Vulnerability of skeletal and autonomic manifestations of memory in the rat to electroconvulsive shock. A series of experiments was performed to probe the phenomenon of sparing of memory by electroconvulsive shock (ECS) when amnesia is assessed by autonomic indices. Differential vulnerability of memory as indexed by skeletal and autonomic responses was determined to be a function of a higher threshold to disruption for autonomically indexed memories. Autonomic responses spared by ECS were found to reflect underlying memory rather than artifact produced by nonassociative factors arising from the interaction of conditioned stimulus (CS), unconditioned stimulus (US), and ECS. Furthermore, retrograde amnesia gradients of different slopes were observed with skeletal and autonomic measures. Two interpretations of these phenomena are discussed. One hypothesis suggests that individual components of a memory are consolidated at different rates, whereas the other concerns the differentail sensitivity of various measures in assessing memory.


Effects of stimulus similarity in discrimination training upon wavelength generalization in pigeons. Thirty pigeons were given variable interval training to peck a 555-nm. light and then were tested for wavelength generalization. The subjects were later assigned to 1 of 3 groups, matched for both relative generalization slope and response rate. One group then received successive discrimination training between the 555-nm. stimulus (S+) and a vertical white line on a 555-nm. background (S minus); another group experienced the same S+ but a vertical white line on a black background as S minus. A third group received a comparable amount of single stimulus training with the 555-nm. value. On a second wavelength generalization test, the first group yielded greater sharpening of generalization than the second group, whereas the third group showed no change from Test 1. These results indicate that the sharpening of generalization gradients by discrimination training is directly related to the similarity  of the discrimination training stimuli.


Food-deprivation-induced behavioral arousal: mediation by hypothalamus and amygdala. Electrolytic lesions of the basomedial hypothalamus eliminated food-deprivation-induced stabilimeter activity in rats that were prevented from becoming obese. Knife cuts lateral to the basomedial area (separating the medial and lateral hypothalamus) potentiated this activity, as did transections posterior to the basomedial region. Anterior transections (between anterior and medial hypothalamus), however, eliminated the effect. Lesions of the stria terminalis and amygdala likewise abolished deprivation-induced locomotor activity, but elevated ab-lib activity to a level comparable with that after deprivation in intact animals. Animals with combined basomedial-stria terminalis lesions behaved like animals with basomedial lesions. These results suggest that food-deprivation-induced locomotor activity in stabilimeter cages is due to a disinhibition of the basomedial hypothalamus by the amygdala via the stria terminalis.


Acoustic startle reflexes in the rat during consummatory behavior. Auditory startle reflexes were elicited in thirsty rats when they were drinking water or were between drinking boutsmthe reaction was greater during drinking, this enhancement developing over the first few seconds after drinking onset. The startle reaction was lowest immediately after the termination of drinking. Reflex enhancement was reduced when thirsty rats drank milk rather than the more preferred water. The reflex was smaller with increased water deprivation, but enhancement produced by drinking was apparent at all levels of deprivation studied, satiety to 4-days deprivation. The inhibitory effect of a preliminary stimulus was not affected by consummatory behavior. Attention is drawn to suggestive parallels between these behavioral effects and other consequences of consummatory activity, primarily having to do with electrophysiological events and arousal processes


Some behavioral effects of transecting ventral or dorsal fiber connections of the septum in the rat. The behavioral effects of large electrolytic lesions in the septal area were compared with those of knife cuts that severed the ventral or dorsal connections of this structure. Rats with septal lesions lost weight and were transiently hyperdipsic. Ventral cuts produced similar effects, but dorsal cuts did not. All three operations decreased the latency to eat in a novel environment, increased the intake of sweetened milk, enhanced acquisition of a food-rewarded running response, and facilitated acquisition of a shuttle box avoidance response, The lesion, but neither of the knife cuts, reduced the effects of punishment and impaired the acquisition of a one-way avoidance response.


Intrahemispheric response competition between vocal and unimanual performances in normam adult human males. Subjects balanced a dowel rod vertically on the left and right index finger singly and while simultaneously repeating phrases. With right-handed subjects who had no left-handed relatives, concurrent verbalization shortened right- but not left-handed balancing. Increased phonetic difficulty of the phrases produced an increased decrement on right-handed balancing, but left-handed balancing was unchanged; it also produced more verbalization errors on trials with the right hand, but not with the left. Concurrent verbalization shortened balancing duration with both hands of left-handers. Right-handers with left-handed relatives produced variable results. Concurrent humming also selectively interfered with right-handed balancing. It was concluded that the results conform to an interpretation based on intrahemispheric interference between incompatible, simultaneously produced sets of responses.


Electroretinographically determined spectral sensitivity in the tawny owl (Strix aluco). The electroretinographic (ERG) responses to single light flashes and to flickering lights were obtained in the tawny owl (Strix aluco). The waveform of the single-flash responses indicated that the owl possesses a duplex retina. Spectral sensitivity was determined with light flickering at a 6 and 25 Hz. The sensitivity curve obtained from the 6-Hz responses has a broad maximum between 500 and 525 nm. The 25-Hz sensitivity curve is narrow with a peak at about 600 nm. The sensitivity curves are compared with behaviorally measured sensitivity curves of the pigeon. A close agreement is found between 25-Hz curve and the pigeon red modulator.


Auditory similarities associated with genetic and experimental acoustic deprivation. Susceptibility to audiogenic seizures has been produced in otherwise non-susceptible mice by acoustic stress and by conductive hearing loss. Both procedures temporarily elevate the absolute threshold of the auditory evoked potential (AEP) and are maximally effective during a circumscribed period of early development. In the genetically SUSCEPTIBLE DBA/2J mouse, AEP thresholds indicated that its auditory system is functionally less mature during this early period than that of the nonsusceptible C57BL/6Jmouse. It was proposed that innate susceptibility found in the DBA/2J mouse results from auditory disuse supersensitivity during a critical developmental period, in support of Saunders' hypothesis for acoustically primed mice. The increased peak-to-peak AEP amplitudes, however, were not believed to be causally related to the audiogenic seizures.


Auditory masking-level differences in the cat. Four cats were trained to avoid shock by responding to the intermittent occurrence of 1-kHz tone pulses at one ear, while a continual train of noise pulses was simultaneously presented either to the signal ear alone or to both ears. Using the masked threshold levels determined with monaural noise as a reference, the amount of unmasking produced by the addition of noise to the nonsignal ear was measured. Significantly lower tonal detection thresholds were observed when noise equal in intensity to that at the signal ear was added to the nonsignal ear. Additional unmasking occurred when the intensity of the noise at the latter ear was raised to a level 10 db. higher than that at the signal ear.


Habenular lesions and feminine sexual behavior of ovariectomized rats: diminished responsiveness to the synergistic effects of estrogen and progesterone. Bilateral electrolytic lesions in the habenula resulted in disruption of estrogen-progesterone-evoked feminine sexual behaviors of ovariectomized female rats. There were no difference between lesioned and sham-operated animals in tests conducted after the administration of estrogen alone. Animals with lesions were characterized by an increased proportion of mounts not followed by lordosis, a decreased proportion of mounts followed by pronounced lordosis, and a decreased proportion of mounts preceded by soliciting behaviors. Lesions had a negligible effect upon the tendency to hold lordotic postures after the male dismounted. The results suggested that the habenula is involved in modulating responsiveness to the synergistic effects of estrogen and progesterone.


Ontogeny of spontaneous locomotor activity in rabbit, rat, and guinea pig. Postnatal locomotor activity was investigated in rabbit, rat, and guinea pig. A peak was found in this behavior at 5 days of age in the rabbit and, in confirmation of earlier studies, at 15-20 days in the rat. Neonatal guinea pigs showed no variation in activity levels due to age. The guinea pig is born at an advanced stage of neural maturation in comparison with the rat, and the rabbit is born at an intermediate stage. This difference accounts for the observed variations in postnatal activity profiles if it is assumed that the behavioral peak coincides with the transition from a stage of primarily mesencephalic arousal system maturation to a stage of primarily diencephalic and telencephalic inhibitory system maturation.


Conditioning insulin effects.

Conditioning insulin effects. It has previously been demonstrated that after a number of insulin injections in rats, an injection of a placebo leads to an elevation in blood sugar. It has been suggested that this apparent conditioned compensatory response is an artifact resulting from stressing the subject (when large doses of insulin are used) or represents a nonassociative phenomenon (when small doses of insulin are used). These two suggestions were rejected on the basis of the results of Experiments 1 and 2, respectively. Experiments 3 and 4 demonstrated that although the behavioral effects of insulin can be conditioned to the injection procedure, such conditioned insulinlike behaviors (contrary to suggestions of many investigators) are not mediated by a pypoglycemic state.


Changes in the antigenic composition of the short ragweed plant during maturation. Whole ragweed plants were collected before and during the ragweed pollination season and extracts of various portions of the plants were analyzed for antigen E (AgE) and for their inhibitory potency in the radioallergosorbent test (RAST). Ragweed stems and roots contained very low, if any, AgE. AgE was present in very small amounts in anthers prior to pollination season, increased with anther and pollen grain maturation, peaked with the appearance of significant airborne pollen grains in mid-August, and fell slowly through late September. Leaf AgE content also rose during mid- and late August, but brief rinsing reduced antigen E content by almost 50%. Significant RAST inhibitory activity was found only in anthers and the activity paralleled the content of AgE.


The direct basophil degranulation test and the intracutaneous test: a comparison using food extracts. The purpose of this study was to compare the direct basophil degranulation test (DBDT) of Hirsch and Zastrow with the intracutaneous (IC) test in subjects with and without histories of food allergy. The DBDT was perfomred by incubating the concentrated leukocytes of subjects with dilutions of the suspected allergenic extract and comparing the number of nondegranulated basophils remaining in the test samples with the number remaining in a control. The test sample with the least number of basophils represents maximal basophil degranulation. The DBDT was perfromed with extracts of the suspected food on 14 subjects with reliable clinical histories and positive IC tests indicative of food hypersensitivity. Thirteen of these 14 food-sensitive subjects also had IC and DDBT8 to the extracts of foods to which they were not clinically sensitive. Fourteen different subjects not allergic to foods were also tested with food extracts by the IC and DBDTS. There was a 92% correlation between the IC test and the DBDT, a 90% correlation between the IC test and the history, and an 86% correlation between the DBDT and the history. We conclude that, in this study of subjects clearly sensitive to foods, the DBDT correlates favorably with the history and IC test.


The use of humidity in asthmatic children. Controversy exists as to the advisability of mist therapy in pulmonary disease. We studied the effects of several forms of humidity on asthmatic airways. Thirty-four children were tested over a period of 8 months as follows: (1) mist with a mean particle size of 3 mu was delivered for 30 min by an ultrasonic nebulizer to 11 children individually in a plastic tent; (2) to another 11 subjects in a tent, mist with a mean particle size of 10 mu was delivered by a jet nebulizer for 30 min;3) 15 patients in a croup room recieved for 30 min water droplets ranging from a microscopic fog to large rain particles (mean 16 mu) generated by a Melco natural fog generator; (4) 10 children were challenged with 3 solutions used commonly for the production of mist: distilled water, half-normal saline, and normal saline. Pulmonary functions were studied on each patient pre- and post-mist exposure. Approximately two thirds of the patients had a significant response, either improvement or deterioration, when challenged with the various forms of mist. No particular group trends were produced either by increasing the mean particle size of humidity, or by using solutions of increasing salinity.


Standardization of tissue culture conditions for spontaneous thymidine-2-14C incorporation by unstimulated normal human peripheral lymphocytes: circadian rhythm of DNA synthesis. The rate of DNA synthesis by human lymphocytes was studied in vitro by measuring unstimulated thymidine-2-14C incorporation (spontaneous lymphocyte blastogenesis; SLB). Freezing lymphocytes and extracting DNA after thawing did not alter the radioactive label count rate and was as efficient as extracting DNA immediately after culture. Omission of fetal calf serum also did not alter the rate of DNA synthesis. Standards established as optimal for studies of SLB were: cell concentration, 1.0 times 10(6)/ml/tube; 14C-TdR concentration, 0.4 mjCi/tube; duration of incubation, 8 hr. In sets of identical samples obtained by specimen division, the variation in counts was 6%. To achieve reproducibility of results; it was essential to count the lymphocytes, and then to ensure that each tube contained almost precisely known numbers of cells. Diurnal variations in the rate of DNA synthesis by circulating lymphocytes of healthy men were measured in vitro by SLB at 2-hr intervals for 24 hr. Leukocyte counts, hematocrit, hemoglobin, plasma cortisol, and body temperature were monitored concurrently. The DNA synthesis rate varied in a 24-hr cycle with peaks at 10 A.M. and 11:00 P.M.., depressions at 4 A.M. and 4 P.M. The rate was correlated with body temperature and hematocrit level, and inversely related to the absolute eosinophil count.


Aspirin intolerance. III. Subtypes, familial occurence, and cross-reactivity with tartarazine. Evidence has been presented supporting the hypothesis that at least 2 different types of mechanisms may be involved in aspirin intolerance, one resulting in bronchospasm and the other producing urticaria/angioedema. Bronchospasm is the predominant symptom of aspirin intolerance in patients who have asthma. In contrast, the predominant symptom of aspirin intolerance in patients who have rhinitis is urticaria/angioedema. In the bronchospastic type of aspirin intolerance, there is a significant correlation with an increased frequency of nasal polyposis, and with a similar ageonset of asthma and aspirin intolerance. These correlations were not present in the urticari/angioedema type. Additional evidence for familial occurrence of aspirin intolerance is presented, and its relationship with subtypes of aaspirin intolerance is discussed. In a double-blind, crossover study with normal control subjects matched by age and sex 15% (6/40) of aspirin-intolerant individuals had significant adverse reactions to tartrazine challenge and not to the placebo. None of the 40 normal control subjects had any adverse reactions.


Prolonged interval hyposensitization therapy in hymenoptera-sensitive patients. The Committe on Insects of the American Academy of Allergy has conducted a 10-year study of 397 patients with Hymenoptera allergy treated with glycerosaline or aqueous whole body mixed Hymenoptera extracts at intervals of 2 or 3 months for the maintenance doses. Patients had few reactions, although in some cases local reactions presented lengthening of the interval. The clinical response was similar to that from conventional therapy using the 4-wk interval for maintenance doses. This type of therapy offers the added advantages of fewer patient visits and decreased cost.


Assessing fungus prevalence in domestic interiors. Single-plate, Andersen sampler collections of mesonphilic imperfect fungi were made at three points in and immediately outside a series of midwestern homes. During frost-free periods, emanations of dark-spored form genera predominated at both points with indoor levels averaging 25% of those in outside air. At these times, volumetric recoveries and those by 30-min exposure of open culture plates have correlated tenuously (r = 0.29) in bedroom air of 20 homes. During winter, form species of Penicillium, Aspergillus, Oospora, Sporothrix, yeasts, etc. predominated indoors, with levels exceeding 1,000 particles/M3 noted in over 18% of homes; outdoor concentrations never exceeded 230 particles/M3. Comparisons of volumetric and open-plate recoveries from 50 homes during winter have revealed an almost random relationship (r = 0.06). These findings reflect the case with which outdoor spore clouds may penetrate structures and obscure evidence of internal fungus cources. The data also imply that, because of size-related undersampling, open plates often seriously misrepresent prevalence levels and occasionally can exclude abundant types from recovery. The fungus flora of enclosed spaces merits further critical study by volumetric techniques of calculable efficiency in a setting that minimizes contamination from without.


Interviewing and counseling skills. Techniques for their evaluation. Assessment of knowledge and cognitive skills has been traditionally included in examinations for certification and licensure of health professionals. Evaluation techniques for assessing complex cognitive and interpersonal skills, however, have not been as widely developed or incorporated in national examination programs. Specifically, the evaluation of interviewing and counseling skills has been complicated by difficulties in: (a) defining what consititutes skillful interviewing and counseling and in specifying criteria against which performance can be assessed; (b) developing evaluation procedures to permit accurate and reliable observations of these activities; (c) solving logistic problems of standardizing the content and format of these evaluation procedures; and (d) establishing standards for identifying individuals who have not yet achieved acceptable levels of proficiency. Progress has been made in defining the criteria for evaluating the interviewing and counseling skills of several categories of health professionals. Definitions can be developed to identify specific behaviors associated with acceptable and unacceptable skills in this area of professional competence. On the basis of these definitions, interaction analysis techniques have been developed for accurate and reliable recording of behavior as it occurs in an interviewing and counseling session. Moreover, the use of actors programmed to portray the roles of patients has enabled the standardization of this evaluation procedure so that examinees can be assessed on the basis of equivalent testing conditions. A number of research studies are under way to determine whether paper-and-pencil, as well as audiovisual, simulations can be substituted for evaluation in a live, interactive setting. However, little has yet been done to identify appropriate procedures for establishing standards of proficiency. Perhaps such efforts will be more feasible when appropriate evaluation techniques are more fully developed. Of relevance in determining whether the evaluation of counseling and interviewing skills is pertinent to dietetics are questions such as: How frequently do dietitians interact with patients? In what settings and for what purposes do these interactions take place? What impact do dietitian-patient interactions have on the quality of the health care provided?


Nutritional considerations for the newborn requiring intensive care. The importance of providing nutrition for the critically ill or low-birth-weight baby is frequently over-looked in the zeal to preserve life. Unfortunately, because of this oversight, a significant factor influencing the quality of that salvaged life may be neglected. Common nutritional problems requiring a team effort have been described to emphasize the need for support by the dietitian. There is increasing evidence that what is appropriate for the term baby may not be ideal for the premature infant. Some of the recognized discrepancies are discussed, and an approach to management outlined. Through prospective evaluation, we hope to gain insight into many of the unanswered and perhaps unrecognized questions regarding nutrition for the intensive care newborn.


Food choices of institutionalized vs. independent-living elderly. Data on food intake of ninety-nine nursing home residents and of ninety-eight independent-living elderly persons with respect to twenty-two food groups were obtained by questionnaire interview. Nutrient intake was calculated by computer and compared with the 1968 Recommended Dietary Allowances. Fewer than half of the respondents in both groups had intakes providing 67 per cent or more the allowances for eight nutrients, and 35 per cent fell below this level for two or more nutrients. There were no significant differences in nutrient intake due to type of living arrangement. However, the nursing home residents had made more changes in eating habits than the independent-living participants, and changes correlated negatively with nutritional scores. Nursing homes might improve residents' nutrient intakes by adjusting menus and food preparation to conform more closely with residents' food preferences.


Natural toxicants in foods.

Natural toxicants in foods. Food constitutes the most complex part of our chemical environment. Naturally occurring substances in food, such as goitrogens and estrogens, are toxicants. However, there is a difference of degree between toxicity and hazard, and the hazard to man in normal good health from naturally occurring toxicants in food is usually slight, because of (a) the small concentrations and (b) antagonistic interactions between toxicants which provide "safety in numbers." Hazard from foods may indeed exist under some circumstances, such as the presence of abnormal contaminants, ingestion of abnormal amounts, or abnormal susceptibility existing in some disease states. However, the major hazards of the dinner table can ordinarily be ascribed to careless food handling, unbalanced or fad diets, or overeating.


The need for better nutritional care. who's responsible? Two major factors seem to be contributing to the problem which underlies the need for better nutritional care to clients: clinical dietitians themselves and the system which supports them. It is felt, however, that the burden of responsibility for improvement weighs more heavily on the individual dietitian than on the system, because systems are composed of functionally related individuals working toward a common goal. Few would argue that the goal of the health care system is a positive state of well-being in the population it serves. Even fewer could argue with the primacy of effective nutritional care in the achievement of that goal. If, however, we want clinical dietitians to be more effective nutritional care in the achievement of the goal. If, however, we want clinical dietitians to be more effective in the future, they must be given the time, expertise, and responsibility to provide this improved nutritional care.


Cooking frozen and thawed roasts: beef, pork, and lamb cuts. Cooking time, yield, and palatability of paired beef, pork, and lamb roasts cooked from the frozen and thawed states were compared. Cooking time for all roasts averaged from 3 to 22 min. per pound longer for meat cooked from the frozen state. The longer cooking time from the frozen state. The longer cooking time from the frozen state was greater for roasts with a large amount of bone and for cuts cooked by braising than for less bony roasts and cuts cooked by roasting. Except for thawed beef rump roasts, which had a higher yield of cooked lean meat, yield of cooked lean meat from the various cuts of beef, pork, and lamb was not affected by the state at the start of cooking. Collectively, all pork roasts had a higher yield of cooked lean meat when cooked from the frozen state. Juiciness and natural flavor of the roasts were not affected by the state at the start of cooking. Lamb leg and rib roasts were more tender when cooked from the thawed state.


Effect of electronic cooking on fatty acids in meats. This study was conducted to investigate the effects of microwave energy and conventional heating on the fatty acid composition of meats and poultry. Data on weight loss and cooking time with both heat treatments are reported. Gas-liquid chromatographic data of the methyl esters of myristic, palmitic, stearic, oleic, linoleic, and linolenic acids revealed no significant difference between fatty acid composition as a result of heat treatment. Decreases in fatty acids appeared to be mainly due to a change in oleic acid. Poultry appeared to be the species most affected by heat treatment. Cooking times were much shorter for the electronic method and varied among species. No significant difference was found in weight loss as a result of treatment of beef or pork. Poultry weight losses were greater for the conventional method.


Radical mastectomy in the aged female.

Radical mastectomy in the aged female. Of 142 female patients over age 75 at The New York Hospital-Cornell Medical Center, 58 underwent radical mastectomy and 40 simple mastectomy for primary breast cancer. After five years, 19 per cent of the radical mastectomy group were cancer-free compared with 35 per cent of the simple mastectomy group. The gross five-year survival rates were 50 per cent and 47 per cent respectively. In the radical mastectomy group, when the axillary nodes did not show cancer at the time of operation, there have been no known recurrences and 70 per cent of the patients have survived at least five years. There was no surgical mortality. These findings support the view that until more controlled data are available, radical mastectomy is still the preferred therapy for primary breast cancer.


Psychopharmacologic investigations in healthy elderly volunteers: MMPI depression scale. The Depression Scale of the Minnesota Multiphasic Personality Inventory (MMPI) was used as a screening test for healthy volunteers in a psychopharmacologic research study. Data were collected on 43 men and 46 women under age 35 versus 33 men and 43 women over age 65 (plus a subsequent group of 40 men over age 65), and comparisons were made with more extensive data from the Mayo Clinic. The evidence indicates that elderly subjects differ strikingly from young subjects in their responses to items in the MMPI self-ratings of depression. Revised information on normative responses is needed. At present there are too many problems of interpretation when the Depression Scale items are applied to t.he elderly.


Iatrogenic and nurisgenic effects of prolonged immobilization of the ill aged. The kinesio, phychopathologic and psychosocial effects of prolonged immobilization of the ill aged are outlined. The iatrogenic (physician-induced) and nurisgenic (nurse-induced) factors related to such functional disabilities are described. Illustrative case histories are given. The syndrome is reversible. Thus physicians and nurses have a continued responsibility to support a sustained rehabilitation program for these patients. The biochemical effects of prolonged inactivity indicate that immobilization of the elderly patient results in adverse physical and psychologic phenomena.


The team approach in a psychogeriatric unit. The importance of a multidisciplinary team approach was recognized when a 14-bed short-term Psychogeriatric Unit was opened in a psychiatric hospital. The limited time available to the psychiatrist in charge placed a heavy clinical responsibility on the paramedical personnel who formed the team. Initially, role distinctions were kept vague and regarded as not overly important. Six months after the Unit opened, all the staff members filled out a questionnaire. They felt that communication within the team was good, that they could fulfill the role of primary therapist, and that they understood their own roles and those of others. All regarded the psychiatrist as the head of the team. The psychiatrist felt that he had the ultimate responsibility for over-all care of the patients, that any attempt ot blur roles caused problems, and that there had been a partial regression to more traditional patterns. Members of the Unit regarded themselves as a team, able to work together and pool skills in treating patients, and thus play a significant part in total care. This attitude proved more valuable than attempting to break away from the medical model or decrying the importance of roles.


The course of life for old people.

The course of life for old people. Various aspects of institutional living for old people are discussed, particularly the imposition of a lifestyle completely foreign to their previous way of existence. Old people who have been living in one manner for about seventy years cannot be expected to adjust readily to another rhythm. The clash of lifestyles creates maladaptive behavior and adjustment problems that have not been adquately studied. Suggestions are made for approaches to resolve these difficulties. In essence, the techniques include reprogramming of institutional living for old people so that they have an opportunity to maintain their customary lifestyle. Examples of such programming are presented.


Soul foods for some older Americans.

Soul foods for some older Americans. The elderly person brings with him a lifetime of food preferences. For him, nutritional adequacy is dependent upon continuation of similar underlying influences and the varying conditions which determine the food intake of any group. The significance of individuality cannot be minimized in assessing nutritional well-being and in developing a plan of action. Among the factors affecting food acceptance and health status are foods which are foods which are considered "soul" by some persons. Recognition of, and respect for, individual food preferences can be invaluable to members of the health professions in providing services to aging Americans.


Management of primary hyperparathyroidism in the elderly. Of 166 surgical patients for whom the diagnosis of primary hyperparathyroidism was established over a 20-year period, about one-third were over 60 years of age. For an additional 9 patients, or operation was advised, usually because of other life-endangering disease and the presence of only a mild degree of hypercalcemia without complications. In recent years, nearly 50 per cent of the patients did not have renal calculi or osteitis fibrosa cystica; this was unrelated to age. Most of the patients with management problems were seen since 1965. Age alone was not a dominant factor in relation to serious complications from hypercalcemia, the presence of other critical disease increasing the risk of operation, or the development of major postoperative complications. The only death from primary hyperparathyroidism occurred in a 74-year old patient who refused re-operation and died from an acute hypercalcemic crisis. A liberal, but selective, policy of surgical treatment is justified for primary hyperparathyroidism in the elderly. Patients for whom the diagnosis of primary hyperparathyroidism is established may be separated into three groups: those for whom early operation is indicated, those for whom operation should be delayed to permit recovery from other life-endangering acute disease, and those for whom operation is unjustified because of minimal uncomplicated hypercalcemia and other serious disease greatly limiting life expectancy. These categories encompass all age groups and are not restricted to the elderly. All patients require periodic re-evaluation.


Hyperlipidemia and its significance in the aged population. Starting in childhood, blood lipid levels rise progressively with each ten-year period until age 70, when cholesterol and triglyceride levels begin to stabilize and then decline. By age 80 there is a precipitous drop to approximately the values noted in persons of the 20-30 age group. Data on 195 residents of a geriatric center are included. Despite the lower average lipid levels, 30 per cent of the elderly show some lipid abnormality. There is a definite increase in the risk of death from coronary artery disease in hyperlipidemic persons as compared to those who are normolipidemic, even during the eighth and ninth age decades. Hyperlipidemia appears to be a significant risk in the elderly, as in persons of any age, and should be treated accordingly.


The use of urokinase in acute myocardial infarction: report of two cases. In the course of a study (now including 53 patients) on the effectiveness of urokinase in the treatment of acute coronary occlusion, coronary angiography was performed in 2 patients before and after the use of this drug. In both instances the angiograms demonstrated obstruction in the coronary-artery branches, with additional narrowing and some collateral circulation. After urokinase therapy, blood flow was restored in the areas previously obstructed. These 2 case reports are presented because they demonstrate this favorable change in coronary blood flow in association with this particular form of therapy. It is hoped that the completed urokinase study may add some information concerning the effect of thrombolysis in the management of myocardial infarction.


Excretion of Schistosoma mattheei eggs from man, baboons and cattle living in their normal environment. Egg excretion of S. mattheei was studied for about a year from man, baboons and cattle living in their normal environment. Although the excretory pattern was not unequivocal from man, there was a tendency of egg counts to decline with time: the baboons showed a seasonal pattern and the cattle a stable pattern throughout the year.


Host-parasite relationship of Bulinus forskalii (Ehrenberg) and Schistosoma intercalatum Fisher 1934, from Cameroun. The susceptibility of 13 different B. forskalii strains from Zaire, Cameroun, Gabon, Senegal, Rhodesia and Tanzania and B. reticulatus wrighti Aden has been tested to infection with Schistosoma intercalatum from Cameroun. The most common prepatent period was 23-28 days. B. forskalii from Zaire, Cameroun and Gabon were excellent intermediate hosts with infection rates varying from 59-0 to 97-4% and with very low death rates, 0-28-4%. The strains from Senegal and Rhodesia had infection rates from 50-0 to 58-4%. B forskalii from Tanzania was refractory. 53-0% of the exposed B. reticulatus wrighti was infected. The total cercariae production per snail varied from 1000-11000. The duration of the infection varied from 8 to 174 days.


A postcoupling method for the demonstration of N-acetyl-beta-D-glucosaminidase in unfixed frozen tissue sections. The localization and activity of the lysosomal enzyme, N-acetyl-beta-glucosaminidase, has been studied in unfixed frozen sections of tissues from normal and hemorrhaged rats with the use of a modified postcoupling technique. Discrete localization of the end product of the reaction was achieved in this method by the incorporation of 20% (w/v) polyvinyl alcohol (molecular weight 14,000) in the incubation medium. Advantages of the present method include the ability to overcome the inhibitory effects on enzyme activity of both tissue fixation and the presence of diazonium salts in the incubation medium. The staining reaction obtained with this technique demonstrates the enzyme activity at specific cytoplasmic sites within cells and has a wider applicability to the comparative study of N-acetyl-beta-glucosaminidase activity in normal and injured tissues.


Different roles of IgG and complement receptors in phagocytosis by polymorphonuclear leukocytes. The functions of IgG and complement receptors in phagocytosis of immune complexes by mouse polymorphonuclear leukocytes were examined by in vitro experiments. The immune complexes were sheep red cells (E) sensitized with IgG antibody (EA) or with antibody and complement (EAC). Inhibition experiments with Fab fragments of rabbit IgG antibody anti-mouse IgG have shown that the complement receptor is primarily involved in the attachment phase, whereas participation of the IgG receptor is necessary for inducing the mechanism of phagocytosis. The possible relevance of these findings for the in vivo mechanism of defense infection, and for the control of antibody synthesis is discussed.


Antibody-dependent cell-mediated cytotoxicity in humans. II. Energy requirement. Antibody-dependent cytotoxicity mediated by human peripheral lymphocytes is an active energy-requiring phenomenon. In this study the relative importance of glycolysis and respiration was analyzed, by measuring the effect of various metabolic inhibitors (sodium azide, antimycin A, 2-deoxy-D-glucose, iodoacetate), alone or in combination, on effector cell efficiency and intracellular ATP level. The inhibition of both aerobic and anaerobic energy production in the effector cells completely abolished cytotoxicity. An inhibition of 50% was observed when the intracellular ATP concentration was decreased to levels corresponding to 30 to 50% of those in the untreated controls.


Genetic studies of a muscular dystrophy of mink. Analysis of breeding data revealed that the muscular dystrophy trait in a pedigree of mink is transmitted in an autosomal recessive manner. Variation in skeletal muscle fiber diameter size is the most pronounced and consistent change in the dystrophic mink. Other changes include centralization of nuclei, degenerative change, increase in endomysial and perimysial connective tissue, and regenerative attempts. These changes are not present in known heterozygotes.


The expression of theta-like antigen by rat peripheral lymphocytes: serologic and functional studies. AKR/Cum mice (Thy-1b = thetaC3H) immunized with nucleated cells from WF rat thymus, Peyer's patches, peritoneal exudate, mesenteric lymph nodes, blood, bone marrow, or spleen produced antibodies cytotoxic for ADR/J  (Thy-1a = thetaAKR) but not for AKR/Cum thymocytes. The specificity of these antibodies for the Thy-1.1 (theta-AKR) antigen was confirmed by tests using thymocytes from backcross mice segregating at the Thy-1 locus. This result suggested that the rat lymphocyte antgen cross-reactive with Thy-1.1 was expressed by at least some members of each of the rat lymphoid cell populations tested. AKR/Cum mice immunized with killed rat cells also produced anti-Thy-1.1 antibodies; thus indicating that further differentiation of the injected cells was not a prerequisite for the anti-Thy-1.1 response. Unexpectedly, about 9% of unimmunized adult AKR/Cum males were found to be producing antibodies against Thy-1.1. To our knowledge, natural antibodies of this specificity have not been previously reported. Finally, it was found that peritoneal exudate cells taken from WF rats previously immunized with EL-4 mouse leukemia cells were neither killed nor functionally inactivated by treatment with anti-Thy-1.1 antibodies and complement.


Two new reciprocal translocations in the German cockroach. Cytology and genetics of T(3;12) and T(7;12). Two new reciprocal translocations in the German cockroach have been analyzed. They were identified cytologically to be T(3;12) and T(7;12). Linkage studies showed that groups XI, IX, and IV are on chromosomes 12, 3, and 7, respectively, and clearly demonstrated sex differences in recombination. Each of these chromosomes have distinctive morphological features that facilitate their identification, and permit breakpoint and centromere localization. A sex difference in fecundity is associated with T(7;12), but not T(3;12). About 40 percent mortality occurred when T(3;12) males or females and T(7;12) females were outcrossed. Outcrossing T(7;12) males produced the expected 50 percent mortality. Cell counts at metaphase I revealed that T(3;12) males exhibit directed segregation, while T(7;12) males do not. Tests for homozygosity indicated that the T(7;12) homozygote is viable. A map of chromosome 12 is presented showing the tentative placement of linkage group XI with respect to interchange breakpoints and chromosome morphology. The results are discussed in relation to possible sex differences in chiasma localization.


Chromosomal polymorphism in Drosophila nasuta. III. Inverted gene arrangements in South Indian populations. Inversion polymorphism, including a total of 33 inverted gene orders, was studied in South Indian populations of D. nasuta nasuta. Of these, the X chromosome has one, chromosome 2 has 10, and chromosome 3 has 22 inversions. D. nasuta nasuta has simple, tandem, included, overlapping, and complex types of paracentrics in its polymorphic system. The phylogenetic considerations of these gene orders are discussed.


Preparation of IgG-binding membrane vesicles from the microvillar brush border of fetal rabbit yolk sac. A one step procedure is described for the production of membrane vesicles from the endodermal microvillar brush border of the fetal rabbit yolk sac splanchnopleur. The vesicles, examined by light and electron microscopy, were shown to consist of biomolecular leaflet unit membrane, coated to varying extents with glycocalyx. By fluorescence microscopy, the homologous immunoglobulin, FITC-IgGR, has been shown to bind to the glycocalyx-coated vesicles as well as the glycocalyx-coated brush border of the intact yolk sac, whereas, the heterologous bovine immunoglobulin, FITC-IgGB, fails to bind under comparable conditions. These observations demonstrate the specificity of the receptors for the homologous IgG.


Splenic regulation of lymphocyte trapping in lymph nodes draining tumor grafts. We measured the trapping of 51chromium-labeled splenic lymphocytes in the lymph nodes and spleens of tumor-inoculated mice at various intervals after inoculation. Both histocompatible and incompatible tumors were studied. Significant trapping occurred in the draining lymph nodes over the entire course of the experiments. The splenic trapping response commenced very early after transplantation and abated after a few days. The magnitude of the lymph node trapping response correlated with the magnitude of antigenic difference between tumor and host. Splenectomy before tumor inoculation had bidirectional effects; it caused a marked augmentation of the trapping response in the early period after tumor inoculation, which declined with time so that late after tumor inoculation, splenectomized animals trapped less well than intact controls. Tumor resection always led to a rapid fall in the trapping response in normal mice. However, tumor resection at the time of the peak trapping response of splenectomized mice produced no change. These results support the notion that lymphocyte trapping is a valid and useful monitor of the immune response to tumors. They also serve to reemphasize the important regulatory role of the spleen plays in the immune response to tumor-associated antigens by demonstrating a new parameter of splenic control; regulation of lymphocyte traffic in response to antigenic stimuli.


Synthesis of surface H-2 alloantigens in murine splenocytes. The synthesis and turnover of cell surface H-2 alloantigens were studied in murine splenocytes by the anti-H-2-bind method to separate precursor-labeled surface from intracellular molecules. Results indicate that newly synthesized H-2 antigen, labeled in either its peptide or carbohydrate portion enters a relatively small pool of intracellular H-2 antigen and then is rapidly transported to the plasma membrane which represents a larger compartment. The simplest interpretation of these findings is that H-2 antigen is synthesized and transported along a conventional secretory pathway. Pulse-chase experiments indicate that H-2 antigens are not readily chased from the plasma membrane and are not shed or internalized during short-term culture. The aforementioned observations are discussed in terms of a cellular heterogeneity.


Structural studies on induced antibodies with defined idiotypic specificities. II. The light chains of anti-p-azophenylarsonate antibodies from A/J mice bearing a cross-reactive idiotype. N-terminal amino acid sequence analyses have been performed on three preparations of light chains of A/J mice. Light chains derived from the IgG of unimmunized animals were compared to light chains of anti-p-azo-phenylarsonate (anti-Ar) antibodies possessing a cross-reacting idiotype (CRI); the latter were derived from the ascites fluid of a single A/J mouse, or from the pooled ascites fluids of 18 A/J mice. The heavy chains of these same two antibody preparations had previously been shown to comprise a single, homogeneous sequence to position 40. With few exceptions, the first 26 positions of light chains derived from unimmunized animals were extremely heterogeneous; the heterogeneity is comparable to that observed in a composite of sequence data on light chains of BALB/c myeloma proteins. Although the light chains obtained from anti-Ar antibodies possessing the CRI (whether from the pool of 18 A/J mice or from a single mouse) were more restricted in their sequence, at several positions as many as four alternative amino acids were detected. These studies indicate that an antibody population with defined idiotypic specificity, and very possibly identical heavy chain sequences, may contain at least four distinct light chains. The feasibility of structural studies on antibodies induced in individual mice is further demonstrated.


Simple radio-immunoassay for the measurement of human and rat IgE levels by ammonium sulfate precipitation. A simple assay for quantitating IgE levels has been developed based on the observation that antibody-bound IgE is insoluble in 33 percent saturated (NH-4)2-SO-4 whereas unbound IgE is not. The method has been applied to human and rat IgE. Some preliminary results on IgE levels in parasite-injected rats are presented.


Distribution of covalently bound and non-covalently bound secretory component on sbuclasses of rabbit secretory IgA. The distribution of non-covalently bound secretory component (SC) on the two subclasses, IgA-f and IgA-g of rabbit secretory IgA (sIgA) was determined; the two subclasses were separated from each other by the use of antibody-immunosorbent columns and were subjected to SDS polyacrylamide gel electrophoresis. No SC appeared to be dissociated from the IgA-f molecules from each of 11 different rabbits; the IgA-g molecules, however, did have SC which was dissociated by SDS. Thus, all of the noncovalently bound SC on rabbit sIgA resides on the IgA-g subclass molecules.


Enduring antibody responses in "normal" rabbits to maternal immunoglobulin allotypes. A majority of rabbits born to mothers heterozygous with respect to the b locus allotypic markers "spontaneously" develop antibodies against the noninherited maternal allotypes. Such antibodies generally appear in the 4- to 5-month-old rabbit, after what may be a transient period of tolerance, and persist at constant levels for at least 5 to 6 months. The finding of a high incidence of measurable antimaternal allotype responses in "normal" rabbits, added to similar findings by others in mice, pigs, and man, underscores the generality of this rather unexpected phenomenon and invites further inquiries into biological significance.


The protein nature of the Thy-1.2 alloantigen as expressed by the murin lymphoblastoid line S-49.1 TB-2-3. This preliminary study was undertaken to investigate the chemical nature of the Thy-1.2 antigen expressed on the murine cell line S-49.1 TB-2-3 (S-49). The presence of the Thy-1.2 antigen was indicated by the inhibition of AKR anti-C3-Thy-1.2 serum induced lysis of 51Cr-primed target cells. It was found that limited digestion of S-49 cells with crude papain yielded a Thy-1.2-containing solution. The protein nature of the Thy-1.2 antigen obtained in this manner was indicated by changes after proteolytic digestion. Separate digestions with crystalline papain, insolubilized papain, and insolubilized protease all destroyed the Thy-1.2 activity. These results suggest that the protein moiety is necessary for Thy-1.2 activity.


Immunochemistry of hepatitis B surface antigen (HBsAg): preparation and characterization of antibodies to the constituent polypeptides. The structural polypeptides of HBsAg were shown to be immunogenic in guinea pigs. Purified 22-nm forms of the ad and any subtypes of HBsAg were solubilized under reducing conditions and electrophoresed in SDS-polyacrylamide gels. Individual polypeptides isolated from both HBsAg/ad and HBsAg/ay subtypes were used to hyperimmunize guinea pigs using Freund's complete adjuvant. All animals produced specific antibodies against native HBsAg as determined by complement fixation, passive hemagglutination, and double-antibody radioimmunoprecipitation assays. Each polypeptide contained within its structure the group-specific HBsAg determinant, a. Equilibrium competitive inhibition studies were conducted to determine the relative affinities of antisera produced against the major HBsAg polypeptides P-1, P-2, and P-6 (23,000, 29,000, and 72,000 daltons, respectively).


Influence of divalent cations upon complement-mediated enzyme release from human polymorphonuclear leukocytes. The complement component, C5a provokes the selective release of granule-associated enzymes from the intact, viable cytochalasin B-treated human polymorphonuclear leukocytes (PMN) in the absence of phagocytosis or cellular adherence to surfaces. Consquently, in this experimental system the influence of divalent cations on these two processes can be disregarded and their effects on enzymes secretion can be studied directly. Cytochalasin B-treated PMN exposed to C5a in calcium and magnesium-free media consistently secreted significant amounts of the granule-associated enzymes, beta-glucuronidase and lysozyme. The basal secretory response was not diminished if cells were preincubated with 5.0 mM EDTA, nor was it influenced if 1.0 mm or 2.0 mM EDTA were present in the reaction mixtures. The addition of calcium (up to 1.5 to 2.0 mM) produced a concentration-dependent enhancement of beta-glucuronidase release, whereas increasing amounts of calcium (above 2.0 mM) inhibited secretion of this enzyme. Lysozyme release was similarly enhanced by the addition of calcium, but inhibition with high concentrations was not observed. Calcium per se, in the absence of C5a, provoked only the release of lysozyme from these cells. The effects of calcium upon enzyme release were not associated with alterations in the state of assembly of cytoplasmic microtubules. These findings provide another example of the role of calcium in "stimulus-secretion coupling" and provide evidence that exocytosis of various granules in human PMN is regulated by independent mechanisms involving calcium.


The immune response in the hamster. VII. Studies on cytophilic immunoglobulin. Hamster 7S IgG1 and IgG2 antibodies to hen-egg albumin (HEA) were tested for their capacity to bind to macrophage cytophilic Ig receptors. Both IgG1 and IgG2 were cytophilic for hamster macrophages though the membrane receptor had a predominant specificity for IgG1. Hamster IgG1 bound primarily to homologous macrophages whereas IgG2 bound to macrophages from other rodent species as well. The binding of hamster Ig to hamster macrophages was inhibited by a wide range of heterologous rodent sera. The only exception was guinea pig serum since guinea pig IgG2 was found to bind only to homologous macrophages. Sheep red blood cells (SRBC) coated with hamster IgG2 were ingested by macrophages more readily than those coated with hamster IgG1. Thus, there appeared to be a paradoxical relationship between the apparently strong affinity of IgG1 for the hamster macrophage Ig receptor and its reactivity weak ingestion promoting activity. Implications of this phenomenon are discussed.


Lymphocyte plasma membranes. V. Specificity and mitogenicity of absorbed anti-lymphocyte sera. Anti-lymphocyte sera against human thymus [ALS-(THY)] were absorbed serially with cultured human lymphoblasts (CHL) or thymus and residual antigen-binding activity was tested. The absorbed ALS were used to bind 125I-labeled antigens from lymphocytes labeled by the lactoperoxidase catalyzed iodination technique. Absorption of ALS(THY) with CHL led to the absorbed serum having less than 5 to 10% of its original antigen-binding activity against labeled CHL antigens while maintaining from 20 to 40% of its original activity against labeled THY. Serial absorption of ALS(THY) with THY led to an equal decrease in activity against both THY and CHI. When the immunoprecipitates from these experiments were examined on polyacrylamide gels containing SDS it was found that serial absorption of ALS(THY) with THY first removed activity against a component of m.w. similar to 48,000 leaving relatively greater activity against material of apparent high molecular wieght. In contrast, absorption of ALS-(THY) with CHL removed the antibodies against the high molecular weight material while leaving activity against the component of m.w. 48,000. When these absorbed ALS were used to induce in vitro lymphocyte proliferation, it was found that ALS(THY) absorbed with CHL, did not. The retention or loss of mitogenicity seemed to correlate with retention or loss of binding activity against the component(s) of m.w. similar to 48,000.


Antigen-antibody complexes produced in chickens tolerant to bovine serum albumin. A radioimmunoassay for circulating soluble antigen-antibody complexes is described. The assay detects complexes either in antigen or antibody excess. Soluble complexes were found in the sera of chickens tolerant to bovine serum albumin (BSA). The complexes appeared in the serum as soon as 7 days following neonatal induction of tolerance. The amount of complexes reached a peak between 1 to 2 weeks of age and disappeared by 6 weeks when responsiveness returned. The complexes were found in the bottom third of a 10 to 40% sucrose density gradient and by analytical ultracentrifugation indicated a size of 22.8S. If tolerant chickens were challenged with BSA at 2, 4 or 6 weeks, the disappearance of complexes was not accelerated, and a proportion of the previously tolerant chickens exhibited a heightened antibody response.


Immune mechanisms in leukemia: suppression of cellular immunity by drugs and x-irradiation. The relative suppressive effects of x-irradiation (XR), cyclophosphamide (CY), prednisolone (PRD), and methotrexate (MTX) on the primary and secondary cellular immune response of C58/wm mice to syngeneic line Ib transplantable leukemia (Ib cells) were quantified. An LD10 dose of each agent was used for immunosuppression. XR, CY, and PRD were markedly suppressive for the primary immune response if given 24 hr before mice were immunized to Ib cells but less immunosuppressive if given 24 hr later. MTX was only slightly immunosuppressive XR, CY, and PRD also suppressed the secondary immune response if given before but not after antigen. The immunosuppressive effect of these agents was evaluated by defining their median immunosuppressive dose or the median time in days required for mice to recover from graded doses of each immunosuppressive agent. For example, the median recovery time from an LD10 of XR, CY, and PRD was 29.3, 19.7, and 3.7 days, respectively. Immunologic competence remaining after XR or drug treatment was quantified in terms of the LD50 dose of Ib cells required to kill recipient mice. For XR, CY, PRD, and MTX it was 10(6.16), 10(2.15), 10(6.90) and greater than 10(7.0) viable Ib cells, respectively. The overall results provided evidence that the primary and secondary cellular immune responses to a weak syngeneic tumor antigen were resistant to immunosuppression once they were initiated. There was a good correlation between the relative immunosuppressive effect of the test agents and the amount that they reduced the number of immune spleen cells. The agents also impaired the immunocompetence of individual spleen cells. Mechanisms by which XR or drugs might exert their immunosuppressive effects were discussed.


Alloantibody-induced cytotoxicity of macrophages. Alloantibodies substantially alter the in vitro nonspecific cytotoxic effect of macrophages on bystanding allogeneic and xenogeneic target cells. Although the specific IgM alloantibody increased significantly the ability to parental macrophages to damage target cells, IgG alloantibody had an opposite effect and suppressed the macrophage cytotoxicity. Macrophages of F1 hybrid mice were less affected by this treatment unless alloantibodies against both parental strains were added together. Parental macrophages exposed in vitro to the concomitant action of both IgM and IgG alloantibodies exhibited a diminished cytotoxicity toward target cells. It is proposed that IgM and IgG alloantibodies induce different conformational changes of the macrophage surface.


Studies on nonidet P40 lysis of murine lymphoid cells. I. Use of cholera toxin and cell surface Ig to determine degree of dissociation of the plasma membrane. Lymphoid cells from A/J mice were iodinated (125I) by the lactoperoxidase lysed with the non-ionic detergent NP-40. The plasma membrane glycolipid receptor for cholera toxin and cell surface immunoglobulin were utilized in immune precipitation systems to characterize the degree of dissociation of the plasma membrane under various conditions. It was found that at 0.1% NP-40 and at cell concentration from 5 to 10 times 10(7) cells/ml, lipid-protein and protein-lipid-protein complexes formed in NP-40 which were soluble after centrifugation at 10(5) times G. Column chromatography of 125I-cell lysates on agarose A-0.5 M in 0.1% or 0.5% NP-40/PBS indicated that the majority of iodinated cell surface material existed as aggregates in detergent micelles. The availability of the oligosaccharide moiety of the glycolipid to interact with the cholera toxin was dependent on both the detergent concentration and the cell concentration used for cell lysis. However, the cell surface immunoglobulin was immunoprecipitable under all conditions of lysis tested.


The detection of phytomitogen-induced changes in human lymphocyte surfaces by laser Doppler spectroscopy. The changes in electrophoretic mobility and isoelectric point produced by incubating human peripheral blood lymphocytes with phytohemagglutinin (PHA) and concanavalin A (Con A) have been characterized by laser Doppler spectroscopy. The results extend and partially confirm older observations made by classical procedures. Incubation with either agent for 90 min at 37 degrees C resulted in stable and reproducible decreases in electrophoretic mobility, and increases in the isoelectric point. The incubation conditions used are known to permit primary attachment of the phytomitogen, capping and endocytosis; nevertheless, at least in the case of Con A, washing the cells with a specific inhibitor for Con A binding, methyl-alpha-D-glucoside (MAG), resulted in complete reversal of the electrokinetic changes, showing that the underlying changes in cell surface constitution detected under these conditions are solely due to reversibly bound Con A. The results suggest that laser Doppler spectroscopic changes could provide a direct assay for specific binding to immunocompetent cell surfaces.


The use of ammonium sulphate precipitation method for the determination of antigen-binding capacity and affinity of anti-tetanus antibodies in human serum. Radioimmunoassay of anti-tetanus antibodies produced in human serum in response to tetanus toxoid immunization was carried out by employing the non-specific precipitation effect of ammonium sulphate described by Farr (1958). The results showed that the method was sensitive and was able to differentiate between immune and non-immune persons. The effects of booster dose injection on the quantity and quality of antibodies produced during immunization were discussed, and the possible use of the method to predict the amount of immunogen, the timing and number of injections required for optimal host response in immunization schedules was suggested.


A comparative study on the uptake in vitro of [3H]thymidine, [131I]5-iodo-2'-deoxyuridine and [3H]deoxycytidine in mouse spleen cells using double isotope autoradiography. The uptake of 3H-labeled thymidine (3H-TdR), 131I-labelled 5-iodo-2'-deoxyuridine (131IUdR) and 3H-labelled deoxycytidine (3H-CdR) by mouse spleen cells in vitro was studied using an autoradiographic method for the separate detection of 3H and 131I in cell smears. The experiment was performed in two steps. In one half of a pooled spleen cell suspension uptake of 3H-TdR and 131IUdR was compared; in the other half of the suspension uptake of 3H-CdR and 131IUdR was compared. Only two nucleated spleen cells were found which had taken up only 3H-CdR. All other scanned cells were double labelled. Generally the nucleotides were taken up according to a rather fixed relation. It was further found that 3H-CdR and 3H-TdR were incorporated to about the same extent. However, cells which were incubated with 131IUdR and 3H-TdR took up the 131IUdR to a lesser extent than cells which were incubated with 131IUdR and 3H-CdR.


Translation of polysomal messenger RNA during epidermal differentiation. Translation in vitro of messenger RNA obtained from preparations of active polysomes isolated from the epidermal basal, spinous, and granular cells of the newborn rat has provided evidence that in the context of differentiation in this tissue, control of protein synthesis is exerted at the level of transcription. The data supporting this hypothesis are reviewed.


Heterogenous proteins in keratohyaline granules studied by quantitative autoradiography. Electron microscopic autoradiography with [3H]histidine, [3H]cystine, I13H]arginine, and [3H]proline was used to study protein synthesis in keratohyaline granules of newborn rats. All 3H-amino acids were incorporated into proteins in the granular cells, and the radioactive proteins appeared in the keratohyaline granules. However, the amount of radioactivity associated with the granules and the pattern of ultrastructural localization of the radioactive proteins differed considerably for each 3H-amino acid. "Histidine-labeled" protein was located mainly in the matrix portion of keratohyaline granules whereas "cystine-labeled" protein accumulated in the dense homogenous deposits. "Arginine-labeled" protein was distributed more diffusely in the organelles of granular cells, but that associated with keratohyaline granules seemed to localize mostly with "histidine-labeled" protein and partly with "cystine-labeled" protein. Large amounts of "proline-labeled" protein were also present in other areas of the cytoplasm than keratohyaline granules. This protein localized in the dense homogeneous deposits, but it seemed to turn over more rapidly than "cystine-labeled" protein, an indication that the dense homogenous deposits consist of at least two different polypeptide chains, one of which contains higher cystine and the other higher proline.


Aspects of epidermal ultrastructure.

Aspects of epidermal ultrastructure. Some problems posed by primarily ultrastructural studies of the epidermis are highlighted and discussed, and on the whole it is concluded that purely morphologic observations are unlikely further to elucidate such questions as the nature and function of keratohyalin, or the dynamic aspects of the general keratinization process. The contribution of freeze-fracture studies to the understanding of the functional morphology of the epidermis is assessed, with particular reference to specialized contacts, and the stratum corneum. Passing reference is made to the epidermal nonkeratinocytes.


Surface adaptations of the vertebrate epidermis to friction. Epidermal surfaces in representative vertebrates specialized for lowered or increased friction were studied with the scanning electron microscope. Microvillous and microridged patterns predominate in aquatic vertebrates. In squamate reptiles, the complex and varied ornamentation of the Oberhäutchen functions both in adhesive modifications and in modulating surface reflectivity. Frictional surfaces in birds and mammals are characterized more by anatomical than by cytologic specializations, the detailing of surface cells being mostly a function of turnover rate.


In vitro growth and maturation of epithelial cells from postembryonic skin. The in vitro growth and maturation of epithelial cells from normal human skin in organ culture, outgrowth culture, and isolated epithelial cell culture are described. In each model, the patterns of growth and maturation differ in growth rates, formation of keratohyaline granules, and keratinization. The differences and similarities in the behavior of epithelial cells in each system are described, some of the physical and chemical factors which alter these patterns are outlined, and the general advantages and limitations of each model as a research tool are discussed.


Lipid synthesis in chick epidermis.

Lipid synthesis in chick epidermis. Lipid synthesis in newborn chick epidermis was studied by electron microscopic autoradiography after injection of tritiated palmitate. The labeled lipid product in the tissue was identified as mostly triglyceride. At the earliest time after injection (6 hr), the radioactive precursor was taken up by all viable cells of the epidermis. Grain density was heaviest over basal cells, moderate over spinous cells, and slight over granular cells; thus lipid incorporation is highest in the basal and spinous regions of the chick epidermis. As time after injection progressed, the increasing amounts of grains over the granular and horny cells and decreasing amounts over the basal and spinous cells reflected the continuous upward displacement of cells from one layer into the next. From the distribution of silver grains within the epidermal cells, it has been concluded that, with the passage of time, triglycerides synthesized by the epidermal cells were mainly located in lipid droplets. The numerous grains associated with the elements of the endoplasmic reticulum indicated that this organelle is involved in aggregating triglyceride molecules into lipid droplets. The fact that grains were seen within the horny cells indicated that part of the horny cell consists of lipid probably derived from the lipid droplets retained by the cells during keratinization.


Epidermolysis bullosa dystrophica-recessive: a possible role of anchoring fibrils in the pathogenesis. The purpose of this study was to define the ultrastructural defects and pathogenesis of epidermolysis bullosa dystrophica-recessive (EBD-R). The only consistent ultrastructural alteration found in EBD-R was an absence of anchoring fibrils. In many specimens of nonblistered, nontraumatized EBD-R skin, absence of anchoring fibrils was the only ultrastructural abnormality observed. The possibility that lack of anchoring fibrils was a secondary change resulting from previous blistering and scarring was eliminated by our observation that anchoring fibrils were consistently absent in the never previously blistered skin of two newborns with EBD-R. In experimentally traumatized skin, the epidermis and dermis separated in the region of the epidermal-dermal junction normally occupied by anchoring fibrils. Basal lamina and dermal microfibril bundles appeared to be normal. Using recombinant grafts, we demonstrated that anchoring fibrils were not formed by EBD-R dermis when combined with EBD-R epidermis or normal epidermis. Anchoring fibrils were formed when normal dermis was combined with normal and EBD-R epidermis. These studies indicate that the defect in EBD-R resides in the dermis and that the defect may be associated with impaired formation of anchoring fibrils.


Skin blisters and hair loss in a rat mutant called vibrissaeless. A radiation-induced autosomal recessive mutant in the rat called vibrissaeless (vb), has been described and studied. Mutants have abnormal hair growth, the hairs being reduced in number and length. Mutant animals form blisters which then erode, crust, and heal without scars. The blisters can be artificially produced by friction and result from intraepidermal separation which is suprabasilar in position. To date, we cannot correlate this abnormality in rats with any known inherited human blistering disease.


Sodium dodecyl sulfate-polyacrylamide gel electrophoresis of proteins of newborn rat skin. I. Cell strata and nuclear proteins. The proteins obtained from separated cells of neonatal rat dermis, four cell populations of epidermis, and an epidermal nuclear preparation were analyzed by sodium dodecyl sulfate (SDS)-polyacrylamide gel electrophoresis. Comparison of the results of the insoluble proteins of the dermis and epidermis show no similarity of the major protein bands, indicating the effective separation of the dermis and epidermis and absence of cross-contamination. The gels of the soluble proteins of the basal, spinous, and granular layers of the epidermid are very similar. Only the pattern of bands of the cornified cells differs in that some of these bands are absent and at least three new bands are present. The insoluble proteins have specific differences in the protein content related to the cell structure. An example is the nuclear protein bands which correspond with the most prominent bands in the gels of basal and spinous layer proteins, but are absent, with the possible exception of one band, from gels of cornified cell proteins.


The fibrous proteins in various types of ichthyosis. The stratum corneum of individuals with ichthyosis vulgaris, sex-linked ichthyosis, lamellar ichthyosis, and epidermolytic hyperkeratosis has been studied. An alpha x-ray diffraction pattern has been observed in all specimens and the solubility of the alpha fibrous proteins appears to be the same as in normal stratum corneum. Sodium dodecyl sulfate (SDS)-polyacrylamide electrophoresis of the fibrous proteins showed variable patterns within the different types of ichthyosis, while amino acid analyses of the proteins were quite similar to those from normal stratum corneum. These data suggest that the fibrous proteins in the ichthyosis are not abnormal, but further studies on the individual polypeptide chains are necessary to rule out more subtle differences.


A method for testing the effects of fluids on rat skin using acrylic chambers. A method is presented whereby test fluids may be kept in contact with the skin of the back of the rat for 5 to 6 days. Methyl methacrylate chambers with hemispherical test domes were made and attached to rubber washers of larger diameter, which in turn were attached to the skin of the back of the rat using an alkyl cyanoacrylate (Eastman 910 adhesive). Each chamber had a removable stainless-steel screw to allow it to be filled and replenished with fluid as required. To prevent the rat gnawing the chambers from its back, twice weekly 4 mm was removed from the lower incisors and 1 1/2 mm from the upper incisors, using a diamond disc in a dental handpiece. The young adult rats were fed a soft diet and after an initial temporary fall in weight, they moved about the cages in a normal manner.


An animal model for screening topical and systemic drugs for potential use in the treatment of psoriasis. A new hairless mouse model using ultraviolet light to stimulate increased epidermal cell turnover and hyperplasia and thus simulate psoriasis has been designed so that drugs may be tested both topically and systemically for possible therapeutic value in this disease. Two methods of determining drug antimitotic activity have been used, the mitotic index and the extraction of epidermal DNA and the determination of the radioactivity of the sample. Results show that 2% 5-fluorouracil in propylene glycol and 2% nitrogen mustard in water topically and cyclophosphamide systemically, which are drugs known to be effective in psoriasis, significantly reduce the mitotic index. DNA synthesis is similarly decreased by the latter two drugs. The effect of the topical agents is shown to be local and not systemic. Cyclophosphamide, which is ineffective topically in psoriasis, is ineffective in the model.


Dichotomy in response to indomethacin in UV-C and UV-B induced ultraviolet light inflammation. In subjects irradiated with both UV-C and UV-B ultraviolet light (UVL), 10 mug of intradermal indomethacin decreased the redness in all 13 of the UV-B irradiated areas but in only 2 of 13 of the UV-C irradiated areas. Higher doses of intradermal indomethacin (50 mug and 100 mug) decreased the redness produced by UV-C irradiation in 6 subjects. It is suggested that the failure of 10 mug of indomethacin to decrease the redness of the UV-C induced inflammation, while decreasing the redness in the UV-B induced inflammation, is consistent with the possibility that prostaglandins participate in UV-B but not UV-C induced inflammation.


Effect of fluocinolone acetonide cream on human skin blood flow. Blood flow rate was measured in the forearm skin of human subjects exposed to ultraviolet irradiation. Blood flow was determined by the 133Xe disappearance technique 18 hr after ultraviolet (UV) irradiation with a Westinghouse RS sunlamp held 10 inches from the skin for 10 min. Ultraviolet irradiation caused skin blood flow to increase. Application of fluocinolone acetonide cream, 0.025%, 4 times in the 16 hr following UV irradiation had no effect on either control skin blood flow or the UV-induced hyperemia.


A comparative study of allergic and primary irritant contact dermatitis with dinitrochlorobenzene (DNCB) in dogs. Attempts were made to induce allergic contact dermatitis in dogs, a species generally considered poorly responsive to experimental allergic contact dermatitis. Yound Beagles were sensitized to 2,4 dinitrochlorobenzene (DNCB) by multiple intradermal injections. Two weeks after sensitization, these dogs were challenged topically with 0.1% DNCB by a standard closed-patch technique. Sensitization evidenced by various degrees of reaction following challenge was established in all of 14 pups used, while 7 nonsensitized control pups did not react to challenge. Primary irritant contact dermatitis was induced in the skin of nonsensitized Beagle pups by 1%, 5%, and 10% solutions of DNCB. In allergic contact dermatitis the sites of challenge were grossly indurated, erythematous, and edematous. Histologically at these sites there was an infiltration of mononuclear cells which reached maximum intensity at 3 to 4 days. Accumulations of lymphoid cells were marked around sweat galnds and hair follicles. Penetration of leukocytes into these cutaneous adnexa was associated with degenerative processes in their cellular structures. Mononuclear cell infiltration into the epidermis was mild. Spongiosis was observed in the epidermis, but vesicle formation was rare. In primary irritant contact dermatitis gross lesions were characterized by severe erythema, edema, and gangreen of the skin. Microscopically, the main lesions were necrosis of the epidermal cells, separation of the epidermis from the dermis, dermal edema, and massive infiltration of the dermis with polymorphonuclear cells.


Pattern of shedding of the Norwalk particle in stools during experimentally induced gastroenteritis in volunteers as determined by immune electron microscopy. In 11 of 23 volunteers the Norwalk virus-like particle was visualized by immune electron microscopy in at least one stool specimen obtained during the acute phase of experimentally induced nonbacterial gastroenteritis. Examination of multiple stool specimens obtained during the course of illness in these 11 volunteers revealed maximal concentration of Norwalk virus-like particle at the onset of illness and shortly thereafter; in no case was the Norwalk particle visualized in stools obtained before the onset of illness. This finding further suggests that the Norwalk particle was the etiological agent of the Norwalk gastroenteritis outbreak. The limit of reliability of our immune electron microscopy assay system for particle counting was examined.


Depressed lymphocyte function after measles-mumps-rubella vaccination. Healthy children receiving routine measles-mumps-rubella vaccine developed an impaired in vitro lymphocyte response to stimulation with antigen (Candida) but not with mitogen (phytohemagglutinin and pokeweed mitogen). Response of lymphocytes was determined by measurement of the amount of [14C]thymidine incorporated by the cells. The impaired response to antigen lasted from one to five weeks after vaccination. There was no alteration in the number of either total or thymus-derived lymphocytes in the peripheral blood after vaccination; These results suggest that viral vaccination causes a depression of lymphocyte function rather than a depletion of functional lymphocytes.


In vitro formation and i vivo clearance of fibrinogen: fibrin complexes. Fbrinogen:fibrin complexes have been previously described in various thrombotic disorders.  To evaluate further the properties of fibrinogen:fibrin complexes, and theirin vitro and in vivo behavior, soluable fibrinogen:fibrin complexes have been formed invitro using mixtures of '131l-fibrinogen ('131l-F) and '125l-fibrin ('125l-fb).  By means of Sepharose 4B chromatography, a macromolecular complex (peak one) containing both moieties could be separated from a lower molecular weight peak two containg noncomplexed material.  The latter eluted at the same position as did intact fibrogen. Both the '131l-F and '125l-fb components of peak one were rapidly catabolized when injected into rabbits with residual blood activity at 24 hours of 8 per cent and 4 per cent, respectively. Peak two behavedas a simple mixture with corresponding 24-hour levels at 31 per cent and 3 per cent.  Gel filtration of postinjuection plasma samples demonstrated that peak one remained as macromolecular complex.  Preinjection crosslinking of the F:fb complex with factor xiii did not substantially change the blood clearance.  Prior blockage of the reticuloendotheial system with Thorotrast or carbon resulted in impaired clearance of peak one.  The data provide evidence that fibrinogen and fibrin can form a macromolecular complex which is stable both in vitro and vivo.  Further, the reticuloendotheialsystem was shown to mediate the the in vivo clearance of this complex.  This latterfinding may be of pathophysiologic significance.


Stimulation of granulopoiesis by liver macrophages. Isolated murine Kupffer cells or liver macrophages release high levels of colony-stimulating activity (CSA) necessary for the proliferation of granulocytic and mononuclear cell colonies in vitro.  CSA was detected in media conditioned by Kupffer cells ata concemtration of 0.25 x 10'6 cells per millilter.  Conditioned media from suspensions of unseparated liver did not stimulate colony formation and, in high concentrations,were inhibitory.  CSA obtained from Kupffer cells was more active on a cell percell basis than CSA OBTAINED FROM LUNG OR PERITONEAL MACROPHAGES.  These studies indicate that liver macrophages can also release CSA and further support the concept that the monocyte-macrophage system may play a role in the regulation of granulopoiesis.


Diminished erythroid ferrochelatase activity in protoporphyria. In two patients with protoporphyria the enzymatic synthesis of aminolevulinic acid and prophobilinogen in erythroid tissue was normal. Boine marrow ferrochelatase activity was less than one-fourth of the mean activity in normal control subjects. Ferrochelatase activity in peripheral blood reticulocytes was less than 10% of controls. This metabolic abnormality provides one biochemical explanation for the increased concentrations of blood protoporphyrin in protoporphyria and clarifies the apparent minimally impaired hemoglobin synthesis in the two case studies.


Tissue trace element and enzyme content in pigs fed a low manganese diet.  I. Arelationship between manganese and selenium. Pigs received a diet containing 0.59 p.p.m. Mn.  Control pigs received the samequantity of the same diet which was supplemented with 22 p.p.m. of Mn.  At the end of6 weeks, pigs fed the low Mn diet had a diminution in tissue Mn levels as well as a diminution in tissue Se content.  Tissue levels of Zn, Cu, Ca, and Mg were notaffected by the dietary regimen.  Indicative of the fact that experimental animals were probably Mn-deficient was a statistically significant decrease in hepatic arginaseactivity that could be enhanced by the addition of Mn.  These studies represent the first experimental evidence that there may be a specific interaction between tissue Se and Mn.  Tissue Se levels were decreased to a statistically significant degree in all tissues studied except the kidney in the Mn-deficient animals.


Studies on a radioimmunoassay for human erythopoietin. A highly purified erythropoietin (ESF) preparation (12,000 units per milligram of protein) was labeled with Na'125I using the Chloramine-T method.  Undamaged immunoreative labeled ESF was separated from the damaged, nonimmunologically receiveESF by Sephadex G-150 fractionation. This undamaged immunreactive ESF was usedin radioimmunoassay for human erythropoietin.  Separation of bound from free antigen was acheived using the double-antibody technique.  Approximately 55 per cent binding wasobserved at an antiserum dilution of 1:1500.  This assay appears to be sensitive enough to detect as little as 0.025 milliunits of the International Reference Preparation erythropoietin.  The estimated levels of thid hormone in normal and anemic uremic human subjects suggests that immunoreactive serum erythropoietin levels are elevated above normal in anemia of uremia.


Urinary iron in patients with sickle cell anamia. Urinary iron excretion was measured in patients with sickle cell anemia and relateddiseases.  Iron concentration in urine was determined by atomic absorption spectrophotometry and daily total iron excretion was calculated from this and total daily urine volume.  Normal subjects excreted a mean of 88 pg Fe per day (95 per cent confidence limitsof 0 to 120 pg).  Nine persons with sickle cell trait had normal Fe excretion rates.However, abnormally high iron excretion was present in the first urine sample obtainedfrom 27/31 patients with SS, 3/7 with SC, 1/2 with CC, and 1 with S-thalassemia. Iron excretion varied  very significantly from day-to-day in individual patients. The results of studies attemting to relate this to increase excretion during activityas compared to rest were negative.  No clear relationship of iron excretion to painfulcrisis could be shown, but remarkable rises in urine iron occurred in two patients who developed a hyperhemolytic crisis.  These studies suggest that urinary iron reflects intravascular hemolysis primarily.  No correlation was evident between urine iron and the patients' age, transfusion history, or serum iron values suggesting increased urinary iron excretion cannot be attributed to iron overload in sickle cell anemia.


Estimation of zinc concentration of parotid saliva by flameless atomic absorption spectrophotometry in normal subjects and in patients with idiopathic hypogeusia. The concentraiton of zinc in parotid saliva was estimated by flameless atomic absorption spectrophotometry.  As small a sample as 5 to 10 mul of whole paratid saliva can be analyzed quickly and reliably, without special sample handling and with littleinterference from other ions normally found in saliva.  Parotid salivary zinc concentration in 34 subjects with normal taste acuity was 51 plus or minus 14 ppb(parts per billion)(mean plus or minus 1 S.D.); parotid salivary zinc concentration in 47 subjectswith idiopathic hypogeusia was 10 plus or minus 6 ppb (mean plus or minus 1 S.D.) which is significantly lower than that in normal subjects (p lessthan 0.001).  This technique is a usual method by which to evaluate parotid salivary zinc, particulary inrelationship to problems of taste, appetite, and nutrition.


Acute thanol effect on chemotaxis and other components of host defense. The effect of alcohol on granulocyte chemotaxis was studies with a radioactive assaysystem.  Chemotaxis was inhibited in vitro by concentrations of alcohol above 400 mg. per cent when present during all steps in the assay, but levels above 800 mg. per cent required for inhibition when alcohol was present only during the granulocyte incubation. No inhibition of chemotactic factor generation was found with alcohol concentration up to 1,500 mg. per cent. Cells and serum exposed to alcohol in vivo by acute intxication of donors demonstrated normal in vitro chemotactic performance, even  when the assay itself was carried out in medium containing 200 mg. of alcohol.  Thestudies do not exclude alcohol's in vivo induction of an inhibitor which must remain present during chemotaxis for inhibition; nor would they have detected an impairment of chemotaxis occurring after the peak blood alcohol concentration.  The intoxicated volunteer subjects were also evaluated for changes in delayed hypersensitivity, serum complement concentration, granulocyte hexose monophosphate shunt activity, and circulating whiteblood cell counts; no consistent changes were seen.


Postnatal fall and rise of circulating 25-hydroxyvitamin D in the rat*. Plasma 25-hydroxyvitamin D levels (5 to 6 ng. per millilter at birth) decreased significantly at age 12 days (1to 2 ng. per millilter) in rat neonates.  At 3 to 4 weeksof age, the plasma concentrations of 25-hydroxyvitamin D had risen to birth levels or higher.  Chromatography of lipid extracts of neonatal tissues following in vivo administration of 'H-25-hydroxyvitamin D' from the milk of mothers who had been given 'H vitamin D' intravenously.  Following intraperitoneal injection of equal (or 3-fold larger doses to older pups) doses of 'H-25-hydroxycholecalciferol, the half-lives of 'H in plasma were 2.9 to 3.0 days and 2.8 to 3.05 days in young and oldersuckling pups, respectively.  These data collectively suggest that young suckling rats,unlike weaning rats, do not receive and/or produce sufficient 25-hydroxyvitamin D to maintain the blood concentration observed at birth.


Ballistocardiographic indicators of prognosis in ischemic heart disease. Bimonthly recordings of ultra-low-frequency acceleration ballistocardiograms overa 2 to 7 year period in 73 patients with ischemic heart disease and 50 matched control subjects within the framework of a clinical follow-up were subjected to measurement of IJ amplitude (reflecting force of contraction), IJ velocity (reflecting contractility), and IJ velocity variation coefficient.  These repeated measurements were correlated with 24-hour vanillylmandelic acid (VMA) excretion in the urine, arthythemia incidence, heart rate, and clinical outcome in each subject.  Moth-to-month variability of the IJ velocity was highly significantly correlated with 24-hour VMA excretionas well as with the likelihood of subsequent myocardial infartion or sudden death.  Data on 24 of the patients with ischemic heart disease were available during a two-year period prior to their death from documented myocardial infarction or presumed fatal arrhythmia without a fresh infarction at autopsy.  Their records were compared with those made during the same time period on individually matched control subjects and on patients with documented ischemic heart disease who survived the period of study.  The mean force of cardiac contraction (IJ amplitude) was consistently lower in the group destined todie early than in the other two groups during the first 18 months.  During the 6 monthsprior to death, however, their tracings show a relatively increased force of cardiac contraction and an increased product of force x pulse rate (referred to as the "drive index"), as well as an increase in the incidence of cardiac arrhythmias.  None of these late increases was observed during comparable periods of time among surviving patients orcontrol subjuects.


The effects of a low level of dietary cadmium on blood pressure, '24Na, '42K, andwater retention in growing rats. The effects of 5 pg Cd per millilter of drinking water on body weight gain, food intake, systolic blood pressure, '24Na, '42K; and water retention and freference for NaCl solution in male and female rats were studied.  After 205 days, Cd had no significant effect on weight gain, food intake, water intake, or feed efficiency.  The'24Na retention of the Cd-fed male and female rats was greater at 161 days than in the control animals and was significantly greater (P less than 0.05) in the Cd-treated females than in the control females at 294 days.  In vivo retention of '42K was significantly greater in the Cd-treated males than in the control males at 189 days, butthe oppisite was true of the Cd-treated females in comparison with female control animals.  There were no significant differences between treatments in '42K retention after 330 days.  No significant differences were found between treatments in systolic blood pressure.  Water retention was significantly greater in the Cd-treated males and females than in the control animals after 320 days.  Preference for 0.20 M NaCl was significantly greater in the Cd-fed males than in the control males at 277 days. Possible mechanisms which might explain the sodium retention in thhe Cd-fed rat are discussed.


Inihibition of human platelet aggregation by dipyridamole and two related compounds and its modification by acid glycoproteins of human plasma. The inhibitory effect of dipyridamole (RA 8) and its two derivatives (RA 233 andSH 869)  on platelet aggregation in platelet-rich plasma (PRP) AND IN SUSPENSIONSOF WASHED PLATELETS WAS EVALUATED USING 3 AGGRESSING STIMULI: ADP, thrombin, and collagen.  Mean effective dose (ED'30) of RA 8 causing 50 percent inhibition of plateletaggregation of washed human platelets by ADP, collagen, or thrombin varied from 1.2 x 10'-7 to 1.8 x 10'-7M.  On the other hand, RA 8 caused little inhibition aggregation in human PRP.  RA 233 and SH 869 produced similiar degrees of inhibition ofplatelet aggregation in human PRP and in suspensions of washed human platelets.Platelet-poor plasma, fraction VI-acid glycoproteins, or purified alpha'1-acid glycoprotein complex was isolated by means of Sephadex G-25 gel filtration.  It is postulated that the formation of this complex leads to the blocking of the capacity of RA 8to inhibit platelet aggragation.  RA 233 and SH 869 had little capacity to form complexes with acid glycoproteins of human plasma.  This may explain the effectiveness of these compounds in inhibiting platelet aggregation in PRP.


Reversible impairment of cerebral DNA synthesis in thiamine deficiency. The effect of thiamine deficiency on rat brain DNA and RNA synthesis was investigated.  Thiamine deficiency, culminating in encephalopathy (symptomatic stage) was induced by dietary thiamine deprivation of 4 to 5 weeks.  The encephalopathy could be completely reversed within 6 hours by paranteral administration of thiamine.  Controls consisted of pair-fed and ad libitum-fed littermates given the same diet supplemented with thiamine.  Brain DNA and RNA synthesis was determined by administration of labeled thymidine, orotic acid, or adenine into the cerebral ventricle and measuring the incorporation of the appropiate labeled precursor into DNA or RNA.  Thiamine deficiency(symptomatic stage) had no effect on net DNA and RNA level in any brain area studied.  Also, no consistent alteration of brain RNA synthesis was shown in severe thiamine seficiency.  By contrast, DNA synthesis in symptomatic thiamine-deficient ratswas reduced to 22, 37, 31, and 19 percent, respectively; of pair-fed control values in the cortex, brain stem, cerebellum, and subcortical structures (p less than 0.05).  Thedegree of depressed DNA synthesis increased with the extent and duration of thiaminedeprivation.  Following reversal of the encephalopathy with parenteral thiamine, DNAsynthesis in all brain areas increased markedly to and above control values.  Thses data indicate that the thiamine deficiency state interferes with the synthesis ofsome discrete DNA pool(s) in the brain.  This effect may be due to thiamine deficiency per se and /or some thiamine-induced impaired food assimilation or utilization.


Dynamics of the immune response in rabbits immunized with spreptococcal extracellular antigens: comparison of the Streptozyme agglutination test with three specific neutralization tests. The dynamics of the immune response to streptococcal extracellular antigens as measured by the streptozyme agglutination test have been defined in experimental animals andcompared with the dynamics of the immune response as determined by three established neutralization tests for streptococcal antibodies (ASO, anti-DNase B,and anti-NADase).  In rabbits immunized with streptococcal extracellular Streptozyme-measured antibodies rose more quickly and peaked earlier than did antibodies to streptolysin O, streptococcal DNase-B, and streptococcal NADase.  Additional studiesrevealed that the early peak was primarily due to 2-mercaptoethanol-sensitive (19S) antibody and that the later rise in Streptozyme-measured antibodies was due to 2-mercaptoethanol-resistant (7S) antibody.  Preliminary observations using sucrose gradient ultracentrifugation tended to confirm this interpretation.  These data provide a possible explanation for the early detection of a streptococcal antibody response by the Streptozyme test which has also been described in humans.  The data suggest a theoretical advantage for the Streptozyme agglutination test in patients with streptococcal infections and their sequealae.  However, the complexity of the Streptozyme reagent suggests that more extensive studies are needed to assure the consistent reproductivity of results with different lots of the test reagent.


Transferrin, iron, and dermatophytes. I. Serum dematophyte inhibitory component definitively identified as unsaturated transferrin. The factor present in normal human serum which inhibits growth of dematophytic fungi is characterized and identified. Serum inhibitory factor (SIF) is nondialyzable, heat stable at 56 degrees C. for 4 hours, and fungistatic. SIF was found to be an inhibitor of the dermatophyte genera Trichophyton, Microsporium, and Epidermophyton as well as the dimorphic yeast Candida albicans. SIF activity directly correlated with a serum's unbound iron-binding capacity (UIBC) in that lower UIBC'S were less inhibitory. Addition of iron to serum neutralized the inhibitory activity and this neutrilization was shown to be specific for iron since zinc, magnesium, managnese, and copper failed to alter serum inhibitory activity. Furthermore, addition of purified iron-free transferrin to a neutralized serum restored the SIF activity in parallel with the UIBC. Removal of transferrin from serum by affinity chromatography was confirmed by polyacrylamide gel electrophoresis and iron-binding assays. Transferrin-free serum produced by this procedure was shown to lack inhibitory activity. These data indicate that SIF is unsaturated transferrin and strongly suggests that it inhibits dermatophytes by binding iron which many organisms need for growth.


Hypoxia-induced thrombocytopenia in mice. In mice hypoxic hypoxia (0.5 atm.) results in a severe and persistent thrombocytopenia with a rapid decline in the platelet count between the fifth and ninth days of hypoxia, after which platelet counts level off at about half their normal value. The thrombocytopenia is not due to the associated polycythemia, splenomegaly, or increased blood volume. There is no significant change in platelet counts of mice made polycythemic by daily injections of 6 units of erythropoietin. Fifteen days of hyperbaria (3 atm.) has no effect on the platelet count of otherwise normal mice. Since there is only a slight decline in platelet count during the first 5 days of hypoxia, the persistent thrombocytopenia appears to be due to either a decreased rate of production of platelets or a structural or metabolic defect in platelets produced under conditions of hypoxia.


Deformability of sickle cells as studied by microsieving. The effect of deoxygenation on deformability of sickle cells (Hb SS RBC) was studied quantitatively by a microsieving technique with the use of polycarbonate filters having micropores of 5 mum in diameter. The rate of pressure rise and the relative resistance during filtration through polycarbonate sieves increased progressively when the P02 of Hb SS RBC suspensions was reduced below 80 mm. Hg. Control studies on Hb AA RBC did not show any significant change in either parameter when deoxygenated. The present study on the filterability of Hb SS RBC and our previous data on the viscometric behavior of Hb SS RBC serve to establish the quantitative relation between P02 and the deformability of Hb SS RBC.