deviations occur in both directions, cultures may be considered different.


Rapid lymphocyte immunoreactivity test utilizing [3H]uridine in vitro. A microculture assay utilizing [3H]uridine incorporation was developed to test murine spleen lymphocyte immunoreactivity in vitro. Parameters of the culture technique which included cell density, doses of LPS, Con A, PHA, [3H]uridine levels, and length of culture time were investigated. Responses were detectable at 4 h for all 3 mitogens, with labeling ranging up to 180% of the control value. By 8 h there was a 200--350% increase in mitogen-induced incorporation of radioactivity. Similar increases were observed in a serum-free system. The responses were the result of increased incorporation of label by stimulated cultures rather than decreased labeling of non-mitogen treated cultures over time. The [3H]uridine incorporation was demonstrated to be the selective response of T or B cell populations when stimulated with appropriate lectins. This assay detects early RNA synthesis, as supported by experimental observations in which accumulation of radioactivity in stimulated lymphocytes was TCA precipitable, resistant to SDS treatment, and inhibited by actinomycin D.


A micro immunoassay method for measuring IgG antibodies using staphylococcal protein-A. A micro radioimmunoassay procedure has been developed for assaying IgG antibodies to ragweed and grass allergen components. The method offers a rapid and reproducible procedure for estimating antibodies in human sera and is well adapted for monitoring immunological responses following hyposensitisation therapy.


Hematological response of rabbits to chronic, repetitive, severe bleedings for the production of antisera. A study was undertaken to determine whether large amounts of blood (antiserum) could be rapidly removed from rabbits over a two-month period using a simple suction technique. It was found that half a blood volume could be readily removed each week (over 900 ml/rabbit/54 days) without a single fatality. The rabbits efficiently replaced the essential components of their blood during the experimental period as shown by a study of their blood parameters. They moderately overcompensated in replacing some of their blood components after a 6-week rest period. The study demonstrates that rabbits are satisfactory (in lieu of larger animals) for supplying relatively large amounts of antisera.


On the stability of IgE antibodies.

On the stability of IgE antibodies. Mouse and rabbit IgE antibody-containing sera do not lose sensitivity capacity when stored at -20 degrees C even for 2 years or when lyophilized.


Use of logit paper in determination of superoxide dismutase activity in human blood cells. Superoxide dismutase activity of the human blood cells was determined by the capacity to inhibit nitrite formation from hydroxylammonium chloride. Relationship between percentage of nitrite formation and amount of purified human erythrocyte superoxide dismutase was plotted on conventional graph paper, double log and logit papers. A comparison of the results showed that a linear relationship was obtained only with the logit paper, and thus a more accurate and simple estimation of the activity can be made on a single determination of the specimens.


A micro-version of the 51Cr release assay for cytotoxic lymphocytes. A micro-version of the 51Cr release assay for cytotoxic lymphocytes has been devised, which is conducted in Terasaki plates, in a total reaction volume of 8 microliter. The conditions necessary to make the microassay equivalent in sensitivity and reproducibility to the standard macroassay are described. In comparison with the standard macroassay, the microassay provides a 10-fold reduction in the number of effector cells employed and represents a 50-fold reduction in reaction volume. The assay has been particularly valuable in the saving of antisera when these are employed to block target cell lysis, or to selectively inactivate cells of a particular phenotype in the effector cell population.


Measurement of functional C2--a method for clinical laboratories. A method is described which measures functional C2 in human serum using the readily available reagents, sensitised sheep erythrocytes, zymosan-treated normal human serum, and guinea pig serum.


The use of the radioimmunoprecipitation-PEG assay (RIPEGA) to quantify circulating antigens in human and experimental schistosomiasis. A new procedure, the radioimmunoprecipitation-PEG assay (RIPEGA) is proposed for the quantitation of total circulating schistosome antigens (CSA) and circulating antigen '4' in patients, mice and rats infected with Schistosoma mansoni. This sensitive and reproducible method was performed by incubation of [125I]anti-S. mansoni rabbit antibodies (for the detection of CSA) or [125I]anti-antigen '4' antibodies (to detect antigen '4') with sera. Separation of free from complexed antibodies was achieved by a 7% polyethylene glycol (PEG) precipitation. In human schistosomiasis, both CSA and antigen '4' were detected. A direct relationship was observed between S. mansoni egg output and the incidence of CSA. Moreover, all the patients with more than 500 eggs/g stool showed antigen '4' in serum. Both CSA and antigen '4' were also detected during the course of S. mansoni infection in mice. CSA was increased in two distinct periods after infection; the first between the 50th and the 70th day and the second after the 80th day of infection. The antigen '4' became detectable in infected mice after 45 days of infection. In rat schistosomiasis, only CSA was studied. It was demonstrated in two distinct periods after infection, between the 4th and the 6th week and between the 11th and the 14th week. Because of its sensitivity and its ability to detect and quantify CSA and circulating antigen '4', the RIPEGA is recommended for the clinical studies of schistosomiasis.


Antibody-dependent cellular cytotoxicity and natural cytotoxicity: effect of pre-treatment of human lymphocytes with deionised water and ammonium chloride. Deionised water is an efficient red blood cell lytic agent with no demonstrable deleterious effects on ADCC and natural cytotoxicity (blood and tonsil). Treatment with isotonic ammonium chloride, however, produces a significant reduction of both ADCC and natural cytotoxicity. This reduction is less pronounced if the treatment is carried out at 4 degrees C and is temporary, recovery occurring over a 24 h period of incubation at 37 degrees C.


Microcytotoxicity assay for cell-mediated immunity enumerating residual target number by 86Rb. Lymphocyte-mediated lysis of target cells grown as monolayers in microtiter wells is readily quantitated by an assay measuring the 86Rb incorporated after attaining isotopic equilibrium. Lysis of fibroblasts by allogeneic lymphocytes sensitized by skin grafts and of tumor cells by syngeneic spleen cells sensitized by intraperitoneal tumor inoculation were readily detected. Weakly cytolytic lymphocyte populations can be assayed by increasing incubation times to 48 h or longer. A potential problem, 86Rb incorporation by lymphocytes sticking to residual target cells, was controlled by comparing 86Rb incorporation by targets incubated with non-immune lymphocytes. Results by 86Rb incorporation were identical to those determined by microscopic counting or 51Cr release. 86Rb incorporation assays should be considered as an alternate to 51Cr release techniques, especially in those experimental systems where the cytolytic potential of a lymphocyte population is so low that lysis can be detected only after long incubation times and/or when the spontaneous release of 51Cr is prohibitively high.


The determination of lymphoid cell chimerism using peripheral blood lymphocytes from murine bone marrow chimeras. A simple, rapid and accurate method was devised for deteriming lymphoid cell chimerism in bone marrow-reconstituted mice. Chimeras were produced by reconstituting lethally irradiated mice with semi-allogeneic bone marrow cells. Lymphocytes from the peripheral blood of individual chimeric mice were purified by sedimentation in dextran solution and differential flotation in Ficoll-Hypaque gradients. From 250--500 microliters of blood, 1--7 X 10(5) cells were routinely obtained. The extent of chimerism was determined serologically by using peripheral blood lymphocytes as target cells in a dye exclusion microcytotoxicity assay. Using this new technique, approximately 80% of the reconstituted mice were found to be repopulated with lymphocytes of the donor type.


Brief communication: technical modifications of the human agarose microdroplet leukocyte migration inhibition assay. Direct leukocyte migration inhibition assays using the capillary tube technique can be used to demonstrate cell-mediated immunity in vitro. Unfortunately, the cumbersome nature of this technique makes it time consuming and difficult to perform. Similar results have been obtained using the direct agarose microdroplet leukocyte migration inhibition assay. In this paper, modifications of the agarose technique are outlined which insure standardization of droplets and ease of performance of the assay. Additionally a technique is described to reduce the time required for calculation of results.


A highly sensitive radioimmunoassay technique for subtyping the antibody to hepatitis B surface antigen. A highly sensitive technique for determining the subtype specificity of antibody to hepatitis B surface antigen (anti-HBs) is described. Immunoadsorbent consisting of controlled pore glass coated with subtype specific HBsAg was used to remove homologous antibody from the test samples before testing them for residual antibody by a commercially available radioimmunoassay (RIA). A total of 73 anti-HBs-positive samples from asymptomatic blood donors were tested. In nearly 80% of these samples the subtype reactivity could be determined by this technique. Only 67% could be typed by conventional liquid phase absorption RIA and 22% by passive hemagglutination inhibition techniques. Among the samples with low anti-HBs titer, ad and ay subtypes were found with equal frequency; however, with the increase in anti-HBs titer, considerably higher proportion of ad specificity was detected.


A rapid screening method for the detection of monospecific antibodies against hemoglobins. A simple procedure for the detection of monospecific antibody against C57BL/6 mouse hemoglobin that would not cross-react with DBA/2 mouse hemoglobin is described. The horse antiserum against C57BL/6 mouse hemoglobin is absorbed with DBA/2 mouse hemoglobin. The absorbed serum is then allowed to react with small amounts of DBA/2 hemoglobin-Sepharose and C57BL/6 hemoglobin-Sepharose in separate tubes, followed by reaction with fluorescein isothiocyanate-conjugated goat antihorse IgG. A strong fluorescence in the C57BL/6 immunoabsorbent and little or no fluorescence in the DBA/2 immunoabsorbent show the presence of monospecific antibody against C57BL/6 hemoglobin. The method has general applicability as antibodies against other hemoglobins and proteins can be detected.


A rapid one-step procedure for purification of mononuclear and polymorphonuclear leukocytes from human blood using a modification of the Hypaque-Ficoll technique. A one-step procedure for purification of mononuclear and polymorphonuclear cells from human blood is described. It is a modification of the Hypaque-Ficoll method with density of 1.095 g/ml. Centrifugation at 200 X g for 20--30 min resulted in the separation of mononuclear and polymorphonuclear cells into 2 distinct bands at the interface. The mononuclear cell fraction contained 83.9 +/- 1.6% lymphocytes and 13.8 +/- 2.3% monocytes, while the other conssisted of highly purified neutrophils (96.4 +/- 1.0%). Leukocyte recovery by this method was always greater than 80% and viability exceeded 98%. Both cell fractions retained their immunological functions.


Testosterone metabolism in basal cell epitheliomas. In basal cell epitheliomas the testosterone metabolism pattern differs from that of the normal surrounding skin. There is a significant reduction in 5 alpha-reductase activity with a consequent decrease in production of dihydrotestosterone and androstanediols. By contrast the 17 beta-hydroxysteroid dehydrogenase activity shows no consistent change.


Differential susceptibility of Propionibacterium acnes, P. granulosum and P. avidum to free fatty acids. The susceptibility of 98 Propionibacterium acnes, P. granulosum and P. avidum strains isolated from acne cases and appropriate reference strains to decanoic, dodecanoic, octadeca-9,12 dienoic, and octadeca-9,12,15 trienoic acids was investigated using minimal inhibitory concentration estimation by an agar dilution techique. The tested acids showed their relative antibacterial activity in the following order: C18:3 delta 9,12,15 greater than C18:2 delta 9,12 greater than C12:0 greater than C10:0 Differences between minimal inhibitory concentration values for P. acnes, and P. avidum versus P. granulosum strains were demonstrated in the cases of octadeca-9,12 dienoic, and octadeca-9,12,15 trienoic acids.


Sebum composition: a comparison of thin-layer chromatography and infrared reflectance spectroscopy. Thin-layer chromatography and infrared reflectance spectroscopy were compared as methods for measuring sebum composition. Solutions of varying known concentrations of free fatty acids and triglycerides were analyzed by both methods. Skin surface lipid samples were similarly analyzed. Infrared spectroscopy produced more variable data than thin-layer chromatography with photodensitometry. This was particularly true at low concentrations of free fatty acids. It is concluded that thin-layer chromatography with photodensitometry is a more accurate method for the measurement of sebum composition.


New methods for assessing epidermal wound healing: the effects of triamcinolone acetonide and polyethelene film occlusion. Epidermal healing of superficial, excised wounds in domestic white pigs was evaluated visually and histologically after separation of the epidermis and dermis. The visual determination of epidermal healing correlated well with the histologic studies of surface re-epithelialization. Wounds healed 40% faster when occluded with polyethelene film. Topical triamcinolone acetonide treatment delayed healing (62% slower than control).


Stimulatory effect of exogenous hyaluronic acid distinguishes cultured fibroblasts of Marfan's disease from controls. Fibroblasts cultured from patients with Marfan's disease show metachromasia with toluidine blue and accumulate increased amounts of glycosaminoglycan (GAG). Compared to fibroblasts from controls, more of the newly synthesized GAG is hyaluronic acid. Cycloheximide has a modest inhibiting effect on GAG accumulation compared to protein inhibition while serum depletion has a greater effect on inhibiting GAG  accumulation than on reducing synthesis of new protein. Exogenous hyaluronic acid restores new accumulation of hyaluronic acid in serum depleted Marfan-derived cultures towards baseline while having almost no effect on cultures derived from controls. The effect is specific for hyaluronic acid as chondroitin sulfate or dextran sulfate are not stimulatory and is not due to stimulation of new protein synthesis.


Phenytoin increases 65zinc absorption in the rat. A single oral dose of 65Zn was given to groups of rats, 6 or 7 in each, which were started on phenytoin. The drug was given in daily doses of 10, 50, and 100 mg for 10 days. The retention of 65Zn was followed by a whole body counter, and the net absorption of 65Zn was calculated. All phenytoin doses studied were found to increase zinc absorption significantly.


A reappraisal of the role of Pityrosporum orbiculare in pityriasis versicolor and the significance of extracellular lipase. Pityrosporum orbiculare is an obligate lipophilic yeast in vitro, which suggests it possesses an extracellular lipase crucial for nutrition. If present in vivo, the enzyme would enable the yeast to utilize skin surface lipids, which may therfore play an important role in the pathogenesis of pityriasis versicolor. Cultured P. orbiculare and biopsy material from patients with pityriasis versicolor were investigated for the presence of lipase by electron microscope histochemistry. At sites of lipase activity, fatty acid hydrolyzed from Tween 80 substrate reacts with Ca++ ions to form an insoluble Ca++ soap. Exchange of Ca++ with Pb++ enables the sites of lipase activity to be visualized as electron dense deposits of insoluble lead soap. Surface lipase activity was apparent when the technique was applied to P. orbiculare grown on lipid containing medium and its specificity confirmed by removal of substrate and inhibition by di-isopropyl fluorophosphate and quinine hydrochloride, but not by sodium fluoride. When the same technique was applied to stratum corneum infected with Pityrosporum furfur (Malassez), no reaction product could be detected. It is postulated that lipase, although critical for fungal nutrition in vitro, is unlikely to be of importance in vivo. Skin surface lipids are therefore probably not relevant to the pathogenesis of pityriasis versicolor.


Chemokinetic and chemotactic factors in psoriasis scale extracts. Soluble solutions of psoriasis scale were prepared by extracting scales in 6 m urea and removing urea by dialysis. Extracts were tested for chemokinetic and chemotactic activity for human polymorphonuclear leukocytes and mononuclear cells in vitro using the migration under agarose assay. Five of 6 extracts demonstrated significant chemotactic activity for polymorphonuclear leukocytes, and 4 or 6 were also chemotactic for mononuclear cells. All extracts augmented random migration of polymorphonuclear leukoyctes (chemokinesis). Checkerboard epxeriments showed extracts were truly chemotactic as well as chemokinetic. The kinetics of polymorphonuclear leukocyte and mononuclear cell chemotaxis toward psoriasis scale extracts were similar to kinetics of chemotaxis toward a bacteria-derived chemotactic factor and zymosan-activated serum. Since zymosan-activated serum and purified C5a were not chemokinetic, psoriasis scale extract was more like a bacteria-culture supernate than these complement factors in augmenting random migration of polymorphonuclear leukocytes. Substances in psoriasis scale may be capable of influencing the inflammatory response.


Ultraviolet light induces epidermal ornithine decarboxylase activity. Hairless mice were irradiated with fluorescent sun lamp tubes (peak emission at 313 nm). A singificant increase in epidermal ornithine decarboxylase activity was found after 2 hr. A maximum 80-fold increase was found after 24 hr, decreasing again at 48 hr. Epidermal DNA synthesis was decreased at 6 hr and 24 hr increasing to a maximum 48 hr after irradiation. These results show that polyamine biosynthetic enzyme activity precedes the delayed increase in epidermal DNA synthesis following ultraviolet light exposure.


Pathological changes in female C3H mice continuously fed diets containing diethylstilbestrol or 17beta--estradiol. To study the long term effects of estrogen administration in mice, virgin female C3H/HeJ mice are being fed diets containing 0, 10, 100 or 500 ppb of diethylstilbestrol (DES) or 0, 100, 1000, or 5000 pph of 17beta-estradiol (E2) from 6 to 110 weeks of age. C3HeB/FeJ mice are being fed diets containing 08 10, 100, or 500 ppb DES FROM 6 TO 136 WEEKS OF AGE. Pathologic studies were conducted on 396 such mice sacrificed at 52 weeks and on over 500 others sacrificed at various intervals. After 52 weeks on 500 ppb DES or 5000 ppb E2, the cervix of both populations often showed stromal mucoid changes and adenosis characterized by focal replacement of squamous by columnar epithelium lining the cervical canal assoicated with glandular downgrowths into the subjacent stroma. The uterine horns showed hyperplastic glands, which often penetrated the muscularis, and focal endometrial and perivascular hyalin deposits. The ovaries showed atrophy with absence of corpora lutea. Ceroid deposits were increased in the ovaries and adrenals. Sternal bony trabeculae were increased. The incidence of uterine cervical adenosis and of mammary hyperplastic alveolar nodules and tumors (mainly type B, Dunn's classification), was higher in C3H/HeJ than in C3HeB/FeJ mice. Mice on lower doses of DES or E2 had less frequent and severe similar changes. Tumors observed to date only in estrogen-treated mice included 4 endometrial adenocarcinomas and an adenoacanthoma of a uterine horn, 14 cervical adenocarcinomas often appearing to arise from areas of adenosis, a vaginal squamous cell carcinoma, a cervical granular cell myoblastoma, 1 sternal and 3 cranial osteosarcomas, and a mesothelioma. The majority of the malignancies occurred in C3H/HeJ mice. These findings indicate that the mammary tumor virus factor facilitates DES-induced mammary tumorigenesis in C3H mice and may contribute to other DES-induced malignant and premalignant lesions.


Lung cancer following exposure to bis(chloromethyl)ether: a case report. A research chemist (non-smoker) worked for two years on an investigation where bis(chloromethyl)ether (BCME) and chloromethyl methyl ether (CMME) were by-products. Twelve years after completion of the study he died of a pulmonary adenocarcinoma that had metastasized to both the bones and soft tissue. The relatively large scale (1--2 mol) on which the chemical reaction was conducted resulted in his inhalation of high doses of both BCME and CMME for this two year period. His case history is discussed with reference to other such reported instances.


Suggested procedures for reducing the pathology workload in a carcinogen bioassay program, Part I. Large test programs have been set up to help assess the carcinogenic potential of chemicals introduced into the environment. Most test protocols used in these programs require large numbers of animals and extensive pathologic evaluation of all test and control animals. In this paper we describe modifications to the present pathology protocol which will reduce the pathology workload of the program and make only small changes in the operational character of the screen. The first modification derives from the fact that a tumorigenic effect may be ruled out by looking at the treated animals only. The second procedure suggested uses simple random samples to provide information about the treated groups with still less pathology work. It is emphasized that these proposed modifications should be regarded as a starting point for further discussion and that we encourage comments from all interested scientists.


Dietary subacute toxicity of ethylene thiourea in the laboratory rat. Ethylene thiourea (ETU) was fed to groups of rats at 0, 1, 5, 125 or 625 ppm for up to 90 days. Other groups of rats received either propylthiouracil (PTU; 125 ppm) or amitrole (50 ppm) in their diets as positive controls. Only those rats which received ETU at 125 or 625 ppm and those ingesting PTU or amitrole demonstrated a measurable toxic response. This toxicity was reflected as an alteration in thyroid function and a significant change in thyroid morphology. Ingestion of 625 ppm ETU or 125 ppm PTU resulted in very substantial decrease in serum triiodothyronine (T-3) and thyroxine (T-4). Marked increases in serum thyroid stimulating hormone (TSH) levels were found in the 625 and 125 ppm ETU rats, the 125 PTU rats, and the rats receiving amitrole, each time this hormone was measured. Rats which ingested 625 ppm ETU also exhibited a decrease in iodide uptake by the thyroid. While a statistically significant increase in serum T-4 and degree of thyroid hyperplasia was observed for rats ingesting 25 ppm ETU for 60 days, normal thyroid hormone levels and thyroid morphology was found in rats on 25 ppm ETU for either 30 or 90 days. Based on diochemical and microscopic changes examined, the no-effect level for dietary ETU in this 90-day study is considered to be 25 ppm.